Case Presentation:

We present a case of a 5 year-old immunocompetent Egyptian immigrant who spent 6 months in an endemic region – the Ohio River Valley – and presented in California with acute onset cough, shortness of breath and chest pain along with poorly localized abdominal pain. Chest CT revealed a right superior anterior mediastinal mass measuring 4.3×3.9×3.7cm with 50% tracheal compression. Mediastinal mass biopsy showed extensive collagen fibroses, lymphocytic infiltrate and necrotic foci, however without detectable granulomas or histologic evidence of malignancy. Although Histoplasma serum and urine antigen and serologic testing were unrevealing, a Histoplasma complement fixation titer greater than 1:64 led to diagnosis of Histoplasmosis-related mediastinitis. The patient was started on intravenous amphotericin B and methylprednisolone, demonstrating clinical improvement within five days. He was continued on posaconazole and prednisone maintenance therapy with an improved complement fixation titer (1:32), inflammatory markers, and initial radiologic evidence of mediastinal mass shrinkage. Despite early improvement in disease burden, mediastinal mass interval enlargement was noted on CT six months after treatment initiation. A sternotomy with debulking and biopsy of the mediastinal mass evidenced fibrous tissue with necrotizing granulomatous inflammation. The patient was then continued on posaconazole therapy with no cardiopulmonary symptoms. 

Discussion:

The characteristic dense fibrous tissue overgrowth and inflammatory infiltrate of mediastinal fat seen in fibrosing mediastinitis (FM) is most closely associated with H. capsulatum infection and is the most common non-malignant cause of mediastinal compression syndromes, especially in endemic regions. In 1988, Loyd et al. reviewed 71 cases of FM and found that the most common symptoms include cough (41 %), dyspnea (31 %), hemoptysis (31 %) and chest pain (23%). Laboratory evidence of histoplasmosis is limited to antigen and serologic tests with relatively low sensitivity. In a 15-year (1991-2005) retrospective Mayo institutional review among 111 patients with known systemic histoplasmosis, 25% had negative serology and 20% had negative urine antigen screen tests. Complement fixation (CF) studies may help distinguish histoplasmosis from malignancy, and a CF titer of >1:32 generally is considered suggestive of acute histoplasmosis. The therapeutic approach to FM remains limited. Some data suggests ketoconazole provides some alleviation in symptoms and disease progression, however results are not widely generalizable. Likewise, corticosteroids have not been shown to effectively control FM. Local therapies intended to mitigate symptoms by opening occluded airways or vasculature have aided select patients, with use of laser therapy, balloon dilatation and stent placement 

Conclusions:

Differentiating Histoplasmosis mediastinitis from malignancy can be difficult given similar symptoms and diagnosis itself is problematic given the poor sensitivity of antigen testing and variable serologic results. Patients most often present with cough, dyspnea, hemoptysis and chest pain, although may be asymptomatic, therefore a high index of suspicion is required for diagnosis. Medical and surgical options for controlling mediastinitis remain limited although some case reports demonstrate successful management with anti-fungal and anti-inflammatory therapy.