Surgical Pathology of Skeletal Coccidioidomycosis

Abstract

Skeletal coccidioidomycosis is a rare complication of pulmonary coccidioidomycosis that remains incompletely characterized, and its histopathologic features have not been systematically evaluated. All skeletal coccidioidal infections (2000 to 2012) were retrieved from the University of Arizona and Mayo Clinic in Arizona pathology archives. Clinical history and histologic features were reviewed. Among 25 patients (median age 40 y; 17 men), infections involved bones (2 cases), joints (6), or both (17), usually in the distal extremities (68%), especially the wrist (32%). History included previously documented coccidioidomycosis (13), autoimmune disease (8), diabetes (6), malignancy (4), and iatrogenic immunosuppression (10). Common symptoms (median 3 mo) included pain/arthralgia (21) and swelling (10). Cultures and serology were positive in 15 of 17 (88%) and 19 of 22 patients (86%), respectively. Treatment included surgical debridement(s) and chronic antifungal medication(s). Histologic review showed granulomas in all cases, ranging from poorly to well formed, with or without necrosis. Spherule density varied widely (mean 4.8/HPF; range <0.1 to 13.5/HPF). Composition of inflammatory infiltrates, degree of necrosis, and extent of fibrosis did not significantly differ between immunocompetent and immunocompromised patients. Eosinophils were only seen in one third of cases; when present, eosinophils were almost always rare. 10 patients experienced recurrent infection, 8 of whom were immunocompromised; the remaining patients recovered. In conclusion, distal extremities are the most common sites of skeletal coccidioidomycosis encountered by surgical pathologists. This condition is strongly associated with autoimmune disorders and immunosuppression. Spherules are sometimes rare, and multiple modalities including serology, culture, and histology may be required for diagnosis.

Coccidioidomycosis Osteoarticular Dissemination

“…Most cases involved one disseminated site only, although in few instances, multisystem dissemination, where 2 or more distinct systems or sites were affected, was described [6,8]. Osteoarticular infections constituted 20% to 56% of disseminated cases [9] and will be reviewed in detail in this article.…”

“…Skeletal coccidioidomycosis generally arises from hematogenous dissemination and can often progress to the destruction of bones or adjacent structures such as joints, tendons, and other soft tissues [4,9]. Skeletal sites of infection do not have a location bias, as any bone could be involved in dissemination, but the reported sites with the most severe disease manifestation have been in the axial skeleton, including the skull, sternum, ribs, and vertebrae [4,27,31,32], with the latter being slightly favored (especially the lumbar and thoracic areas), where C. immitis frequently disseminates [5,27,31].…”

“…Skeletal coccidiomycosis cases often appear with nonspecific features, mimicking other conditions such as malignant tumor, tuberculous osteomyelitis, as well as bone infections caused by other microorganisms [4,9]. Caraway and colleagues described two different cases of coccidioidal osteomyelitis that were misdiagnosed as primary bone tumors [43].…”

“…Differentiating coccidioidomycosis infection from those other diseases is of utmost importance given the therapeutic and prognostic implications. Accurate diagnosis of skeletal coccidioidomycosis requires a very high level of rigor and a multidisciplinary approach combining laboratory analysis (histopathology, immunology, and microbiology) and imaging (such as Radiographs and MRI), especially in immunocompetent patients, and people from endemic areas [9,31,55,60].…”

Challenges in the Diagnosis of Invasive Fungal Infections in Immunocompromised Hosts

“…Mesothelial and bronchial cells may at times show mild cytologic atypia and GMS stain was particularly helpful for the identification of very small spherules in BAL specimens [38]. Recently, two recent series of coccidioidomycosis with unusual presentation in pleural and skeletal presence of spherules was lower in pleural coccidioidomycosis (mean density < 1/10 high-power field (HPF)) than in skeletal coccidioidomycosis (mean density 4.8/HPF) and in the latter, it was higher in immunocompromised patients (median 4.3/HPF versus 1.6/HPF) [39,40]. Granulomatous inflammation was present in both locations of the disease but was universal in the pleural form while they were observed in only one third of patients with the skeletal localization.…”