A proposal for a TNM staging system for extramammary Paget disease: Retrospective analysis of 301 patients with invasive primary tumors.

BACKGROUND: Although extramammary Paget disease (EMPD) usually appears as carcinoma in situ, it sometimes becomes invasive (iEMPD) and fatal. However, a TNM staging system for iEMPD has yet to be established. OBJECTIVE: The aim of this study was to establish a TNM staging system for iEMPD. METHODS: We retrospectively collected iEMPD patients treated at 12 institutes in Japan. Factors reported to be associated with survival such as distant metastasis, lymph node (LN) metastasis, and primary tumor status were evaluated using the log-rank test. RESULTS: We enrolled 301 iEMPD patients, of whom 114 had remote metastases (49 had both distant and LN metastasis; 2, distant metastasis only; and 63, LN metastasis only) and the remaining 187 patients had no remote metastasis. Distant metastasis (M1) showed worse survival (P<0.00001). In the analysis of the 250 patients without distant metastasis, LN metastasis also showed worse survival (P<0.00001). Among the patients with LN metastasis, 2 or more LN metastases (N2) showed worse survival than did single LN metastasis (N1, P=0.02). Lastly, in the analysis of the 187 patients without metastasis, tumor thickness of over 4mm or lymphovascular invasion showed worse survival (T2, P<0.05 and P<0.001, respectively). Patients with neither of these features were defined as T1. From these results, we propose this TNM staging system: stage I, T1N0M0; stage II, T2N0M0; stage IIIa, anyTN1M0; stage IIIb, anyTN2M0; stage IV, anyTanyNM1. Other than stages II and IIIa, each stage had a statistically distinct survival curve. CONCLUSION: We propose a TNM staging system for EMPD using simple factors for classification that could provide important prognostic information in managing EMPD. However, accumulation of more patient data and further revision of the system are required.

Pagetoid dyskeratosis in dermatopathology.

Pagetoid dyskeratosis (PD) is an incidental pathologic finding that appears in several skin conditions. In an attempt to better understand PD and its incidence in dermatopathology, the authors have analyzed all skin biopsies performed over the period of 1 year in our Department of Dermatology and examined their clinical and dermatopathological variables. The criteria used for a keratinocyte to be considered a PD cell were: (1) a size larger than normal, (2) the presence of pycnotic nucleus, (3) a clear halo surrounding the nucleus, and (4) a pale eosinophilic cytoplasm. A total of 3565 biopsies were analyzed, PD cells being found in 80 cases (2.24%). Melanocytic nevi were the commonest skin lesions in which PD was observed, followed by soft fibromas, angiofibromas, and acrochordons. Most lesions were located on the head, neck, and trunk. Most cases displayed fewer than 15 PD cells per field. PD cells were normally located in the mid epidermis (frequently in clusters). The biopsies usually revealed indirect signs of rubbing, although PD cells were also found in places where rubbing was unlikely. Here, the authors report the largest series of PD analyzed to date, expanding our understanding of this striking pathological observation.

Reconstructive strategy and classification of penoscrotal defects.

OBJECTIVE: To classify defects in the penoscrotal region according to their specific anatomic sites. METHODS: From January 2002 to December 2012, 20 male patients underwent reconstruction for penoscrotal defects. The causative factors were Fournier's gangrene in 12 patients, extramammary Paget's disease in 4, skin tumors in 3, and deformity after a burn injury in 1. The defects were categorized according to their anatomic location: penis (P), and right (r) and left (l) scrotum (Sr and Sl), inguinal area (Ir and Il), and perianal area (Ar and Al). RESULTS: Seven patients with defects in the penis received skin grafts. Defects affecting more than 2 anatomic regions or extensive defects (>100 cm(2)) were reconstructed by free tissue transfer. Other defects were reconstructed by perforator-based island flap coverage. All of the flaps survived without complications. CONCLUSION: We introduce a classification that provides a simple way to specify the anatomic location and extent of a defect. This classification will permit more effective and straightforward reconstruction in the penoscrotal region.

Immunohistochemistry of p63 in primary and secondary vulvar Paget's disease.

Vulvar Paget's disease (VPD) is classified into primary and secondary types. Differentiation of these subsets in biopsy specimen is important for appropriate therapy. Expression profile of cytokeratin (CK) 7 and CK20, gross cystic disease fluid protein-15 and uroplakin III has been reported as a differentiation marker of primary and secondary VPD. To examine the role of p63 immunostaining in differential diagnosis between primary VPD and VPD secondary to urothelial carcinoma (VPD-UC), expression of p63 was examined in nine cases of VPD. Paget cells in seven cases of VPD without UC did not express p63. In two cases of VPD associated with UC, Paget cells and UC cells had identical CK expression profile. UC cells were positive for p63 in both cases. In one case, Paget cells were positive for p63 and examination of the resected specimen showed that VPD was secondary to UC. In another case, Paget cells were negative for p63 and this was diagnosed as primary VPD independent of UC. This indicates that p63 is absent in Paget cells in primary VPD and is therefore useful in differentiating primary VPD from VPD-UC.

Paget's disease of the vulva: clinicopathologic study of type 1 cases treated at a single institution.

The aim of this study was to evaluate clinicopathologic characteristics of primary cutaneous Paget's disease of the vulva. Between 1986 and 2005, 22 patients with primary cutaneous Paget's disease of the vulva (type 1) were treated at Tohoku University Hospital. Medical records were reviewed for pathologic diagnosis, patient age, associated neoplasms, type(s) of eczema, symptom duration, treatment, surgical procedures, recurrence, and length of follow-up. Patient age ranged from 51 to 85 years (median 71.5 years). Median duration of symptoms was 24 months (range 2-60 months). Type 1a (intraepithelial) Paget's disease accounted for 18 patients, with 3 type 1b (invasive) cases and 1 type 1c (intraepithelial disease with underlying adenocarcinoma) case. Mean length of follow-up was 53.7 months, and median follow-up was 49 months (range 6-199 months). Only two patients had an associated internal malignancy: T-cell leukemia and breast cancer. Mapping biopsy was performed in 14 of the 18 type 1a cases. All patients were free of disease at the surgical margins and are alive without recurrence. The four patients with type 1b or 1c disease had lymph node metastases. Two has died of disease, and two are alive with no recurrence. The rate of secondary malignancy seems to be low in primary cutaneous Paget's disease of the vulva. Mapping biopsy with careful examination of characteristic skin surface may be useful for surgery of type 1a cases. Inguinal lymphadenectomy is recommended in cases with question of invasion or known underlying adenocarcinoma.

Potential diagnostic utility of CDX-2 immunophenotyping in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare condition whose importance is amplified by its association with either cutaneous or internal malignancy. Recently it has been shown that EMPD is not a single disease but can be divided into cutaneous and endodermal subtypes. The authors studied 12 new cases of immunohistochemically well-characterized EMPD, including HER-2/neu and CDX-2 immunophenotyping. The latter represents a novel application of this nuclear transcription factor, considered to be a relatively specific IHC marker for gastrointestinal-type epithelium. Cutaneous EMPD, accounting for 10 of the 12 (83%) cases, was CDX2-/HER2+; endodermal EMPD, accounting for 2 of the 12 (17%) cases, was CDX2+/HER2-. Four of the 12 cases (33%) were associated with a malignancy (two cutaneous adenocarcinomas, two colorectal carcinomas). The two cases of cutaneous adenocarcinoma occurred in the cutaneous group (2/10 [20%]), while the two cases of rectal carcinoma (one invasive, one in situ) occurred in the endodermal group (2/2 [100%]). Since EMPD subtypes have specific implications with regard to cancer risk, immunophenotyping should be performed in all cases. CDX-2 immunoreactivity may be useful in the subtyping of EMPD.

Enfermedad de Paget extramamaria primaria de escroto / Primary scrotal extramammary Pagets disease

Presentamos un caso de enfermedad de Paget extramamaria (EPEM) en un varón de 78 años de edad. Clínicamente se presentó una lesión nodular a nivel del escroto no dolorosa. El examen histológico reveló una formación tumoral compuesta por células epiteliales con amplio citoplasma eosinófilo y núcleo vesiculoso, que conformaban estructuras ductales localizadas en la unión dermoepidérmica y dermis superficial. Focalmente penetraban en la epidermis subrayacente. La resección quirúrgica fue el tratamiento de elección (AU)

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.