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AIMS: Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions. METHODS AND RESULTS: Five patients were male and the median age was 79 years (ranges: 59-95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases. CONCLUSION: Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.
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ABSTRACT: We report a very unusual case of melanocytic neoplasm appearing clinically as a 0.5-cm dome-shaped pigmented papule on the chest of a 63-year-old man. Microscopically, it was an asymmetric, entirely dermally based neoplasm characterized by a multinodular, vaguely plexiform architecture composed of moderately pleomorphic spindled melanocytes with ample, dusty pigmented cytoplasm and scattered multinucleated cells. The tumor cells were strongly positive for Melan-A, HMB45, S100, and PRAME, whereas p16 showed diffuse nuclear loss. ß-catenin presented a strong and diffuse cytoplasmic staining, while nuclei were negative. Despite an increased cellularity, mitotic count was low (1/mm 2 ). Fluorescence in situ hybridization revealed no copy number alteration in melanoma-related genes ( CDKN2A, MYB, MYC, CCND1 and RREB1 ). DNA and RNA sequencing identified KIT c.2458G>T and APC c.6709C>T mutations. No further genetic alteration was detected including TERT-promoter (TERT-p ) hot-spot mutation. A re-excision was performed. A sentinel lymph node biopsy was negative. Clinical investigations revealed no extracutaneous involvement. The patient is disease-free after a follow-up period of 8 months. Given the peculiar morphologic and molecular findings, we hypothesize the lesion may represent a novel subtype of an intermediate grade melanocytic tumor (melanocytoma).
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Melanoma , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Hibridização in Situ Fluorescente , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Mutação , Melanócitos/patologia , Antígenos de NeoplasiasRESUMO
ABSTRACT: Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We present a series of 10 patients with giant congenital melanocytic nevi (CMN) in which a secondary proliferation (11 lesions) with schwannian and/or perineuriomatous differentiation developed in the course of the disease. The age of the patients (4 male and 6 female) at the time of surgery and histological assessment varied from 3 months to 57 years. Histopathologically, the following subgroups were delineated: (1) nodular/tumoriform "neurotization" in CMN, (2) diffuse neurofibroma-like proliferation within CMN, (3) plexiform neurofibroma-like proliferation within CMN, and (4) diffuse perineuriomatous (hybrid schwannomatous-perineuriomatous) differentiation in CMN. We review the pertinent literature, including the role of recently identified Schwann cell precursors which are believed to represent the nerve-associated state of neural crest-like cells that persists into later developmental stages.
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Diferenciação Celular , Nevo Pigmentado , Células de Schwann , Neoplasias Cutâneas , Humanos , Nevo Pigmentado/patologia , Nevo Pigmentado/congênito , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/congênito , Masculino , Feminino , Lactente , Células de Schwann/patologia , Criança , Adolescente , Adulto , Pré-Escolar , Pessoa de Meia-Idade , Adulto JovemRESUMO
Spitz tumors represent a heterogeneous group of challenging melanocytic neoplasms, displaying a range of biological behaviors, spanning from benign lesions, Spitz nevi (SN) to Spitz melanomas (SM), with intermediate lesions in between known as atypical Spitz tumors (AST). They are histologically characterized by large epithelioid and/or spindled melanocytes arranged in fascicles or nests, often associated with characteristic epidermal hyperplasia and fibrovascular stromal changes. In the last decade, the detection of mutually exclusive structural rearrangements involving receptor tyrosine kinases ROS1, ALK, NTRK1, NTRK2, NTRK3, RET, MET, serine threonine kinases BRAF and MAP3K8, or HRAS mutation, led to a clinical, morphological and molecular based classification of Spitz tumors. The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.
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Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Humanos , Nevo de Células Epitelioides e Fusiformes/patologia , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/diagnóstico , Melanoma/patologia , Melanoma/genética , Melanoma/diagnósticoRESUMO
ABSTRACT: BAP1-inactivated melanocytic tumors represent a subset of epithelioid melanocytic neoplasms resulting from biallelic inactivation of the BAP1 gene and by a driver mutation that activate the MAP kinase pathway, most commonly BRAFV600E. They occur sporadically or, less common, in the setting of BAP1 tumor predisposition syndrome caused by a BAP1 germline mutation that predisposes to several malignancies including cutaneous and uveal melanoma. To date, only few cases of BAP1-inactivated melanomas have been reported. We present a case of a 35-year-old woman presented with a melanocytic lesion microscopically composed of 3 distinct melanocytic populations, suggesting a stepwise progression model to melanoma from a conventional nevus through a melanocytoma stage. This progression was also supported from a molecular viewpoint given BRAFV600E, BAP1, and TERT-p hot spot mutations detected by targeted mutational analysis. Four atypical melanocytic lesions were removed from the patient's back, and the same A BAP1 c.856A>T, p.(Lys286Ter) mutation was detected on either tumoral or normal tissue samples. To the best of our knowledge, this is the first case of BAP1-inactivated melanoma with a documented TERT-p hot spot mutation manifesting as the first presentation of BAP1 tumor predisposition syndrome.
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Melanoma , Síndromes Neoplásicas Hereditárias , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Feminino , Humanos , Adulto , Mutação em Linhagem Germinativa , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Melanoma/patologia , Melanócitos/patologia , Mutação , Nevo de Células Epitelioides e Fusiformes/patologia , Síndromes Neoplásicas Hereditárias/patologia , Ubiquitina Tiolesterase/genéticaRESUMO
ABSTRACT: Spitz tumors are melanocytic neoplasms characterized by specific, mutually exclusive driver molecular events, namely genomic rearrangements involving the threonine kinase BRAF and the tyrosine kinase receptors ALK , NTRK1 , NTRK2 , NTRK3 , MET , RET , ROS1 , and MAP3K8 or less commonly, mutations in HRAS or MAP2K1 . We hereby report 5 Spitz tumors with a SQSTM1::NTRK2 fusion. All patients were woman with the ages at diagnosis ranging from 30 to 50 years. Locations included the lower extremity (n = 3), forearm, and back (one each). All the neoplasms were superficial melanocytic proliferation with a flat to dome-shaped silhouette, in which junctional spindled and polygonal dendritic melanocytes were mainly arranged as horizontal nests associated with conspicuous lentiginous involvement of the follicular epithelium. Only one case showed heavily pigmented, vertically oriented melanocytic nests resembling Reed nevus. A superficial intradermal component observed in 2 cases appeared as small nests with a back-to-back configuration. In all lesions, next-generation sequencing analysis identified a SQSTM1::NTRK2 fusion. A single case studied with fluorescence in situ hybridization for copy number changes in melanoma-related genes proved negative. No further molecular alterations were detected, including TERT-p hotspot mutations.
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Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Proteína Sequestossoma-1/genética , Proteínas Tirosina Quinases/genética , Nevo de Células Epitelioides e Fusiformes/genética , Hibridização in Situ Fluorescente , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genéticaRESUMO
ABSTRACT: We report an unusual case of schwannoma with glandular elements that demonstrated apocrine decapitation secretion. The glandular structures were embedded within the tumor, varied in shape and size, and were lined by a double-to-multilayered epithelium, with the inner layer composed of monomorphous cuboidal to columnar cells, focally with apocrine decapitation secretion, and the outer layer representing myoepithelial cells. A normal eccrine unit was observed near the lesion. Immunohistochemical studies showed that all luminal cells of the glandular structures stained positive for CK7, whereas myoepithelial cells expressed S100 and p63, and epithelial membrane antigen highlighted the luminal border. CK20 and neuroendocrine markers were negative in the glandular elements.Our findings suggest that the origin of the glandular elements in our case was represented by entrapped glands. Two theories may explain the epithelial hyperplasia observed in the present case as follows: the obstructive effect theory and the inductive ability of a mesenchymal proliferation to produce epidermal or adnexal changes. We suggest that, in a subset of cases, the origin of the glandular elements might represent entrapped glands, wherein their histomorphology/cytomorphology recapitulates the elements comprising the normal adjacent tissue. Further research is necessary to elucidate the histogenesis of glandular schwannoma.
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Decapitação , Neurilemoma , Humanos , Extremidades , Células Epiteliais , Diferenciação CelularRESUMO
ABSTRACT: Cuticular poroma is a rare variant of poroma composed of exclusively or predominantly cuticular cells, namely of large cells with ample eosinophilic cytoplasm. We report 7 cases of this rare tumor identified among 426 neoplasms diagnosed as poroma or porocarcinoma. The patients were 4 males and 3 females, ranging in age from 18 to 88 years. All presented with a solitary asymptomatic nodule. The location included knee (2 cases), shoulder, thigh, shin, lower arm, and neck (each 1). All lesions were surgically removed. No evidence of disease was observed in 5 patients with available follow-up (range 12-124 months).Microscopically, all neoplasms were composed of variably sized, focally closed packed, or interconnecting nodules constituted mostly of cuticular cells. Small poroid cells were a focal feature in 5 tumors, whereas in the remaining 2 cases, poroid cells with conspicuous but still in minority. Five neoplasms were somewhat asymmetric, with irregular outlines. Ductal differentiation and intracytoplasmic vacuoles were seen in 6 tumors. Other features variably encountered were conspicuous intranuclear pseudoinclusions, cystic change, occasional multinucleated cells, increased mitoses, and stromal desmoplasia. Four of the 5 tumors analyzed with next-generation sequencing yielded YAP1::NUTM1 fusions. In addition, various mutations, mostly of unknown significance were identified in one neoplasm.
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Porocarcinoma Écrino , Poroma , Neoplasias das Glândulas Sudoríparas , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Poroma/genética , Poroma/patologia , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia , Fatores de Transcrição/genética , Porocarcinoma Écrino/genéticaRESUMO
Spitz tumors are melanocytic neoplasms morphologically characterized by spindled and/or epithelioid cells and specific stromal and epidermal changes associated with mutually exclusive fusion kinases involving ALK, ROS1, NTRK1, NTRK2, NTRK3, MET and RET, BRAF and MAP3K8 genes or, less commonly, HRAS mutation. RAF1 fusions have been recently detected in cutaneous melanocytic neoplasms, including conventional melanoma, congenital nevus and BAP-1 inactivated tumors. We report herewith three Spitz neoplasms with a RAF1 fusion, including a previously reported CTDSPL::RAF1 fusion and two novel PPAP2B::RAF1 and ATP2B4::RAF1 fusions. Two cases were classified as Spitz nevus, while the remaining neoplasm was classified as Spitz melanoma at the time of the diagnosis, given 9p21 homozygous deletion and positive sentinel lymph node biopsy. We suggest that RAF1 fused melanocytic neoplasms can represent a novel subgroup of Spitz tumors, with a RAF1 fusion representing an oncogenic driver.
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Melanoma , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Humanos , Proteínas Tirosina Quinases/genética , Homozigoto , Proteínas Proto-Oncogênicas/genética , Deleção de Sequência , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Nevo de Células Epitelioides e Fusiformes/genética , Receptores Proteína Tirosina Quinases/genéticaRESUMO
BAP1-inactivated melanocytic tumor (BIMT) is a group of melanocytic neoplasms with epithelioid cell morphology molecularly characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, and a mutually exclusive mitogenic driver mutation, more commonly BRAF. BIMTs can occur as a sporadic lesion or, less commonly, in the setting of an autosomal dominant cancer susceptibility syndrome caused by a BAP1 germline inactivating mutation. Owing to the frequent identification of remnants of a conventional nevus, BIMTs are currently classified within the group of combined melanocytic nevi. "Pure" lesions can also be observed. We studied 50 BIMTs from 36 patients. Most lesions were composed of epithelioid melanocytes of varying size and shapes, resulting extreme cytomorphological heterogeneity. Several distinctive morphological variants of multinucleated/giant cells were identified. Some hitherto underrecognized microscopic features, especially regarding nuclear characteristics included nuclear blebbing, nuclear budding, micronuclei, shadow nuclei, peculiar cytoplasmic projections (ant-bear cells) often containing micronuclei and cell-in-cell structures (entosis). In addition, there were mixed nests of conventional and BAP1-inactivated melanocytes and squeezed remnants of the original nevus. Of the 26 lesions studied, 24 yielded a BRAF mutation, while in the remaining two cases there was a RAF1 fusion. BAP1 biallelic and singe allele mutations were found in 4/22 and 16/24 neoplasms, respectively. In five patients, there was a BAP1 germline mutation. Six novel, previously unreported BAP1 mutations have been identified. BAP1 heterozygous loss was detected in 11/22 lesions. Fluorescence in situ hybridization for copy number changes revealed a related amplification of both RREB1 and MYC genes in one tumor, whereas the remaining 20 lesions studied were negative; no TERT-p mutation was found in 14 studied neoplasms. Tetraploidy was identified in 5/21 BIMTs. Of the 21 patients with available follow-up, only one child had a locoregional lymph node metastasis. Our results support a progression of BIMTs from a conventional BRAF mutated in which the original nevus is gradually replaced by epithelioid BAP1-inactivated melanocytes. Some features suggest more complex underlying pathophysiological events that need to be elucidated.
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Nevo de Células Epitelioides e Fusiformes , Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Criança , Humanos , Hibridização in Situ Fluorescente , Nevo de Células Epitelioides e Fusiformes/genética , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genéticaRESUMO
Long regarded as ectopic or supernumerary breast tissue, anogenital mammary-like glands (AGMLG) are now considered a normal constituent of the anogenital area. AGMLG are presumed to be the origin for various benign and malignant lesions. Changes in AGMLG compatible with usual ductal hyperplasia and atypical ductal hyperplasia considered as precursor lesions and its presence in specimens can be explained by their role in the pathogenesis of primary extramammary Paget disease. In this report, we presented four cases of invasive squamous cell carcinoma accompanied by non-neoplastic atypical changes in ductal portions of AGMLG compatible with atypical ductal hyperplasia in breast adjacent to the carcinoma. This is a reactive phenomenon similar to that seen in apocrine/eccrine glands adjacent to squamous cell carcinoma. In a limited biopsy specimen, these areas should not be mistaken for adenocarcinoma.
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Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma de Células Escamosas/patologia , Doença de Paget Extramamária/patologia , Neoplasias Vulvares/patologia , Idoso , Idoso de 80 Anos ou mais , Glândulas Apócrinas/patologia , Mama/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Períneo/patologia , Vulva/patologia , Neoplasias Vulvares/cirurgiaRESUMO
Lichen aureus is a variant of pigmented purpuric dermatoses. The usual histopathology of lichen aureus is characterized by a subepidermal dense, band-like lymphocytic infiltrate, extravasated erythrocytes, and hemosiderin deposits. We report three patients with lichen aureus on the extremities with similar clinical, dermoscopic, and histopathological findings characterized by a dense band-like relatively deep dermal infiltrate accompanied by extravasation of erythrocytes and hemosiderin deposits occasioning a resemblance to a lymphoproliferative disorder.
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Transtornos da Pigmentação/patologia , Pseudolinfoma/complicações , Púrpura/diagnóstico , Dermatopatias/patologia , Adulto , Dermoscopia/métodos , Diagnóstico Diferencial , Eritrócitos/patologia , Feminino , Hemossiderina/análise , Humanos , Imuno-Histoquímica/métodos , Linfócitos/patologia , Transtornos Linfoproliferativos/metabolismo , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Plasmócitos/patologia , Pseudolinfoma/patologia , Púrpura/patologiaRESUMO
Extramammary Paget disease (EMPD) is a rare neoplasm with uncertain histogenesis, usually presenting in the anogenital area, most commonly in the vulva. The disease is characterized by slow grow and high recurrence rates. This article reviews the epidemiological, clinical, morphological, genetic and treatment features of EMPD of the vulva reported in recent years.
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Doença de Paget Extramamária/patologia , Neoplasias Vulvares/patologia , Diagnóstico Diferencial , Feminino , Humanos , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/epidemiologia , Prognóstico , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/epidemiologiaRESUMO
ABSTRACT: Trichoblastoma (TB) is a benign biphasic follicular neoplasm with differentiation toward the germinative cells and a specific follicular mesenchyme. We subtyped 349 sporadic TB according to a classification proposed by Ackerman. Two hundred forty-six (246/349, 70.5%) neoplasms were comprised of mixed subtypes. TB composed exclusively of a single pattern was less common (103/349, 29.5%). The most common pure subtype was cribriform TB followed by small nodular TB. Twelve cases (12/349, 3.4%) had unique features and are reported herein as novel histopathologic subtypes of the neoplasm.
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Doenças do Cabelo/patologia , Folículo Piloso/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
ABSTRACT: Sebaceous neoplasms occur sporadically or in the setting of Muir-Torre syndrome. The data regarding the correlation of pathologic features and DNA mismatch repair (MMR) staining pattern in sebaceous tumors of the skin are very scanty and based on relatively small series of patients. The goal of this study was to correlate MMR staining pattern with selected morphological features in a series of 145 sebaceous neoplasms (sebaceous adenoma, sebaceoma, and extraocular sebaceous carcinoma) from 136 patients. Cystic change, intratumoral mucin deposits, squamous metaplasia in the absence of keratoacanthoma-like changes, ulceration, intratumoral and peritumoral lymphocytes (in cases without epidermal ulceration), and intertumoral heterogeneity proved to be significantly associated with MMR deficiency. Identification of any of these changes, alone or in combination, should prompt further investigation of the patient to exclude Muir-Torre Syndrome. Our study also confirms the previously published observation that the diagnosis and tumor location are significantly associated with MMR deficiency.
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Adenoma/metabolismo , Adenoma/patologia , Carcinoma/metabolismo , Carcinoma/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias das Glândulas Sebáceas/metabolismo , Neoplasias das Glândulas Sebáceas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/metabolismo , Extremidades , Face , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/metabolismo , Proteína 1 Homóloga a MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Couro Cabeludo , Tronco , Adulto JovemRESUMO
ABSTRACT: Primary cutaneous desmoplastic melanoma (DM) is a group of rare melanocytic tumors arising on severely sun-damaged skin, histologically characterized by the proliferation of spindled melanocytes in a prominent desmoplastic stroma, with a range of morphological presentations. In this article, we report a unique case of primary cutaneous DM composed of a nodular proliferation of highly pleomorphic spindled and epithelioid cells, pseudoglandular structures, clear cell change, and unusual collagen rosettes. Immunohistochemical analysis showed a strong and diffuse positivity for S-100 protein, SOX-10, nestin, p75 (nerve growth factor receptor), WT1, and p53. Molecular analysis detected a mutation in the NF1 gene [c.4084C > T, p.(Arg1362Ter)], 2 different pathogenic mutations in TP53 [c.742C > T, p.(Arg248Trp), AF:12%, COSM1640831 and c.528C > G, p.(Cys176Trp), AF:12%, COSM11114], and a mutation in GNAS [c.601C > T, p.(Arg201Cys), AF: 9%, COSM123397]. To the best of our knowledge, this is the first case reporting collagen rosettes and pseudoglandular features in primary cutaneous DM.
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Colágeno Tipo IV/metabolismo , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso de 80 Anos ou mais , Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Imuno-Histoquímica , Masculino , Melanoma/metabolismo , Mutação , Neurofibromina 1/genética , Neoplasias Cutâneas/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
ABSTRACT: Specific alterations involving MAPK genes (MAP3K8 fusions, MAP3K3 fusions) have been recently detected in a subgroup of spitzoid neoplasms that seem to constitute a distinctive clinicopathologic group, occur mostly in younger patients (median age 18 years) and present with atypical histologic features associated with frequent homozygous deletion of CDKN2A, qualifying a high proportion of them as Spitz melanoma (malignant Spitz tumor). Apart from lesions with spitzoid morphology harboring MAP3K8 or MAP3K3 fusion, a single case with MAP2K1 deletion has been identified. The authors report herein 4 melanocytic lesions with a MAP2K1 mutation, all showing similar microscopic appearances, including spitzoid cytology and dysplastic architectural features, resembling so-called SPARK nevus, suggesting that these lesions may represent another distinctive group.
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MAP Quinase Quinase 1/genética , Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/patologia , Adulto , Feminino , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genéticaRESUMO
Intralymphatic histiocytosis is a rare reactive skin condition characterized by a nonspecific clinical presentation and, microscopically, by the collections of mononuclear histiocytes within the lumina of dilated lymphatic vessels. We report a rare case of intralymphatic histiocytosis associated with rosacea and prominent periocular edema (Morbihan disease). The patient is a 56-year-old woman with a 12-year history of rosacea who suddenly developed edema of the right upper eyelid that persisted 6 months before she sought medical advice. Because of an unclear clinical diagnosis, surgical excision of the edematous upper eyelid was performed. The histologic slides showed interstitial edema of the dermis with dilated vascular channels and small epithelioid cell granulomas around hair follicles. In addition, there were aggregates of cells inside numerous lymphatic vessels that were immunohistochemically positive for CD45, CD4, CD68, CD163, CD64, CD14, CD11c, and lysozyme and negative for CD3, CD20, CD30, CD56, S100, CD1a, and langerin.
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Doenças Palpebrais/patologia , Histiocitose/patologia , Vasos Linfáticos/patologia , Rosácea/complicações , Doenças Palpebrais/complicações , Feminino , Histiocitose/complicações , Humanos , Pessoa de Meia-IdadeRESUMO
We report a case of a polypoid atypical Spitz tumor with a prominent fibrosclerotic stromal component, harboring a CLIP2-BRAF fusion, which has hitherto been not reported in melanocytic lesions. The neoplasm occurred in a 78-year-old male patient and appeared microscopically as a predominantly dermal, barely symmetrical, polypoid lesion composed mainly of epithelioid cells showing moderate degree of nuclear pleomorphism with ample amphophilic cytoplasm arranged in nests, fascicles, or single units. The mitotic rate was 2/mm, and the mitoses were confined to the upper portion of the lesion. The Breslow thickness was 2.3 mm. The stroma contained conspicuous plumped fibroblasts and thickened collagen bundles associated with dilated medium-sized vessels. Focally, sclerotic areas were found. A moderately dense, lymphocyte-predominant inflammatory infiltrate scattered through the whole lesion was seen. Despite strong nuclear and cytoplasmic positivity of p16, FISH revealed homozygous loss in locus 9p21. A CLIP2-BRAF fusion was found by next-generation sequencing. No other genetic alterations including a TERT-promoter mutation was found. The patient is disease-free without recurrence or evidence of metastatic disease after 5 years and 2 months of follow-up.
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Nevo de Células Epitelioides e Fusiformes/genética , Nevo de Células Epitelioides e Fusiformes/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Idoso , Aberrações Cromossômicas , Cromossomos Humanos Par 9/genética , Humanos , Masculino , Proteínas Associadas aos Microtúbulos/genética , Fusão Oncogênica , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
BRCA1-associated protein (BAP1)-inactivated melanocytic tumor (BIMT) is a group of epithelioid melanocytic neoplasms characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21. They occur sporadically or in the setting of an autosomal-dominant cancer susceptibility syndrome that predisposes to the development of different internal malignancies. Most of these cutaneous lesions are associated with a BRAF-mutated melanocytic nevus and therefore are included in the group of combined nevi in the last WHO classification of skin tumors. Apart from a BRAF mutation, an NRAS mutation has been reported in rare cases, whereas in some lesions no driver mutation has been detected. Here, we report 2 cases of BIMTs with a BAP1 mutation and a RAF1 fusion. Both lesions proved to be BRAF and NRAS wild type and were associated with a conventional melanocytic nevus with dysplastic junctional features. We suggest that RAF1 fusions can represent an underlying driver genetic event in these cases. Our study extends the morphological and molecular spectrum in BIMTs.