February 2021*

A 16-year-old girl with chronic diarrhea

Contributors: 

Shahbaz Ali Khan, MD

Fellow – Gastrointestinal and Hepatobiliary Pathology

Department of Pathology and Laboratory Medicine

Indiana University School of Medicine

Jingmei Lin, M.D., Ph.D.

Assistant Professor, Department of Pathology and Laboratory Medicine

Indiana University School of Medicine

*This case has been peer reviewed

Clinical history: 

A 16-year-old girl was in her usual state of health when she received first dose of HPV vaccine and developed an urticarial type eruption on her chest, back, and arms. The rash resolved after initial treatment with antihistamines and prednisone. At the same time, she also developed diarrhea, described as loose, brown, watery stools occurring five to six times a day. The volume of the stool was not more than usual. It was not associated with lack of appetite, nausea, vomiting, abdominal pain, melena or hematochezia. She had no sick contacts and no recent travel history. Her mother had history of irritable bowel syndrome. She was prescribed Imodium and directed to consume lactose-free and gluten-free diet. Over the course of 10 weeks, this approach proved to be of little benefit and she underwent extensive evaluation to determine the etiology of chronic diarrhea.

On lab work-up she was found to be anemic (hemoglobin: 10.5 g/dl), with elevated platelet count (821 k/mm3), elevated alkaline phosphatase (746 U/l), mildly elevated transaminases, and elevated serum IgG (2790 mg/dl), and elevated IgA (384 mg/dl). Serology was negative for anti-tissue transglutaminase antibody, anti-endomysial antibody and viral hepatitis. Stool ova and parasite exam and stool pathogen panel including Clostridium difficile testing was negative. Stool elastase and chymotrypsin were within normal limits.

Additional diagnostic work-up included esophagogastroduodenoscopy, colonoscopy and CT scan of abdomen and chest. CT abdomen was unremarkable and CT chest showed a solid, well circumscribed, anterior mediastinal mass (7.5 cm) which was biopsied and diagnosed as Thymoma.

Microscopic examination 

Upper and lower gastrointestinal tract biopsies showed chronic active gastritis (negative for H. pylori), duodenal mucosa with intact villous architecture, no intra-epithelial lymphocytosis and loss of goblet and Paneth cells. Terminal ileum showed villous blunting, loss of goblet and Paneth cells, and focal acute inflammation. Colon biopsies showed loss of goblet cells, prominent crypt apoptosis, and intraepithelial lymphocytosis. No architectural abnormalities or granulomas were identified in the colon biopsies. Additional testing for anti-enterocyte and anti-goblet cell antibodies was recommended.

Gastrointestinal biopsy findings and diagnosis of thymoma lead to additional serologic testing which demonstrated presence of acetylcholine receptor antibodies thus establishing the diagnosis of myasthenia gravis.

Over the course of following three months, she underwent thymectomy, had lost significant weight due to malabsorption and had two episodes of myasthenia crisis. She was treated with intravenous immunoglobulin (IVIG) and dexamethasone, which dramatically improved her myasthenia symptoms but diarrhea persisted.  The frequency of diarrhea decreased from six stools per day to four stools per day with dexamethasone (8 mg daily). As of last follow-up, tapering of dexamethasone and a trial of rituximab was under consideration and no data was available for anti-enterocyte and anti-goblet cell antibodies.

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Fig. 1: Duodenum with intact villous architecture, no intra-epithelial lymphocytosis, minimal basal crypt lymphocytosis and loss of goblet and Paneth cells - H&E stain

 

 Fig. 1             

Fig. 2: Terminal ileum with villous blunting and loss of goblet and Paneth cells - H&E stain

 Fig. 2

Fig. 3:  Duodenum – Alcian Blue PAS stain demonstrating complete lack of goblet cells

 Fig. 3

Fig.4:  

 Colon – Intact architecture, increased intra-epithelial lymphocytosis, increased crypt apoptosis and loss of goblet cells - H&E stain

Fig.  4

Fig. 5: Colon –increased intra-epithelial lymphocytosis, increased crypt apoptosis and loss of goblet cells

 Fig. 5

Fig. 6:  Colon - prominent crypt apoptosis and loss of goblet cells - H&E stain

Fig. 6

February 2021 Final Diagnosis and Discussion