Pathologic Quiz Case: A Healthy 31-Year-Old Man With Sinusitis

A 31-year-old previously healthy man presented with a 6-month history of nasal congestion and sinusitis. During the 6-month period, he was treated with antibiotic therapy, but his symptoms persisted. His current complaints included worsening of the nasal congestion and right eye “bulging,” with the right eye pressing on his glasses. His medical history was significant only for allergic rhinitis.

The patient was seen by an ophthalmologist for his eye symptoms. Significant clinical findings included 7 mm of proptosis on the right eye. His vision was 20/25 in the right eye and 20/20 in the left. Right globe motility was reduced in all gazes. The findings from the pupil examination were normal. Friable laminated material and tissue filled most of the view on bilateral nasal endoscopic examination. There was no regional adenopathy or evidence of meningismus.

Computed tomography and magnetic resonance imaging demonstrated a heterogeneous mass with pan-sinus involvement, affecting the right side more than the left. A computed tomographic scan of the mass demonstrated extensive remodeling of bone, including erosion of the inferomedial wall of the right orbit and the base of the anterior cranial fossa (Figure 1). The magnetic resonance imaging signal characteristics of the mass were consistent with inspissated mucin.

The patient was evaluated by the otolaryngology service and taken to the operating room for endoscopic sinus debridement. The surgical specimen consisted of multiple fragments of soft, friable, gray-tan tissue (Figure 2). The histology showed large amounts of laminated mucinous material with marked eosinophilia, chronic inflammation, and fungal elements (Figure 3). The presence of fungal elements entrapped within laminated lakes of mucin was confirmed with Gomori methenamine-silver stain. There was no evidence of fungal invasion into orbital soft tissue or bone, no purulent exudate, no granulomatous inflammation, and no evidence of vasculitis. A fungal culture on Sabouraud dextrose agar grew a dark mold with black pigmentation on the reverse, which microscopically showed a dark yellow-brown mycelium composed of uniform hyphae with parallel walls and distinct septations. The macroconidia seen had 4 to 5 cells separated by transverse septa and had a curved or “boomerang” appearance (Figure 4).

What is your diagnosis?

Pathologic Diagnosis: Allergic Fungal Sinusitis Secondary to Curvularia lunata

In 1983, Katzenstein et al1 described allergic Aspergillus sinusitis as a newly recognized form of sinusitis. Since that time, numerous other fungi, including Curvularia, have been identified to cause the same clinical entity, and the term allergic fungal sinusitis (AFS) was coined.

The prevalence of AFS is unknown. Gourley et al2 reviewed 200 consecutive cases of chronic sinusitis requiring surgery and found 14 cases (7%) of AFS. Allergic fungal sinusitis usually occurs in young immunocompetent patients ranging in age from early childhood to their late 40s, and it demonstrates equal sex distribution. Many of the patients have a history of atopy, allergic rhinitis, and nasal polyps. Symptoms typically include nasal obstruction, discharge, and multiple medical and surgical treatments for recurrent sinusitis. The diagnostic criteria of AFS include (1) chronic rhinosinusitis (confirmed by computed tomographic scan); (2) the presence of allergic mucin (predominantly eosinophils and their degenerated by-products); and (3) the presence of fungal organisms within that mucin confirmed by histology or culture.3 

Surgical specimens from patients with AFS consist of thick inspissated mucus and tissue from the involved sinus. The nature of this mucin was defined as allergic mucin with the histologic features described by Katzenstein et al4 in 1983. Microscopically, allergic mucin consists of numerous clumps of eosinophils, Charcot-Leyden crystals, and fungal hyphae.

Many reports of AFS have unfortunately equated compressive bone erosion with the concept of invasive disease. This results in therapeutic confusion, since invasive fungal sinusitis is a completely different clinicopathologic entity from AFS and requires far more aggressive therapy, including toxic antifungal agents such as Amphotericin B. Bone erosion in AFS is poorly understood, but may be related to pressure generated by the expanding mass or to inflammatory mediators.5 Our case demonstrated quite well the marked radiographic bone changes that can be seen in AFS.

Fungal organisms in the surgical specimens can be identified using Gomori methenamine-silver stain, but this does not aid in distinguishing the dematiaceous fungi from Aspergillus or Zygomycetes species.6 The Fontana-Masson stain can distinguish the pigmented fungi because the organism's pigment is similar to that of melanin. A fungal culture is the definitive way to identify the causative organism. In our case, C lunata was identified.

Curvularia is a dematiaceous (darkly pigmented) mold classified in the group of asexual fungi called Hyphomycetes. The organism has septate hyphae and produces curved cylindrical spores that contain 3 transverse septa. The organism is easily grown on Sabouraud dextrose agar, and the colonies have a velvety green-gray appearance with black pigmentation on the reverse. The dematiaceous molds are commonly found in soil and on plants. They rarely cause invasive disease, but can invade and disseminate in immunocompromised patients. Dematiaceous molds are the most common cause of AFS in immunocompetent hosts. Besides Curvularia, other dematiaceous molds causing sinusitis include Bipolaris, Exserohilum, Alternaria, and Cladosporium species.6 

The treatment of choice for AFS consists of endoscopic debulking surgery of the sinuses with debridement of impacted mucin and aeration of diseased sinuses.6 Treatment of the hypersensitivity component of the disease is a therapeutic cornerstone of AFS. Pharmaceutical options include systemic and more preferably inhaled nasal steroids. Recurrences are common. The patient described in this case was treated with endoscopic sinus debridement, a short course of oral prednisone, and a long-term course of inhaled nasal steroids. Antifungal agents were neither required nor indicated. He has regained normal ophthalmic and nasal sinus function, without evidence of recurrent active disease at 24 months.