Faculty Bibliography

Background: In addition to respiratory distress, GI symptoms have been reported in COVID-19 patients at various stages of the disease. Among the GI symptoms that have been reported, diarrhea, nausea, vomiting, abdominal pain and GI bleeding were often seen. Age and comorbid conditions such as obesity, HTN, DM and/or CAD have been considered as risk factors for COVID-19 patients for severe disease. GI manifestations in COVID-19 patients appeared to act as a sign for a serious condition. The virus has been identified in the stool and in rectal swabs of some infected patients, even after a negative nasopharyngeal test. There is a lack of reports on pathological alterations of the GI tract in COVID-19 infected patients.
Design(s): 16 PCR confirmed COVID-19 patients (11 males and 5 females) were included in the study. Biopsy or resection specimens were taken from the esophagus (4), stomach (6), small intestine (5), appendix (3), colon (5) and gallbladder (3). Clinical information including demographics, comorbidities, GI symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): The age of the patients ranged from 10 to 84 years old, with an average of 47 years. Eight (50%) patients had at least one comorbid condition, two patients (12.5%) had prior history of cancer, and six patients had no significant medical history. Abdominal pain and GI bleeding were the most common presenting symptoms. Histologically, acute and chronic inflammation was seen in 14 of 16, and 15 of 16 cases, respectively. Eight cases showed severe acute inflammation with ulceration. The mucosal changes included nonspecific reactive change, hypermucinous, atrophic/ischemic changes, and necrosis, were indiscriminately noticed in these cases. Four cases showed intraepithelial lymphocytosis. Viral like inclusions were found in four cases. Microthrombi were identified in 5 cases with an average patient age of 60 years. Notably, microthrombi were seen in about 5 out of 8 (62%) patients with comorbidities. The patients with microthrombi had a higher D dimer test value than those without thrombus. Three patients died shortly after operation, and two of them showed microthrombi in the tissue specimens.
Conclusion(s): Acute and chronic inflammation were indiscriminately seen in these cases. Microthrombi were dominantly found in aging patients with comorbidities, suggesting microthrombi in the GI tract may be a histologic indication for severe COVID-19 patients with GI symptoms

Background: Digestive symptoms are often seen in COVID-19 patients with poor outcomes. The Viral RNA is mostly positive in the stool of these patients, and has a longer delay before viral clearance. However, its diagnostic value and significance for guiding clinical treatment remain unknown. And the pathologic alterations in the GI tract in COVID-19 patients have not been well defined. We evaluated rectal swab SAS-CoV-2 test and histopathologic changes in the small intestine in autopsy patients.
Design(s): 18 autopsy cases with confirmed SAS-CoV2 infection were included. Nasal, bronchial, and rectal swab SARS-CoV-2 PCR were performed at the time of autopsy. Clinical information included demographics, comorbidities, presenting symptoms, related laboratory tests were collected. Histopathologic evaluation was performed and correlated with clinical properties.
Result(s): 83% (15/18) of patients were male. Median age is 50 years. 7/18 (38.9%) patients had diarrhea in addition to cough, fever and other symptoms. Except in one case, all patients had underlying comorbidities of diabetes, hypertension and /or obesity. In the small intestine, acute inflammation was not seen in any cases. 5/18 displayed mild and one showed moderate chronic inflammation. Hypermucinous change was found in six patients but not associated with diarrhea. 3 cases had microthrombi identified in the sections. Notably, obviously increased D dimer in lab tests were noticed in all patients. Postmortem 17/17 (100%) nasal, 18/18 (100%) bronchial and 7/16 (43.8%) rectal swabs showed SARS-CoV-2 PCR positivity. 3 of 7 (42.9%) patients with diarrhea are positive in rectal swab for SARS-CoV-2.
Conclusion(s): There are no specific COVID-19 changes in the small intestine. More investigations are needed, especially on tissues from different locations of the GI tract. Data from rectal swab testing suggests that it is not ideal for diagnosing COVID-19, guiding treatment, or predicting small intestinal pathology

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.

Background: Neuroendocrine tumors (NETs) have been well studied and most organs have criteria which allow for neuroendocrine hyperplasia (NH) or a preneoplastic state before a neuroendocrine proliferation is defined a neuroendocrine tumor. In the lung, neuroendocrine proliferations <5mm are designated tumorlets. In the stomach, neuroendocrine proliferations range from NH to neuroendocrine dysplasia, and the designation of NET does not occur unless the proliferation is >5mm. In the pancreas, neuroendocrine proliferations with a diameter of <5 mm are termed neuroendocrine microadenomas. However in the appendix, there is no provision for NH and there are no established minimal size criteria for appendiceal NETs in the current 5th edition WHO book, which considers all NETs to have malignant potential. Also the current CAP protocol applies to all appendiceal NETs regardless of size, forcing pathologists to diagnose NETs despite studies demonstrating small appendiceal NETs (<1cm) to be indolent.
Design(s): A single institution database of adult patients with appendectomies containing the word "neuroendocrine" and "carcinoid" was queried from January 2004 to December 2012. Patients with neuroendocrine carcinoma, goblet cell carcinoid, and patients without follow up were excluded.
Result(s): 32 patients were included in the study. The mean age at diagnosis was 40.3 years (18-79). Females represented 59.3 % (19/32) of all patients. All appendiceal NETs were incidentally identified in a background of acute appendicitis. Tumor size ranged from 1 mm to 17 mm and the depth of extension ranged from submucosa to mesoappendix. One patient underwent a right hemicolectomy because of tumor size > 1cm. In long term follow up (7-15 years), none of these patients had disease recurrence. (Table presented)
Conclusion(s): The majority of appendiceal NETs are small incidental findings associated with acute appendicitis. In this setting, neural proliferation and mucosal expansion can often be seen and it is reasonable for NH to also represent inflammatory/reactive changes rather than a neoplastic process given their indolent behavior and long term survival rate (100%). In the appendix, we propose NH is part of the inflammatory process and should not be classified as a NET unless it is >5mm. We advocate the terminology of appendiceal NH in neuroendocrine proliferations <5mm in keeping with size criteria in other organs. This change in terminology from NET to NH may reduce unnecessary medical surveillance, overtreatment, and patient anxiety

Background: Alpha-1 antitrypsin deficiency (AATD) arises from inherited autosomal co-dominant SERPINA1 mutations that lead to liver and lung disease. Clinical manifestations within the liver are variable and include chronic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. While the risk of liver disease with homozygous AATD is established, the prevalence of clinically significant liver disease in heterozygotes is not well described. Accumulating evidence suggests that heterozygous AATD (HAATD) acts as a co-factor for other liver diseases, but little is known about its effect on pathologic fibrosis. We investigate the stage of liver fibrosis in patients with histologic evidence of HAATD compared to controls with a wide range of chronic liver diseases.
Design(s): Our database was retrospectively searched to obtain 23 liver biopsy and resection specimens with evidence of chronic liver disease and intracytoplasmic alpha1 anti-trypsin (AAT) globules stained by immunohistochemistry. The group with histologic evidence of possible HAATD was compared to control cases of liver biopsies obtained from patients with chronic liver disease without evidence of AAT globules. Clinicopathologic data included age, gender, race, genotype, chronic liver disease type (chronic cholestatic disease, fatty liver disease, Hepatitis B or C, auto-immune hepatitis, hemochromatosis, and unknown cause), liver disease stage, and clinical follow-up. Statistical analyses were performed to assess correlation between clinicopathologic variables and disease groups.
Result(s): Compared to controls, subjects in the HAATD cohort had a higher rate of stage 4 fibrosis (52.17% vs 21.67%, p = 0.017). The control specimens were relatively evenly distributed among stages 1-4 fibrosis (Table). Of the 7 HAATD patients who underwent subsequent genetic testing, 6 patients were found to have heterozygous SERPINA1 mutations (5 PI*MZ, 1 PI*SZ). There were no significant differences in age, race, or gender between control and HAATD groups. (Table presented)
Conclusion(s): Histologic and immunohistochemical evidence of AAT globules was associated with a higher stage of concurrent liver disease. These results add to the growing body of literature which suggests that HAATD may potentiate the progression of concurrent liver diseases. In addition, histologic and immunohistochemical evidence of AAT globules may be useful in the early diagnosis of HAATD

BACKGROUND:Osseous metaplasia of the gastrointestinal tract is exceedingly rare. Associated with colorectal cancer, juvenile polyps , and inflammatory polyps, the exact etiology is still unknown. We present a case report on a young male with recurrent rectal polyps and rectal bleeding. Histopathology revealed an inflammatory polyp with focal osseous metaplasia. CASE PRESENTATION/METHODS:A 30-year-old male without significant past medical history but with a significant smoking history of 10 pack-years. He initially presented to the colorectal clinic approximately 8 months prior with complaints of rectal pain and bleeding. The patient subsequently underwent colonoscopy which demonstrated a friable 2-cm mass at the dentate line. He was taken to the operating room for a transanal mass excision which, at the time, pathologic examination demonstrated a hyperplastic polyp with no evidence of dysplasia or malignancy. The patient returned to the clinic 8 months later with similar complaints of rectal bleeding. He denied any constitutional symptoms, weight loss, abdominal pain, diarrhea, or constipation. Upon rectal examination, he was noted to have a soft palpable mass blood on digital rectal exam. The patient was taken for repeat colonoscopy and was found to have a recurrent mass at the dentate line. Given the recurrent mass, the patient was taken for a re-excision in the operating room. Histopathology returned showing a 1.8 × 1.5 × 1.5 cm inflammatory polyp with focal osseous metaplasia. CONCLUSION/CONCLUSIONS:Osseous metaplasia of the gastrointestinal tract is a rare occurrence that can be associated with benign polyps or malignancy. Certain markers have been shown to be linked to this process and polypectomy remains the gold standard of treatment; however, further research is warranted.