Adult T-Cell Leukemia/Lymphoma and Epstein-Barr Virus–Positive DLBCL: A Rare Concomitant Association

Introduction

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive malignancy of mature CD4-positive T cells commonly associated with the human T-lymphotropic virus 1 (HTLV-1). This hematological neoplasm presents in a variety of clinical forms, ranging from indolent to acute, with poor prognosis often linked to its advanced stages.¹ The Epstein-Barr virus (EBV), a well-known oncogenic virus, is frequently involved in the pathogenesis of various lymphoid malignancies, including diffuse large B-cell lymphoma (DLBCL).² The coexistence of ATLL with EBV-positive DLBCL is an exceptionally rare and complex phenomenon, with limited case reports detailing this dual malignancy. The presence of both EBV-positive DLBCL and ATLL in the same patient raises significant diagnostic and therapeutic challenges because both conditions require distinct treatment approaches.³

This case report presents the clinical course, histopathological findings, and treatment strategies for a patient diagnosed with composite ATLL and EBV-positive DLBCL. By discussing this rare occurrence, we aim to contribute to a better understanding of the diagnostic complexities and potential treatment paradigms for such dual malignancies.

Case Report

We present the case of a 47-year-old woman with multiple comorbidities, including hepatitis B, gastric ulcers, and irritable bowel syndrome, as well as a known allergy to ceftriaxone, which manifests as an erythematous cutaneous reaction at the injection site. Clinically, the patient presented with generalized lymphadenopathy (bilateral lateral cervical, submandibular, right supraclavicular, and bilateral inguinal regions), marked physical asthenia, exertional dyspnea, sweating, weight loss, and diarrhea. Additionally, the patient exhibited swallowing and speech disturbances along with mild intellectual disability.

During abdominal examination, diffuse mild tenderness is noted, both spontaneously and on palpation, and the spleen is palpable 5 cm below the costal margin. Biologically, the patient showed the following:

• Leukocytosis: white blood cell count, 18,060/mm³
• Lymphocytosis: lymphocyte count, 6050/mm³
• Monocytosis: monocyte count, 4470/mm³
• Mild thrombocytopenia: platelet count, 112,000/mm³

The patient also exhibited mild anemia (hemoglobin level, 12.7 g/dL) with hypochromia present on a peripheral blood smear. The smear showed polymorphic lymphocytes and lymphomonocytes, some with intensely basophilic cytoplasm, raising suspicion for an underlying hematologic condition.

Biochemical findings included the following:

• Elevated lactate dehydrogenase level: 591 IU/L
• Increased liver enzyme levels: aspartate aminotransferase, 120.9 IU/L; alanine aminotransferase, 112.7 IU/L
• Hypercalcemia: calcium level, 14.57 mg/dL
• Reduced renal function: estimated glomerular filtration rate, 49.55 mL/min/1.73 m²

Additionally, positive Clostridioides difficile glutamate dehydrogenase testing suggested an associated infectious component. Results of a bone marrow biopsy revealed high cellularity with a polymorphic appearance, 17% lymphocytes in the aspirate, and 50% lymphocytic infiltration. A subsequent node biopsy confirmed acute, lymphomatous ATLL. Imaging revealed metabolically active supradiaphragmatic lymphadenopathy with a Deauville score of 4 to 5. The patient was initiated on the CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], and prednisone) regimen with central nervous system prophylaxis (intrathecal administration of methotrexate and dexamethasone). During chemotherapy, the patient experienced multiple infectious complications, including pulmonary cryptococcosis, COVID-19, C difficile enterocolitis, pneumonia, and severe aplasia secondary to chemotherapy.

After completing 7 cycles, the patient developed a painful, firm, round-oval lesion of 7 to 8 cm in diameter in the upper third of the right thigh. It was palpable with well-defined borders, crusts, and a central necrotic area approximately 3 cm to 3.5 cm in size, with a purplish color (Figure 1).

Biologically, she presented with severe pancytopenia:

• Leukopenia: white blood cell count, 820/mm³
• Neutropenia: absolute neutrophil count, 610/mm³
• Severe anemia: hemoglobin level, 6.5 g/dL
• Thrombocytopenia: platelet count, 142,000/mm³

Results of a subcutaneous biopsy revealed another malignancy: DLBCL, EBV-positive, with intense expression of CD20 and CD30 (Figures 2-5).

Based on the diagnostic findings, a complete positive diagnosis of composite ATLL with EBV-positive DLBCL was given. Two weeks after the official diagnosis, the patient died due to multiple complications.

Discussion

This case highlights the diagnostic and therapeutic challenges observed in a 47-year-old woman with multiple associated comorbidities. Initially, the clinical findings and biological tests were concerning for a lymphoproliferative disorder due to generalized lymphadenopathy, exertional dyspnea, marked physical asthenia, weight loss associated with leukocytosis, lymphocytosis, monocytosis, mild anemia, and thrombocytopenia. The suspicion was enforced by the bone marrow and node biopsies, which confirmed the first malignant disorder: acute, lymphomatous ATLL. PET-CT imaging then revealed numerous metabolically active supradiaphragmatic lymphadenopathies, with a Deauville score of 4 to 5. Due to the poor status of the patient, the CHOP protocol with central nervous system prophylaxis was initiated. The evolution was unfavorable, with multiple infectious episodes in between cycles due to the severe postchemotherapy aplasia. The most notable infections were pulmonary cryptococcosis, COVID-19, C difficile enterocolitis, and pneumonia. Postchemotherapy aplasia is a serious, extremely frequent complication that can be followed by severe infections due to a patient’s compromised immune system.⁴

Protocols recommend administrating granulocyte colony-stimulating factor (G-CSF) from day 6 for 5 days.⁵ In our case, the administration of G-CSF did not prevent the severe aplasia and its infectious complications.

Moreover, another particularity was the presentation of a new, painful, firm, round-oval lesion after 7 cycles of treatment. Following the necessary investigations (histopathological analysis, immunohistochemical tests, PET-CT imaging), the positive diagnosis of EBV-positive DLBCL was made. Biologically, the patient was severely neutropenic and anemic. The B-cell lymphoma had a rapid, aggressive evolution, and the patient died 2 weeks after receiving a diagnosis.

A review of the literature identified 2 case reports on patients with severe immunodeficiency and composite lymphoma at the time of diagnosis,^3,6 matching the presentation of our patient. One patient developed cytomegalovirus retinitis and a tumor shortly after,¹ and the second patient also had miliary tuberculosis and human adenovirus 11–induced hemorrhagic cystitis.⁵ These findings highlight the development of hematological neoplasm, especially B-cell lymphomas, in severe immunodeficient states in patients with ATLL.

Conclusion

This case exemplifies the aggressive nature of ATLL and its potential to lead to secondary malignancies in immunocompromised patients. It underscores the complexity of treating such patients, highlighting the importance of close monitoring for secondary malignancies, the challenges of infection control in immunosuppressed patients, and the need for palliative care to manage complications and improve quality of life during such a severe disease course. The development of secondary DLBCL in this patient serves as a stark reminder of the high risk for malignancy in immunocompromised states and reinforces the need for vigilant screening and management strategies to address the multifaceted nature of these conditions.

References

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2. Shibusawa M, Kidoguchi K, Tanimoto T. Epstein-Barr virus-positive diffuse large B cell lymphoma. In: Gallamini A, Juweid M, eds. Lymphoma [Internet]. Exon Publications; 2021.

3. Sakamoto H, Imaizumi Y, Niino D, et al. Composite adult T-cell leukemia/lymphoma and Epstein-Barr virus-positive diffuse large B-cell lymphoma. Article in Japanese. Rinsho Ketsueki. 2020;61(4):305-311. doi:10.11406/rinketsu.61.305

4. Ba Y, Shi Y, Jiang W, Feng J, et al. Current management of chemotherapy-induced neutropenia in adults: key points and new challenges: Committee of Neoplastic Supportive-Care (CONS), China Anti-Cancer Association Committee of Clinical Chemotherapy, China Anti-Cancer Association. Cancer Biol Med. 2020 Nov 15;17(4):896-909. doi: 10.20892/j.issn.2095-3941.2020.0069. Epub 2020 Dec 15. PMID: 33299642; PMCID: PMC7721096.

5. R-CHOP-21. Thames Valley Cancer Alliance, Oxford University Hospitals NHS Foundation Trust. Accessed March 12, 2026. https://tinyurl.com/3ktcdp2b

6. Tobinai K, Ohtsu T, Hayashi M, et al. Epstein-Barr virus (EBV) genome carrying monoclonal B-cell lymphoma in a patient with adult T-cell leukemia-lymphoma. Leuk Res. 1991;15(9):837-846. doi:10.1016/0145-2126(91)90468-9