Primary Subcutaneous Mucormycosis (Zygomycosis)

A Case Report

MANJUNATH S. VADMAL, M.D.,f KUN-YOUNG CHUNG, and STEVEN I. HAJDU, M .D.f

fDivision o f Surgical Pathology and Cytopathology, Department of Laboratories, North Shore University Hospital, Manhasset, NY 11030

tDepartment o f Pathology, The Mount Vernon Hospital, Mount Vernon, NY 10550

ABSTRACT

A case of mycormycosis presenting primarily as a subcutaneous mass of the left leg in an immunocompetent individual is described. The mass that was diagnosed ini tially as a non-specific foreign body granulomatous process recurred a year later. Histopathological examination of the primary and recurrent lesions revealed partly degenerated hyphae associated with acute necrotizing and chronic granulomatous inflammation. Histomorphological features of primary subcutaneous mucormycosis without predisposing factors have not been previously reported.

Mucormycosis is a rare fungal infection usu Case Report ally seen in patients with long-standing dia A 67-year-old black male with history of hyperten betic ketoacidosis, immunosuppression or sive cardiovascular disease, chronic obstructive pulmo trauma. Although rhinocerebral infection is nary disease and chronic ethyl alcohol use was seen in the most common form of the disease, occa July 1995 for a painful, purulent swelling on the medial aspect of the left ankle. There was no history of trauma, sionally pulmonary, gastrointestinal or cutane fever or systemic symptoms. The lesion was biopsied ous types have also been described.1,2 Cutane and sent for routine culture and histopathologic exam ous manifestations of mucormycosis are seen ination. Microscopically, the lesion was interpreted as an acute necrotizing inflammation with a non-specific either as superficial ulcers in diabetics, gan foreign body giant cell reaction. Routine culture failed grenous cellulitis in trauma or bum wound to grow any microorganisms. A year later, the lesion infection, and uncommonly as a dissemi recurred at the same site as a slightly painful, indurated lesion of uncertain duration. On examination, a firm, nated disease in leukemic patients.3,4,5 His well demarcated, non-ulcerated, subcutaneous nodule tomorphological features of a primary cutane measuring 2.5 cm in diameter was noted just below ous mucormycosis without systemic involve the left medial malleolus. There was no history of diabe tes mellitus or risk factors for HIV infection. Presurgical ment in a non-immunosuppressed patient laboratory tests such as complete blood count and serum are described. electrolytes, including blood glucose, were within normal 55 0091-7370/99/0100-0055 $00.00 © Institute for Clinical Science, Inc. 56 VADMAL, CHUNG, AND HAJDU limits. The lesion was excised and was sent for histo isms have been exclusively described in pathologic examination only. The underlying bone was unremarkable. patients with metabolic acidosis (diabetic Microscopic examination of the primary and recurrent ketoacidosis), immunosuppression or trauma. lesions revealed nodules composed of chronic granuloma Rhinocerebral/rhinofacial form is the most tous and acute necrotizing inflammation in the deep der mis and subcutis [figure 1], Few nodules had a central common but occasionally pulmonary, gastro cavitary lesion filled with necrotic debris. Aggregates of intestinal and cutaneous forms may also foamy epithelioid histiocytes, reactive lymphocytes, occur.1,2 Mycotic infections of skin and subcu plasma cells and multinucleated giant cells were predomi nant in granulomatous areas. The tissue surrounding the taneous tissue are more commonly caused by nodules was dense and collagenous. On hematoxylin and Blastomyces, Chromoblastomyces, Cryptococ eosin stained sections, occasional, irregular, broad, refrac- cus, Coccidioidomyces and Candida. How tile and degenerated structures were observed within the histiocytes and giant cells [figure 2], Periodic acid-Schiff ever, mucormycosis of the cutaneous and sub (PAS) and Gomori methenamine silver (GMS) stained cutaneous tissues is relatively uncommon and sections revealed broad, non-septate hyphae that were have occasionally been reported.3,4,5 either cylindrical, irregular or distorted in shape [figure 3] within the cavitary lesions and in the wall of the nodules Mucormycosis can be diagnosed in histo and giant cells. The hyphal wall varied in thickness with pathologic sections by hematoxylin and eosin irregular branching. Where large hyphae were cross stain (H&E) with the aid of PAS or GMS sectioned, they resembled small arterioles. The histomorphological features were consistent with mucor species, stain. Microscopically, the fungus is character and the diagnosis of subcutaneous mucormycosis was ized by broad, non-septate hyphae that are made on both initial and recurrent lesions. The fungus either cylindrical, irregular or distorted in could not be characterized further as cultures were not obtained from the recurrent lesion. shape. The hyphal branching is irregular and After the diagnosis of subcutaneous mucormycosis, the the walls of the hyphae vary in thickness. patient received a short course of Amphotericin-B in addi tion to complete debridement of the tissue surrounding Where large hyphae are cross-sectioned, the nodule. Reexamination of the area four weeks and six they may resemble yeast cells or cross months later revealed a completely healed area with no sectioned arterioles. The fungal infection is residual lesion. almost always accompanied by either a granu lomatous infiltrate composed of epithelioid Discussion and multinucleate giant cells or a predomi nantly polymorphonuclear leukocyte infiltrate Mucormycosis, or Zygomycosis, is a rare forming microabscesses. fungal infection caused predominantly by Traditionally, characterization of the fungus members of the family Mucoraceae of the to species requires examination of the culture order Mucorales. Fungus commonly isolated morphology. Clinically, in most instances, cul clinically belongs to the genera Absidia, Mucor tures are not obtained due to lack of symptoms or Rhizopus. Infections caused by these organ specific to mycotic infections. Also, frequently

F i g u r e 1. Acute suppurative and necrotizing inflammation associated with Mucor infection (original magnifica tion xl25). PRIMARY SUBCUTANEOUS MUCORMYCOSIS (ZYGOMYCOSIS)

F igure 2. Chronic granulomatous inflammatory nodule with multinucleated histiocytes containing cross-sectioned, refractile hyphae of Mucor. (original magnification x250). cultures may not grow any organisms and, and treated adequately. Primary mucormyco once again, one has to depend on morphologi sis of the skin and subcutaneous tissue without cal details in tissue sections to make the diag systemic involvement has been reported in two nosis. In a recent article, Jensen, et al,e by cases.7,8 Both patients had predisposing fac using monoclonal antibodies, reviewed the tors, such as acquired immunodeficiency syn application of iinmunohistochemistry, espe drome and crushing injury. Biopsies in both cially to formalin-fixed paraffin-embedded tis cases revealed typical hyphae and were treated sues, for the diagnosis of various mycotic infec appropriately with no recurrence. tions. However, these antibodies are not In summary, primary mucormycosis (Zygo- widely available commercially, thus making it mycosis) of cutis and subcutis is rare. The difficult for diagnostic purposes. mycotic infection is always accompanied by The case of chronic, recurrent, subcutane chronic granulomatous or purulent inflamma ous mucormycosis we described has several tion. On H&E stain, partly degenerated, unusual features. The patient did not have pre refractile, hyaline hyphae are readily confused disposing factors for mycotic infections. He for foreign particles. PAS or GMS stain is nec was non-diabetic, non-immunocompromised, essary to demonstrate the diagnostic hyphal and there was no history of trauma. As the structures. Treatment includes, complete exci initial lesion was incompletely excised, it sion or debridement of the lesion with sys recurred a year later when it was diagnosed temic Amphotericin-B. Left untreated or inad

F igure 3. Gomori Mathenamine Silver (GMS) stain showing multiple cross-sectioned hyphae. Occasional distorted cylindrical forms with irregular branching are also present (original magnification x400). 58 VADMAL, CHUNG, AND HAJDU equately removed, the lesion may become 3. Huffnagle KE, Southern PM Jr, Byrd LT, Gander locally destructive or recur with extension into RM. Apophysomyces elegans as an agent of zygomycosis in a patient following trauma. J Med Vet Mycol deep tissues that may require mutilating sur 1992;83-86. gery or amputation. 4. Meyer RD, Kaplan MH, Ong M, Armstrong D. Cuta neous lesions in disseminated mucormycosis. JAMA 1973;225:737-738. Acknowledgement 5. Wilson CB, Siber GR, O’Brien TF, Morgan AP. Phy- We thank Mei L. Wu for her excellent secre comycotic gangrenous cellulitis. A report of two cases tarial assistance. and a review of the literature. Arch Surg 1976;111: 532-538. R eferences 6 . Jensen HE, Schonheyder HC, Hotchi M, Kaufman L. Diagnosis of systemic mycoses by specific immunohis- tochemical tests. Mycopathol 1996;104:241-258. 1. Sugar AM. Agents of mucormycosis and related spe cies. In: Mandell GL, Douglas RG, Bennett JE, eds. 7. Hopwood V, Hicks DA, Thomas S, Evans EG. Pri Principles and practice o f infectious diseases. New mary cutaneous zygomycosis due to Absidia corymif- York, NY: Churchill-Livingstone Inc; 1990:1962- era in a patient with AIDS. J Med Vet Mycol 1992; 1972. 30:399-402. 2. Skahan KJ, Wong B, Armstrong D. Clinical manifes 8 . Padhye AA, Koshi G, Anandi V, Ponniah J, Sitaram V, tations and management of mucormycosis in the com Jacob M, Mathai R, Ajello L, Chandler FW. First case promised patient. In: Wamock DW, Richardson MD, of subcutaneous zyzygomycosis caused by Saksenaea eds. Fungal infection in the compromised patient. vasiformis in India. Diagn Microbiol Infect Dis England: John Wiley & Sons; 1991:153-190. 1988;9(2):69-77.