Pathologic Quiz Case: A 56-Year-Old Woman With Anterior Nasal Pain and Intermittent Epistaxis

A 56-year-old white woman presented with a history of borderline serous tumor of the ovary. In 1997 she had a total abdominal hysterectomy and bilateral oophorectomy. She did well until 2000 when she developed a papillary serous tumor implant in her peritoneum. In 2000 the patient was given 6 cycles of chemotherapy, from which developed a therapy-related acute myelogenous leukemia (t-AML) in September 2003. She received induction chemotherapy with high dose of cytarabine and mitoxantrone for 4 weeks. She became neutropenic (white blood cell count, 400/μL), with intermittent fever, and she complained of nasal congestion, anterior nasal pain, and intermittent epistaxis. Physical examination of the nose showed a 1.0 × 0.5-cm anterior septal necrotic lesion with crusting. A computed tomographic scan showed normal maxillary sinuses. The patient subsequently underwent endoscopic sinus examination and debridement of the necrotic tissue, with culture.Endoscopic sinus examination revealed a 1.0 × 0.5-cm anterior nasal septal necrotic lesion. The overlying mucosa was slightly edematous with a dusky appearance. The septal cartilage was intact without perforation. The necrotic lesion was biopsied and debridement was performed. The specimen sent to the surgical pathology laboratory showed multiple small fragments of squamous mucosa with ulceration and necrosis mixed with blood clot (Figure 1). Gomori methenamine silver stain of the necrotic tissue revealed numerous hyphae elements with microconidia (Figure 2).Tissue sent to the microbiology laboratory was cultured on Sabouraud dextrose agar at 30°C for 2 weeks, producing grayish white and woolly colonies (Figure 3). Microscopic examination of the colonies demonstrated septated hyphae and muriform conidia with a zigzag appearance (Figure 4).What is your diagnosis?Alternaria is a fungus of the class Deutermycetes and the family Dematiaceae. Fungi of this genus have generally been regarded as nonpathogenic contaminants when isolated from clinical specimens. Alternaria species are ubiquitous, common saprophytes found in soil, various plants, and other substrata.1 When isolated from a clinical specimen, their significance is unclear. It must be determined whether the isolate is the primary etiologic agent, an agent of superinfection, or a simple laboratory contaminant. The organism should be isolated on repeat culture and correlated with clinical findings.2There is strong evidence that Alternaria alternate was the significant pathogen in this case. It was the only organism cultured from the nasal lesion, and repeated culture from the nose confirmed the same fungus. Furthermore, it presented clinically as a destructive nasal septal lesion; the organism was confirmed by Gomori methenamine silver stain. There are 3 common species of the genus Alternaria: alternate, tenuissima, and chartarum.3 Definitive identification of different species is based on conidial morphology. Microscopic examination revealed the characteristic muriform conidia with short beaks and branched conidiopores and conidia 24 to 27 μm long and 8 to 9 μm wide. The conidia have both transverse and longitudinal septations (zigzag appearance).2There are only limited case reports of human Alternaria species infection in the literature. It seems well established that Alternaria may cause superficial infection of the skin.4 A majority of the reported cases occurred in patients who either had severe underlying disease or were immuno-compromised. The skin lesions appeared as weeping, nonhealing ulcers, erythematous macules, or violaceous nodules. Reported sites of the lesions were the dorsal hands, fingers, elbows, knees, or feet. Histologically, the lesions may reveal the pattern of microabscess formation in the dermis and subcutis or of granulomatous inflammation.Alternaria species infections have also presented as sinusitis and maxillary osteomyelitis.5 The clinical presentations were nasal pain, chronic nasal irritation, partial obstruction, and sometimes perforation. Roentgenograms of the lesions showed mainly well-circumscribed lesions, occasionally osteolytic. The biopsy materials generally showed granulomatous or suppurative inflammation with ulceration and necrosis. Gomori methenamine silver stain usually demonstrated branching, thick-walled hyphae elements. Most cases of fungal infection of the nasal sinuses occur in immunocompetent patients. Alternaria species have been repeatedly isolated from healthy people with allergic sinusitis.6 The treatment options for Alternaria infection of the nasal sinuses are local excision and debridement, local injection of nystatin, and oral antifungal therapy with amphotericin B or ketoconazole.A high awareness of Alternaria infection in both clinicians and laboratorians is essential to make a timely pathologic diagnosis, especially when the patient is immunosuppressed. Many patients achieve complete recovery after aggressive treatment. This patient received a combination of surgical (local debridement) and antifungal (amphotericin B) therapy. Her Alternaria infection was controlled: multiple subsequent cultures of her nasal sinus content were negative for the organism. Unfortunately, the patient died of bacterial sepsis and disseminated intravascular coagulation 3 months later.