American Journal of Dermatopathology最新文献

Abstract: Pilomatrical tumors include pilomatricoma, melanocytic matricoma, and pilomatrical carcinoma. Similar to the normal anagen hair follicle bulb, they may be associated with benign and, rarely, with atypical pigmented dendritic melanocytes. It has been recently suggested that the term "melanocytic matricoma" be replaced with "pilomatricoma with melanocytic hyperplasia" (PMMH). Occasional cases of PMMH show intermediate grades of histological atypia. Their clinical behavior is uncertain. Interestingly, we found in one of these atypical tumors a molecular characterization compatible with a malignant profile. In this study, we compare this case with the molecular profiles of two PMMHs, one atypical PMMH, whose histology was previously published, and of two unpublished cases: a pilomatrical carcinoma and a large matrical tumor of difficult categorization. We also correlate histology with the molecular results. Although histologically the six cases form a morphological continuum with increasing grades of architectural and cytological atypia, our molecular analysis distinctly segregates the lesions into two molecular groups. The first group exhibits only isolated alterations in CTNNB1, a low tumor mutational burden, and a relatively stable chromosomal profile. The second group, by contrast, demonstrates mutations of TP53, biallelic inactivation of CDKN2A or RB1, and an elevated tumor mutational burden, in addition to mutations in CTNNB1 or loss of APC. The tumors in the second group are clearly different from the benign PMMHs. Atypical PMMHs could represent an early stage in the development of tumors that, since their beginning, have a malignant molecular profile different from that of PMMHs and can progressively drive their evolution toward overt malignancy.

Abstract: Merkel cell carcinomas (MCCs) exhibit diverse molecular profiles, often categorized by their association with Merkel cell polyoma virus (MCPyV). MCPyV-associated MCCs typically display a low tumor mutational burden (TMB), lacking both somatic mutations and ultraviolet signature. By contrast, MCPyV-negative MCCs commonly arise in sun-exposed skin and frequently exhibit a high TMB, along with TERT promoter mutation (TPM) and somatic mutations, particularly in TP53 and RB1. Gene fusions are exceedingly rare in MCCs, and their specific frequency and fusion transcripts remain largely unexplored. Here, we present a unique case of MCPyV-associated MCC characterized by NSD3::FGFR1 fusion, representing a novel fusion transcript not previously reported in MCCs. A 72-year-old White man presented with a cyst-like nodule on the left elbow, which had progressively increased in size over a span of 6 months. Excisional biopsy specimen revealed a neuroendocrine carcinoma diffusely expressing CK20 (perinuclear dot-like), synaptophysin, CD56, NSE, and MCPyV, consistent with MCC. Next-generation sequencing identified a NSD3::FGFR1 fusion without any additional somatic mutations, including TP53 and RB1 mutations, or TPM. Although NSD3::FGFR1 fusion has been sporadically reported in other solid tumors, such as pulmonary squamous cell carcinoma, its identification in an MCC is unprecedented to our knowledge. This novel finding not only underscores the uniqueness of our case but also contributes to the evolving understanding of the molecular landscape of MCCs, particularly MCPyV-associated MCCs.

Abstract: In 2022-2023 mpox outbreak led to declaration of a public health emergency. Smallpox vaccination has led to increased immunity and a decrease in clinical disease. The role of vaccination in immunosuppressed patients is not well understood. We present an atypical case of cutaneous mpox, presenting in a fully vaccinated, immunosuppressed, HIV-negative patient as an initial isolated, subcutaneous neck mass. We review the diagnostic dilemma and workup for these atypical cases.

Abstract: A 53-year-old woman from Missouri (United States) with a 2-year history of kidney transplant presented to our dermatology department with multiple acneiform lesions on the face and numerous erythematous papules and nodules on both arms and legs. Biopsies revealed a very atypical florid pseudoepitheliomatous hyperplasia, at first interpreted, in light of the history of immunosuppression, as an invasive squamocellular carcinoma, associated with an unusual dense histiocytic infiltrate and nodular aggregates of foamy histiocytes. After the acute onset of fever, pancytopenia, and signs of ulcerative colitis, disseminated histoplasmosis was suspected. A biopsy taken from a rectal ulcer revealed numerous histiocytes with intracellular yeasts that were positive for periodic acid-Schiff and Grocott-Gomori methenamine silver fungal stains. Antifungal therapy with amphotericin B and itraconazole led to the healing of the skin lesions with scarring and postinflammatory hyperpigmentation. This case is an exceptional example that warns pathologists that (1) florid pseudoepitheliomatous hyperplasia can be undistinguishable from invasive squamocellular carcinoma, and complete excision of fast-growing lesions is always advised in case of doubt; (2) a dense infiltrate of foamy histiocytes may be the spy to a systemic infection, and a careful clinical and pathologic screening should be promptly initiated.

Abstract: Dermatofibrosarcoma protuberans (DFSP) is a rare slow-growing soft tissue sarcoma that is usually found on the trunk or extremities. This report highlights an exceedingly rare case in which a DFSP arose on the digit of a 43-year-old man. Clinical and histologic analysis revealed an atypical CD34-positive tumor with differentials including DFSP and multiple similar entities. However, fluorescence in situ hybridization studies revealed a COL1A1 translocation to the platelet-derived growth factor B (22q13.1) locus, t(17;22)(q22;q13), confirming the diagnosis of DFSP. Although rare, this case highlights the importance of including DFSP on the differential in CD34-positive acral tumors, with cytogenetic analysis crucial for accurate diagnosis and treatment.

Abstract: Malignant tenosynovial giant cell tumor (MTGCT) is a rare and aggressive variant of tenosynovial giant cell tumors, with fewer than 60 reported cases. Although typically localized to joints and soft tissues, cutaneous presentations of MTGCT are exceedingly rare, with only a handful of documented cases involving direct dermal invasion. Here we report the case of an 88-year-old man with a history of nonmelanoma skin cancers who presented with a friable, ulcerated 2.5 cm nodule on the midchest. The lesion, present for approximately 1 month, was excised and found to be a malignant TGCT. Histopathology revealed a neoplasm with multinucleated giant cells and malignant features such as numerous and atypical mitotic figures, necrosis, and severe cellular pleomorphism. Immunohistochemistry showed positivity for CD45 and CD68, with weak partial expression of smooth muscle actin, and negative for CD34, P40, SOX10, pancytokeratin, CD163, CD1a, S100, and Melan-A, confirming the diagnosis. The patient underwent complete surgical excision. This case highlights a rare presentation of MTGCT with direct cutaneous involvement, adding to the sparse literature on this malignancy. Early recognition and accurate diagnosis of such unusual presentations are crucial because of the tumor's aggressive potential.

Abstract: A 66-year-old male patient presented to our department with subcutaneous nodules in both lower extremities accompanied by pain. Skin pathology suggested pancreatic panniculitis. Subsequent imaging and histopathology identified a rare case of pancreatitis-panniculitis-polyarthritis syndrome secondary to a primary hepatic neuroendocrine tumor. This case highlights the rare association between nonpancreatic conditions and pancreatic panniculitis.

Abstract: Congo red (CR) remains the most commonly used stain by pathologists to detect amyloid deposition. CR, however, has limitations including variable sensitivity with potential of false negative results. We investigated the staining intensity of CR in comparison to commercially available cytokeratin immunohistochemical markers in a series of primary cutaneous amyloidosis originating from keratin filaments.

Abstract: Late-onset focal dermal elastosis is an uncommon elastic disorder seen in older individuals and biopsies demonstrate an increase in elastic fibers. Elastosis of the oral cavity is reported uncommonly. The aim of this study is to describe oral biopsies with similar histopathologic features to late-onset focal dermal elastosis and to introduce the term "focal oral elastosis." We included oral biopsies that showed increased elastic fibers confirmed by Verhoeff-van Gieson histochemical stain. We identified 6 oral biopsies with prominent elastosis. There were 4 men, and the median age was 64.5 years. Elastosis was present in 5 nodular lesions and 1 papule. Lesions occurred on the gingiva (33.3%), palatal mucosa (33.3%), buccal mucosa (16.7%), and upper lip (16.7%). Deposition of amorphic bluish/amphophilic material in the subepithelial areas was seen in all cases confirmed with the Verhoeff-van Gieson stain. Our case series demonstrates the presence of elastic fibers in reactive lesions such as oral fibromas.