A novel technique to diagnose non-melanoma skin cancer by thermal conductivity measurements: Correlations with cancer stromal factors.

The skin surface temperature reflects the physiological state of the human body. Quantitative methods of identification of skin cancers based on accurate measurement of effective thermal conductivity (ETC) are among the promising diagnostic tools for differentiating non-invasive and invasive melanomas before surgical treatment. To validate these findings, in this report, the diagnostic methods for invasive and non-invasive extramammary Paget's disease (EMPD) and squamous cell carcinoma (SCC) were further tested by measuring the absolute value of skin surface temperature and the ETC of the skin. In addition, to investigate the stromal factors that might affect ETC, immunohistochemical staining for LL37, periostin (POSTN), MMP12, and MMP28 was performed. The invasive SCC and EMPD group showed a relatively higher skin surface temperature compared to the in situ SCC group. The non-invasive EMPD and SCC group showed significantly lower values of ETC at lesions, whereas the invasive EMPD group showed significantly higher ETC values at lesions compared to healthy skin. Immunohistochemical staining showed that the percentage of LL37-producing cells was significantly increased in invasive EMPD and SCC compared to that in non-invasive EMPD and SCC. Moreover, Spearman's rank correlation test showed a significant inverse correlation between the percentage of MMP12-positive cells and increased levels of ETC-expressing areas in EMPD and SCC (r = -.5997). The present study suggested that differences in ETC could be a novel high-accuracy diagnostic technique for non-melanoma skin cancer, especially for detecting dermal invasion of SCC and EMPD.

"Pigmented Extramammary Paget Disease"-A Potential Mimicker of Malignant Melanoma and a Pitfall in Diagnosis: A Case Report and Review of the Literature.

Extramammary Paget disease (EMPD) is a rare intraepithelial carcinoma and an uncommon variant of Paget disease affecting areas of the apocrine-rich skin of the perineum, vulva, and less commonly, axilla. Women in their sixth to eighth decades are commonly affected. It is exceedingly rare for EMPD to present on the face, chest, abdomen, or other nonapocrine sites and even more unusual for EMPD to present as a pigmented lesion. The relationship between Paget cells in pigmented extramammary Paget disease (PEMPD) and reactive proliferation and colonization by melanocytes has been poorly explored. The relevance of this rare entity resides in its potential to be misdiagnosed clinically and histopathologically as malignant melanoma in situ. Therefore, application of a panel of immunostains and careful analysis and interpretation of these findings are essential to arrive at the correct diagnosis. We report a new case of PEMPD on a nonapocrine site. The specimen was examined by routine microscopy including hematoxylin and eosin stain as well as immunostains. Histologic examination revealed characteristic features of PEMPD confirmed with immunohistochemical stains.

"Extramammary-Type" Paget Disease of the Breast.

BACKGROUND: Mammary Paget disease and extramammary Paget disease (EMPD) have different prognoses. Because they are indistinguishable on histopathological grounds, they must be distinguished on a topographical basis. OBJECTIVE: To study cases of Paget disease of the breast, which show similarities to EMPD. METHODS: Cases were selected by 2 different approaches: (1) those with an exceptionally good evolution and no evidence of subjacent tumor and (2) those expressing MUC5AC. RESULTS: Five cases were collected. All cases showed an indolent behavior with a known long clinical history in 2 cases (9 and 25 years, respectively) and a long follow-up in all cases but one (4-8 years). In all cases but one, surgery was performed, and no parenchymal tumor was found (either intraductal or infiltrating). All cases expressed cytokeratin 7 and MUC5AC without expression of MUC2, S100, or p40. LIMITATIONS: The short number of cases is a limitation of this study. In addition, case 5 is recent, so we have a very short follow-up. CONCLUSIONS: Some cases of mammary Paget disease behave like EMPD with slow progression and with no underlying associated tumor. Immunoexpression of MUC5AC might be a clue to identify them.

Cervical metastases originating from a primary rectal adenocarcinoma due to a pagetoid spread.

Vulvar Paget disease is a rare skin disorder, considered an in situ adenocarcinoma. It is characterized by intraepithelial Paget cells, of which the origin is unclear. About 75% of cases have a cutaneous origin; the other 25% originate from an intestinal or urological malignancy. We report the first case of retrograde pagetoid spread from a rectal adenocarcinoma to the vulva and cervix. A 66-year-old woman presented with postmenopausal bleeding and a history of Crohn disease. Gynecological workup revealed vulvar and endocervical lesions consisting of Paget cells and adenocarcinoma, respectively. A rectal adenocarcinoma with in situ adenocarcinoma was diagnosed. The surgical specimen demonstrated Paget cells in the squamous epithelium of the anus and vulva. Immunohistochemistry demonstrated an intestinal phenotype of these cells. Genetic testing revealed the same TP53 mutation in tumor cells of the rectal adenocarcinoma and vulvar and endocervical lesions, demonstrating that the Paget cells originated from the same intestinal tumor.

Syringocystadenocarcinoma Papilliferum In Situ-Like Changes in Extramammary Paget Disease: A Report of 11 Cases.

The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface.

Primary invasive extramammary Paget disease on penoscrotum: a clinicopathological analysis of 41 cases.

To investigate the clinicopathological and immunohistochemical features and prognostic factors for invasive extramammary Paget disease (EMPD) on penoscrotum, we described the clinical presentations, histopathology, and follow-up courses of 41 cases. The age of the patients ranged from 42 to 84 years. All the patients were treated with wide surgical excision, and 14 were confirmed to have lymph node metastasis. During follow-up, 18 patients (43.9%) developed local or distant recurrence, and 13 patients (31.7%) died of the disease. Histologically, glandular formation with true lumina within the epidermis was found in 29 cases, and signet ring cells were seen in 11 cases. In invasive components, nodular/micronodular growth pattern, glandular formation, and strands/solid sheets existed in 95.1% (39/41), 43.9% (18/41), and 24.4% (10/41) of the cases, respectively. More than half of the cases had at least 2 different types of invasive growth pattern. CK7 was diffusely positive in all cases, whereas CK20 was focally positive in 8 cases. GCDFP-15 was expressed to a variable degree in 24 cases. Presence of strands/solid sheets, lymphovascular invasion, and perineural invasion in invasive EMPD were found to be correlated with higher lymph node metastatic rate. Univariate analysis revealed that patients with one of the following prognostic factors: delay in diagnosis more than 7.5 years, depth of invasion more than 1 mm, invasive pattern of strands/solid sheets, marked inflammation, lymphovascular invasion, and lymph node metastasis at diagnosis, had significantly shorter cancer-specific survival. We concluded that invasive EMPD is a rare malignant skin neoplasm with morphological diversity. Invasive pattern of strands/solid sheets is significantly associated with both lymph node metastasis and worse prognosis. Delay in diagnosis, depth of invasion, marked inflammation, lymphovascular invasion, and regional lymph node status are important prognostic factors.

Psoriasis with extramammary paget disease in a male: a case report.

Psoriasis is a chronic inflammatory skin disease that is characterized by erythematous, sharply demarcated papules and plaques covered by scales. Extramammary Paget disease (EMPD) is a uncommon neoplastic condition of apocrine gland-bearing skin and its occurrence in combination with psoriasis is very rare. We report an interesting case of a 61-year-old male with extensive psoriasis presented with penoscrotal EMPD, which was confirmed by histopathological stain.

Extramammary Paget's disease: evaluation of the adnexal status of 53 cases.

Extramammary Paget's disease (EMPD) is a distinct form of malignant skin neoplasm. The clinicopathological significance of cutaneous adnexal involvement in EMPD has not been investigated in detail. Surgical specimens were obtained from 53 patients with primary EMPD. Tumor involvement of cutaneous adnexal structures was evaluated using histological parameters. The degree of involvement was scored on a scale of 0-2: 0, no involvement; 1, involvement of the upper portion of the adnexa; 2, involvement of the lower portion of the adnexa. A score of 2 was regarded as significant. The presence of comedo necrosis was also examined. Adnexal involvement was identified in 46 cases (86.8%). Comedo necrosis was observed in 6 cases (11.3%). The proportions of each parameter in in situ cases were as follows: significant adnexal involvement (score 2) in 15/26 (57.7%), and comedo necrosis in 3/26 (11.5%). The corresponding proportions in cases with invasion were 21/27 (77.8%) and 3/27 (11.1%), respectively. No significant differences in adnexal involvement and comedo necrosis were detected between in situ EMPD and invasive EMPD (p>0.05). The current study suggests that the degree of adnexal involvement and the presence of comedo necrosis are not associated with tumor progression in EMPD.

Extramammary Paget disease of the vulva with underlying mammary-like lobular carcinoma: a case report and review of the literature.

Extramammary Paget disease of the vulva accounts for 1%­2% of the neoplasms of the anogenital area. Very rarely, extramammary Paget disease of the vulva has been associated with an underlying mammary-like carcinoma, usually ductal, extremely rarely mixed ductal and lobular. We report the case of a 60-year-old female with a recurrent extramammary Paget disease of the vulva. Pathological examination of the wide excision of the vulva revealed an extramammary Paget disease with an underlying invasive carcinoma composed of medium size cells organized in single files, a morphology similar to that of an invasive lobular breast carcinoma. Immunohistochemical staining showed a comparable profile in the Paget cells and in the invasive tumoral cells: CEA and CK7 positivity; GCDFP-15, ER focal positivity. E-cadherin and HER2 were diffusely positive. S100 and CK20 were negative. HER2-CISH was amplified. The diagnosis of extramammary Paget disease of the vulva with an underlying mammary-like lobular carcinoma was made. Despite the characteristic lobular features, the immunohistochemical profile differs from the typical profile of a lobular carcinoma of the breast. The implications in term of prognostic and therapeutic significance need to be further studied.

Ultrastructural Examination of a Case of Pagetoid Bowen Disease Exhibiting Immunohistochemical Features in Common With Extramammary Paget Disease.

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

Co-existence of extramammary Paget's disease and Bowen's disease of vulva.

Extramammary Paget's disease and Bowen's disease are histologically similar and immunohistochemistry is often required to make the diagnosis. We present a case of vulval Paget's disease with Bowen's disease in an elderly female. Strong positivity for cytokeratin 7, anti CAM 5.2, carcinoembryonic antigen (CEA) and periodic acid-Schiff (PAS) stain in clitoral, left labial and interface regions of the vulvectomy specimen confirmed the diagnosis of Paget's disease (PD) while positive staining for p63 in the right labial and interface regions helped in establishing the diagnosis of concurrent Bowen's disease (BD).

Florid vulval Paget disease exhibiting p16 immunoreactivity and mimicking classic VIN.

The diagnosis of vulval Paget disease is generally relatively straightforward but may be difficult, especially when the Paget cells are few in number. We report 2 cases of the opposite scenario where the Paget cells were present in such large numbers and formed confluent sheets such that they effaced the residual keratinocytes. There were associated epidermal hyperplastic changes in the form of acanthosis, papillomatosis, and hyperkeratosis, and the overall morphology resulted in close mimicry of classic (undifferentiated/human papillomavirus-related) vulval intraepithelial neoplasia. There was focal intraepidermal clefting in both cases, resulting in an acantholytic appearance. In both cases, the Paget cells were strongly positive with p16 that further heightened the mimicry of vulval intraepithelial neoplasia. The Paget cells were diffusely positive with cytokeratin 7, CAM5.2, carcinoembryonic antigen, and epithelial membrane antigen and with mucin stains, and molecular tests for human papillomavirus were negative. The p16 immunoreactivity, which has not previously been reported in vulval Paget disease, prompted us to stain a small number of additional cases of more typical vulval Paget disease with this marker. Four of 5 additional cases were positive with varying degrees and patterns of immunoreactivity. Florid vulval Paget disease may morphologically mimic vulval intraepithelial neoplasia, and this mimicry may be exacerbated by p16 immunoreactivity.

Prostate carcinoma metastatic to the skin as an extrammamary Paget's disease.

AIM: The current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified. DISCUSSION AND CONCLUSIONS: We review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1395450057455276.