Co-Occurrence of Hotspot Point Mutation and Novel Deletion Mutation of TERT Promoter in Solid Variant Papillary Thyroid Carcinoma in a Patient with Synchronous Esophageal Cancer.

(1) Introduction: Telomerase reverse transcriptase (TERT) promoter mutations are associated with unfavorable clinical outcomes in papillary thyroid carcinomas (PTCs). Two substitution mutations, C228T (c.1-124C>T) and C250T (c.1-146C>T), make up most of the mutations and occur in a mutually exclusive manner. (2) Case presentation: A 72-year-old man was initially referred to a tertiary hospital for treatment of esophageal cancer. Preoperative imaging revealed a 3.2 cm thyroid nodule pathologically diagnosed as PTC on needle biopsy. The patient underwent thyroid lobectomy with esophagectomy and was finally diagnosed with synchronous solid variant PTC (SVPTC) and esophageal squamous cell carcinoma. Sanger sequencing using DNA from the thyroid tumor showed an indel mutation, c.1-132_1-124delinsT, composed of a deletion (c.1-132_1-125del) as well as a hotspot mutation (c.1-124C>T(C228T)) in the TERT promoter. (3) Conclusions: This is the first report of PTC harboring a novel deletion along with a hotspot mutation in the TERT promoter in a patient with synchronous esophageal squamous cell carcinoma.

Abdominopelvic Metastasis of Endometrial Serous Carcinoma Initially Misdiagnosed as Early-Stage Low-Grade Endometrioid Carcinoma: The Importance of Recognizing Minimal Uterine Serous Carcinoma.

Minimal uterine serous carcinomas (MUSCs) include serous carcinomas with invasion confined to the endometrium (superficial serous carcinoma) and those without stromal invasion (serous endometrial intraepithelial carcinoma). Although these tumors are confined to the endometrium proper, they have highly metastatic potential for disseminating to extra-uterine sites. We report here a case of MUSC that was initially misdiagnosed as early-stage low-grade endometrioid carcinoma but later metastasized to the abdominopelvic peritoneum. The patient was a 61-year-old woman who was diagnosed with grade 1 endometrioid carcinoma of the endometrium and underwent total hysterectomy. Because the tumor was confined to the endometrium (International Federation of Gynecology and Obstetrics stage IA), no further treatment was performed. However, several metastatic tumor masses were detected in the vaginal stump and abdominopelvic peritoneum 7 years after the surgery. Histologically, the metastatic tumor tissues showed high-grade carcinoma. A review of previous hysterectomy slides showed multiple separate foci of atypical glandular proliferation measuring up to 0.8 cm in the greatest dimension and consisting of markedly atypical cells involving the surface and atrophic glands. The tumor showed a predominantly glandular architecture without evident papillary growth or stromal invasion. However, it had large, pleomorphic nuclei showing a high nuclear-to-cytoplasmic ratio, conspicuous eosinophilic nucleoli, and numerous mitotic figures. Characteristically, the tumor showed marked nuclear atypia immediately appreciated at low magnification in the background of well-formed glandular structures, indicating a significant discordance between nuclear and architectural features. On immunostaining, both the uterine and metastatic tumor tissues exhibited diffuse and strong p16 expression and mutant pattern of p53 expression, confirming the diagnosis of serous carcinoma. In summary, the case findings support that failure to preoperatively recognize high-risk endometrial carcinoma is associated with worse outcomes. Complete surgical staging and accurate pathological diagnosis are critical for patients with serous carcinoma even at the early clinical stage.

Superficially Spreading Endocervical Adenocarcinoma in situ with Multifocal Microscopic Involvement of the Endometrial Surface: A Case Report with Emphasis on the Potential for Misdiagnosis Based on Endometrial Curettage Specimens.

Misdiagnosis of endocervical adenocarcinoma (EAC) as endometrial endometrioid carcinoma (EEC) is one of the major concerns when evaluating endometrial curettage specimens. It is difficult to differentiate EAC involving the endometrium from EEC, particularly when the specimens have only a few small tumor fragments. We report a case of endocervical adenocarcinoma in situ (AIS) with multifocal microscopic involvement of the endometrium. The endometrial curettage specimen obtained from an 82-year-old woman consisted of a large volume of blood and fibrin, with small endometrial tissue fragments showing microscopic foci of atypical glandular proliferation. Based on the presence of complex glands with stratified mucin-poor columnar epithelium and intermediate-grade nuclear atypia, a preoperative diagnosis of grade 1 EEC was made. However, the hysterectomy specimen revealed an endocervical AIS involving the endocervix and low uterine segment. Frequent mitotic figures and apoptotic bodies, characteristic of AIS, were present. The endometrium showed a few microscopic foci of atypical glandular proliferation involving the surface only. Their histological features were similar to those of the endocervical AIS. Immunohistochemically, the atypical glands exhibited block p16 positivity. The final diagnosis was a superficially spreading endocervical AIS with multifocal microscopic involvement of the endometrial surface epithelium. In summary, small tumor tissues in an endometrial curettage may lead to misdiagnosis of AIS or EAC as EEC, especially when the pathologists are unaware of the possibility of microscopic endometrial involvement of AIS or EAC. The origin of the tumor can be correctly determined based on a combination of histological features and immunostaining. Endocervical AIS involving the endometrium should be included in the differential diagnosis of neoplastic glandular lesions in endometrial curettage specimens. An accurate diagnosis in these cases is important because of its significant implications for clinical management.

Dedifferentiated endometrioid carcinoma of the uterus : report of four cases and review of literature.

BACKGROUND: Dedifferentiated endometrioid adenocarcinoma (DEAC) is rare and is known to be more aggressive than high-grade endometrioid carcinoma. Differentiating between the two is important to provide appropriate treatment for patients. CASE PRESENTATION: This is a retrospective study including four cases of DEAC of the uterus, which was diagnosed and treated in our Obstetrics and Gynecology department between January 2013 and December 2015. Clinical, pathological, and immunohistochemical staining features are discussed. Each tumor was composed of undifferentiated carcinoma (UC) and low-grade endometrioid carcinoma with abrupt transition between them. Two patients showed recurrence or progression within one month postoperatively and died at the last follow-up. An immunohistochemical study showed PAX-8, ER, PR, and E-cadherin expression in UC component. CONCLUSIONS: DEAC should not be underdiagnosed as conventional endometrioid adenocarcinoma due to its fulminant clinical course. Therefore, UC, including DEAC, should be further categorized to provide intensive treatment to improve patient survival.

PD-L1 Expression and Combined Status of PD-L1/PD-1-Positive Tumor Infiltrating Mononuclear Cell Density Predict Prognosis in Glioblastoma Patients.

BACKGROUND: Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy. METHODS: PD-L1 expression and PD-1-positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated. RESULTS: PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053). CONCLUSIONS: PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity.