Ovarian Sertoli-Leydig cell tumors (SLCTs) are uncommon sex cord-stromal tumors associated with both germ-line and somatic DICER1 mutations, the frequency of which has varied widely in different studies (0% to 62.5%). The current World Health Organization Classification includes 3 histologic types of SLCTs (well-differentiated, moderately differentiated, and poorly differentiated); heterologous elements and/or retiform patterns may be present in moderately and poorly differentiated neoplasms. We investigated the frequency of DICER1 mutations in a series of 38 ovarian tumors initially diagnosed as SLCTs, and explored whether identified mutations were associated with specific morphologic features. Specialist pathology review performed blinded to molecular results confirmed 34 tumors to be SLCTs (22 moderately differentiated, 8 poorly differentiated; 4 well-differentiated), while the remaining 4 neoplasms were considered not to represent SLCTs. Of the 34 cases diagnosed as SLCTs, 30 (88%) harbored ≥1 DICER1 mutation. All 30 moderately differentiated/poorly differentiated SLCTs contained mutations, but we did not find deleterious DICER1 mutations in the 4 well-differentiated SLCTs. Our study reports the highest DICER1 mutation frequency to date in SLCTs, with 100% of moderately differentiated and poorly differentiated tumors being DICER1-mutated. This suggests that DICER1 mutation may be a defining feature of these neoplasms. Although the number of cases is limited, well-differentiated SLCTs appear to be DICER1-independent. Moderately differentiated and poorly differentiated SLCT components often coexist with each other and form part of a spectrum, while well-differentiated SLCTs usually occur in pure form, suggesting that fundamentally, these represent 2 separate and independent tumor types with a different pathogenesis. We suggest that all patients with ovarian SLCTs undergo germ-line DICER1 mutation testing.

Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is one of the most aggressive pediatric cancers. Patients with stage IV high-risk neuroblastoma receive an intensive multimodal therapy ending with an immunotherapy based on a chimeric monoclonal antibody ch14.18. Although the use of ch14.18 monoclonal antibody has significantly increased the survival rate of high-risk neuroblastoma patients, about 33% of these patients still relapse and die from their disease. Ch14.18 targets the disialoganglioside, GD2, expressed on neuroblastic tumor (NT) cells. To better understand the causes of tumor relapse following ch14.18 immunotherapy, we have analyzed the expression of GD2 in 152 tumor samples from patients with NTs using immunohistochemical stainings. We observed GD2 expression in 146 of 152 samples (96%); however, the proportion of GD2-positive cells varied among samples. Interestingly, low percentage of GD2-positive cells before immunotherapy was associated with relapse in patients receiving ch14.18 immunotherapy. In addition, we demonstrated in vitro that the sensitivity of neuroblastoma cell lines to natural killer-mediated lysis was dependent on the proportion of GD2-positive cells, in the presence of ch14.18 antibody. In conclusion, our results indicate that the proportion of tumor cells expressing GD2 in NTs should be taken in consideration, as a prognostic marker, for high-risk neuroblastoma patients receiving anti-GD2 immunotherapy.

We believe that determination of TNF-alpha in cystic fluid simultaneously with other parameters can be an additional parameter for clinical diagnosis of inflammed cysts.

GATA binding protein 3 (GATA3) immunohistochemistry is primarily used as a marker of breast and urothelial differentiation, particularly in metastatic settings. In the gynecologic tract it also serves a robust marker for mesonephric and trophoblastic tumors. However, expression has also been described in more common malignancies of gynecologic tract including ovarian, endometrial, and cervical carcinomas. Data on the distribution of GATA3 expression in gynecologic malignancies is somewhat limited, particularly across different histologic subtypes of ovarian, endometrial, and cervical carcinomas. To assess the rates of GATA3 expression among common gynecologic cancers of various histologic types, 100 ovarian carcinomas, 64 endometrial carcinomas/atypical hyperplasias, 16 cervical squamous cell carcinomas (SCCs), and 14 endocervical adenocarcinomas were evaluated by immunohistochemistry for GATA3 positivity. Eight percent of endometrial carcinomas expressed GATA3, including 2 serous carcinomas, 1 carcinosarcoma, and 1 case of atypical hyperplasia. Six percent of ovarian carcinomas were GATA3-positive including 2 clear cell carcinomas, 2 mucinous adenocarcinomas, and 2 high-grade serous carcinomas. Thirty-eight percent of cervical SCCs showed weak to moderate staining in up to 50% of tumor cells. All endocervical adenocarcinomas were entirely negative for GATA3. In summary, GATA3 shows focal weak to moderate expression in a subset of endometrial and ovarian carcinomas. In contrast, usual-type endocervical adenocarcinomas are typically negative for GATA3, which can be helpful in differentiating them from mesonephric proliferations or carcinomas. A larger proportion of cervical SCCs express GATA3, therefore caution should be exercised when using this stain in the setting of a lower genitourinary carcinomas.