p53 Abnormal (Copy Number High) Endometrioid Endometrial Carcinoma Has a Prognosis Indistinguishable From Serous Carcinoma.

Among the 4 molecular subgroups of endometrial carcinoma, the p53 abnormal (copy number high) subgroup has the worst prognosis; however, the histologic characteristics of this subgroup are not well established. Also, it is not well established whether low-grade tumors can belong to the p53 abnormal molecular subgroup and if so, what is the prognostic significance of the p53-mutated molecular subgroup in low-grade tumors. In the current study, we included 146 p53-mutated endometrial carcinomas and performed molecular subgrouping either based on a combination of immunohistochemical studies for p53 and MMR protein expression and POLE mutation testing (81 cases) or based on array-based and sequencing-based technologies (65 cases). We excluded cases that belonged to the POLE mutant or MSI molecular subgroups and only studied p53 abnormal (molecular subgroup) endometrial carcinomas (125 cases). In 71 cases, the molecular subgroup was determined by a combination of immunohistochemical studies and POLE mutation testing, and in 54 cases by array-based and sequencing-based methods. We reviewed 1 to 2 representative digital slides from each case and recorded the morphologic characteristics as well as clinical, treatment, and survival follow-up data. Overall, 47 cases were classified as endometrioid carcinoma, 55 serous carcinoma, and 23 other histotypes. Eight cases were FIGO 1, 21 were FIGO 2, and 91 were FIGO 3. A significant proportion of the cases (24.2%) were histologically classified as low-grade (FIGO 1 or 2) endometrioid carcinoma. There was no morphologic characteristic that showed prognostic implication. There was no significant difference in survival among different histotypes (P=0.60). There was no significant difference in survival among low-grade endometrioid (FIGO 1 or 2) versus high-grade (FIGO 3) tumors (P=0.98). Early-stage (stage I), low-grade tumors showed no significant survival advantage over early-stage, high-grade tumors (P=0.16) and this was more evident in FIGO 2 tumors. Although not statistically significant, the FIGO 2 tumors showed a trend toward worse survival than FIGO 3 tumors. Among the cases with available treatment data, more patients with early-stage high-grade tumors received adjuvant treatment, compared to patients with early-stage low-grade tumors, possibly explaining this trend (P=0.03). In conclusion, the findings of our study suggest that low-grade p53 abnormal endometrioid endometrial carcinomas (especially FIGO 2 tumors) have an aggressive course, with a prognosis similar to high-grade tumors. Furthermore, our study suggests that patients who had early-stage low-grade p53 abnormal disease might have been undertreated because of the "low-grade" histotype.

GATA3 Expression in HPV-associated and HPV-independent Vulvar Squamous Cell Carcinomas: Patterns of Expression and Prognostic Significance.

Substantial diminution or loss of GATA3 expression is reportedly frequent in human papillomavirus-independent (HPVI), p53-mediated vulvar intraepithelial neoplasia. Herein, we study GATA3 expression in vulvar squamous cell carcinoma (VSCC) and assess its clinicopathologic significance. Eighty-six cases of VSCC diagnosed at a single institution were immunohistochemically assessed for their expression of GATA3, as well as any possible relationships with patient outcomes and other clinicopathologic parameters. Given that GATA3 expression pattern in the normal vulvar epidermis is typically strong basal staining with a uniform upward extension until at least the mid epidermal layers, VSCCs were scored using a previously reported tripattern system: pattern 0 (>75% tumor staining), pattern 1 (25% to 75% staining), and pattern 2 (<25% staining). Severe loss of GATA3 expression (pattern 2) was present in both human papillomavirus-associated (HPVA) and HPVI VSCC but was significantly more common in HPVI cases ( P <0.001). Among 52 HPVA VSCCs, 16 (30.7%), 15 (28.8%), and 21 (40.3%) cases showed patterns 0, 1, 2 staining whereas among 34 HPVI VSCCs, the respective frequencies were 1 (2.9%), 5 (14.7%), and 28 (82.3%). None of the 30 p53 abnormal VSCCs showed pattern 0 staining (0%). Five (16.6%) and 25 (83.3%) showed patterns 1 and 2 staining, respectively. On univariate analysis, the pattern 2 cohort showed a significantly worse overall survival (OS) and disease-free survival (DFS) than the pattern 0 or 1 cohort ( P =0.011 and 0.024, respectively), but this finding was not independent of stage on multivariate analysis ( P =0.34; hazard ratio: 1.82; 95% CI: 0.55-6.06). Subgroup analysis of the p53 wild-type cases showed significantly worse OS for pattern 2 than the pattern 0 or 1 cohorts, independent of stage ( P =0.04; hazard ratio: 6.5; 95% CI: 1.08-39.8). Subgroup analysis of p53 abnormal cases, however, showed no difference in OS and DFS among the 3-tiered GATA3 cohorts. In summary, loss of GATA3 may be seen in both HPVA and HPVI VSCCs but is significantly more common in HPVI SCCs. Loss or substantial diminution of GATA3 expression (pattern 2) is a negative prognostic factor in vulvar SCCs, but only in the p53 wild-type subset, where its negative prognostic significance appears to be independent of stage.

Primary Synovial Sarcoma of the Uterine Cervix: First Case Report.

Synovial sarcoma is a translocation associated soft tissue malignancy frequently affecting young adults. The classic translocation is t(X;18)(p11.2;q11.2): SS18-SSX1/2/4 fusion. Synovial sarcoma tends to favor the distal extremities but can also arise in other locations. To date, no case of primary synovial sarcoma of the uterine cervix has been reported. We report a 42-yr-old woman with no prior history who presented to clinic with vaginal spotting for 3 mo and was found to have a large mass in the uterine cervix. The mass was evacuated from the vagina and sent for pathologic diagnosis. Sections showed proliferation of monotonous spindle cells with scant eosinophilic cytoplasm, round to slightly irregular nuclei, variable nucleoli and frequent mitosis in a background of delicate capillary and occasional thick-walled vessels. No malignant epithelium was identified in the entire specimen. On immunohistochemical workup tumor cells were negative for pan cytokeratin, OSCAR, EMA, chromogranin, S100, SMA, desmin, myogenin, WT1, CD117, CD34, and BRG1. CD45 was positive in a few inflammatory cells. Cyclin D1 showed partial weak to moderate nuclear reactivity. CD99 demonstrated strong diffuse membranous reactivity and BCL-2 showed strong cytoplasmic staining in 60% of tumor cells. Florescence in situ hybridization results for EWSR1, BCOR, and CIC gene rearrangements were negative, however, florescence in situ hybridization results for SS18 (SYT) (18q11) gene rearrangement was positive. A diagnosis of monophasic synovial sarcoma was rendered. We review the differential diagnoses of tumors with similar morphology and discuss the diagnostic process. With this case report it is imperative to include synovial sarcoma in differential diagnosis list of sarcomas of uterus and cervix.

Tumor-Infiltrating Lymphocyte Volume Is a Better Predictor of Disease-Free Survival Than Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma.

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer. METHODS: We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups. RESULTS: TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance. CONCLUSIONS: Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.

Sinonasal undifferentiated carcinoma: clinicopathological spectrums and diagnosis reappraisal.

Sinonasal undifferentiated carcinoma (SNUC) is defined as undifferentiated carcinoma of the sinonasal tract without glandular or squamous features and not otherwise classifiable. SNUC is a rare tumor, with a long list of differential diagnoses, and often poses a considerable diagnostic challenge. In addition, recent advances in molecular and immunohistochemistry techniques have recognized several new entities that were previously included in the SNUC category. These include SMARCB1 (INI-1)-deficient carcinoma, NUT (nuclear protein in testis) carcinoma, adamantinoma-like Ewing sarcoma, and the most recently described and rarer SMARCA4 (BRG)-deficient carcinoma. In this study, we retrospectively reviewed 11 cases with an original diagnosis of SNUC. We found that a significant portion of those cases can be reclassified into specific entities, with potential impact on therapy and prognosis because of misclassification in 2 of these cases.