Pulmonary Cryptococcosis Mimicking Lung Cancer: A Diagnostic Challenge

Pulmonary cryptococcosis, although rare, maybe seen in both immunocompromised and immunocompetent patients. Cryptococcosis presenting as a lung mass mimicking lung cancer is very rare. Here, we report our experience with pulmonary cryptococcosis presenting as a lung mass mimicking malignancy in an immunocompetent patient. In this case, the patient presented to us with left-sided pleural effusion and lung mass on computed tomography (CT) of the chest. Bronchoscopy and endobronchial ultrasound (EBUS)-guided fine needle aspiration cytology (FNAC) was performed, which showed cryptococcal organisms. He responded well to oral anti-fungal therapy without any need for surgical interventions.


Introduction
Cryptococcosis, also known as torulosis, is a subacute or chronic mycotic infection caused by Cryptococcus neoformans.Infection is acquired by the inhalation of aerosolized particles.The clinical presentation of cryptococcosis varies along a spectrum, from asymptomatic pulmonary colonization to severe pneumonia with respiratory failure and life-threatening meningitis [1].Pulmonary cryptococcosis in immunocompromised patients can be severe and can be rapidly progressive, whereas in immunocompetent patients, it may be asymptomatic and usually remains confined to the lung as pulmonary nodules, although some may develop serious meningitis and disseminated infection [2].There are only a few case reports of pulmonary cryptococcosis presenting as lung mass in immunocompetent patients.

Case Presentation
A 50-year-old male confectioner with no history of diabetes mellitus, hypertension, or other comorbidities presented to our outpatient department with a six-month history of fever, cough with expectoration, and left-sided pleuritic chest pain associated with loss of weight and appetite.He was a non-smoker and nonalcoholic and had no history of high-risk behavior or exposure to birds.Initially treated with antibiotics by a local physician without much improvement, he was referred to our hospital for further management.On presentation, he had no neurological symptoms and was hemodynamically stable, afebrile, conscious, and oriented.Respiratory system examination revealed decreased breath sounds in the left infra-axillary and infra-scapular area, while the rest of the systemic examination was within normal limits.Initial investigations, such as complete blood counts, renal function tests, liver function tests, and blood sugars, were within normal limits except for leukocytosis with eosinophilia.Chest radiograph revealed a left-sided pleural effusion and left hilar prominence.Sputum examinations for tuberculosis (acid fast bacilli smear and GeneXpert) were negative.Pleural fluid analysis revealed lymphocytic predominant exudative effusion with low adenosine deaminase (24.8 U/L).Malignant cytology was negative.A contrast-enhanced computed tomography (CECT) of the chest showed an enhanced left hilar mass with ipsilateral pleural effusion (Figure 1).The patient was initiated on oral fluconazole (400 mg/day) due to the mild-to-moderate nature of the disease.A repeat chest radiograph done after four weeks of treatment showed significant improvement of symptoms along with the resolution of pleural effusion.A repeat CECT of the chest (Figure 4) after five months of therapy showed complete resolution of pleural effusion with a decrease in the size of the mass.
The patient was asymptomatic on regular follow-up, and the plan was to continue fluconazole for six more months along with monitoring of liver function tests.

Discussion
Cryptococcosis is primarily a disease of immunocompromised individuals, especially those with HIV infection and transplant recipients.Other predisposing factors include type 2 diabetes mellitus, chronic liver and kidney disease, chronic steroid use, and defects of cell-mediated immunity.However, 10-40% of patients with cryptococcosis may not have any apparent predisposing factors [3].The disease is caused by encapsulated yeast, Cryptococcus, which was previously considered as two biotypes of the same species (Cryptococcus neoformans var.gatii and Cryptococcus neoformans var.neoformans) but is now recognized as separate species, with Cryptococcus neoformans predominantly reported from immunocompromised patients, while Cryptococcus gattii infection has been associated with immunocompetent patients [4].Inhalation of spores from environmental sources, such as pigeon droppings, rotten vegetation, and Eucalyptus trees, is the main source of infection.
Depending on the immune status of the individual, symptoms and radiological findings may vary, making the diagnosis of cryptococcosis extremely difficult [5].Clinical manifestations can vary depending on the immune status of the individual.Cryptococcal meningitis is the most common manifestation in both immunocompetent and immunocompromised individuals.Pulmonary cryptococcosis is the second most common manifestation and is more common in immunocompetent patients [6].
The most common radiological findings of pulmonary cryptococcosis are single or multiple pulmonary nodules, masses mimicking lung cancer as seen in our case, air space consolidation, and patchy interstitial or alveolar infiltrates [7].In our review of immunocompetent individuals with isolated pulmonary cryptococcosis masquerading as pulmonary masses, we found eight case reports treated with antifungal therapy and, in some cases, with lobectomy, as listed in Table 1.Diagnosis of cryptococcosis depends on the site of infection, and it requires the demonstration of yeast cells in normal sterile tissues.Cultures from blood, sputum, and other body fluids are usually diagnostic [16].In our case, we demonstrated yeast cells from bronchial washings using various staining techniques, such as mucicarmine, Giemsa's stain, and periodic acid Schiff (PAS).The culture showed growth of Cryptococcus gattii.

Presentation Imaging and investigations
The management of pulmonary cryptococcosis depends on the immune status of the patient and the symptoms.The Infectious Disease Society of America guidelines recommend the use of fluconazole in mild to moderate pulmonary disease in immunocompetent patients and amphotercin B plus flucytosine in severe cases [17].Therefore, in our case, the patient was treated with oral fluconazole and had significant symptomatic and radiological improvement.

Conclusions
Our case underscores the significance of vigilance in recognizing pulmonary cryptococcosis as a potential culprit for lung masses that bear a resemblance to lung cancer, even in immunocompetent individuals.It is crucial to include this condition in the list of differential diagnoses for such lesions.Furthermore, it is imperative to administer prompt and robust medical intervention to avoid resorting to surgical measures.In light of these findings, it is evident that timely clinical, radiological, and histopathological evaluation plays a pivotal role in the successful management of pulmonary cryptococcosis.

FIGURE 1 :
FIGURE 1: Computed tomography (CT) of the chest Black arrow showing a left hilar mass and white arrow showing ipsilateral effusion

FIGURE 2 :
FIGURE 2: Bronchoscopy image of the left upper lobe White arrow showing mucosal erythema

FIGURE 3 :
FIGURE 3: Mucicarmine and peroidic acid-Schiff (PAS) stain of bronchoalveolar lavage fluid Black arrows showing round to oval encapsulated yeast demonstrating Cryptococcus

FIGURE 4 :
FIGURE 4: Follow-up computerized tomography (CT) of the chest Black arrow showing decrease in the size of the hilar mass and resolution of pleural effusion -old female with fever, chills, asthenia, jaundice, and cough with scant production of sputum Heterogeneous mass in the left upper lobe, with air bronchogram adjacent -old male with a two-month history of fever, sweats,nonproductive cough, and weight loss of 4 kg and pain in the tip of the right shoulder and weakness in the right arm and Horner syndrome on the right side