What's Behind the Hoarseness, Laryngeal Obstruction in a Healthy Nonsmoker?

Why did an otherwise healthy non-smoker in his 60s have steadily worsening hoarseness and shortness of breath for the past year? That was the diagnostic puzzle facing Kenneth W. Altman, MD, PhD, of Geisinger Medical Center in Danville, Pennsylvania, and colleagues in a case reported in JAMA Otolaryngology–Head & Neck Surgery.

On presenting to the clinic, the patient said he had not experienced any throat pain, cough, difficulty swallowing, or reflux symptoms, nor had he had a fever or unexplained weight loss. He told clinicians that he was a lifelong non-smoker, had not undergone any surgery to the head or neck, and had not been exposed to radiation. His medical records indicated that his primary care physician had prescribed inhaled corticosteroids for suspected asthma, but that treatment did not improve the patient's symptoms.

Physical examination found the patient very hoarse and stridulous. However, examination of his neck revealed nothing unusual. Clinicians performed a videostroboscopy that revealed severe swelling of his laryngeal mucosa, primarily affecting the false vocal folds, interarytenoid, and postcricoid regions. The patients right true vocal fold was immobile, with compensatory squeeze of the false vocal folds and no mucosal wave.

CT scan of the neck with contrast showed that the free edges of the true vocal folds were irregular. However, there was no signs to suggest a neoplasm or cervical lymphadenopathy.

They performed an urgent direct laryngoscopy with a biopsy and a modified barium swallow study, which revealed aspiration. The scope showed that the patient's laryngeal mucosa was swollen, irregular, and friable, and there was considerable constriction of the airway. Given the risk of airway obstruction, clinicians performed a tracheotomy at the time of direct laryngoscopy, and placed a gastrostomy tube to address risk of aspiration.

Hematoxylin-eosin stain of the biopsy specimen showed numerous epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, findings that were consistent with necrotizing granulomatous inflammation. Acid-fast bacteria stain returned negative results, and a Grocott methenamine silver stain revealed broad-based budding yeast engulfed by multinucleated giant cells. Based on these findings, clinicians arrived at a provisional diagnosis of blastomycosis. PCR testing confirmed the presence of this rare fungal infection.

The patient was prescribed long-term treatment with itraconazole. At 2-month follow-up, clinicians noted that the patient was less hoarse, and he was tolerating tracheostomy capping. A follow-up modified barium swallow study indicated restoration of normal swallowing function, so his gastrostomy tube was removed.

At 5-month follow-up, a repeat videostroboscopy showed reduced supraglottic edema with increased mobility of true vocal folds, and eventually, the tracheostomy tube was removed.

Discussion

Clinicians reporting this rare case of laryngeal blastomycosis noted that "diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis." Data suggest that this invasive fungal infection of the larynx is "frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs," the team cautioned.

First described by Gilchrist in 1894, "blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment, and yeast in the human body" when aerosolized conidia from disruption of soil are inhaled, case authors explained. The fungus is most likely to grow in the Great Lakes and Mississippi-Ohio River valley regions.

According to the CDC, in the five states where blastomycosis is reportable – Arkansas, Louisiana, Michigan, Minnesota, and Wisconsin – yearly incidence rates are approximately one to two cases per 100,000 population. Of these states, Wisconsin is thought to have the highest incidence of the infection, with yearly rates ranging from 10 to 40 cases per 100,000 persons in some northern counties.

While the lungs are affected most often, blastomycosis infection can also involve the skin, bone, genitourinary, and central nervous systems, they wrote, adding that the first reported case of blastomycosis of the larynx dates back to 1918.

Typically, blastomycosis presents initially with an "insidious onset of hoarseness," they noted, often followed by symptoms such as cough, shortness of breath, and pain or difficulties swallowing. However, infection is asymptomatic in about 50% of cases.

Little data have been published to guide treatment of this condition, case authors wrote, but management typically involves laryngoscopy with tissue biopsy for stains and cultures. "Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies," they noted, with histology investigations showing "nonspecific inflammatory infiltrates and reactive surface epithelial changes."

Clinically, infection may manifest with inflammatory changes, including granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cell, the group wrote.

Regarding diagnostic histopathology, the case authors explained that "blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains."

Isolation of blastomyces in cultures can provide a definitive diagnosis in a few weeks, although real-time PCR assays offer quicker diagnosis, authors noted. Infection is usually managed with 6 to 12 months of itraconazole therapy, which in most cases, resolves the symptoms.

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