bromochloroacetic-acid and Paget-Disease--Extramammary

Esophageal squamous cell carcinoma in situ (SCCIS) with diffuse pagetoid features is a recently recognized rare variant of squamous cell carcinoma. A histopathological study of a specimen from a 70-year-old male Japanese patient is reported. The patient died of respiratory failure due to rapidly progressing metastatic pulmonary tumors of unknown origin 73 days after the onset of hemosputum. Autopsy disclosed widespread metastasis of choriocarcinoma in the absence of tumors of the testes or other common sites of germ cell tumors. Elevation of human chorionic gonadotropin (hCG-beta) levels was later detected in the stored serum. Serial histological evaluation of the entire esophagus revealed a small primary site of choriocarcinoma in a background of diffuse SCCIS, mainly of pagetoid type, accompanied by several small foci of submucosally invasive squamous cell carcinoma and primary mucoepidermoid carcinoma. These stimulated nodal metastasis independently of the choriocarcinoma. The SCCIS did not alter the gross mucosal appearance. This is the first reported case of diffuse pagetoid SCCIS combined with choriocarcinoma. Morphological findings and previous studies suggest that the extensive SCCIS of the esophagus resulted from pagetoid spread of tumor cells. The invasive squamous cell carcinoma, mucoepidermoid carcinoma and choriocarcinoma are suggested to have originated from the overlying SCCIS.

Topics: Aged; alpha-Fetoproteins; Autopsy; Carcinoma, Mucoepidermoid; Carcinoma, Squamous Cell; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Esophageal Neoplasms; Fatal Outcome; Humans; Immunohistochemistry; Keratins; Male; Paget Disease, Extramammary; Tissue Polypeptide Antigen

Extramammary Paget's disease most commonly occurs on the female external genitalia and rarely occurs in the perianal region and male external genitalia. We present the clinical and pathologic features of 5 cases of perianal Paget's disease and review the literature.. Clinical and pathologic data were recorded for 5 cases of perianal Paget's disease. Cases were studied retrospectively with special stains, including periodic acid-Schiff, mucicarmine, Alcian blue, carcinoembryonic antigen, S100 protein, pan-keratin, gross cystic disease fluid protein-15 (GCDFP-15), lysozyme, CD15 (Leu-M1), cytokeratin 7 (CK7), and cytokeratin 20 (CK20).. Three (60%) of 5 patients had concurrent rectal adenocarcinomas. All cases reacted positively for pankeratin, although the intensity and distribution of staining varied. Both cases not associated with an underlying carcinoma showed strong GCDFP-15 and CK7 expression and an absence of CK20 expression. The 3 cases associated with an underlying malignancy demonstrated CK7 and CK20 expression and an absence of GCDFP-15 expression. All cases were negative for lysozyme and CD15 (Leu-M1).. The 5 cases reported herein demonstrate that perianal Paget's disease is a heterogeneous entity. The high frequency of associated underlying malignancies and resultant poor clinical outcomes highlight the importance of an aggressive search for a second malignancy. In some cases, perianal Paget's disease merely represents a cutaneous manifestation of an underlying rectal adenocarcinoma and demonstrates a CK7+/CK20+/GCDFP-15-/lysozyme-/Leu-M1- immunophenotype and signet ring Paget's cells. Other cases represent primary adenocarcinomas of the skin, which are associated with a CK7+/CK20-/GCDFP-15+/lysozyme /Leu-M1- immunophenotype and an excellent prognosis if adequately resected. Immunohistochemical studies, particularly CK20 and GCDFP-15, are useful adjuncts in distinguishing primary and secondary perianal Paget's disease.

Topics: Aged; Anus Neoplasms; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoembryonic Antigen; Carrier Proteins; Fatal Outcome; Female; Glycoproteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Lewis X Antigen; Male; Membrane Transport Proteins; Middle Aged; Muramidase; Paget Disease, Extramammary; Retrospective Studies

Topics: Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunologic Techniques; Keratins; Melanoma; Mesenchymoma; Paget Disease, Extramammary; Protein Precursors; S100 Proteins; Vulvar Neoplasms

Pigmented extramammary Paget disease (PEMPD) is a rare intraepithelial carcinoma which can clinically resemble other pigmented neoplasms. Similarities to melanoma on dermoscopy, histopathology, and reflectance confocal microscopy (RCM) increase the risk of misdiagnosis and, consequently, mismanagement. Here, we describe a case of a 67-year-old African American woman with a large, pigmented axillary patch that exhibited features of melanoma on RCM, guiding the clinician to perform an excisional biopsy. While traditional histopathology resembled melanoma, immunohistochemistry staining was performed and revealed PEMPD. We highlight an uncommon clinical presentation of PEMPD disease and identify morphologic mimickers of melanoma on RCM-as well as differentiating features.

Topics: Aged; Axilla; Biopsy; Black or African American; Dermoscopy; Diagnosis, Differential; Diagnostic Errors; Female; Humans; Hyperpigmentation; Hyperplasia; Immunohistochemistry; Keratins; Melanocytes; Melanoma; Microscopy, Confocal; Paget Disease, Extramammary

A panel of immunohistochemical markers may be used to differentiate between pagetoid Bowen disease (PBD) and primary extramammary Paget disease (EMPD) in selected cases. Although diffuse staining with cytokeratin 7 (CK7), CAM5.2, carcinoembryonic antigen, epithelial membrane antigen (EMA), and gross cystic disease fluid protein 15 generally supports diagnosis of EMPD, cases have been reported where PBD also expressed CK7, EMA, and CAM5.2. Based on these findings, some authors suggested that the 2 entities may arise from the same multipotent stem cell, capable of further differentiation toward squamous and secretory lines. To the best of our knowledge, this issue has never been investigated by comparing PBD and EMPD at the ultrastructural level. We performed the first ultrastructural study of a case of PBD exhibiting common immunohistochemical features with EMPD. The lesion displayed some ultrastructural features often observed in Bowen disease and some that are typically found in EMPD. These findings indicate the presence of a bidirectional differentiation--secretory and squamous--within the same lesion, thus supporting the hypothesis that PBD and primary EMPD may arise from a common progenitor cell.

Topics: Aged; Bowen's Disease; Carcinoembryonic Antigen; Carrier Proteins; Glycoproteins; gp100 Melanoma Antigen; Humans; Keratins; Male; Melanoma-Specific Antigens; Membrane Transport Proteins; Mucin-1; Paget Disease, Extramammary; Receptor, ErbB-2; S100 Proteins; Skin Neoplasms; Transcription Factors; Tumor Suppressor Proteins; Ultrasonography

Perianal Paget's disease is an uncommon intraepidermal carcinoma characterized by the presence ofPaget cells. It usually affects older patients and commonly presents as chronic perianal pruritus with scaly plaques. The disease is categorized into primary perianal Paget's disease ofcutaneous origin and secondaryperianal Paget's disease, which is due to extension of a visceral malignancy such as that of the anorectum or colon. Cytokeratin 7 (CK7), cytokeratin 20 (CK20), and gross cystic disease fluid protein-15 (GCDFP15) expression are useful for differentiation between these two types. A tumor immunohistochemical profile of CK7+/CK20-/GCDFP15+ suggests the primary type, whereas CK7+/CK20+/GCDFP15- suggests the secondary type. The expression of caudal homeobox 2 (CDX2) suggests the secondary type from anorectal or colonic adenocarcinoma. However, approximately one- third of patients without visceral malignancy have a tumor that is CK7+/CK20+/GCDFP15-. Two percents of primary perianal Paget ' disease can express CDX2. The author reports a case ofan 86-year-old man who presented with chronic perianalpruritus and a scaly plaque. A skin biopsy showed intraepidermal Paget cells with immunohistochemical profile of CK7+/CK20+/GCDFPJ5-/CDX2+. Initially, secondary perianal Paget's disease from colorectal adenocarcinoma was suspected. However, extensive investiga- tions found no visceral malignancy. The patient underwent wide excision of the perianal skin. Pathological examination showed diffuse intraepidermal Paget cells withfocal dermal invasion by intestinal-type adenocarcinoma and signet-ring cell differentiation. In conclusion, thefinal diagnosis was primary perianal Paget's disease withfocal adenocarcinona and signet- ring cell differentiation. The disease was consistent with primary perianal Paget's disease, because no visceral malignancy was found.

Topics: Aged, 80 and over; Anus Neoplasms; Carrier Proteins; Glycoproteins; Humans; Keratin-7; Keratins; Male; Membrane Transport Proteins; Paget Disease, Extramammary; Perineum

Topics: Aged; Biomarkers; Biomarkers, Tumor; Bowen's Disease; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Neoplasms, Second Primary; Paget Disease, Extramammary; Skin Neoplasms; Vulvar Neoplasms

Vulvar Paget's disease is sub-classified into three types based upon its origin. It might be a primary vulvar disease (type 1) or associated with a non-cutaneous adenocarcinoma-rectal, colonic, cervical (type 2) or linked with an urothelial neoplasia (type 3). Type 1lesions must be considered as potentially invasive. Their immunophenotype is CK7+/CK20-. Classically, in case of depth of invasion below 1mm, nodal metastases are exceptional. We report a case of type 1 Paget's disease in a postmenopausal woman with superficial invasion and multiple inguinal nodal metastases.

Topics: Aged; Biomarkers, Tumor; Female; Frontal Lobe; Humans; Keratins; Lymphatic Metastasis; Meningeal Neoplasms; Meningioma; Neoplasm Invasiveness; Neoplasms, Second Primary; Paget Disease, Extramammary; Peptidyl-Dipeptidase A; Postmenopause; Receptor, ErbB-2; Receptors, Estrogen; Vulvar Neoplasms

Apocrine carcinomas are rare, the immunohistochemical characterizations that are incomplete. The purpose of this study was to determine the immunohistochemical characteristics of mucin core proteins and keratins in apocrine carcinoma, extramammary Paget's disease (EMPD) and apocrine nevus.. We report four cases of apocrine carcinomas along with immunohistochemical analyses: (i) an axillary apocrine carcinoma with an apocrine nevus, (ii) an inguinal apocrine carcinoma, (iii) a vulvar apocrine carcinoma with EMPD and (iv) an axillary apocrine carcinoma with EMPD and an apocrine nevus.. The tumor cells of apocrine carcinomas, EMPD and apocrine nevi displayed a positive reaction to MUC-1 and CK7 and a negative reaction to CK20. Apocrine carcinomas had high molecular weight (HMW) cytokeratin(+)/CK5(+)/CK14(-)/MUC5AC(-), EMPD with underlying apocrine carcinoma had HMW cytokeratin(-)/CK5(-)/CK14(-)/MUCA5AC(-) and the apocrine nevi had HMW cytokeratin(+)/CK5(+)/CK14(+)/MUCA5AC(+).. The immunohistochemical findings suggest that apocrine carcinomas, apocrine nevi and EMPD with underlying apocrine carcinomas are quite different, even though they are all derived from apocrine glands.

Topics: Adult; Aged; Aged, 80 and over; Apocrine Glands; Biomarkers, Tumor; Carcinoma, Skin Appendage; Humans; Immunohistochemistry; Keratins; Male; Mucins; Nevus; Paget Disease, Extramammary; Sweat Gland Neoplasms

Extramammary Paget's disease (EMPD) is considered to be an intraepithelial adenocarcinoma. Typically involved anatomical sites are the vulvar, perianal, perineal, scrotal and penile regions. Clinically, the lesions present as well-defined, moist, erythematous plaques usually accompanied by pruritus. An unusual feature of EMPD is its association with cutaneous, adnexal-structure adenocarcinomas and its association with internal malignancies. Histopathological examination shows epidermal acanthosis and elongated rete ridges. Paget's cells are large intraepidermal cells with a large nucleous and abundant pale cytoplasm. Recent studies of perianal and vulvar EMPD have described distinct immunohistochemical subtypes termed cutaneous and endodermal. Cutaneous EMPD is characteristically positive for cytokeratin (CK)7, negative for CK20, and positive for gross cystic disease fluid protein (GCDFP)15+, whereas endodermal EMPD shows a CK7+ CK20+ GCDFP15- phenotype. Surgery remains the treatment of choice, with either wide surgical excision or Mohs' micrographic surgery. We present a case of EMPD with an underlying carcinoma, which combined immunohistochemical findings suggestive of the cutaneous subtype (positive for CK7, GCDFP15, mucin (MUC)1, human epidermal growth factor receptor (HER)2/neu positive) and the endodermal subtype, frequently associated with internal malignancy (CK20, MUC2, CDX-2 positve); however, our patient had no associated internal malignancy.

Topics: Aged; Fatal Outcome; Genital Neoplasms, Male; Groin; Humans; Keratins; Male; Neoplasm Proteins; Paget Disease, Extramammary; Scrotum

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

To investigate a possible follicular origin of extramammary Paget's disease (EPD). EPD is a predominantly intraepidermal tumour with extensive involvement of adnexal structures and high recurrence rates suggesting a follicular stem cell origin. Cytokeratin (CK) 15 and CK19 are considered markers for follicular stem cells located in the hair follicle bulge region.. Formalin-fixed paraffin-embedded tissues of 12 cases of primary EPD (three anal, nine vulvar) were studied immunohistochemically with antibodies to CK15 and CK19. All cases of EPD showed polygonal Paget cells in the interfollicular epidermis, hair follicles, sebaceous and apocrine glands distributed individually, in nests and in gland-like areas. The polygonal Paget cells were intimately associated with small, flat, mitotically active, 'compressed' keratinocytes. The large Paget cells uniformly expressed CK19 in 12/12 EPD. The small 'compressed' keratinocytes showed strong cytoplasmic CK15 staining in 9/12 EPD with focal accentuation, while the polygonal Paget cells were negative.. These histological and immunohistochemical observations allow the following conclusions: (i) the small, flat, 'compressed' keratinocytes are an integral part of EPD; (ii) the dual cell population is reminiscent of sebaceous glands with mature sebocytes and germinative keratinocytes; (iii) since both cell types express cytokeratins typical for follicular differentiation, EPD may be a proliferation of adnexal stem cells residing in the infundibulo-sebaceous unit of hair follicles and adnexal structures.

Topics: Aged; Anus Neoplasms; Cell Proliferation; Female; Hair Follicle; Humans; Immunohistochemistry; Keratin-15; Keratinocytes; Keratins; Male; Paget Disease, Extramammary; Sebaceous Glands; 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

Among intraepidermal malignancies of epithelial origin, Bowen's disease, bowenoid actinic keratosis (BAK), intraepidermal malignant eccrine poroma (MEP), and Paget's disease may pose diagnostic difficulties.. Histologic features and immunohistochemical profiles of 24 cases of Bowen's disease, 21 cases of BAK, 18 cases of intraepidermal MEP, and 11 cases of Paget's disease were analyzed.. Using multivariate logistic regression test, multinuclear giant cells and solar degeneration were found to be the only histologic parameters of diagnostic help. On the other hand, a widespread positive reaction for CK 5/8, CK 7, CK 19, and negative reaction for CK 10, was a helpful feature in the differentiation of Paget's disease from Bowen's disease and BAK. The widespread and strong expression of CK 10 was seen in almost all cases of Bowen's disease in contrast to BAK. The widespread expression of CK 5/8 and CK 7, and negative reaction for CK 10, was in favor of Paget's disease, compared to intraepidermal MEP. On the other hand, widespread expression of CK 19 was a common finding in intraepidermal MEP, in contrast to Bowen's disease.. An immunohistochemical panel may provide significant hints on the differentiation of common intraepidermal malignancies, especially in problematic cases.

Topics: Bowen's Disease; Diagnosis, Differential; Humans; Keratins; Keratosis; Neoplasms, Glandular and Epithelial; Paget Disease, Extramammary; Paget's Disease, Mammary; Regression Analysis; Skin Neoplasms; Sweat Gland Neoplasms

Clear cells of Toker are intraepithelial cells with clear to pale staining cytoplasm and bland cytologic features found with H&E staining in approximately 10% of normal nipples. Toker cells have been hypothesized as a precursor of extramammary Paget's disease (EMPD), although Toker cells have not been identified as a normal component of genital skin. Using immunohistochemistry, we studied 11 vulvectomies for the presence of Toker cells in association with mammary-like glands of the vulva (MLG). A retrospective study of 11 vulvectomies was performed using routine hematoxylin and eosin staining, as well as immunohistochemical staining for cytokeratin 7 (CK7). Control sections of skin not involving the milk line from age-matched patients were also examined. Four of eleven vulvectomies (36%) demonstrated Toker cells with CK7 staining. Toker cells were associated with the openings of the ducts of mammary-like glands of the vulva. Toker cells were not seen in control tissues. Toker cells occur as a normal constituent of genital skin in association with mammary-like glands of the vulva. Previous morphologic, immunohistochemical, and ultrastructural evidence have pointed to Toker cells as a precursor of EMPD. The demonstration of Toker cells in genital skin strengthens the evidence of their role in the development of EMPD.

Topics: Adult; Aged; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Middle Aged; Paget Disease, Extramammary; Retrospective Studies; Skin; Vulva

Clear cells of Toker are intraepithelial cells with clear to pale staining cytoplasm and bland cytologic features found in approximately 10% of normal nipples. Toker cells have been hypothesized as a precursor of extramammary Paget's disease (EMPD), although the distribution of Toker cells outside of the nipples has not been studied. Using immunohistochemistry, we studied 20 cases of accessory nipples for the presence of Toker cells.. A retrospective study of 20 cases of accessory nipples was performed using routine hemotoxylin and eosin staining, as well as immunohistochemical staining for CK7, CK20, EMA, and GCDFP-15.. Thirteen out of 20 accessory nipples (65%) demonstrated Toker cells with CK7 staining. Toker cells in six of the 13 cases were also positive for EMA. Only one case with Toker cells showed immunoreactivity for antibodies to GCDFP-15.. Toker cells occur outside the normal nipple epidermis in the epidermis of accessory nipples. The distribution of Toker cells along the milk line correlates with the distribution of most cases of EMPD along the milk line, especially in the groin and axillae. Further studies are necessary to define the relationship between Toker cells and EMPD.

Topics: Apolipoproteins; Apolipoproteins D; Biomarkers; Carrier Proteins; Choristoma; Female; Glycoproteins; Humans; Immunohistochemistry; Keratins; Male; Membrane Transport Proteins; Mucin-1; Nipples; Paget Disease, Extramammary; Retrospective Studies; Skin Neoplasms

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

Paget disease of the vulva can be mimicked by several disease entities histopathologically, but most of these entities can be clinically distinguished from vulvar Paget disease. However, vulvar Paget disease is in itself a heterogeneous group of epithelial neoplasms that can be similar both clinically and histopathologically. The subtypes of vulvar Paget disease include primary Paget disease arising from a pluripotent stem cell within the epithelium of the vulva, and secondary Paget disease of the vulva. Secondary vulvar Paget disease results from spread of an internal malignancy, most commonly from an anorectal adenocarcinoma or urothelial carcinoma of the bladder or urethra, to the vulvar epithelium. We have recently proposed that these lesions be classified as primary (of cutaneous origin) or secondary (of extracutaneous origin). These subtypes can present similarly as eczematoid skin lesions and may appear similar on routine hematoxylin and eosin-stained slides. Immunohistochemical studies can help differentiate between them. Our current study includes 17 patients with a pathologic diagnosis of vulvar Paget disease. We performed a panel of immunohistochemical stains, including cytokeratin (CK) 7 and 20, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and uroplakin-III (UP-III). Of these 17 patients, 14 (80%) had primary intraepithelial cutaneous Paget disease, 13 without invasion and 1 with associated invasion. Three patients had urothelial carcinoma with spread to the vulva, manifesting as secondary vulvar Paget disease. Immunohistochemically, primary vulvar Paget disease is immunoreactive for CK 7 and GCDFP-15, but uncommonly for CK 20. Vulvar Paget disease secondary to anorectal carcinoma demonstrates CK 20 immunoreactivity but is usually nonreactive for CK 7 and consistently nonimmunoreactive for GCDFP-15. Vulvar Paget disease secondary to urothelial carcinoma is immunoreactive for CK 7 and CK 20 but nonimmunoreactive for GCDFP-15. In addition, we propose the use of a new, commercially available antibody, UP-III, which is specific for urothelium and, in our experience, is immunoreactive in secondary vulvar Paget disease of urothelial origin. The distinction between these 3 types of Paget and Paget-like lesions is essential in that the specific diagnosis has a significant influence on current treatment. The difference in surgical approach to the subtypes of vulvar Paget disease justifies classifying them into disti

Topics: Biomarkers, Tumor; Carcinoma, Transitional Cell; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratin-7; Keratins; Membrane Glycoproteins; Paget Disease, Extramammary; Urinary Bladder Neoplasms; Uroplakin III; Urothelium; Vulvar 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

A large percentage of cases of perianal Paget disease are associated with an internal cancer, most commonly rectal adenocarcinoma. Immunostains for cytokeratin 7, cytokeratin 20, and gross cystic disease fluid protein 15 are useful in identifying cases associated with rectal adenocarcinoma. The Paget cells and rectal adenocarcinoma cells of these lesions typically have a cytokeratin 7(+)/cytokeratin 20(+)/gross cystic disease fluid protein 15(-) immunophenotype. It is not known whether rectal adenocarcinoma unassociated with perianal Paget disease has the same cytokeratin profile as rectal adenocarcinoma associated with perianal Paget disease.. To evaluate the immunohistochemical cytokeratin 7 and 20 profile of resected rectal adenocarcinoma unassociated with perianal Paget disease as well as that of normal anal glands from hemorrhoidectomy specimens.. We performed immunohistochemistry for cytokeratins 7 and 20 on tissues from 30 cases of rectal adenocarcinoma unassociated with perianal Paget disease and 12 hemorrhoidectomy specimens from 12 cases with normal anal glands. We defined positive staining as any immunoreactivity within the neoplastic cells.. Twenty-six of 30 cases of rectal adenocarcinoma (87%) had a cytokeratin 7(-)/cytokeratin 20(+) immunophenotype, similar to the immunophenotype of cases of nonrectal large intestine adenocarcinoma. In 4 cases (13%), neoplastic cells coexpressed cytokeratins 7 and 20. Anal glands stained strongly for cytokeratin 7 but were negative for cytokeratin 20 in all cases, and the anal transitional zone mucosa had a similar immunophenotype.. Rectal adenocarcinoma unassociated with perianal Paget disease has a cytokeratin profile similar to that of nonrectal large intestine adenocarcinoma. These data suggest that rectal adenocarcinoma unassociated with perianal Paget disease has a different cytokeratin profile than rectal adenocarcinoma associated with perianal Paget disease.

Topics: Adenocarcinoma; Anal Canal; Colonic Neoplasms; Hemorrhoids; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Paget Disease, Extramammary; Rectal Neoplasms

Two cases of vulvar Paget's disease are described in two women aged 75 and 60 years, with onset several years earlier as eczema-like manifestations, and evolving into erosive, slightly infiltrative lesions. In both cases immunohistochemical examination revealed positivity for cytokeratins CK7 and CK20. This finding suggested the diagnosis of primitive vulvar Paget's disease, a relatively benign form, unlike the aggressive and rapidly progressive secondary vulvar Paget's disease.

Topics: Aged; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Paget Disease, Extramammary; Vulvar Neoplasms

Bowen disease is a variant of squamous cell carcinoma in situ. In some cases a pagetoid growth pattern can be observed with cytologically atypical clear cells arranged singly and in nests. The differential diagnosis of pagetoid Bowen disease includes primarily Paget disease and malignant melanoma in situ, as well as other less common entities. Two cases of pagetoid Bowen disease are described, one in a 65-year-old man with a thigh lesion and the other in a 25-year-old man with a lesion in the penile/scrotal region. Neither patient had clinical evidence of an internal malignant neoplasm. In both cases, the neoplastic cells were positive for cytokeratin (CK) 7 and CK 19 and were negative for CK 18, CK 20, carcinoembryonic antigen, GCDFP-15, c-erbB2, S100, and HMB-45. In aggregate, these findings support the diagnosis of pagetoid Bowen disease. Previously, others have shown that CK 7 is an almost invariable marker of Paget disease. Thus, we report these two cases to illustrate that CK 7 can be expressed by pagetoid Bowen disease and should not be a cause of confusion in the differential diagnosis.

Topics: Adult; Aged; Biomarkers, Tumor; Bowen's Disease; Diagnosis, Differential; Humans; Immunohistochemistry; Keratin-7; Keratins; Male; Neoplasm Proteins; Paget Disease, Extramammary; Skin Neoplasms

Despite the similarity in clinical appearance, there is a significant difference in the prognosis between primary extramammary Paget's disease (EPD) and the pagetoid spread of underlying regional internal malignancy (secondary EPD, pagetoid phenomenon). Fifteen cases of primary EPD (11 carcinoma in situ and four invasive carcinoma), seven cases of secondary EPD (five colorectal adenocarcinoma and two urothelial carcinoma), and six cases of anal canal carcinoma were retrieved and analysed immunohistochemically using six kinds of monoclonal anticytokeratin antibodies. No expression of cytokeratins 1, 5, 10, 13 and 14 was observed in any cases examined in this study. All 15 cases of primary EPD had the immunophenotype cytokeratin (CK)7+/CK20-. CK20 expression was diffusely positive in six cases of secondary pagetoid spread (two urothelial carcinoma and four colorectal adenocarcinoma), and focally in one case (a colorectal adenocarcinoma). In anal canal carcinoma, three of six cases showed CK20 diffuse expression and the remaining three cases expressed CK20 focally. CK7 expression was observed in three of six cases of anal canal carcinoma and in two of five cases of secondary EPD associated with colorectal adenocarcinoma. The combination of CK7 and CK20 demonstrates these to be useful markers in distinguishing 'primary' EPD from a pagetoid spread of extracutaneous malignancies. Namely, immunophenotypes other than CK7+/CK20- in Paget cells suggest underlying regional internal malignancy.

Topics: Adenocarcinoma; Anus Neoplasms; Biomarkers, Tumor; Carcinoma, Transitional Cell; Colorectal Neoplasms; Diagnosis, Differential; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Neoplasm Proteins; Paget Disease, Extramammary

Extramammary Paget disease (EPD) is an uncommon cutaneous malignant neoplasm that arises in areas rich in apocrine glands (perineum, vulva, and axilla). Apocrine gland origin or apocrine differentiation of cells of EPD has been suggested. Estrongen, progesterone, and androgen hormone receptors have been reported to exhibit a characteristic pattern of expression in mammary apocrine type carcinomas; however, their expression in EPD has not been elucidated fully. By using immunohistochemical methods, we studied the expression of steroid receptors in EPD on formalin-fixed paraffin-embedded tissue samples from 28 patients with EPD without associated visceral malignant neoplasms or adnexal carcinoma. Androgen receptor (AR) was identified in 15 of 28 cases. The proportion of AR-positive cells varied from 1% to more than 75%; 8 cases expressed AR in more than 10% of cells. Strong AR expression also was seen in the invasive carcinoma arising from 1 case of EPD. All cases lacked immunohistochemically detectable estrogen and progesterone receptors. The immunophenotype characteristic of apocrine carcinomas (AR-positive, estrogen receptor-negative, progesterone receptor-negative) was seen in a substantial proportion of EPD cases. Results suggest that AR expression is a factor in pathogenesis of EPD. This may be important for the therapy of recurrent or invasive disease.

Topics: Adult; Aged; Apocrine Glands; Cell Count; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Skin Neoplasms

Topics: Humans; Keratins; Paget Disease, Extramammary; Sensitivity and Specificity

Pale cells resembling those of paget's disease have been seen as an incidental finding within the epidermis in a variety of benign papules most commonly located in intertriginous areas. This lesion, called pagetoid dyskeratosis, is considered a reactive process in which a small part of the normal population of keratinocytes is induced to proliferate. Among the inductors friction is suspected. As far as we know, these cells have not been reported in the penis.. Here we describe the location of the lesion in the foreskin and the incidence of this lesion in a group of 281 unselected patients surgically treated for phimosis. In selected cases histochemical staining and immunohistochemical studies were performed.. Pagetoid dyskeratosis was found in 105 cases (37.4%) but only in 5 cases (1.8%) the lesion was conspicuous. The cells of pagetoid dyskeratosis show an immunohistochemical profile different from the surrounding keratinocytes characterized by premature keratinization. Pagetoid dyskeratosis cells must be distinguished from the artefactual clear cells of the epidermis, from reactive melanocytes, and from pale-cell acanthosis. In cases in which pagetoid dyskeratosis shows a florid expression there is a hazard of overdiagnosis to the patient. The main differential diagnosis includes extramammary Paget's disease, pagetoid squamous cell carcinoma in situ, epidermotropic metastasis, superficial spreading malignant melanoma, clear cell papulosis, and penile koilocytoses.. The pathologist should be familiar with the histologic features of pagetoid dyskeratosis in the foreskin in order to avoid misdiagnosis and unnecessary treatment. Routine histologic study is usually sufficient to identify the lesion.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Division; Child; Child, Preschool; Diagnosis, Differential; Humans; Infant; Infant, Newborn; Keratinocytes; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Penis; Phimosis; Skin Neoplasms

Histologically, extramammary Paget's disease and mammary Paget's disease (MPD) are characterized by large atypical cells distributed throughout the epidermis. Although classic examples of these disorders are easily diagnosed on morphologic grounds, some cases may cause differential diagnostic problems. Immunohistology with a wide variety of antibodies has been used as an aid for the identification of Paget cells, for their distinction from other entities, and for investigation of the origin or nature of the disorder. Recently, cytokeratin 7 has been proposed as a specific and 100% sensitive marker for Paget's disease. We studied 22 cases of mammary Paget's disease and 22 cases of extramammary Paget's disease with and without an underlying malignancy for their reactivity with monoclonal antibodies to cytokeratin 7 (CK7) and cytokeratin 20 (CK20). Our studies show that anti-CK7 is an effective but not 100% sensitive marker for Paget cells, staining 21 of 22 cases of mammary Paget's disease and 19 of 22 cases of extramammary Paget's disease, whereas CK20 stained 0 of 17 cases of mammary Paget's disease and 6 of 19 cases of extramammary Paget's disease. We also demonstrate that CK7, but not CK20, highlights intraepidermal clear cells with bland nuclear features (Toker cells) that have been reported in 11% of normal nipples. By using CK7 as a marker, however, we were able to identify Toker cells in most of the nipples we studied: 8 of 15 nipples from mastectomy patients without Paget's disease, and 15 of 18 autopsy cases (both male and female) with normal breasts and nipples. It also permitted us to perform more extensive phenotyping on them, showing that Toker cells share similar antigens with Paget cells and with cells lining the underlying normal lactiferous ducts. In 7 of 15 cases containing CK20-positive Merkel cells, CK7 was also seen to stain Merkel cells. In infrequent cases, Toker cells or Merkel cells may be so numerous focally that a CK7 stain may raise the possibility of involvement of the nipple by Paget's disease. An awareness of the CK7 reactivity of Toker cells and Merkel cells as well as attention to the cytologic features of the case should avoid this problem.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Breast Neoplasms; Epidermis; Female; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Immunoenzyme Techniques; Keratin-7; Keratins; Male; Merkel Cells; Middle Aged; Nipples; Paget Disease, Extramammary; Paget's Disease, Mammary; Phenotype

Perianal Paget's disease is rare, and its relationship to an associated internal regional cancer has been ill defined. We analyzed the histologic and immunohistochemical features of perianal Paget's disease in 11 patients to determine the frequency and relationship of associated regional internal carcinoma and to gain insight into its histogenesis. Of five patients with documented rectal adenocarcinoma, it was discovered synchronously with the Paget's disease in four and, subsequently, in one. Paget's cells of signet ring type predominated in four cases. Intraepithelial glands with intraluminal dirty necrosis were present in four cases. The immunophenotype in four cases studied was cytokeratin (CK)7+/CK20+/gross cystic disease fluid protein- (GCDFP) in both the intraepithelial Paget's cells and the invasive rectal adenocarcinoma. Six patients did not have documented rectal carcinoma. The Paget's cells in four were CK7+/CK20-/GCDFP15+. Three of these had purely intraepithelial Paget's disease, and invasive or metastatic disease developed in none after wide local excision. Bilateral inguinal lymph node metastases developed in the fourth patient, and the patient died 8 months after diagnosis of Paget's disease. In two patients, the Paget's cells were CK7+/CK20+/GCDFP15-. Recurrent intraepithelial perianal Paget's disease developed in one patient at 7 months; the patient was alive without disease at 24 months, and the other patient had several intraepithelial recurrences of perianal Paget's disease, and, subsequently, a large perianal tumor of uncertain cell type developed at 108 months, which led to the patient's death. We conclude that there are two types of perianal Paget's disease. One type has endodermal differentiation with gastrointestinal-type glands containing intraluminal dirty necrosis, numerous signet ring cells, CK20 positivity, and GCDFP15 negativity. Such cases are especially likely to be associated with synchronous or metachronous rectal adenocarcinoma. The other type is a primary cutaneous intraepithelial neoplasm in which the Paget's cells display sweat gland differentiation, including GCDFP15 positivity; it generally lacks gastrointestinal-type glands, intraluminal dirty necrosis, and CK20 positivity. The CK7 is a sensitive, albeit nonspecific, marker for Paget's cells.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Rectal 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

To identify a sensitive marker for extramammary Paget's disease and to identify histochemical and immunohistochemical features that suggest occult pelvic cancer in patients with extramammary Paget's disease, we retrieved all cases between 1983 and 1992 with a Standardized Nomenclature of Medicine code of extramammary Paget's disease in the Vanderbilt University Medical Center (Nashville, Tenn) surgical pathology archives. All were stained for alcian blue/dPAS (periodic acid-Schiff), mucicarmine, AE1/AE3, cytokeratin (CAM 5.2), cytokeratin (CK) 7, CK 20, carcinoembryonic antigen (CEA), orthokeratin, prostate-specific antigen, and S-100. Sixteen cases (2 men, 14 women) were retrieved. Two had pelvic malignancies: one rectal adenocarcinoma and one transitional carcinoma. Only CK7 marked all cases. Mucins were sensitive but focal, a potential problem in small biopsy specimens. The transitional tumor had a unique staining profile (CEA- and mucin-negative). CK20 strongly marked Paget cells associated with rectal cancer; its presence suggests a large bowel lesion but is not specific. No case expressed prostate-specific antigen; its presence in a man suggests prostatic carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Alcian Blue; Antiporters; Apolipoproteins; Apolipoproteins D; Biomarkers; Biopsy; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Carmine; Carrier Proteins; Coloring Agents; Female; Glycoproteins; Histocytochemistry; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Membrane Proteins; Membrane Transport Proteins; Middle Aged; Mucins; Paget Disease, Extramammary; Pelvic Neoplasms; Prostate-Specific Antigen; Retrospective Studies; S100 Proteins

Vulvar Paget's disease (VPD) is the most common type of extramammary Paget's disease; however, the frequency of dermal invasion and its clinical significance are unclear, as are the frequency and relationship of an associated regional internal cancer. Thus, we studied the clinicopathologic and immunohistochemical features of 19 patients with VPD. Patients ranged in age from 56 to 86 years (median 65). VPD was entirely intraepithelial (IE-VPD) in 13 patients. Three patients developed IE-VPD recurrence and one developed deeply invasive and metastatic VPD at 10.8 years. Five patients had invasive Paget's disease (INV-VPD) characterized by clinically occult microscopic foci of superficial dermal invasion, ranging in depth from 0.3 to 0.9 mm. All five patients were alive without disease after 12 months to 17 years (median 66 months). A regional internal cancer (CA ASSOC-VPD) occurred in one patient whose VPD was preceded by a deeply invasive grade 3 transitional cell carcinoma of the urinary bladder 9 months earlier. Immunophenotypes of 16 cases with IE-VPD or INV-VPD were CK7+/CK20-/GCDFP15+ in 14 cases and CK7+/CK20+/GCDFP15+ in two cases, with concordant immunophenotypes of the intraepithelial and invasive components in all cases studied. The patient with CA ASSOC-VPD had a CK7+/CK20+/GCDFP15- immunophenotype in the invasive TCC of the urinary bladder and the VPD. We conclude that the predominant form of VPD begins as a primary cutaneous intraepithelial neoplasm that is universally CK7+/GCDFP15+. Foci of unsuspected synchronous dermal invasion by Paget's cells can be expected in almost one third of cases. Subsequent progression into an invasive carcinoma occurs less often. Foci of "minimally invasive" carcinoma (<1 mm) probably do not adversely affect prognosis, whereas deeply invasive carcinoma behaves as a fully malignant adenocarcinoma. The rarer form of VPD appears to result from secondary intraepithelial spread from an associated regional internal carcinoma. The finding of Paget's cells that are CK20+/GCDFP15- suggests the presence of a regional internal carcinoma with a corresponding immunophenotype.

Topics: Aged; Aged, 80 and over; Apolipoproteins; Apolipoproteins D; Biomarkers, Tumor; Carcinoma, Transitional Cell; Carrier Proteins; Female; Glycoproteins; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Membrane Transport Proteins; Middle Aged; Neoplasm Invasiveness; Paget Disease, Extramammary; Urinary Bladder Neoplasms; Vulvar Neoplasms

There are a variety of routine and immunohistochemical stains used to diagnose mammary and extramammary Paget's disease (MPD and EMPD). Most of the stains commonly used, however, show a positive reaction in the Paget's cells in all cases. We wanted to assess which immunohistochemical stain is the best for the diagnosis of MPD and EMPD, as well as the best stain for identifying small foci of tumors in evaluating tumor margins. We evaluated nine cases of MPD and nine cases of EMPD, which were randomly chosen, with a battery of immunohistochemical stains. These stains included cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, Ber-EP4, and CAM 5.2. Cytokeratin 7 was the only immunohistochemical stain that stained all of the cases diffusely, and, in all of the cases, the staining of the Paget's cell was intense and specific within the epidermis. We concluded that cytokeratin 7 is the immunohistochemical stain of choice in the diagnosis of Paget's disease. Because cytokeratin 7 seems to identify single cells, it might also be valuable in evaluating surgical margins for small foci in a tumor such as EMPD, which might have a multifocal origin.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoembryonic Antigen; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Neoplasms; Paget Disease, Extramammary; Paget's Disease, Mammary; Staining and Labeling

Epidermotropic metastases from internal malignancies are exceedingly rare. We report two examples of epidermotropic metastatic breast carcinoma with striking intraepidermal involvement. The first case mimicked melanoma because the neoplastic cells contained melanin and were disposed both as single units and as nests at the dermoepidermal junction and throughout the epidermis. In the second case, the neoplastic cells were seen as isolated neoplastic cells with large, pale cytoplasm scattered throughout the epidermis, closely resembling extramammary Paget's disease. Immunohistochemical studies in both cases demonstrated the epithelial nature of intraepidermal neoplastic cells, which showed an immunophenotype identical to the neoplastic cells present in the dermis: positive staining with anti-cytokeratins, CEA, EMA, and GCDFP-15 and negative with anti-S-100 protein and HMB-45. These findings ruled out the possibility of a collision lesion, or simultaneous occurrence of melanoma and metastatic breast carcinoma. Pagetoid intraepidermal spread of metastatic breast carcinoma, as in our two cases, is exceptional. We also discuss the histogenetic similarities between our findings and those of mammary and extramammary Paget's disease, as well as the differential diagnosis of other cutaneous disorders characterized by pagetoid intraepidermal spread of neoplastic cells.

Topics: Aged; Antigens, Neoplasm; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Diagnosis, Differential; Epidermis; Female; Humans; Immunohistochemistry; Keratins; Melanins; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Paget Disease, Extramammary; Paget's Disease, Mammary; S100 Proteins; Skin Neoplasms

Topics: Carcinoembryonic Antigen; Carcinoma; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Follow-Up Studies; Humans; Hypopharyngeal Neoplasms; Keratins; Laryngeal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Paget Disease, Extramammary; Penile Neoplasms; Skin 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

Formalin-fixed and paraffin-embedded tissue specimens of six cases of extraocular sebaceous carcinoma were studied immunohistochemically with eight anti-keratin monoclonal antibodies, 34 beta B4, 35 beta H11, Ks13.1, Ks19.1, PKK1, LP34, KL1 and AE1. The staining patterns of sebaceous carcinoma were compared with those of normal sebaceous glands and other skin cancers which should be distinguished from sebaceous carcinoma histopathologically. The other skin cancers compared were eccrine porocarcinoma, malignant clear cell hidradenoma, extramammary Paget's disease with underlying adenocarcinoma, malignant trichilemmoma, and squamous cell carcinoma. Most cases of sebaceous carcinoma were stained with 35 beta H11, Ks19.1, LP34, KL1 and AE1, while normal sebaceous glands were positive only with 35 beta H11, LP34, KL1 and AE1. By immunostaining, sebaceous carcinoma was distinguishable from extramammary Paget's disease with underlying adenocarcinoma, squamous cell carcinoma, malignant trichilemmoma, and eccrine porocarcinoma, but was not clearly distinguishable from malignant clear cell hidradenoma. These findings demonstrate that sebaceous carcinoma shows positive reactions with antibodies to simple epithelial keratin, probably as a result of neoplastic transformation, and that immunohistochemical examination using anti-keratin monoclonal antibodies is useful in distinguishing sebaceous carcinoma from several other skin cancers.

Topics: Acrospiroma; Adenocarcinoma, Sebaceous; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Keratins; Neoplasms, Basal Cell; Paget Disease, Extramammary; Sebaceous Gland Neoplasms; Skin Neoplasms; Sweat Gland Neoplasms

Extramammary Paget disease appears in anogenital, axillary, or other areas. In this study, the authors addressed the question of whether the histogenesis of 35 cases of Paget disease arising at different sites was the same.. Specimens of 35 cases of extramammary Paget disease (16 genital; 9 invasive carcinomas of genital; 6 axillary; 1 periumbilical; and 3 perianal), 4 cases of mammary Paget disease, 4 cases of breast carcinomas, and 6 cases of anal carcinomas of perianal spread from primary rectal adenocarcinomas were retrieved and stained by the avidin-biotin-complex method, using various kinds of monoclonal antikeratin antibodies.. There was no significant difference in cytokeratin expression among these cases of extramammary Paget disease. Simple epithelial keratins were expressed in Paget cells in extramammary Paget disease, but no expression of differentiation-specific or noncornifying stratified squamous epithelial keratins was observed, regardless of the degree of invasion. Paget cells in extramammary Paget disease revealed a similar cytokeratin expression to that in secretory cells of normal apocrine or eccrine glands. In addition, there was no significant difference in cytokeratin expression in tumor cells among extramammary and mammary Paget disease, breast carcinomas, and anal carcinomas.. Cases of Paget disease arising at different locations could not be distinguished from each other based on cytokeratin expression. In addition, antikeratin antibodies against simple epithelial keratins were demonstrated to be more useful for the identification of Paget cells in the paraffin sections than were conventional antibodies, such as an antibody against carcinoembryonic antigen (CEA).

Topics: Antibodies, Monoclonal; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Eccrine Glands; Gene Expression Regulation, Neoplastic; Humans; Keratins; Neoplasm Invasiveness; Paget Disease, Extramammary; Paget's Disease, Mammary; Protein Precursors; Urogenital Neoplasms

The ability of a panel of monoclonal antibodies generated in this laboratory to identify "pagetoid" melanoma cells and distinguish them from true Paget's adenocarcinoma cells in a retrospective analysis of vulvar neoplasms was investigated. Paraffin blocks of formalin and Carnoy's fixed tissue from 15 cases of vulvar Paget's disease and 11 cases of primary vulvar melanoma were retrieved and sections were incubated with the following panel of monoclonal antibodies: HMB45, a melanoma-specific monoclonal antibody; and 35 beta H11 and 34 beta E12, two different anti-cytokeratin monoclonal antibodies, to low molecular and high molecular weight cytokeratins, respectively. The anti-melanoma monoclonal antibody (HMB45) positively identified the melanoma cells, distinguishing them from normal melanocytes, in all 11 cases of melanoma. In contrast, the HMB45 antibody failed to react with the intraepithelial neoplastic cells in all cases of Paget's disease. These latter malignant cells were strongly positive only with the monoclonal anti-low molecular weight cytokeratin antibody 35 beta H11. This latter antibody absolutely distinguished tumor cells from neighboring uninvolved squamous epithelium, which was positive only with the monoclonal antibody 34 beta E12. Using this panel of monoclonal antibodies, the surgical margins could also be better evaluated; in at least one case the surgical margin thought by histological evaluation to be free of tumor was demonstrated by immunocytochemistry to be positive for tumor. In the vulvectomy specimens obtained in both diseases, Paget's or melanoma cells were identified in sections histologically interpreted as free of tumor. Thus, a panel of monoclonal antibodies is able to identify, with high sensitivity and specificity, vulvar melanoma cells and absolutely distinguish them from vulvar Paget's cells and can help in evaluating surgical margins in a more accurate manner.

Topics: Antibodies, Monoclonal; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Keratins; Melanoma; Molecular Weight; Paget Disease, Extramammary; Retrospective Studies; Sensitivity and Specificity; Vulvar Neoplasms

The histologic and immunohistochemical characteristics of 49 skin biopsy specimens from 49 patients with extramammary Paget's disease were studied. Patients with extramammary Paget's disease with and without underlying malignant disease were identified. Associated malignant lesions, present in 16 patients (33%), were transitional cell carcinoma of the bladder (n = 8), adenocarcinoma underlying the skin (n = 3), adenocarcinoma of the anus (n = 1), adenocarcinoma of the vulva (n = 1), apocrine carcinoma (n = 1), prostate carcinoma (n = 1), and carcinoma metastatic to the lung (n = 1). The main histologic feature was the presence of Paget's cells, predominantly at the base of the epidermis. In 6% of the cases, well-defined nests of large Paget's cells mimicked melanocytic nests. Carcinoembryonic antigen and Cam 5.2 (a monoclonal antibody that stains 40-kDa, 45-kDa, and 52.5-kDa low molecular weight keratins) were localized to the Paget's cells in 42 of 45 (93%) and 29 of 41 cases (71%), respectively. Forty-four of 46 lesions (96%) were mucin positive, as determined by Hale's colloidal iron stain. Absence of staining for colloidal iron and carcinoembryonic antigen occurred somewhat more frequently in patients with underlying malignant disease than in patients without tumors (13% vs. 0% mucin negative and 13% vs. 3% carcinoembryonic antigen negative, respectively). Although immunohistochemical staining for low molecular weight keratin may be used to confirm the diagnosis of extramammary Paget's disease, Cam 5.2 is not as sensitive as the colloidal iron or carcinoembryonic antigen stain.

Topics: Aged; Aged, 80 and over; Anus Neoplasms; Carcinoembryonic Antigen; Female; Genital Neoplasms, Male; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mucins; Paget Disease, Extramammary; S100 Proteins; Skin Neoplasms; Vulvar Neoplasms

We report a case of extramammary Paget's disease in ovarian mature cystic teratoma. The patient was a 70-year-old Japanese woman who complained of lower abdominal pain. Examination showed elevation of carcinoembryonic antigen and CA 19-9. Ultrasonography and computer tomography revealed a cystic tumor of the left ovary. The gross appearance of the resected ovary was typical for mature cystic teratoma. Microscopic observation revealed a lesion of Paget's disease within the squamous epithelium. The tumor cells had intracytoplasmic mucin and positive immunoreactivity for carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin; but they were negative for S-100 protein and vimentin. On multiple and serial sections, underlying adenocarcinomas were not found either in the ovary or other primary sites. From these pathological findings, we concluded that the disease was an intraepithelial adenocarcinoma, possibly derived from multipotential cells in squamous epithelium of ovarian mature cystic teratoma. This is the first reported case, to our knowledge, of extramammary Paget's disease arising in mature cystic teratoma of the ovary.

Topics: Adenocarcinoma; Aged; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Dermoid Cyst; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Mucin-1; Ovarian Neoplasms; Paget Disease, Extramammary; S100 Proteins; Vimentin

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

We examined the presence and the distribution of epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and keratin in 4 cases (6 specimens) of mammary Paget's disease and 9 cases (18 specimens) of extramammary Paget's disease utilizing immunoperoxidase technique. Paget's cells in 23 out of 24 specimens were demonstrable for EMA. Positive staining was observed for CEA in every specimen. Among the 24 specimens, 16 showed positivity for keratin. In addition, CEA was positive in Paget's cells and the staining for CEA was stronger than that of EMA and keratin. On the other hand, some Paget's cells were negative for EMA of keratin although other positive cells were observed in the same sections. This findings indicates that Paget's cells might express CEA and/or EMA and/or keratin depending on their differentiation. EMA is present in most organs showing glandular differentiation, and anti-keratin antibody used in this study recognizes not only keratinocytes but glandular cells. Thus, our study suggests Paget's cells are of glandular origin.

Topics: Antigens; Biomarkers; Carcinoembryonic Antigen; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Mucin-1; Paget Disease, Extramammary; Paget's Disease, Mammary

Utilizing three different anti-keratin antibodies and the avidin-biotin peroxidase complex system on sections of formalin-fixed paraffin-embedded tissues and on cryostat sections, immunohistochemical localization of keratin type intermediate filaments in mammary Paget's disease and extramammary Paget's disease was investigated. Anti-keratin antibodies EAB-903 and EAB-904, which recognize 66K and 57K dalton keratin peptides, did not decorate any Paget's cells in either mammary or extramammary Paget's disease. On the other hand, anti-keratin antibody MAK-6, which recognizes 52.5K, 50K, 48K, 45K and 40K daltons keratin peptides, did decorate Paget's cells in both Paget's diseases. These staining properties of Paget's cells were the same as those of secretory cells in normal human sweat glands and mammary glands. Anti-keratin antibody MAK-6 is thought to be useful in the diagnosis of mammary and extramammary Paget's diseases.

Topics: Antibodies, Monoclonal; Carcinoma, Intraductal, Noninfiltrating; Humans; Keratins; Paget Disease, Extramammary; Paget's Disease, Mammary

Sweat gland origin of Paget disease is demonstrated by the presence of carcinoembryonic antigen (CEA). We studied the expression of CEA and keratin in two cases of extramammary Paget disease. Our results are commented.

Topics: Carcinoembryonic Antigen; Humans; Immunohistochemistry; Keratins; Paget Disease, Extramammary; Skin Neoplasms

A case of extra-mammary Paget's disease with a mucin-negative small biopsy is reported. Study of a small series of vulvar Paget's disease demonstrated that areas devoid of mucin in the mm range are frequently found, creating the conditions for diagnostic problems in small biopsies. In this situation, positive immunoreactions for carcinoembryonic antigen and low molecular weight cytokeratins and a negative reaction for S-100 protein serves to differentiate Paget's disease from other pagetoid lesions.

Topics: Aged; Biopsy; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Mucins; Paget Disease, Extramammary; S100 Proteins; Vulvar Neoplasms

Six cases of extramammary Paget's disease were immunohistochemically investigated with several antikeratin monoclonal antibodies. Paget cells and surrounding epidermal keratinocytes were equally stained with an antikeratin monoclonal antibody, HKN-4, which recognizes a broad spectrum of keratins. However, Paget cells were clearly distinguished from the surrounding epidermal keratinocytes by HKN-2, which does not react with keratins of secretory cells but does react with keratins of ductal and myoepithelial cells of sweat glands and with epidermis and hair tissue of the normal skin. The HKN-2 did not bind to Paget cells, but the surrounding keratinocytes were positive. CK7, LE41, RGE53, and LP2K, which recognize simple epithelium-type keratins 7 (molecular weight [MW], 54,000; type II), 8 (MW, 52,500; type II), 18 (MW, 45,000; type I), and 19 (MW, 40,000; type I), respectively, stained Paget cells but not the surrounding keratinocytes. Two cases of Merkel cell carcinoma, examined as controls, showed positivity to LE41 and RGE53 but not to CK7 and LP2K. Since in the normal skin the secretory cells of sweat glands showed the same keratin expression as that of Paget cells, Paget cells of extramammary Paget's disease may be derived from or differentiate to the secretory cells of sweat glands.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged; Paget Disease, Extramammary; Penile Neoplasms; Skin Neoplasms; Sweat Glands; Vulvar Neoplasms

Pale cells that resemble those of Paget's disease have been found within apparently normal epidermis in a variety of benign papules. Although they have been considered an artifact, they show characteristic premature keratinization. In contrast to other dyskeratotic processes they mature into orthokeratotic squamae. The histopathologic, ultrastructural and immunocytochemical features of these cells are illustrated, and the differential diagnosis is reviewed.

Topics: Adolescent; Adult; Child; Diagnosis, Differential; Epidermis; Female; Humans; Keratins; Male; Microscopy, Electron; Middle Aged; Paget Disease, Extramammary; Skin Diseases; Skin Neoplasms; Staining and Labeling

Twenty-one cases of Paget's disease have been studied using histochemical, ultrastructural, and immunohistochemical methods. Eight of the tumors involved the nipple, and 13 were extramammary (11 vulvar and two anal). The antibodies used were directed against different classes of cytokeratin proteins, epithelial membrane antigen, carcinoembryonic antigen, gross cystic disease fluid protein-15, and S-100 protein. The findings of this study provide conclusive evidence that Paget's cells, regardless of their location, are adenocarcinoma cells. Intracytoplasmic mucin is scanty in Paget's cells within the nipple, but typically plentiful in the extramammary sites where the cells are frequently signet-ring cells. The common mechanism for the evolution of Paget's disease is extension of cells from an underlying carcinoma, but the possibility that some cases, particularly in the vulva, develop from intraepithelial precursors cannot be excluded.

Topics: Antibodies, Monoclonal; Anus Neoplasms; Apolipoproteins; Apolipoproteins D; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma, Intraductal, Noninfiltrating; Carrier Proteins; Female; Glycoproteins; Humans; Keratins; Membrane Proteins; Membrane Transport Proteins; Mucin-1; Paget Disease, Extramammary; Paget's Disease, Mammary; Protein Precursors; S100 Proteins; Vulvar Neoplasms

The differentiation of Paget's disease from Bowen's disease and Pagetoid superficial spreading melanoma may represent diagnostic difficulties. The special stains used in their differential diagnosis are nonspecific and not always sensitive. Therefore, the expression of cytokeratins of different molecular weights (54, 57, and 66 kilodaltons [kD]) was studied in 26 intraepithelial neoplasms in formalin-fixed paraffin-embedded tissues with the use of an avidin-biotin complex (ABC) method with monoclonal cytokeratin antibodies. These included 9 cases of Paget's disease, 11 cases of Bowen's disease, and 6 cases of Pagetoid superficial spreading melanoma. Paget cells from vulva and breast were always positive for 54-kD cytokeratin, variable for 57-kD cytokeratin, and negative for 66-kD cytokeratin. The neoplastic cells in all 11 cases of Bowen's disease were stained for 57-kD and 66-kD cytokeratins but not for 54-kD cytokeratin. The neoplastic cells in all cases of melanoma did not express any of the cytokeratins studied. The results indicate that antibodies to cytokeratins of different molecular weights may be used as a diagnostic tool in the distinction of Paget's disease from Bowen's disease and melanoma.

Topics: Antibodies, Monoclonal; Bowen's Disease; Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Squamous Cell; Female; Humans; Keratins; Melanoma; Paget Disease, Extramammary; Paget's Disease, Mammary; Skin; Skin Neoplasms; Vulvar Neoplasms

The malignant intraepithelial proliferations--malignant melanoma level I, bowenoid epithelial dysplasia, and mammary as well as extramammary Paget's disease--may cause differential diagnostic difficulties. We have examined 12 cases of malignant melanoma level I, nine cases of bowenoid epithelial dysplasia, 17 cases of extramammary and five cases of mammary Paget's disease for S100 protein, carcinoembryonic antigen (CEA), cytokeratin, and keratin to evaluate the sensitivity and specificity of these reactions with regard to their differential diagnostic value. Antibodies against S100 reacted specifically with the tumor cells in intraepithelial malignant melanomas; antibodies against CEA reacted specifically with the tumor cells in Paget's disease; and cytokeratin and keratin antibodies reacted with the epithelial tumor cells in Paget's disease as well as in bowenoid epithelial dysplasia. However, only antibodies to CEA and keratin showed 100% sensitivity. We conclude that the investigated antibodies may be of differential diagnostic value in cases of intraepidermal neoplasias, but that a negative reaction does not exclude diagnosis of these diseases.

Topics: Bowen's Disease; Breast Neoplasms; Carcinoembryonic Antigen; Carcinoma; Diagnosis, Differential; Humans; Immunologic Techniques; Keratins; Melanoma; Paget Disease, Extramammary; Paget's Disease, Mammary; Retrospective Studies; S100 Proteins; Skin Neoplasms

Topics: Aged; Aged, 80 and over; Female; Genitalia; Humans; Immunoenzyme Techniques; Keratins; Male; Microscopy, Electron; Middle Aged; Paget Disease, Extramammary; Skin Neoplasms

A case of perianal and perineal extramammary Paget's disease in a male is reported. The presence of gross cystic disease fluid protein--a new marker of apocrine epithelia--in Paget's cells provides additional insight into the histopathogenesis of this condition. This marker may be a valuable diagnostic adjunct in evaluating intra-epithelial malignancies at a variety of anatomic sites.

Topics: Aged; Anal Canal; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Carcinoembryonic Antigen; Carrier Proteins; Glycoproteins; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Male; Membrane Transport Proteins; Neoplasm Proteins; Paget Disease, Extramammary; Perineum; Skin Neoplasms; Sweat Glands

The patterns of expression of cytokeratin polypeptides which are closely correlated to routes of differentiation of epithelial cells were studied in extramammary Paget's disease. Cytokeratins of uninvolved and involved epidermis were analyzed by two-dimensional gel electrophoresis of microdissected tissue preparations as well as by immunofluorescence microscopy using cytokeratin antibodies with different specificities. In uninvolved epidermis, cytokeratins Nos. 1, 5, 6, 10, 11, 14, and 16, characteristic of keratinocytes, were found. Epidermis infiltrated by Paget's cells contained the same components and, in addition, cytokeratins Nos. 7, 8, 18, and 19, the latter being characteristic of simple and glandular epithelia, including apocrine and eccrine skin glands. By immunohistochemistry, broad-spectrum antibodies to cytokeratins decorated both keratinocytes and Paget's cells. Antibodies selective for cytokeratins Nos. 1, 10, and 11 stained suprabasal keratinocytes but not Paget's cells. In contrast, antibodies to cytokeratin No. 18 were negative on keratinocytes but the Paget's cells were selectively stained, as were the secretory cells but not the ductal cells in apocrine and eccrine glands. The results show that the cytoskeleton of Paget's cells is different from that of keratinocytes and ductal cells of skin glands and suggest that these tumor cells express the glandular type cytokeratins Nos. 7, 8, 18, and 19. This provides cell biologic support for a relationship of cells of Paget's disease to secretory cells of apocrine and eccrine glands. The histogenesis of extramammary Paget's cells is discussed in relation to these findings.

Topics: Aged; Fluorescent Antibody Technique; Humans; Immunoelectrophoresis, Two-Dimensional; Keratins; Male; Paget Disease, Extramammary; Peptides; Skin; Skin Neoplasms; Staining and Labeling

The expression of cytokeratins in Paget cells in mammary and extramammary Paget's disease was studied using different keratin antibodies and immunofluorescence microscopy. Antibodies to epidermal keratin did not react with the Paget cells but stained the surrounding epidermis. Two monoclonal cytokeratin antibodies (PKKI and RGE 53), which reacted typically with simple glandular epithelia in normal tissues, brightly stained the Paget cells and left the surrounding epidermal cells unstained. The results indicate that Paget cells are derived from mammary or sweat duct epithelium rather than from epidermal cells.

Topics: Antibodies, Monoclonal; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Epithelium; Female; Fluorescent Antibody Technique; Humans; Keratins; Paget Disease, Extramammary; Paget's Disease, Mammary; Skin Neoplasms; Sweat Glands

Three mouse monoclonal anti-human cytokeratin antibodies were made against human sole epidermis. One of these (KA4) was shown to react with a variety of human simple epithelium, including eccrine and apocrine sweat glands and the luminal cells of the breast ducts and lobules, but failed to decorate interfollicular stratified squamous epithelium. This antibody reacted by the immunoblot technic with cytokeratins of Mr values 54, 46, and 40 kdaltons. KA4 reacted strongly with clear cells found in 11% of breast epithelium in clinically uninvolved nipples and with all Paget's cells in four cases of mammary and five cases of extramammary Paget's disease. These findings suggest a common cellular phenotype for Paget's cells and relates them to a population of cells found in breast epithelium.

Topics: Aged; Anal Gland Neoplasms; Animals; Antibodies, Monoclonal; Antigen-Antibody Reactions; Carcinoembryonic Antigen; Carcinoma, Intraductal, Noninfiltrating; Collodion; Electrophoresis, Polyacrylamide Gel; Female; Histocytochemistry; Humans; Keratins; Mice; Mice, Inbred BALB C; Middle Aged; Paget Disease, Extramammary; Paget's Disease, Mammary; Phenotype; Rabbits; S100 Proteins; Vulvar Neoplasms

The histogenesis of extramammary Paget's disease has long remained unresolved and controversial. In an attempt to delineate the origin of the neoplastic cells in this disease, the immunoperoxidase localization of gross cystic disease fluid protein (GCDFP-15), a marker of apocrine epithelium, carcinoembryonic antigen (CEA), and keratin proteins, was determined for seven cases of extramammary Paget's disease (five vulvar, one anogenital, and one axillary). Immunoreactivity for GCDFP-15 was localized within Paget cells in six of our seven cases, including five cases from the vulva and one case from the axilla. CEA was present in the Paget cells in all seven cases. None of the Paget cells exhibited immunoreactivity for keratin proteins. Within normal skin, eccrine glands were immunoreactive for both keratin and CEA, whereas GCDFP-15 localized only to apocrine ducts and glands. Our findings strongly support an apocrine cell derivation for extramammary Paget's disease.

Topics: Aged; Apocrine Glands; Apolipoproteins; Apolipoproteins D; Axilla; Carcinoembryonic Antigen; Carrier Proteins; Female; Glycoproteins; Humans; Immunoenzyme Techniques; Keratins; Membrane Transport Proteins; Middle Aged; Paget Disease, Extramammary; Skin Neoplasms; Sweat Glands; Vulvar Neoplasms

The plasma membrane ultrastructure of the extramammary Paget cells was characterized by freeze-fracture electron microscopy, which was first employed for the study of Paget cells. The Paget cell plasma membrane revealed a flat fractured plane with much fewer and smaller desmosome-particle aggregations than those of the keratinocyte. No gap junctions were detected. Many intramembranous particle-free vesicles were seen in the intercellular spaces. Particle-free blebs projecting from the plasma membranes were seen on some cell surfaces. These features greatly differed from those of keratinocytes. On the other hand, an increase of gap junctions was noticed o the keratinocytes around or in the Paget's disease lesions.

Topics: Aged; Cell Membrane; Freeze Fracturing; Humans; Intercellular Junctions; Keratins; Male; Microscopy, Electron; Paget Disease, Extramammary; Skin Neoplasms

Topics: Age Factors; Aged; Cell Differentiation; Cell Membrane; Cytoplasm; Cytoplasmic Granules; Desmosomes; Female; Gonadal Steroid Hormones; Histocytochemistry; Humans; Keratins; Microscopy, Electron; Mitochondria; Paget Disease, Extramammary; Ribosomes; Skin; Vulva

Topics: Desmosomes; Endoplasmic Reticulum; Epithelial Cells; Female; Glycogen; Golgi Apparatus; Humans; Keratins; Lysosomes; Microscopy, Electron; Microtubules; Middle Aged; Mitochondria; Mitosis; Paget Disease, Extramammary; Ribosomes; Skin Neoplasms