BACKGROUND: Recently a somatic point mutation in the FOXL2 gene has been characterized in ovarian adult type of granulosa cell tumor (ATGCT) (94.6%), thecomas (12.5%), but not in juvenile type of ovarian granulosa cell tumor, other ovarian sex cord tumors and ovarian surface epithelial neoplasms. Whether this mutation is present in testicular ATGCT or incompletely differentiated sex cord stromal tumor (ISCST) is not known. DESIGN: Four ATGCTs, 4 ISCST were immunohistochemically investigated with anti-FOXL2 and 3 ovarian ATGCTs were used as positive control. RESULTS: Weak-to-moderate immunoreactivity was found in all tested testicular and ovarian tumors. PCR and direct sequencing were used for detection of c.402C>G of the FOXL2 gene. No mutation was found in any of the testicular ATGCTs or ISCSTs whereas all ovarian tumors showed the c.402C>G point mutation of the FOXL2 gene. CONCLUSIONS: On the basis of this small series of these rare testicular neoplasms, it seems that the c.402C>G mutation of the FOXL2 gene frequently found in adult type of ovarian GCT does not play any significant role in the development of ATGCT and ISCST.

• MeSH
• bodová mutace genetika   MeSH
• buněčná diferenciace MeSH
• dítě MeSH
• dospělí MeSH
• forkhead transkripční faktory genetika   metabolismus   MeSH
• genetické asociační studie MeSH
• gonadální stromální nádory diagnóza   genetika   patologie   MeSH
• imunohistochemie MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mutační analýza DNA MeSH
• nádor z folikulárních buněk diagnóza   genetika   patologie   MeSH
• nádory vaječníků diagnóza   genetika   patologie   MeSH
• předškolní dítě MeSH
• senioři MeSH
• testikulární nádory diagnóza   genetika   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Pathogenic germline mutations c.1100delC and p.I157T in the CHEK2 gene have been associated with increased risk of breast, colon, kidney, prostate, and thyroid cancers; however, no associations have yet been identified between these two most common European founder mutations of the CHEK2 gene and ovarian cancers of any type. Our review of 78 female heterozygous carriers of these mutations (age > 18 years) found strikingly higher proportion of adult-type granulosa cell tumors of the ovary (AGCTs) among ovarian cancers that developed in these women (~36%) compared to women from the general population (1.3%). Based on this finding, we performed a cross-sectional study that included 93 cases previously diagnosed with granulosa cell tumors, refined and validated their AGCT diagnosis through an IHC study, determined their status for the two CHEK2 mutations, and compared the prevalence of these mutations in the AGCT cases and reference populations. The prevalence ratios for the p.I157T mutation in the AGCT group relative to the global (PR = 26.52; CI95: 12.55-56.03) and European non-Finnish populations (PR = 24.55; CI95: 11.60-51.97) support an association between the CHEK2p.I157T mutation and AGCTs. These rare gynecologic tumors have not been previously associated with known risk factors and genetic predispositions. Furthermore, our results support the importance of the determination of the FOXL2p.C134W somatic mutation for accurate diagnosis of AGCTs and suggest a combination of IHC markers that can serve as a surrogate diagnostic marker to infer the mutational status of this FOXL2 allele.

• Publikační typ
• časopisecké články MeSH

The existence of a true mixed germ cell-sex cord stromal tumor (MGSCT) of the testis remains controversial. Based on our experience with rare testicular tumors in this spectrum, we sought to perform a detailed clinicopathologic and molecular study of MGCSCT. Eight cases of testicular MGSCT were morphologically reviewed, screened for chromosomal aberrations (using array comparative genomic hybridization (aCGH) and low pass genomic sequencing), and analyzed by next generation sequencing (The Illumina TruSight Tumor 170). Immunohistochemistry for OCT3/4, Nanog, SALL4, DMRT1, and inhibin was performed on the cohort. Clinical data and follow-up were assessed by medical record review. All patients were karyotypically normal men aged 27-74 years (median 41). All tumors had a similar biphasic morphology characterized by various proportions of the sex cord component resembling granulosa cell tumor of adult type and the germ cell component cytomorphologically akin to spermatocytic tumor. Germ cells were haphazardly scattered throughout the tumor or arranged in larger groups, without tubular formation. In 4 cases, atypical mitoses were found within the germ cells. Additionally, in 2 cases there was invasion into the spermatic cord, adjacent hilar soft tissue and into the tumor capsule, which contained both tumor components. Immunohistochemically, focal nuclear expression of DMRT1 was found in the germ cell component in 7/7 analyzable tumors, while SALL4 was positive in 6 cases and negative in one case. All tumors were negative with OCT3/4 and Nanog. The sex cord stromal component had immunoreactivity for inhibin in 7/7 analyzable cases. Four of 8 cases were cytogenetically analyzable: 4/8 by low pass genomic sequencing and 2/8 by aCGH. The results of both methods correlated well, revealing mostly multiple chromosomal losses and gains. One case revealed loss of chromosome 21; 1 case had loss of chromosomes 21 and 22 and partial gain of 22; 1 case had loss of chromosomes 22 and Y, partial loss of X, and gain of chromosomes 20, 5, 8, 9, 12, and 13; and the remaining one gain of chromosomes 20, 3, 6, 8, 2x(9), 11, 2x(12), 13, 14, 18, and 19. Three cases were analyzable by NGS; clinically significant activating mutations of either FGFR3 or HRAS were not detected in any case. Follow-up was available for 4 patients (12, 24, 84, and 288 months) and was uneventful in all 4 cases. The identification of extratesticular invasion of both the germ cell and sex cord stromal components, the DMRT1 expression, and the presence of atypical mitoses in germ cells argue for the neoplastic nature of the germ cell component. The molecular genetic study revealing multiple chromosomal losses and gains in a subset of the cases provides the first evidence that molecular abnormalities occur in testicular MGSCT. Multiple chromosomal aneuploidies, namely, recurrent losses of chromosomes 21 and 22 and gains of 8, 9, 12, 13, and 20, indicate that the germ cell component might be related to the morphologically similar spermatocytic tumor, which is characterized by extensive aneuploidies including recurrent gains of chromosomes 9 and 20 and loss of chromosome 7. In summary, our data support that rare examples of true MGSCT of the testis do exist and they represent a distinct tumor entity with admixed adult-type granulosa cell tumor and spermatocytic tumor components.

• MeSH
• aneuploidie * MeSH
• biopsie MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• germinální a embryonální nádory chemie   genetika   patologie   MeSH
• gonadální stromální nádory chemie   genetika   patologie   MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy * MeSH
• nádorové biomarkery analýza   genetika   MeSH
• senioři MeSH
• srovnávací genomová hybridizace MeSH
• testikulární nádory chemie   genetika   patologie   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• nádory mužských pohlavních orgánů klasifikace   patologie   MeSH
• Publikační typ
• atlasy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• onkologie
• patologie

• MeSH
• mužské pohlavní orgány MeSH
• nádory MeSH
• urologické nádory MeSH

• Konspekt
• Patologie. Klinická medicína

This updated volume is an ideal point-of-care reference for the accurate diagnosis of the full range of non- neoplastic and neoplastic conditions of the female genital tract, including common and uncommon entities. Nakladatelská anotace. Kráceno

• MeSH
• diferenciální diagnóza MeSH
• gynekologická onemocnění * MeSH
• nádory ženských pohlavních orgánů MeSH
• Publikační typ
• atlasy MeSH

• Konspekt
• Gynekologie. Porodnictví
• NLK Obory
• gynekologie a porodnictví
• NLK Publikační typ
• kolektivní monografie

• MeSH
• mužské urogenitální nemoci diagnóza   patologie   MeSH
• nádory ledvin diagnóza   patologie   MeSH
• Publikační typ
• atlasy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• andrologie
• urologie