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.
Analysis of lymphocytic and collagenous colitis in children and adolescents
July 2021—Microscopic colitis is characterized by chronic watery diarrhea, endoscopically normal findings, and abnormal histology. The disorder is most prevalent in adults. Pediatric cases are rare and may vary in presentation. The authors searched their pathology data system from 1984 to 2019 for patients younger than 18 years of age who had a lymphocytic colitis (LC) or collagenous colitis (CC) pattern of injury. They retrieved 27 cases (23 LC and four CC). LC was not only more prevalent but also affected slightly younger individuals (mean, 9.8 versus 12.25 years). Immune dysregulation was documented in 11 (41 percent) patients. Most patients presented with watery diarrhea (n = 26, 96 percent) and abdominal pain (n = 18, 67 percent), nausea/vomiting (n = 5, 19 percent), flatulence (n = 6, 22 percent), or weight loss (n = 1, four percent). A subset (n = 10, 37 percent) of patients demonstrated endoscopic abnormalities. Some patients with LC and CC displayed focal cryptitis or crypt abscess formation (n = 7, 26 percent) and focally increased crypt apoptosis (n = 9, 33 percent) in the absence of chronic injury. Clinical follow-up data were available for 23 (85 percent) patients who had variable clinical responses recorded. Only eight patients experienced complete resolution of symptoms. Twelve patients (11 LC and one CC) had follow-up biopsies, one of whom developed histologic features of inflammatory bowel disease and one of whom was found to have a CTLA-4 gene mutation. This study concluded that pediatric patients with microscopic colitis may have atypical clinical, histologic, and endoscopic findings and variable clinical responses. Underlying inflammatory or genetic conditions, or both, eventually may be unmasked. Genetic testing may be helpful in a small subset of patients.
Windon AL, Almazan E, Oliva-Hemker M, et al. Lymphocytic and collagenous colitis in children and adolescents: Comprehensive clinicopathologic analysis with long-term follow-up. Hum Pathol. 2020;106:13–22.
Correspondence: Dr. Annika L. Windon at annika.windon@vumc.org
A postmortem portrait of COVID-19
The authors conducted a study that represents the largest compilation of clinical and postmortem data from decedents with COVID-19. The objective of the study was to assess the pre-existing diseases and pathologic conditions of decedents with SARS-CoV-2 infection through autopsy. The authors presented comprehensive data from 135 autopsy evaluations of COVID-19–positive decedents, including histologic evaluation of all organ systems in most cases. Thirty-six attending pathologists or residents at 19 medical centers or forensic institutions in the United States and Brazil performed the postmortem examinations. Data from each autopsy were collected through the online submission of multiple-choice and open-ended survey responses. Patients dying of COVID-19 or with the disease had an average of 8.89 pathologic conditions documented at autopsy, spanning prior chronic disease and acute conditions acquired during hospitalization. Virtually all decedents had more than one pre-existing disease, averaging 2.88 diseases when they acquired COVID. Systemic hypertension was reported in 86 (64 percent) decedents, diabetes mellitus in 70 (52 percent), obesity in 46 (34 percent), and coronary artery disease in 34 (25 percent). Only 10 (seven percent) decedents had no pre-existing conditions reported. Clinical conditions during hospitalization were cited 395 times for the 135 autopsied decedents and predominantly encompassed acute failure of multiple organ systems or impaired coagulation, or both. Myocarditis was rarely cited. The authors concluded that cause-of-death statements in autopsy reports and death certificates may not reflect the severity or spectrum of comorbid conditions in those dying of COVID-19 or with the disease. If supported by additional research, this finding may have implications for public health decisions and reporting during the pandemic.
Hooper JE, Padera Jr RF, Dolhnikoff M, et al. A postmortem portrait of the coronavirus disease 2019 (COVID-19) pandemic: a large multi-institutional autopsy survey study. Arch Pathol Lab Med. 2021;145(5):529–535.
Correspondence: Dr. Alex K. Williamson at awilliamson@northwell.edu
A study of hepatoid teratoma, hepatoid yolk sac tumor, and hepatocellular carcinoma
Rare hepatoid teratomas in testicular germ cell tumor patients mimic hepatoid yolk sac tumors and hepatocellular carcinoma. The authors compared the features of two metastatic hepatoid teratomas, 12 hepatoid yolk sac tumors, and 16 hepatocellular carcinomas. The mean ages of patients were 36, 40, and 62.5 years, respectively. The hepatoid teratomas formed sheets of hepatocyte-like cells with macrovesicular fat arranged in vague lobules with intervening fibrous bands containing biliary ductule-like structures and abortive portal triads. They lacked basement membrane deposits. On immunohistochemical study, both of the tumors were diffusely positive for glypican-3, arginase, and HepPar-1 (two of two), whereas stains for CK19 (two of two) and CK7 (one of two) were restricted to ductule-like structures. Villin was positive in hepatocytes and ductules in one of the tumors. Both hepatoid teratomas were negative for SALL4 and CDX2. Hepatoid yolk sac tumors formed nests, trabeculae, cords, and occasional gland-like structures, and most (10 of 12; 83 percent) produced intercellular basement membrane. No Mallory-Denk bodies were seen. Stains for SALL4 (100 percent), glypican-3 (100 percent), CK19 (88 percent), CDX2 (88 percent), and villin (75 percent) were positive, whereas stains for HepPar-1 highlighted rare tumor cells (70 percent), and stains for arginase were mostly negative (26 percent). All hepatocellular carcinomas lacked basement membrane deposits, with Mallory-Denk bodies occurring in 50 percent. Stains for HepPar-1 (100 percent) and arginase (94 percent) were positive, for glypican-3 were infrequent (19 percent), and for SALL4, CK19, villin, and CDX2 were negative. In summary, hepatoid teratomas were distinguished from hepatoid yolk sac tumors by the formation of ductules and abortive portal tracts, lack of basement membrane deposits, more consistent staining for arginase and HepPar-1, and negativity for SALL4 and CDX2. And hepatocellular carcinomas, unlike hepatoid yolk sac tumors, were negative for SALL4, CK19, villin, and CDX2, and they had Mallory-Denk bodies and lacked basement membrane deposits.
Al-Obaidy KI, Williamson SR, Shelman N, et al. Hepatoid teratoma, hepatoid yolk sac tumor, and hepatocellular carcinoma: a morphologic and immunohistochemical study of 30 cases. Am J Surg Pathol. 2021;45:127–136.
Correspondence: Dr. Thomas M. Ulbright at tulbrigh@iu.edu
Classification of gastric neuroendocrine tumors from long-term PPI users
Proton pump inhibitors are among the most widely used medications in the United States. Most proton pump inhibitor (PPI) users have persistent hypergastrinemia during treatment. However, gastric neuroendocrine tumors diagnosed in long-term PPI users have rarely been reported in the literature. The tumors demonstrate diverse clinical and histopathological features, and it is not clear whether they can be classified as type III sporadic tumors. The authors conducted a study in which they retrospectively characterized 66 gastric neuroendocrine tumors from patients who were treated at two tertiary care medical centers and did not have atrophic gastritis and gastrinoma. The evaluation involved 38 tumors from patients who had used PPIs for at least one year and 28 tumors from patients without long-term PPI use (a control group, with type III tumors). Compared with controls, long-term PPI users tended to have tumors that were pT1 and pT2 (98 versus 79 percent; P = .09) and that were less likely to invade the serosa (three versus 18 percent; P = .08) or lymphovascular spaces (11 versus 32 percent; P = .06). Based on Kaplan–Meier analysis, long-term PPI users had significantly longer overall survival rates than controls (P = .035). During follow-up, three control patients developed distant metastases (P = .06) and seven died (P = .002), while no deaths or distant metastases were reported for long-term PPI users. However, five long-term PPI users and none of the controls developed additional gastric neuroendocrine tumors. These results show that the gastric neuroendocrine tumors of long-term PPI users are probably less aggressive than type III sporadic tumors and have an indolent disease course. The findings support classifying the gastric neuroendocrine tumors in long-term PPI users as a separate subtype.
Trinh VQH, Shi C, Ma C. Gastric neuroendocrine tumours from long-term proton pump inhibitor users are indolent tumours with good prognosis. Histopathology. 2020;77(6):865–876.
Correspondence: Dr. Changqing Ma at mac2@upmc.edu