—  SPECIALTY CONFERENCE  —

Infectious Disease Pathology

Case 5 - Subcutaneous Basidiobolomycosis (subcutaneous phycomycosis)

Ronald Neafie
Armed Forces Institute of Pathology
Washington, DC


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Clinical History:
The patient was a 5-year-old Zairian boy with a soft tissue tumor on the left lower leg that had been increasing in size for three months. On examination, the patient appeared healthy and well nourished. A well-defined, firm, non-tender area of soft tissue swelling extended from mid thigh to mid calf. The overlying skin was warm to palpation, thickened, hyperpigmented and desquamating in areas. X-ray of the limb was unremarkable. Because of the possibility of a malignant soft tissue tumor, the skin and soft tissue of the left upper calf was biopsied. Grossly, the specimen consisted of a 0.7 cm punch biopsy of skin excised to a depth of 1.1 cm. The epidermal surface was dark brown and the subcutaneous tissue was yellow adipose tissue with areas of possible myxoid tissue.

Diagnosis: Subcutaneous Basidiobolomycosis (subcutaneous phycomycosis)


Case 5 - Figure A
Case 5 - Figure B

Description:
Microscopic examination reveals pseudoepitheliomatous hyperplasia, but no ulceration. There is chronic inflammation of the upper dermis consisting of histiocytes, lymphocytes, plasma cells, and eosinophils. The lower dermis is marked by an increase in eosinophils and the beginning of microabscess and granuloma formation. In addition to the chronic inflammatory cells, subcutaneous tissue is characterized by necrosis, granuloma and microabscess formation, and an intense eosinophilia.

Fungal elements are scattered throughout the subcutaneous tissue. The fungus appears predominantly in the form of hyphae. The hyphae are up to 15 mm wide and can be observed in hematoxylin-eosin stained sections. However, they are more easily observed by the Gomori methenamine-silver (GMS) and the periodic acid-Schiff (PAS) staining techniques. The hyphae are thin-walled, rarely septate, occasionally haphazardly branched, and sometimes partially collapsed. Some hyphae contain nuclei. Occasionally hyphae are surrounded by an eosinophilic amorphous material (Splendore-Hoeppli phenomenon).

In addition to hyphae, zygospores are also present. The zygospores are spherical and up to 30 mm in diameter. They have a thin outer wall, foamy cytoplasm, and a nucleus containing a large nucleolus. Zygospores also stain readily with hematoxylin and eosin.

Discussion:
Subcutaneous basidiobolomycosis, also called subcutaneous phycomycosis, is infection caused by Basidiobolus ranarum, previously referred to as Basidiobolus haptosporous and Basidiobolus meristosporus .1,2  Basidiobolus ranarum belongs to the class Zygomycetes and order Entomophthorales. Members of Entomophthorales usually produce septate hyphae and form zygospores.

Clinically, the typical lesion is a single, painless, sharply circumscribed, hard subcutaneous mass. The lesion is slow growing and freely movable. The most common site is the buttock or thigh, but lesions have also been reported to begin in the neck, face, and trunk. In time, lesions may spread to adjacent areas, but hematogenous spread is virtually unknown. Massive lymphedema may give the lesion an elephantoid appearance. The fungus is thought to be acquired by percutaneous inoculation.

Basidiobolus ranarum is found in decaying vegetable matter, soil, and the gastrointestinal tracts of reptiles, fish, amphibians, and bats. The disease occurs most frequently in tropical Africa and Southeast Asia. Children are most commonly infected and males more frequently than females. Adults are only occasionally infected. There appear to be no predisposing factors.

The histopathologic changes, in conjunction with the appropriate clinical history, are pathognomonic for subcutaneous basidiobolomycosis (subcutaneous phycomycosis) and allow a definitive diagnosis even without culture. There are three cardinal features: 1) a mixed suppurative and granulomatous response 2) a prominent tissue eosinophilia and 3) the presence of thin-walled, broad hyphae with some surrounded by an eosinophilic amorphous material. In addition, there is no vascular invasion by B. ranarum or infarction. Zygospores are rarely observed in subcutaneous tissue. Zygospores closely resemble trophozoites of free-living amebae(Acanthamoeba and Balamuthia species). However, hyphae always occur along with the zygospores thus eliminating an infection caused by free-living amebae.

The treatment for subcutaneous basidiobolomycosis is a saturated solution of potassium iodide. Ketoconazole has also been effective. Spontaneous resolution has been reported, but surgical excision is not curative.

Gastrointestinal Basidiobolomycosis:
Gastrointestinal basidiobolomycosis is also caused by Basidiobolus ranarum. The first culturally proven case of gastrointestinal basidiobolomycosis occurred in a four-year-old Brazilian boy and was published in 1980.3  He had lesions involving the stomach and transverse colon and died on the twelfth day of admission due to complications of his infection. The authors postulated that three other reported cases, although without culture, were probably also gastrointestinal basidiobolomycosis. The histopathologic changes and morphologic features of the fungus are identical to those seen in subcutaneous phycomycosis.

Schmidt et al., in 1986 4 published the first culturally proven case of gastrointestinal basidiobolomycosis in the United States in a 69-year-old diabetic man. Lesions involved his duodenum, ileum, cecum, and ascending colon. He was treated with amphotericin B, but died 6 weeks after presentation. A second case of gastrointestinal basidiobolomycosis acquired in the United States was published by Pasha et al., in 1997 5 in a 49-year-old woman from Arizona. She had resection of the rectosigmoid colon, was treated with itraconazole, and had no evidence of residual disease 6 months after her surgical procedure. Yousef et al., in1999 6 reported a cluster of 6 cases of gastrointestinal basidiobolomycosis occurring in four Phoenix, Arizona, area hospitals. In addition to the classic histopathologic changes round structures were observed in 4 of the 6 cases. They were 20 to 40 mm in diameter and contained a nucleus-like structure with surrounding flocculent material. These round structures are identical to those observed in the subcutaneous tissue of the 5-year-old Zairian boy and are interpreted as zygospores.

According to Lyon et al. in 2001 7 there were 15 reported cases of gastrointestinal basidiobolomycosis worldwide. Half of these 7 patients apparently acquired their infections in Arizona, although it is unclear how the fungus is introduced into the host's gastrointestinal tract. All 7 patients had abdominal pain as the primary symptom and all had blood eosinophilia. All 7 patients responded well to itraconazole.

Infections caused by Basidiobolus ranarum, whether involving subcutaneous tissue or gastrointestinal tract, can readily be distinguished from mucormycosis. Mucormycosis is caused by fungi belonging to the order Mucorales and includes such representatives as Rhizopus oryzae, Mucor circinelloides, and Absidia corymbifer. Mucormycosis usually involves immunocompromised patients, and the typical tissue reaction is suppurative necrosis with vascular invasion by hyphae. Prominent tissue eosinophilia does not occur nor does eosinophilic amorphous material (Splendore-Hoeppli phenomenon) surround the hyphae.

Conidiobolomycosis must be distinguished from basidiobolomycosis since the 2 diseases are histopathologically identical. Conidiobolomycosis usually refers to infection caused by Conidiobolus coronatus and involves the face (also called nasofacial phycomycosis). Lesions begin in the submucosa of the nose, extending slowly to adjacent tissue. The disease can last for years and there is no satisfactory treatment. Conidiobolus incongruus has caused deep fungal infections in 3 patients. The histopathologic changes in the tissues of these 3 patients is identical to those caused by C. coronatus and B. ranarum.

References

  1. Kwon-Chung, K.J. and J.E. Bennett. Entomophthoramycosis, In: Medical Mycology. Lea & Febiger, Philadelphia. 1992:447-463.
  2. Binford CH, Connor CH. Pathology of Tropical and Extraordinary Diseases. Washington, DC: Armed Forces Institute of Pathology: 1976:591-593.
  3. de Aguiar E, Moraes WC, Londero AT. Gastrointestinal entomophthoromycosis caused by Basidiobolus haptosporus. Mycopathologia. 1980:72:101-105.
  4. Schmidt JH, Howard RJ, Chen CL, et al. First culture-proven gastrointestinal entermophthoromycosis in the United States: a case report and review of the literature. Mycopathologia 1986:95:101-104.
  5. Pasha TM, Leighton JA, Smilack JD, et al. Basidiobolomycosis: and unusual fungal infection mimicking inflammatory bowel disease. Gastroenterol 1997;112:250-254.
  6. Yousef OM, Smilack JD, Kerr DM, Ramsey RR, Rosati L, Colby TV. Gastrointestinal Basidiobolomycosis: morphologic findings in a cluster of six cases. Am J Clin Pathol. 1999;112:610-616.
  7. Lyon GM, Smilack, Komatsu KK, et al. Gastrointestinal basidiobolomycosis in Arizona: clinical epidemiological characteristics and review of the literature. Clin Infect Dis 2001;32:1448-1455.