Histoplasmosis presenting as fibrosing mediastinitis and superior vena cava obstruction

Dear editor

A 47-year-old woman, a known case of type II diabetes mellitus (controlled on medications), presented with swelling of the face and neck for three months, accompanied by increased facial erythema over the same period. The facial symptoms were more pronounced in the morning. The patient reported significant weight loss. There was no history of thyroid disease, and any significant environmental/occupational exposure. On examination, facial plethora, distended neck veins, and venous prominences were present over the anterior chest wall. Whole-body FDG-PET/CT scan showed FDG avid soft tissue in the mediastinum predominantly in the right paratracheal location, encasing and narrowing the superior vena cava (SVC) [Figure 1]. Contrast-enhanced computed tomography (CECT) scan of the thorax revealed mediastinal nodes/soft tissue in the right paratracheal, subcarinal, and AP window regions, with some areas showing heterogenous attenuation [Figure 2]. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) from the lower right paratracheal (4R) station showed necrosis. Microbiological tests, including AFB smear, GeneXpert, MGIT culture, and fungal stains, were negative. The tuberculin skin test showed induration of 35 mm. Empirical antitubercular therapy (ATT) was initiated based on clinic-radiological findings. However, two months after ATT, persistent symptoms prompted further evaluation for non-response. Repeat CECT revealed soft tissue in pre-vascular, bilateral hilar, right paratracheal, AP window, pre-tracheal and sub-carinal location, and soft tissue completely encasing the SVC and distal left brachiocephalic vein with significant luminal narrowing. Autoimmune workup (ANA, ANCA, ENA profile), serum ACE, serum IgG4 levels, and serum galactomannan were negative. Urinary Histoplasma antigen test was positive. Inj. Liposomal Amphotericin B was initiated in view of a presumed diagnosis of mediastinal histoplasmosis. Oral itraconazole and tapering doses of prednisolone were advised upon discharge. Two months later, the patient presented with worsening SVC obstruction features and underwent SVC stenting [Figure 3]. Following stenting, the patient experienced symptomatic improvement. At last follow-up (more than a year following SVC stent placement), the patient was doing well on anticoagulation, in symptom-free status.

Figure 1.

FDG-PET/CT scan showing FDG avid paratracheal soft tissue

Figure 2.

Contrast-enhanced CT chest showing soft tissue mass in the right paratracheal region completely encasing SVC with luminal narrowing

Figure 3.

CT image showing the SVC stent in place

Fibrosing mediastinitis is an uncommon condition characterized by the abnormal proliferation of soft tissue in the mediastinum.[1] It poses a diagnostic challenge because the clinical presentation is varied, and establishment of an etiological diagnosis is difficult.[2] The aetiology of fibrosing mediastinitis encompasses many conditions, like Infective (Histoplasma, Tuberculosis, Coccidioides, Aspergillus), Inflammatory (Sarcoidosis, IgG4-related disorders, ANCA-associated vasculitis), and miscellaneous (Mediastinal radiation, Methysergide exposure, Silicosis) and occasionally Idiopathic. Histoplasma-associated fibrosing mediastinitis is more commonly reported from North America.[3] There is limited literature on fibrosing mediastinitis from the Indian region. Clinically patients present with non-specific signs and symptoms of cough, exertional dyspnoea, haemoptysis, chest pain, and features due to compression of mediastinal major bronchovascular structures.[4] Acute complications, like pulmonary infarction, superior vena cava syndrome (facial swelling, redness, headache), or obstructive pneumonia, can occur. Diagnosis should be considered in patients living in endemic areas for Histoplasma with slowly progressive symptoms or obstruction of SVC with an unclear aetiology and with abnormal appearing mediastinum on chest radiographs. Diagnosis is established on the clinic-radiological basis with contrast-enhanced CT findings consistent with fibrosing mediastinitis. However, a biopsy may be required to rule out the malignancy. CT findings consist of heterogeneously enhancing soft tissue mass that crosses the fat planes with/without the presence of calcification and circumferential compression of mediastinal structures. There are no clear guidelines for the treatment of fibrosing mediastinitis. Treatment is symptomatic and supportive and the amelioration of the life-threatening complications.[5] Glucocorticoids were used in various cases and the results are not consistent. Involved bronchovascular structures include large airways, pulmonary arteries/veins, superior vena cava, and rarely oesophagus. Life-threatening complications due to the compression effect can be managed by interventions. SVC obstruction has been described as a complication of mediastinal histoplasmosis.[6] In a case series involving 57 patients, 40 patients underwent endovascular stenting of the pulmonary artery, pulmonary vein, and superior vena cava with significant improvement and reduction in pressure gradient following stenting. However, symptomatic recurrent stenosis requiring further intervention was seen in 28% and the median time to restenosis was 115 months.[7]

This case also highlights the fallacy of using the tuberculin skin test in isolation for a diagnosis of TB. There are no clear guidelines regarding the diagnosis and management of fibrosing mediastinitis and is dependent on the clinic-radiological feature and decision of the treating physician. Further studies are needed to understand the pathogenesis and guide appropriate treatment for this rare condition.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.