Disseminated Mucormycosis in an Immunocompromised Patient with Richter Transformation of Chronic Lymphocytic Leukemia: A Case Report of Concurrent Findings on [18F]-Fluorodeoxyglucose PET-CT

Abstract

A case of chronic lymphocytic leukemia/small lymphocytic lymphoma with Richter transformation. After initiating R-CHOP chemotherapy, patient developed severe neutropenia and necrotizing cellulitis, necessitating an above-knee amputation. Subsequent positron emission tomography-computed tomography (PET-CT) imaging revealed new lesions suggestive of an abscess, confirmed as mucormycosis upon biopsy. This report highlights the importance of fludeoxyglucose PET-CT in detecting fungal infections in immunocompromised patients and its role in disease management.

 

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Keywords

FDG PET/CT - infection - lymphoma - mucormycosis - Richter transformation

Introduction

Mucormycosis is an opportunistic systemic fungal infection with a rapidly progressive, life-threatening clinical course owing to the notorious angioinvasive nature of the causative fungi of the order Mucorales. With the background of an uncontrolled diabetes or an immunocompromised state (e.g., human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome [AIDS], neutropenia, posttransplant status, patients on steroids, and immunosuppressants), patients often have a predisposition to develop opportunistic infections, inclusive of, however, not limited to systemic mycoses.

Richter transformation is development of an aggressive B-cell lymphoma from an otherwise low-grade, indolent lymphoma, for example, chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) with a dismal prognosis, characterized by sudden clinical deterioration and rapid progression of nodal disease.[1]

We hereby present this unusual case of disseminated mucormycosis highlighted on [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) scan, manifesting against a background of neutropenia in a patient of CLL/SLL undergoing Richter transformation.

 

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Case Presentation

A 35-year-old male, diagnosed with low-grade, indolent non-Hodgkin's lymphoma, in keeping with CLL/SLL, was kept on observation. In mid-2024, the patient presented with sudden-onset, rapid enlargement of the axillary nodes, along with multiple episodes of fever, fatigue, night sweats, and myalgias. Laboratory investigations revealed anemia and thrombocytopenia and the FDG PET-CT revealed multiple lymphadenopathy with marrow lesions, following which a biopsy was done from the axillary node suggesting CD20, CD5, and CD23 positivity with a Ki-67 of 80%, establishing a clinicopathological diagnosis of accelerated CLL/SLL, that is, Richter transformation.[1]

Patient was planned for chemotherapy after a tumor board decision. Post-one cycle of chemotherapy with R-CHOP regimen, patient developed severe neutropenia with an unprecedented fulminating necrotizing cellulitis of the left lower limb due to mucormycosis, warranting an above-knee amputation and was started on intravenous liposomal amphotericin-B and isavuconazole.

Few weeks later postamputation, the patient developed a mass over the right inguinal region, clinically suspected to be a progression of the lymphomatous disease, and hence, a restaging of the disease with PET-CT scan was done.

Prechemotherapy PET-CT scan ([Fig. 1]) revealed multiple supra- and infradiaphragmatic adenopathy with marrow lesions, all of which showed FDG avidity, consistent with the high-grade transformation of the lymphoma, which showed decrease in size and metabolism on the subsequent postchemotherapy PET-CT scan ([Fig. 2]). However, the latter also unraveled presence of well-defined centrally necrotic lesions with peripheral FDG avidity and enhancement in the adductor longus and magnus muscles of the right thigh ([Fig. 2D]) and in the left psoas major ([Fig. 2E]) with perilesional edema—imaging features suggestive of abscess. An FDG-avid, ill-defined necrotic soft tissue was also noted along the amputation margin, associated with bony erosion of the remnant femur. The morphological features exhibited by the lesions involving the muscles and the surgical site were different altogether from that of a lymphomatous involvement.

Fig. 1 Prechemotherapy fludeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) showing multiple hypermetabolic supra- and infradiaphragmatic adenopathy with marrow involvement (A: maximum intensity projection [MIP] image; B: coronal fused PET-CT image; C: coronal CT image.

Fig. 2 Postchemotherapy fludeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) images: (A) maximum intensity projection (MIP) image, (B) coronal fused PET-CT, and (C) coronal CT showing decrease in the size of the hypermetabolic enhancing solid nodes involved by the lymphomatous disease, however, with new-onset lesion in the right proximal thigh (marked with black and white arrows). Images (D) and (E) show necrotic abscesses in the right adductor magnus muscle (arrow) and left psoas muscle (notched), respectively.

Histopathological examination of the right proximal thigh mass and the surgical site soft tissue revealed presence of necrosis and inflammatory cells, along with broad, pauciseptate hyphae with right angle branching—typically suggestive of mucormycosis ([Fig. 3]).

Fig. 3 (A) Hematoxylin and eosin (H&E) section from the abscess in the right adductor magnus muscle showing fungal hyphae (black arrow) interspersed against a background of acute inflammatory infiltrates. (B) Special staining with Grocott methenamine silver (GMS) stain highlighting broad, pauciseptate, wide-angled branching hyphae (black arrows), suggestive of Mucor.

 

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Discussion

Mucormycosis is a rare, opportunistic systemic mycosis with a grave prognosis, primarily affecting patients with uncontrolled diabetes and deranged immunocompetency (e.g., neutropenia, patients on chemotherapy or immunosuppressants, posttransplant patients, or patients with HIV/AIDS) and often proceeds rapidly with a fatal clinical course because of its angioinvasiveness, leading to tissue necrosis.[2]

Clinical presentation of mucormycosis varies according to the site of involvement and commonly encountered forms include rhinocerebral, pulmonary, gastrointestinal, and disseminated forms, of which the most common and most lethal form is the rhinocerebral one.[2] Disseminated forms are rarer and are characterized by the involvement of ≥ 2 noncontiguous sites, and have been frequently reported in patients with hematological malignancy having neutropenia or in posttransplant patients.[2] [3]

In our patient of CLL/SLL undergoing a Richter transformation, an abrupt deterioration of the clinical profile was noted, worsened by neutropenia postchemotherapy, predisposing the patient to a serious risk of contracting infections, which was unraveled to be a disseminated systemic mycosis on FDG PET-CT imaging with imaging features not in concordance with the lymphomatous disease.

Clinical aspects of mucormycosis have been adequately discussed in the literature, but only a limited number of articles have reported the FDG PET-CT imaging features and their implications, with almost negligible addressing the disseminated form.[3] [4] [5]

Although specific diagnosis is made on culture or histopathology, FDG PET-CT serves an important role in the management of mycotic infections by unveiling the extent of the disease, guiding biopsies, and posing as a valuable scaffold in the assessment of response to the antifungal treatment.

A combined approach is crucial and highly recommended in the management of mucormycosis comprising of surgical interventions (complete debridement or amputation) for source control and systemic antifungal treatment (amphotericin-B or azoles) and FDG PET-CT can provide valuable information in assisting the early initiation of treatment and thus improving the outcomes.[2] [6]

FDG PET-CT has become a part and parcel in the management of malignant diseases; however, at the same time, it has evolved as a sensitive imaging modality for infections and inflammations and one has to be vigilant of the differentiating imaging features between a malignant versus an infective/inflammatory etiology while reporting a PET-CT scan.

 

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Conflict of Interest

None declared.

• References

• 1 Douglas M. Richter transformation: clinical manifestations, evaluation, and management. J Adv Pract Oncol 2022; 13 (05) 525-534
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• 3 Sharma P, Mukherjee A, Karunanithi S, Bal C, Kumar R. Potential role of18F-FDG PET/CT in patients with fungal infections. AJR Am J Roentgenol 2014; 203 (01) 180-189
• 4 Liu Y, Wu H, Huang F, Fan Z, Xu B. Utility of 18 F-FDG PET/CT in Diagnosis and Management of Mucormycosis; 2013. [Online]. Accessed June 14, 2025 at: www.nuclearmed.com
• 5 Gallo F, Vija L, Le Grand S. et al. Diagnosis of an intestinal mucormycosis ‘fungus ball’ located with PET/CT with [¹⁸F] FDG-PET/CT. Eur J Hybrid Imaging 2019; 3 (01) 21
• 6 Facchinelli D, Marchesini G, Nadali G, Pagano L. Invasive fungal infections in patients with chronic lymphoproliferative disorders in the era of target drugs. Mediterr J Hematol Infect Dis 2018; 10 (01) e2018063

Publication History

Article published online:
08 July 2025