CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; and Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.
Intraoperative pathologic examination in the era of molecular testing for differentiated thyroid cancer
Diagnostic thyroidectomy is typically indicated for indeterminate thyroid cytology results. Traditionally, intraoperative pathologic examination (IOPE) helped guide the extent of initial surgery. Preoperative molecular testing of fine-needle aspiration cytology has emerged as another diagnostic adjunct, is highly specific for thyroid cancer, and can lead to appropriate initial total thyroidectomy. The authors hypothesized that preoperative molecular testing obviates the need for routine IOPE during lobectomy. In a retrospective, consecutive cohort study, they compared the outcomes of 670 patients undergoing thyroidectomy. Cohort A (January 2005 to December 2006) received surgery without molecular testing, and cohort B (January 2008 to September 2010) underwent preoperative molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARg mutations, as well as cytology assessment by the 2007 modified Bethesda criteria. In both cohorts, IOPE was performed during lobectomy, and a positive result prompted total thyroidectomy. The authors found that in cohort B, total thyroidectomy was more often the initial surgery (B 62 percent versus A 45 percent; P=.001), and a positive molecular test result was the only factor prompting initial total thyroidectomy in 18 (nine percent) patients. Among 315 patients who had initial lobectomy, thyroid cancer was infrequently diagnosed by IOPE in both cohorts (A 3.6 percent versus B 1.7 percent; P=.5). The sensitivity of IOPE in detecting differentiated thyroid cancer of 1 cm or greater decreased by more than 60 percent with routine use of molecular testing and the Bethesda criteria (A 18.4 percent versus B 5.9 percent). After lobectomy, differentiated thyroid cancer of 1 cm or greater was equally likely to be diagnosed in both cohorts (P=.1), but follicular variant papillary thyroid cancer was more common in cohort B (B 74 percent versus A 45 percent; P=.02). The authors concluded that together with the Bethesda cytologic criteria, preoperative molecular testing allows for an increased rate of initial definitive total thyroidectomy and eliminates the need for routine intraoperative pathologic examination during diagnostic lobectomy.
McCoy KL, Carty SE, Armstrong MJ, et al. Intraoperative pathologic examination in the era of molecular testing for differentiated thyroid cancer. J Am Coll Surg. 2012;215:546–554.
Correspondence: Dr. Kelly L. McCoy at mccoykl@upmc.edu
Clinical outcome of atypical endometrial hyperplasia diagnosed on endometrial biopsy
The authors conducted a study to review the rate of concurrent endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia (AEH) and to determine the features of concurrent endometrial carcinoma and their impact on the subsequent management of AEH. They reviewed a retrospective series of 219 AEHs diagnosed locally in routine practice over 24 years and followed by a repeat biopsy or hysterectomy. A series of 65 cases with a malignant diagnosis on preoperative sampling served as a control group. The authors obtained clinicopathologic parameters and collected and analyzed published data on the risk of malignancy and features of malignant tumors after a diagnosis of AEH. The study also reported on 2,571 patients diagnosed in 31 additional published studies. This showed a wide variation in the positive predictive value (PPV) of AEH for detecting endometrial cancer (six percent to 63 percent), with an overall PPV of 37 percent. This variation is not only based on the differences among studies, but also on the degree of atypia (mild/moderate [PPV, 13 percent] or severe [PPV, 50 percent]), type of subsequent intervention (biopsy versus hysterectomy), and, more importantly, time period of diagnosis (approximately 20 percent in studies published before the 1990s and up to 40 percent to 48 percent in recently published cases). Of the cases with a benign outcome, approximately 40 percent to 50 percent showed AEH, with a potential risk of progressing to invasive carcinoma in 25 percent of cases. Malignant tumors after AEH diagnosis are associated with features of good prognosis with endometrioid morphology, lower grade, and early stage. Although the overall PPV of AEH is 37 percent, a figure of 40 percent to 48 percent is expected in cases currently diagnosed in routine practice. The authors concluded that providing qualifying criteria for AEH will help identify its various associated risks and therefore should be included in routine pathology reports whenever possible. Unless there is a clinical contraindication, hysterectomy should be performed to treat concurrent carcinoma and to reduce the risk of subsequent carcinoma in nonmalignant cases with residual AEH.
Rakha E, Wong SC, Soomro I, et al. Clinical outcome of atypical endometrial hyperplasia diagnosed on an endometrial biopsy: institutional experience and review of literature. Am J Surg Pathol. 2012;36(11):1683–1690.
Correspondence: E. Rakha at emadrakha@yahoo.com
Evaluation of pleomorphic lobular carcinoma of the breast relative to histological grade
Pleomorphic lobular carcinoma is considered a biologically aggressive variant of invasive lobular carcinoma of the breast. However, there is no consensus on the definition and whether this subtype adds useful information to histological grade. The authors studied 202 grade two or three invasive lobular carcinomas. They categorized the tumors according to the components of histological grade: tubules, pleomorphism, and mitoses. Pleomorphic lobular carcinoma was defined as a carcinoma with a lobular growth pattern and marked nuclear pleomorphism (pleomorphism three). Breast cancer-specific survival was used to analyze prognosis. Grade three pleomorphic lobular carcinomas (tubules three, pleomorphism three, mitoses two, and tubules three, pleomorphism three, mitoses three) had a worse prognosis than grade two carcinomas (tubules three, pleomorphism two, mitoses one). Grade two lobular carcinomas with marked nuclear pleomorphism (tubules three, pleomorphism three, mitoses one) had a similar prognosis to grade two carcinomas with moderate pleomorphism (tubules three, pleomorphism two, mitoses one). Survival was associated with mitotic score but not with nuclear pleomorphism on univariate and multivariate analyses. A non-classical growth pattern was seen more frequently in all subgroups with marked nuclear pleomorphism and was associated with worse survival. Histological grade and nodal status were independent of prognostic factors. The authors concluded that histological grade, in particular the mitotic component, in invasive lobular carcinomas is of prognostic importance, but pleomorphic type does not provide additional useful prognostic information.
Rakha EA, van Deurzen CHM, Paish EC, et al. Pleomorphic lobular carcinoma of the breast: Is it a prognostically significant pathological subtype independent of histological grade? Mod Pathol. 2013;26:496–501.
Correspondence: Dr. A. H. Lee at andrew.lee@nuh.nhs.uk