Abstract
Pulmonary fungal infections are typically opportunistic but can also develop in immunocompetent hosts. These infections frequently present with diverse imaging appearances, often mimicking more common pulmonary or mediastinal conditions.
We report the case of a 64 year old male with cough, shortness of breath and chest heaviness whose imaging features (neural formainal extension; destruction of adjacent ribs and vertebral bodies and chest wall invasion) initially suggested a malignant peripheral nerve sheath tumor. However, biopsy performed twice confirmed the lesion to be a cryptococcal infection.
This case highlights that fungal infections in immunocompetent individuals may present as invasive mass-like lesions. Consequently, infections—particularly fungal etiologies—should remain an important consideration in the differential diagnosis of thoracic masses, even in patients without overt immunosuppression.
Keywords: Lung mass, Malignant peripheral nerve sheath tumor, Pulmonary fungal infection, Cryptococcosis, Cryptococcoma, Case report
Introduction
Cryptococcosis is a fungal infection caused by Cryptococcus neoformans or Cryptocococcus gatti [1]. These are ubiquitous, encapsulated, yeast-like fungi that commonly thrive in soil, decaying wood, and pigeon droppings [2]. Most infections are acquired through inhalation of infectious droplets, leading primarily to pulmonary disease. In immunocompromised hosts such as patients with hematological malignancies, Human immuno-deficiency virus (HIV) or people who have undergone organ transplantation, the infection may disseminate beyond the lungs [3,4]. Apart from the lungs, dissemination to the central nervous system (CNS), skin/ subcutaneous tissue, eyes, prostate, liver, adrenal glands, lymph nodes, peritoneum and even bones can occur with such infections [5,6].
Pulmonary cryptococcosis (PC) has a multitude of imaging manifestations such as nodules (< 3 cm in size) and masses (>3 cm in size) predominantly in peripheral location with smooth margins and variable lobar predominance; ground glass opacities, air space consolidation, interstitial thickening, milliary nodules, cavitations, calfications and pleural effusions [4]. Mediastinal involvement in cryptococcosis is rare and usually present in immunocompetent hosts manifesting as lymphadenopathy, cryptococcomas and pleural effussions [1,7]. PC often presents with nonspecific symptoms such as fever, cough, chest pain, weight loss, and hemoptysis; however, the majority of cases are asymptomatic [8].
Posterior mediastinal masses are characterized by the following features on imaging that have been summarized in Table 1 [9]. Some common differentials for posterior mediastinal masses include neurogenic tumors; extra-medullary hematopoesis; meningoceles; neuroenteric cysts; lymphoma; lipoma / liposarcoma; diaphragmatic hernias; infectious spondylodiscitis and foregut duplications cysts [10].
Table 1.
Imaging characteristics of posterior mediastinal masses.
| Characteristics of posterior mediastinal masses on imaging: |
|---|
| Bony changes involving the vertebral column or ribs––most specific sign. |
| Mass will silhouette the aortic knuckle and descending aorta |
| Pulmonary artery can be seen through the mass––positive hilum overlay sign. |
| Widening of the neural foramina with dumbbell like extension through the intervertebral foramina. |
| Azygo-esophageal recess and paraspinal lines may be displaced on radiographs |
| Air fluid levels may be seen in lesions of the esophagus. |
| Negative cervico-thoracic sign. |
| Epicenter of lesion in paravertebral compartment with anterior displacement of contents of visceral compartment. |
PC presenting as a posterior mediastinal mass is rare and is not typically included in the differential diagnosis of such masses. In our case, locally aggressive imaging features initially suggested a malignant peripheral nerve sheath tumor which was proved to be a cryptoccocoma twice on histopathology, which guided appropriate therapeutic management.
Case presentation
A 64-year-old male presented to the emergency department with nonspecific respiratory complaints, including shortness of breath, chest heaviness, and cough since 3 months which had increased since 3 days. He also reported intermittent low-grade fever for the past four months. The patient had no history of malignancy, diabetes mellitus, corticosteroid or antibiotic use, and organ transplantation. No neurological symptoms were reported by the patient.
Respiratory examination revealed dull percussion and reduced breath sounds over the right upper chest. The remainder of the systemic examination including neurological examination was unremarkable. Vital signs including temperature and electrocardiogram were within normal limits. Laboratory investigations, including routine blood tests such as complete blood count, renal function tests, liver function test and urine routine microscopy were within normal limits. Serology for HIV, hepatitis B and C was also negative.
A portable chest X-ray demonstrated an ill-defined radiopacity over the right upper lobe. Subsequent computed tomography (CT) of the chest revealed a minimally enhancing heterogenous large soft tissue density mass measuring approximately 10.4 × 10.2 × 8.9 cm in size in the apical region of right hemithorax (Fig. 1C). It was abutting the chest wall and adjacent C1-C4 vertebral bodies causing patchy areas of destruction of the adjacent vertebra and ribs (Fig. 1B). The lesion showed extension into the intramuscular plane of right posterior chest wall via the intercostal spaces (Fig. 1A). Medially, the lesion was insinuating into the right neural foramina following which a diagnosis of neurogenic tumor was made (Fig. 1A). Magnetic Resonance Imaging (MRI) of the neck and chest was performed to assess involvement of the central spinal canal, epidural extension and spinal cord compression. MRI of the neck and chest revealed an T1 iso T2/STIR high signal intensity mass with lobulated margins in the right upper lobe of the lung (Figs. 2 A, B and C). The mass showed restricted diffusion (Fig. 2 D). It also showed heterogenous enhancement in post contrast images with non—enhancing cystic/necrotic areas (Fig. 2 E). Similar to the CT, the mass was seen insinuating into the adjacent right neuralforamina causing its widening with mild contralateral deviation of the spinal cord to the left side. However, no signal intensity changes were noted within the cord. Medially, the mass was abutting the superior venacava, trachea and esophagus with indistinct interfaces. The adjacent D1, D2 and D3 vertebral bodies showed T1 low T2/STIR high signal intensity marrow edema. These areas showed enhancement in post contrast images—suggesting invasion. Considering all these a provisional diagnosis of malignant peripheral nerve sheath tumor was made.
Fig. 1.
((A) Axial CECT of the chest in soft tissue window; (B) Axial sections of the chest in bone window; (C) Sagittal contrast sections of the chest)) with green triangle showing the minimally enhancing right apical region mass, orange star showing the intermuscular extension of the mass, red arrow showing right neural foraminal extension and blue and yellow arrows showing rib and vertebral erosion respectively.
Fig. 2.
((A) Axial T1W images; (B) Axial T2W images; (C) Coronal STIR images)) : showing T1 iso T2/STIR heterogenous high signal intensity mass (green triangle) showing extension into the intra-muscular plane of posterior chest wall (orange star) and red arrow showing extension into the right neural foramina. 2 C shows STIR high signal intensity changes in the adjacent D2 and D3 vertebral bodies. (D) Axial DWI AND ADC images showing areas of restricted diffusion. (E) Sagittal post contrast images : Showing the heterogenous enhancement of the mass with non enhancing cystic and necrotic components in both the mass (green triangle) and chest wall portion of the mass (orange star).
To establish a definitive diagnosis and guide potential treatment, a tissue biopsy of the mass was performed, which revealed cryptococcal infection (Fig. 3). Due to the aggressive appearance of the lesion on imaging, malignancy was still considered, and a repeat biopsy was performed, confirming cryptococcal infection yet again. A final diagnosis of pulmonary cryptococcosis was made following which antifungal therapy was initiated. Injection Amphotericin B at 1 mg/kg/day was given for 2 weeks followed by oral fluconazole 400 mg/kg/day for 10 weeks. The patient is now on follow up in the pulmonology and thoracic surgery departments and has symptomatically improved following the initiation of antifungal agents.
Fig. 3.
Histopathological slides of the biopsied tissue showing round encapsulated cryptococcus.
Discussion
The estimated annual incidence of C. neoformans infection is about 0.4-0.9 per 100,000 population in immunocompetent individuals, whereas in immunocompromised patients—particularly those with HIV—the incidence rises sharply to 6-10% [11].
There are limited number of case reports on the mediastinal involvement in pulmonary cryptocococcosis which have been summarized in Table 2 [6,7,[11], [12], [13], [14], [15]]. Consistent with existing literature, mediastinal involvement of cryptococcosis is more frequently observed in immunocompetent individuals, as demonstrated in our case. Radiologically, mediastinal cryptococcosis presents roughly equally as lymphadenopathy or cryptococcomas based on the existing literature. The posterior mediastinum is an especially uncommon location for cryptococcal disease with only one case by Qu et al. [14] reporting such a location. In our case not only did the lesion occupy this compartment but also demonstrated aggressive features such as rib erosion, vertebral marrow changes, and foraminal widening—features that strongly mimicked malignant peripheral nerve sheath tumor. Such invasive features were also seen in cases reported by Lopes et al. and Samy et al. [1,6].
Table 2.
Literature review of existing cases of crytococcosis with mediastinal involvement.
| Study | Patient (age/sex) | Immune status | Mediastinal location | Mediastinal involvement | Initial misdiagnosis | Diagnostic method |
|---|---|---|---|---|---|---|
| Murakami et al. [12] | 28 y male | Immunocompetent | Hilar & mediastinal nodes | Enlarged lymph nodes | Lymphoma | Lymph node biopsy |
| Chen et al. [7] | 45 y male | Immunocompetent | Mediastinal lymph nodes | Multiple nodal enlargements | Lymphoma | Excisional biopsy |
| Okachi et al. [13] | 26 y female | Immunocompetent | Middle mediastinum | Massive lymphadenopathy | Malignant tumor | Mediastinal biopsy |
| Qu et al. [14] | 34 y male | Immunocompetent | Posterior mediastinum | Cryptococcoma (mass) | Neoplasm | Surgical resection specimen |
| Lopes et al. [6] | 52 y female | Immunocompetent | Superior mediastinum (adjacent to thyroid) | Mass extending near thyroid | Thyroid neoplasia | Biopsy |
| Lee et al. [15] | 12 y male | Immunocompetent | Right infrahilar / mediastinum | Large mass | Malignant tumor | Thoracoscopic biopsy |
| Zhang et al. [11] | 55 y male | Immunocompetent | Mediastinal nodes | Generalized lymphadenopathy | Lymphoma | Biopsy |
| Samy et al. [1] | 29 y female |
Immunocompetent | Middle mediastinum | Crytococcoma | Tuberculosis | Autopsy |
Cryptococcosis is classically diagnosed by culture, though this is time-consuming and often requires large specimen volumes. Serum and CSF cryptococcal antigen testing provides excellent sensitivity, while molecular methods help differentiate Cryptococcus from other yeasts, particularly in antigen-negative cases. Tissue biopsy remains crucial, especially in uncommon presentations like ours and those summarized in Table 2, where histopathology confirmed the diagnosis [12].
Surgical resection is rarely beneficial in cryptococcosis and also precludes assessment of therapeutic response or disease progression. Antifungal agents represent the treatment of choice, though outcomes are influenced by host immunity, pathogen virulence, and the timeliness of intervention [16]. According to the Infectious Diseases Society of America (IDSA) for severe pulmonary cryptococcosis, the drug of choice is amphotericin-B along with intravenous flucytosine, followed by oral fluconazole [6].
Conclusion
This case describes a rare presentation of pulmonary cryptococcosis as a posterior mediastinal mass mimicking malignancy. It underscores the importance of biopsy in confirming the diagnosis, thereby avoiding unnecessary surgery / oncologic therapy and enabling timely antifungal therapy. Our findings add to the scarce literature and emphasize considering fungal infections in the differential diagnosis of mediastinal lesions, even in immunocompetent hosts.
Patient consent
Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Footnotes
Competing Interests: The authors have declared that no competing interests exist.
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