Cellular leiomyoma (CL) represents an uncommon variant of uterine leiomyoma with limited data concerning its immunohistochemical and molecular profile. We performed a comprehensive analysis of 52 CL cases all of which were analyzed immunohistochemically. Molecular analysis was possible in 32 cases with sufficient DNA, and 38 cases with sufficient RNA. The immunohistochemical results showed a high expression of smooth muscle markers (calponin (100%), desmin (100%), smooth muscle actin (98.1%), caldesmon (96.1%), transgelin (96.1%), smooth muscle myosin heavy chain (86.5%), and smoothelin (61.5%)). Concerning markers of endometrial stromal differentiation, the expression of CD10 was observed in 65.4% cases (42.2% with H-score > 50), and IFITM1 in 36.5% cases (1.9% with H-score > 50). 36.5% showed HMGA2 overexpression at the IHC level, associated with increased mRNA expression in 14/14 cases. The rearrangement of the HMGA2 gene was detected in 13.2%. Chromosome 1p deletion was found in 19.3%, while 9.4% of tumors showed a pathogenic mutation in the MED12 gene. In conclusion, CL is immunohistochemically characterized by a high expression of "smooth muscle" markers commonly associated with a co-expression of "endometrial stromal" markers, where IFITM1 shows superior performance compared to CD10 regarding its specificity for differentiation from endometrial stromal tumors. The sensitivity of smoothelin in CL seems rather low, but no data is available to assess its specificity. On a molecular level, the most common mutually exclusive aberration in CL affects HMGA2, followed by chromosome 1p deletions and MED12 mutations.

• MeSH
• Chromosomes chemistry   metabolism   MeSH
• Leiomyoma * pathology   MeSH
• Humans MeSH
• Mediator Complex genetics   metabolism   MeSH
• Mutation MeSH
• Uterine Neoplasms * pathology   MeSH
• Endometrial Neoplasms * genetics   MeSH
• Neprilysin analysis   MeSH
• HMGA2 Protein MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Making the distinction between primary mucinous and metastatic ovarian tumors is often difficult, especially in tumors with a primary source from the gastrointestinal tract, pancreas and biliary tree. The aim of the following paper is to provide an overview of the problematics, with a focus on the possibilities of the differential diagnosis at the macroscopic, microscopic and immunohistochemical level. MAIN BODY: The three main aspects of mucinous ovarian tumors are described in detail, including the comparison of the available diagnostic algorithms based on the evaluation of mostly macroscopic features, characterization of the spectrum of microscopic features, and a detailed analysis of the immunophenotype comparing 20 antibodies with the assessment of their statistical significance for differential diagnosis purposes. Specific features, including Krukenberg tumor and pseudomyxoma peritonei, are also discussed. CONCLUSION: Despite the growing knowledge of the macroscopic and microscopic features of ovarian mucinous tumors and the availability of a wide range of immunohistochemical antibodies useful in this setting, there still remains a group of tumors which cannot be precisely classified without close clinical-pathological cooperation.

• MeSH
• Gastrointestinal Tract pathology   MeSH
• Humans MeSH
• Adenocarcinoma, Mucinous pathology   MeSH
• Ovarian Neoplasms pathology   MeSH
• Pancreas pathology   MeSH
• Peritoneal Neoplasms pathology   MeSH
• Pseudomyxoma Peritonei diagnosis   pathology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable. CASE PRESENTATION: Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM_004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM_006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM_005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient. CONCLUSIONS: Our result support the theory that at least some mesonephric-like ovarian adenocarcinomas are of Müllerian origin. The serous borderline tumor seems to be a precursor of mesonephric-like adenocarcinoma, which has been proven in our case by both tumors sharing the same mutations, and the presence of cumulative molecular aberrations in the mesonephric-like adenocarcinoma.

• MeSH
• Adenocarcinoma diagnosis   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mesonephroma pathology   MeSH
• Biomarkers, Tumor analysis   MeSH
• Uterine Neoplasms diagnosis   pathology   MeSH
• Ovarian Neoplasms diagnosis   pathology   MeSH
• Ovary pathology   MeSH
• Precancerous Conditions pathology   MeSH
• Cystadenoma, Serous diagnosis   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH

Hepatocyte nuclear factor 1 beta (HNF1B) is transcription factor which plays a crucial role in the regulation of the development of several organs, but also seems to be implicated in the development of certain tumours, especially the subset of clear cell carcinomas of the ovary and kidney. Depending on the type of the tumour, HNF1B may act as either a tumour suppressor or an oncogene, although the exact mechanism by which HNF1B participates in the process of cancerogenesis is unknown. Using immunohistochemical approach and methylation and mutation analysis, we have investigated the expression, epigenetic, and genetic changes of HNF1B on 40 cases of colorectal adenomas and 105 cases of colorectal carcinomas. The expression of HNF1B was correlated with the benign or malignant behaviour of the lesion, given that carcinomas showed significantly lower levels of expression compared to adenomas. In carcinomas, lower levels of HNF1B expression were associated with recurrence and shortened disease-free survival. The mutation analysis revealed three somatic mutations (two frameshift and one nonsense) in the carcinoma sample set. Promoter methylation was detected in three carcinomas. These results suggest that in colorectal cancer, HNF1B may play a part in the pathogenesis and act in a tumour suppressive fashion.

• MeSH
• Epigenesis, Genetic * MeSH
• Hepatocyte Nuclear Factor 1-beta genetics   MeSH
• Colorectal Neoplasms genetics   metabolism   pathology   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local genetics   metabolism   pathology   MeSH
• DNA Methylation * MeSH
• Survival Rate MeSH
• Biomarkers, Tumor genetics   MeSH
• Follow-Up Studies MeSH
• Prognosis MeSH
• Promoter Regions, Genetic MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH