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; Shaomin Hu, MD, PhD, staff pathologist, Cleveland Clinic; S. Emily Bachert, MD, breast pathology fellow, Brigham and Women’s Hospital, Boston; and Amarpreet Bhalla, MD, assistant professor of pathology, Albert Einstein College of Medicine, Montefiore Medical Center.
Morphological spectrum of immune checkpoint inhibitor therapy-associated gastritis: importance of awareness
October 2020—Immune checkpoint inhibitors are frequently used to treat a variety of solid tumors. These drugs involve upregulation of cytotoxic T cells, which can lead to immune-related adverse events, including those involving the gastrointestinal tract. The authors conducted a study to characterize the histological features of immune checkpoint inhibitor therapy-associated gastritis. Gastric biopsies from patients on immune checkpoint inhibitor therapy who had clinical suspicion of drug-associated gastrointestinal injury were identified. The predominant histological pattern of injury, distribution of injury, degree of tissue eosinophilia, and prominence of apoptosis were recorded. Medical chart review was used to obtain presenting symptoms, treatment, and follow-up data. The 12 patients included in the study group were treated for various tumors with ipilimumab, nivolumab, pembrolizumab, or ipilimumab in combination with nivolumab. Symptoms at presentation included nausea, vomiting, and diarrhea. Chronic active gastritis with intra-epithelial lymphocytosis and prominent apoptosis was seen in eight of 12 patients and was the most useful combination for diagnosing drug-induced gastritis in these patients. Four patients showed focal enhancing gastritis with a lymphohistiocytic cuff around inflamed glands, reminiscent of Crohn’s disease. One of those four patients was homozygous for the ATG16L1 Crohn’s disease-associated gene variant but had no history of inflammatory bowel disease. Ten patients responded to medication withdrawal and steroid therapy, and two required treatment with infliximab. The authors concluded that awareness of the morphological spectrum of immune checkpoint inhibitor therapy-associated gastritis is important for diagnosing and managing these patients.
Johncilla M, Grover S, Zhang X, et al. Morphological spectrum of immune checkpoint inhibitor therapy-associated gastritis. Histopathology. 2020;76(4):531–539.
Correspondence: Dr. A. Srivastava at srivastava@bwh.harvard.edu
Mesonephric-like carcinoma of endometrium: a subset of endometrial carcinoma with aggressive behavior
Endometrial mesonephric-like carcinomas are uncommon, with fewer than 50 reported cases to date. While previous studies have characterized the histologic, immunohistochemical, and molecular features of the disease, information about outcome is limited. The authors conducted a single-institution study of 23 uterine mesonephric-like carcinomas (MLCa) that characterized the behavior of such neoplasms. They reviewed the histologic features, IHC results, molecular profile, and clinical information (stage, treatment, follow-up) for uterine MLCas treated at their institution from 2004 to 2019. The behavior of MLCa was compared with that of low-grade endometrioid carcinoma (ECa) and uterine serous carcinoma (USC) treated at the same institution during the same time frame. All MLCas had a mixture of previously described architectural and cytologic features, most notably ductal or tubular architecture (21 of 23), nuclei resembling those of papillary thyroid carcinoma (18 of 23), and at least focal intraluminal eosinophilic secretions (20 of 23). Immunoperoxidase studies facilitated diagnosis in 22 patients: CD10, 10 of 10; calretinin, five of 15; estrogen receptor (10 percent or fewer nuclei), six of 21; progesterone receptor, one of 15; GATA3, 15 of 16; and TTF-1, 11 of 16. Fourteen of 17 patients tested had a KRAS mutation—seven as the only alteration and seven with additional mutations in PIK (n = 5), PTEN (n = 2), and CTNNB1 (n = 1). One patient had mutations in PTEN, PIK, and CTNNB1 without KRAS, and two had no detectable somatic mutation. Overall, 48 percent of patients presented with International Federation of Gynecology and Obstetrics stage 3 or 4 disease with the uterine risk factors of more than 50 percent myometrial invasion (20 of 23), lymphovascular space invasion (16 of 23), and cervical stromal invasion (seven of 23). Twenty patients had adjuvant therapy—seven with radiation only and 13 with chemotherapy with or without radiation—and three patients had unknown therapy or declined it. Of 21 patients with known follow-up, 17 had recurrences or never achieved remission, with the lung being the most common recurrence site (n = 9), and seven died of disease. The median progression-free survival was 18.2 months for MLCa, compared with 183 months for ECa and 67.1 months for USC. The median overall survival for MLCa was 70.6 months, compared with 139.1 months for USC. (Median survival was not reached for ECa.) Uterine MLCa is uncommon, and most tumors are recognized by architectural heterogeneity, vesicular overlapping nuclei with grooves, and eosinophilic luminal secretions. The typical immunoprofile includes low to absent expression of hormone receptors but at least focal expression of GATA3 or TTF-1, or both. Most patients tested had a KRAS mutation, although genetic mutations typically associated with ECa are not uncommon. Compared with more commonly encountered types of ECa, MLCa is more aggressive and tends toward earlier and distant recurrence.
Euscher ED, Bassett R, Duose DY, et al. Mesonephric-like carcinoma of the endometrium: a subset of endometrial carcinoma with an aggressive behavior. Am J Surg Pathol. 2020;44(4):429–443.
Correspondence: Dr. Elizabeth D. Euscher at edeusche@mdanderson.org
Spectrum of hepatic manifestations of common variable immunodeficiency
Common variable immunodeficiency has a heterogenous clinical presentation and can be challenging to diagnose. Distinct histologic changes have been linked with common variable immunodeficiency (CVID) in several organ systems, which can help identify the correct diagnosis. The authors conducted a study that examined a cohort of hepatic CVID biopsies to better define the spectrum of histologic and biochemical alterations. They reviewed 26 liver biopsies from 24 patients with CVID that were obtained at four institutions between 2010 and 2019. Histologic slides were examined, and pathologic, biochemical, and clinical features were recorded. A control cohort of 21 patients with nodular regenerative hyperplasia (NRH) but lacking CVID was also examined. Liver function tests were frequently abnormal, especially alkaline phosphatase (median, 193 IU/L) and aspartate transaminase (median, 56 U/L), which were elevated in 23 and 17 of 25 biopsies, respectively. Fifteen patients had CVID involvement of other organs. Two female patients showed unequivocal histologic features of primary biliary cholangitis, including florid duct lesions, prominent bile duct injury, and positive antimitochondrial antibodies. Among the 24 other biopsies, mild to moderate portal and lobular inflammation were present in 18 and 17 of 24 biopsies, respectively. Overall, 22 of 24 biopsies showed nodular regenerative hyperplasia-like changes. Plasma cells were absent. A distinct pattern of pericellular fibrosis was present in 23 of 26 biopsies overall. Involvement ranged from focal centrizonal fibrosis to bridging fibrosis and was accompanied by increased intrasinusoidal lymphocytes in 13 of 24 biopsies. Pericellular fibrosis was identified in one of 21 biopsies in the control cohort. Additional findings included granulomatous inflammation or nonhepatocellular foreign body-type multinucleate giant cells, which were identified in four biopsies. Three of six biopsies examined also demonstrated focal hepatocellular copper deposition. The authors concluded that hepatic disease in CVID is often associated with elevated alkaline phosphatase and aspartate transaminase and is characterized histologically by mild nonspecific portal and lobular hepatitis, absence of plasma cells, nodular regenerative hyperplasia-like changes, and, less commonly, typical histologic features of primary biliary cholangitis.
Crotty R, Taylor MS, Farmer JR, et al. Spectrum of hepatic manifestations of common variable immunodeficiency. Am J Surg Pathol. 2020;44(5):617–625.
Correspondence: Dr. Vikram Deshpande at vikramdirdeshpande@gmail.com