Contributed by Martina Pejchal, MD, PhD and Jennifer Picarsic, MD
A 6-year-old female was admitted for fever, rectal bleeding, and a worsening of her long-standing abdominal pain. Her history consists of a multi-visceral transplant (partial stomach, small bowel, large bowel, pancreas, and liver) at age 2 secondary to microvillous inclusion disease. The patient has had multiple issues with her transplant including TPN-induced liver damage, multiple episodes of mild and moderate acute cellular rejection and adenovirus enteritis, low-grade EBV enteritis and colitis, Candidal esophagitis, and gastritis.
The latter two infections were treated with Cipro, Bactrim, and Nystatin (in addition to her prophylactic regimen) for over one month prior to her admission. The patient's Tacrolimus (FK506) level was within normal range (5-15 ng/ml) for one month prior to this admission. However, over the two previous months, she did have several spikes in her levels, concomitant with treatment for her latest episode of acute cellular rejection two months ago.
Upon admission the patient was found to have E coli sepsis with blood cultures positive for ESBL. The patient was treated with meropenem therapy, after which her blood cultures remained negative. Other clinical microbiological assays during this admission were negative including CMV PCR, Legionella urinary antigen, stool viral culture, C. difficile, and rotavirus. Epstein-Barr Virus (EBV) PCR demonstrated 12,200 copies/mL (the patient has a history of being an EBV high load carrier).
Current imaging findings:
Images of mucosal thickening/nodularity of the colon and ileum from colonoscopy.
Esophagogastroduodenoscopy and colonoscopy completed four weeks after admission showed multiple lower third plaques in the (native) esophagus, normal native stomach, nodular allograft gastric mucosa with friability, regenerative mucosa in allograft duodenum, friable allograft ileum, nodular allograft cecum and colon, and multiple erythematous native rectosigmoid nodules near the anastomosis with mucosal bands.
Biopsies were taken of allograft tissues (duodenum, stomach, ileum, colon, colon nodules) as well as native esophagus and colon.
Shown are images of initial colonic biopsy (H&E 4x, PAS 10x and 100x, Gram stain 100x and Warthin Starry stain 100x), and subsequent biopsies (H&E 100x and Von Kossa stain 100x).
A colonoscopy with biopsies upon admission revealed early recovery from severe allograft rejection with re-epithelialization and crypt drop-out with enteritis and fragments with ulceration, granulation tissue and increased mucosal macrophages, which contained Warthin-Starry positive, weakly gram-negative staining bacilli-like bacteria within phagocytosing macrophages. The same pattern was also seen in the native colon. The differential at this time included Whipple's disease (Tropheryma whipplei), Campylobacter, and Bartonella as possible etiologic agents with no distinctive Michaelis Gutmann bodies were noted at this time. The special stains did not reveal a Whipple's pattern and a 16s ribosomal RNA sequencing with Tropheryma whipplei-specific PCR was negative. EBER in situ hybridization stain for EBV revealed only a latency pattern.
Repeat biopsies continued to show no rejection but a persistent diffuse mucosal histiocytic infiltrate in the allograft and native colonic biopsies, as well the allograft small bowel and stomach biopsies. The small bowel showed a blunted villous architecture and the lamina propria expanded with a similar population of medium to large macrophages with abundant eosinophilic granular cytoplasm, round to ovoid nuclei, and no nucleoli. The macrophage population was also seen in the antral mucosa, but only minimal lamina propria inflammation was present in allograft duodenum. These subsequent biopsies now showed characteristic intracytoplasmic inclusions (Michaelis-Gutmann bodies) within the large macrophages, which are also known as von Hansemann macrophages (H&E (40x and 100x).
The Michaelis-Gutmann (MG) bodies were highlighted with Von Kossa (a stain for calcium) and PAS (not shown).