The clinico-pathological spectrum of plaque-type blue naevi and their potential for malignant transformation.

AIMS: Plaque-type blue naevi are rare melanocytic tumours presenting as large, pigmented plaques at birth or during childhood. There is a risk for malignant transformation, but no larger comprehensive studies exist and the diagnosis is challenging, especially on limited biopsy material. The aim is to describe the clinicopathological features and behaviour of the disease more comprehensively. METHODS AND RESULTS: We retrieved eight plaque-type blue naevi, presenting as large, pigmented plaques (median = 7 cm; range = 3-26) most frequently affecting the scalp (four) followed by the cheek, arm, abdominal wall and gluteal cleft (one each), with a slight female predilection. Median age at time of biopsy was 39.5 years (range = 15-90), but three tumours had been present at birth and one since childhood. Histopathologically, the tumours were poorly circumscribed and composed of cellular fascicles of uniform spindle cells in a background of variably prominent pigmented dendritic cells affecting dermis and subcutaneous tissues. The majority had mutations in GNAQ. One tumour showed malignant transformation, characterised by an expansile nodule of pleomorphic epithelioid melanocytes with rhabdoid morphology, high mitotic activity and areas of necrosis. This patient developed metastatic melanoma to lymph nodes. All patients are alive with a median follow-up of 60 months. CONCLUSION: Plaque-type blue naevi are diagnostically challenging tumours with risk for malignant transformation. Awareness and familiarity with the salient clinicopathological features are necessary for reliable diagnosis, and long-term clinical follow-up is required to monitor for malignant transformation.

Distant metastasis from morphologically low-grade spiradenocarcinoma: A report of two cases.

Malignant tumors arising from benign eccrine spiradenomas are rare. They are divided by morphology into low-grade and high-grade spiradenocarcinomas, with prognosis and metastatic potential closely linked to their histopathologic features. Tumors with low-grade morphology are known for their indolent behavior, with only two reported instances of metastatic spread. We report herein two further low-grade metastatic spiradenocarcinomas resulting in distant metastasis. Both tumors showed a background of a benign spiradenoma and subtle histopathologic signs of malignant transformation, characterized by loss of the dual-cell population, up to moderate cytological atypia and increased mitotic activity. Both patients developed metastases to the lungs years after the initial presentation, and one showed additional lymph nodal disease. We show that even the morphologically low-grade tumors may rarely show more aggressive behavior. Although often challenging, recognition of the morphologically low-grade malignant spiradenocarcinoma and long-term follow-up of the patients are important to detect metastatic disease.

Cutaneous Myoepithelial Neoplasms on Acral Sites Show Distinctive and Reproducible Histopathologic and Immunohistochemical Features.

Cutaneous myoepithelial neoplasms are a heterogenous group of neoplasms with mixed tumors typically affecting the head and myoepitheliomas showing a predilection for the extremities. Their malignant counterparts, myoepithelial carcinoma, and malignant mixed tumor are exceptionally rare in the skin, and the morphologic criteria for malignancy are only poorly defined. The aim of the present study was to characterize the clinicopathologic features of myoepithelial neoplasms presenting on acral skin. The clinical and histopathologic features of 11 tumors were recorded, and follow-up was obtained. Immunohistochemistry was performed for S100, SOX10, glial fibrillary acidic protein, keratins, epithelial membrane antigen, p63, p40, smooth muscle actin, desmin, and PLAG1. The tumors mainly affected the feet of adults (range: 26 to 78 y; median: 47 y) with a predilection for the great toe and a male predominance of 1.8:1. Most tumors (91%) displayed a lobular architecture composed of solid and nested growth of epithelioid cells with plasmacytoid features in a myxoid or angiomatous stroma. Scattered cytologic atypia and rare duct differentiation were frequently noted. Three tumors with confluent cytologic atypia, infiltrative growth, and lymphovascular invasion were classified as malignant. By immunohistochemistry, the tumors were positive for S100, SOX10, keratins AE1/AE3, CK5/6 and CK7, and PLAG1. Local recurrence and bilateral pulmonary metastasis were observed in a patient presenting with a histopathologically benign-appearing tumor. Two patients with malignant tumors experienced local recurrences, and 1 developed metastasis to soft tissue, lung, and mediastinal lymph nodes. All patients are currently alive, all but 1 with no evidence of disease after a median follow-up interval of 96 months (range: 2 to 360 mo). In conclusion, acral myoepithelial neoplasms show distinctive and reproducible histopathologic and immunohistochemical features. They are best regarded as a distinctive subset of mixed tumors with features reminiscent of their salivary gland counterparts. While most tumors pursue a benign disease course, histopathologic features appear to be a poor indicator of prognosis.

The clinicopathologic spectrum and genomic landscape of de-/trans-differentiated melanoma.

Dedifferentiation and transdifferentiation are rare and only poorly understood phenomena in cutaneous melanoma. To study this disease more comprehensively we have retrieved 11 primary cutaneous melanomas from our pathology archives showing biphasic features characterized by a conventional melanoma and additional areas of de-/trans-differentiation as defined by a lack of immunohistochemical expression of all conventional melanocytic markers (S-100 protein, SOX10, Melan-A, and HMB-45). The clinical, histologic, and immunohistochemical findings were recorded and follow-up was obtained. The patients were mostly elderly (median: 81 years; range: 42-86 years) without significant gender predilection, and the sun-exposed skin of the head and neck area was most commonly affected. The tumors were deeply invasive with a mean depth of 7 mm (range: 4-80 mm). The dedifferentiated component showed atypical fibroxanthoma-like features in the majority of cases (7), while additional rhabdomyosarcomatous and epithelial transdifferentiation was noted histologically and/or immunohistochemically in two tumors each. The background conventional melanoma component was of desmoplastic (4), superficial spreading (3), nodular (2), lentigo maligna (1), or spindle cell (1) types. For the seven patients with available follow-up data (median follow-up period of 25 months; range: 8-36 months), two died from their disease, and three developed metastases. Next-generation sequencing of the cohort revealed somatic mutations of established melanoma drivers including mainly NF1 mutations (5) in the conventional component, which was also detected in the corresponding de-/trans-differentiated component. In summary, the diagnosis of primary cutaneous de-/trans-differentiated melanoma is challenging and depends on the morphologic identification of conventional melanoma. Molecular analysis is diagnostically helpful as the mutated gene profile is shared between the conventional and de-/trans-differentiated components. Importantly, de-/trans-differentiation does not appear to confer a more aggressive behavior.

Muir-Torre syndrome in a haemodialysis patient.

Muir-Torre syndrome (MTS) is a rare inherited cancer syndrome with variable penetrance. MTS follows an autosomal-dominant pattern of inheritance, and is a subtype of Lynch syndrome [formally known as hereditary non-polyposis colorectal cancer (HNPCC)]. MTS is caused by mutations in one of several mismatch repair genes. Patients typically present with sebaceous neoplasms (sebaceous adenoma, sebaceous epithelioma, or sebaceous carcinoma) or with multiple keratoacanthomas. These patients also have an increased lifetime risk of visceral malignancies, typically affecting the colon, ovary, endometrium, genitourinary tract and small bowel. We describe a case of MTS in a haemodialysis patient and implications for transplant listing.

Rhabdomyoblastic differentiation in malignant melanoma in adults: report of 2 cases.

Two cases of malignant melanoma are reported in adults exhibiting rhabdomyoblastic differentiation to alert pathologists to this rare variant of malignant melanoma. One of the cases presented as a metastasis in a submandibular lymph node, and the other was a primary skin melanoma. There are only a few published reports on melanocytic tumors with rhabdomyoblastic differentiation, mainly occurring in giant congenital nevi. Both cases reported here were confirmed by immunohistochemistry. Both cases were also studied by electron microscopy, and one showed distinctive ultrastructural features of striated muscle.