Spitz nevus with a novel TFG-NTRK2 fusion: The first case report of NTRK2-rearranged Spitz/Reed nevus.

Fusions of ALK, ROS1, NTRK1, NTRK3, RET, MET, MERTK, FGFR1, ERBB4, LCK, BRAF, MAP3K8, MAP3K3, and PRKDC and mutation of HRAS have so far been discovered as the genetic alterations associated with the pathogenesis of Spitz neoplasms. This report presents the first case of NTRK2-rearranged Spitz/Reed nevus. The patient was a 39-year-old male with a pigmented macule rapidly growing on his shoulder. Histopathologically, the lesion was a junctional melanocytic nevus composed of large nests of spindled melanocytes with abundant eosinophilic cytoplasm associated with a hyperplastic epidermis. These findings fulfilled the diagnostic criteria of a pigmented spindle cell nevus of Reed (variant of Spitz nevus). Immunohistochemistry for pan-Trk revealed diffuse cytoplasmic positivity in the tumor cells, but immunoexpression of ALK, ROS1, and BRAF V600E was not seen. A novel, in-frame, TFG-NTRK2 fusion was identified by RNA sequencing. This case report expands the list of genetic alterations in Spitz neoplasms and the spectrum of NTRK2-rearranged tumors.

Nevo de Spitz y otros tumores spitzoides en la infancia. Parte 1: aspectos clínicos, histológicos e inmunohistoquímicos / Spitz Nevus and Other Spitzoid Tumors in Children-Part 1: Clinical, Histopathologic, and Immunohistochemical Features

El nevo de Spitz es una neoplasia melanocítica de células epitelioides o fusiformes que suele aparecer en la infancia. Su naturaleza es benigna, aunque en ocasiones puede mostrar unas características difíciles de distinguir del melanoma. En las últimas décadas se han clasificado las neoplasias melanocíticas spitzoides en 3tipos: nevus de Spitz, tumor de Spitz atípico y melanoma spitzoide. El tumor de Spitz atípico hace referencia a las neoplasias melanocíticas spitzoides que tienen unas características histopatológicas atípicas insuficientes para realizar el diagnóstico de melanoma y cuyo potencial maligno, actualmente, es incierto. Nuestro objetivo es revisar los aspectos clínicos, dermatoscópicos, histopatológicos e inmunohistoquímicos de este conjunto de tumores

A Spitz nevus is a melanocytic neoplasm of epithelioid and/or spindle cells that usually appears in childhood. These lesions are by nature benign, but their features can sometimes make them difficult to distinguish from melanomas. Spitzoid melanocytic lesions have been grouped into 3 types in recent decades: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas. Atypical Spitz tumors are spitzoid melanocytic proliferations that have atypical histopathologic features that are insufficient to support a diagnosis of melanoma. The malignant potential of these lesions is at present uncertain. This review examines the clinical, dermoscopic, and histopathologic features of this group of lesions

Spindle cell proliferations of the sigmoid colon, rectum and anus: a review with emphasis on perineurioma.

A wide range of spindle cell proliferations are found uncommonly in the sigmoid colon, rectum and anus. They usually present as polyps, and include reactive lesions and benign and malignant neoplasms which may be primary or metastatic. They are less frequently described in the literature compared to those in the upper gastrointestinal tract, and may be underdiagnosed. The widespread use of sigmoidoscopy in symptomatic patients and bowel cancer screening programmes means that histopathologists must be aware of, and adopt a logical approach to, diagnosing spindle cell proliferations in biopsy and polypectomy specimens. This is particularly relevant given the strong association of some mesenchymal polyps with hereditary cancer syndromes. This review article will focus on perineurioma and the recent debate in relation to its overlap with fibroblastic polyp. The clinical, endoscopic, histological and immunohistochemical features of spindle cell proliferations which should be considered in the differential diagnosis of perineurioma will be discussed. There is also a brief reference to malignant spindle cell tumours of diagnostic importance.

Dermatofibrosarcoma protuberans: a tumor in the wide spectrum of the bland-looking spindle cell lesions of the breast.

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor, usually occurring as a cutaneous lesion localized to the trunk or extremities; although it has a high rate of local recurrence, its metastatic potential is very low and complete surgical excision is frequently curative. Most of the cases reported as "DFSP of the breast" are tumors arising in the subcutaneous tissue infiltrating the underlying breast parenchyma. To the best of our knowledge, only 5 cases of DFSP of the breast have been reported to date. We herein present a rare case of DFSP of the breast parenchyma in a 41-year-old female with emphasis on the diagnostic clues and the differential diagnosis with other benign and malignant spindle cell lesions of the breast.

Regresión espontánea de tres nevus melanocíticos congénitos medianos / Spontaneous Regression of Medium-Sized Congenital Melanocytic Nevi: Report of 3 New Cases

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The color of skin: black diseases of the skin, nails, and mucosa.

Gradations in skin color are a consequence of differing amounts of melanin and their varying distribution. Although many darkly pigmented skin lesions are melanocytic and can be attributed to melanin content, the color of a black lesion can also be due to blood, necrotic tissue, or exogenous pigment. The source, pattern, and distribution of the color in black lesions usually offer important insight into its etiology. This contribution reviews conditions that can take on a black color, discussing the cause of the hue and any additional impact sun exposure may have.

Cutaneous Spindle Cell Neoplasms: Pattern-Based Diagnostic Approach.

CONTEXT: - Spindle cell neoplasms arising in the skin comprise a heterogeneous group of tumors with divergent lineages. Cutaneous spindle cell neoplasms are relatively common and present surgical pathologists with diagnostic challenges. Recognition of their histopathologies is important for correct diagnosis and management. The current review presents a pattern-based diagnostic approach to common cutaneous spindle cell neoplasms that often cause diagnostic difficulties. OBJECTIVE: - To provide a useful guide for diagnosis of cutaneous spindle cell neoplasms. DATA SOURCES: - PubMed (US National Library of Medicine) reports and the authors' personal experiences are reviewed. CONCLUSIONS: - The authors briefly summarize the histologic features and differential diagnoses of common cutaneous spindle cell neoplasms.

Superficial malignant peripheral nerve sheath tumor with overlying intradermal melanocytic nevus mimicking spindle cell melanoma.

Malignant peripheral nerve sheath tumors are rare soft tissue sarcomas with histological and immunohistochemical similarities to spindle cell melanoma. Although spindle cell melanoma is significantly more common, both tumors may express S100 and lack staining for HMB-45, Melan-A or MITF. Here we present a case of superficial malignant peripheral nerve sheath tumor with diffuse S100 positivity arising in a subtle neurofibroma in close proximity to an intradermal melanocytic nevus. This configuration had led to prior misdiagnosis as a desmoplastic melanoma arising in the nevus and to sentinel lymph node biopsy. Identification of the background neurofibroma, as well as CD34 positivity raised consideration of a low grade malignant peripheral nerve sheath tumor, which was confirmed via observation of Schwannian differentiation on electron microscopy. The importance of distinguishing these two tumors is stressed owing to the difference in management.

Tumor fibroso solitario de la mama: presentación de caso y revisión de la literatura / Solitary fibrous tumor of the breast: Case report and literature review

El tumor fibroso solitario, previamente denominado hemangiopericitoma, es un tumor mesenquimal benigno compuesto por células fusiformes con forma ovoide dentro de las fibras de colágeno. Su presentación en mama es poco frecuente; se han reportado alrededor de 50 casos en la literatura. Presentamos el caso de una mujer de 36 años con lesión en la mama derecha con características fenotípicas e inmunohistoquímicas de tumor fibroso solitario. Además, realizamos una revisión de la literatura de los casos publicados (AU)

Solitary fibrous tumor, previously called hemangiopericytoma, is a benign mesenchymal tumor composed of ovoid spindle cells within collagen fibers. Its presentation in the breast is rare, with around 50 cases reported in the medical literature. We present the case of a 36-year-old woman with a right breast mass with phenotypic and immunohistochemical features of solitary fibrous tumor. In addition, we provide a review of published cases in the literature (AU)

Pleomorphic spindle cell dermal neoplasm with dot-like keratin reactivity: keratin-positive AFX or carcinoma?

Atypical fibroxanthoma (AFX) is an uncommon cutaneous neoplasm of pleomorphic myofibroblast-like cells. Diagnosis requires exclusion of other undifferentiated spindle and pleomorphic cell neoplasms by immunohistochemistry. We report two patients with p63-non-reactive spindle cell neoplasms which resembled AFX but demonstrated anomalous dot-like immunolabeling with antibodies to high molecular weight keratin and keratin 5. One case recurred locally, suggesting such lesions may behave aggressively. Whether these lesions represent keratin-positive dermal sarcomas or poorly differentiated carcinomas is debatable. Regardless of exact classification, our experience suggests such cases should be managed as high-risk non-melanoma skin cancers.

Spitz nevus and Reed nevus.

Spitz and Reed nevi, also called spindle and/or epithelioid cell nevi, are a special group of melanocytic lesions due to their peculiar clinical, dermoscopic and histopathological features. The study of these nevi is of great interest because both their nomenclature and classification are still a matter of discussion. Most importantly, the difficulty to differentiate them from melanoma can lead to inadequate therapies. In this context, dermoscopy, a link between clinical and anatomopathological examinations, appears as a helpful diagnostic tool whose accuracy can reach 93%. "Borderline" lesions are still a great challenge and object of research, including molecular studies. The present study explores the relevant characteristics of these nevi, with emphasis on dermoscopic findings, aiming at understanding their natural history, as well as discussing treatment and patient follow-up.

Spitz nevus and Reed nevus / Nevo de Spitz e nevo de Reed

Spitz and Reed nevi, also called spindle and/or epithelioid cell nevi, are a special group of melanocytic lesions due to their peculiar clinical, dermoscopic and histopathological features. The study of these nevi is of great interest because both their nomenclature and classification are still a matter of discussion. Most importantly, the difficulty to differentiate them from melanoma can lead to inadequate therapies. In this context, dermoscopy, a link between clinical and anatomopathological examinations, appears as a helpful diagnostic tool whose accuracy can reach 93%. "Borderline" lesions are still a great challenge and object of research, including molecular studies. The present study explores the relevant characteristics of these nevi, with emphasis on dermoscopic findings, aiming at understanding their natural history, as well as discussing treatment and patient follow-up.

Os nevos de Spitz e de Reed, ou também chamados nevos de células fusiformes e/ou epitelióides, formam um grupo especial de lesões melanocíticas, por suas características peculiares, tanto clínicas como dermatoscópicas e histopatológicas. Torna-se grande o interesse no estudo desses nevos, pois tanto a nomenclatura como a classificação ainda são motivos de debate e, sobretudo, a dificuldade de diferenciação com o melanoma pode gerar condutas terapêuticas inadequadas. Neste contexto, surge a dermatoscopia, elo entre o exame clínico e o anatomopatológico, como método diagnóstico auxiliar importante cuja acurácia pode chegar a 93%. A grande dificuldade ainda são as lesões "borderline", motivo de pesquisas, incluindo estudos moleculares. O presente estudo aborda os aspectos relevantes das características destes nevos, com ênfase nos achados dermatoscópicos, buscando o entendimento da sua história natural, além da discussão quanto ao tratamento e seguimento dos pacientes.

Nevo de células fusiformes de Reed na conjuntiva / Spindle cell nevus of Reed in the conjunctiva

Os autores relatam um caso de nevo de Reed, lesão que apresenta aspecto histológico de malignidade, mas tem evolução benigna. Paciente de 48 anos, masculino, cor parda, apresentava pterígio nasal no olho direito, associado a uma lesão pequena e pouco pigmentada localizada na cabeça do mesmo. Realizou-se exérese de ambos, sem intercorrências, sem sinais de recidiva. O exame histopatológico revelou lesão com bordas definidas, restrita ao epitélio, constituída por células fusiformes perpendiculares à superfície, com pigmentação melânica esparsa. O diagnóstico inicial foi nevo de Spitz, mas, posteriormente, chegou-se à conclusão que se tratava do nevo de células fusiformes de Reed. O presente relato é o segundo na literatura mundial e o primeiro no Brasil.

The authors report one case of nevus of Reed, which has histological aspect of malignancy, but a benign evolution. A 48-years-old brown skin male presented nasal pterygium in right eye, associated with a small and poorly pigmented lesion located on the pterygium head. Both were excised without complications and, currently, there is no recidivation. The histopathological examination revealed one lesion with defined edges, limited to the epithelium, consisted of spindle cells perpendiculars to the surface and with sparse melanin pigmentation. The initial diagnosis was Spitz nevus, but, afterwards, we concluded that was the spindle cell nevus of Reed. This report is the second in the international literature and the first in Brazil.

Pigmented spindle cell nevus: clues for differentiating it from spindle cell malignant melanoma. A comprehensive survey including clinicopathologic, immunohistochemical, and FISH studies.

Pigmented spindle cell nevus (PSCN), also known as Reed nevus, is a distinctive melanocytic tumor that can show worrisome clinical and histologic features mimicking a malignant melanoma. From a series of 46 pigmented spindle cell melanocytic lesions, including 22 PSCN and 24 spindle cell malignant melanomas (SCMMs), we collected clinical and histopathologic characteristics and evaluated cell cycle and apoptosis regulators by immunohistochemistry. Moreover, fluorescence in situ hybridization (FISH) using probes targeting 6p25 (RREB1), 11q13 (CCND1), 6q23 (MYB), and centromere 6 was performed. PSCN presented in younger people, frequently in women, and were small lesions under 7 mm in diameter affecting the lower limbs, whereas SCMMs arose more frequently in the trunk, upper limbs, and head and neck region. Histologically, symmetry, good lateral demarcation, and uniformity of cellular nests were significantly differential features of PSCN, whereas pagetoid and adnexal spread were frequently seen in both tumors. Immunohistochemical markers that significantly differed from melanomas were Ki-67, cyclin D1, and survivin. FISH was positive in 1 of 15 PSCN and was negative in 4 of 15 SCMMs. These results correlated to a sensitivity of 73% and a specificity of 93%. In conclusion, in the evaluation of pigmented spindle cell melanocytic tumors, the integration of clinical and histologic assessment is essential. However, ancillary techniques such as proliferation antigen Ki-67, cyclin D1, survivin, and FISH can be useful as adjunctive tools.

The staining pattern of pigmented spindle cell nevi with S100A6 protein.

BACKGROUND: Spitz nevi typically show strong diffuse staining with S100A6, whereas staining in melanomas is commonly patchy and weak. To our knowledge, S100A6 has not been studied in pigmented spindle cell nevus (PSCN), considered by many to be a variant of Spitz nevus. METHODS: Forty-six archived PSCNs were stained with S100A6 and then categorized by predominant cell size and staining pattern. RESULTS: Eighteen (55%) of the small cell predominant nevi showed patchy staining, eight showed diffuse staining and seven were negative for S100A6. Two predominantly large-celled 'PSCNs' were diffusely positive and had many histopathological attributes of classical Spitz nevi. On review, these two cases were reclassified as Spitz nevi and excluded from the remainder of this study. Of the nevi with mixed cell size, one had no expression of S100A6. In the remaining tumors, the small cells showed patchy staining in eight (80%) and diffuse staining in two (20%). The large cells showed patchy staining in four (40%) and diffuse staining in six (60%). CONCLUSION: In contrast to the strong diffuse S100A6 staining typical of Spitz nevi, the small spindle cells of PSCN commonly show patchy staining or fail to stain completely. In melanocytic neoplasms composed of small spindle cells, patchy S100A6 staining should not be interpreted as evidence of supporting a diagnosis of melanoma.

Glioma angiocéntrico. Presentación de un caso / Angiocentric glioma: a tumour with ependymal type differentiation

El glioma angiocéntrico se incluye como una nueva entidaden la última clasificación de la OMS dentro la categoría«otros tumores neuroepiteliales» y considerado grado 1. Presentamosun caso en un niño de 10 años con una neoplasiacerebral hemisférica que se manifestó clínicamente con crisisepilépticas. Radiológicamente la tumoración era hiperintensaen T2. Histológicamente presentaba, como rasgos distintivos,células monomorfas bipolares fusiformes conpatrón angiocéntrico, y pseudorrosetas radiales. Las técnicasde inmunohistoquímica mostraban expresión para PGFA, yuna característica positividad para EMA en forma de gotascitoplasmáticas o formaciones tubulares microscópicas. Laneoplasia fue extirpada en su totalidad no detectándose recidivasen controles radiológicos, en seis años de seguimiento(AU)

The latest WHO classification included angiocentricglioma as a new entity in the category of «other neuroepithelialtumours» and considered it a grade 1 tumour. We presenta case in a 10 year old boy with a brain tumour clinicallymanifested as seizures. Radiologically the tumour wasT2-hyperintense. Histologically, distinctive features weremonomorphous bipolar spindle cells in an angiocentric pattern,and radial pseudorosettes. The immunohistochemicalstudy showed expression for GFAP, and a characteristicpositivity for EMA as dot-like or cytoplasmic tubularmicroscopic formations. The tumour was excised as a wholeand no recurrences were detected in six years of followupwith imaging techniques(AU)