Paget's Disease Of Vulva Research Articles

Long-term outcome of perianal Paget's disease.

Extramammary Paget's disease of the perianal region is a rare finding that often results in delayed diagnosis and treatment. Although the natural history of the disease is not well characterized, it historically has been associated with other cancers. This study summarizes the history and treatment of all patients diagnosed with perianal Paget's disease at a single institution. Charts of all patients with a diagnosis of extramammary Paget's disease of the perianal region confirmed or treated at Memorial Sloan-Kettering Cancer Center between 1950 and 2000 were reviewed. Patients with vulvar Paget's disease or Bowen's disease were excluded except when Paget's disease of the perianal region was diagnosed first. Whenever possible, follow-up information was updated. Estimates of overall and disease-free survival were made by the method of Kaplan and Meier. Twenty-seven patients with a median age of 63 years were diagnosed with perianal Paget's disease. Most patients (74 percent) were treated with wide excision. Local recurrence occurred in 37 percent of all patients treated and in 30 percent of patients (6/20) undergoing a wide excision as part of their treatment. An invasive component was identified in 44 percent of patients (12/27) with perianal Paget's disease. Six patients (22 percent) required a colostomy as part of the treatment for their disease. Adjuvant chemoradiotherapy was used in 22 percent of patients (6/27) who had more aggressive disease. At a median follow-up of 67 months, 56 percent (15/27) had no evidence of disease, and two patients had died of metastatic disease. The overall and disease-free survival at five years was 59 and 64 percent, respectively, which decreased to 33 and 39 percent, respectively, by ten years. Perianal Paget's disease is a rare finding even at a large referral center. The disease process is generally a prolonged one marked by frequent recurrences, and the treatment of first choice is wide excision. Patients with invasive malignancies require more extensive surgery. The role of chemoradiotherapy remains undefined in this disease.

Vulvar Paget Disease: One Century After First Reported

OBJECTIVES.: To provide a critical assessment of the published literature on vulvar Paget disease and to allow individualized approaches to affected patients. MATERIALS AND METHODS.: A computerized search for studies published in the literature up to June 2002 was carried out using Ovid(c) and Medline databases. We excluded single case reports, letters to editors, and abstracts. RESULTS.: Historical and epidemiological aspects of vulvar Paget disease are summarized. Clinical and histopathological data support a recent proposal to classify vulvar Paget disease into two categories, primary and secondary, with significant clinical and prognostic implications. The treatment for primary vulvar Paget disease is wide and deep surgical excision. Inguinofemoral lymphadenectomy is added in the management of invasive neoplasms. In the presence of secondary Paget disease, therapy must be directed toward treatment of associated carcinoma. CONCLUSIONS.: The subclassification of vulvar Paget disease is essential for correct clinical management and treatment. Immunohistochemistry may assist in this important distinction.

Uroplakin-III to distinguish primary vulvar Paget disease from Paget disease secondary to urothelial carcinoma

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 distinct lesions, which may be aided by the use of immunohistochemistry, including UP-III. HUM PATHOL 33:545-548. Copyright 2002, Elsevier Science (USA). All rights reserved.

Vulvar Paget disease of urothelial origin: A report of three cases and a proposed classification of vulvar Paget disease

Extramammary Paget disease is generally considered a distinct entity that can involve the genital tract skin and may be associated with underlying adenocarcinoma. Evidence is presented that vulvar Paget disease represents a heterogeneous group of epithelial neoplasms that can be similar both clinically and histopathologically. Three cases of vulvar Paget-like disease that were manifestations of urothelial carcinoma are investigated. Vulvar Paget disease can be classified based on the origin of the neoplastic Paget cells as either primary (of cutaneous origin) or secondary (of noncutaneous origin). Each classification has 3 subtypes: primary, intraepithelial cutaneous Paget disease of the usual type; intraepithelial cutaneous Paget disease with invasion, and intraepithelial cutaneous Paget disease as a manifestation of underlying skin appendage adenocarcinoma; secondary, Paget disease of anorectal origin, Paget disease of urothelial origin, and Paget disease of other origin. This subclassification is based on a review of the literature and the current study of 3 patients with Paget-like disease of urothelial neoplastic origin. The 3 subtypes of vulvar Paget disease studied here can present similarly as eczematoid skin or vulvar mucosal lesions and may appear similar on routine hematoxylin and eosin–stained slides. Immunohistochemical studies can be used to help differentiate them. The distinction between these 3 types of 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 distinct lesions to avoid potential confusion and unnecessary surgery. HUM PATHOL 33:549-554. Copyright 2002, Elsevier Science (USA). All rights reserved.

Low-dose mitomycin C, etoposide, and cisplatin for invasive vulvar Paget's disease

Abstract.Watanabe Y, Hoshiai H, Ueda H, Nakai H, Obata K, Noda K. Low-dose mitomycin C, etoposide, and cisplatin for invasive Paget's disease.We report the effect of low-dose mitomycin C, etoposide, and cisplatin (low-dose MEP) therapy for three patients with invasive vulvar Paget's disease (invasive VPD) who declined radical vulvectomy and skin grafting. One patient achieved a complete response, while the other two showed partial responses (PR) without grade 3 or 4 adverse effects. The two patients with PR were undergone partial vulvectomy and inguinal lymph node dissection. All patients have no sign of recurrence for 10 months after chemotherapy. Our present results suggest that low-dose MEP is an effective and safe chemotherapy for invasive VPD and low-dose MEP may significantly improve postoperative quality of life in patients with invasive VPD by avoiding extensive vulvar resection and skin grafting.

Differential expression of mucin genes in mammary and extramammary Paget's disease.

Paget's disease (PD) of the skin is characterized by intraepidermal adenocarcinoma cells, which contain clear cytoplasm and abundant mucin. Nearly all cases of mammary PD (MPD) are associated with underlying ductal carcinoma of the breast, whereas in the majority of cases of extramammary PD (EMPD) no underlying regional malignancy is identified. Mucins are high molecular weight glycoproteins produced by epithelial cells. Different mucin genes are expressed in various types of tissues such as mammary glands, intestinal mucosa, and adnexal structures of the skin. We studied the immunohistochemical expression of apomucin MUC1, MUC2, MUC5AC in MPD, and EMPD. MUC1 is commonly expressed in most cases of PD. MUC5AC is a unique mucin that is exhibited in the majority of cases of EMPD, but not in any MPD. Of the 13 patients with MPD who all had associated breast ductal carcinoma, both Paget cells and underlying ductal carcinoma exhibited the phenotype (MUC1+MUC2-MUC5AC-). This mucin phenotype is also expressed by Toker cells, which have been identified in the epidermis of five of 50 nipples in mastectomies without MPD. Of the three patients with perianal PD who all had associated rectal adenocarcinoma, Paget's cells expressed MUC2 constantly but expressed MUC1 and MUC5AC variably. Seven patients with intraepidermal vulvar PD and two patients with scrotal-penile PD had no identifiable underlying malignancy. Paget cells from all of these nine cases of EMPD expressed a uniform phenotype of mucin (MUC1+MUC2-MUC5AC+). One case of vulvar PD associated with underlying apocrine carcinoma had a phenotype (MUC1+MUC2-MUC5AC-) identical to that of normal apocrine glands. The skin appendage and Bartholin's glands from 20 normal-appearing vulvar skin samples and anal glands from 10 hemorrhoidectomies were also studied. Only Bartholin's gland expressed a mucin phenotype identical to that of intraepidermal EMPD. The results of the present study indicate that 1) MPD may arise from either mammary glands or epidermal Toker cells, 2) intraepidermal EMPD in the anogenital areas may arise from ectopic MUC5AC+ cells originating from Bartholin's or some other unidentified glands, and 3) unique expression of MUC2 in perianal PD indicates its origin from colorectal mucosa. We conclude that the study of mucin gene expression is useful in identifying the histogenesis of PD.

Transitional Cell Carcinoma of the Bladder Mimicking Recurrent Paget's Disease of the Vulva: Report of Two Cases, with One Occurring in a Myocutaneous Flap

Background. Transitional cell carcinoma of the bladder may spread superficially along and beyond the urogenital epithelium, mimicking vulvar Paget's disease.Cases. These two cases illustrate unusual aspects of transitional cell carcinoma of the bladder and vulvar Paget's disease. Both patients had a history of breast cancer and previously had multiple operations for recurrent vulvar Paget's disease; one patient had a radical vulvectomy with transverse rectus abdominal muscle flap reconstruction. Both had a history of recurrent transitional cell carcinoma of the bladder. Both presented with recalcitrant transitional cell carcinoma of the bladder and clinically recurrent vulvar Paget's disease. Pathologic evaluation, however, revealed pagetoid spread of carcinoma in situ (CIS) throughout the urothelium, with an invasive component in the cervix and extension of the CIS into the rectum in one patient.Conclusion. If the history of the patient includes transitional cell carcinoma of the bladder and vulvar Paget's disease, histologic evaluation is needed for accurate diagnosis and proper treatment.

Proliferative epidermal lesions associated with anogenital Paget's disease.

A series of 35 cases of Paget's disease (PD) of the vulva and perianal area were studied to characterize the spectrum of proliferative epidermal lesions that occur in this rare disease but generally have been overlooked. The study group consisted of 8 men and 27 women with a median age of 66 years. Nineteen patients (54%) had one or more benign proliferative epidermal lesions, including 7 of 22 patients (32%) with vulvar PD and 12 of 13 patients (92%) with perianal PD. Two patients also had malignant squamous cell neoplasms. Three categories of epidermal hyperplasia were identified: (1) squamous hyperplasia NOS (34%), (2) fibroepithelioma-like hyperplasia (32%), and (3) papillomatous hyperplasia (29%). Small nests of hyperplastic squamous cells protruding into the dermis simulated microinvasive squamous carcinoma in three of these cases. None of the nine papillomatous hyperplasias tested for HPV by in-situ hybridization were positive. The squamous hyperplasia NOS and the papillomatous hyperplasia did not show a predilection for an anatomic site. In contrast, fibroepithelioma-like hyperplasia occurred in 69% of perianal PD compared with only 9% of vulvar cases. There was no association between the type of epidermal hyperplasia and the presence of a regional internal cancer. Two patients with vulvar PD had malignant squamous lesions, including one with squamous cell carcinoma in-situ (CIS) of classic type and one patient with invasive squamous cell carcinoma (InvSCC); the latter also had invasive PD. The malignant squamous component in both patients was positive for HPV 16/18, whereas the associated Paget's cells were HPV-negative. The finding of fibroepithelioma-like hyperplasia in the anogenital skin should prompt a thorough search for Paget' s cells. Papillomatous hyperplasia may be misinterpreted as condyloma acuminatum when Paget's cells are few in number and have koilocytotic-like vacuolar change or for warty (condylomatous) carcinoma when pseudoinvasive foci are present. When Paget's cells are florid and diffusely infiltrate an acanthotic epidermis, classic CIS may be misdiagnosed. Cytokeratin 7 immunostain is an excellent marker for intraepithelial and invasive Paget's cells that aids in their distinction from hyperplastic and malignant squamous cells.

Paget's disease of the vulva: Prevalence of associated vulvar adenocarcinoma, invasive Paget's disease, and recurrence after surgical excision

Objective: Our aim was to determine the prevalence of associated vulvar adenocarcinoma, invasive Paget's disease, and recurrence of Paget's disease of the vulva. Study Design: A retrospective review of tumor and pathology registries at 8 institutions is presented. Patients with recurrent disease were excluded. Histologic slide review was performed. Results: The median age of the 100 patients was 70 years. The median duration of pruritus before surgery was 2 years. Thirty-four percent of patients experienced a recurrence at a median of 3 years. There was a 12% prevalence of invasive vulvar Paget's disease and a 4% prevalence of associated vulvar adenocarcinoma. One patient died of Paget's disease with associated vulvar adenocarcinoma. Conclusions: Paget's disease of the vulva is rarely associated with an underlying vulvar adenocarcinoma or invasive Paget's disease, but there is a high recurrence rate. (Am J Obstet Gynecol 1999;180:24-7.)

Synchronous Paget's Disease of the Vulva and Breast

We report the first case of synchronous Paget's disease of the vulva and breast diagnosed within a period of 7 months. This is the fourth case of mammary Paget's disease associated with either preceding or following vulvar Paget's disease documented in the literature. With consideration of increasing age of the population, and the fact that vulvar Paget's disease affects elderly women and that breast cancer is the most common malignancy of women in the United States, one can anticipate the occurrence of these two conditions to be more prevalent in the future.

Vulvar Paget's disease: a clinicopathologic and immunohistochemical study of 19 cases.

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.

Flow cytometric DNA analysis of extramammary Paget's disease of the vulva.

Vulvar extramammary Paget's disease (EMPD) is an uncommon disease entity that occurs predominantly in postmenopausal white women. The clinical behavior of this neoplasm is extremely variable, reflecting the various histological patterns that have been reported with this lesion. Flow cytometry has been used as a method of obtaining prognostic information about a number of gynecological neoplasms, yet to date there have been no flow cytometric studies performed on this unusual neoplasm. We performed flow cytometric analysis of 14 cases of paraffin-embedded vulvar EMPD in patients ranging from 45 to 86 years of age. We correlated histological features and clinical recurrence risk with DNA analysis. Although we were unable to show a statistically significant correlation between DNA ploidy or S-phase and time to recurrence, we did show a statistically significant correlation between DNA ploidy and histological features. Aneuploidy appears to be associated with in situ sweat gland adenocarcinoma, invasive carcinoma, and lymphatic invasion. These results suggest that Paget's cells with aneuploid DNA stem lines may be associated with the potential for aggressive biologic behavior.

Paget's disease and melanoma of the vulva: Use of a panel of monoclonal antibodies to identify cell type and to microscopically define adequacy of surgical margins

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 35βH11 and 34βE12, 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 HMB4S 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 35βH11. This latter antibody absolutely distinguished tumor cells from neighboring uninvolved squamous epithelium, which was positive only with the monoclonal antibody 34βE12. 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.

Normal Histology and Nomenclature of the Vulva, and Malignant Neoplasms, Including Vin

In this article, vulvar anatomy and histology are reviewed, and nonneoplastic and neoplastic epithelial disorders are presented. Included are lichen sclerosus, squamous cell hyperplasia, vulvar intraepithelial neoplasia, vulvar Paget's disease, and squamous cell carcinoma. Current terminology, tumor measurements, and staging for vulvar carcinoma are reviewed.

Expression of C-erbB-2 Oncoprotein in Mammary and Extramammary Paget's Disease

Formalin-fixed, paraffin-embedded tissue sections from 45 patients with mammary and extramammary Paget's disease were stained immunohistochemically with the use of a polyclonal antiserum directed against a 14-amino acid segment of the c-erbB-2 oncoprotein. Positive membrane staining, which correlates with gene amplification, was found in 15 of 19 cases (79%) of mammary Paget's disease, 4 of 13 cases (31%) of vulvar Paget's disease, none of 8 cases of scrotal Paget's disease, and none of 5 cases of perianal Paget's disease. Of the 19 patients with mammary Paget's disease, specimens of underlying breast tissue were available from 14; all contained a concurrent ductal adenocarcinoma. Concordance of c-erbB-2 antigen staining between the underlying breast carcinoma and the pagetoid component was observed in 12 cases. Of the 13 patients with vulvar Paget's disease, 2 had superficial stromal invasion, and 3 had underlying, deeply invasive adenocarcinomas. One superficially invasive case was positive for c-erbB-2 expression. One additional case of vulvar Paget's disease had an associated primary pagetoid endocervical adenocarcinoma that spread into the endometrium; both the endocervical and vulvar components stained positively for the c-erbB-2 antigen. The results of this study indicate that the c-erbB-2 oncoprotein may play a role in the pathogenesis of extramammary Paget's disease. These results also suggest that the c-erbB-2 oncoprotein may function in vivo to promote intraepithelial spread of adenocarcinoma cells.

Immunohistochemical features of Paget's disease of the vulva with and without adenocarcinoma.

Six cases of vulvar Paget's disease (VP) with associated adenocarcinoma and 10 cases of VP without adenocarcinoma were compared immunohistochemically with B72.3, a pan-carcinoma marker developed against human mammary tumor cells, anti-carcinoembryonic antigen (anti-CEA), anti-epithelial membrane antigen (anti-EMA), anti-gross cystic disease fluid protein (anti-GCDFP-15), antihuman estrogen receptors (anti-ER), and anti-S-100 protein (anti-S-100). B72.3 reacted with 15/16 (94%) of the cases, anti-CEA reacted with 15/16 (94%), anti-EMA reacted with 16/16 (100%), anti-GCDFP-15 reacted with 14/16 (81%), and none of the 16 cases reacted with anti-ER or anti-S-100. There was no statistically significant difference in the percentage of cases binding antibodies between VP without adenocarcinoma and VP with adenocarcinoma. However, B72.3 and anti-CEA stained VP without adenocarcinoma significantly more strongly than VP with adenocarcinoma (p less than 0.05 and p less than 0.025). VP without adenocarcinoma tended to bind anti-GCDFP-15 more strongly than VP with adenocarcinoma, but without statistical significance. Paget cells stained differently than the cells in their associated adenocarcinoma in two of six cases. In both of these cases, the Paget cells and adenocarcinoma were noncontiguous. In contrast, three of the remaining four cases contained adenocarcinoma contiguous with Paget cells. Immunocytochemistry with B72.3 seems to be as useful as anti-GCDFP-15 in identifying VP.

Metastatic Vulvar Paget's Disease Responding to Combination Chemotherapy: Case Report

No effective chemotherapy for advanced extramammary Paget's disease has yet been established. A case of vulvar Paget's disease with systemic metastases was treated with a mitomycin C, vincristine and cisplatin combination chemotherapy, by which the vulvar lesion and serum CEA were clearly decreased. After surgery and 5-fluorouracil treatment, a similar combination chemotherapeutic regimen was administered to treat a recurrence, however, the lesions became resistant.

Vulvar Paget's disease: The need to exclude an invasive lesion

Nineteen patients with intraepithelial Paget's disease of the vulva were treated surgically. Of these patients, five also had invasive Paget's disease of the vulva, two with only minimally invasive lesions. The latter two patients and one patient with a grossly invasive lesion progressed from intraepithelial Paget's disease. One patient had an associated carcinoma of the periurethral glands and an invasive Paget's lesion of the vagina. Since 5 of 19 patients (26%) had an associated noncontiguous carcinoma, the recommended initial workup included sigmoidoscopy, cystoscopy, mammogram, and colposcopy. Koilocytosis was found in 67% of patients. Exclusion of an invasive lesion from intraepithelial Paget's disease was determined to be necessary because (1) the incidence of minimally invasive Paget's lesions may be significant; (2) intraepithelial Paget's disease has the capacity to become invasive; (3) the rate of associated invasive Paget's disease and/or underlying adnexal malignancies may exceed 20%; (4) grossly invasive lesions may be occult; and (5) the survival rate for grossly invasive lesions is low. Simple vulvectomy at a depth of at least 0.5 cm of subcutaneous tissue is recommended as optimal treatment for intraepithelial Paget's disease.

Mucin‐negative biopsy in extra‐mammary Paget's disease. A diagnostic problem

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.

Antibody to S‐100 protein aids the separation of pagetoid melanoma from mammary and extramammary Paget's disease

We evaluated the usefulness of immunohistological staining for S-100 protein in differentiating mammary and extramammary Paget's disease from primary malignant melanoma of superficial spreading (pagetoid) type. This technique was compared to both the mucicarmine and periodic acid-Schiff (PAS) methods. The tumor cells of 10 melanomas contained abundant cytoplasmic S-100 protein. In tissues from mammary and extramammary Paget's disease, S-100 protein was detected in myoepithelial cells, Langerhans cells, and Schwann cells of cutaneous nerves, but was not present in tumor cells. The mucicarmine stain was most useful for vulvar Paget's disease, mucicarminophilic material being present in 9/10 cases. In mammary Paget's disease, only 2/8 cases stained by the mucicarmine technique. Cytoplasmic PAS-positive material was present in the tumor cells of 9/10 cases of vulvar Paget's disease, but was noted in only 1/9 cases of mammary Paget's disease. Melanoma cells from two cases stained weakly with both mucicarmine and PAS indicating that these stains are not specific for Paget's disease in this comparison. The PAS and mucicarmine stains are helpful in differentiating anogenital Paget's disease from pagetoid melanoma, but are less useful in mammary Paget's disease. Immunohistological demonstration of S-100 protein provides an additional diagnostic tool to aid the separation of Paget's disease from pagetoid melanoma.