Faculty Bibliography

AIMS/OBJECTIVE:Clear cell carcinoma of ovary (CCC) is considered a high-grade malignancy by default and the role of histological grading for assessing clinical outcome is not established. We aimed to evaluate histopathological features associated with clinical outcome in CCC patients. METHODS AND RESULTS/RESULTS:Seventy-six cases of CCC with available clinical follow-up information were studied. Histopathological features, including tumour size, architectural patterns, nuclear atypia, mitotic activity, intratumoral and peritumoral inflammation, presence of endometriosis, peritumoral and intratumoral budding, were evaluated. Multivariate analysis was performed with logistic regression and Kaplan-Meier survival curves with the log-rank test were used for survival analysis. Forty cases (53%) presented at stage I. Complete response to treatment was achieved in 65%, while 35% of patients had tumour recurrence or progression of disease despite treatment. At last follow-up, 13% had died of disease, 20% were alive with disease and 67% had no evidence of disease. Higher stage (P = 0.0016) and presence of intratumoral budding (P = 0.0454) were independently associated with recurrence/disease progression. Advanced stage (P = 0.0011), presence of lymph node involvement (P = 0.0003), intratumoral budding (P = 0.0023) and peritumoral budding (P = 0.0334) were significantly associated with shorter survival. Intratumoral budding was significantly associated with recurrent/progressive disease (P = 0.0195) and also shorter survival (P = 0.0277) within the cohort of low-stage (I/II) patients as well. CONCLUSION/CONCLUSIONS:We have shown that besides the classic prognostic factors of stage and lymph node status, the presence of tumour budding is associated with poorer outcome in patients with CCC. Specifically, evaluation of intratumoral budding may help to more clearly predict prognosis in patients with early-stage disease.

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors that co-express smooth muscle and melanocytic markers. They have a predilection for gynecologic organs where they present a unique diagnostic challenge due to morphologic and immunohistochemical overlap with more common smooth muscle and stromal tumors. Limited information regarding natural history owing to rarity of this tumor makes accurate risk stratification difficult. Five different prognostic classification systems (2 for PEComa of all sites and 3 specific for gynecologic PEComa) have been proposed. We have described clinicopathologic features of 13 new cases of gynecologic PEComa, and tested all 5 prognostic algorithms in a total of 67 cases of gynecologic PEComa (54 cases from previously published studies). Receiver Operating Characteristic curves were built and area under curve (AUC) was calculated to evaluate predictive accuracy. The 'modified gynecologic-specific criteria' showed high sensitivity and specificity and yielded the highest AUC (0.864). The earlier version of it, 'gynecology-specific criteria' suffered from lower specificity (AUC = 0.843). Post hoc McNemar test confirmed significant difference between the performances of 'modified gynecology-specific criteria' and 'gynecology-specific criteria' (p = .008). The 'original' Folpe criteria for PEComas of all sites showed low specificity, had lower AUC (0.591) and was inapplicable in 18% of cases. Its two later versions ('revised' Folpe criteria and 'modified' Folpe criteria) also yielded lower AUC (0.690 and 0.591respectively). We have shown that 'modified gynecologic-specific' algorithm predicts clinical outcome of gynecologic PEComa with high accuracy and have validated its use for prognostic stratification of gynecologic PEComa.

Background: Clear cell carcinoma of ovary (CCCO) accounts for 5-25% of ovarian carcinomas. Considered a high-grade malignancy by default, the role of histological grading for assessing clinical outcome is not established in CCCO. We aimed to evaluate histopathological features predictive of clinical outcome in patients with CCCO.
Design(s): Pathology database was searched after IRB approval. A total of 69 cases of CCCO were studied. Slides from primary tumor resection were reviewed blinded to outcome. The original diagnosis of CCCO was confirmed and the following histopathologic features were recorded: percentage of solid component, degree of nuclear atypia, mitotic activity, intratumoral inflammation, presence of small tumor nests (intratumoral single cells or clusters of <5 cells in non-hyalinized stroma, Figure 1A-B), tumor budding (peritumoral single cells or clusters of <5 cells), lymph node involvement and endometriosis. Information regarding age at diagnosis, clinical stage, treatment and followup was obtained from medical charts. Kaplan-Meier survival curves with log rank test, Fisher's exact test and Mann-Whitney test were used for statistical analysis.
Result(s): Median patient age was 52 years (range 26-75 years). Forty-nine (71%) tumors were associated with endometriosis and 37 (53%) presented at stage I. Ten (15%) patients died of disease, 14 (20%) were alive with active disease and 45 (65%) had no evidence of disease at last follow-up (median follow-up: 34.2 months, range 1.2 - 230.6). Advanced stage, positive lymph nodes and presence of small tumor nests were significantly associated with shorter overall survival (p=0.006, p<0.001, p=0.004, respectively; Figure 2A-C) and recurrence/progression despite treatment (p<0.0001, p=0.0011, p=0.0003, respectively; table 1). Also, within the cohort of low stage patients (stage I and II), presence of small tumor nests was associated with recurrence/disease progression (p=0.0014; table 1). None of the other studied features reached statistical significance for assessment of prognosis.
Conclusion(s): Besides the classic prognostic factors of stage and lymph node status, presence of small tumor nests seems to be associated with poorer outcome in patients with CCCO. Specifically, in patients with early stage disease, evaluation of small tumor nests may help to better determine prognosis. These findings should be further evaluated in larger studies