bromochloroacetic-acid and Vulvar-Neoplasms

Although spindle cell carcinoma (SC) is a common neoplasm in the oral cavity, upper respiratory tract, and other head and neck areas, its occurrence in the vulva is rare. We report a case of this rare condition with immunohistochemical, ultrastructural, and human papillomavirus (HPV) testing. The neoplastic cells were positive for vimentin, keratins (AE1-AE3, keratin 902, and keratin 903), and epithelial membrane antigen. Ultrastructurally, they showed primitive junctions and tonofilaments. HPV testing by polymerase chain reaction was negative. In addition, we review the clinicopathologic findings of the four well-documented cases of vulvar SC that have been reported previously in the English language literature.

Topics: Aged; Biomarkers, Tumor; Carcinoma; DNA, Viral; Fatal Outcome; Female; Humans; Immunohistochemistry; Intercellular Junctions; Intermediate Filaments; Keratins; Lichen Sclerosus et Atrophicus; Mucin-1; Neoplasm Proteins; Papillomaviridae; Polymerase Chain Reaction; Vimentin; Vulvar Neoplasms

Cellular angiofibroma is a rare tumor. We report a vulvar case in a 37 year old woman. This nodular, well circonscribed tumor consists of bland spindle cells, numerous thin or thick often hyalinized vessels and adipocytes. The stromal cells are positive for vimentin and negative for CD34, protein S100, smooth muscle actin, desmin, epithelial membrane antigen and cytokeratin. Cellular angiofibroma is a benign tumor that has to be differentiated from aggressive angiomyxoma, angiomyofibroblastoma, glomangiopericytoma, spindle cell lipoma, solitary fibrous tumor and perineurioma.

Topics: Actins; Adult; Angiofibroma; Antigens, CD34; Desmin; Diagnosis, Differential; Female; Humans; Keratins; Mucin-1; S100 Proteins; Stromal Cells; Vimentin; Vulvar Neoplasms

Extraocular sebaceous carcinoma is an uncommon neoplasm usually localized on the head and neck. Sebaceous glands are abundant on the vulva, but vulvar sebaceous carcinoma is an uncommon neoplasm. To our knowledge, there are only five previously reported cases of sebaceous carcinoma on this location. We report an additional case of vulvar sebaceous carcinoma associated with Bowen's disease in the overlying epidermis. The patient also had bowenoid papulosis involving the skin of labia majora. We analyzed by immunohistochemistry, Southern blot hybridization, and polymerase chain reaction (PCR) techniques for the presence of DNA of human papilloma viruses (HPVs) in the specimen of sebaceous carcinoma and in lesions of bowenoid papulosis. Immunohistochemistry, Southern blot hybridization, and PCR studies in specimens of bowenoid papulosis lesions and sebaceous carcinoma did not detect DNA of HPVs. A significant increase in intranuclear p53 staining was demonstrated in several areas of neoplastic aggregations of sebaceous carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Proliferating Cell Nuclear Antigen; Sebaceous Gland Neoplasms; Skin; Vulvar Neoplasms

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

We report a case of vulvar epithelioid sarcoma with metastases to the scalp, an inguinal lymph node, lungs, liver, and kidneys. Epithelioid sarcoma typically involves the extremities of young men and may be confused histologically with various benign and malignant processes. Only five cases of primary vulvar epithelioid sarcoma have been previously reported. The present case represents the first report of cutaneous metastases from this primary site. We also review the literature pertaining to the clinical, pathologic, and immunohistochemical features of this rare tumor.

Topics: Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Sarcoma; Scalp; Skin Neoplasms; Vulvar Neoplasms

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

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

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

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

Ectopic breast tissue is defined as glands located outside of the breast. Ectopic breast tissue should be excised because it may develop benign or malignant pathologic processes. Although lactation changes can occur, lactating adenoma in the vulva are extremely rare.. We report a case of a young woman who presented with multiple vulvar masses during her pregnancies. The masses were excised, and histology confirmed multiple vulvar lactating adenomas.. Vulvar lactating adenoma may be misdiagnosed as adenocarcinoma in frozen diagnosis and aspiration cytology if breast tissue is not anticipated. Although the incidence of ectopic mammary tissue of the vulva is low, this possibility should be considered when evaluating patients with mass lesions of the vulva in the appropriate clinical setting.

Topics: Actins; Adenoma; Adult; Breast; Choristoma; Female; Humans; Keratins; Lactation; Membrane Proteins; Pregnancy; Pregnancy Complications, Neoplastic; Receptor, ErbB-2; 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

Vulvar epithelioid sarcoma is a rare, undifferentiated soft-tissue sarcoma, with a high rate of local relapse, regional nodal spread and distant metastases. The aim of this study was to investigate the clinical features, diagnosis, treatment and prognosis of this malignancy.. We studied the clinicopathologic features of 20 cases of vulvar epithelioid sarcoma, of which 4 cases were admitted to our hospital from 1999 to 2009. All of the patients received radical local excision with inguinofemoral lymphadenectomy. Seven patients were treated without adjuvant therapy. Seven patients received postoperative radiotherapy only and three underwent chemotherapy. Chemotherapy plus radiotherapy were given postoperatively in three.. The patients ranged in age from 23 to 80 years (median: 36 y). The tumors ranged from 1 to 10 cm in their greatest diameter (median: 5.1 cm). All cases showed immunoreactivity for both vimentin and cytokeratin. Follow-up information on all 20 patients was available, and covered periods ranging from 3 to 104 months.11 patients were alive with no evidence of disease. 2 patients developed lymph node metastases but alive. 7 patients had died of the disease. Survival of the early stage (I-II) patients was significantly longer than those in the advanced stage (III-IV) (median, 21 vs. 6 months, P < 0.01). There was no significant difference between survival of patients with or without inguinofemoral lymphadenectomy (median, 11.5 vs. 6 months, P = 0.086).. Because of the relatively frequent misdiagnosis, a differential diagnosis combined with immunohistochemistry is needed to determine an early and accurate diagnosis. The tumor markers exhibiting immunoreactivity includ vimentin, epithelial membrane antigen (EMA) and cytokeratin (CK). Radical local excision with adequate margin (at least 2 cm) and bilateral inguinofemoral lymphadenectomy is effective for the treatment of vulvar epithelioid sarcoma. The role of adjuvant therapy, chemotherapy and radiation remains unclear but merits consideration.

Topics: Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Female; Follow-Up Studies; Humans; Keratins; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Mucin-1; Neoplasm Staging; Radiotherapy, Adjuvant; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Survival Rate; Vimentin; Vulva; Vulvar Neoplasms; Young Adult

Epithelioid sarcoma of the vulva is an extremely rare neoplasm with aggressive behavior and poor outcome. Herein, we report a case of vulvar epithelioid sarcoma presenting in a 17-year-old very early in her pregnancy. The patient presented with an asymptomatic nodule of the right labia majora of 1-year duration. Computerized tomographic scans showed enlarged inguinal lymph nodes and numerous lung nodules. Positron emission tomography was performed and revealed no suspicious lesions for metastatic disease. The patient underwent local excision of her vulvar lesion. On the basis of morphology and extensive immunohistochemistry, the lesion was classified as epithelioid sarcoma. The patient was referred to radiation therapy and upon evaluation, she was found to be in her sixth week of gestation. The patient continued with her pregnancy and underwent a lymph node dissection, which was positive. We review the literature of only the well-documented cases extensively studied by immunohistochemical analysis. We summarize the clinical presentation, clinical impression, treatment modalities, and outcomes of these cases. On account of the rarity of this disease in the vulva, there is no clear consensus on treatment modalities, but it seems that early aggressive surgical resection is the treatment of choice, with the role of adjuvant therapy to be determined.

Topics: Adolescent; Antigens, CD34; Female; Humans; Keratins; Platelet Endothelial Cell Adhesion Molecule-1; Pregnancy; Pregnancy Complications, Neoplastic; Sarcoma; Vulvar Neoplasms

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

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

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

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

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

Nodal involvement is one of the most significant prognostic factors in squamous cell carcinoma (SCC) of the vulva. We conducted a retrospective analysis of 31 women with histologically node-negative SCC from a population-based cohort of Grampian women. Median follow-up was 42 months after radical vulvectomy with groin node dissection. In total, 13 women (42%) were found to have micrometastases on immunohistochemistry. The risk of recurrence was almost 20-fold higher in those with micrometastases compared to those without (hazard ratio=19.6 (95% CI 2.3-171).

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Vulvar Neoplasms

Trichogenic tumors are very rare in genital skin and often cause diagnostic problems because they are mitotically active and they share some histologic features with basal cell carcinomas (BCCs). We present the clinical and histologic features of 16 vulvar trichogenic tumors (6 plaque-like, 10 nodular; average age, 65 years) in comparison with 16 BCCs (11 plaque-like, 5 nodular; average age, 78 years). All trichogenic tumors, except 1 case with HSV infection, were nonulcerated tumors. Superficial plaque-like trichogenic tumors featured basal keratinocyte proliferations with peripheral nuclear palisading but no clefting at the epithelial-stromal interface. Nodular trichogenic tumors consisted of solid lobules of squamous cells and anastomosing cords and reticulations of follicular germinative cells with mitoses and apoptosis. Large pink cells with trichohyaline granules and melanocytes resembling the inner hair sheath, and clear cells resembling the outer root sheath were common. Most cysts were keratinized, but some fluid-filled cysts showed apocrine and sebaceous differentiation. The well-defined mesenchymal component of trichogenic tumors was pale and mucinous, and contained fibrocytes and fibrillary collagen bundles. All BCCs showed surface ulcerations and clefting at the stromal-epithelial interface. BCCs showed no trichogenic differentiation and lacked an organized mesenchymal tumor component. The tumor stroma of BCCs was paucicellular, mucinous, or granulation tissue-like with an inflammatory infiltrate.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Basal Cell; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Neoplasms, Adnexal and Skin Appendage; Skin Neoplasms; Vulvar Neoplasms

Identification of early invasion in vulvar intraepithelial neoplasia 3 (VIN 3) and cervical intraepithelial neoplasia 3 (CIN 3) may be difficult with the use of routine hematoxylin-eosin staining. Presence of obscuring inflammation and tangential tissue sectioning are the most common diagnostic pitfalls.. To examine the utility of double immunostaining for cytokeratin-collagen IV or cytokeratin-laminin in the detection of early invasion in VIN 3 and CIN 3.. The study group consisted of 10 cases of "VIN 3, suspicious for invasion" and 10 cases of "CIN 3, suspicious for invasion." The negative control group consisted of VIN 3 (n = 15) and CIN 3 (n = 10). The positive control group consisted of cases of invasive vulvar carcinoma (n = 11) and invasive cervical carcinoma (n = 25). All cases were double immunostained for cytokeratin and collagen IV and, in a separate reaction, for cytokeratin and laminin. The continuity of the basement membrane and the presence of stromal invasion were assessed in the stained sections.. The staining for collagen IV and laminin yielded identical results. A well-defined, continuous basement membrane was visualized in all cases of VIN 3 and CIN 3. A discontinuous or absent basement membrane was observed around the malignant cells on the invasive tumor front in all cases of vulvar and cervical carcinoma. In 2 of 10 cases of VIN 3, suspicious for invasion and in 4 of 10 cases of CIN 3, suspicious for invasion definitive foci of microinvasion were identified with the use of double immunostaining. A well-defined, continuous basement membrane was present in the remaining cases "suspicious for invasion.". Double immunostaining for cytokeratin- collagen IV or cytokeratin-laminin is useful for evaluation of early invasion in equivocal cases of VIN 3 and CIN 3.

Topics: Adenocarcinoma; Basement Membrane; Biomarkers, Tumor; Collagen Type IV; Female; Humans; Keratins; Laminin; Neoplasm Invasiveness; Retrospective Studies; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vulvar Neoplasms

Acantholytic carcinoma is a subtype of squamous carcinoma, characterized by tubular and alveolar formations as a consequence of the acantholysis. We report a case of vulvar squamous acantholytic carcinoma (VSAC) in a 69-year-old woman, who was admitted to our institution for vulvar pruritus and the presence of a large, bilateral, exophytic, and ulcerated lesion, measuring 7 x 8 cm. The patient had never received vulvar or pelvic radiation therapy. Pathological examination with an immunohistochemical study showed features of VSAC and high p16 protein expression. Molecular study by polymerase chain reaction amplification of DNA tumor revealed a weakly positive signal for human papillomavirus. In conclusion, our case, which is the first case of VSAC with polymerase chain reaction analysis and immunohistochemical expression of p16 protein, suggested that this neoplasm could be related to human papillomavirus infection.

Topics: Acantholysis; Aged; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Humans; Immunohistochemistry; Keratin-14; Keratins; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Tumor Virus Infections; Vimentin; Vulvar Neoplasms

In early stage vulvar carcinoma patients, there is at trend towards individualized treatment in order to reduce morbidity and sequela following inguinal lymph node dissection. However, recurrences in the groin are almost always fatal. In the present study, we address the occult lymph node metastases in vulvar squamous cell carcinoma patients by using serial sectioning and immunostaining of lymph nodes in a larger series of vulvar carcinoma patients and relate the findings to clinical follow-up data.. From 75 vulvar squamous cell carcinoma patients staged surgical FIGO I-III, 421 lymph nodes found negative at the hematoxylin & eosin (H&E) routine investigation were scrutinized. From formalin-fixed and paraffin-embedded tissues, sections were cut with 150 mum interval and stained with H&E and cytokeratin AE1/AE3. Two classes were used to describe the amount of tumor cells: <100 cells and >100 cells.. Positive cytokeratin AE1/AE3 staining was found in 25/421 (6%) of the lymph nodes. Occult lymph node metastases were found in 17/75 (23%) of the patients. Correlation was found between lymph node metastasis and site of recurrence (P = 0.01). Twenty-eight percent of the patients had relapse.. The present study underlines the importance of serial sectioning and immunostaining of lymph nodes in the search for micrometastases in vulvar carcinoma patients. However, the results of the present study do not suggest a more thorough examination of non-sentinel lymph nodes in vulvar carcinoma patients where the sentinel lymph nodes are thoroughly examined.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Keratins; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Retrospective Studies; Staining and Labeling; Vulvar Neoplasms

Topics: Acrospiroma; Adult; Carcinoembryonic Antigen; Female; Humans; Immunohistochemistry; Keratins; Middle Aged; Mucin-1; Sweat Gland Neoplasms; Vulvar Neoplasms

Primary villoglandular adenocarcinomas of the vulva are rare, and only seven cases have been described to date. Hypotheses about the origin of this neoplasm remain highly speculative. We report the case of a 58-year-old woman who developed this very uncommon malignant tumor. Immunohistochemical studies of the tumor revealed positive staining for cytokeratins 7 and 20 and a negative staining for estrogen and progesterone receptors. Special stains showed the presence of intracellular mucin. No other primary lesion was found on clinical evaluation and extensive investigation. The patient was first treated by radical hemivulvectomy, followed by ipsilateral inguinal lymph node dissection and laparoscopic right salpingo-oophorectomy for an incidental finding of an ovarian cyst. The patient remained free of disease 16 months after the initial surgery.

Topics: Adenocarcinoma; Biomarkers, Tumor; Cloaca; Disease-Free Survival; Female; Humans; Intermediate Filament Proteins; Keratin-20; Keratin-7; Keratins; Middle Aged; Mucins; Vulvar Neoplasms

Epidermal keratinocytes respond to low-dose light irradiation by inducing signaling cascades that lead to long-term effects on gene transcription thereby protecting cells against damage. In contrast, little is known about immediate light-induced alterations of structural proteins. We have made the intriguing observation that light produces fundamental changes in the properties of the keratin filament system of cultured epidermoid A-431 cells. A short light exposure (1-10 min) causes the keratin cytoskeleton to become immediately resistant to the tyrosine phosphatase inhibitor orthovanadate, which otherwise disrupts the keratin filament network completely in just a few minutes. This protective effect is inducible throughout the entire visible spectrum and is elicited by normal room light (<200 Lux). Exposure of cells to monochromatic light of various wavelengths is therefore equally effective. In addition, the acquisition of orthovanadate resistance has been directly monitored in living cells; a partially disrupted keratin cytoskeleton recovers to a completely filamentous network in half an hour. Finally, the protective light effect is largely reversed in 2 h and can be mimicked by preincubation with the p38 kinase inhibitor SB203580. In contrast, the mitogen-activated protein kinase inhibitor PD98059 and epidermal growth factor inhibit orthovanadate action to a lesser extent. Taken together, these observations suggest a stabilizing function of light on the keratin filament network; this may be of relevance to the treatment of skin diseases with reduced keratin stability.

Topics: Drug Resistance; Epidermal Cells; Female; Humans; Intermediate Filaments; Keratins; Phosphorylation; Protein Tyrosine Phosphatases; Tumor Cells, Cultured; Ultraviolet Rays; Vanadates; Vulvar 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

A 26-year-old Hispanic woman complaining of "itching" and "herpetic lesions" on the vulva for 9 months was seen at a university hospital. On physical examination, multiple vulvar masses were noted. Biopsies taken from these lesions showed invasive keratinizing squamous cell carcinoma. The vulvectomy specimen revealed 4 tumor masses, the largest located on the mons pubis. Although the incidence of vulvar intraepithelial neoplasia has increased in recent years, only very few cases of invasive carcinoma have been reported in young women. The tumors that occur at a younger age characteristically have basaloid or warty histology, in contrast to those occurring in older women, which usually are well-differentiated keratinizing carcinomas. We believe this is an unusual case of vulvar squamous cell carcinoma. In addition to our patient's young age, her tumor had a histologic profile usually found in lesions of an elderly woman. The tumor was negative for human papillomavirus by polymerase chain reaction analysis and was positive for p53 by immunohistochemistry.

Topics: Adult; Biopsy; Carcinoma, Squamous Cell; Female; Humans; Immunoenzyme Techniques; Keratins; Lymph Node Excision; Neoplasm Invasiveness; Polymerase Chain Reaction; Tumor Suppressor Protein p53; Vulvar 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

We have previously described vulva carcinoma-derived A-431 subclone AK13-1, which stably expresses fluorescently labeled cytokeratin filaments (CKFs). Time-lapse fluorescence microscopy of these cells permits the continuous monitoring of the dynamics of the CKF cytoskeleton in vivo. To study mechanisms and principles of CKF disassembly as it occurs, e.g., during mitosis and liver disease, we have treated cells with the phosphatase inhibitor okadaic acid (OA), which induces complete CKF network breakdown within 3-5 h without significantly affecting the organization of the actin- and tubulin-based cytofilaments. In time-lapse movies, we find that the network breakdown starts at the cell periphery and proceeds toward the cell center, where residual filaments become compacted into a prominent perinuclear ring. The progressing disassembly is paralleled by an increase of diffuse fluorescence throughout the cytoplasm and the appearance of non-filamentous spheroidal aggregates. They are formed in the filament-free cell periphery from non-filamentous precursors and can sometimes be detected in the proximity of desmosomes. Other aggregates are either found in close apposition to CKFs or are generated directly from the compacted perinuclear material. Primary granules later fuse, thereby producing structures of considerable size. We show that CKF network breakdown and granule formation rely on metabolic energy and that the continued presence of OA is needed for its completion. We conclude that phosphorylation/dephosphorylation is an important mechanism regulating CKF network dynamics in vivo with far-reaching implications for the understanding of epithelial plasticity and pathology.

Topics: Adenosine Triphosphate; Cytoskeletal Proteins; Cytoskeleton; Desmoplakins; Enzyme Inhibitors; Epithelial Cells; Female; Green Fluorescent Proteins; Humans; Indicators and Reagents; Keratins; Luminescent Proteins; Microscopy, Fluorescence; Okadaic Acid; Phosphorylation; Recombinant Fusion Proteins; Stress Fibers; Time Factors; Tumor Cells, Cultured; Vulvar Neoplasms

Metastases to inguinofemoral lymph nodes in patients with carcinoma of the vulva alter the prognosis and treatment of this disease. Our goal was to determine if immunohistochemical staining could reveal occult metastatic nodal disease not detected with routine hematoxylin and eosin staining. We retrospectively examined a total of 110 lymph nodes from 10 patients who had undergone lymph node dissection and found to have all negative nodes. Paraffin embedded lymph nodes were immunostained with a monoclonal antibody directed against multiple low- and high-molecular weight cytokeratins. Micrometastases were not detected in any lymph nodes examined with immunohistochemistry. All positive and negative controls yielded satisfactory results. It is concluded that immunohistochemistry with cytokeratin antibodies does not provide greater sensitivity than routine hematoxylin and eosin staining for the detection of nodal metastases in vulvar carcinoma.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Prognosis; Retrospective Studies; Vulvar Neoplasms

We report a unique case of a salivary gland type of "hybrid carcinoma" arising within a Bartholin's gland adenoma. The tumor was characterized by large areas of an epithelial-myoepithelial carcinoma similar to that of the salivary gland with a peripheral infiltrative pattern of an adenoid cystic carcinoma (ACC).

Topics: Adenoma; Bartholin's Glands; Biopsy; Carcinoma, Adenoid Cystic; Epithelium; Female; Humans; Immunohistochemistry; Keratins; Lymph Node Excision; Middle Aged; Neoplasms, Multiple Primary; S100 Proteins; Salivary Gland Neoplasms; Vulvar Neoplasms

The poor prognosis of malignant rhabdoid tumor is emphasized and histopathological criteria for distinction from epithelial sarcoma of the vulva are discussed. Immunohistochemical analyses were performed by using nine different antigens including vimentin, cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, desmin, muscle-specific actin, S-100 protein, AP-15, neuron specific enolase. This is the sixth reported case of a malignant rhabdoid tumor of the vulva. The patient died eight months after the initial diagnosis in spite of a combination of surgery, adjuvant chemotherapy and external radiotherapy.

Topics: Adult; Biomarkers, Tumor; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Recurrence, Local; Rhabdoid Tumor; Skin Neoplasms; Vimentin; Vulvar Neoplasms

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

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

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

Radical vulvectomy for the treatment of a vulvar carcinoma inevitably entails severe psychosexual consequences for the patients. Thus, for such tumors, reliable histological prognostic parameters are needed to allow; when appropriate, the use of less radical operative measures. One possible approach to this problem might be to examine tumors immunohistochemically for the presence of cytoskeletal components. To assess the utility of this method, we applied a panel of antibodies directed against cytokeratins (CKs) and vimentin to a groups of vulvar carcinomas (62 primary and 35 recurrent tumors) and examined the results for possible correlations with the course of disease and various clinical parameters. all of the investigated CKs typical of squamous epithelia had no prognostic relevance. In contrast, the present of CKs typical of glandular differentiation as well as vimentin, suggesting early dedifferentiation, resulted in a less favorable prognosis. Thus, the procedures applied in the present study may have a role to play a decisions concerning the appropriate therapy for such tumors.

Topics: Female; Humans; Keratins; Lymph Nodes; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Vimentin; Vulvar Neoplasms

We report two cases of synovial sarcoma arising in the vulva. The patients were 30 and 37 years old and presented with a painless mass that was interpreted clinically as a cyst. The tumors were 2.0 and 1.2 cm in greatest diameter. Histologically, they were composed of epithelial cells forming solid nests and gland-like and papillary structures surrounded by spindle-shaped cells. Immunohistochemically, the epithelial cells stained for cytokeratin and the spindle-shaped cells for vimentin. Ultrastructurally, the epithelial cells had prominent intercellular junctions and narrow microvilli and were separated from the spindle-shaped cells by a basal lamina. The spindle-shaped cells were closely apposed with focal intercellular contacts. One tumor recurred locally 3.5 years after excision, but the patient was alive and well 1 year after a re-excision and radiation therapy. The other patient was alive and well 4 years after an excision. These tumors are the first reported examples of synovial sarcoma arising in the vulva.

Topics: Adult; Diagnosis, Differential; Epithelium; Female; Humans; Immunoenzyme Techniques; Keratins; Neoplasm Recurrence, Local; Sarcoma, Synovial; Vimentin; Vulvar Neoplasms

A carcinoma of the clitoris showed a variety of histologic features not usually encountered in squamous cell carcinoma of the vulva. In addition to poorly differentiated nonkeratinizing squamous cell carcinoma, there were large areas showing a transitional cell carcinoma pattern, as well as foci of spindle and anaplastic cells. The clitoral neoplasm also differed in its cytokeratin (CK) profile from that described in invasive squamous cell carcinoma of the vulva, especially with regard to the widespread staining for CK 18 and 19 in the former. Thus, our study suggests that some carcinomas of the clitoris differ from those of ordinary squamous cell carcinomas of the vulva. More cases should be studied using immunohistochemical methods in order to establish the full histopathologic and CK range of the former.

Topics: Aged; Carcinoma, Transitional Cell; Clitoris; Female; Humans; Keratins; Vulvar Neoplasms

Histologic grade seems to be of limited prognostic significance in patients with vulvar carcinoma. However, the study of cytokeratin expression is of potential interest because it allows a more precise evaluation of the degree of squamous differentiation. This study was conducted to investigate whether differences in cytokeratin expression exist between normal vulvar epithelium and vulvar carcinoma and whether these differences are prognostically significant.. The expression of several differentiation markers, i.e., cytokeratin (CK) 10, CK 13, and involucrin, was studied in samples of 41 vulvar carcinomas. The expression of CK 8, 10, 13, and 14 was compared with CK expression in normal vulvar epithelium and was correlated with tumor grade and tumor growth pattern. Tumor growth pattern was considered type A if infiltrating tumor cell nests showed a layer of small, basaloid cells bordering the surrounding mesenchymal tissue and was considered type B if this was not the case. Prognosis was based on whether disease recurred or not.. Sixteen patients had disease recurrence. No prognostic significance of tumor grade was found. Tumor growth pattern was prognostically significant: in patients with a type A tumor, recurrence was observed less often than in patients with a type B tumor (P = 0.03). Cytokeratin 14, typical for basal cells of normal vulvar epithelium, was expressed in all tumors, whereas CK 8 was not expressed in any tumor. A relationship between tumor growth pattern and the concordant expression of differentiation markers was observed: in 55% of type A tumors and in none of type B tumors, concordant expression of CK 10, CK 13, and involucrin was found.. The expression of differentiation markers in vulvar carcinoma is related strongly to the tumor growth pattern, and this pattern is prognostically significant.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Multivariate Analysis; Prognosis; Protein Precursors; Recurrence; Vulvar Neoplasms

The immunohistochemical expression patterns of cytokeratins 8 and 18 and vimentin were examined in frozen sections of 120 human mucosal squamous cell carcinomas with special emphasis on the topological distribution in the tumour. This was done in order to evaluate in squamous cell carcinoma a particular expression pattern observed recently by us in transitional cell carcinoma of the urinary tract and designated as an 'interface phenomenon'. This phenomenon implying maximum expression of cytokeratins 8 and 18 at the tumour front, and to a lesser extent also in areas of intratumorous stroma contact, was also found in about 50 per cent of the squamous cell carcinomas examined. It was even found for vimentin, which contrasted with transitional cell carcinoma. The percentages of occurrence of the phenomenon varied for the different sites of origin of the tumour. Tumour grade did not influence the results. These findings further support the idea that invasive carcinoma cells interacting with the stromal micro-environment display a characteristic intermediate filament phenotype that deviates from the pattern expected on the basis of their direction of differentiation. These changes might reflect phenotype involved in invasive, migrating, and proliferating activities.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Immunoenzyme Techniques; Keratins; Lung Neoplasms; Neoplasm Invasiveness; Neoplasm Proteins; Vimentin; Vulvar 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

A case of vulvar paraganglioma is reported. Following presentation with vulvar pain, a 1-cm nodule was excised from the labium minus of a 58-year-old woman. Histologically, the tumor was composed of nests of round eosinophilic cells with moderately pleomorphic nuclei, beneath an intact squamous epithelium. Ultrastructural studies indicated two cell types within the neoplasm: chief cells with numerous small neurosecretory granules and peripheral slender sustentacular cells. A reticulin stain confirmed the "zellballen" nature of the neoplasm, and the neoplastic cells showed moderate argyrophilia on a Grimelius stain. The immunoperoxidase stains for chromogranin and neuron-specific enolase were strongly positive in the neoplastic chief cells. Immunostaining using anti-S-100 antibody confirmed the finding of sustentacular cells by identifying many slender cellular processes among the chief cells. These light and electron microscopic findings are diagnostic of paraganglioma, an entity not previously reported in the vulva to our knowledge.

Topics: Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Female; Histocytochemistry; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Middle Aged; Organelles; Paraganglioma; Staining and Labeling; Vulvar Neoplasms

We report an undifferentiated sweat gland carcinoma of the vulva in an 80-year-old woman. The tumor, which was located in the right labium majus, resembled an epithelioid sarcoma histologically; it had a granulomatous appearance with multiple tumor nodules containing epithelioid tumor cells. The tumor also contained rhabdoid cells; a large cluster of them showed histological features indistinguishable from those of a malignant rhabdoid tumor. Immunohistochemically, the tumor cells reacted not only for epithelial markers such as cytokeratins, EMA, and CEA, which are known to be expressed by epithelioid sarcoma, but also for CA125 and with monoclonal antibodies recognizing sweat gland structures--namely, EKH5 and EKH6. For comparison, two epithelioid sarcomas and two extrarenal malignant rhabdoid tumors were also studied. Of these tumors, only one extrarenal rhabdoid tumor reacted with EKH5, and none reacted for CA125. Electron-microscopic examination of the present tumor showed the presence of discontinuous basal laminae and tonofibril-like structures as well as primitive cell junctions and interdigitating filopodia. From these findings, we conclude that the tumor was an undifferentiated sweat gland carcinoma mimicking an epithelioid sarcoma. Findings in this case support the idea of the diverse histogenesis of extrarenal malignant rhabdoid tumors and indicate that electron microscopy is important for differentiating epithelioid sarcoma from skin adnexal carcinoma.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Carcinoembryonic Antigen; Carcinoma; Cell Transformation, Neoplastic; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Sarcoma; Skin Neoplasms; Sweat Gland Neoplasms; Sweat Glands; Vulvar Neoplasms

The expression of AE1, AE2, AE3, and CAM 5.2 antikeratin monoclonal antibodies was investigated in 68 vulvar specimens by an avidin-biotin complex (ABC) method. They included normal vulva (NV, 10), non-neoplastic epithelial disorders (NNED, 31), vulvar intraepithelial neoplasia (VIN, 17), and squamous cell carcinoma (SCC, 10). AE1 weakly stained the basal cell layer in NV, exhibited a uniform suprabasal stain in hyperplasia, failed to stain dysplastic areas in VIN I-II, and was patchy and disorganized in VIN III and SCC. AE2 stained the upper third of the epithelium in NV, NNED, and VIN I-II, but it failed to stain VIN III basaloid and SCC; VIN III bowenoid was focally positive. AE3 offered little information, because it stained all lesions; VIN III and SCC, however, exhibited a patchy and disorganized stain. CAM 5.2 was expressed in only half of the cases of VIN III basaloid and in one case each of VIN I-II and SCC. We conclude that keratin expression varies according to the degree of dysplasia; AE1 may serve to separate certain cases of NNED from VIN I-II; AE2 and CAM 5.2 are useful to differentiate both histologic types of VIN III.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; Precancerous Conditions; Vulva; Vulvar Neoplasms

One hundred and ten women who underwent vulvectomy and inguinal-femoral lymphadenectomy for stages I-IV vulvar squamous cell carcinoma were studied. The most important factors that affected the inguinal lymph node status in the order of importance were vascular invasion, clinical stage, tumor thickness, depth of stromal invasion, and amount of keratin. Fourteen (88%) of 16 tumors with vascular invasion in the primary tumor metastasized. In the absence of vascular invasion, 18 (19%) of 94 tumors metastasized. Overall, 82% of tumors were correctly classified into lymph node negative and positive groups on the basis of vascular invasion. Tumor thickness and depth of stromal invasion had a similar accuracy in predicting lymph node status. The risk of lymph node metastasis increased from 0% when tumor thickness or depth of stromal invasion was less than 2 mm, to over 20% when depth of stromal invasion was greater than 2 mm, and to over 40% when tumor thickness exceeded 4 mm. A combination of vascular invasion, tumor thickness (or depth of stromal invasion), and the amount of keratin correctly classified 97% (76/78) of the lymph node negative group and 63% (20/32) of the positive group with an overall accuracy of 87%. The probability of having lymph node metastasis was computed for individual patients on the basis of one or more pathologic parameters using a logistic regression model. This feasibility is an important step toward individualized therapy for vulvar carcinoma.

Topics: Carcinoma, Squamous Cell; Female; Humans; Keratins; Lymphatic Metastasis; Neoplasm Invasiveness; Neoplasm Staging; Recurrence; Regression Analysis; Risk Factors; Survival Rate; Vulvar Neoplasms

A polyclonal keratin antibody (pK), a marker for epithelial cells, was used to evaluate lymph nodes (LNs) from patients with invasive squamous carcinomas of the cervix (CxCa) or vulva (VCa) to determine whether this technique could increase the detection of metastases (mets) over that obtained by light microscopy using a routine hematoxylin and eosin (H&E)-stained slide. The LN status of 15 cases of stage 1B CxCa and 14 cases of VCa was determined using a routine H&E slide. Subsequently, all LNs were resectioned and examined using a pK immunoperoxidase stain. In 329 lymph nodes from 14 cases of CxCa and 9 cases of VCa originally classified as LN-negative, only a single met was detected by the pK technique. In five cases of VCa and one case of CxCa (121 LNs), with LN mets or LN tumor emboli on the original H&E, three additional microscopic foci of mets were detected by pK. Of the four foci of mets discovered by pK, one was visible in retrospect on the original H&E section, and all four were easily identified on examination of a serial H&E section adjacent to the pK section. These results suggest that pK stains are unlikely to significantly increase our sensitivity in detecting mets in CxCa and VCa, beyond merely further sectioning and H&E staining of nodes.

Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Eosine Yellowish-(YS); Female; Hematoxylin; Humans; Immunoenzyme Techniques; Keratins; Lymph Nodes; Lymphatic Metastasis; Staining and Labeling; Uterine Cervical Neoplasms; Vaginal Smears; Vulvar Neoplasms

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

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

The clinicopathologic features of five cases of verrucous carcinoma of the vulva and their staining pattern with antikeratin monoclonal antibodies AE1 and AE3 were compared with those of conventional squamous cell carcinoma. Two patients had local recurrences but none died of the tumor. AE1 and AE3 antibodies stained the entire epithelial thickness in both verrucous and squamous cell carcinoma, but in the former the positivity was uniform and homogeneous everywhere, while in squamous cell carcinoma the positivity was extremely disorganized and patchy. The pattern of expression of monoclonal antibodies AE1 and AE3 confirms that verrucous carcinoma is an extremely well-differentiated squamous neoplasm in contrast to squamous cell carcinoma, which is heterogeneous from a viewpoint of differentiation.

Topics: Aged; Antibodies, Monoclonal; Carcinoma, Papillary; Female; Humans; Immunohistochemistry; Keratins; Retrospective Studies; Vulvar Neoplasms

Epithelioid sarcoma (ES) and malignant rhabdoid tumor (MRT) have heretofore been regarded as two separate clinicopathologic entities. However, they have some histologic similarities, and both represent histogenetic and phenotypic enigmas. This study reports the pathologic and immunohistochemical findings of four vulvar neoplasms occurring in young women that represented diagnostic dilemmas because of their similarity to both ES and MRT. Only one case had the classic histologic features of ES, whereas, in our opinion, the other three cases fulfilled the histologic criteria of MRT, despite the fact that two of the three cases were reported earlier as examples of ES. Neither electron microscopy nor immunohistochemistry has been found to be helpful in separating ES from MRT, mainly because they share several ultrastructural and immunophenotypic features. The behavior of these vulvar tumors--ours and the few published examples of ES--is generally aggressive, more in keeping with MRT than classic ES. We believe that some, if not most, putative ES of the vulva are in fact MRT, a neoplasm with an unfavorable prognosis.

Topics: Adult; Cell Nucleus; Female; Humans; Immunohistochemistry; Keratins; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Organelles; Rhabdomyoma; Sarcoma; Vimentin; Vulvar 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

Two monoclonal antibodies (MAb) specific for differentiation-related epidermal keratins have been developed. They represent specific molecular probes for different stages of epidermal differentiation. Antibody DE-K10 is chain-specific for cytokeratin polypeptide no. 10 (56.5 kD) expressed in all suprabasal layers of the epidermis. Antibody DE-SCK is specific for modified stratum corneum keratins and thus represents a marker for the terminal step of epidermal differentiation. Since the epitopes identified by both antibodies are preserved in formalin-fixed, paraffin-embedded tissue sections, these antibodies can be used for retrospective studies of differentiation in various pathological processes. We have used antibody DE-K10 to study the cytokeratin 10 expression in 26 stage II or III vulvar squamous cell carcinomas. Preliminary data suggest an increased risk of recurrence in cytokeratin 10 negative tumours.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epidermis; Female; Humans; Immunoblotting; Keratins; Middle Aged; Neoplasm Recurrence, Local; Vulvar Neoplasms

Using specific monoclonal antibodies (DE-K10 and DE-SCK respectively), the expression of some differentiation-related epidermal keratins was studied in 38 human vulvar squamous carcinomas. In the epidermis, expression of keratin 10 (K10) strictly paralleled the extent of differentiation; it was absent in the basal layer, appeared in the first suprabasal layers and increased in concentration towards the granular layer. However, K10 was rarely detected (1 case out of 12) in early stages of vulvar squamous carcinomas (tumours less than 2 cm, clinical stage I) regardless of the tumour grade. In larger and more advanced tumours (greater than 2 cm, clinical stages II and III), K10 was detected in 21 out of 26 cases. Its expression appeared to be related to maturation of malignant keratinocytes, being preferentially detected in more-differentiated parts. Occasionally however, cells that did not show histological signs of keratinisation were also K10-positive. Modified stratum corneum keratins (recognized specifically by monoclonal antibody DE-SCK) were detected in the most keratinized areas (horn pearls and their close vicinity) of some K10-positive tumours, i.e., in a pattern close to their normal expression in terminally differentiated epidermal cells. These data suggest differences in the regulation of K10 expression during the differentiation processes in the normal keratinising squamous epithelium and in squamous carcinomas. While the normal pattern of vulvar epithelial differentiation is accompanied by an increasing expression of K10, malignant keratinocytes, also when these are histologically moderately or well differentiated, cease expressing this keratin in the early stages of tumour development.

Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Keratins; 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

Desmosomes are not formed in epithelial cell cultures growing in media with low (less than or equal to 0.1 mM) concentrations of Ca2+ (LCM) but appear rapidly upon shift to media of normal calcium concentrations (NCM). Previous authors using immunolocalization of desmoplakin, a marker protein for the desmosomal plaque, in LCM-grown cells have interpreted positively stained, dense, cytoplasmic aggregates on intermediate filaments (IF) bundles as preformed plaque units which upon NCM shift would move to the plasma membrane and contribute to desmosome formation. Studying various cell cultures, including primary mouse keratinocytes and human A-431 cells, we show that most, probably all, desmoplakin-positive aggregates in LCM-grown cells are associated with membranous structures, mostly vesicles, and also contain other desmosomal markers, including desmoglein, a transmembrane glycoprotein. We interpret such vesicles as residual desmosome-derived domains endocytosed upon cell dissociation. Only keratinocytes grown for long times (2-4 wk) in LCM are practically free from such vesicles. In addition, we demonstrate that certain cells such as A-431 cells, when passaged in LCM and in the absence of stable junctions, are able to continually assemble "half-desmosomes" on the plasma membrane which in turn can be endocytosed as plaque-bearing vesicles. We also show that in LCM the synthesis of several desmosomal proteins (desmoplakins I and II, plakoglobin, desmoglein, "band 6 protein") continues and that most of the plaque protein, desmoplakin, is diffusely spread over the cytoplasm, apparently in a soluble monodisperse form of approximately 9S. From our results we propose that the plaque proteins occur in small, discrete, diffusible entities in the cytoplasm, in concentrations that are relatively high in LCM and low in NCM, from which they assemble directly, i.e., without intermediate precursor aggregates on IFs in the cytoplasm, on certain plasma membrane domains in a Ca2+ dependent process.

Topics: Animals; Calcium; Carcinoma, Squamous Cell; Cell Line; Cells, Cultured; Cytoskeletal Proteins; Desmogleins; Desmoplakins; Desmosomes; Epidermal Cells; Epithelial Cells; Female; Fluorescent Antibody Technique; gamma Catenin; Immunoassay; Intermediate Filaments; Keratins; Membrane Glycoproteins; Microscopy, Electron; Tumor Cells, Cultured; Vulvar Neoplasms

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

Squamous cell carcinomas have recently been shown to contain increased numbers of epidermal growth factor (EGF) receptors. Since EGF has an important role in epithelial growth and differentiation, it is possible that modulation of its receptor may have an important role in neoplasia. In an attempt to further explore the relationship of EGF receptor expression to malignant transformation, we examined 14 squamous cell carcinoma cell lines of the esophagus for the number and affinity of EGF receptors. Seven cell lines were newly isolated by this laboratory and recently characterized. The seven additional cell lines were obtained from Japan (4 cell lines) and South Africa (3 cell lines). Surprisingly, we found that esophageal carcinomas contained lowered quantities of surface EGF receptors (2- to 100-fold) and that the affinity of the EGF receptor was increased (6- to 100-fold) when compared to normal esophageal epithelial cells. Moreover, the biologic response of esophageal carcinoma cells to EGF differed markedly from that of other squamous cell tumor cells exhibiting elevated numbers of receptors, such as A431 and SCC-15. Human esophageal carcinoma cells were maximally stimulated by the addition of 5 ng/ml of EGF, similar to normal esophageal keratinocytes, but in contrast to normal cells were not inhibited by the higher concentrations tested (up to 40 ng/ml). On the other hand, addition of any EGF to the medium (beyond that normally present in serum) was found to dramatically inhibit the growth of A431 and SCC-15 cells. Our findings indicate that squamous cell neoplasia is not dependent upon increased numbers of cell surface EGF receptors, that EGF receptor number may have a determinant role in EGF cell toxicity, and that the stimulatory response of cells to EGF may reflect a complex function of EGF receptor number, affinity, and occupancy.

Topics: Carcinoma, Squamous Cell; Cell Line; Epidermal Cells; Epidermal Growth Factor; ErbB Receptors; Esophageal Neoplasms; Esophagus; Female; Humans; Japan; Keratins; Kinetics; Receptors, Cell Surface; South Africa; Vulvar Neoplasms

We describe cDNA clones of mRNAs encoding human cytokeratins nos. 8 and 18, and the amino acid sequences deduced from their nucleotide sequences. Human cytokeratin no. 8 is a typical cytokeratin of the basic (type II) subfamily, which is highly homologous to the corresponding bovine and amphibian (Xenopus laevis) proteins; however, unlike the amphibian protein, it does not contain glycine-rich oligopeptide repeats in its carboxyterminal 'tail' domain. Comparison with the reported amino acid sequences of two fragments of human 'tissue polypeptide antigen' (TPA), a widely used serodiagnostic carcinoma marker, revealed sequence identity, indicating that this serum component is derived from the intracellular cytokeratin no. 8 present in diverse kinds of epithelia and epithelium-derived tumors. Human cytokeratin no. 18 is very similar to the corresponding murine protein but contains two additional blocks of 4 and 5 amino acids in the 'head' portion. These cDNA clones and the RNA probes derived therefrom were used to detect specifically mRNAs by Northern-blot assays of RNAs from various carcinomas and cultured carcinoma cells. Using in situ hybridization on frozen sections of tumor-containing tissues, notably lymph nodes containing metastatic breast carcinoma, we were able to demonstrate the specificity and sensitivity of this procedure. The potential value for cell-biological research and pathology of being able to detect a mRNA encoding a given cytokeratin polypeptide in situ is discussed.

Topics: Amino Acid Sequence; Base Sequence; Carcinoma, Squamous Cell; Cell Line; Cloning, Molecular; DNA; Epithelium; Female; Humans; Keratins; Nucleic Acid Hybridization; Protein Biosynthesis; RNA, Messenger; Transcription, Genetic; Vulvar Neoplasms

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

Four cases of squamous cell carcinoma with sarcoma-like stroma located in the vulva (1), vagina (2) and cervix (1) of postmenopausal women are presented. The gross and microscopic features are very similar to those of similarly named tumors occurring in the upper respiratory and digestive tract and in the skin. Light microscopic, electron microscopic, and immunohistochemical examination provided convincing evidence that these tumors are composed solely of squamous cell carcinoma, which has undergone a spindle cell sarcoma-like transformation in the deeper portions. Follow-up revealed an aggressive clinical course in three of the four patients, who died of their tumor between 2 and 45 months after presentation. At the time of death, two of the patients had widespread metastases and the other had massive local recurrence.

Topics: Aged; Carcinoma, Squamous Cell; Carcinosarcoma; Diagnosis, Differential; Female; Fibroma; Follow-Up Studies; Genital Neoplasms, Female; Histocytochemistry; Humans; Keratins; Middle Aged; Sarcoma; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms

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

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

Topics: Adenoma, Sweat Gland; Adolescent; Cell Aggregation; Cell Nucleolus; Cell Nucleus; Cell Wall; Cytoplasm; Cytoplasmic Granules; Endoplasmic Reticulum; Epithelial Cells; Female; Glycogen; Golgi Apparatus; Humans; Keratins; Microscopy; Microscopy, Electron; Middle Aged; Mitochondria; Sweat Gland Neoplasms; Synaptic Vesicles; Vulvar Neoplasms