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A Rare Case of Chronic Diarrhea
CLINICAL CHALLENGES AND IMAGES IN GI A Rare Case of Chronic Diarrhea Mohamed Kaif,1 Paul Fitzmorris,2 and Frederick Weber1 1
Division of Gastroenterology and Hepatology and 2Division of Internal Medicine, University of Alabama at Birmingham, Birmingham, Alabama
Question: A 58-yearold African-American man with wellcontrolled hypertension and diabetes presented with 18 months of 6–8 watery loose brown stools per day, nocturnal stools, and 40-pound weight loss. He denied steatorrhea and stool frequency was unaffected by fasting. He denied any abdominal pain, nausea, vomiting, melena, hematochezia, fevers, or chills. He did not have any history of abdominal surgery. Medications included irbesartan and sitagliptin, both of which had been started well after the onset of diarrhea. On examination, he was a thin man with poor skin turgor, an unremarkable abdominal examination, and no rashes or lymphadenopathy. Significant laboratory results included a hemoglobin of 11.6, a mean corpuscular volume of 72, potassium of 2.5, and magnesium of 1.2. Ferritin was 12 and transferrin saturation was 8%. Routine infectious stool studies, tissue transglutaminase, and human immunodeficiency virus-1/2 antibodies were negative. Colonoscopy showed edematous but otherwise normal-appearing mucosa throughout; biopsies showed a heavy, chronic inflammatory infiltrate in the epithelium without crypt architectural distortion, potentially consistent with microscopic lymphocytic colitis. His diarrhea improved initially with budesonide but returned within a few weeks and progressed to 20 bowel movements daily. He also continued to lose weight and stool fat was 56 g/d. Esophagogastroduodenoscopy revealed edematous, scalloped duodenal mucosa (Figure A); representative duodenal histopathology is depicted in Figure B. What is your diagnosis? Look on page 511 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.11.007
Gastroenterology 2015;148:510–512
CLINICAL CHALLENGES AND IMAGES IN GI Answer to the Clinical Challenges and Images in GI Question: Image 2 (page 510): Enteropathy-Associated T-Cell Lymphoma, Type II
Biopsies of the duodenum showed a dense lymphocytic infiltrate of atypical, monomorphous cells with marked epitheliotropism as well as villous blunting (Figure B). Immunohistochemical stains are depicted, showing positivity for CD3 (Figure C), co-expression of CD 56 (Figure D), co-expression of CD8 (Figure E), and CD4 stain highlighting only background lymphocytes (Figure F). Flow cytometry of the duodenum revealed an aberrant population of T cells accounting for 77% of all cells, and T-cell receptor gene rearrangement was positive for clonal expansion of T cells. Similar findings were found on biopsies from repeat colonoscopy. CT of the abdomen and pelvis, endoscopic ultrasound, and flow cytometry of the blood and bone marrow were negative. Clinicopathologic findings were consistent with enteropathy-associated T-cell lymphoma, type II (EATL II). EATL is a rare peripheral T-cell lymphoma that arises from mature T cells of the gastrointestinal tract. EATL has an estimated annual incidence of 0.5-1 per million people in Western countries. Males in the sixth and seventh decades of life are affected most commonly. The most common presenting symptoms and signs are pain, nausea, vomiting, and weight loss. Type I EATL, which occurs in >80% of cases, is characterized by nonmonomorphic cells and has a well-established relationship with celiac disease, with patients often expressing HLA DQ2/DQ8. Type II EATL is characterized by monomorphic cells and is not associated with celiac disease. The tumor cells in type I EATL are CD3þ, CD5, CD7þ, CD8/þ, CD4, CD103þ, TCRþ/, and contain cytotoxic molecules; in contrast, type II EATL has a distinct immunophenotype of CD3þ, CD4–, CD8þ, CD56þ, and TCRþ, as was seen in our patient. EATL may occur in any part of the gastrointestinal tract, but affects predominantly the small bowel. Grossly, tumors can be multifocal and can form ulcers, nodules, plaques, strictures, or masses, and frequently present with bowel perforation. Prognosis is poor owing to low chemosensitivity, rapid tumor growth, and a tendency to dissemination; 5-year survival is approximately 25%, and overall median survival is 7–10 months. Standard treatment is not established, but combination primary debulking and systemic anthracycline-containing chemotherapy with or without radiation is generally recommended. Our patient received CHOP chemotherapy and had a dramatic improvement in his diarrhea. This case highlights that EATL should be a part of the differential diagnosis in a patient presenting with diarrhea, weight loss, and intraepithelial lymphocytosis, even without gross lesions, particularly if there is no improvement with treatment for other considered causes.
511
CLINICAL CHALLENGES AND IMAGES IN GI References 1. 2. 3.
Yang Y, Batth S, Chen M, et al. Enteropathy-associated t cell lymphoma presenting with acute abdominal syndrome: a case report and review of literature. J Gastrointest Surg 2012;16:1446–1449. Ferreri A, Zinzani L, Govi S, et al. Enteropathy-associated T-cell lymphoma. Crit Rev Oncol Hematol 2011;79:84–90. Sieniawski M, Lennard A. Enteropathy-associated T-cell lymphoma: epidemiology, clinical features, and current treatment strategies. Curr Hematol Malig Rep 2011;6:231–240.
For submission instructions, please see the Gastroenterology web site (www.gastrojournal.org).
512
Division of Gastroenterology and Hepatology and 2Division of Internal Medicine, University of Alabama at Birmingham, Birmingham, Alabama
Question: A 58-yearold African-American man with wellcontrolled hypertension and diabetes presented with 18 months of 6–8 watery loose brown stools per day, nocturnal stools, and 40-pound weight loss. He denied steatorrhea and stool frequency was unaffected by fasting. He denied any abdominal pain, nausea, vomiting, melena, hematochezia, fevers, or chills. He did not have any history of abdominal surgery. Medications included irbesartan and sitagliptin, both of which had been started well after the onset of diarrhea. On examination, he was a thin man with poor skin turgor, an unremarkable abdominal examination, and no rashes or lymphadenopathy. Significant laboratory results included a hemoglobin of 11.6, a mean corpuscular volume of 72, potassium of 2.5, and magnesium of 1.2. Ferritin was 12 and transferrin saturation was 8%. Routine infectious stool studies, tissue transglutaminase, and human immunodeficiency virus-1/2 antibodies were negative. Colonoscopy showed edematous but otherwise normal-appearing mucosa throughout; biopsies showed a heavy, chronic inflammatory infiltrate in the epithelium without crypt architectural distortion, potentially consistent with microscopic lymphocytic colitis. His diarrhea improved initially with budesonide but returned within a few weeks and progressed to 20 bowel movements daily. He also continued to lose weight and stool fat was 56 g/d. Esophagogastroduodenoscopy revealed edematous, scalloped duodenal mucosa (Figure A); representative duodenal histopathology is depicted in Figure B. What is your diagnosis? Look on page 511 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.
Conflicts of interest The authors disclose no conflicts. © 2015 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2014.11.007
Gastroenterology 2015;148:510–512
CLINICAL CHALLENGES AND IMAGES IN GI Answer to the Clinical Challenges and Images in GI Question: Image 2 (page 510): Enteropathy-Associated T-Cell Lymphoma, Type II
Biopsies of the duodenum showed a dense lymphocytic infiltrate of atypical, monomorphous cells with marked epitheliotropism as well as villous blunting (Figure B). Immunohistochemical stains are depicted, showing positivity for CD3 (Figure C), co-expression of CD 56 (Figure D), co-expression of CD8 (Figure E), and CD4 stain highlighting only background lymphocytes (Figure F). Flow cytometry of the duodenum revealed an aberrant population of T cells accounting for 77% of all cells, and T-cell receptor gene rearrangement was positive for clonal expansion of T cells. Similar findings were found on biopsies from repeat colonoscopy. CT of the abdomen and pelvis, endoscopic ultrasound, and flow cytometry of the blood and bone marrow were negative. Clinicopathologic findings were consistent with enteropathy-associated T-cell lymphoma, type II (EATL II). EATL is a rare peripheral T-cell lymphoma that arises from mature T cells of the gastrointestinal tract. EATL has an estimated annual incidence of 0.5-1 per million people in Western countries. Males in the sixth and seventh decades of life are affected most commonly. The most common presenting symptoms and signs are pain, nausea, vomiting, and weight loss. Type I EATL, which occurs in >80% of cases, is characterized by nonmonomorphic cells and has a well-established relationship with celiac disease, with patients often expressing HLA DQ2/DQ8. Type II EATL is characterized by monomorphic cells and is not associated with celiac disease. The tumor cells in type I EATL are CD3þ, CD5, CD7þ, CD8/þ, CD4, CD103þ, TCRþ/, and contain cytotoxic molecules; in contrast, type II EATL has a distinct immunophenotype of CD3þ, CD4–, CD8þ, CD56þ, and TCRþ, as was seen in our patient. EATL may occur in any part of the gastrointestinal tract, but affects predominantly the small bowel. Grossly, tumors can be multifocal and can form ulcers, nodules, plaques, strictures, or masses, and frequently present with bowel perforation. Prognosis is poor owing to low chemosensitivity, rapid tumor growth, and a tendency to dissemination; 5-year survival is approximately 25%, and overall median survival is 7–10 months. Standard treatment is not established, but combination primary debulking and systemic anthracycline-containing chemotherapy with or without radiation is generally recommended. Our patient received CHOP chemotherapy and had a dramatic improvement in his diarrhea. This case highlights that EATL should be a part of the differential diagnosis in a patient presenting with diarrhea, weight loss, and intraepithelial lymphocytosis, even without gross lesions, particularly if there is no improvement with treatment for other considered causes.
511
CLINICAL CHALLENGES AND IMAGES IN GI References 1. 2. 3.
Yang Y, Batth S, Chen M, et al. Enteropathy-associated t cell lymphoma presenting with acute abdominal syndrome: a case report and review of literature. J Gastrointest Surg 2012;16:1446–1449. Ferreri A, Zinzani L, Govi S, et al. Enteropathy-associated T-cell lymphoma. Crit Rev Oncol Hematol 2011;79:84–90. Sieniawski M, Lennard A. Enteropathy-associated T-cell lymphoma: epidemiology, clinical features, and current treatment strategies. Curr Hematol Malig Rep 2011;6:231–240.
For submission instructions, please see the Gastroenterology web site (www.gastrojournal.org).
512