Chronic lymphocytic lymphoma complicated by Mycobacterium avium and Scedosporium apiospermum

Dhiran Sivasubramanian¹, Bala Vignesh Kalyanasundaram², Nithish Nanda Palanisamy³, Sivakumar Nagaraju⁴

¹ Department of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, USA

² Department of Neurology, Mayo Clinic College of Medicine and Science, Phoenix/Scottsdale, USA

³ Department of Internal Medicine, Coimbatore Medical College, Coimbatore, India

⁴ Department of Pulmonary and Critical Care, Lovelace Medical Centre, Albuquerque, USA

Corresponding author’s e-mail: nithishnanda1207@gmail.com

Received: 11/06/2025
Accepted: 30/06/2025
Published: 17/07/2025

Conflicts of Interests: The Authors declare that there are no competing interests.
Patient Consent: Written informed consent for the publication of his case was obtained from the patient.
This article is licensed under a Commons Attribution Non-Commercial 4.0 License

How to cite this article: Sivasubramanian D, Kalyanasundaram BV, Palanisamy NN, Nagaraju S. Chronic lymphocytic lymphoma complicated by Mycobacterium avium and Scedosporium apiospermum. EJCRIM 2025;12:doi:10.12890/2025_005621

ABSTRACT

Introduction: Chronic lymphocytic leukaemia (CLL), the most common adult leukaemia in Western countries, poses unique management challenges, particularly when complicated by opportunistic infections. This report presents a rare case of CLL with concurrent Mycobacterium avium and Scedosporium apiospermum infections—pathogens increasingly recognized for causing severe disease in immunocompromised individuals. Their coexistence highlights the need for heightened awareness of diverse infectious complications in CLL patients.
Case description: We present a case of a 78-year-old male with CLL receiving chemotherapy, who developed burning pain in the tongue and oral mucosa, accompanied by a non- productive cough. He was initially diagnosed with pneumonia, but further investigation revealed co-infection involving M. avium and S. apiospermum.
Discussion: The coexistence of M. avium and S. apiospermum underscores the complexity of infectious complications in CLL. The patient’s chemotherapy was halted due to active pneumonitis observed on imaging in order to improve his leukocyte count. Antifungal therapy was not initiated due to a lack of evidence of invasive fungal infection. Antimycobacterial therapy for M. avium complex was initiated.
Conclusion: This case highlights the necessity of a multidisciplinary approach and continued research to optimize management strategies and improve outcomes in CLL patients with dual infections.

KEYWORDS

Opportunistic infection, chronic lymphocytic leukaemia/small lymphocytic lymphoma, anti-fungal treatment, pulmonary mycobacterium avium complex disease

LEARNING POINTS

• A high index of suspicion is needed for rare infections, such as Mycobacterium avium and Scedosporium apiospermum, when typical symptoms are absent or mild in immunocompromised patients with chronic lymphocytic leukaemia.
• An individualized, evidence-based approach is needed in choosing the treatment for opportunistic organisms while withholding cancer therapy.

INTRODUCTION/BACKGROUND

Chronic lymphocytic leukaemia (CLL) is a malignancy characterized by the clonal expansion of mature B lymphocytes, making it the most prevalent leukaemia in adults in Western countries^[1]. It is known for its multifaceted challenges, and when coupled with opportunistic infections, patient management becomes more complex. This case report examines an instance of CLL complicated by a co-infection involving M. avium and S. apiospermum. M. avium, a member of the non- tuberculous mycobacteria, is known to cause disseminated infections in immunocompromised individuals^[2]. On the other hand, S. apiospermum, a filamentous fungus, has been increasingly identified as a causative agent of invasive fungal infections in those who are immunocompromised^[3]. This coexistence highlights the importance of recognizing and addressing diverse infectious complications in CLL patients.

CASE DESCRIPTION

A 78-year-old Caucasian male with a past medical history of CLL diagnosed 7 months ago, on chemotherapy with rituximab and venetoclax, stage three chronic kidney disease with a history of Raynaud’s disease, and herpes zoster, presented with chief complaints of burning pain to his tongue and oral mucosa and a non-productive cough for the past 3 days. He was previously diagnosed with pneumonia and had been on antibiotics recently. He denied any chest pain or discomfort, fever, shortness of breath, loss of weight or appetite, or night sweats. The patient had no other co-morbidities. He stated that he was a nonsmoker and consumed alcohol occasionally. The patient, now retired, gave a history of occupational exposure as a carpenter for many years. There was no significant family history. He was vaccinated for coronavirus disease 2019.

His vital signs at presentation were a heart rate of 60 beats per minute, respiratory rate of 15 per minute, blood pressure of 105/56 mmHg, oxygen saturation of 97% on room air, and a body temperature of 36.7°C. The patient was alert and oriented. The cardiac examination was normal. On pulmonary examination, normal vesicular breath sounds were heard in all lung fields. The abdomen was soft and flat on examination, with no organomegaly. White patches were seen on the tongue and oral mucosa. Blood investigations showed leukopenia with a white blood cell count of 2400 cells/mm³ and mild thrombocytopenia of 136 ×10³/µl (Table 1). Other routine investigations were within the reference range (Table 1).

A chest X-ray showed mild right infra hilar pneumonitis and calcified remnants of an old granulomatous process (Fig. 1). Computed tomography (CT) scan of the chest showed tree-in-bud nodular opacities in the right lung (Fig. 2), suggesting active pneumonitis.

Due to these CT findings, the chemotherapy was held. The patient was started on amoxicillin, but he developed rashes and itching. Therefore, treatment was switched to levofloxacin. As symptoms did not improve over a few weeks, the patient underwent a bronchoscopy. Bronchoscopy revealed no significant endobronchial or inflammatory issue in both lungs and a bronchoalveolar lavage was performed. The lavage was sent for culture, acid-fast bacilli (AFB) smear, and cell cytology. The bronchial culture grew S. apiospermum and the AFB culture grew M. avium complex (MAC). The chemotherapy regimen was halted due to the active pneumonitis. The patient was started on a MAC regimen for the non- cavitary nodular bronchiectatic form which includes azithromycin 500 mg orally thrice weekly, rifampin 600 mg thrice weekly, and ethambutol 25 mg/kg thrice weekly for at least 12 months after cultures are negative^[4]. This regimen has demonstrated effectiveness in achieving sputum culture negativity. During the administration of antimycobacterial therapy, close monitoring of liver function, renal parameters, and other potential adverse effects is crucial. The patient was not treated for Scedosporium as there are no signs of active infection.

DISCUSSION

The American Cancer Society estimates that there will be approximately 23,690 new cases of CLL in 2025 in the United States, with about 4,460 expected deaths, confirming its status as the most prevalent leukaemia in the Western world^[1]. Furthermore, the global incidence of CLL has witnessed a notable increase, with a reported 107% rise in associated mortality rates, highlighting a concerning trend in the management of this disease^[1].

CLL primarily affects the aging male population, with the median age at diagnosis being 65 years^[5]. This lymphoproliferative disorder is characterized by the chronic accumulation of neoplastic B cells, leading to progressive symptoms manifesting as fatigue, unexplained weight loss, and a heightened susceptibility to infections because the disease itself and treatment regimens compromise the immune system^[5]. While chemotherapy has significantly improved prognoses for patients with CLL, it is crucial to acknowledge that all therapeutic modalities induce myelosuppression. This side effect can greatly compromise the body’s innate defence mechanisms, making patients highly susceptible to infections, particularly opportunistic pathogens that complicate recovery and management. The patient was receiving rituximab, a monoclonal antibody that effectively targets CD20 on B cells, employing various mechanisms to neutralize malignant B cells, including complement-mediated cytotoxicity and antibody-dependent phagocytosis^[6]. However, this treatment is also associated with risks such as hypogammaglobulinemia and neutropenia, which contribute to the increased likelihood of opportunistic infections. In contrast, venetoclax, while having lesser-known immunosuppressive properties, has also been linked to neutropenia, which can exacerbate the immunosuppressive risk already imposed by rituximab^[7]. This combination of treatments illustrates the delicate balance required in chemotherapy due to patients’ susceptibility to infections. The heightened risk of opportunistic infections in patients undergoing chemotherapy is compounded by potential delays in diagnosis. Mycobacterial infections, such as those caused by M. avium, present particular challenges because they are often difficult to identify through standard culture methods. Co-infections with multiple species, while rare, can complicate the diagnostic process, necessitating timely recognition and management of infections. Scedosporium species are recognized as environmental colonizers of the respiratory tract^[3]. Detection of S. apiospermum in bronchoalveolar lavage fluid from an immunocompromised patient, especially in the context of concurrent MAC, raises a critical question: does this represent colonization or invasive infection requiring treatment? The distinction is essential, as S. apiospermum is an emerging, opportunistic mold that can be either a colonizer or a life-threatening pathogen in immunocompromised hosts^[3,8,9].

S. apiospermum is frequently isolated from respiratory samples in immunocompromised patients, particularly those with underlying lung disease, solid organ or hematopoietic stem cell transplantation, or profound immunosuppression (e.g., neutropenia, corticosteroid use)^[8-12]. The clinical spectrum ranges from asymptomatic colonization to invasive pulmonary or disseminated disease, with the latter associated with high morbidity and mortality, mortality rates in transplant recipients and those with hematologic malignancy can exceed 50%^[9-11].

The need for treatment of the fungal infection is determined by evidence of invasive disease rather than colonization. Key factors that support a diagnosis of infection and thus the need for antifungal therapy include:

Clinical symptoms: New or worsening fever, cough, dyspnoea, haemoptysis, or pleuritic chest pain in the absence of another clear aetiology^[3,4].

Radiological findings: New or progressive pulmonary infiltrates, nodules, cavitary lesions, or consolidation on chest imaging, particularly if these findings are unexplained by other pathogens or processes^[3,12,13].

Histopathologic evidence: Demonstration of hyphal invasion in tissue (e.g., lung biopsy) is the gold standard for diagnosis but is often not feasible in severely immunocompromised patients^[3,13].

Microbiological context: Repeated isolation of S. apiospermum from sterile sites or in conjunction with compatible clinical and radiological findings increases the likelihood of true infection ^[3,9,13].

In the absence of the above features, the finding of this organism might be merely a colonizer^[3,9,13]. However, the risk of progression from colonization to invasive disease is unpredictable, particularly in those with ongoing or profound immunosuppression, and warrants close clinical and radiological monitoring^[10-12]. Our patient had no signs of invasive fungal disease based on the above guidelines and hence the treatment was not initiated, in contrast to Jimeno et. al where antifungal treatment was given since the patient had evidence of invasive fungal infection^[14].

Physicians must carefully weigh the risks against the benefits of starting treatment, particularly in immunocompromised individuals, where treatment regimens need to be tailored to individual patient needs. Effective management of such infections involves a nuanced understanding of their presentation and the potential for rapid deterioration in the patient’s condition if not promptly addressed.

CONCLUSION

This case report highlights the challenges of managing CLL patients with opportunistic infections. It underscores the importance of individualized treatment strategies, close monitoring for adverse effects, and a multidisciplinary approach to optimize patient outcomes in the complexity of managing dual infections in an immunocompromised patient. Continued research and clinical experience will further enhance our understanding and treatment options for such rare co-infections.