CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editors: Rouzan Karabakhtsian, MD, PhD, professor of pathology and director of the Women’s Health Pathology Fellowship, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY; Nicole Panarelli, MD, associate professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center; Shaomin Hu, MD, PhD, gastrointestinal/liver pathology fellow, University of Chicago; and S. Emily Bachert, MD, pathology resident, Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington.
An analysis of smooth muscle tumors of the gastrointestinal tract
July 2020—Smooth muscle tumors represent the second most common mural mesenchymal neaoplasm in the gastrointestinal tract, yet established criteria for prognostically assessing these tumors are lacking. The authors conducted a study on a large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions to identify potential prognostic features. At each location, expert gastrointestinal or soft tissue pathologists, or both, assessed pathologic features. IHC confirmation was required. The analysis included cases from the esophagus (n = 97, 24 percent), stomach (n = 180, 44 percent), small bowel (n = 74, 18 percent), and colorectum (n = 56, 14 percent). Patients ranged in age from 19 to 92 years (mean, 55 years), and 57 percent were female. Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 (14 percent) patients. Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in the study progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and three mitoses/5 mm2 for discriminating between progressive and nonprogressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < .0001 for all features). Age, gender, and margin status were not significantly associated with progression (P = .23, .82, and .07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. The authors concluded that, based on these findings, nonesophageal gastrointestinal smooth muscle tumors measuring more than 10 cm or showing a minimum of three mitoses/5 mm2 may behave aggressively. Therefore, close clinical follow-up is recommended for these patients.
Alpert L, Al-Sabti R, Graham RP, et al. Smooth muscle tumors of the gastrointestinal tract: an analysis of prognostic features in 407 cases. Mod Pathol. 2020. doi:10.1038/s41379-020-0492-5.
Correspondence: Dr. L. Alpert at lindsay.alpert@uchospitals.edu
P16 expression in primary vulvar extramammary Paget disease
P16 IHC has been widely used in facilitating the diagnosis of human papillomavirus-related usual type vulvar intraepithelial neoplasm. However, studies of p16 expression in primary vulvar extramammary Paget disease (EMPD) are limited. The authors assessed p16 expression by IHC in 40 cases of primary vulvar EMPD, including 34 cases of intraepithelial vulvar EMPD and six cases of invasive vulvar EMPD, and they correlated p16 expression patterns with disease progression. Overall, p16 expression was present in 36 (90 percent) cases, including 20 (50 percent) cases with a focal staining pattern and 16 (40 percent) cases with a diffuse staining pattern. The 20 cases with a focal p16 staining pattern represented intraepithelial vulvar EMPD. A diffuse p16 staining pattern was present in 10 of 30 (33.3 percent) cases of intraepithelial EMPD and in six of six (100 percent) cases of invasive vulvar EMPD. Negative p16 staining was present in four intraepithelial EMPD cases. Using a highly sensitive RNA in situ hybridization method, the authors did not detect high-risk HPV in the selected 10 cases with a diffuse p16 staining pattern—six cases of intraepithelial EMPD and four cases of invasive EMPD. The authors also observed that intraepithelial EMPD had predominantly cytoplasmic p16 immunoreactivity, and nuclear p16 immunoreactivity was primarily found in invasive EMPD components. The authors concluded that their study demonstrated that p16-positive immunostaining is seen in the majority of primary vulvar EMPD that is not related to human papillomavirus infection. Therefore, it is important to be able to recognize the overlapping p16 immunostaining patterns in vulvar EMPD and usual type vulvar intraepithelial neoplasm to render the correct diagnosis.
Zhang G, Zhao Y, Abdul-Karim FW, et al. P16 expression in primary vulvar extramammary Paget disease. Int J Gynecol Pathol. 2020;39(2):105–110.
Correspondence: Dr. Bin Yang at yangb@ccf.org
INSM1 as a marker for lung neuroendocrine tumors in cytologic and surgical specimens
Insulinoma-associated protein 1 (INSM1) is an IHC marker for neuroendocrine differentiation with potentially superior sensitivity and specificity. However, the performance of INSM1 in pulmonary cytology cell block material (CB) has not been well established. The authors conducted a study in which they used INSM1, CD56, synaptophysin, and chromogranin A to immunostain typical and atypical carcinoid, small cell lung carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma CBs, and 563 surgical specimens. The latter comprised 17 typical carcinoid, 14 atypical carcinoid, eight small cell lung carcinoma, 10 large cell neuroendocrine carcinoma, 58 squamous cell carcinoma, 415 adenocarcinoma, and 17 large cell carcinoma cases, and 24 other tumor types. The sensitivity, specificity, and positive and negative predictive values for INSM1 were 92.3 percent, 100 percent, 78.9 percent, and 99 percent in the CBs and 89.8 percent, 98.1 percent, 81.5 percent, and 99 percent in the surgical specimens, respectively, with 86.2 percent concordance. The sensitivity, specificity, and positive and negative predictive values for the other neuroendocrine markers were 97.4 percent, 93.3 percent, 97.4 percent, and 93.3 percent in the CBs for CD56 and 93.9 percent, 93.6 percent, 58.2 percent, and 99.4 percent in the surgical specimens for CD56, respectively; 89.7 percent, 100 percent, 100 percent, and 75 percent in the CBs for synaptophysin and 93.4 percent, 91.2 percent, 50.5 percent, and 99.4 percent in the surgical specimens for synaptophysin, respectively; and 66.7 percent, 100 percent, 100 percent, and 53.6 percent in the CBs for chromogranin A and 75.5 percent, 98.6 percent, 84.1 percent, and 97.7 percent in the surgical specimens for chromogranin A, respectively. INSM1 combined with CD56 maximized the sensitivity to 100 percent, with 93.3 percent specificity in the CBs. The study results further establish the high sensitivity and specificity of INSM1 in the largest pulmonary cytologic and surgical cohorts to date. INSM1 matched or surpassed the performance of neuroendocrine markers, and combining it with CD56 appeared to maximize test performance.