bromochloroacetic-acid and Fibroadenoma

The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1-3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5-S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.

Topics: Adolescent; Adult; Antigens, Neoplasm; Biomarkers, Tumor; Breast Neoplasms; Diagnosis, Differential; Diagnostic Errors; Female; Fibroadenoma; Humans; Keratins; Male; Melanins; Melanoma-Specific Antigens; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurilemmoma; Peripheral Nervous System Neoplasms; Pigmentation Disorders; Prognosis; S100 Proteins; Sacrococcygeal Region; Sarcoma, Clear Cell; Spinal Nerve Roots; Syndrome; Vimentin

Metaplastic breast carcinoma (MBC) is a rare type of invasive breast carcinoma, and chondroid differentiation is even rarer. Here we report a case of MBC with extensive chondroid differentiation in a 38-year-old woman who presented with a lump in her left breast. Ultrasound findings were most compatible with those of giant fibroadenoma. A histopathological examination revealed a malignant lesion comprising neoplastic epithelial cells arranged in solid nests, with large areas of chondroid differentiation. Neoplastic chondroid cells exhibited a positive reaction for S-100, patchy positive reaction for pan-cytokeratin (AE1/AE3) and negative reaction for epithelial membrane antigen. Both carcinomatous and chondroid cells exhibited p53 overexpression. Sentinel lymph node biopsy revealed no tumorous involvement.

Topics: Adult; Breast Neoplasms; Carcinoma; Cell Differentiation; Diagnosis, Differential; Female; Fibroadenoma; Humans; Keratins; Metaplasia; Neoplasm Invasiveness; Treatment Outcome; Tumor Suppressor Protein p53; Ultrasonography, Mammary

We herein report a case of the breast fibroadenoma with foci of so-called immature variant of the conventional ductal hyperplasia. This type of usual ductal hyperplasia is histologically characterised by encircling intraductal proliferation of large cells with pale to amphophilic cytoplasm and large nuclei which vary in shape and in staining quality of the chromatin. We showed here, using the cytokeratin immunohistochemistry, that the proliferating cells were not of immature but rather mature immunohistochemical phenotype. Because of the presented discordance between immature histology and mature immunohistological profile we suggest that this rare type of usual ductal hyperplasia should be called "immature-like".

Topics: Adult; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Fibroadenoma; Humans; Immunohistochemistry; Keratins

Topics: Diagnosis, Differential; Fibroadenoma; Humans; Keratins; Lipoma; Male; Middle Aged; Mucin-1; Neoplasms, Multiple Primary; Thymoma; Thymus Neoplasms; Vimentin

A fibroadenoma was diagnosed in the left udder of a 3-month-old female Chios lamb. No recurrence was observed after surgery. Grossly, the tumor had a whitish-gray lobular appearance, and the lobules were interlaced with thin septa. Microscopically, the tumor was composed of proliferating fibroepithelial tissue, including differentiated ducts lined by whorls and interlacing bundles of abundant loose fibrovascular stroma. Immunohistochemistry revealed the ductal epithelium to be positive for pancytokeratin (AE1/AE3) and loose fibrovascular stroma was positive for vimentin and basal cells covering the ductal epithelium of alpha-smooth-muscle actin. Immunostaining for the estrogen and progesterone receptors was negative. A diagnosis of mammary fibroadenoma was made based on the histological and immunohistochemical findings.

Topics: Animals; Female; Fibroadenoma; Keratins; Mammary Glands, Animal; Mammary Neoplasms, Animal; Sheep; Sheep Diseases; Vimentin

Nerve growth factor receptor (NGFR) is a transmembrane glycoprotein without intrinsic tyrosine kinase activity, whose expression is not restricted to neural cells. NGFR is reported to act as a tumour suppressor, negatively regulating cell growth and proliferation. NGFR expression was immunohistochemically analysed in normal breast tissue and in 140 benign, biphasic and preinvasive breast lesions, in 22 tumours with myoepithelial differentiation and in two cohorts of breast cancer patients: a series of 245 invasive breast carcinomas studied with tissue microarrays and 37 high-grade invasive ductal carcinomas with basal-like immunophenotype. NGFR consistently displayed membrane reactivity in myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, intralobular fibroblasts, vascular adventitia and nerve bundles. Myoepithelial cells of benign proliferations and pre-invasive lesions were consistently positive for NGFR. Scattered NGFR-positive cells were observed in solid areas of six out of nine cases of hyperplasia of usual type, whereas in flat atypia, lobular carcinoma in situ and virtually all cases of ductal carcinoma in situ (97.5%), NGFR was restricted to the myoepithelial layer. Positivity for NGFR was observed in 11 out of 245 (4.5%) breast carcinomas, nine out of 20 (45%) metaplastic breast carcinomas and 14 out of 37 (38%) basal-like breast carcinomas. NGFR expression in invasive tumours significantly correlated with that of cytokeratins 5/6 (P<0.05), 14 (P<0.0001) and 17 (P<0.0005) and EGFR (P<0.0001) and displayed an inverse correlation with oestrogen and progesterone receptors (both, P<0.0001). NGFR showed a statistically significant association with longer disease-free (P<0.05) and overall survival (P<0.01) in the cohort of patients with basal-like carcinomas. This study demonstrates the usefulness of NGFR as a new adjunct marker to identify myoepithelial cells in preinvasive lesions and myoepithelial differentiation in breast carcinomas. Furthermore, provisional data in a small number of basal-like breast carcinomas suggest that NGFR may identify a subgroup of basal-like breast carcinomas with good prognosis.

Topics: Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Epithelial Cells; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Immunohistochemistry; Keratin-14; Keratin-5; Keratin-6; Keratins; Myoepithelioma; Neoplasm Invasiveness; Nerve Tissue Proteins; Receptors, Estrogen; Receptors, Growth Factor; Receptors, Nerve Growth Factor; Receptors, Progesterone; Survival Analysis

We have used a recently described model in which a ras oncogene is expressed in cytokeratin 5 (K5)-expressing cells on doxycycline administration to explore the effects of this oncogene in salivary glands of adult mice. Inducible expression of a mutated K-ras gene under the control of the K5 promoter led to the development of hyperplastic and dysplastic epithelial lesions and carcinomas, with an incidence of 100% and a minimum latency of a week. All major salivary glands were affected, as well as a set of previously undescribed buccal accessory salivary glands located on the apex of the masseter muscle, close to the oral angle. The tumors appear to arise from the cytokeratin 5-positive basal cell compartment. Myoepithelial cells participated in the hyperplasias but not in carcinomas, because the tumors are negative for smooth muscle actin. Carcinomas did not accumulate immunoreactive p53 but are positive for p63, as assayed by immunohistochemistry using an antibody against the N terminus of DeltaN p63, a splice variant of p63 that can inhibit p53 transcriptional activity. In this study, we provide evidence that the ras oncogene, targeted to a specifically sensitive cell compartment within the salivary glands, can trigger a series of event that are sufficient for full carcinogenesis.

Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Proliferation; Cheek; Female; Fibroadenoma; Gene Expression Regulation, Neoplastic; Genes, ras; Keratins; Male; Mice; Mice, Transgenic; Mouth Mucosa; Promoter Regions, Genetic; Salivary Gland Neoplasms; Salivary Glands; Submandibular Gland

Topics: Adenoma, Sweat Gland; Biomarkers, Tumor; Eccrine Glands; Female; Fibroadenoma; Humans; Keratins; Middle Aged; Polyps; Sweat Gland Neoplasms; Treatment Outcome; Uterine Cervical Neoplasms

While squamous cell carcinoma and pseudocarcinomatous hyperplasia have been documented as pre-existing lesions in cases of reactive eccrine syringofibroadenoma (ESFA), to the best of our knowledge carcinoma occurring in a solitary ESFA has not yet been reported. We present one such case in a 91-year-old female who had a dome-shaped, reddish tumor on the extensor side of the left forearm.. We review the histopathological, immunophenotypical and ultrastructural findings of this tumor, including the keratin expression profile.. Histopathologically, long, branching, anastomosing, thin and thick strands of small cuboidal epithelial cells were extending from the surface epidermis into the dermis. In the center of the tumor, there were irregular-shaped nests of atypical tumor cells invading downward into the dermis. Ultrastructurally, duct-like lumina lined with cuboidal tumor cells were present in the epithelial cords. From these findings, the present case was diagnosed as solitary eccrine syringofibroadenocarcinoma (ESFAC). Keratin expression studies revealed that cells of the thick strands, except for the luminal and basal cells, were positive for differentiation-specific keratins, keratins 1 and 10, and that cells of the thin strands were positive for keratins 5 and 14.. Histopathological, immunophenotypical and ultrastructural evidence, as well as the pattern of keratin expression, suggest differentiation of the present malignant tumor towards the eccrine dermal duct. This case is the first reported case of ESFAC as far as we know.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Eccrine Glands; Female; Fibroadenoma; Humans; Immunohistochemistry; Keratins; Sweat Gland Neoplasms; Syringoma; Treatment Outcome

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

Eccrine syringofibroadenoma (ESFA) is a rare disorder which shows differentiation toward the eccrine sweat apparatus. There is a controversy concerning the pathogenesis and precise differentiation of this tumor. We report a case of ESFA and its differentiation pattern by an analysis of cytokeratin expression. Using paraffin-embedded materials, histopathological and immunohistochemical studies were performed. Staining patterns of the luminal, peripheral, and inner cells of the tumor strands closely matched or mimicked those of the luminal, outer and intermediate cells of the normal eccrine dermal duct, respectively. The case of ESFA reported revealed a pattern of differentiation suggestive of an eccrine duct origin.

Topics: Adenoma, Sweat Gland; Aged; Aged, 80 and over; Eccrine Glands; Fibroadenoma; Humans; Immunohistochemistry; Keratins; Male; Skin Neoplasms; Sweat Gland Neoplasms; Syringoma

It is not known how tightly regulation of cytokeratin (CK) protein expression is correlated with transcriptional activity in breast cancer. The level of control of CK expression in the normal mammary gland and in breast cancer has been assessed by combining in situ hybridization with riboprobes, and with immunohistochemistry using monospecific antibodies. In normal mammary gland, luminal cells showed abundant hybridization with complementary RNA (cRNA) probes for CK7, CK8, CK18, and CK19. Proteins of these CKs were correspondingly distributed except for that of CK19, which showed a heterogeneous staining. In primary carcinomas, both messenger RNAs (mRNAs) and proteins of CK8 and CK18 were generally expressed to a degree similar to that of normal epithelia, but a lower level of mRNA and protein of CK18 was observed in metastatic carcinomas. Reduced expression of CK7 and CK14 was observed in all carcinomas, and the correlation between mRNA and protein for these two cytokeratins was unbalanced, whereas the expression of CK19 mRNA and the proportion of its protein-positive cells were increased. The results suggest that these major CKs in normal mammary gland epithelia are regulated at the transcriptional level except for CK19, which is partially under the posttranscriptional control. The alterations observed in breast cancer are not only reflected by the reduced or increased expression of individual cytokeratins, but characterized by partial loss of the normal regulation of cytokeratin expression.

Topics: Adult; Breast; Breast Neoplasms; Carcinoma; Female; Fibroadenoma; Humans; Immunohistochemistry; In Situ Hybridization; Keratins; Reference Values; RNA, Messenger

Malignant progression of tumour cells is caused by the accumulation of genetic defects, which when combined will generate a large phenotypic diversity. Simultaneous quantitation of a large number of gene products in tumour cells is desirable, but difficult to achieve. We have here quantitated the levels of a number of abundant polypeptides in human breast carcinoma cells using two-dimensional gel electrophoresis (2-DE; PDQUEST). For this purpose, tumour cells were prepared from the tissue of 17 breast carcinomas. Fibroadenoma tissue was used as reference for benign cells. An increase of the spot density of the PCNA polypeptide was observed in rapidly proliferating tumour cells, confirming the validity of the procedures used. In the set of 24 polypeptide spots with known identity, decreases in cytokeratin and tropomyosin levels were observed. The levels of all cytokeratin forms resolved (CK7, CK8, CK15 and CK18) were significantly lower in carcinomas than in fibroadenomas. The levels of tropomyosin 2 and 3 were lower in carcinomas than in fibroadenomas. In contrast, the levels of some members of the stress protein family (pHSP60, HSP90 and calreticulin) were higher in carcinomas. Furthermore, changes in the expression of lactate dehydrogenase and GT-pi, but not in nm23, were observed. We conclude that simultaneous analysis of multiple polypeptides in human carcinomas can be achieved by 2-DE and may be useful in prognostic studies, and that malignant progression of breast carcinomas results in the decreased expression of cytokeratin polypeptides. This phenomenon must be considered in studies where cytokeratins are used as markers to identify the epithelial cell compartment in breast carcinomas.

Topics: Breast Neoplasms; Carcinoma; Cell Cycle Proteins; Cytoskeletal Proteins; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Female; Fibroadenoma; Glutathione Transferase; Heat-Shock Proteins; Humans; Keratins; Monomeric GTP-Binding Proteins; Neoplasm Proteins; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; Transcription Factors

To carry out a comprehensive study of cytokeratin expression in benign and malignant breast epithelium and breast myoepithelial cells; to examine changes in the cytokeratin profile in malignant and benign epithelium and in carcinomas of increasing histological grade.. Frozen sections from fibroadenomas (19 cases), fibrocystic disease (19 cases), and infiltrating ductal (68 cases), lobular (seven cases), and mucinous carcinomas (three cases) were examined using a panel of monoclonal antibodies.. The luminal epithelium in all fibroadenomas and all cases of fibrocystic disease, as well as tumour cells in most carcinomas, reacted with the specific antibodies to cytokeratins 7, 8, 18, and 19 and to antibodies which included these cytokeratins in their specificities (Cam 5.2, AE1, AE3, RCK102, and LP34). In a few ductal carcinomas none of the tumour cells reacted for cytokeratins 7, 8, or 18. Three ductal carcinomas expressed cytokeratin 14. Only occasional cases expressed cytokeratins 3, 4, 10, and 13. Antibodies which included cytokeratins 5 and 14 in their specificities detected myoepithelial cells less efficiently than antiactin antibodies.. The cytokeratin profiles in the luminal epithelium in benign breast disease and in tumour cells in most carcinomas are similar in most cases. Some carcinomas, however, are negative for cytokeratins 7, 8, or 18. This may provide a means of predicting the biological behaviour of a histologically borderline lesion.

Topics: Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Epithelium; Female; Fibroadenoma; Fibrocystic Breast Disease; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Proteins

Ten cases of so-called "tubular" adenoma and six cases of fibroadenoma of the breast have been investigated with an immunohistochemical technique with the aim of providing both more details on their immunophenotype and of ascertaining the possible relationships between tubular adenoma and fibroadenoma. Smooth Muscle Actin, Cytokeratin 14, GFAP, S-100 Protein and Vimentin immunoreactivity have clearly demonstrated that cells with myoepithelial immunophenotype are one of the major cell components in breast adenomas. Epithelial Membrane Antigen (EMA), Human Milk Fat Globule II (HMFG II), Estrogen and Progesterone receptors have been detected in adluminal epithelial cells exclusively. Furthermore, Smooth Muscle Actin and Vimentin highlighted an abundant myofibroblastic component, intermingled with tubular structures in both tumor types. A low percentage (10-22%) of adluminal cells and of myofibroblasts showed Ki-67 immunoreactivity in tubular adenomas and in fibroadenomas, whereas only rare myoepithelial cells demonstrated Ki-67 positivity in both tumor types. These data seem to indicate that several cell components of both epithelial and mesenchymal origin (epithelial cells, myoepithelial cells, myofibroblasts) are involved in the genesis of tubular adenomas. The morphological and immunohistochemical features of tubular adenomas closely resemble, in some areas of the tumors, those of fibroadenoma. Therefore, they may represent histogenetically related neoplasms with exuberant ductular component in tubular adenomas and predominant stromal component in fibroadenoma.

Topics: Actins; Adenoma; Adolescent; Adult; Breast Neoplasms; Female; Fibroadenoma; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Middle Aged; Mucin-1; Muscle, Smooth; Receptors, Estrogen; Receptors, Progesterone; S100 Proteins; Vimentin

The luminal cell layer of acrosyringia contains heterogeneous globular keratohyalin granules, some of which contain basophilic and eosinophilic components. Using immunoelectron microscopy we found that the majority of the granules, which are basophilic, are strongly reactive to an anti-filaggrin antibody, while the minority, which are eosinophilic, are not. Similar heterogeneous keratohyalin granules were observed in syringomas and in an eccrine syringofibroadenoma. Since such granules are not normally observed in other human cutaneous epithelia, it is suggested that these composite keratohyalin granules with partial filaggrin immunoreactivity might serve as a useful marker for acrosyringial differentiation in both normal and pathological material.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Cytoplasmic Granules; Eccrine Glands; Epidermis; Extremities; Female; Fibroadenoma; Filaggrin Proteins; Humans; Hyalin; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Microscopy, Electron; Microscopy, Immunoelectron; Middle Aged; Skin Diseases; Sweat Gland Neoplasms; Syringoma

Duct ectasias (n = 2) and different types of benign canine mammary tumours (n = 19) were studied immunohistochemically with monoclonal antibodies (MoAbs) directed against various human keratin types (K), alpha-smooth muscle actin, vimentin, and desmin. In the duct ectasias and in most tumours the epithelial structures revealed an inner and outer cell layer. The inner cell layer was characterized by labelling with K 7, 8, 18, 19 and mostly also with K 4 and/or K 10 MoAbs. The outer cell layer was almost invariably labelled by K 14, K 14 and 17, and a-smooth muscle actin MoAbs. The labelling patterns of both duct ectasias and tumours corresponded largely to the patterns observed in normal mammary gland tissue, although a more distinct heterogeneity was seen. Tumours histomorphologically assumed to be of a myoepithelial origin did not show immunohistochemical features of myoepithelial cells. The myoepithelial nature of the vast majority of spindle-shaped cells present in the adenomas of the complex type and in the fibroadenomas of the benign mixed type could not be confirmed immunohistochemically. These cells, however, unequivocally expressed vimentin, suggesting proliferation of stromal cells in these tumours, which in the fibroadenomas of the benign mixed type may show metaplasia to bone or cartilage. In the duct ectasias and in some tumours, a fraction of elongated stromal cells, probably representing myofibroblasts, was labelled with the alpha-smooth muscle actin MoAb.

Topics: Actins; Adenoma; Animals; Antibodies, Monoclonal; Desmin; Dilatation, Pathologic; Dog Diseases; Dogs; Female; Fibroadenoma; Immunoenzyme Techniques; Immunophenotyping; Intermediate Filament Proteins; Keratins; Male; Mammary Glands, Animal; Mammary Neoplasms, Animal; Mastitis; Papilloma, Intraductal; Vimentin