bromochloroacetic-acid and Carcinoma-in-Situ

Submucosal glands (SMGs) present throughout human esophagus with clusters at either the upper third or lower third of the organ. SMGs tend to atrophy with age, and neoplasms arising in these glands are rare. In order to bring convenience to diagnosis, we summarize the histopathologic characteristics of all esophageal submucosal gland tumors (SGTs). Due to the morphological similarity, the nomenclature of salivary tumors is adopted for SGTs. However, there is great confusion about the definition and histogenesis of these tumors, especially the malignant subtypes. In the literature, esophageal mucoepidermoid carcinoma and adenoid cystic carcinoma usually adjoin the surface squamous epithelium and coexist with intraepithelial neoplasia or invasive squamous cell carcinoma (SCC). In addition, the typical gene alterations of salivary tumors have not been reported in these SGTs. Therefore, we propose to apply stringent diagnostic criteria to esophageal SGTs so as to exclude mimickers that are SCCs with various degree of SMG differentiation.

Topics: Aged, 80 and over; Atrophy; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophagus; Humans; Keratins; Male; Mucin-5B; Neoplasms, Glandular and Epithelial; Retrospective Studies

To investigate the clinicopathological and immunohistochemical features, diagnosis and differential diagnosis of nipple adenoma of the breast.. Morphological observation and immunohistochemistry were applied to 18 cases of nipple adenoma with a review of the related literatures.. The neoplasms were localized at nipples or under the areola of breast, adherent to the epidermis, mainly composed of dilated ducts in a tubular appearance associated with fibrotic matrix. The glandular epithelium showed various type of proliferation, forming thick layers or complex structures such as papillae, micropapillae, tufts, fronds, arcades or bridges accompanying with solid or cribriform cell nests. The tumor cells were crowding, lack of an uniform morphology and polarity with intact myoepithelial cells around the ducts. By immunostaining, the glandular epithelium was diffusely positive for 34betaE12, patchily positive for CK5/6, and negative for p53 and c-erbB-2. The myoepithelium, positive for p63, smooth muscle actin and Calponin, was well preserved and outlining the ducts.. Nipple adenoma is an infrequent type of benign breast neoplasm, presenting as sclerosing papilloma, papillomatosis or florid sclerosing adenosis. It is easily confused with atypical ductal hyperplasia/low grade ductal carcinoma in situ, invasive ductal carcinoma or low grade adenosquamous carcinoma. A correct diagnosis is based on the peculiar location and morphology of the tumor, and immunohistochemistry is helpful in some cases.

Topics: Adenoma; Adult; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Adenosquamous; Carcinoma, Ductal, Breast; Diagnosis, Differential; Female; Humans; Keratin-5; Keratins; Middle Aged; Nipples

Pathways to breast cancer have been difficult to define using morphology alone. Although epithelial hyperplasia of usual type (HUT) is associated with moderately elevated breast cancer risk, molecular evidence placing it in a cancer precursor pathway is not clear-cut. Recent evidence suggests that small numbers of cytokeratin 5/6 positive cells are precursors of separate lineages which acquire either cytokeratin 8/18/19 or smooth muscle actin (SMA) and cytokeratin 14 on separate pathways to fully differentiated epithelial and myoepithelial phenotypes (and may ultimately lose cytokeratin 5/6 expression). Immunohistochemistry shows that most HUT have a mixed precursor phenotype resembling normal breast with co-expression of cytokeratin 5/6, 8/18/19 and SMA, in contrast to atypical ductal hyperplasia (ADH) and ductal carcinoma in situ which typically have a 'mature' luminal phenotype positive for cytokeratin 8/18/19 but lacking cytokeratin 5/6 expression. While this supports the idea of a biological discontinuity between HUT and ADH/DCIS, caution is called for in the diagnostic use of these reagents until greater experience has been accumulated, and other published data do show features of HUT intermediate between normal breast lobules and ADH.

Topics: Breast; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Cell Transformation, Neoplastic; Epithelium; Female; Humans; Hyperplasia; Keratins; Loss of Heterozygosity; Neoplasm Invasiveness; Neoplasm Staging; Phenotype; Precancerous Conditions

To review basic and clinical aspects of cytoskeletal keratin expression in normal cervical epithelia as well as in preneoplastic and malignant epithelia of the uterine cervix.. The results of extensive studies from our group and other groups on keratin phenotyping in normal premalignant and malignant cervical epithelia were summarized.. All studies involving keratin expression in the cervix were reviewed, as were general studies on keratin expression in which the cervix was mentioned and studies relevant to understanding cervical cancer etiology (36 studies).. From these studies, keratin phenotypes of the various epithelia were derived. The phenotypes were correlated to existing theories on the development of cervical carcinoma.. It is possible to distinguish the various epithelial types in the normal cervix based on their keratin expression patterns. Reserve cells display a bidirectional keratin pattern, comprising keratins typical of both squamous and simple types of differentiation, reflecting the bipotential nature of these cells. Cervical intraepithelial neoplasia can be divided into two subpopulations, one characterized by the reserve cell keratin phenotype and the other by a keratin phenotype typical of nonkeratinizing squamous epithelia. The first population also contains the simple keratins, the relative percentage of which increases with increasing degree of dysplasia. We therefore suggest that these lesions are progressive in nature. Carcinomas show a differentiation-related keratin expression pattern in addition to the basic reserve cell keratin phenotype. Adenocarcinomas also have been shown to express most of the reserve cell keratins. The latter observation indicates a common progenitor for both carcinoma types.

Topics: Carcinoma in Situ; Cervix Uteri; Epithelium; Female; Forecasting; Humans; Keratins; Metaplasia; Precancerous Conditions; Research; Uterine Cervical Neoplasms

Topics: Carcinoma in Situ; Epithelium; Female; Humans; Keratins; Neoplasm Invasiveness; Precancerous Conditions; Vulva; Vulvar Diseases; Vulvar Neoplasms

Polyclonal and monoclonal antibodies to cytokeratin polypeptides were used to study the expression of these intermediate filament proteins in normal, squamous metaplastic, and neoplastic epithelium of the uterine cervix, in order to investigate the morphogenesis of early epithelial changes preceding cervical squamous cell carcinoma. A polyclonal keratin antiserum showed a positive reaction in all different epithelial cell types of the uterine cervix. A positive reaction was also found in subcolumnar reserve cell hyperplasia, in squamous metaplastic and dysplastic cells, and in (squamous) carcinoma in situ. A monoclonal antibody specific for columnar epithelium (RGE 53) gave a positive reaction in endocervical columnar cells and in some immature metaplastic cells but was negative in subcolumnar reserve cells, squamous (metaplastic) cells, dysplastic cells, and most cases of carcinoma in situ. Another monoclonal cytokeratin antibody (RKSE 60) pointed to early keratinization in light microscopically nonkeratinizing squamous (metaplastic) and dysplastic epithelium. A possible overlap in staining patterns of RGE 53 and RKSE 60 was seen in some cases of immature metaplasia. Morphologic changes occurring in the transformation zone upon dedifferentiation are accompanied by alterations in cytokeratin expression. Similarities in cytokeratin expression were found between dysplasia and carcinoma in situ on one hand and subcolumnar reserve cell hyperplasia and squamous metaplasia on the other. This study favors an epithelial origin and a squamoid nature of subcolumnar reserve cells.

Topics: Adult; Antibodies, Monoclonal; Carcinoma in Situ; Cervix Uteri; Female; Humans; Hyperplasia; Keratins; Metaplasia; Middle Aged; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

To study the diagnostic performance of the Urinary Bladder Cancer (UBC) test in patients with superficial bladder carcinoma.. One hundred one patients in follow-up for superficial bladder cancer (pTa, pT1, carcinoma in situ) were recruited for this study. Each patient underwent cystoscopy and transurethral resection or biopsy, with subsequent histologic confirmation in the case of abnormalities. In addition, specimens were assessed with an immunoenzymometric assay for cytokeratin expression (the UBC test), and the urinary creatinine concentration was determined to correct for different degrees of urinary dilution. Different methods were applied to calculate the diagnostic value of the UBC test.. Both noncorrected and corrected median values of the UBC test were comparable between patients with and without a recurrent bladder tumor. The overall sensitivity, specificity, and positive and negative predictive values of the noncorrected UBC test was 20.7%, 84.7%, 35.3%, and 72.6%, respectively. For the corrected UBC test, the corresponding values were 20.7%, 79.2%, 28.6%, and 71.3%. The area under the receiver operating characteristic curve was not significantly different from 0.50, indicating no diagnostic value of the UBC test in this study.. The diagnostic value of this new urinary marker appears insufficient for the follow-up of patients with superficial bladder cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Carcinoma in Situ; Creatinine; Cystoscopy; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Predictive Value of Tests; Regression Analysis; ROC Curve; Sensitivity and Specificity; Statistics, Nonparametric; Urinary Bladder Neoplasms

Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva's anatomic location.. To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties.. One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6).. Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95, 1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96, 1.20, and 1.08, respectively; P < .001).. There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Humans; Keratins; Observer Variation; Vulvar Neoplasms

To systematically describe the clinical and histopathological features of a case series of conjunctival carcinomatous lesions underlying as-and also masquerading-pyogenic granuloma.. Nine cases of conjunctival carcinomatous lesions underlying a pyogenic granuloma (which were clinically predominant) were retrospectively identified. Patients' records were analysed for demographic data, clinical appearance and the postoperative course. Formalin-fixed paraffin-embedded specimens were routinely processed and stained with H&E and periodic acid-Schiff. Immunohistochemical stains for cytokeratin were performed in selected cases.. All nine tumours were located in the conjunctiva (bulbar, tarsal, limbal conjunctiva) of patients between 44 and 80 years. The lesions exhibited clinical features of pyogenic granuloma which dominated the clinical appearance. Additional features comprised a papillomatous appearance of the adjacent conjunctiva, a more whitish aspect of the lesion and a history of squamous cell carcinoma (SCC) respectively surgery for other entities. Histopathological analysis revealed a carcinomatous lesion (conjunctival intraepithelial neoplasia or SCC) at the base of a classic pyogenic granuloma in all nine cases. Surgical removal (R0 resection) was performed. Three cases received adjuvant mitomycin C or interferon α2b treatment. Two lesions locally recurred within 2 years after initial presentation.. Carcinomatous lesions may be accompanied by a pyogenic granuloma which may dominate the clinical pictures. As the tumour is usually located at the base of the lesion, a complete surgical excision followed by histopathological analysis is mandatory for each lesion appearing as conjunctival pyogenic granuloma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Conjunctival Neoplasms; Diagnosis, Differential; Female; Granuloma, Pyogenic; Humans; Interferon alpha-2; Keratins; Male; Middle Aged; Mitomycin; Retrospective Studies

Lymphoepithelioma-like carcinoma (LELC) is a rare finding in the upper urinary tract. The presenting clinical findings mimic those of other more common upper-tract tumors, such as urothelial carcinoma. Preoperative imaging has not been shown to reliably predict the diagnosis of LELC. This tumor can be misdiagnosed as a reactive inflammatory lesion or lymphoma if the proper immunohistochemical stains for cytokeratin are not used.

Topics: Aged; Carcinoma in Situ; Carcinoma, Transitional Cell; Female; Humans; Keratins; Kidney Neoplasms; Lymphatic Metastasis; Neoplasms, Multiple Primary; Ureteral Neoplasms

Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear-cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient's recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation.

Topics: Biomarkers, Tumor; Brain Neoplasms; Carcinoma in Situ; Cell Differentiation; Diagnosis, Differential; Epithelial Cells; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Keratins; Male; Middle Aged; Mucin-1; Neuroglia; Radiography; Temporal Lobe

We explore diagnostic utility of a multicolor excitation multimodal nonlinear optical (NLO) microscopy for noninvasive detection of squamous epithelial precancer in vivo. The 7,12-dimenthylbenz(a)anthracene treated hamster cheek pouch was used as an animal model of carcinogenesis. The NLO microscope system employed was equipped with the ability to collect multiple tissue endogenous NLO signals such as two-photon excited fluorescence of keratin, nicotinamide adenine dinucleotide, collagen, and tryptophan, and second harmonic generation of collagen in spectral and time domains simultaneously. A total of 34 (11 controlled and 23 treated) Golden Syrian hamsters with 62 in vivo spatially distinct measurement sites were assessed in this study. High-resolution label-free NLO images were acquired from stratum corneum, stratum granulosum-stratum basale, and stroma for all tissue measurement sites. A total of nine and eight features from 745 and 600 nm excitation wavelengths, respectively, involving tissue structural and intrinsic biochemical properties were found to contain significant diagnostic information for precancers detection (p<0.05). Particularly, 600 nm excited tryptophan fluorescence signals emanating from stratum corneum was revealed to provide remarkable diagnostic utility. Multivariate statistical techniques confirmed the integration of diagnostically significant features from multicolor excitation wavelengths yielded improved diagnostic accuracy as compared to using the individual wavelength alone.

Topics: Animals; Carcinoma in Situ; Collagen; Cricetinae; Early Diagnosis; Epidermis; Keratins; Mesocricetus; Microscopy; Multivariate Analysis; NAD; Neoplasms, Squamous Cell; Nonlinear Dynamics; Optical Imaging; Tryptophan

To study the clinical and morphological features as well as immunophenotype of tubulolobular carcinoma of the breast (TLC).. Eight cases of TLC were retrieved from 97 cases of invasive lobular carcinoma between January 2005 and March 2010 in the Peking Union Medical College Hospital. The clinical features and pathologic findings were studied and immunohistochemistry was performed for the expression of ER, PR, HER2, p53, E-cadherin, CK34βE12 and CK8.. Among the breast cancer patients, the incidence of TLC was about 1.0% (8/880). The mean age of the patients was 59 years, with a range of 45 to 79 years. All patients were asymptomatic, with incidental finding of a mass in the breast on health examination. Common findings on sonography included a hypoechoic nodule with irregular shape and spiculated margin. Histologically, the small uniform tumor cells were arranged in a mixed pattern showing single cells, single-cell files or cords, small round to angulated tubules, and infiltrating lobular or targetoid patterns around ducts that were specific for classical invasive lobular carcinoma. Low or intermediate grade intraepithelial neoplasms which had similar cellular morphology with the invasive tumor often appeared in the periphery, including ductal carcinoma in situ, lobular carcinoma in situ and intraductal papillary carcinoma. Immunohistochemistry of the tumor cells showed intense reactivity to ER (7/8) and PR (8/8), but no reactivity to HER2 or p53. Both the tubules and single-cell file or cords expressed E-cadherin (7/8), CK34βE12 (5/8), and CK8 (8/8) with a uniform staining pattern. All patients underwent modified radical mastectomy and 2/8 patients had metastatic carcinoma in the axillary lymph nodes. Seven patients were followed up for 28 to 75 months and remained well, including one patient that had a new breast mass 60 months after surgery, but had no treatment up to now.. TLC is a rare variant of invasive breast cancer and reveals mixed histologic features of both tubular and lobular carcinoma with common expression of E-cadherin, CK8 and CK34βE12. A better understanding of TLC would enable pathological diagnosis to be made reasonably and accurately.

Topics: Aged; Breast Neoplasms; Cadherins; Carcinoma in Situ; Carcinoma, Lobular; Female; Follow-Up Studies; Humans; Immunohistochemistry; Keratin-8; Keratins; Lymphatic Metastasis; Mastectomy, Modified Radical; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Treatment Outcome

Invasive lobular carcinoma (ILC) represents 15% of invasive human breast tumours. This report describes the morphological and immunohistochemical features of three canine mammary tumours comparable with human ILC. These tumours were composed of a non-delimited proliferation of discrete cells infiltrating fibrous connective tissue. Multifocal in-situ carcinoma associated with invasive lesions was present. Invasive tumour cells and in-situ lesions expressed cytokeratin and CK34betaE12, but not E-cadherin. Based on these morphological and immunohistochemical characteristics, the tumours were classified as canine ILC.

Topics: Animals; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Lobular; Dog Diseases; Dogs; Female; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Mastectomy; Neoplasm Invasiveness

Besides worse prognosis of bladder cancer with squamous differentiation (pure squamous cell carcinoma (SCC) or mixed urothelial carcinoma (UC/SCC)), high-grade non-keratinising squamous differentiation is difficult to identify in haematoxylin-eosin stainings. This study aims to validate routine immunohistochemical markers for squamous differentiation in a larger cohort of patients. Tissue microarrays of 89 pure SCCs and mixed UC/SCCs, 66 urothelial carcinomas (UC), precursor lesions and normal urothelium were stained for cytokeratin (CK) 5/6, CK 5/14, CK 7, CK 20 and uroplakin III. Electron microscopy was performed to confirm the differentiation. Pure SCCs displayed staining throughout the epithelium for CK 5/6 (76.6% (36/47)) and CK 5/14 (95.8% (46/48)), focal staining for CK 7 (28.9% (13/45)) and no staining for CK 20 and uroplakin III (both 0% (0/48)). UCs exhibited a basal or diffuse staining for CK 5/6 (30.2% (16/53)) and CK 5/14 (57.1% (32/56)), focal positivity for CK 7 (83.6% (46/55)), CK 20 (50.9% (29/57)) and uroplakin III (21.8% (12/55)). Each marker discriminated SCC and UC significantly (p < 0.01). A third subgroup rarely showed full epithelial staining for CK 5/6 (14.3% (1/7)) and CK 5/14 (28.6% (2/7)), focal staining for CK 7 (85.7% (6/7)) and no staining for CK 20 and uroplakin III (both 0% (0/7)). Electron microscopy could prove both, SCC and UC characteristics, revealing a transient type. A staining pattern with CK 5/6- and CK 5/14-positivity plus CK 20- and uroplakin III-negativity identified squamous differentiation in bladder tumours and revealed a third type of squamous transdifferentiation.

Topics: Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cell Count; Cell Differentiation; Cystectomy; Humans; Keratins; Phenotype; Prognosis; Tissue Array Analysis; Urinary Bladder Neoplasms; Urothelium

Assessing epithelial dysplasia to predict malignant transformation remains problematic in many tissues because grading systems are poorly structured and individual features poorly defined. Dysplasia grading is criticised for lack of reproducibility and poor predictive value. Grading systems for upper aerodigestive tract dysplasia have evolved over several decades and are not supported by good outcome experimental data..  This study analysed the individual features of dysplasia in 86 oral dysplastic lesions and determined the reproducibility of scoring for each, and correlated them with other features and clinical factors using complex clustering analyses.. A uniform pattern of dysplasia was found in 37 lesions, focal dysplasia in 36 and in 13 lesions dysplasia formed complex discontinuous patterns. There was wide variation in reproducibility of scoring of individual features and many, including thickness, some types of rete morphology, basaloid cell anisonucleosis, basal dyscohesion, and dyskeratosis as deep single cells correlated with sub-sites. Rete morphology, type of keratinisation, hyperchromatism of the basaloid compartment, prickle cell anisonucleosis and extension down salivary ducts correlated with smoking. Conventional grading and oral intraepithelial neoplasia (OIN) grading by 'thirds affected' showed strong correlation overall but scores obtained with the OIN system tended to a higher grade at all sites except soft palate/fauces. There was poor correlation between the systems for moderate dysplasia and also severe dysplasia at some sites. Individual features could not be shown to cluster to form distinct patterns of dysplasia.. These variations may account in part for the lack of reproducibility and poor predictive value of the grading systems in current use and could inform the design of future grading systems.

Topics: Carcinoma in Situ; Cell Adhesion; Cell Nucleus; Cell Transformation, Neoplastic; Chromatin; Epithelial Cells; Epithelium; Female; Humans; Keratins; Leukoplakia, Oral; Lip Neoplasms; Male; Mitosis; Mouth Floor; Mouth Mucosa; Mouth Neoplasms; Neoplasm Grading; Palatal Neoplasms; Palate, Soft; Precancerous Conditions; Reproducibility of Results; Salivary Ducts; Tongue Neoplasms

Interobserver reproducibility in the diagnosis of benign intraductal proliferative lesions has been poor. The aims of the study were to investigate the inter- and intraobserver variability and the impact of the addition of an immunostain for high- and low-molecular weight keratins on the variability. Nine pathologists reviewed 81 cases of breast proliferative lesions in three stages and assigned each of the lesions to one of the following three diagnoses: usual ductal hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ. Hematoxylin and eosin slides and corresponding slides stained with ADH-5 cocktail (cytokeratins (CK) 5, 14. 7, 18 and p63) by immunohistochemistry were evaluated. Concordance was evaluated at each stage of the study. The interobserver agreement among the nine pathologists for diagnosing the 81 proliferative breast lesions was fair (κ-value=0.34). The intraobserver κ-value ranged from 0.56 to 0.88 (moderate to strong). Complete agreement among nine pathologists was achieved in only nine (11%) cases, at least eight agreed in 20 (25%) cases and seven or more agreed in 38 (47%) cases. Following immunohistochemical stain, a significant improvement in the interobserver concordance (overall κ-value=0.50) was observed (P=0.015). There was a significant reduction in the total number of atypical ductal hyperplasia diagnosis made by nine pathologists after the use of ADH-5 immunostain. Atypical ductal hyperplasia still remains a diagnostic dilemma with wide variation in both inter- and intraobserver reproducibility among pathologists. The addition of an immunohistochemical stain led to a significant improvement in the concordance rate. More importantly, there was an 8% decrease in the number of lesions classified as atypical ductal hyperplasia in favor of usual hyperplasia; in clinical practice, this could lead to a decrease in the number of surgeries carried out for intraductal proliferative lesions.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Observer Variation; Precancerous Conditions; Reproducibility of Results

A rigid confocal endoscope has been developed to assess the oral squamous epithelium of mice and to determine sensitivity, specificity, and accuracy of this new technology.. This endoscope is connected to the commercially available Heidelberg Retina Tomograph (HRT). HRT is a device with a 670-nm diode laser designed to acquire topographical measurements of the optic nerve head. Real-time rigid confocal endoscopy is demonstrated by imaging the epithelial lesions of a mice model. Six-week-old male C57Bl/6 mice were randomly divided into a non-treated group (n = 10) and into a 4-nitroquinoline 1-oxide (4-NQO)-treated group (n = 50). In the 4-NQO-treated group, the mice obtained 4-nitroquinoline 1-oxide in the drinking water (100 microg/ml) to induce tumourigenesis in the mouse tongue. The 4-NQO-solution was diluted in the drinking water for mice. After an 8-16-week carcinogen treatment with 4-NQO (ad libitum), mouse tongues were dissected within 3 h after CO(2) overdose. After confocal microscopy of all lesions of the tongue, conventional histopathological investigation was performed.. The inter-rater reliability for the two observers of the confocal microscopic findings was found to be Kappa = 0.59 (P < 0.001). The penetration depth varied in the healthy tissue of the underside of the tongue throughout this study and was measured between 104 and 240 microm. In keratotic lesions, the penetration depths were diminished and varied between 80 and 140 microm. Strong keratinization inhibits the evaluation of the epithelium. For differentiation between low-grade and high-grade squamous intra-epithelial lesions, a sensitivity and specificity of 73% and 88% was reached.. The animal experiment with this non-invasive new technology indicates that this imaging technology facilitates the detection of pre-cancerous lesions of the underside of the oropharynx. Human studies on oropharyngeal and laryngeal lesions are needed to prove the applicability of this method in the field of otorhinolaryngology.

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinogens; Carcinoma in Situ; Cell Membrane; Cell Nucleus; Disease Models, Animal; Endoscopes; Endoscopy; Epithelial Cells; Epithelium; Equipment Design; Keratins; Leukoplakia, Oral; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Mouth Mucosa; Precancerous Conditions; Predictive Value of Tests; Random Allocation; Sensitivity and Specificity; Tongue Neoplasms

To investigate the pathological diagnostic features and the differential diagnosis of radial sclerosing lesions of the breast.. Morphological observation and immunohistochemistry were applied to forty-four cases of radial sclerosing lesions of the breast.. All forty-four patients were females, the mean age was 40.3 years (range 17 to 54 years). In the 31 consultation cases, 13 were misdiagnosed as carcinoma. The lesions had a radiating outline, and a central scar area where squeezed or pressed irregular shaped tubules were frequently seen. Dilated tubules and proliferated ducts or lobules were seen radically arranged at the periphery accompanied sometimes with the apocrine glands or columnar cell metaplasia and hyperplasia. Aside, there were 14 cases displaying necroses and 8 cases showing atypical ductal hyperplasia. Immunostaining showed myoepithelial cells around the pseudo-infiltrating tubules, and the florid proliferating epithelial cells were positive for CK5/6.. Radial sclerosing lesions of the breast possess characteristic histological features, and may be misdiagnosed as carcinoma. The lesions should be differentiated from ductal carcinoma in situ, lobular neoplasia, tubular carcinoma and invasive ductal carcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Breast; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Diagnosis, Differential; Diagnostic Errors; Female; Humans; Hyperplasia; Keratin-14; Keratin-5; Keratins; Middle Aged; Sclerosis; Young Adult

Topics: Aged; Carcinoma in Situ; Conjunctival Neoplasms; Humans; Keratins; Male; Severity of Illness Index

Oral verrucous hyperplasia (OVH) and oral erythroleukoplakia (OEL) are two oral precancerous lesions with relatively high malignant transformation potential. One of the best cancer prevention strategies is to use a conservative and effective treatment modality to eliminate oral precancers to stop their further malignant transformation. Our previous studies have shown that the topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) using the 635-nm light-emitting diode (LED) light is very effective for OVH and OEL lesions.. Because the laser machine is a more-popular light source than the LED device in PDT clinics, in this study 40 OVH and 40 OEL lesions were treated once a week with the same PDT protocol but using the 635-nm laser light to evaluate whether this laser light-mediated topical ALA-PDT was also effective for OVH and OEL lesions.. We found that all the 40 OVH lesions exhibited complete response (CR) after an average of 3.6 PDT treatments. Of the 40 OEL lesions, 38 showed CR after an average of 3.4 PDT treatments and two showed partial response (PR). Better PDT outcomes were significantly associated with OVH and OEL lesions with the smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer.. This study indicates that the laser light-mediated topical ALA-PDT is also very effective for OVH and OEL lesions. Therefore, we suggest that topical ALA-PDT using either the LED or laser light may serve as the first-line treatment of choice for OVH and OEL lesions.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Biopsy; Carcinoma in Situ; Erythroplasia; Female; Humans; Hyperplasia; Keratins; Leukoplakia, Oral; Low-Level Light Therapy; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Photochemotherapy; Photosensitizing Agents; Precancerous Conditions; Remission Induction; Treatment Outcome

The definition of atypical ductal hyperplasia (ADH) encompasses qualitative and quantitative criteria. Qualitative criteria include cytological and architectural features similar to those of low grade ductal carcinoma in situ (DCIS), the quantitative criteria are characterized by metric features (2 mm or 2 ductules) or by the confines of lobules. In this article we discuss the morphology of ADH, the status of ADH in the low grade pathway of breast carcinoma development and its clinical significance. Furthermore, we comment some special forms of atypical epithelial proliferations of the ductal type.

Topics: Biopsy; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Cell Division; Epithelial Cells; Female; Humans; Hyperplasia; Keratins; Loss of Heterozygosity

Proliferative epithelial breast lesions include a wide variety of benign hyperplastic and noninvasive neoplastic lesions, as well as invasive carcinomas. Mammographically these lesions may show microcalcifications, architectural distortions or mass lesions. The task of the pathologist begins with a preoperative diagnosis by means of minimally invasive biopsy. His diagnosis forms the basis for not only the radiological-pathological correlation diagnosis, but also for the management of benign proliferative breast disease lesions, as well as therapeutic decisions in the case of malignant lesions.In daily practice, immunohistochemistry is the method of choice for clarifying difficult cases. The aim of this chapter is to describe the relevant markers in breast pathology and to provide an algorithmic approach to different proliferative breast disease lesions.

Topics: Biomarkers; Biopsy; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Diagnosis, Differential; Epithelium; Female; Fibrocystic Breast Disease; Humans; Hyperplasia; Immunohistochemistry; Keratins

Microglandular adenosis (MGA) of the breast is widely known as a benign lesion that can mimic invasive carcinoma. In situ and invasive carcinomas have been described as arising in MGA, but which cases of MGA will progress to carcinoma is unclear. Criteria for distinguishing uncomplicated MGA, MGA with atypia (AMGA), and carcinoma arising in MGA (MGACA) are not standardized. The primary objective of this study was to illustrate the clinical, histopathologic, and immunophenotypical characteristics of MGA, AMGA, and MGACA in an effort to provide criteria for distinguishing the 3 types. We retrospectively identified 108 cases seen at M.D. Anderson Cancer Center between 1983 and 2007 that had a diagnosis of MGA. Of the 108 cases, 65 cases had available material for review. Inclusion criteria were glands of MGA expressing S-100 protein and lacking myoepithelial layer (smooth muscle actin negative). Eleven out of 65 cases qualified to have an MGA component; myoepithelial layer was detected in the remaining 54 cases and were classified as adenosis. Out of the 11 MGA patients, there were 3 patients with uncomplicated MGA, 2 had AMGA, and 6 had MGACA. Staining indices for the cell cycle markers p53 and Ki-67 were used to compare the 3 tumor categories. Additional staining for other tumor markers [estrogen and progesterone receptors, HER2, epidermal growth factor receptor (EGFR), c-kit, CK5/6, and CK18] were performed. Patient demographics, tumor radiologic features, and clinical follow-up data were collected for all cases. Multiple invasive histologic components were identified in each of the MGACA cases. All invasive MGACAs had a duct-forming component. In addition, basal-like component was present in 2 cases, aciniclike in 2, matrix producing in 4, sarcomatoid in 1, and adenoid cystic in 1. All tumors had strong and diffuse CK8/18 and EGFR expression but no estrogen receptor, progesterone receptor, HER2 (ie, triple negative), or CK5/6 expression. C-kit was focally expressed in 2 of the MGACAs. Ki-67 and p53 labeling indices was < 3% in all MGAs, 5% to 10% in the AMGAs, and > 30% in MGACAs. In a follow-up ranging from 14 days to 8 years, none of the MGA cases recurred. One of the AMGA cases recurred as invasive carcinoma in a background of AMGA after 8 years following incomplete excision of the lesion. Three out of 6 MGACA cases (50%) required multiple consecutive resections ending up with mastectomy due to involved margins by invasive or in situ carcinoma. Two ou

Topics: Actins; Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Cell Transformation, Neoplastic; Diagnosis, Differential; Diagnostic Errors; Disease Progression; ErbB Receptors; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Mastectomy; Middle Aged; Neoplasm Invasiveness; Precancerous Conditions; Proto-Oncogene Proteins c-kit; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; S100 Proteins; Texas; Time Factors; Treatment Outcome; Tumor Suppressor Protein p53

The histological resemblance between extramammary Paget disease and Bowen disease has been described since Bowen's original article was published in 1912.. We herein describe a case of vulval primary extramammary Paget disease in a 61-year-old women with the histological features of Bowen disease.. Histological examination of a biopsy specimen showed acanthosis with full-thickness cellular atypia, focal hyperkeratosis and parakeratosis in the epidermis, and no characteristic Paget cells were observed. However, histological examination of an operative specimen revealed areas characteristic of Paget disease and Bowen disease. Overall, the areas characteristic of Bowen disease and Paget disease occupied 6% and 32% of the total operative specimen, respectively. The two areas were sharply separated. Immunohistochemical findings showed carcinoembryonic antigen to be expressed in areas containing Paget cells, but not in the areas characteristic of Bowen disease. Cytokeratin 7 (CK7) (OV-TL 12/30) and CK8 (35betaH11) were strongly expressed in both of these areas. The staining for high-molecular-weight cytokeratins was negative in both of these areas.. Our findings indicated that primary extramammary Paget disease and squamous cell carcinoma in situ arose multifocally from a common cell in the epidermis.

Topics: Biomarkers, Tumor; Bowen's Disease; Carcinoembryonic Antigen; Carcinoma in Situ; Female; Humans; Keratins; Middle Aged; Neoplasms, Multiple Primary; Paget Disease, Extramammary; Skin Neoplasms; Treatment Outcome; Vulvar Neoplasms

In this study, the expression patterns of Galectin-3 (Gal-3) and the frequency of infiltrating CD1a positive dendritic cells (DCs) were determined in 82 cases of vulvar tissues, consisting of normal squamous epithelia (NE, N = 10), vulvar condylomas (VC, N = 24), high grade vulvar intraepithelial neoplasias (HG-VIN, N = 26) of common type, and invasive keratinizing squamous cell carcinomas (SCC, N = 22) by a standard immunohistochemical method using monoclonal antibodies to investigate their differential expression in vulvar squamous dysplasia and infiltrating carcinomas with an emphasis on neoplastic transformation and progression. Gal-3 expression was cytoplasmic, nuclear or membranous in NE, VCs, and HG-VINs, with negative or weak and occasionally moderate reactivities. In SCCs, exclusively cytoplasmic staining patterns with moderate or strong reactivity in 59% of cases were observed (p < 0.0001, chi-square test); Gal-3 expression was not related with stage, grade, and recurrence. The frequency of CD1a positive DCs increased from NE and VCs to highest numbers in HG-VINs, was lowest in SCCs (p < 0.0001, ANOVA), and was not related with stage and grade, but with recurrence in SCCs (p = 0,048, t-test). This study indicates that qualitative and quantitative changes of Gal-3 immunoexpression and infiltration by CD1a positive DCs in vulvar NE, VCs, and HG-VIN lesions, respectively, compared with SCCs play a role in the development of an infiltrative phenotype, and may provide adjunctive criteria in the diagnosis of invasion of vulvar squamous epithelia.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD1; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Condylomata Acuminata; Dendritic Cells; Female; Galectin 3; Humans; Immunohistochemistry; Keratinocytes; Keratins; Middle Aged; Neoplasm Invasiveness; Phenotype; Vulva; Vulvar Neoplasms

Topics: Adenoma, Sweat Gland; Aged, 80 and over; Carcinoma in Situ; Cystadenocarcinoma, Papillary; Epidermis; Female; Humans; Keratin-7; Keratins; Paget Disease, Extramammary; Sweat Gland Neoplasms; Syringoma

Some examples of lobular carcinoma in situ (LCIS) may be composed in part of signet ring cells. Such proliferations have been considered examples of pleomorphic LCIS based on pathological features of the more conventional component. However, the occurrence of LCIS composed entirely of signet ring cells is extraordinarily rare. This report describes an example of an in situ proliferation that was composed almost entirely (>95%) of signet ring cells, which was unassociated with an invasive carcinoma and which showed comedo-type necrosis. There was only focal lobulocentric distention by lesional cells, as is typical of classic LCIS. However, discrete, ductal-type cross-sectional profiles showed a purely intraepithelial proliferation of remarkably discohesive signet ring cells. The signet ring cells had intermediate-grade nuclear atypia, no significant mitotic activity and were positive for mucicarmine and PAS stains (the latter with and without diastase predigestion). The cells displayed marked immunoreactivity for high-molecular-weight keratin (stained by 34beta E12 antibody), MUC1, gross cystic disease fluid protein-15, cytokeratin 7 and were negative for cytokeratin 20, E-cadherin, progesterone receptor and HER2/neu. It is concluded that this is an example of a purely signet ring variant of pleomorphic LCIS.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Lobular; Carcinoma, Signet Ring Cell; Carmine; Cell Proliferation; Female; Humans; Immunohistochemistry; Keratins; Mucin-1; Mucins; Periodic Acid-Schiff Reaction; Treatment Outcome

This study characterizes the morphologic features and the endogenous fluorescence in the stratified squamous epithelia of the 7,12-dimethylbenz(a)anthracene-treated hamster cheek pouch model of carcinogenesis using multiphoton laser scanning microscopy (MPLSM). MPLSM allows high-resolution, three-dimensional image data to be collected deeper within thick tissue samples with reduced phototoxicity compared with single-photon imaging. Three-dimensional image stacks of normal (n = 13), precancerous (dysplasia, n = 12; carcinoma in situ, n = 9) and cancerous tissue [nonpapillary squamous cell carcinoma (SCC), n = 10, and papillary SCC, n = 7] sites in the hamster cheek pouch were collected in viable, unsectioned tissue biopsies at a two-photon excitation wavelength of 780 nm. Five features were quantified from the MPLSM images. These included nuclear density versus depth, keratin layer thickness, epithelial thickness, and the fluorescence per voxel in the keratin and epithelial layers. Statistically significant differences in all five features were found between normal and both precancerous and cancerous tissues. The only exception to this was a lack of statistically significant differences in the keratin fluorescence between normal tissues and papillary SCCs. Statistically significant differences were also observed in the epithelial thickness of dysplasia and carcinoma in situ, and in the keratin layer thickness of dysplasia and SCCs (both nonpapillary and papillary). This work clearly shows that three-dimensional images from MPLSM of endogenous tissue fluorescence can effectively distinguish between normal, precancerous, and cancerous epithelial tissues. This study provides the groundwork for further exploration into the application of multiphoton fluorescence endoscopy in a clinical setting.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cheek; Cricetinae; Epithelial Cells; Fluorescence; Keratins; Male; Mesocricetus; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton; Mouth Neoplasms; Precancerous Conditions

Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials.. To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications.. Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry.. Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p = 0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p = 0.423).. COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Cyclooxygenase 2; Epithelium; Herpesvirus 4, Human; Humans; Immunohistochemistry; Keratins; Membrane Proteins; Microcirculation; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Staging; Peroxidases; Prostaglandin-Endoperoxide Synthases

Primary small cell carcinoma of the breast is exceedingly rare, with fewer than 25 reported cases. The case presented herein is that of a 61-year-old woman with a 2.5-cm mass of the left breast. She underwent mastectomy with axillary node dissection. Histologic examination revealed sheets and nests of small, hyperchromatic, malignant cells with indistinct nucleoli and scant cytoplasm. High-grade solid and comedo ductal carcinoma in situ also was present. Two of 5 axillary lymph nodes contained metastatic disease. Immunohistochemical analysis demonstrated weak immunoreactivity for cytokeratin, neuron-specific enolase, and bcl-2. This histologic and immunohistochemical profile was consistent with that of a primary small cell carcinoma. Interestingly, this neoplasm lacked immunoreactivity for E-cadherin. E-cadherin expression has been documented in all 11 (100%) of 11 previously reported cases of primary small cell carcinoma of the breast, suggesting that this tumor is a form of ductal carcinoma. To our knowledge, this is the first reported case of E-cadherin-negative small cell carcinoma of the breast, which raises the question of a possible lobular histogenesis in some of these neoplasms.

Topics: Biomarkers, Tumor; Breast Neoplasms; Cadherins; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Small Cell; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Middle Aged; Phosphopyruvate Hydratase; Proto-Oncogene Proteins c-bcl-2; Treatment Outcome

The mechanisms of invasive tumour development from pre-invasive CIS are unknown. We examined changes in functional parameters of the tubular wall according to the increase in CIS cells and tubular size. Immunohistochemistry was performed on 37 testicular specimens from 25 patients with carcinoma in situ and/or malignant germ cell tumour for the detection of actin/myosin in myocytes, and laminin/integrin alpha 6 in the basement membrane of seminiferous tubules. Tumour cells were detected by PlAP, Sertoli cells by inhibin alpha and vimentin and by cytokeratin 18/connexin 26 immunoreactivity, which is selectively expressed together with CIS. Areas showing clusters of tumour cells surrounded by a fibrous sheet could be identified as enlarged tubules because of focal Sertoli cell-specific co-expression of inhibin alpha, vimentin, cytokeratin 18, and connexin 26 immunoreaction. These clusters exhibited an intact basement membrane shown by a persistent laminin/integrin alpha 6 immunoreactivity, but myocytes had lost their contractility indicated by the loss of myosin/actin immunoreactivity. They often showed septa originating from the fibrous sheet containing numerous capillaries. Focal areas of syncytiotrophoblastic cells within classical seminoma also expressing inhibin alpha, cytokeratin 18, and connexin 26 could be differentiated from single Sertoli cells within tumor cell clusters by typical hCG but absence of vimentin immunoreactivity. In contrast to the current concept of CIS cells passing the tubular wall, these data provide evidence for an additional theory, i.e. that the switch from pre-invasive CIS to invasive tumour takes place in situ by tubular enlargement due to tumour cell proliferation followed by Sertoli cell degeneration and conversion of the tubular wall into connective tissue.

Topics: Actins; Adult; Basement Membrane; Carcinoma in Situ; Cell Division; Chorionic Gonadotropin; Germinoma; Humans; Immunohistochemistry; Integrin alpha6; Keratins; Laminin; Male; Middle Aged; Seminiferous Tubules; Sertoli Cells; Testicular Neoplasms

Topics: Actins; Adult; Breast Neoplasms; Cadherins; Carcinoma in Situ; Carcinoma, Lobular; Female; Humans; Immunohistochemistry; Keratin-14; Keratins; Muscle, Smooth; Myoepithelioma; Neprilysin; S100 Proteins

We report a case of mucinous adenocarcinoma of the renal pelvis associated with bladder carcinoma in situ (CIS). Transitional cell carcinoma (TCC) of the renal pelvis and CIS were also observed adjacent to the adenocarcinoma. Immunohistochemical assessment of the pelvic adenocarcinoma revealed positive expressions for mucin, epithelial membrane antigen, cytokeratin 7, cytokeratin 19 and carcinoembryonal antigen, but not vimentin or chromogranin. Based on the histopathological examinations, the adenocarcinoma of the renal pelvis in the present case may have a similar biological nature to conventional TCC and probably originated by development of pre-existing TCC of the renal pelvis.

Topics: Adenocarcinoma, Mucinous; Aged; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Transitional Cell; Humans; Keratin-7; Keratins; Kidney Neoplasms; Kidney Pelvis; Male; Mucin-1; Mucins; Neoplasms, Multiple Primary; Urinary Bladder Neoplasms

Epithelial cancers are believed to originate from transformation of tissue stem cells. However, bone marrow-derived cells (BMDCs), which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy. We show that although acute injury, acute inflammation, or transient parietal cell loss within the stomach do not lead to BMDC recruitment, chronic infection of C57BL/6 mice with Helicobacter, a known carcinogen, induces repopulation of the stomach with BMDCs. Subsequently, these cells progress through metaplasia and dysplasia to intraepithelial cancer. These findings suggest that epithelial cancers can originate from marrow-derived sources and thus have broad implications for the multistep model of cancer progression.

Topics: Animals; Apoptosis; Bone Marrow Cells; Bone Marrow Transplantation; Carcinoma in Situ; Cell Differentiation; Cell Fusion; Disease Progression; Female; Gastric Mucosa; Gastritis; Helicobacter felis; Helicobacter Infections; Keratins; Male; Mesenchymal Stem Cells; Metaplasia; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mucins; Muscle Proteins; Parietal Cells, Gastric; Peptides; Phenotype; Stem Cells; Stomach Neoplasms; Trefoil Factor-2

We examined histologically the bile duct lesions from 53 patients with end-stage primary sclerosing cholangitis (PSC) and compared them with similar lesions found in 25 surgically excised carcinomas of the extrahepatic bile ducts not associated with PSC. Of the 53 cases of PSC, 50 bile ducts were obtained at liver transplantation, two common bile ducts were segmentally resected for almost complete obstruction, and the entire extrahepatic biliary tract of another case was obtained at autopsy. Twenty bile ducts from patients who died without evidence of biliary tract disease served as controls. A modest increase in the number of intramural glands (mild hyperplasia) was noted in 13 cases (24.5%) of PSC. A marked increase in the number of intramural glands (florid hyperplasia) was found in 14 cases (26.4%) of PSC. In one case of florid hyperplasia, there was perineural and intraneural invasion of benign hyperplastic glands, which still maintained their lobular pattern. All cases of florid hyperplasia of intramural glands were accompanied by extensive fibrosis and marked nerve proliferation. Three of 24 (12.5%) invasive adenocarcinomas of the extrahepatic bile ducts showed mild hyperplasia of intramural glands without excessive nerve proliferation. Four invasive adenocarcinomas and one in situ carcinoma of the extrahepatic bile ducts showed florid hyperplasia of intramural glands (16%). The hyperplastic intramural glands were p53 negative and had low proliferative activity as measured by the low MIB-1 labeling index. In contrast, both in situ and invasive carcinoma expressed p53 protein and had a high MIB-1 labeling index. Focal high-grade dysplasia was found in one case of PSC (1.8%) and a small invasive adenocarcinoma in another (1.8%). Hyperplasia of intramural glands of the extrahepatic bile ducts is a reactive process that lacks specificity and is part of the morphologic spectrum of end-stage PSC. The incidence of dysplasia in PSC is low. Small invasive adenocarcinomas may be incidentally found in end-stage PSC, and detecting their presence before liver transplantation may be impossible.

Topics: Adenocarcinoma; Adult; Aged; Bile Duct Neoplasms; Carcinoma in Situ; Cholangitis, Sclerosing; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging

In cultured neuroblastoma cells, hypoxia induces a dedifferentiated phenotype. We tested whether hypoxia-induced dedifferentiation also occurs in vivo in mammary ductal carcinoma in situ with its well-defined lesions and distinct areas of necrosis. Ductal carcinoma in situ cells surrounding the central necrosis have high hypoxia inducible factor-1alpha protein levels, down-regulated estrogen receptor-alpha, and increased expression of the epithelial breast stem cell marker cytokeratin 19; lose their polarization; and acquire an increased nucleus/cytoplasm ratio, hallmarks of poor architectural and cellular differentiation. The hypoxia-induced changes were confirmed in cultured breast cancer cells. We propose that hypoxia-induced dedifferentiation is a mechanism that promotes tumor progression in breast cancer.

Topics: Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Cell Differentiation; Cell Hypoxia; Down-Regulation; Estrogen Receptor alpha; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Keratins; Necrosis; Receptors, Estrogen; Transcription Factors; Tumor Cells, Cultured; Up-Regulation

Previous studies have shown that basal-type cytokeratins (CKs) can distinguish usual ductal hyperplasia (UDH) from the spectrum of atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Indeed, expression of these CKs is weak or absent in ADH, DCIS and LCIS. However, the diagnostic usefulness of D5/16B4 antibody (anti-CK5/6) has never been compared with that of 34betaE12 antibody (anti-CK1/5/10/14). We performed immunostaining of CK 5/6 and CK1/5/10/14 on 100 breast lesions, including UDH ( n=31), ADH ( n=5), DCIS ( n=54) and LCIS ( n=10). Abundant immunostaining was observed in all UDH using both antibodies. Four of five of the ADH cases showed less than 5% of CK5/6 stained cells, the remaining case showed 30% of labeled cells. With 34betaE12 antibody, three of five of the ADH cases showed less than 5% labeled cells, while two cases showed more than 30% of stained cells. None of the 54 DCIS or the 10 LCIS was labeled by D5/16B4, while a lack of 34betaE12 immunostaining was observed in only 15 of 54 DCIS and 2 of 10 LCIS. We confirmed that D5/16B4 antibody directed against CK5/6 is useful in distinguishing UDH from the spectrum of ADH/DCIS/LCIS. We also demonstrated that D5/16B4 is far a more specific marker than 34betaE12 antibody.

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cell Count; Female; Humans; Hyperplasia; Immunohistochemistry; Keratin-5; Keratins; Sensitivity and Specificity

Although the histopathologic differential diagnosis of pagetoid neoplasms is broad, unique histopathologic identifiers and clinical correlation can often identify the process. However, in the case of mammary Paget's disease (MPD) or extramammary Paget's disease (EPD) without an obvious underlying malignancy, distinction from pagetoid squamous cell carcinoma in situ (PSCCIS) can be challenging. Our goal was to better define the immunohistochemical staining patterns of these three entities in the hope of determining distinctive staining patterns.. We evaluated nine cases of PSCCIS, five cases of MPD, and 10 cases of EPD with the immunohistochemical antibodies CAM 5.2 and CK 5/6. In addition, only PSCCIS was stained with CK 7, as the staining patterns of CK 7 in MPD and EPD are well known from prior studies.. CAM 5.2 diffusely stained all cases of MPD and EPD and failed to stain any case of PSCCIS. Furthermore, CK 7 only focally stained two of the 10 cases of PSCCIS. CK 5/6 was difficult to interpret due to the high functional background staining of the normal keratinocytes in the epidermis.. Based on these results, our data supports the use of CAM 5.2 and CK 7 immunoperoxidase markers in differentiating between difficult cases of PSCCIS and MPD or EPD. An antibody panel consisting of S-100, CAM 5.2, and CK 7 will aid in the accurate diagnosis of almost all pagetoid neoplasms of the breast or genital skin.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Keratinocytes; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Skin Neoplasms

Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale.. Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by > or = 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability.. Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers.. Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation of a biologically more aggressive cell clone and the myoepithelial cell layer breakdown possibly associated with tumor progression or invasion.

Topics: Breast; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Collagen Type IV; Disease Progression; DNA Mutational Analysis; DNA, Neoplasm; Epithelial Cells; Female; Humans; Immunohistochemistry; Keratins; Laminin; Loss of Heterozygosity; Microsatellite Repeats; Muscle, Smooth; Neoplasm Invasiveness; Receptors, Estrogen

We have established a highly sensitive and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method to detect axillary lymph node metastases of breast cancer. Amplifying cytokeratin 19 (CK19) mRNA transcripts using real-time TaqMan PCR made it possible to quantify axillary metastatic burden. Metastases in 358 axillary lymph nodes obtained from 23 breast cancers of 22 patients were investigated by conventional haematoxylin and eosin (H&E) staining, immunohistochemical staining and quantitative RT-PCR assay. The detection rates of axillary lymph node metastasis using H&E staining, immunohistochemistry and RT-PCR assay were 4.5, 5.9 and 13.1%, respectively. RT-PCR assay was the most sensitive of these three methods for detecting lymph node metastases. Cytokeratin 19 mRNA expression values of both histologically and immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001), and those of histologically negative, but immunohistochemically positive lymph nodes were significantly higher than the values for lymph nodes judged to be negative by both histological and immunohistochemical methods (P<0.0001). Furthermore, metastatic rates of sentinel nodes were higher than the rates of nonsentinel lymph nodes as measured by all three methods. These results indicate that quantitative RT-PCR assay is a sensitive and reliable method for detecting lymph node metastasis. Furthermore, quantification of metastases in sentinel lymph nodes by quantitative RT-PCR assay may be useful to assess the entire axillary burden of breast cancer patients.

Topics: Adult; Aged; Axilla; Breast Neoplasms; Carcinoma in Situ; Cell Line, Tumor; DNA Primers; Female; Gene Amplification; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Sentinel Lymph Node Biopsy; Staining and Labeling

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Lobular; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Mucins; Nipples; Paget's Disease, Mammary

Although intratubular embryonal carcinoma has been described adjacent to invasive embryonal carcinoma, to our knowledge it has not been reported as an isolated finding. We present in this report the histologic and immunohistochemical findings of 2 cases of intratubular embryonal carcinoma. One case was exclusively intratubular embryonal carcinoma without an invasive component in the same testis. A malignant mixed germ cell tumor in the contralateral testis had been previously excised. The second case is predominantly composed of intratubular embryonal carcinoma adjacent to a malignant mixed germ cell tumor. In one case, the intratubular embryonal carcinoma was immunoreactive for CD30, AE1/AE3, cytokeratin 7 focally, and p53. It was negative for cytokeratin 20, p21, and alpha-fetoprotein. These findings are strongly supportive of the opinion that intratubular embryonal carcinoma is the precursor of invasive embryonal carcinoma.

Topics: Adult; Anion Exchange Protein 1, Erythrocyte; Antiporters; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Embryonal; Germinoma; Humans; Immunohistochemistry; Keratin-7; Keratins; Ki-1 Antigen; Male; Neoplasms, Multiple Primary; Precancerous Conditions; Testicular Neoplasms; Tumor Suppressor Protein p53

Breast biology and pathology are currently shaped by the two-cell concept that recognizes only glandular and myoepithelial cells. In the present study, we have visualized a previously unidentified cell population within the epithelial compartment of the breast, which displays the phenotypic characteristics of a committed stem cell. Immunofluorescence double labeling with digital image processing and Western blotting were applied to normal breast tissue as well as to noninvasive and invasive breast cancers using antibodies to basal cytokeratin 5 (Ck5), glandular cytokeratins 8/18 (Ck8/18/19), and smooth muscle alpha-actin (SMA) as markers for myoepithelial cells (SMA). A distinct population of cells was identified that expressed Ck5 in the absence of Ck8/18/19 or SMA. These cells differentiate toward glandular epithelial or myoepithelial Ck5-negative end cells passing through either Ck5/Ck8/18/19 or Ck5/SMA-positive intermediates. Our experiments clearly demonstrate a precursor or committed stem cell function of the Ck5-positive cell that is responsible for regeneration of the human adult breast epithelium. However, the observation that the vast majority of breast cancers display the glandular epithelial immunophenotype strongly suggests that the neoplastic cells derive from a late stage of the glandular epithelial differentiation pathway. The significance of this new cell biological model is that it might serve as a tool to unravel the regulatory mechanisms that govern regeneration and abnormal proliferation of breast epithelium at the cellular level.

Topics: Actins; Adult; Aged; Biomarkers; Blotting, Western; Breast; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Cell Lineage; Epithelial Cells; Female; Fluorescent Antibody Technique, Indirect; Humans; Image Processing, Computer-Assisted; Keratins; Lactation; Middle Aged; Muscle, Smooth; Stem Cells

p63, a homologue of the tumor suppressor gene p53, is expressed in embryonic, adult murine, and human basal squamous epithelium and encodes both transactivating and dominant negative transcript isoforms. Mouse embryos functionally deficient in p63 fail to replenish basal squamous epithelial cells, resulting in multiple defects that include absent genital squamous epithelium. This study investigated the expression of p63 in the human cervical transformation zone and early cervical neoplasia.. Tissue localization of p63 was determined by immunohistochemistry in a wide range of epithelia. A correlation was also made between p63 expression and squamous basal cell (keratin 14), endocervical columnar cell (mucicarmine), and cell-cycle specific (Ki-67) markers.. p63 expression by immunostaining delineated basal and parabasal cells of maturing ectocervical squamous mucosa, squamous metaplasia in the cervix, and basal and subcolumnar cells of the cervical transformation zone. In atrophic epithelia immunostaining for p63 was present in all cell strata. In early cervical neoplasia, p63 expression was inversely correlated with both squamous cell maturation and nonsquamous differentiation in CIN. This biomarker also identified basal cells in a subset of preinvasive cervical neoplasms with endocervical cell differentiation that were bcl-2 and keratin 14 negative.. In the lower female genital tract, p63 is preferentially expressed in immature cells of squamous lineage and is not linked to cell proliferation. The broader range of p63 expression relevant to keratin 14 and bcl-2 indicates that p63 may identify additional subsets of benign and neoplastic epithelial basal cells in the cervical transformation zone and may be useful in studying cell differentiation in the early stages of neoplastic change in this region.

Topics: Adenocarcinoma; Atrophy; Biomarkers, Tumor; Carcinoma in Situ; Cell Cycle; Cell Differentiation; Cervix Uteri; DNA-Binding Proteins; Epithelium; Female; Gene Expression; Genes, Tumor Suppressor; Humans; Keratin-14; Keratins; Ki-67 Antigen; Membrane Proteins; Phosphoproteins; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The term ocular surface squamous neoplasia (OSSN) encompasses conjunctival and corneal intraepithelial neoplasia through to invasive squamous cell carcinoma of the ocular surface. The disease is related to prolonged exposure to solar ultraviolet light and has been proposed as an acquired immune deficiency syndrome-associated tumor. To the authors' knowledge, very few reports describing the cytology of these lesions have been published.. Impression cytology (IC) samples collected from the eyes of patients with a range of ocular surface diseases were available for study. From these, 267 sets of impressions had subsequent histopathology that had been collected within 6 months of the IC, and which indicated the presence of OSSN. The IC from these cases was used to describe the cytomorphology of intraepithelial and invasive OSSN.. Within the intraepithelial group, keratinized dysplastic cells that often were accompanied by hyperkeratosis, syncytial-like groupings, and nonkeratinized dysplastic cells were described. Within the invasive group, cases with significant keratinization and an additional group of cases with little keratinization and sometimes also prominent macronucleoli were described. Keratinized cases were the most numerous in both the intraepithelial and invasive groups. A description also was given of a low number of cases with cytology and also subsequent histopathology indicating the presence of intraepithelial OSSN, in the absence of a clinically detectable lesion.. This detailed description of the cytomorphology of a high number of cases of OSSN with confirmation by histopathology should assist others with little experience of the cytology of these lesions to examine them with increased confidence. Cancer (Cancer Cytopathol)

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Conjunctival Neoplasms; Cornea; Cytodiagnosis; Eye Neoplasms; Humans; Keratins; Neoplasm Invasiveness

Sebaceous gland carcinoma usually arises from meibomian or Zeis glands deep within the eyelid, but it can rarely arise within the conjunctival epithelium without a deep component. We describe a woman with a history of chronic blepharoconjunctivitis unresponsive to topical medications. Examination disclosed confluent papillary hypertrophy of the upper palpebral conjunctiva and deposits of white flaky material. Tarsoconjunctival punch biopsy revealed intraepithelial sebaceous gland carcinoma. Management consisted of frozen section-controlled complete tumor excision with removal of the entire posterior lamella of the right upper eyelid, cryotherapy to the margins, and reconstruction. Histopathologic analysis confirmed primary sebaceous gland carcinoma localized to the conjunctival epithelium without involvement of underlying meibomian or Zeis glands or the caruncle. Patients with unexplained chronic unilateral blepharoconjunctivitis or papillary hypertrophy of the palpebral conjunctiva should be considered for biopsy to rule out neoplasia, even when there is no sign of an underlying eyelid mass.

Topics: Adult; Apolipoproteins; Apolipoproteins D; Biomarkers; Biomarkers, Tumor; Carcinoma in Situ; Carrier Proteins; Conjunctival Neoplasms; Female; Glycoproteins; Humans; Keratins; Membrane Transport Proteins; Mucin-1; Neoplasm Proteins; Sebaceous Gland Neoplasms

Pagetoid dyskeratosis is considered a selective keratinocytic response in which a small part of the normal population of keratinocytes is induced to proliferate. Pagetoid dyskeratosis has been found incidentally in the squamous epithelium of the skin in various locations and in the ectocervix in uterine prolapse. In cases in which these pale cells are conspicuous, there is a hazard of overdiagnosis. It has been suggested that friction is the most probable inductor of the lesion. To the best of our knowledge, pagetoid cells have not been reported in surgically resected hemorrhoids.. We here describe the location of pagetoid dyskeratosis in the squamous epithelium of hemorrhoids and the incidence of this lesion in a group of 100 unselected patients surgically treated for hemorrhoidal disease. In addition to the conventional histologic method, special staining procedures and an immunohistochemical study of cytokeratins were performed in selected cases.. Pagetoid dyskeratosis was found in 68 cases (68%) and was a prominent finding in 22 cases (22%). The cells of pagetoid dyskeratosis were strongly positive for high-molecular weight cytokeratin. These cells showed an immunohistochemical profile that was different from that of the surrounding squamous cells and indicative of premature keratinization.. In hemorrhoidal disease, the cushions are susceptible to trauma as a result of prolapse. In this setting, friction may be the stimulus for the appearance of pagetoid dyskeratotic cells. These cells must be distinguished from the artifactual clear cells of the squamous epithelium, glycogen-rich cells, and koilocytes. The lesion must also be distinguished from extramammary Paget disease, pagetoid spread of carcinoma cells, pagetoid Bowen disease, and pagetoid melanoma. Pathologists should be familiar with the histologic features of pagetoid dyskeratosis in hemorrhoidectomy specimens to avoid misdiagnosis. Routine histologic study is usually adequate for recognizing this lesion.

Topics: Adult; Aged; Anus Neoplasms; Carcinoma in Situ; Coloring Agents; Diagnosis, Differential; Epithelium; Female; Hemorrhoids; Histocytochemistry; Humans; Keratinocytes; Keratins; Male; Middle Aged; Paget Disease, Extramammary

Seventeen examples of a variant of ductal carcinoma in situ (DCIS) composed exclusively or predominantly of spindle cells arranged in fascicles, whorls, and solid sheets are described. The fascicular arrangement of the spindle cells simulates the "streaming" phenomenon associated with ordinary intraductal epithelial hyperplasia (IDH). This process also resembles the myoid, solid form of intraductal myoepithelial proliferation. The women ranged in age from 38 years to 79 years with a mean age of 59.3 years. Five patients presented with a palpable mass. The remaining tumors were discovered using mammography. The radiological appearances of the lesions raised concern for carcinoma, but there were no distinctive mammographic findings to suggest an unusual variant of DCIS. Cytological preparations were suspicious for malignancy in two patients and were reported as malignant in another case. Sixteen patients were treated with wide local excision, and one woman had a partial mastectomy. The tumors measured from 3 mm to 15 mm (mean 8.65 mm). In three cases, minute foci of stromal invasion were associated with the spindle cell DCIS. In another specimen, a 2.7-cm invasive ductal carcinoma of no special type was identified in an area away from the foci of the spindle cell DCIS. None of the patients has experienced recurrence or metastasis during the relatively short mean follow-up period of 16.2 months (range 4-77 months). Spindle cell DCIS is distinguished from the streaming pattern of ordinary IDH by its solid growth pattern, lack of secondary spaces or peripheral fenestrations, uniformity of appearance and distribution of nuclei, cytological atypia in the range of low to intermediate-grade DCIS, and negative immunoreaction with CK-34betaE12 (HMW-CK903). When fenestrations are present, they are evident in areas of cribriform DCIS that merge with the solid, spindle cell areas in hybrid ducts harboring both patterns. This admixture, with conventional cribriform DCIS, and the association with foci of invasive ductal carcinoma in some cases further help recognition and confirmation of this lesion as in situ carcinoma. When there is no transition from the spindle cells to recognizable cribriform DCIS, distinction from intraductal myoepithelial hyperplasia (myoepitheliosis) requires immunostains for actin and S-100 protein. Recognition of this pattern of DCIS is important in order to avoid its frequent misclassification as a benign lesion.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Cell Division; Diagnosis, Differential; Endothelium; Female; Follow-Up Studies; Humans; Hyperplasia; Immunohistochemistry; Keratins; Mammography; Middle Aged; Treatment Outcome

Cancer presumably arises from stem cells, preserved in an undifferentiated status since fetal development, or from a dedifferentiation of mature cells that return into a fetal phenotype with the potential for proliferation and renewal. Dedifferentiation in this context could represent a transient phase, passed through by cells, before they switch to redifferentiation, metaplasia or neoplasia. Cytokeratin-7 (CK7) is present in fetal, largely absent in normal adult, and transiently neoexpressed in metaplastic and neoplastic epithelial cells of the stomach according to previous observations. CK7 neoexpression in the stomach could, hence, define a fetal-like, dedifferentiated, cellular phenotype during the development of metaplasia and neoplasia. To test this hypothesis, we investigated CK7 expressions in fetal stomachs, non-neoplastic control stomachs, and neoplastic stomachs exhibiting metaplasia, intraepithelial neoplasia, and early cancer. Proliferation and beta-catenin expression of CK7-positive cells were also evaluated. The chronology of CK7 expression was studied during the experimental gastritis-cancer sequence in Mongolian gerbils. Our results show that metaplastic and neoplastic changes in the gastritis-cancer sequence are related to dedifferentiated epithelial cells which are defined by CK7 expression and can phenotypically be linked to fetal cells at the start of gastric pit development. The dedifferentiated cells exhibit a low proliferation and beta-catenin accumulation, similar to stem cells. Thus, the "stem cell" and "dedifferentiation" hypotheses for cancer origin could complement one another, and dedifferentiation-redifferentiation processes might be decisive for carcinogenesis in the stomach.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Carcinoma in Situ; Cell Transformation, Neoplastic; Child; Disease Models, Animal; Epithelial Cells; Female; Fetus; Gastric Mucosa; Gastritis; Gerbillinae; Gestational Age; Helicobacter Infections; Helicobacter pylori; Humans; Keratin-7; Keratins; Male; Metaplasia; Middle Aged; Stomach; Stomach Neoplasms

Various molecular markers have been used for the detection of circulating breast cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). Using nested RT-PCR, we compared the specificity and sensitivity of human mammaglobin (hMAM), epidermal-growth-factor receptor (EGF-R), and cytokeratin 19 (CK-19) expression as markers for circulating carcinoma cells in the peripheral blood of patients with breast cancer. Blood samples from 12 patients with ductal carcinoma in situ, 133 patients with invasive breast cancer, 20 patients with hematological malignancies, 31 healthy volunteers, and tumor tissues from 40 patients with invasive breast cancer were screened for mRNA encoding hMAM, EGF-R, or CK-19 by nested RT-PCR. In all breast cancer tissues, mRNA for hMAM, EGF-R, and CK-19 was detectable. In blood samples from patients with invasive breast cancer, 11 (8%), 13 (10%), and 64 (48%) were positive for mRNA encoding hMAM, EGF-R, or CK-19, respectively. Blood samples from none of the healthy volunteers and patients with hematological disorders were positive for hMAM, while CK-19 mRNA was found in the blood of 12 (39%) healthy volunteers and transcripts for EGF-R and CK-19 were detectable in 5 (25%) and 2 (10%), respectively, of the patients with hematological malignancies. Only hMAM mRNA expression in blood correlated with clinical parameters such as nodal status, metastasis, and CA 15-3 serum levels. In summary, hMAM transcripts detectable in blood by RT-PCR represent the most specific molecular marker for hematogenous spread of breast cancer cells. With the nested RT-PCR method, aberrant EGF-R mRNA expression might occasionally be found in hematological malignancies, whereas CK-19 mRNA expression proved to be rather nonspecific. The prognostic value of hMAM RT-PCR-based tumor cell detection in peripheral blood should be further tested and validated in prospective studies.

Topics: Adult; Aged; Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; ErbB Receptors; Female; Gene Expression; Hematologic Neoplasms; Humans; Keratins; Mammaglobin A; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins; Tumor Cells, Cultured; Uteroglobin

Topics: Biopsy, Needle; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; False Positive Reactions; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Seeding

This study was performed to determine the diagnostic value of keratin 5/6 (CK 5/6) immunophenotyping on routinely processed breast tissues.. Six hundred and ninety-nine breast lesions, including normal tissues as well as benign and malignant lesions in 321 formalin-fixed, paraffin-embedded samples from 158 different patients were investigated immunohistochemically, following wet autoclave pre-treatment for antigen retrieval. In normal breast tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in varying amounts. While myoepithelial immunoreactivity was most pronounced in the duct system, luminal epithelial immunoreactivity was strongest in the terminal duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an expression, whereas in ductal in-situ carcinomas (DCIS) and in infiltrating ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive immunostaining for CK 5/6.. Immunophenotyping of keratin 5/6 expression can be helpful in the diagnosis of atypical hyperplasias and in-situ carcinomas of the breast. It is particularly valuable in the differential diagnosis between benign and atypical proliferative lesions.

Topics: Breast; Breast Neoplasms; Carcinoma in Situ; Cell Division; Diagnosis, Differential; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; Neoplasm Invasiveness

Transitional cell carcinoma (TCC), a neoplasm of urinary bladder urothelial cells, generally appears in either of two forms, papillary non-invasive or invasive TCC, although intermediate forms can occur. Each has a distinctive morphology and clinical course. Altered expression of the p53 and pRb genes has been associated with the more serious invasive TCC, suggesting that the loss of activity of these tumor suppressor proteins may have a causal role in this disease. To test this hypothesis directly, transgenic mice were developed that expressed the simian virus 40 large T antigen (TAg) in urothelial cells under the control of the cytokeratin 19 gene (CK19) regulatory elements. In one CK19-TAg lineage, all transgenic mice developed highly invasive bladder neoplasms that resembled invasive human bladder TCCs. Stages of disease progression included development of carcinoma in situ, stromal invasion, muscle invasion, rapid growth, and, in 20% of affected mice, intravascular lung metastasis. Papillary lesions never were observed. Western blot analysis indicated that TAg was bound to both p53 and pRb, which has been shown to cause inactivation of these proteins. Our findings support suggestions that (i) inactivation of p53 and/or pRb constitutes a causal step in the etiology of invasive TCC, (ii) papillary and invasive TCC may have different molecular causes, and (iii) carcinoma in situ can represent an early stage in the progression to invasive TCC.

Topics: Alkaline Phosphatase; Animals; Antigens, Polyomavirus Transforming; Blotting, Western; Carcinoma in Situ; Carcinoma, Transitional Cell; Cell Lineage; Disease Models, Animal; Disease Progression; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Mice; Mice, Transgenic; Neoplasm Invasiveness; Neoplasm Transplantation; Precancerous Conditions; Retinoblastoma Protein; Transplantation, Heterologous; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Lobular; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen

Keratinization of the ocular surface epithelium is associated with various disorders impairing vision. We immunohistochemically determined whether the ocular surface epithelia express involucrin, and whether its expression pattern may differ in benign vs. malignant disorders. Expression of cytokeratins was also examined to provide further information relative to the epithelial differentiation.. We evaluated 17 specimens; 6 specimens of the normal ocular surface epithelia, 3 specimens from cases of conjunctival intraepithelial neoplasia (CIN), 6 of conjunctival squamous cell carcinoma (SCC) and 2 of conjunctivae from cases of superior limbic keratoconjunctivitis (SLK).. Corneal epithelium exhibited intracellular immunoreactivity for involucrin. Four of the 6 specimens of bulbar conjunctival epithelium showed involucrin immunoreactivity in the perimembranous region, whereas the fornical conjunctiva was negative. Cornified envelope in SLK specimens was positive for involucrin. The CIN showed its immunoreactivity in the perimembranous region in all levels of the hyperproliferative epithelium without keratinization, i.e., similar to the bulbar conjunctiva. The neoplastic cells of well-differentiated SCC showed involucrin in the perimembranous region, and those of moderately- to poorly-differentiated SCC have involucrin in their cytoplasm. The expression pattern of cytokeratins was unrelated to grade of malignancy in ocular SCC.. The epithelia of normal subjects and of CIN expresses involucrin without keratinization. In contrary, the keratinized SLK epithelium markedly expresses involucrin in the cornified envelope. The subcellular immunolocalization of involucrin in the ocular SCC may help in evaluating the differentiation, i.e., malignancy, of neoplastic cells.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Squamous Cell; Conjunctiva; Conjunctival Diseases; Conjunctival Neoplasms; Epithelium; Eye Proteins; Female; Filaggrin Proteins; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Keratoconjunctivitis; Male; Middle Aged; Protein Precursors

Histopathological identification of invasive breast carcinoma in its earliest phases is fraught with pitfalls. Preinvasive malignant lesions complicated by radial scar, sclerosing adenosis, and lobular cancerization, among other lesions, may simulate invasive carcinoma. Fibrosis, inflammatory reaction, and other stromal changes around in situ carcinoma may mask microinvasive foci on routine stains. Conventional immunohistochemistry to demonstrate basement membrane or myoepithelial cell layer may not, by itself, be unequivocally diagnostic of invasion. We performed a novel double immunoenzyme labeling technique using an avidin-biotin complex peroxidase-diaminobenzidine system for smooth-muscle actin followed by an alkaline phosphatase anti-alkaline phosphatase-new fuchsin system for cytokeratin antigen on formalin-fixed, paraffin-embedded histology sections to evaluate 32 such problematic cases. The initial histologic impression with hematoxylin and eosin staining alone was as follows-first group: microinvasive carcinoma-10; second group: carcinoma in situ--"stromal invasion cannot be ruled out"--15; third group: frankly infiltrating carcinoma of various grades and morphologic types-6. The last group served as positive control for invasion. One fibroadenoma with fine-needle-aspiration-induced artifact simulating stromal invasion was also included. The double immunoenzyme labeling technique imparted a dark brown color to the myoepithelial cells and a vivid red color to the epithelial cells, making individual or loosely cohesive groups of malignant epithelial cells infiltrating the stroma easily detectable, whereas their in situ counterparts were contained within dark brown myoepithelial boundaries. The TNM 1997 definition of pT1mic, i.e., extension of malignant cells in the stroma with no focus measuring >0.1 cm, was followed to classify microinvasion. In the first group, microinvasion was confirmed in six cases but was not demonstrable in four. In the second group, definite invasion was identified in five cases, ruled out in nine, and in one case the suspicion of early invasion could not be entirely ruled out even after double immunoenzyme labeling. Thus, it was possible to render a definite opinion regarding presence or absence of invasion in 24 of 25 (96%) cases diagnosed as or suspected to be microinvasive. The precise and simultaneous elucidation of topography between malignant cells and myoepithelial cells on a single permanent section makes this tech

Topics: Actins; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Invasiveness; Sclerosis

The dysplastic corneal epithelium is characterized by the abnormal proliferation of epithelial cells. The phenotypes of these cells have not been elucidated. We investigated whether such epithelium expresses the phenotypes of corneal or conjunctival epithelial cells.. The corneas and conjunctivae from four normal subjects and from one patient with epithelial dysplasia of the central cornea were immunostained for IV and VII collagens and for cytokeratins. Monoclonal antibodies against collagen IV reacted to the [alpha1(IV)]2alpha2(IV) or alpha5(IV) molecule. Anti-cytokeratin antibodies were used to define epithelial cell types. The ultrastructure of the basement membrane (BM) of each specimen also was examined.. Type VII collagen immunoreactivity was detected in all the specimens of epithelial BM. The anti-collagen IV [alpha1(IV)]2alpha2(IV) antibody labeled the conjunctival BMs, not the BMs of the corneal epithelia, of each subject. The normal corneal epithelial BM, not the BM of the conjunctival or dysplastic corneal epithelium, was immunolabeled with anti-alpha5(IV) antibody. The pattern of cytokeratin expression in the corneal epithelial dysplasia resembled that seen in the normal conjunctivae. Small breaks in the BM of dysplastic corneal epithelium were ultrastructurally revealed. The number of hemidesmosomes in the dysplastic corneal epithelium was decreased as compared with that in the normal BM.. The composition of collagen types within the BM and the cellular phenotype of the dysplastic epithelium in the cornea resembled those of conjunctival epithelium, not of the cornea.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Basement Membrane; Carcinoma in Situ; Collagen; Conjunctiva; Corneal Diseases; Epithelium, Corneal; Extracellular Matrix; Eye Neoplasms; Female; Humans; Immunoenzyme Techniques; Keratins; Laminin; Male; Middle Aged

To determine the rate of diagnostic uncertainty in rendering diagnoses on prostate needle biopsies and to examine pathology practice variables that influence that rate.. Anatomic pathology departments participating in the College of American Pathologists Q-Probes laboratory quality improvement program retrospectively reviewed their last 50 consecutive prostate needle biopsy diagnoses. For each diagnosis, participants provided information concerning patients' prostate-specific antigen levels; number, locations, and laterality of biopsy specimens; number of tissue levels examined; performance of high-molecular-weight cytokeratin immunoperoxidase staining; and acquisition of consultations from general pathologists or experts in prostate pathology. Characteristics of pathology practices included yearly surgical and prostate needle biopsy caseloads, number of pathologists rendering biopsy diagnoses, use of standard descriptive checklists, access to patients' prostate-specific antigen and digital rectal examination results, percentages of prostate needle biopsies routinely submitted for internal consultations, and presence of departmental experts in prostate pathology.. Three hundred thirty-two public and private institutions located in the United States (n = 318), Canada (n = 6), Australia (n = 5), United Kingdom (n = 2), and Guam (n = 1).. The rate of diagnostic uncertainty in prostate needle biopsy diagnoses.. Participants submitted diagnoses on a total of 15 753 prostate needle biopsy cases, of which 33.4% were adenocarcinoma; 55.5% were benign; 3.9% were carcinoma in situ, prostatic intraepithelial neoplasia, or both; and 7.1% were diagnostically uncertain. The median rate of diagnostic uncertainty was 6%, ranging from 0 at the 10th percentile to 14% at the 90th percentile of all participating laboratories. Performing high-molecular-weight cytokeratin immunoperoxidase staining resolved diagnostic uncertainty in 68% of cases in which it was performed, and obtaining intradepartmental and extradepartmental consultations resolved diagnostic uncertainty in 70% to 87% of cases for which they were obtained. Knowledge of patients' prostate-specific antigen results and examining multiple biopsy cores had marginal effects on the rate of uncertainty. Thoroughness of prostate gland sampling and examination of multiple tissue block levels were not associated with the aggregate rate of diagnostic uncertainty. We found no particular pathology departmental practices or institutional demographic characteristics associated with institutional rates of diagnostic uncertainty.. Use of high-molecular-weight cytokeratin immunoperoxidase staining and obtaining intradepartmental and extradepartmental consultations may be effective in reducing diagnostic uncertainty in prostate biopsies.

Topics: Adenocarcinoma; Biopsy, Needle; Carcinoma in Situ; Humans; Immunoenzyme Techniques; Keratins; Male; Palpation; Pathology; Prostate-Specific Antigen; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Quality Control; Rectum; Sensitivity and Specificity

A variety of studies have investigated the role of low molecular weight (LMW) and high molecular weight (HMW) cytokeratin (CK) expression in the normal breast and invasive breast carcinomas. A few studies with small numbers of cases have addressed this issue in intraductal proliferations of the breast. This study investigates the expression of these CKs in a large series of ductal intraepithelial neoplasias of the breast. We examined 150 ductal carcinomas in situ (DCIS), 35 cases of intraductal hyperplasia (IDH), and 15 cases of atypical intraductal hyperplasia (AIDH). Immunohistochemistry was performed using monoclonal antibodies against CK-34betaE12 (HMW CK), CK-8, and CK-19 (LMW CK) on formalin-fixed, paraffin-embedded tissue. The intensity (0, +1, +2, +3) and percentage of positive intraductal cells (0-100%) were multiplied to obtain a score from 0 to 300. The immunoprofiles of IDH, AIDH, and DCIS were categorized into four groups showing negative or low (0-60), moderate (61-100), high (101-200), and very high (201-300) scores. All cases of IDH showed an intensely positive reaction (high to very high scores) for CK-34betaE12. In contrast, 90% of the DCIS showed a negative or only focal and weak reaction (negative or low score) for this antigen. The remaining 10% of DCIS showed a positive immunoreaction for CK-34betaE12 with moderate to high scores. All cases of florid IDH and 96% of cases of DCIS expressed CK-8 intensely with high to very high scores. Although CK-19 was strongly expressed in 97% of cases of IDH (high to very high scores), a very high score was also found in 80% of cases of DCIS that were positive for CK-19. Of the 15 AIDHs, 80% had a negative or only focal reaction (negative or low score) for CK-34betaE12 and the remaining 20% had a moderate to high score for this antigen. Although CK-8 was strongly positive in 87% of cases of AIDH (high to very high scores), only 53.5% of AIDHs showed intense positivity for CK-19. The present study clearly shows that the immunoprofile of IDH is different from DCIS as far as HMW CK is concerned. Although florid IDH is characterized by a diffuse and intense immunoreaction for HMW CK, the lack of or only weak positivity for HMW CK (CK-34betaE12) is, in most cases, a hallmark of ductal carcinoma in situ. The immunoprofile of AIDH is very similar to that of DCIS. The expression of CK-8 and CK-19 is not useful in separating the various categories of ductal intraepithelial proliferations of the breast. We r

Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Cell Division; Female; Humans; Immunohistochemistry; Keratins

Nephrogenic Adenoma (NA) is a rare lesion of the urinary tract, considered a metaplastic response to chronic inflammation, trauma or immunosuppression.. We report two cases of NA arising in the urinary bladder of patients with previous history of recurrent urinary tract infections due to neuropsychiatric disease. Pathological examination of the lesions, resected by transurethral (TUR) management, revealed a papillary proliferation of tubules and cysts lined by cuboidal to low-columnar cells without atypia. Immunohistochemistry showed positivity for Cam 5.2, CK7 and EMA. MIB 1 count demonstrated a positivity in 12/200 cells in case 1 and < 2/200 in case 2. No expression of nuclear p53 was evident.. NA is a benign unusual neoplasm which might be misdiagnosed as clear cell adenocarcinoma of the bladder or prostatic adenocarcinoma. Its recognition is important because it is a benign lesion cured by a conservative resection and no additional therapy is generally required.

Topics: Adenocarcinoma; Adenocarcinoma, Clear Cell; Adenoma; Antigens, Nuclear; Biomarkers, Tumor; Calbindin 2; Carcinoma in Situ; Carcinoma, Transitional Cell; Diagnosis, Differential; Epithelial Cells; Female; Humans; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Metaplasia; Middle Aged; Mucin-1; Neoplasm Proteins; Neoplasms, Multiple Primary; Nuclear Proteins; Prostatic Neoplasms; Protein Isoforms; S100 Calcium Binding Protein G; Urinary Bladder Neoplasms

The histogenesis of mammary Paget's disease is controversial. The purpose of this study was to investigate the mechanism of tumour spread in the nipple epidermis by examining 28 cases of mammary Paget's disease associated with underlying intraductal carcinoma.. The atypical cells in the epidermis displayed a spectrum of cytological changes ranging from small-sized atypical cells located in the basal cell layer to large-sized atypical cells characteristic of Paget's cells in the upper layer of the epidermis. Serial sectioning revealed the presence of isolated, scattered and small atypical cells in the basal cell layer at the periphery of the epidermal lesion. The atypical cells, including those in the basal cell layer showed positive immunostaining for cytokeratin 7 and Her2/neu oncoprotein. Electron microscopy examination demonstrated the presence of intercellular junctions of desmosomal-like or desmosomal types between tumour cells and adjacent squamous cells. Furthermore, examination of the intraductal carcinoma of the breast tissue in cases of Paget's disease as well as control cases of intraductal carcinoma also revealed areas of skip lesions of intraductal carcinoma.. In view of these changes, it is unlikely that tumour expansion or tumour cell motility are sufficient explanations to account for the pattern of tumour spread in both the epidermis and the duct epithelium with skip lesions. A 'field effect' in the duct system harbouring intraductal carcinoma and the adjacent epidermis may play an important role in the tumour cell spread in the epidermis as well as in the ductal epithelium.

Topics: Breast Neoplasms; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Epidermis; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasm Invasiveness; Nipples; Paget's Disease, Mammary; Receptor, ErbB-2

Two cell lines derived from vaginal intraepithelial neoplasias (VAINs) expressing human papillomavirus (HPV) 33 (VAIN I, UT-DEC-1) and 16 (VAIN II, UT-DEC-2) E6-E7 mRNA were studied in organotypic culture for their keratins and cell cycle regulatory proteins in relation to replicative aging. Early-passage UT-DEC-1 and UT-DEC-2 cells reproduced epithelial patterns consistent with VAIN. Cells from later passages resembled full-thickness intraepithelial neoplasia (UT-DEC-1) and microinvasive cancer (UT-DEC-2). The morphological changes were compatible with these cell lines' ability for anchorage-independent growth at later passages. Simple epithelial keratins were aberrantly expressed in both cell lines. K18 (absent in normal vaginal keratinocytes) and K17 expression increased in UT-DEC-1 and UT-DEC-2 cells at late passages. No marked differences in expression of p53 (wild type in both cell lines), mdm-2 or PCNA were detected in parallel with progression. The expression of p21WAF1/cip1 localized mostly to the upper half of the epithelium at early passage and was more intense in the HPV 16-positive UT-DEC-2 cell line expressing K10. In Northern blot analyses, the transcription pattern of the HPV 33 E6-E7 of the UT-DEC-1 cell line changed during later passages, whereas that of the HPV 16 E6-E7 of the UT-DEC-2 cell line remained unaltered. The present characterization of the phenotype of these cell lines derived from natural squamous intraepithelial lesions shows an association between simple epithelial-type keratin expression and progressive changes in growth and morphology, but fails to demonstrate consistent changes in the expression of cell cycle regulatory proteins studied in parallel with progression.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Adhesion; Cell Culture Techniques; Cell Cycle Proteins; Cellular Senescence; Disease Progression; Epithelial Cells; Female; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Keratins; Neoplasm Proteins; Papillomaviridae; Papillomavirus Infections; Phenotype; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; RNA, Messenger; RNA, Neoplasm; Tumor Cells, Cultured; Tumor Virus Infections; Vagina

Six hundred and ninety-three Chinese patients with non-metastatic nasopharyngeal carcinoma (NPC) were treated at one institution under a uniform protocol between 1984 and 1989. The tumour histology of these patients was subjected to a standardized review and classified into two distinct groups of World Health Organization (WHO) type I (keratinizing squamous cell carcinoma) (n = 13) or WHO types II and III (non-keratinizing carcinoma and undifferentiated carcinoma) (n = 662). The differentiation between the two groups was uncertain in 18 patients. The patient characteristics and clinical outcome after a uniform treatment policy of the two groups were not statistically significantly different. The low incidence of WHO type I NPC may account for the lack of prognostic significance of this histological subtype in Chinese populations.

Topics: Actuarial Analysis; Biopsy; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Confidence Intervals; Disease-Free Survival; Female; Humans; Incidence; Iridium Radioisotopes; Keratins; Male; Middle Aged; Nasopharyngeal Neoplasms; Neoplasm Recurrence, Local; Odds Ratio; Prognosis; Proportional Hazards Models; Radiopharmaceuticals; Radiotherapy Dosage; Survival Rate; Treatment Outcome; World Health Organization

The presence of specific keratins can be of diagnostic value for studying normal and neoplastic epithelium of the vulva. The aim of the present study was to investigate normal, preneoplastic and neoplastic epithelium of the vulva. Keratins 5, 6 and 18, identified by a polyspecific anti-human CK antibody (clone LP 34, DAKO), and the keratin subtypes 7, 10, 14, 18, 19 and 20 of normal, dysplastic and malignant vulval epithelium (paraffin-embedded sections) were detected by immunohistochemical APAAP staining. Keratins 5, 6, and 18 (clone LP 34) and keratin subtype 10 are expressed in the upper third of the normal vulval epithelium. In mild and moderate intraepithelial neoplasia only a few cells express these keratins. In patients with severe intraepithelial neoplasia (VIN III) the expression of these keratins seems to be associated with recurrence of the disease. In biopsy specimens of patients without recurrence we find positive results for keratins 5, 6 and 18 (clone LP 34) and keratin 10. If patients have a recurrence of the disease, expression of these keratins is only diffuse or is absent. The expression of these keratin subtypes in vulval carcinomas is mostly seen in differentiated cells. There was no association between recurrence and keratin pattern. We have not found any other expression of the tested keratin subtypes in VIN and in vulval carcinoma.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma in Situ; Cell Transformation, Neoplastic; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Recurrence, Local; Precancerous Conditions; Prognosis; Vulva; Vulvar Neoplasms

We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes.. 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells.. All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only.. Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.

Topics: Adolescent; Adult; Carcinoma in Situ; Cell Differentiation; Humans; Keratins; Male; Middle Aged; Sertoli Cells; Testicular Neoplasms

In Western countries, esophageal squamous cell carcinoma is usually advanced at presentation and is rarely diagnosed in situ. The authors studied an in situ squamous cell carcinoma that occupied the entire mucosa of a 9 cm length of esophagus, causing dysphagia for solid food in a woman aged 68 years.. The esophagectomy specimen contained a circumferential region of depressed tan mucosa in the middle and lower thirds, bordered above and below by normal squamous mucosa, without ulcer, stricture, or mass. The entire lesion was submitted for histology and evaluated with immunostains for cytokeratins and markers of Paget's cells, p53 mutation, and proliferation.. The lesion involved 45 cm2 of mucosa. Large, atypical cells with frequent mitoses occupied the basal layers of the squamous epithelium and were often separated from more superficial maturing cells by acantholysis. Pagetoid spread of tumor cells into nonneoplastic surface and gland duct epithelium was prominent. The tumor cells expressed cytokeratins of low molecular weight, p53 gene product, and proliferating cell nuclear antigen (PCNA), but lacked markers usually seen in Paget's cells in the breast or vulva. No invasion was evident.. This extensive in situ squamous cell carcinoma of the esophagus resulted from pagetoid spread of tumor cells. These cells had a phenotype suggestive of origin from primitive epidermal stem cells and also had overexpressed p53 and PCNA, but they lacked the capacity to penetrate the basement membrane. Flat, erythematous areas of esophageal mucosa seen during endoscopy could represent early squamous cell carcinoma and should be biopsied.

Topics: Aged; Basement Membrane; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Division; Deglutition Disorders; Epithelium; Esophageal Neoplasms; Esophagectomy; Female; Gene Expression Regulation, Neoplastic; Genes, p53; Humans; Keratins; Mitosis; Mucous Membrane; Mutation; Paget Disease, Extramammary; Phenotype; Proliferating Cell Nuclear Antigen; Tumor Suppressor Protein p53

Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract.. In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus.. Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found.. BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.

Topics: Actins; Adult; Age Factors; Aged; Aged, 80 and over; Antigens, Differentiation; Apoptosis; Carcinoma in Situ; Carcinoma, Basosquamous; Carcinoma, Squamous Cell; Cell Differentiation; Cell Division; Diagnosis, Differential; Epithelium; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Mucous Membrane; Necrosis; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; S100 Proteins; Sex Factors; Survival Rate

Two histopathologic lesions are considered putative precursors of prostate cancer, but the supportive evidence for one (prostatic intraepithelial neoplasia, or PIN) is much greater than the other (atypical adenomatous hyperplasia, or AAH). High grade PIN is the most likely precursor of carcinoma, arising in the peripheral zone, but probably does not account for well-differentiated cancer arising in the transition zone. The biological significance of atypical adenomatous hyperplasia of the prostate (AAH) is inconclusive at the time. The histological and cytological features of AAH are intermediate between BPH and low grade carcinoma, suggesting that AAH may be a precursor of well differentiated transition; zone carcinoma. In the recent time new findings on morphogenetic aspects of normal and abnormal prostatic growth i.e. stem cell models are discussed and topics about grading and proliferative activities, frequency and histological changes associated with aging as well as clinical relevance of PIN and AAH. This paper reviews the results and discussion at the second international consultation meeting on PIN in Mayo Clinic, Rochester, Nov. 3-4 th. 1995, following the first international consultation meeting of AAH and PIN and origin of the prostatic carcinoma in Ancona, Sept. 11-12 th 1994.

Topics: Adenocarcinoma; Adult; Aged; Apoptosis; Biopsy; Carcinoma in Situ; Cell Differentiation; Cell Division; Cell Nucleus; Humans; Incidence; Keratins; Male; Middle Aged; Nucleolus Organizer Region; Prostatic Hyperplasia; Prostatic Neoplasms

The increased glucose uptake seen in cancer cells correlates with the expression of human erythrocyte glucose transporter (Glut1) protein in certain human malignancies.. Our purpose was to determine Glut1 expression in cutaneous neoplasms.. A polyclonal anti-Glut1 antibody (MYM) and a standard ABC immunoperoxidase technique were used to determine Glut1 expression in invasive squamous cell carcinomas (SCCs), SCC in situ, basal cell carcinomas (BCCs), melanomas, actinic keratoses (AKs), seborrheic keratoses, common acquired nevi, and scars with regenerative epidermal hyperplasia.. All of the cases of SCC in situ, 14 of 15 (93%) of the SCC, and 13 of 15 AKs (87%) showed intense membranous staining for Glut1. Glut1 staining was present in the epidermis of 8 of 15 scars (53%) but was not detected in any BCC, even in areas of focal keratinization and squamous metaplasia. Glut1 reactivity was absent in the melanomas and seborrheic keratoses.. Glut1 expression in a cutaneous lesion strongly suggests a proliferative lesion of the squamous cell type.

Topics: Antibodies; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Division; Cicatrix; Dermatitis, Seborrheic; Epidermis; Epithelial Cells; Gene Expression Regulation, Neoplastic; Glucose; Glucose Transporter Type 1; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Keratosis; Melanoma; Monosaccharide Transport Proteins; Neoplasm Invasiveness; Nevus; Regeneration; Skin Neoplasms

A 55-year-old woman, who was found to have malignant squamous cells on a routine cervical smear, underwent a conization biopsy, followed by hysterectomy with bilateral salpingo-oophorectomy. No gross tumor was present in the uterus, but both ovaries, which were of normal size, contained multiple cysts filled with light brown, soft material. Microscopic examination showed squamous cell carcinoma in situ of the cervix with contiguous spread to the endometrium, fallopian tubes, and ovaries; squamous cell carcinoma extensively replaced the endometrial and tubal epithelium, focally invaded the wall of the fallopian tubes, and involved the parenchyma of both ovaries. Although an invasive cervical carcinoma occasionally spreads to the ovary, this case illustrates that exceptionally an in situ tumor spreads along the epithelium of the upper genital tract and the ovarian surface and invades the ovary and tubes. The detection of human papillomavirus DNA in the cervical, endometrial, tubal, and ovarian tumors by the polymerase chain reaction suggests a role for human papilloma virus infection in this case.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Endometrial Neoplasms; Fallopian Tube Neoplasms; Female; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Middle Aged; Ovarian Neoplasms; Papillomaviridae; Uterine Cervical Neoplasms

Presented is a case report of a urinary bladder carcinoma that had an unusual morphology and phenotype. A 65-year-old Japanese man complained of gross hematuria. Cytological examination of the urine before a partial cystectomy revealed small, round atypical cells with a high nuclear/cytoplasmic ratio, scant cytoplasm, and hyperchromatic nuclei with coarse and granular chromatin in a bloody background. Several tumor cells had relatively large and vesicular nuclei with prominent eosinophilic nucleoli and obscure perinucleolar halos. A small number of large atypical urothelial cells were also recognized. The tumor recurred locally 3 months after the operation. The urine cytology during recurrence showed the same features without the atypical urothelial cells. These cytological findings suggested a case of small cell undifferentiated carcinoma (SCUC) combined with transitional cell carcinoma (TCC). An histology of the resected specimen before the recurrence revealed that the SCUC was consistent with a variant type of SCUC proposed for the lung and showed transition with TCC in situ. M-VAC chemotherapy after a total cystectomy was less effective. The patient died 6 months after diagnosis. A variant subtype of SCUC of the urinary bladder associated with TCC in situ has not been previously reported. Although this histological type is very rare, its earlier cytological detection is needed for appropriate therapy.

Topics: Aged; Biomarkers, Tumor; Carcinoma; Carcinoma in Situ; Carcinoma, Transitional Cell; Cytodiagnosis; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Lewis X Antigen; Male; Microscopy, Electron; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

To test and optimize photodynamic therapy of early cancers in the upper aero-digestive tract and oesophagus, we sought an appropriate animal model, which was found in the 7,12-dimethylbenz[a]anthracene-induced early squamous cell carcinoma in the Golden Syrian hamster. This chemically induced neoplasm is shown, by histology and immunohistochemistry, to pass through similar stages of early cancer development as its human counterpart. Its time sequence is highly reproducible, leading to a well differentiated carcinoma in situ and microinvasive carcinoma in the hamster cheek pouch over a period of 10 weeks.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cheek; Cricetinae; Disease Models, Animal; Esophageal Neoplasms; Keratins; Male; Mesocricetus; Mouth Neoplasms; Neoplasm Invasiveness; Photochemotherapy; Precancerous Conditions

Epidermoid carcinomas were induced in hamster buccal pouches with use of 7.12 dimethylbenz[a]anthracene (DMBA). In five animals that served as tumor controls (Group 1), right buccal pouches were painted with DMBA (0.5% solution in mineral oil) thrice weekly for 14 weeks. In five animals (Group 2), right buccal pouches were painted with DMBA and reduced glutathione (GSH) was administered systemically by mouth. Five animals (Group 3) received vitamin E instead of glutathione. An additional 20 animals (Groups 4, 5, 6, and 7) were untreated, vehicle, glutathione, and vitamin E controls, respectively. Glutathione and vitamin E were given in doses of 10 mg/kg in 0.5 ml of mineral oil thrice weekly on days alternate to DMBA painting. Treatment by GSH and vitamin E reduced the number and size of tumors that were formed. Histopathologically, there were also fewer sites of dysplasia, carcinoma in situ, and early invasive epidermoid carcinoma than in the tumor control animals. The formalin-fixed and paraffin-embedded buccal pouch sections were stained immunohistochemically with use of monoclonal antibodies for cytokeratins. These included high-molecular-weight keratins (50,000-68,000 mol wt) 10, 13, and 8 (k10, k13, and k8, respectively). Oral carcinomas and dysplastic sites exhibited basal and suprabasal (spinous layer) high levels of k10, k13, and k8 staining. Treatment with GSH or vitamin E increased the suprabasal staining for high-molecular-weight keratins and reduced the protein expression for k10, k13, or k8. This pattern of staining was observed in dysplastic as well as in carcinoma sites. These results indicate that cytokeratin protein expression could contribute to a common biomarker analysis for chemoprevention.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antidotes; Antioxidants; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cheek; Cricetinae; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Glutathione; Immunohistochemistry; Keratins; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Vitamin E

To determine the effect of retinoic acid on the development of severe dysplasia or carcinoma in situ from endocervical cells containing human papillomavirus (HPV) type 16.. Two independent lines of HPV 16-immortalized endocervical cells were reconstructed into two squamous epithelial tissues using the organotypic raft culture system to examine the differentiated phenotype. The effect of retinoic acid on dysplastic morphology of differentiation of the epithelia was examined by light microscopy of stained sections and electron microscopy. The endocervical cell type cytokeratin expression pattern was determined by indirect immunofluorescence using specific monoclonal antibodies. Ribonucleic acid expression of the HPV 16 E7 oncogene was examined by in situ hybridization.. Untreated HPV 16-immortalized endocervical cells were reconstructed into squamous dysplastic lesions resembling carcinoma in situ observed in women. Retinoic acid-treated rafts formed epithelia composed of two to three cell layers of columnar-like cells resembling simple epithelium of the endocervix. Electron microscopy and cytokeratin expression patterns confirmed the histology of a differentiated endocervical phenotype after treatment with retinoic acid. Expression of HPV 16 E7 was modestly lower in treated epithelia, preferentially in basal cells.. Retinoic acid prevents the histology and cytokeratin differentiation markers of carcinoma in situ of HPV 16-immortalized endocervical cells. Because the epithelia closely mimic HPV 16-containing severe dysplasias and native endocervical epithelium in women, this immortalized endocervical cell-raft system may be useful as a model to assess the efficacy of agents such as retinoic acid for preventing progression of these lesions to malignant cervical carcinoma.

Topics: Carcinoma in Situ; Cell Line, Transformed; Cell Transformation, Neoplastic; Cells, Cultured; Cervix Uteri; Female; Humans; Keratins; Microscopy, Electron; Papillomaviridae; Tretinoin; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

To determine p53 expression in cells in bladder washings and to relate this to DNA content and clinical outcome.. Washings from 102 patients (41 with newly diagnosed superficial tumours [pTa and pT1], 49 with recurrent superficial tumours and 12 with carcinoma invading bladder muscle) were studied. In 39 cases, the primary bladder tumour was also analysed. The rates of tumour recurrence and progression were determined for the new superficial tumours and related to both p53 expression and DNA content.. Cells positive for p53 were detected in 22 of 90 (24%) washings from patients with superficial bladder cancer. P53 expression correlated with tumour stage (P < 0.05), grade (P < 0.05) and abnormal DNA content (P < 0.05). The analysis of pure urothelial (cyto-keratin-positive) cells improved the detection of DNA abnormalities (P < 0.001). In 74% of cases where both washings and tumour were analysed, the results for DNA content agreed. Of 41 new superficial tumours, 27 (66%) recurred (11 were p53-positive, 16 were p53-negative, P = 0.221; 17 had abnormal DNA content, 10 were diploid, P = 0.069). Four patients progressed (one was p53-positive, P = 0.315 and all had abnormal DNA content, P = 0.072).. P53-positive cells can be detected in washings using flow cytometry and were more commonly detected in association with aneuploid tumours. At short-term follow-up, flow cytometric analysis of DNA content in washings had greater predictive value than had p53 expression. Few washings contained aneuploid cells when the primary tumour contained diploid cells, although the collection of washings is a convenient way of sampling tumour cells.

Topics: Aged; Carcinoma in Situ; Disease Progression; DNA, Neoplasm; Flow Cytometry; Follow-Up Studies; Humans; Keratins; Neoplasm Recurrence, Local; Ploidies; Tumor Suppressor Protein p53; Urinary Bladder Neoplasms

In this study, the histological, cytological, and electron microscopical features of cervical atypical reserve cell hyperplasia are presented. The most important feature of atypical reserve cells in smears is the absence of cytoplasm. Thus, they must be recognized on the absence and not on the presence of a feature, which makes identifying these cells a controversial issue. These stripped nuclei are erroneously believed to be degenerated cylindrical cells, and accordingly are ignored. The atypical reserve cell nuclei are easily damaged in the smear process; however, the MIB-1 staining shows that these disrupted nuclei are derived from proliferating cells. In a follow-up histological study of cases diagnosed as mild dysplasia in a smear, it was found that the presence of MIB-1 positive staining atypical reserve cells was closely related to the development of carcinoma in situ. Recognizing the atypical reserve cells and observing their proliferating activity in a smear might prove to be more important than focusing on the better-known dysplastic cells.

Topics: Antibodies, Monoclonal; Biomarkers; Carcinoma in Situ; Cervix Uteri; Female; Humans; Hyperplasia; Keratins; Ki-67 Antigen; Neoplasm Proteins; Nuclear Proteins; Precancerous Conditions; Uterine Cervical Neoplasms; Vaginal Smears

Of 291 immunosuppressed renal transplant recipients (RTRs) with surviving allografts attending the Royal London Hospital, 171 patients (59%) were found to have warty keratoses. On histological analysis, the lesions in 50 patients (17%) showed partial-thickness dysplasia, and 34 (12%) had one or more invasive squamous cell carcinoma (SCC) and/or one or more in situ SCC or full-thickness dysplasia. We examined the claim that squamoproliferative lesions in RTRs possess distinctive histopathological features that differ from those of similar lesions occurring sporadically in the nonimmunosuppressed population. We compared 40 squamoproliferative lesions from RTRs with 40 matched squamoproliferative lesions from nonimmunosuppressed patients; lesions were coded and their source was unknown to the assessors. Two dermatopathologists independently assessed the cases and gave scores for 11 histological features that have been reported to be characteristic of such lesions in the immunosuppressed population. These included a warty architecture, koilocytes, and multinucleate giant cells. Using these criteria, it was not possible to distinguish lesions of immunosuppressed patients from those of immunocompetent people.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cytoplasmic Granules; Diagnosis, Differential; Epithelium; Female; Giant Cells; Graft Survival; Humans; Hyalin; Immunocompetence; Immunosuppression Therapy; Keratins; Keratosis; Kidney Transplantation; Male; Neoplasm Invasiveness; Papilloma; Skin Neoplasms; Transplantation, Homologous; Warts

To obtain more insight into the proliferative function of basal and secretory cell types in human prostate, we studied the immunoprofile of three well-characterized proliferation-associated antigens (Ki-67, PCNA, MIB 1) in normal and hyperplastic prostate tissue. Distinction between labeled basal and secretory cell types was made by simultaneous demonstration of the proliferation-associated antigens and basal cell-specific cytokeratins in identical sections. In normal and hyperplastic acini, approximately 70% of labeled cells were of the basal cell phenotype. These data clearly suggest that the proliferative compartment of the normal and hyperplastic epithelium is located in the basal cell layer. Compared to normal and hyperplastic conditions, severe proliferative abnormalities were detected in high-grade prostate intraepithelial neoplasias (PIN), as documented by the extension of the proliferative compartment up to the luminal border. Conversely, approximately 70% of proliferating cells detected in atypical hyperplasias that progressed in invasive carcinomas were localized in the remaining basal cell layer. These findings may indicate the proliferative role of basal cells in the epithelial renewal, and the development of hyperplastic and neoplastic disorders in the human prostate.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Carcinoma in Situ; Carcinoma, Acinar Cell; Cell Division; Epithelial Cells; Epithelium; Humans; Immunohistochemistry; Immunophenotyping; Keratins; Ki-67 Antigen; Male; Neoplasm Proteins; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

Histologic review of 48 radical prostatectomy specimens containing both prostatic adenocarcinoma (PC) and high-grade prostatic intraepithelial neoplasia (PIN) resulted in 23 cases containing neoplastic cribriform gland (CGs) at the periphery or within PC fields. The histologic characteristics of CG PIN mimic those of CG PC in that a discernible basal cell layer defines CG PIN, while CG PC lacks a basal layer. To detect the presence of basal cells in CGs, step sections were immunostained with monoclonal antibody 34 beta E12 to high-molecular-weight cytokeratins (HMCK) found in basal cells, but not in PC cells. Optimal staining of formalin-fixed sections required pepsin predigestion followed by 14-hour monoclonal antibody incubation at 4 degrees C. Of 436 CG foci identified, 239 (55%) were outlined by a circumferential HMCK-positive layer (identifying PIN); 182 (42%) totally lacked this layer (identifying PC), with appropriate internal controls; and 15 (3%) stained indeterminately. In an attempt to distinguish CG PIN from PC by routine histologic examination alone, CGs with open, round spaces were classified as classic (156 foci); nonclassic CGs (265 foci) featured irregular oblong to slitlike spaces. Cribriform gland PIN defined by HMCK outlining was more often nonclassic (193 CG foci) in histologic pattern, and CG PC was usually "classic" (110 CG foci) (chi 2 = 75; P < .001). We conclude that (1) more than half (55%) of the CGs in the PC tumors studied contain a basal cell layer fulfilling the definition of PIN; (2) focal and isolated HMCK positivity is found amid PC, and thus the overall pattern of staining together with morphological features is critical to correctly exclude carcinoma; (3) grading of PC on the basis of the presence of CGs may lead to erroneous results if PIN foci are misinterpreted as PC; and (4) since CG PIN is usually found in intimate anatomic association with PC, HMCK staining to detect basal cells in isolated CGs encountered in biopsy specimens may be a useful diagnostic discriminant.

Topics: Adenocarcinoma; Carcinoma in Situ; Humans; Immunohistochemistry; Keratins; Male; Prostatic Neoplasms

Intratubular germ cell neoplasia (ITGCN) is now considered to be the preinvasive phase of testicular germ cell tumors with the exceptions of spermatocytic seminoma, pure yolk sac tumor, and mature teratoma. Pagetoid spread of ITGGN into rete testis is a common yet unpublished finding in these cases. We reviewed 100 cases of testicular germ cell tumors from the Surgical Pathology service of Parkland Memorial Hospital (Dallas, TX) to evaluate the frequency of this pattern of spread. Additional sections were obtained from selected cases and were stained with anti-placental alkaline phosphatase, anti-low molecular weight keratin (clone AE1), and various lectins to highlight the process. Pagetoid spread of ITGCN into rete testis was identified in 24 of 60 cases (40%) in which histologic sections contained both ITGCN and rete testis. The incidence of pagetoid ITGCN involvement of the rete testis was lower in pure seminoma (seven of 25 cases [28%]) than in testes containing nonseminomatous germ cell tumors (17 of 35 cases [49%]). AE1 stained the epithelial cells of the rete testis but not the cells of the ITGCN, whereas placental alkaline phosphatase stained the neoplastic cells but not the epithelial cells of the rete testis. These stains were useful in delineating two cases in which the pagetoid involvement was so extensive that they were misdiagnosed as invasive seminomas. Pagetoid spread of ITGCN is a relatively common finding in testicular germ cell tumors and rarely can be mistaken for invasive seminoma. Immunohistochemistry can be helpful in distinguishing florid pagetoid spread from invasive seminoma.

Topics: Adolescent; Adult; Alkaline Phosphatase; Carcinoma in Situ; Cell Transformation, Neoplastic; Diagnosis, Differential; Epithelium; Germinoma; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Orchiectomy; Paget Disease, Extramammary; Seminoma; Testicular Neoplasms

Topics: Actins; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cell Division; Female; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratins

The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ.

Topics: Actins; Breast; Breast Neoplasms; Carcinoma in Situ; Diagnosis, Differential; Epithelium; Female; Humans; Hyperplasia; Immunohistochemistry; Keratins; S100 Proteins

This study compares the diagnostic reliability of conventional mucin histochemistry and immunocytochemical techniques in distinguishing mammary Paget's disease from superficial spreading malignant melanoma and primary intraepidermal carcinoma. Formalin-fixed, paraffin-embedded archival tissue was used and comprised 13 cases of mammary Paget's disease, five cases of superficial spreading melanoma, and six cases of intraepidermal carcinoma. Sections from each case were stained for the presence of mucin using diastase periodic-acid-Schiff (d-PAS) with and without an alcian blue counterstain as well as immunocytochemistry for cytokeratin (CAM 5.2), epithelial membrane antigen (NCRC-11) and c-erb B-2 (21N). Mucin staining in intraepidermal carcinoma and malignant melanoma was consistently negative. Diastase-resistant PAS positivity was seen in six of 13 cases of mammary Paget's disease and eight of 13 cases using an alcian blue counterstain. NCRC-11 showed positive immunoreactivity in four of six cases of intraepidermal carcinoma, one in five cases of melanoma, and five of 13 cases of mammary Paget's disease. Positive immunoreactivity using CAM 5.2 and 21N was seen in all cases of mammary Paget's disease, with consistent negative immunoreactivity in the other tumor types. We conclude that CAM 5.2 and 21N should be used in the investigation of mammary Paget's disease in preference to conventional mucin stains.

Topics: Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma in Situ; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Melanoma; Membrane Glycoproteins; Mucin-1; Mucins; Paget's Disease, Mammary; Proto-Oncogene Proteins; Receptor, ErbB-2

An immunohistochemical study of squamous metaplasia (n = 10), dysplasia (n = 18), squamous cell carcinoma (n = 48) and 3 cases of adenosquamous carcinoma of the uterine cervix with anti-56KD keratin and 68KD keratin antibodies was performed. In the cases of squamous metaplasia, there were two types of staining of which one type had 56KD positive and 68KD negative and another type had both positive. In the cases of dysplasia, there were two types of staining the same as in squamous metaplasia. But in the cases of carcinoma in situ (CIS) (n = 25), there were three types of staining of which the first type had both 56KD and 68KD negative (n = 7), the second type had 56KD positive and 68KD negative (n = 15), and the third type had both 56KD and 68KD positive (n = 3). In invasive carcinoma (n = 23), there were two types of staining the same as in dysplasia of which one type had 56KD positive and 68KD negative (n = 17) and another type had both positive (n = 6). The keratin negative cases in CIS showed morphologically atypical reserve cell hyperplasia composed of atypical small cells with round nuclei and had a small lesion compared with other types. This result suggested that keratin negative CIS was an early form of CIS which was keratin positive. The results indicating that all dysplasia had 56KD keratin positive and CIS had not always 56KD keratin positive suggested that dysplasia was not always a precursor lesion of CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Antibodies, Monoclonal; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Cervix Uteri; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Metaplasia; Molecular Weight; Neoplasms, Multiple Primary; Uterine Cervical Neoplasms

We investigated the use of three monoclonal antikeratin antibodies on routinely formalin-fixed and paraffin-embedded punch and cone biopsies of the normal human uterine cervix and its metaplastic and premalignant lesions. Monoclonal antibodies used were AE8, which is specific for keratin 13; 34BE12, which reacts with keratins of the stratified squamous epithelium; and CAM5.2, which is specific for keratin 8. All these antibodies performed well in routinely processed surgical pathology material. AE8 antibody stained the suprabasal layer of the normal squamous epithelium. Squamous metaplasia and dysplasia were stained in 50% of the cases. Normal suprabasal distribution of the keratin 13, however, was lost in all positive dysplasia cases. CAM5.2 reacted with normal columnar cells in all cases, and squamous metaplasia was focally positive in 20% of the cases. Dysplasia showed a positive reaction in 30% to 40% of the cases. The 34BE12 antibody was reacting with the full thickness of the squamous epithelium. Squamous metaplasia and dysplasia were positive in 80% of the cases. In addition, 34BE12 stained reserve cell hyperplasia, making it a useful marker for this condition. Our results demonstrate that keratin immunohistochemistry with the above-listed antibodies gives pathogenetically interesting information on cervical lesions.

Topics: Antibodies, Monoclonal; Carcinoma in Situ; Cervix Uteri; Condylomata Acuminata; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Diseases; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The keratin expression pattern in oral stratified epithelium is related to the cellular differentiation level. The normal pattern shows the keratin pair K5 and K14 in the stratum basale whereas K1 and K10, or K4 and K13, are the two pairs associated with differentiating suprabasal cells. Monoclonal and polyclonal antibodies to individual keratins (K10, K13 and K14) were used in a two-color immunofluorescence staining method to study their coexpression in single cells. Altered keratin expression in premalignant and malignant lesions indicated abnormal differentiation. Monospecific keratin antibodies were suggested to be useful for evaluation of epithelial differentiation changes in oral dysplasias and oral squamous cell carcinomas.

Topics: Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Epithelium; Fluorescent Antibody Technique; Humans; Keratins; Leukoplakia, Oral; Microscopy, Fluorescence; Mouth Mucosa; Mouth Neoplasms; Photography; Precancerous Conditions

Results of an immunohistochemical study in normal urothelium and transitional cell carcinomas of the bladder are presented. Paraffin-embedded material was confronted with immunoantisera against carcinoembryonic antigen (CEA), keratin (K), cytokeratin (CK) and epithelial membrane antigen (EMA). Immunohistochemical findings confirm the changes in reactivity of dysplastic urothelium and carcinoma in situ for CEA, CK and EMA, in comparison with normal urothelium. Statistically significant differences were also found, depending upon tumor stage, in staining of transitional cell carcinomas for K and CK. Expression of CK correlated with the tumor differentiation grade: normal urothelium and well-differentiated carcinomas showed a specific pattern of immunostaining for the basal cells, this pattern being lost in poorly differentiated carcinomas.

Topics: Adult; Aged; Antigens, Differentiation; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Transitional Cell; Epithelium; Female; Humans; Keratins; Male; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasm Staging; Urinary Bladder Neoplasms

A detailed immunohistochemical study has been carried out on 63 breast lesions with epitheliosis, ductal carcinoma in situ and clinging carcinoma (lobular cancerization), using antibodies directed against keratins 5/14 and 14, 15, 16, 18, 19, vimentin, smooth muscle actin, collagen IV and laminin. The results have shown that epitheliosis on the one hand and ductal in situ and clinging carcinoma on the other are immunohistochemically different epithelial lesions. Epitheliosis appears to be epithelial hyperplasia with keratin 5/14 and keratin 14, 15, 16, 18, 19-positive cells. Compared to epitheliotic cells tumor cells of clinging carcinoma, lobular cancerization and ductal carcinoma in situ expressed only luminal keratins 14, 15, 16, 18, 19 in 85% of the cases studied; whereas in 15% there was a basal keratin expression. From our results we conclude that the clinging carcinoma (lobular cancerization) represents the initial morphological step in the development of ductal carcinoma in situ and thus may be interpreted as a minimal ductal neoplasia. With the immunohistochemical demonstration of basal and luminal keratins it may be possible in individual cases to differentiate between benign and malignant in situ lesions of the breast.

Topics: Actins; Antibodies, Monoclonal; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Collagen; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Laminin; Muscles; Vimentin

In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained. A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas. Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used. One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas. However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected. A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67. This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Cell Division; Female; Humans; Keratins; Neoplasm Invasiveness; Reference Values

Twenty-seven uterine cervical biopsies with histological diagnoses ranging from normal through dysplasia to invasive carcinoma were analysed for cytokeratin pattern in two-dimensional gel electrophoresis. No direct correlation between histological diagnosis and cytokeratin pattern was observed.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Female; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The cytokeratin pattern and the presence of human papillomavirus (HPV) were analyzed in 53 uterine cervical biopsies. The biopsies were histologically characterized and the diagnosis ranged from normal through dysplasia to carcinoma. The cytokeratins were identified by their immunological reactivity with the monoclonal antibodies AE1 and AE3. The tissue was typed for the presence of HPV types 11, 16 and 18. We have previously shown that there was no correlation between the expression of cytokeratins No. 14, 15, 16 and 19 (K14, K15, K16 and K19) and the histological diagnosis of cervical biopsies. The present study shows that the cytokeratin pattern cannot be correlated to HPV infection of the cervical tissue either.

Topics: Autoradiography; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunoblotting; Intermediate Filaments; Keratins; Papillomaviridae; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Observations differ on the pre-invasive malignant lesions associated with the various categories of testicular germ cell tumours. Such lesions have been found to be similar in appearance and are assumed to be composed of multipotent cells, or conversely a distinctive pre-invasive stage has been reported in association with each form of germ cell neoplasm. This study was undertaken to see whether distinctive morphological and immunohistochemical features of carcinoma in situ adjacent to various categories of germ cell tumours could be established. Carcinoma in situ adjacent to seminomas, teratomas and mixed germ cell tumours in 18 adults was indistinguishable morphologically. Placental alkaline phosphatase was demonstrated immunohistochemically but vimentin and low molecular weight cytokeratins were uniformly absent in these abnormal germ cells from all three groups. These findings support the concept of a multipotent pre-invasive malignant cell for both seminoma and teratoma in the adult. Carcinoma in situ was not seen adjacent to 15 spermatocytic seminomas, nor was placental alkaline phosphatase demonstrated in tubules adjacent to these tumours. These negative findings are additional evidence that spermatocytic seminoma differs from classical seminoma in its histogenesis. Carcinoma in situ, as defined morphologically and immunohistochemically in adults, was not identified adjacent to yolk sac tumours and differentiated teratomas in 20 prepubertal testes. The possibility that pre-invasive malignancy in children may not resemble that in adults must be considered when assessing the malignant potential of cryptorchid testes on biopsies taken during orchidopexy.

Topics: Adult; Alkaline Phosphatase; Antibodies, Monoclonal; Carcinoma in Situ; Child, Preschool; Dysgerminoma; Humans; Infant; Keratins; Male; Mesonephroma; Retrospective Studies; Sertoli Cells; Spermatogonia; Teratoma; Testicular Neoplasms; Vimentin

Epitheliosis is a benign intraluminal proliferation in the breast ducts and lobules that needs to be distinguished from ductal carcinoma in situ (DCIS). The histogenesis and differentiation of cells comprising epitheliosis have been the subject of some controversy. We evaluated the expression of a high-molecular-weight keratin (34 beta E12), muscle-specific actin (HHF-35), and S-100 protein immunoreactivity in formalin-fixed sections of the breast with epitheliosis and DCIS. In 28 of 30 cases of epitheliosis, there was strong HMW keratin immunoreactivity in the streaming sheetlike intraluminal proliferations. In contrast, 35 of 40 cases of DCIS (nonpapillary and papillary) were nonreactive for HMW keratin; the other five were weakly reactive. Furthermore, in 10 cases of DCIS, some ducts had isolated or small aggregates of HMW keratin-positive benign cells on the luminal aspects of the neoplastic proliferation that were reminiscent of a pagetoid pattern. Muscle actin-stained sections were analyzed to assess myoepithelial (ME) cell participation in epitheliosis. Muscle actin-positive ME cells were present at the periphery of the involved ducts but were absent or rare within epitheliosis. The distribution of ME cells--i.e., at the periphery of the spaces involved--was similar in DCIS and epitheliosis. S-100 protein was weakly but relatively consistently expressed by epitheliosis, but all cases of DCIS were negative. Six cases of atypical ductal hyperplasia included in the study were negative for HMW keratin, muscle actin, and S-100 protein. The immunohistochemical profile of epitheliosis indicates that it is primarily an epithelial proliferation with strong HMW keratin and weak S-100 protein expression but without ME cell participation. The distinct differences in HMW keratin expression of epitheliosis and intraductal carcinoma appear to reflect a consistent antigenic difference in these two biologically distinct forms of proliferation.

Topics: Actins; Biomarkers, Tumor; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; S100 Proteins

This study assesses the incidence, histogenesis, and significance of eccrine sweat duct involvement in Bowen's disease (BD). In a review of 96 cases of BD, four showed eccrine duct involvement on hematoxylin and eosin-stained histologic sections. One case was analyzed for deoxyribonucleic acid (DNA) ploidy by using computerized image analysis on Feulgen-stained slides. Sections were also stained immunohistochemically, using antibodies to carcinoembryonic antigen (CEA), gross cystic disease fluid protein (GCDFP), and S-100 protein, and for cytokeratins (CAM 5.2, AE 1/3). Our results showed that, in BD, (a) the eccrine sweat ducts can be extensively involved by atypical cells, (b) the atypical eccrine duct cells had an aneuploid DNA pattern, and (c) the atypical eccrine duct cells were negative for CEA, GCDFP, and S-100 protein but were positive for cytokeratins. We conclude that (a) the frequency of eccrine duct involvement in BD is relatively low (approximately 4 to 9%), (b) the aneuploid DNA pattern makes a benign squamous metaplasia unlikely, (c) the immunohistochemical results exclude coincidental Paget's disease or carcinoma of eccrine sweat glands, (d) the involvement of eccrine sweat ducts may represent a direct extension of the neoplastic epidermal keratinocytes, and (e) this process may have practical implications in the recurrence of superficially treated cases of BD.

Topics: Bowen's Disease; Carcinoma in Situ; Carcinoma, Squamous Cell; DNA, Neoplasm; Eccrine Glands; Humans; Immunohistochemistry; Keratins; Spectrophotometry; Sweat Gland Neoplasms

From January 1977 to December 1988, 19 patients with biopsy-proven Paget's disease of the vulva underwent simple or radical vulvectomy at the University of Miami/Jackson Memorial Medical Center. All vulvectomy specimens were evaluated immunocytochemically for the expression of carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA) and low-molecular-weight keratins 8 and 18 (LMK), both in areas containing neoplastic cells and in histologically negative surgical margins. Neoplastic Paget's cells stained positively for CEA in all cases; they were positive for EMA and LMK in 18 and 17 cases, respectively. In all eight cases with underlying in situ or invasive carcinomas, CEA, EMA and LMK were localized in the underlying tumors as well. None of the histologically proven negative margins reacted for CEA, EMA or LMK on immunocytochemistry. CEA appears to be a valuable immunocytochemical marker for extramammary Paget's disease; EMA and LMK are also expressed by the majority of such cases. None of these markers, however, is of added value in identifying Paget's cells in surgical margins if those margins appear negative on routine hematoxylin-and-eosin staining.

Topics: Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma in Situ; Female; Humans; Keratins; Membrane Glycoproteins; Middle Aged; Molecular Weight; Mucin-1; Neoplasm Invasiveness; Paget Disease, Extramammary; Vulvar Neoplasms

Using immunohistochemistry, the distribution patterns of basement membrane components type VII collagen (monoclonal antibody LH7.2), type IV collagen, and laminin were investigated in normal and malignant human breast tissue and compared with that of keratin 14 (monoclonal antibody LL002), which is expressed only by the basal (myoepithelial) cells in the secretory epithelia of the mammary gland. In normal breast tissue as well as in intraductal carcinomas, a more or less continuous basement membrane was observed at the epithelial stromal interface. Unlike laminin and type IV collagen, type VII collagen was not detected in the basement membrane of blood vessels. The keratin 14 antibody stained the basal cell layer of normal ducts and ducts with in situ cancer. In 85% of the invasive carcinomas no basement membrane or basal cells were detected. In 13 cases, however, laminin, type IV collagen, and/or type VII collagen were detected around tumor nests and individual tumor cells. Five of these tumors also showed a positive reaction with the keratin 14 antibody. In five cases keratin 14 expression was found without detectable basement membrane components. It is concluded that 18 of 103 invasive ductal breast carcinomas examined in this study exhibit a basal cell phenotype as determined from the expression of keratin and the deposition of basement membrane components.

Topics: Basement Membrane; Biomarkers; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Humans; Immunohistochemistry; Keratins; Neoplasm Invasiveness; Reference Values; Tissue Distribution

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Invasiveness

Adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) of the uterine cervix are rare tumors that have often been regarded as a single entity. We studied 28 cases of these neoplasms, with 14 cases in each category. Most patients were over 60 years of age, and there was a high proportion of black women. The majority of the women with ACC presented with postmenopausal bleeding and had an obvious mass on pelvic examination. Despite the tumors' architectural similarity to ACC of the salivary gland, microscopic examination of the cervical carcinomas showed necrosis, a high mitotic rate, and greater nuclear pleomorphism. In all but one of the cases, the tumor cells were negative for S-100 protein on immunoperoxidase staining--a finding that provides evidence against a myoepithelial component. However, S-100-positive dendritic cells were present in the stroma of the tumors and among the neoplastic cells. The patients with ABC were usually asymptomatic, without a gross abnormality of the cervix. Microscopic examination disclosed small nests of basaloid cells, almost always beneath, and often arising from, in situ or small invasive squamous cell carcinomas. In contrast to ABC, ACC was often complicated by local recurrence or distant metastasis. We conclude that ACC of the uterine cervix differs from ACC of salivary gland origin and is also distinct clinically and pathologically from cervical ABC.

Topics: Aged; Aged, 80 and over; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Female; Humans; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; S100 Proteins; Uterine Cervical Neoplasms

Seven consecutive cases of primary spindle celled tumours of the breast have been studied immunohistologically using antisera to the intermediate filament proteins (IFP) vimentin, cytokeratin, and desmin, and with an antibody to epithelial membrane antigen. Representative paraffin sections were examined using a peroxidase-antiperoxidase method. In three cases, very occasional foci of epithelial differentiation were apparent by conventional microscopy, and in one case, adjacent ductal carcinoma in situ was present. The remaining three cases were composed of spindle cell elements entirely, with no evidence of epithelial differentiation morphologically. Immunoreactivity of spindle cell elements for vimentin was found in all seven cases, and for cytokeratin in six cases. One case showed immunoreactivity for vimentin, cytokeratin, and desmin, and one case only for vimentin. Epithelial membrane antigen was not identified in the spindle cell elements of any tumour, but was present in the invasive epithelial component of three cases and the in situ component of one case. We conclude that many spindle cell tumours of breast show immunohistological evidence of epithelial differentiation and can be regarded as spindle cell carcinomas. However, in some cases IFP expression may be complex and histogenesis cannot be determined. This technique can aid histological diagnosis in some cases.

Topics: Adult; Aged; Antigens; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Desmin; Female; Humans; Intermediate Filament Proteins; Keratins; Membrane Glycoproteins; Middle Aged; Mucin-1; Vimentin

It has been suggested that cytokeratin CAM 5.2 is a useful marker to indicate malignant transformation and invasive potential in cervical neoplasia. In this study we examined normal ectocervical epithelium, endocervical squamous metaplasia, cervical intra-epithelial neoplasia (CIN) and invasive carcinoma by the indirect immunoperoxidase method using commercially available CAM 5.2. Positive staining was seen in 12 of 42 (28%) invasive carcinomas and in 2 of 26 specimens of CIN III. No positive staining was observed in any case of CIN II (22 specimens), CIN I (19), squamous metaplasia (21) or normal ectocervical epithelium (16). These results suggest that although CAM 5.2 expression is found in only 28% of cervical squamous carcinoma, it is highly specific for malignant transformation of cervical squamous epithelium. In view of its potential diagnostic value in doubtful cases of CIN III and squamous cell carcinoma, the specificity and sensitivity of CAM 5.2 expression in cervical neoplasia need to be examined in other laboratories under various processing schedules.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Neoplasms

The expression of low molecular weight cytokeratins (normally expressed only in simple epithelia) in intraepithelial neoplasia of grade CIN III or greater in cervical biopsies has recently been described by Bobrow et al. Our study of 127 cases confirms this finding and in addition we compare the use of three monoclonal antibodies, namely NCL-5D3, CAM 5.2, and PKK1, in demonstrating the phenomenon. Both NCL-5D3 and CAM 5.2 give consistently negative results for non-neoplastic stratified squamous epithelium, as well as CIN I and CIN II lesions, whilst staining about 30 per cent of CIN III biopsies and most carcinomas. PKK1, on the other hand, stained 50 per cent of non-neoplastic epithelia and thus did not serve as a marker of severe dysplasia. The possible implications of these observations are discussed.

Topics: Antibodies, Monoclonal; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Humans; Keratins; Staining and Labeling; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

In twenty-three cases of laryngeal dysplasia frozen mucosal strips were examined with four monoclonal and one polyclonal keratin antibody. The expression of specific keratin polypeptides was studied in different degrees of dysplasia with regard to the subunits expressed in normal and carcinomatous laryngeal epithelium in the same patient. An alteration in the expression of the subunits of cytokeratin in favour of low molecular weight polypeptides takes place in the transformation of normal epithelium to squamous cell carcinoma. This alteration seems to occur at an early stage and is present already in mild dysplasia. The results suggest that with a suitable antibody dysplastic laryngeal epithelium can be distinguished from normal epithelium, and also on some cases, mild dysplasia from more severe degrees of dysplasia. CAM 5.2, which identifies lower molecular weight cytokeratin proteins (50, 43 and 38 kD), is such an antibody, and can be a valuable diagnostic aid in the histological interpretation of laryngeal dysplasia.

Topics: Antibodies, Monoclonal; Carcinoma in Situ; Epithelium; Humans; Immunoenzyme Techniques; Immunohistochemistry; Keratins; Laryngeal Neoplasms; Larynx

Prostatic intra-epithelial neoplasia (PIN, or intraductal dysplasia) is considered a precursor of invasive carcinoma, characterized by proliferation and anaplasia of cells lining prostatic ducts and acini. The highest grade of PIN, Grade 3, is thought to represent carcinoma in situ. To quantitate the degree of disruption of the basal cell layer in human prostatic ducts and acini as a potential marker of early invasion in PIN, a monoclonal antibody to keratin proteins of 49, 51, 57, and 66 kd which selectively labels the prostatic basal cell layer was used. A total of 1093 acini with PIN were identified in 14 cases with invasive carcinoma. Tumor cells consistently failed to be decorated with this antibody. The frequency of disruption of the basal cell layer increased with increasing grades of PIN, with disruption present in 0.7% of cases of PIN 1, 15% of cases of PIN 2, and 56% of cases of PIN 3. The amount of disruption of the basal cell layer also increased with increasing grades of PIN, with loss of more than one third of the basal layer in 52% of foci of PIN 3 compared with less than 2% in lower grades of PIN. Disruption of the basal layer was more common in acini adjacent to invasive carcinoma than in distant acini. These findings suggest that early invasion in prostate cancer is characterized by disruption of the basal layer, and that invasion occurs commonly in association with foci of high-grade prostatic intra-epithelial neoplasia.

Topics: Antibodies, Monoclonal; Carcinoma in Situ; Humans; Keratins; Male; Neoplasm Invasiveness; Prostatic Neoplasms

A laryngeal squamous cell carcinoma in situ with an underlying spindle cell nodule (pseudosarcoma) was immunohistochemically labeled with antibodies to tissue-specific intermediate filament proteins, including desmin, vimentin, and cytokeratin. Two distinct populations of cells were found within the lesion: cytokeratin-positive cells, corresponding to the carcinomatous component of the tumor, and vimentin-positive spindle cells in the subepithelial nodule. In view of the strict specificity of antivimentin and anticytokeratin for cells of mesenchymal and epithelial origin, respectively, it is proposed that the two components of the pseudosarcoma in our case are not morphologic variants of the same tumor, and that the subepithelial nodule represents a mesenchymal lesion. These results can, however, not be extrapolated to other cases since in some the spindle cell component may represent metaplastic epithelial cells. In view of the difficulties encountered in reaching a correct diagnosis in these lesions, it is recommended to use intermediate filament typing to elucidate the nature of the spindle cells in this controversial tumor.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Epithelium; Fibroma; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratins; Laryngeal Neoplasms; Male; Middle Aged

For six patients with partial or total laryngectomies with extensive mucosal hyperplasias, we generated DNA histograms from multiple mucosal sites using Feulgen-stained tissue sections and microspectrophotometric microscopy. Aneuploid DNA histograms were identified in the mucosa of all six specimens, indicating that neoplastic transformation had occurred. The histologic characteristics of neoplastic change included thickened or hyperplastic epithelium, surface maturation or keratinization, often a proliferation of small, immature basallike cells in the depths of the epithelium, and evidence of abnormal epithelial maturation as evidenced by focal areas of cytoplasmic keratinization in the lower portions of the mucosa. We think this histologic expression of intraepithelial neoplasia is more common than the "classic" form of carcinoma in situ with full mucosal replacement by proliferating immature basallike cells. Keratin is a common reaction in laryngeal mucosa, and its presence on the surface or in the depths of the epithelium does not militate against the diagnosis of severe intraepithelial neoplastic transformation.

Topics: Aged; Carcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; DNA, Neoplasm; Epithelium; Humans; Hyperplasia; Keratins; Laryngeal Mucosa; Laryngeal Neoplasms; Male; Middle Aged

Antibodies against tissue polypeptide antigen (TPA) and keratins of high molecular weight (62-67 kD) were used to indicate different stages of cell differentiation. The immunohistochemical study was carried out by indirect immunofluorescence. In dysplasia, particularly in CIN grades II to III, TPA labeling comprised not only basal layer cells (as seen in normal mucosa) but more superficial layers as well. Expression of keratins of high molecular weight was reduced to small foci of keratinization and scattered dyskeratotic cells. In typical small cell anaplastic carcinoma in situ, TPA antibodies were observed to label all epithelial cell layers. There was no reactivity with antibodies against keratins of high molecular weight. In invasive cancer, TPA staining was closely related to the degree of maturation. Nonkeratinized tumor zones were entirely labeled by TPA antibodies, whereas keratinized tumor foci were negative for TPA except for peripheral tumor cell layers. In invasive cancer, keratins of high molecular weight were restricted to differentiated portions of the tumor. Our immunohistochemical findings support the present concepts of TPA (as a member of the heterogeneous keratin family) as an indicator of cell differentiation. Immunohistochemical demonstration of keratins of different molecular weight offers a method of assessing squamous differentiation at the cervical transformation zone and in cervical cancer and precancer.

Topics: Antigens, Neoplasm; Biopsy; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Fluorescent Antibody Technique; Humans; Keratins; Neoplasm Staging; Peptides; Tissue Polypeptide Antigen; Uterine Cervical Neoplasms

Two monoclonal antibodies, KA 1 and KA 4, raised against human epidermis, were biochemically and immunologically characterized and were shown to react with specific cytokeratin polypeptides. On frozen sections of human mammary gland, these antibodies distinguish between myoepithelial and luminal epithelial cells. We present evidence that in these cells KA 1 antibody recognized cytokeratin 5 and KA 4 antibody cytokeratin 19. In normal mammary tissue, KA 4 antibody invariably reacted with the epithelial cells lining the lumina of acini, ductules, ducts, and sinus. In contrast, KA 1 antibody decorated only the myoepithelial and basal epithelial cells of acini, ducts, and sinus. In ductules, however, KA 1 also stained the luminal cells. All 73 invasive lobular and ductal carcinomas studied reacted with KA 4 antibody; five of these were also positive, apparently in the same tumor cells, with KA 1. The tumor cells of in situ carcinomas were also stained in a homogeneous pattern with KA 4 antibody; KA 1 antibody reacted only with the surrounding myoepithelium. In epithelial hyperplasias, the proliferating cells were decorated by KA 1 and KA 4 antibodies in a heterogeneous pattern. Other antibodies were used for comparison. The results are discussed with respect to epithelial differentiation and pathogenesis and to the application of such antibodies for immunohistodiagnosis of mammary lesions.

Topics: Adenoma; Antibodies, Monoclonal; Antibodies, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Epithelium; Female; Fibroma; Fluorescent Antibody Technique; Humans; Keratins; Lactation; Neoplasm Proteins; Papilloma; Pregnancy

Thirty-five women with biopsy-proven Paget's disease of the nipple were treated over a 10 year period at the Breast Cancer Unit, Guy's Hospital. Twenty-four (69%) patients had Paget's disease without a palpable mass in the breast; eleven (31%) presented with a palpable mass and Paget's disease of the nipple. Definitive treatment consisted of modified radical mastectomy in 32 patients, radiotherapy only in 2, and one patient had no definitive treatment. All 11 patients with Paget's disease and an associated lump proved to have invasive ductal carcinoma; five also had associated positive axillary nodes. Nine of the 23 patients with nipple changes only, treated by mastectomy, also had invasive carcinoma; three of these had positive axillary nodes. The remaining 14 patients with nipple changes only were found to have in situ ductal carcinoma, which was extensive in the majority of cases. In 13 cases, histological sections of the nipple were examined by immunohistochemical staining which showed that the Paget's cells expressed a keratin phenotype that was specifically characteristic of simple epithelial cells as seen in glandular epithelium. This was quite unrelated to the normal keratin phenotype of the surrounding skin keratinocytes. Clinical, pathological, and immunohistochemical data suggest a mammary origin of the abnormal cells in Paget's disease of the nipple. Mastectomy appears to be the treatment of choice.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Female; Follow-Up Studies; Humans; Immunochemistry; Keratins; Middle Aged; Nipples; Paget's Disease, Mammary

Topics: Breast; Breast Neoplasms; Carcinoma; Carcinoma in Situ; Carcinoma, Intraductal, Noninfiltrating; Female; Fibronectins; Humans; Immunoenzyme Techniques; Keratins; Laminin; Neoplasm Proteins

Twenty cases of infiltrating lobular carcinoma (12 of classical type, five of trabecular type and three of alveolar type) and one case of lobular carcinoma in situ were studied by transmission electron microscopy. The in situ component in three of the infiltrating carcinomas was also studied. The ultrastructure of the tumour cells in the alveolar variant of infiltrating lobular carcinoma was the same as seen in the tumour cells of lobular carcinoma in situ. The tumour cells in infiltrating lobular carcinoma of the classical and trabecular types had more irregular nuclei and were more organelle- and filament-rich. Immunohistochemical staining for the presence of alpha-lactalbumin was proved in 19 per cent of the cases, casein 81 per cent, CEA in 65 per cent and prekeratin in 90 per cent. The light microscopic separation of some subgroups of infiltrating lobular carcinoma may be difficult, in particular the distinction between the classical and the trabecular variants. Unfortunately, our study shows that these distinctions cannot easily be made either by electron microscopy or by light microscopic immunohistochemistry with antibodies against prekeratin, CEA, casein and alpha-lactalbumin.

Topics: Adult; Aged; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Carcinoma in Situ; Caseins; Cell Nucleus; Female; Humans; Intermediate Filament Proteins; Keratins; Lactalbumin; Microscopy, Electron; Middle Aged; Protein Precursors

Carcinoma of the uterine cervix is said to frequently show a combination of squamous epithelial and glandular epithelial characteristics. In the present study, immunohistochemical localization of keratin and secretory component (SC) was studied to clarify these characteristics of cancers of the cervix, and the following results were obtained. Demonstration of the localization of keratin and SC was useful in providing functional markers of the squamous and glandular epithelium of the cervix. In epidermoid carcinomas, the squamous epithelial character of the keratinizing carcinomas was strongest and decreased in the large cell non-keratinizing, followed by the small cell non-keratinizing carcinomas. The glandular character of these lesions decreased in the same order. Subclassification of CIS did not reveal any major changes with either kind of staining. So-called bipotential differentiation was found in 21% of the epidermoid, 53% of the adenocarcinomas and 13% of the CIS. In the clinical stages of epidermoid carcinomas, the stage I and II cases more frequently showed squamous characteristics than did the stage 0 cases.

Topics: Adenocarcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulin Fragments; Keratins; Secretory Component; Uterine Cervical Neoplasms

The distribution of carcinoembryonic antigen (CEA), secretory component (SC), fat globule membrane antigens ( FGMA ), and keratin was determined immunohistochemically in 22 invasive adenocarcinomas of various types and in 9 adenocarcinomas in situ of the uterine cervix. In the invasive adenocarcinomas 77% were positive for CEA, 47% for SC, 89% for keratin, and 77% for FGMA . In adenocarcinomas in situ 67% were positive for CEA, 11% for SC, and 44% for keratin. The location of the markers was variable in the cells, and the cells in a tumor were irregularly positive. For a given histologic type there were several phenotypes. No correlation was found between histologic types of invasive adenocarcinomas and the various phenotypes. It remains to be shown whether a particular phenotype has a particular biological behavior. The detection in the serum of the markers shown in histologic preparations could be useful in the postsurgical monitoring.

Topics: Adenocarcinoma; Adipose Tissue; Adult; Aged; Antigens, Neoplasm; Antigens, Surface; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Adenoid Cystic; Female; Histocytochemistry; Humans; Keratins; Middle Aged; Radioimmunoassay; Secretory Component; Uterine Cervical Neoplasms

The PAP immunocytochemical technique utilizing specific keratin antibody was applied to paraffin sections from 36 cervical biopsies. Normal squamous epithelium and condylomas had similar patterns of keratin production with intense staining of intermediate and upper layers, while basal cells remained negative. Dysplasia, carcinoma in situ and infiltrating squamous carcinoma showed uneven distribution of keratin with the least amount seen in the areas with high mitotic rate and anaplasia. All large cell squamous carcinomas demonstrated presence of significant amounts of keratin. Squamous carcinomas of the small cell type were essentially keratin-free.

Topics: Adenocarcinoma; Carcinoma in Situ; Carcinoma, Squamous Cell; Cervix Uteri; Condylomata Acuminata; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

A case of polypoid carcinosarcoma of the esophagus is presented. Histologically the bulk of the tumor consisted of a sarcomatous tissue having large foci of osseous and cartilagenous differentiation and infiltrating deeply the wall, whereas a superficially, invasive squamous cell carcinoma associated with in-situ carcinoma was located at the base and luminal surface of the polypoid tumor. Intermingling of the carcinomatous and sarcomatous elements was found only in areas where they appeared to be collided. Ultrastructurally the sarcomatous portion contained cells with fibroblastic features but with no typical epithelial characteristics. Immunoperoxidase staining of the paraffin-embedded histologic sections for keratin proteins revealed, however, some positive spindle cells indicative of epithelial nature in the sarcomatous area, but the great majority of the sarcoma cells were devoid of keratin. These combined findings strongly suggest that the sarcomatous component in our case of true carcinosarcoma is derived from mesenchymal transformation (metaplasia) of the squamous carcinoma cells. The findings were discussed in light of the previous pertinent literature.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Carcinosarcoma; Esophageal Neoplasms; Humans; Keratins; Male; Middle Aged; Neoplasms, Multiple Primary; Osteoclasts

Antibodies against different fractions of keratins can be helpful in various fields of special pathology. Antibodies against "small" and "large" keratins permit to evaluate epithelial maturation in skin and oral mucosa. In addition, disturbances of keratinization during inflammatory processes and malignant transformation can be analyzed. The main application of antibodies against the entire fractions of keratins is the detection of the epithelial nature of a neoplasm. By this tool, particular problems in surgical pathology concerning differential diagnosis can be handled in an easier way. Among the different tissues and their neoplasms, examples of the analysis of thymus tumours and salivary gland tumours are presented. Immunoreactivity with keratin antibodies depends crucially on tissue processing. In the normal diagnostic procedure, good results are regularly obtained if cryostat or Bouin-fixed paraffin-embedded sections are used.

Topics: Adenoma; Carcinoma in Situ; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cytoskeleton; Humans; Keratins; Mouth Mucosa; Mouth Neoplasms; Parakeratosis; Salivary Gland Neoplasms; Salivary Glands; Skin; Skin Neoplasms; Thymus Gland; Thymus Neoplasms

14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

Topics: Adenocarcinoma; Antigens, Neoplasm; Carcinoembryonic Antigen; Carcinoma in Situ; Carcinoma, Papillary; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Urinary Bladder Neoplasms

We report 34 cases of bowenoid papulosis of the genitalia. In each case, the patient had numerous reddish brown or violaceous papular lesions, some distinctly verrucoid, situated on the genitalia. Although clinically the lesions invariably appeared benign, histologic examination of specimens from the genital lesions in each patient showed changes of squamous cell carcinoma in situ. Many of the patients gave a history of preceding viral lesions on the genitalia. Therapy in all cases was conservative but thoroughly ablative. We view bowenoid papulosis as a new entity whose biologic behavior if untreated is as yet unknown.

Topics: Adolescent; Adult; Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Nucleus; Epidermis; Female; Humans; Hyperplasia; Keratins; Male; Penile Neoplasms; Perineum; Vulvar Neoplasms

Topics: Candidiasis, Oral; Carcinoma in Situ; Diagnosis, Differential; Epithelium; Erythroplasia; Humans; Keratins; Keratosis; Leukoedema, Oral; Leukoplakia, Oral; Lichen Planus; Lupus Erythematosus, Discoid; Melanins; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Nevus; Precancerous Conditions; Risk; Sebaceous Glands; Smoking; Stomatitis

Oral carcinoma in situ (CIS) as a histopathologic entity was studied in seventy-seven patients to determine the clinical and histologic parameters of the disease. There were forty-nine male and twenty-eight female patients, with 45.1 per cent of the lesions being described clinically as white, 15.9 per cent as red, and 8.5 per cent as a combination of the two. The high-risk sites for CIS were floor of the mouth (23.2 per cent of all lesions), tongue (22.0 per cent), and lips (in males only, 19.5 per cent). Histologically, there was a considerable range of variation in surface keratinization, thickness of epithelium, and certain cytologic alterations. The most consistent of all cytologic changes was loss of orientation of cells. There is no information available concerning possible regression of oral CIS, as is known for CIS of uterine cervix. Furthermore, there is no information concerning the frequency of or the period of transition from oral CIS to invasive carcinoma or whether all oral carcinoma is preceded by CIS. Further studies on this disease are essential.

Topics: Adult; Aged; Carcinoma in Situ; Cell Nucleus; Color; Cytoplasm; Epithelial Cells; Female; Humans; Keratins; Lip Neoplasms; Male; Middle Aged; Mouth Floor; Mouth Mucosa; Mouth Neoplasms; Palatal Neoplasms; Precancerous Conditions; Sex Factors; Tongue Neoplasms

The occurrence of intracytoplasmic desmosomes in normal, hyperplastic, and hyperkeratotic epithelia, in carcinoma-in-situ and in invasive carcinoma of the human oral cavity is demonstrated by electron microscopy. The mechanism for formation of these structures by invagination, separation and by intracytoplasmic incorporation of plasma membrane-desmosome-complexes are described in various oral epithelia, and other possible mechanisms are discussed. Intracytoplasmic desmosomes may occur in normal and pathological keratinocytes of all layers of the oral epithelium. Their ultrastructure in the peripheral cytoplasm is similar to that of the regular desmosomes on the cell surface. However, as they migrate centripetally, they show signs of degeneration, suggesting dissolution by lysosomal enzyme systems. Various surface membrane alterations involved in the formation of intracytoplasmic desmosomes may lead to a reduction of plasma membrane material and of desmosome structures and to defective intercellular adhesion. The intracytoplasmic incorporation of desmosome structures is a ubiquitous phenomenon exhibited by epithelial keratinocytes under certain physiological or pathological conditions.

Topics: Carcinoma in Situ; Carcinoma, Squamous Cell; Cell Membrane; Cytoplasm; Desmosomes; Epithelial Cells; Epithelium; Humans; Keratins; Mouth Neoplasms; Palate; Tongue; Tongue Neoplasms

Topics: Acantholysis; Carcinoma in Situ; Electrons; Humans; Keratins; Microscopy, Electron; Pemphigus