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• W2925366918 abstract "To the Editor: Merkel cell carcinoma (MCC) is a rare primary cutaneous neoplasm characterized by neuroendocrine differentiation.1 Histopathologically, MCC belongs to the category of “small blue cell neoplasms,” being characterized by monomorphic cells with round-to-oval nuclei, finely dispersed chromatin, and scant cytoplasm. MCC cells express a combination of low molecular weight cytokeratins (CK20 and/or CK7) and neuroendocrine markers. A significant breakthrough in understanding the molecular pathogenesis of MCC occurred in 2008, when a novel human polyomavirus (Merkel cell polyomavirus, MCPyV) was shown to be clonally integrated in the host genome of approximately 80% of MCC cases.1,2 Most of MCC cases are dermal-based lesions, showing variable extension into the subcutis and/or the epidermis. Although epidermotropism is a well-known histological scenario, only 10 cases of MCC confined to the subcutis (“panniculitic MCC”) have been reported in the available literature (Table 1).3–10 Here, we report the first case of panniculitic MCC with an indisputable positivity for MCPyV, as established by immunohistochemistry. We believe that our findings raise further questions regarding MCC cell of origin.TABLE 1.: Summary of Reported Cases of Panniculitic Merkel Cell CarcinomaA 75-year-old man with no significant medical history presented to our clinic with a 1-year history of a painless, growing subcutaneous mass localized to the right gluteal region. On physical examination, the subcutaneous tumor appeared as a mobile mass with normal overlying skin, measuring 4 cm in diameter. Punch biopsy of the gluteal mass revealed a deep, sheet-like proliferation of primitive round blue cells almost filling the subcutaneous layer (Fig. 1A); tumoral cells exhibited finely granular chromatin, indistinct nucleoli, and scant cytoplasm (Fig. 2A). The neoplastic growth, which was consistent with neuroendocrine carcinoma, was entirely confined to the hypodermis. Mitotic rate was high, and necrotic cells were frequent. By immunohistochemistry, most neoplastic cells expressed CK20 in a paranuclear dot-like configuration (Fig. 2B); staining for CK7 was negative. The tumor was diffusely positive for synaptophysin and NSE, whereas TTF-1 and S100 were not expressed. Immunohistochemistry for MCPyV large T-antigen (LTA) with CM2B4 antibody was diffusely positive in the sheet-like proliferation but not surrounding tissues (Fig. 1B), with predominantly nuclear labeling of neoplastic cells (Fig. 2C). A final diagnosis of panniculitic MCPyV-positive MCC was rendered. Treatment consisted of surgical excision of the tumoral mass down to the fascia followed by adjuvant radiotherapy. The patient responded to treatment and was disease-free after a 12-month follow-up.FIGURE 1.: A, Scanning magnification view demonstrating sheet-like growth of primitive round blue cells confined to the subcutis. B, Strong and diffuse expression of MCPyV LTA labeling neoplastic cells but sparing surrounding tissues (A, hematoxylin and eosin, original magnification ×20; B, original magnification ×20).FIGURE 2.: A, High-power view revealing diffuse proliferation of small round blue cells with finely granular chromatin, indistinct nucleoli, and scant cytoplasm. B, Expression of CK20 in a paranuclear dot-like pattern. C, Strong, diffuse, predominantly nuclear expression of MCPyV LTA in neoplastic cells (A, hematoxylin and eosin, original magnification ×200; B, original magnification ×400; C, original magnification ×400).Subcutaneous involvement by MCC is a fairly common occurrence; extension into the subcutis, however, typically follows the growth of primarily dermal-based lesions.1 Among the only 11 reported cases of panniculitic MCC, 8 tumors, including the present case, were assessed for immunohistochemical expression of CK20 and CK7: 7 cases showed the conventional CK20(+) phenotype, whereas only 1 case stained positive for CK7 and negative for CK20.3–10 In addition, none of reported cases of panniculitic MCC showed evidence of divergent differentiation. Importantly, our case is the first panniculitic MCC to be assessed for MCPyV infection with the CM2B4 immunostaining. MCC shows a typical predilection for chronically sun-exposed areas, suggesting a major role of ultraviolet radiation exposure in its pathogenesis.1 UV-induced carcinogenesis, however, is unlikely to be involved in development of panniculitic MCC. Available evidence suggests that MCPyV-positive and MCPyV-negative MCC subsets develop through different molecular pathways, respectively, thus representing distinct clinicopathological entities.1,2 The clinicopathological characteristics of reported cases of panniculitic MCC (ie, expression of a CK7(−)/CK20(+) phenotype, absence of divergent differentiation, and lack of association with chronic sun damage), including our case, seem to suggest that panniculitic MCC mostly belongs to the MCPyV-positive MCC subset; further data, however, are needed to confirm this conclusion. Panniculitic MCC is indistinguishable from metastases of extracutaneous neuroendocrine carcinomas on morphological grounds alone.8 Importantly, the immunohistochemical expression of LTA using the CM2B4 antibody has been shown to be highly specific for MCC; therefore, positive staining for LTA may provide unquestionable aid in the distinction between MCC and non-MCC small round cell neoplasms. Ultrastructural as well as immunophenotypical features suggest that MCC cells differentiate toward cutaneous Merkel cells (MCs).1 Whether MC should be regarded as MCC cell of origin, however, is a subject of controversy. Recent evidence supports the view that most skin epithelial neoplasms derive from stem cells located in the basal layer of the interfollicular epidermis or in the bulge area of hair follicles.1,11 These epithelial stem cells could also account for the genesis of MC and MCC, respectively. Indeed, MCs seem to derive from epidermal stem cells, through a stepwise maturation process featuring the sequential activation of a MC-specific set of genes, including Atoh1, Sox2, and Isl1.12 The occurrence of panniculitic MCC, however, seems to be hardly justified by the existence of epidermal or bulge region hair follicle stem cells. A complementary explanation may lie in the identification of label-retaining cells with myoepithelial features and stem cell behavior, localized in the basal layer of the secretory acinar region of sweat glands, lying at the border of the dermis and subcutis13; accordingly, secretory coil-derived stem cells might serve as cells of origin of deep-seated neoplasms with adnexal differentiation, including MCC. Such a scenario, however, remains highly speculative; further research is needed to test this hypothesis." @default.
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• W2925366918 date "2020-02-01" @default.
• W2925366918 modified "2023-10-16" @default.
• W2925366918 title "Merkel Cell Polyomavirus–Positive Panniculitic Merkel Cell Carcinoma: A Rare Neoplasm of Unknown Histogenesis" @default.
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