DP18 The histopathological diagnosis of primary, invasive, metastatic, extramammary Paget disease

Abstract We present a diagnostic journey for an extremely rare presentation of primary, invasive, metastatic extramammary Paget disease (EMPD) arising directly from the adnexal structures of the skin. An 84-year-old male patient presented with an asymptomatic, unilateral, intertriginous rash of the left groin, of ambiguous provenance and unresponsive to conventional treatments. Following the appearance of a fleshy nodule within the rash, two biopsies were taken. Shortly thereafter the patient was admitted with confusion. Computed tomography scanning demonstrated significant metastatic disease in the liver with lucencies in the central canal of T9. It did not identify an alternative primary source. The patient unfortunately deteriorated and required palliation. Given the extreme rarity of the condition, histopathological diagnosis relied on a remarkable cascading series of immunocytochemical stains. Initial pathology demonstrated atypical epithelioid cells with abundant cytoplasm forming a 4.5-mm tumour extending from the superficial to deep dermis. Immunocytochemistry showed positivity for AE1/3, cytokeratin (CK)7 and epithelial membrane antigen, common markers of epithelial cell origin. Pagetoid spread was identified and, as staining for P40, CK5/6, melan-A and S100 were negative, excluding a squamous or melanocytic source, the lesion was felt best described as an invasive CK7+ carcinoma. The histological features, site and immunophenotype raised the possibility of a rare diagnosis of EMPD, although metastatic spread from another site had yet to be excluded. Carcinoembryonic antigen staining was positive, which would be anticipated in EMPD, although this marker of epithelial cell dysfunction is also expressed in colonic and lung adenocarcinomas. Therefore, although supportive, it was not definitive. Positive expression of gross cystic disease fluid protein-15, typically expressed in mammary ducts but also in EMPD, leant further weight to the diagnosis. Lack of expression of further site-specific markers (thyroid transcription factor-1, CDX2 and NKX3.1) made a primary from the lung, gastrointestinal tract or prostate, respectively, very unlikely. Taken with the initial negativity of P40, the most appropriate diagnosis was felt to be a primary, invasive, metastatic EMPD arising directly from the skin. EMPD accounts for 1% of all anogenital cancers. Primary cases are rarer, and the incidence reduces further when considering cases with proven invasive and metastatic disease. A study from the Mayo Clinic in 2016 identified only 10 such cases on their registry over a 14-year period, only five of which were confirmed (Padrnos L, Karlin N, Halfdanarson TR. Mayo Clinic Cancer Center experience of metastatic extramammary Paget disease 1998–2012. Rare Tumours 2016; 8: 6804). This case is therefore a fascinating account of the histopathological process for identifying this exceptionally rare tumour.