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1.
Am J Dermatopathol ; 46(8): 483-491, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38842402

RESUMO

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.


Assuntos
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 Jovem
2.
Mod Pathol ; 35(5): 664-675, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34857909

RESUMO

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.


Assuntos
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/genética
3.
Pediatr Dev Pathol ; 23(6): 424-430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790583

RESUMO

INTRODUCTION: Somatic internal tandem duplication of 3' of BCOR (BCOR ITD) has been found in clear cell sarcomas of the kidney (CCSK), soft tissue undifferentiated round cell sarcomas/primitive myxoid mesenchymal tumors of infancy (URCS/PMMTI), and a subgroup of central nervous system high-grade neuroepithelial tumors (CNS-HGNET). BCOR ITD+ tumors share morphologic features. Expression of OLIG2 and epidermal growth factor receptor (EGFR) has been reported in CNS-HGNET with BCOR ITD. Here, we characterize OLIG2 and EGFR expression in URCS/PMMTI with BCOR ITD. METHODS: Paraffin blocks of 9 polymerase chain reaction-confirmed soft tissue BCOR ITD+ tumors (URCS/PMMTI) were immunophenotyped for OLIG2 and EGFR expression and scored semiquantitatively by percentage of positive cells and intensity of staining as negative, 1+, 2+, and 3+. Fluorescence in situ hybridization (FISH) for EGFR amplification was performed (amplification EGFR/CEP7 ratio ≥2.0). RESULTS: All 9 tumors showed membrane/cytoplasmic expression of EGFR, strong and diffuse (3+) in 8 cases; weak (+2) in 1. FISH detected no EGFR amplification. OLIG2 was negative in all. CONCLUSIONS: EGFR is overexpressed in pediatric URCS/PMMTI with BCOR ITD and may be related to transcriptional upregulation of EGFR by BCOR ITD. OLIG2 negative staining differentiates URCS/PMMTI from CNS-HGNET. This finding may further support the possibility that these tumors have a different stem cell of origin.


Assuntos
Biomarcadores Tumorais/metabolismo , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Sequências de Repetição em Tandem , Biomarcadores Tumorais/genética , Pré-Escolar , Receptores ErbB/metabolismo , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Estudos Retrospectivos , Sarcoma/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/patologia , Regulação para Cima
4.
Front Med (Lausanne) ; 11: 1402577, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086952

RESUMO

Diagnosing skin diseases in children can be a complex interdisciplinary problem. Incontinentia pigmenti (IP), also known as Bloch-Sulzberger syndrome, is a rare hereditary genodermatosis related to a mutation in the IKBKG gene. We present a family case of IP described from the perspective of various specialists, including dermatologists, oncologists, geneticists, dentists, and trichologists. The peculiarity of this case is the development of squamous cell carcinoma (SCC) on the shin of a 10-year-old female patient with IP. The patient had a positive family history: her mother and two sisters also displayed clinical manifestations of IP with involvement of skin, teeth and hair. The presence of exons 4-10 deletion in the IKBKG gene in all affected females was confirmed by detailed genetic evaluation using long-range PCR, and also high degree of X-chromosome inactivation skewing was demonstrated. The family underwent a comprehensive examination and was followed up for 2 years with successful symptomatic treatment of dermatologic manifestations. Recommendations were also made regarding dental and hair problems. By the end of the follow-up period, patients had stabilized, with the exception of a 36-year-old mother who developed generalized morphea. The study demonstrates the varying expressiveness of clinical symptoms among family members and emphasizes the importance of timely diagnosis for effective management of patients with IP.

5.
Am J Surg Pathol ; 48(3): 309-316, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38155550

RESUMO

Pediatric adrenocortical neoplasms (ACNs) are extremely rare tumors in contrast to their adult counterparts. Distinguishing benign from malignant is challenging based on pure morphologic grounds. Previously, 2 scoring systems were proposed in pediatric ACN, including the Wieneke criteria (WC) and its modified version (modified WC [mWC]). In adults, the reticulin algorithm (RA) has proven inexpensive, reliable, predictive, and reproducible; however, it has been validated only recently in children in a limited number of cases. This study aims to assess the RA utility compared with other scoring systems in a series of 92 pediatric ACNs. All cases were individually scored, and mitotic rate cutoffs were recorded. Reticulin alterations were classified as quantitative and qualitative. Outcome data were available in 59/92. The median age was 5 years (0.1 to 18 y) with an M:F of 0.6. Clinical presentation included virilization (39%), Cushing syndrome (21%), other symptoms (4%), and asymptomatic (36%). The reticulin framework was intact in 27% and altered in 73% of cases, showing qualitative (22%), quantitative (73%), and both (5%) alterations. In patients with favorable outcomes, 59% showed either intact reticulin or qualitative alteration compared with the unfavorable outcome group, where 90% showed quantitative alterations. All scoring systems WC ( P < 0.0001), mWC ( P = 0.0003), and the adult/pediatric RA ( P < 0.0001) had predictive value. The RA is comparable to WC and mWC, easier to apply, and is the most sensitive histopathological approach to identifying aggressive behavior in pediatric ACN. Its integration into the WC might be helpful in ACN of uncertain malignant potential and deserves further investigation.


Assuntos
Neoplasias do Córtex Suprarrenal , Reticulina , Adulto , Criança , Humanos , Pré-Escolar , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Algoritmos , Síndrome
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