Modified Masaoka stage and size are independent prognostic predictors in thymoma and modified Masaoka stage is superior to histopathologic classifications.

INTRODUCTION: The prognostic value of histopathologic classifications of thymoma is debated. Problematic reproducibility might cause this controversy. We studied the prognostic significance of three histopathologic classifications of thymomas after three thoracic pathologists agreed upon thymoma subtype and invasion. We also compared the outcome to established prognostic parameters. METHODS: Patients, surgically treated for thymic epithelial neoplasm at Mayo Clinic (1942-2008), were staged according to the modified Masaoka staging and the recently proposed staging by Moran. Three thoracic pathologists independently classified all cases according to the World Health Organization, Bernatz, and proposed Suster and Moran classification. Only thymoma that all three pathologists diagnosed as the same histopathologic subtype and extent of invasion were included in outcome analysis. RESULTS: In 214 (proposed Suster and Moran classification), 145 (World Health Organization classification), and 120 cases (Bernatz classification), reviewers agreed upon subtype of thymoma and invasion and follow-up was available. Median follow-up time was 7.5-7.7 years (range between classifications). All histopathologic classifications were associated with overall survival (OS) and disease-free survival (p ≤ 0.0001 to p = 0.048); only Bernatz classification was independent of modified Masaoka staging associated with OS (p = 0.04). Modified Masaoka stage predicted outcome independent of all histopathologic classifications and resection status and strongly correlated with the proposed Moran stage (correlation coefficient, 0.95). Thymoma size and age were prognostic parameters for OS independent of any histopathologic classification. CONCLUSIONS: Histopathologic classifications of thymomas are associated with prognosis but are in general not independent predictors of outcome. Modified Masaoka stage and proposed Moran staging are independent prognostic parameters for thymoma and superior to histopathologic classifications.

Reproducibility of 3 histologic classifications and 3 staging systems for thymic epithelial neoplasms and its effect on prognosis.

Data regarding the prognostic significance of the histopathologic classifications of thymic epithelial neoplasms are contradictory, perhaps reflecting issues in reproducibility. We studied the effect of reproducibility of 3 histopathologic classifications on prognosis and investigated the interobserver agreement on invasion and its effect on staging and prognosis. A total of 456 patients who underwent surgery for thymic epithelial neoplasm at Mayo Clinic Rochester (1942 to 2008) were staged (modified Masaoka, proposed Moran, proposed IASLC/ITMIG) and independently classified by 3 thoracic pathologists (World Health Organization, proposed Suster & Moran [S&M], and Bernatz). Interobserver agreement was moderate to substantial for all histopathologic classifications (κ values: 0.65, 0.52, 0.74 for World Health Organization, Bernatz, and S&M, respectively). All histopathologic classifications were significant for overall survival (OS) and disease-free survival (DFS) (all reviewers). If adjusted for Masaoka, only Bernatz classification for one reviewer and all histopathologic classifications for another reviewer were significant for OS. Interobserver agreement for invasion was substantial (κ=0.61) and almost perfect for Masaoka, Moran, and IASLC/ITMIG stage (κ values: 0.85, 0.81, and 0.92, respectively). The correlation coefficient for Masaoka and Moran staging was 0.93. Masaoka and IASLC/ITMIG staging were significant for OS and DFS (all reviewers). If adjusted for any histopathologic classification, Masaoka was significant for OS and DFS (all reviewers). In conclusion, reproducibility of histopathologic classifications has some effect on outcome. S&M is the most reproducible classification. Reproducibility of invasion has no effect on the prognostic value of staging. Masaoka, Moran, and IASLC/ITMIG staging are almost perfectly reproducible. The strong correlation between Masaoka and Moran staging suggests similar prognostic strength.

Characterization of precursor lesions in the endometrium and fallopian tube epithelium of early-stage uterine serous carcinoma.

To determine if selected cases of uterine serous carcinoma (USC) arise from tubal rather than endometrial epithelium. Bilateral fallopian tubes from 38 women with pure USC were entirely submitted for histopathologic examination using the protocol Sectioning and Extensively Examining the FIMbria (SEE-FIM). Non-neoplastic endometrium was extensively sampled. Immunohistochemistry for p53 was performed on all paraffin blocks of fallopian tube and non-neoplastic endometrium. Endometrial intraepithelial carcinoma (EIC) was present in 22 cases (58%). Endometrial p53 foci were identified in 3 patients. There were 11 cases (29%) with fallopian tube involvement; 9 of 11 had tubal wall invasion or lymphatic involvement without serous tubal intraepithelial carcinoma (STIC) and were, therefore, classified as metastatic from the endometrium. STIC was identified in 3 patients (8%). There were 3 cases with tubal p53 foci in non-neoplastic epithelium. EIC was present in 58% of patients, further supporting EIC as a precursor lesion to USC. STIC was present in 8%, suggesting that the fallopian tube may in fact represent the primary lesion in a minority of patients with USC. This finding may account for the early multifocal disease distribution observed in these patients.

Diagnostic significance of cell kinetic parameters in World Health Organization type A and B3 thymomas and thymic carcinomas.

The prognostic importance of histologic classifications of thymic epithelial neoplasms is controversial. Evidence suggests that difficulties in reproducibility affect prognostic studies. Two thoracic pathologists independently classified 80 cases of type A or B3 thymoma and thymic carcinoma according to World Health Organization (WHO) classification. Ki-67 labeling index (LI) was used to identify cutoff points between WHO types. Recursive partitioning (Rpart) and ad hoc methods separated the data points. The pathologists agreed on type A (n = 31), type B3 (n = 21), and thymic carcinoma (n = 14). Ki-67 LI differed between types A and B3 (P < .001) and between thymic carcinoma and type A (P < .001) or type B3 (P = .001). Mitotic activity differed between thymic carcinoma and type A (P < .001) or type B3 (P < .001). Rpart revealed Ki-67 LI greater than 14.0% only in thymic carcinoma; cases with Ki-67 LI less than 5.1% did not represent thymic carcinoma. Ad hoc analysis showed Ki-67 LI greater than or equal to 13.5% represents thymic carcinoma; only type A had Ki-67 LI less than 2%. The pathologists disagreed on histologic type in 14 cases. In 11 of 14 cases with available Ki-67, the Rpart method predicted the WHO type; in 7 of 14 cases, the ad hoc method predicted the WHO type. In conclusion, Ki-67 LI is helpful in differentiating thymic epithelial neoplasms, with Ki-67 LI less than 2% and greater than or equal to 13.5% distinguishing type A thymoma and thymic carcinoma, respectively.

Diagnostic concordance of histologic lung cancer type between bronchial biopsy and cytology specimens taken during the same bronchoscopic procedure.

CONTEXT: The diagnosis of lung cancer is often confirmed by cytology and biopsy specimens obtained during a bronchoscopic procedure. At our institution, these specimens are read by different pathologists, and the rate of concordance was not known. OBJECTIVES: To evaluate the concordance rate in the diagnosis of lung cancer types between cytology and biopsy specimens and to correlate discordance with patient outcome. DESIGN: Specimens obtained during the same procedure, between January 1, 2000, and December 31, 2005, were identified. Cases with cytology and biopsy specimens positive for cancer were evaluated for concordance of histologic type, small cell versus non­small cell lung carcinoma. Cases with different types were considered discordant, and slides were reviewed. RESULTS: Of 231 cases, 225 (97.4%) had concordant diagnoses. Discordance was the result of misinterpretation of undifferentiated carcinoma, overinterpretation of squamous dysplasia, interpretation of suboptimal specimens with necrosis and crush artifact, and sampling error. CONCLUSIONS: Even though the cytology and biopsy specimens were reviewed by different pathologists, the concordance rate for histologic type at our institution was high, emphasizing that this is a safe practice. The few discordant cases did not affect the patient's outcome.