Case 5 -
Wade S. Samowitz
University of Utah Medical Center
Salt Lake City, UT
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A 57 year old insulin-dependent diabetic man presented at an outside institution with lower abdominal
pain, anorexia, fatigue, low grade fevers and constipation. The WBC count was 16,400/Ál with 8%
eosinophils. CT showed an 18 cm mass involving the transverse colon and stomach. Left colon biopsy
showed "active colitis with epithelioid granulomas." The presumptive diagnosis was Crohn's disease and
treatment with mesalamine was begun. Subsequent enlargement of the mass prompted surgical resection of a
segment of colon and part of the greater curvature of the stomach. Histologic interpretation was
"diverticular disease with perforation and foreign body reaction." The patient was discharged but was
then admitted to our institution because of an enlarging mass now involving the pancreatic tail and left
kidney. Slides from the initial operation were reviewed at our institution.
The wall of the bowel is involved by numerous necrotizing, and occasional non-necrotizing,
granulomas. There are also large areas of necrosis with both eosinophils and neutrophils which are
ringed by giant cells. Numerous eosinophils are present both within and outside of the granulomas;
associated with the eosinophil infiltration are Charcot-Leyden crystals. The mucosa of the bowel is
relatively unaffected by this granulomatous process. Large, thin-walled, irregularly branched fungal
hyphae with occasional septae are present within the granulomas and in areas of necrosis. These are
surrounded by a thick eosinophilic cuff, the Splendore-Hoeppli phenomenon.
Case 5 - Figure 1
Submucosa granuloma with hyphal form with Splendore-Hoeppli phenomenon.
Case 5 - Figure 2
Large area of necrosis in muscularis propria and submucosa ringed by giant cells.
Case 5 - Figure 3
Giant cells and pallisading histiocytes at the edge of the area of necrosis.
Case 5 - Figure 4
Hyphae (both longitudinal and in cross-section) with Splendore-Hoeppli phenomenon.
Case 5 - Figure 5
Hyphae with Splendore-Hoeppli phenomenon.
Case 5 - Figure 6
Prominent eosinophil infiltrates.
Case 5 - Figure 7
Cross-section of hyphal element with Splendore-Hoeppli phenomenon at bottom of photomicrograph; numerous Charcot-Leyden crystals above the fungus.
Case 5 - Figure 8
Numerous hyphae with Splendore-Hoeppli phenomenon.
Gastrointestinal Basidiobolomycosis is an extremely rare disease, with 8 cases reported from the
United States, mostly in residents of Arizona .
World-wide a little over 20 cases in total (including
the 8 from the US) have been reported, including cases from Nigeria, Brazil, Kuwait, Iran, Saudi Arabia
and the Netherlands
The etiologic agent of this disease is Basidiobolus
ranarum. Like the agents of Mucormycosis (here defined as infections due to fungi belonging to
the order Mucorales), which it histologically resembles, it is a member of the class Zygomycetes;
however, it belongs to the order Entomophthorales rather than Mucorales. Basidiobolus ranarum and another member of Entomophthorales, Conidiobolus coronatus, are more commonly associated with skin and soft tissue
infections in individuals from tropical areas of Africa, South America, and Asia.
Infection due to B. ranarum and C. coronatus
typically occurs in immunocompetent individuals. B. ranarum is found in
decaying plants and soil and as a commensal in the intestinal tracts of many animals, including frogs,
toads, turtles, chameleons, horses and dogs . Skin and soft tissue infection due to this agent is
thought to be due to traumatic implantation . The mode of transmission of gastrointestinal disease is
uncertain, although a case control study of cases in the US postulated ingestion of soil, animal feces,
or food contaminated by these substances . This study also suggested that therapy with ranitidine and
duration of residence in Arizona were risk factors for the disease.
The clinical presentation of gastrointestinal Basidiobolomycosis includes abdominal pain, fever,
constipation, anorexia and weight loss; rarely nausea and vomiting and lower gastrointestinal tract
bleeding may be seen . Abdominal masses, usually involving the colon, are present. These masses may
also involve the stomach, duodenum, liver, biliary system and pancreas. Most patients exhibit a
The histologic appearance of gastrointestinal Basidiobolomycosis is quite distinctive . It is
typically a mural disease with marked wall thickening; the mucosa is much less involved, although it
often shows focally increased eosinophils. Numerous granulomas are present in the wall of the bowel and
subserosa, surrounding areas of necrosis or abscesses composed of eosinophils, neutrophils or both.
Prominent eosinophil infiltrates outside of the granulomas are also commonly present, and Charcot-Leyden
crystals may be seen. Within the granulomas hyphal forms surrounded by a thick eosinophilic cuff
(Splendore-Hoeppli phenomenon) are present. These hyphae are large (8-40 um in width), thin-walled,
irregularly branched, and contain occasional septae. Hyphal walls can be seen on H and E, and typically
do not stain well with fungal stains like GMS or PAS.
The differential diagnosis includes Crohn's disease  and Mucormycosis. A predominantly mural,
granulomatous disease like gastrointestinal Basidiobolomycosis could be confused with Crohn's disease.
Besides the lack of fungi in Crohn's disease, mucosal disease is usually more prominent than in
Basidiobolomycosis. Mucormycosis usually occurs in immunodeficient individuals or in uncontrolled
diabetics. Mucormycosis also typically shows prominent vascular invasion and tissue necrosis and lacks
the well-formed granulomas and the Splendore-Hoeppli phenomenon seen with B.
ranarum. C. coronatus (and other species like C. incongruus) may appear histologically identical to B.
ranarum. Visceral involvement is very rare with Conidiobolomycosis and some individuals with
disseminated disease are immunocompromised. Culture and/or serum antibodies can distinguish
Basidiobolomycosis from Conidiobolomycosis.
As with most other infectious organisms, culture is extremely important. B.
ranarum has a characteristic beaked zygospore . Also, the organism forcibly ejects spores that
may then be seen on the cover of the Petri dish
Since B. ranarum
does not survive at 4 degrees Centigrade, culture of fresh tissue is imperative.
Treatment of gastrointestinal Basidiobolomycosis usually involves a combination of surgical resection
and prolonged antifungal therapy . The organism is often resistant to amphotericin B, but is usually
responsive to itraconazole. Lack of or inappropriate treatment often leads to a fatal outcome ;
appropriate therapy appears to be associated with a good outcome .
This patient was initially treated with the liposomal form of amphotericin B without a response.
Subsequent testing revealed resistance to amphotericin but susceptibility to itriconazole. Itriconazole
thereapy led to defervescence and resolution of leukocytosis and peripheral eosinophilia. A right
hemicolectomy was performed due to persistence of the mass and colonic obstruction. The patient was
discharged on long-term itriconazole.
- Lyon GM, Smilack JD, Komatsu KK, et al. Gastrointestinal basidiobolomycosis in Arizona: clinical and epidemiological characteristics and review of the literature. Clin Infect Dis 2001 May 15; 32(10): 1448-55.
- Geramizadeh B, Modjalal M, Nabai S, et al. Gastrointestinal zygomycosis: a report of three cases. Mycopathologia 2007 Jul; 164(1): 35-8.
- van den Berk GE, Noorduyn LA, van Ketel RJ, et al. A fatal pseudo-tumour: disseminated basidiobolomycosis. BMC infectious diseases 2006; 6: 140.
- Al Jarie A, Al-Mohsen I, Al Jumaah S, et al. Pediatric gastrointestinal basidiobolomycosis. The Pediatric infectious disease journal 2003 Nov; 22(11): 1007-14.
- Hussein MR, Musalam AO, Assiry MH, et al. Histological and ultrastructural features of gastrointestinal basidiobolomycosis. Mycological research 2007 Aug; 111(Pt 8): 926-30.
- Khan ZU, Khoursheed M, Makar R, et al. Basidiobolus ranarum as an etiologic agent of gastrointestinal zygomycosis. Journal of clinical microbiology 2001 Jun; 39(6): 2360-3.
- Nemenqani D, Yaqoob N, Khoja H, et al. Gastrointestinal basidiobolomycosis: an unusual fungal infection mimicking colon cancer. Archives of pathology & laboratory medicine 2009 Dec; 133(12): 1938-42.
- Zavasky DM, Samowitz W, Loftus T, Segal H, Carroll K. Gastrointestinal zygomycotic infection caused by Basidiobolus ranarum: case report and review. Clin Infect Dis 1999 Jun; 28(6): 1244-8.
- Pfaller MA, Diekema DJ. Unusual fungal and pseudofungal infections of humans. Journal of clinical microbiology 2005 Apr; 43(4): 1495-504.
- Yousef OM, Smilack JD, Kerr DM, et al. Gastrointestinal basidiobolomycosis. Morphologic findings in a cluster of six cases. American journal of clinical pathology 1999 Nov; 112(5): 610-6.
- Pasha TM, Leighton JA, Smilack JD, et al. Basidiobolomycosis: an unusual fungal infection mimicking inflammatory bowel disease. Gastroenterology 1997 Jan; 112(1): 250-4.
- Gugnani HC. A review of zygomycosis due to Basidiobolus ranarum. European journal of epidemiology 1999 Nov; 15(10): 923-9.