A thirteen-year-old girl was admitted to our hospital due to recurrent right pneumonia throughout the previous three years. She lost 3 kg in body weight in the preceding weeks but did not have fever or night sweats. She was born in Israel to parents of North African descent, with her mother completing treatment for Hodgkin's lymphoma 1.5 years before the girl's admission. During the years 1997-1999, when the patient was between six and eight years old, the family lived in Panama, Mexico and Florida.
Upon physical examination, she appeared well and had no signs of respiratory distress. Lung auscultation revealed decreased breath sounds over the right lung. There was no clubbing, and the rest of the exam was unremarkable. The basic laboratory results were insignificantly remarkable with no significant elevation of inflammatory markers.
A chest radiograph showed consolidation in the right lower lobe (RLL), with pleural thickening and effusion, and with resultant marked right lower lobe volume loss (Figure 1).
The recurrence of pneumonia focusing in the areas of the right middle and lower lobes (RML & RLL), demanded elimination of an anatomical disorder of the airways or foreign body aspiration; therefore, a direct anatomical investigation was accomplished by bronchoscopy. The bronchoscopy revealed severe obstruction of the right bronchus intermedious and a complete obstruction of the bronchus to the RML due to external compression.
Bronchoalveolar lavage (BAL) sampling was done to look for relevant infectious etiologies. Bacterial cultures, acid-fast staining, and silver staining were all negative for bacteria, tuberculosis, or fungus.
A chest computed tomography (CT) was done for assessing the external compression shown by bronchoscopy and for ruling out additional relevant, though less probable, etiologies for recurrent right pneumonia. Additional etiologies for recurrent right pneumonia include some congenital anomalies such as congenital pulmonary airway malformation or a diaphragmatic hernia. The chest CT showed subcarinal and right hilar masses (3.6 and 2 cm, resp.) with prominent calcifications. These calcifications severely compressed the right bronchial tree, right pulmonary artery, and right inferior pulmonary vein (RPA and RPV), causing complete atelectasis of the RML (Figure 2).
In the differential diagnosis of the calcified mass, the first to be considered were tuberculosis, fungal infection, and a malignancy. Other options included nodule calcification due to a granuloma formation in response to a healed infection, for example, a healed varicella pneumonia. It may have also represented the noncaseating granulomatous disease such as sarcoidosis or primary pulmonary amyloidosis. Another rare nonmalignant tumor to be considered was pulmonary chondroma as a part of the Carney triad which typically affects young females. Last but not the least, calcification of the lung parenchyma may be present secondary to calcium and phosphate metabolism abnormalities or to a benign inflammatory stimulus leading to calcifying fibrous pseudotumour (CFPT) of the lung.
An elaborated series of tests were completed due to suspected tuberculosis. PPD (Mantoux test) was negative as was the mother's (as a possible source). A quantiferon test and gastric fluid culture yielded the same results. Specimens of bronchoalveolar lavage fluid, pleural fluid, and pleural biopsy all came back negative for TB as well as for malignancy, granulomas, fungi, or other pathologies. In addition to a pleural biopsy, a biopsy from the calcified mass was also obtained by a transbronchial biopsy. Though the biopsy detected a few inflammatory cells alongside fibrous tissue, it did not reveal any infectious pathogens, granulomas, or other specific pathologies.
Extensive evaluation showed negative results for other relevant infectious etiologies (except for what will be mentioned below), immune deficiencies, and autoimmune diseases. Serum angiotensin-converting enzyme activity was also within normal limits.
The patient's previous residence in areas endemic for histoplasmosis (U.S. and Mexico) gave us a clue to histoplasmosis infection as a possible source for our findings. Histoplasmosis antibody tests (performed by the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, United States) were weakly positive with regard to the complement fixation test (titer of 1:8) and negative for the immunodiffusion test.
The clinical picture, imaging studies, serology results (although borderline), and past residence in areas endemic for histoplasmosis together with negative findings of other possible etiologies, all pointed to the diagnosis of histoplasmosis-related FM.
A series of complementary tests were done to better demonstrate the compression, to evaluate the severity of the lung disease, and for quantitative follow-up.
Cardiac magnetic resonance imaging (MRI) demonstrated normal ventricular function and narrowing of the RPA and RPV (Figure 3). Pulmonary function testing (PFT) revealed a mildly restrictive pattern with normal CO diffusion to alveolar gas (DLCO/VA). On a perfusion/ventilation scan (V/Q), the ventilation scan showed a mild ventilation defect at the RT lower lobe, while the perfusion scan showed a severe perfusion defect in the middle and lower RT lobes. Cardiopulmonary exercise test (CPET) results displayed suboptimal peak O2 consumption with a normal respiratory reserve.
After ruling out a malignancy, but before TB test results returned, antitubercular treatment was commenced along with prednisone for two weeks due to the pleural involvement and the bronchial obstruction. As soon as the TB test results were found to be negative, the patient was slowly weaned off this treatment.
After the diagnosis of histoplasmosis-related FM became the most probable diagnosis, we started treatment with itraconazole (200 mg twice a day) for three months. In addition, several trials of bronchoscopic balloon dilatation of the right intermedious bronchus were performed but achieved only transient relief.
Presently, after 13 years of follow-up, the patient functions normally regarding daily tasks but experiences some limitations during strenuous physical activity. She experiences annual or sometimes biannual symptoms of a chest infection which are treated with antibiotics.
Upon physical examination, she shows no signs of respiratory distress, with an SpO2 of 100% on room air and good air entry to both lungs.
Throughout the follow-up period, no significant changes in the classified mass's size or impact were documented on CT scans. MRI images also showed no change. Lung function tests and physiologic respiration abilities on CPET remain intact compared to baseline.
The patient is now married and has delivered two healthy children, both with regular vaginal deliveries following an uncomplicated pregnancy, under tight multidisciplinal supervision.