Cytologic Grading Is an Independent Prognostic Factor in Epithelioid Diffuse Malignant Pleural Mesothelioma.
Kyuichi Kadota, Kei Suzuki, Camelia Sima, Valerie W Rusch, Prasad S Adusumilli, William D Travis. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Other than the poor prognostic categories of sarcomatoid and biphasic histologic subtypes, there is no established grading system for epithelioid diffuse malignant pleural mesothelioma (DMPM). For epithelioid DMPM, tumor and nodal stage are the only validated prognostic markers. We sought to investigate whether cytologic grading can further stratify survival among epithelioid DMPM patients.
Design: H&E slides of 232 epithelioid DMPM patients (14 stage I, 54 stage II, 123 stage III, 34 stage IV) from a single institution (1989 to 2009) were reviewed. We classified the tumors into 4 histologic patterns: trabecular, tubulopapillary, micropapillary, and solid. We evaluated cytologic features including nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, presence of intranuclear inclusion, prominence of nucleoli, mitotic count, and presence of atypical mitosis. Lymphatic and vascular invasion was also evaluated. Log-rank tests and Cox proportional hazard models were used to analyze the association between histological variables and overall survival.
Results: Overall median survival of epithelioid DMPM was 1.36 years. Patients with < 10% tubulopapillary (P<0.001) and ≥ 10% solid pattern (P=0.006) correlated with poor prognosis. On univariate analysis, nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitosis (P<0.001) were associated with poor survival. Tumors were graded into I-III using nuclear atypia and mitotic count.
|Cytologic grade||N||Median survival (years)|
|Grade I (score 2-3)||107||2.34|
|Grade II (score 4-5)||91||1.14|
|Grade III (score 6)||34||0.41|