Contributed by Andrew Walls, MD and Chad Rund, MD
An 18 year-old woman presented to the emergency room with a five-day history of right upper abdominal pain accompanied by nausea with hematemesis, generalized malaise, cephalgia without provocation, fever, and diarrhea. She was a non-smoker, non-drinker and was not taking any medications (prescribed, over-the-counter, or supplements).
Routine blood work showed mild elevations in AST, ALT, and lipase; leukopenia with an absolute lymphocytosis associated with reactive/atypical lymphocytes seen by a manual differential; hypokalemia; and normal red cell indices.
Abdominal and chest CT as well as a plain film chest roentgenograph were unremarkable. Abdominal ultrasound demonstrated a mildly thickened gallbladder wall with some pericholecystic fluid; no calculi were seen. Nuclear hepatobiliary scan demonstrated patent cystic and common bile ducts.
The clinical impression was acute cholecystis versus a non-specific viral syndrome. She was taken to the operating room. A liver biopsy, cholecystectomy, and appendectomy were performed. The liver biopsy demonstrated a chronic active hepatitis with a portal and lobular pattern of inflammation, and a morphologic differential diagnosis included autoimmune, drug-induced, and viral hepatitis. The gallbladder demonstrated chronic inflammation, was devoid of stones, and a diagnosis of acalculous cholecystitis was rendered. The appendix demonstrated marked epithelial lymphocytosis.
An upper endoscopy demonstrated distal esophageal nodules approximating the distal gastroesophageal junction and a solitary gastric body nodule with central ulceration. Biopsies were taken. The duodenum was unremarkable.
Additional laboratory work-up demonstrated: negative CMV IgG/IgM; negative Hepatitis A, B, and C testing; negative Monospot testing (twice with a two-week interval between testing); positive ANA (Reference: <1:40) with a centromere pattern; negative AMA, and positive ASMA at 1:20 (Reference: <1:20).
The esophageal and gastric body biopsies were received for consultative review. On review of the routine histology, a striking mixed inflammatory infiltrate was present consisting of a lymphoid infiltrate composed of small-to-intermediate sized cells with scattered immunoblasts, eosinophils, plasma cells, and monocytoid cells diffusely expanding the lamina propria with infiltration between the gastric glands and pits (Figures 1, 2, and 3). Focal neutrophilic collections were seen (not shown). A Helicobacter pylori immunostain was negative (not shown). CD34 and S100 immunostains were also negative (not shown). CD20 and CD3 immunostains demonstrated a polytypic lymphoid population with CD20 positive immunoblasts (Figures 4 and 5). In situ hybridization for Epstein-Barr virus (EBER) was positive (Figure 6).