*4.4.2 Mediastinal granuloma*

It is characterized by forming a semi-liquid adenopathy block, formed by the union of a group of necrotic lymph nodes, most frequently subcarinal and paratracheal. Macroscopically, the necrotic material has the appearance and consistency of a paste, surrounded by a thin capsule (2–3 mm).

As in the case of mediastinal adenitis, mediastinal granuloma can be an accidental discovery, often asymptomatic. Very rarely, in small children, between 2 and 5 years old, it can compress the central airways, the esophagus, or the superior vena cava, as it is known that in these children, the vessels and airways are more flexible [18, 19].

Clinically, it can manifest early after the acute infection, after a few weeks or months, but it can remain subclinical for years when calcifications are detected.

Most of the time, the symptomatology is determined by complications, with adhesion to the neighboring structures and fistulization, with the drainage of the content in the bronchi, pulmonary parenchyma, or esophagus [20]. This liquid usually has a purulent appearance. After the drainage takes place, a new latent phase may appear. The reappearance of symptoms after a certain period can predict an unfavorable evolution over time. Sometimes, drainage to the esophagus can determine the evolution toward sepsis due to the occurrence of retrograde bacterial enteric infection [21, p. 39]. Also, sometimes a fistulization can occur in the pulmonary parenchyma, with the appearance of pneumonic infiltrate or drainage in the pleural or pericardial space, which is extremely rare but urgently requires a surgical pericardial window [22].

Symptomatic mediastinal granuloma requires surgical treatment, but the approach must be made selectively, in the case of adhesions, precisely so as not to cause damage to the surrounding organs. In the case of bacterial superinfections due to fistulization, broad-spectrum antibiotic therapy is necessary in addition to the usual recommended antifungal therapy. Treatment of patients with mediastinal granuloma with itraconazole 200 mg once or twice daily for 6 to 12 weeks in symptomatic patients is reasonable, especially in early mediastinal granuloma, shortly after infection. In the case of asymptomatic mediastinal granuloma, surgical treatment is not recommended [23].

*Granulomatous mediastinitis* can be the first presentation of histoplasmosis in the form of a mediastinal mass detected on chest X-ray. The CT appearance is of a heterogeneous formation with paratracheal or subcarinal localization, secondary to caseous necrosis at the level of granulomas; internal calcifications may be present [8]. Also, the CT examination can highlight the occurrence of complications: for example, extrinsic compression of the trachea, esophagus, or superior vena cava, respectively fistulization at the mediastinal level, confirmed by the presence of air inclusions at the level of the granuloma. Fistulization at the pulmonary level can be highlighted by a parenchymal infiltrate of the pneumonic type [24].

*Fibrosing mediastinitis* appears secondary to a chronic inflammatory process with excessive deposits of fibrous tissue at the mediastinal level, which can obstruct the upper respiratory tract and pulmonary vessels. It can be focal (80% of cases, frequently in the case of histoplasmosis) or diffuse (20%). We are thinking of fibrosing mediastinitis in the case of people aged between 20 and 30 years. Although the prevalence is 1 in 100,000 infected patients, it is significant in endemic areas because there are millions of people affected [3]. The symptomatology is determined by the degree of damage to the adjacent structures. The most common symptom is hemoptysis, but the complications can vary depending on the neighboring structures affected [25]. Thus, in unilateral occlusion of the pulmonary artery, pulmonary infarction can be associated with damage to the entire lung. In the case of slow onset of the occlusion, we can have superior vena cava syndrome as a consequence. Most of the time, the damage is unilateral, but patients with fibrosing mediastinitis must be monitored periodically. The CT appearance is variable, with the appearance of a hilar or mediastinal mass (in localized form) or with a fibrosing infiltrative appearance (in diffuse form) with soft tissue density, which obliterates the mediastinal fatty atmosphere and determines the cuffing of the main vessels, with the risk of pulmonary hypertension or obstruction of the superior vena cava [26].

### **4.5 Forms of extrapulmonary histoplasmosis**

In addition to pulmonary manifestations, in some cases (5%) cardiac (pericarditis) [27], skin (erythema multiforme, erythema nodosum) [7], rheumatological (arthritis), ocular manifestations may appear, but these represent a sterile inflammation as part of a systemic response, rather than a disseminated disease.

### *4.5.1 Progressive disseminated histoplasmosis and meningitis*

Approximately 5–20% of patients have CNS involvement. This could include a mass lesion, encephalopathy, and meningitis. Medical therapy is initiated for all patients with progressive disseminated histoplasmosis and meningitis [2].
