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.

• MeSH
• dítě MeSH
• epiteloidní a vřetenobuněčný névus * genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory kůže * genetika   patologie   MeSH
• névus * MeSH
• pigmentový névus * genetika   patologie   MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• thiolesterasa ubikvitinu genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• dospělí MeSH
• epiteloidní a vřetenobuněčný névus genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• MAP kinasa-kinasa 1 genetika   MeSH
• melanom genetika   patologie   MeSH
• nádory kůže genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Intraperitoneal malignant cells detection in patients with gastric cancer is associated with a significant decrease in overall survival. The overall accuracy of cytological examination of peritoneal lavages, however, is quite low, and intraperitoneal recurrence has been observed even in patients with negative cytology. Immunocytochemistry and molecular techniques have been investigated to improve high-risk patients' identification with variable results. The aim of this study was to compare the performance of different laboratory methods applied to peritoneal washing, to improve the cytological identification of malignant cells. METHODS: We prospectively evaluated 21 patients who underwent surgery and peritoneal lavage for gastric cancer. Among them, 18 had negative cytology and three were positive for malignant cells. For each patient, immunohistochemistry with BerEP4 antibody was performed on seriate sections of cellblock preparation at different levels, using the method reported for sentinel nodes in other types of cancer. Paired frozen quotes of washing fluids were evaluated by qRT-PCR with primer for mRNA of Ceacam5. RESULTS: In 4 of 18 patients with previous negative routine cytology, isolated neoplastic cells in seriate sections of the cellblock inclusion have been found. Results showed to be coherent with molecular analysis for CEA mRNA. CONCLUSION: The sensitivity and specificity of peritoneal washing analyses should be notably improved by immunohistochemistry applied to multilevel cellblock sectioning. The method is less expensive and more widely applicable than molecular analysis, in each laboratory setting. This approach allows detection of minimum peritoneal seeding in patients with gastric cancer.

• MeSH
• ascitická tekutina metabolismus   patologie   MeSH
• GPI-vázané proteiny genetika   metabolismus   MeSH
• karcinoembryonální antigen genetika   metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory žaludku metabolismus   patologie   MeSH
• peritoneální výplach metody   normy   MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH