Approach Considerations

The workup of AIDS-related lymphoma includes laboratory studies, imaging studies, and biopsies. Specific choices in the workup should be guided by the patient's signs and symptoms (see Presentation/History and Physical). In addition, opportunistic infections should be evaluated.

Laboratory Studies

Laboratory studies should include the following:

Complete blood count (CBC) with differential
Complete metabolic panel (CMP)
Lactate dehydrogenase (LDH)
Tumor lysis assays (potassium, phosphorus, calcium, uric acid)
CD4 count
HIV viral load
Hepatitis B and C screening

Imaging Studies and Procedures

Position emission tomography (PET) and/or computed tomography (CT) are generally used for staging purposes.^[30] Bone marrow biopsy is recommended for unexplained cytopenias.^[31] In addition, endoscopy or bronchoscopy may be considered if gastrointestinal (GI) tract or pulmonary involvement is suspected.^{[32, 33]}

If central nervous system (CNS) involvement is suspected, neuroimaging with contrast-enhanced MRI or CT and lumbar puncture is recommended.^[34] All patients with HIV-related Burkitt lymphoma and selected patients with diffuse large B-cell lymphoma (DLBCL) who are at high risk for CNS involvement should undergo CNS evaluation.^[35]

Cerebrospinal fluid (CSF) analysis should include the following studies:

Cell count
Protein and glucose level
Cytology
Flow cytometry
Immunoglobulin heavy-chain (IgH) rearrangement studies
Polymerase chain reaction (PCR) for Epstein-Barr virus and JC virus

Tissue Evaluation

Histological confirmation is usually obtained with biopsy of involved tissue. Excisional biopsy or multiple core biopsies are preferred, while fine needle aspirations (FNA) are suboptimal.

In primary CNS lymphoma, diagnosis can also be obtained by cerebrospinal fluid evaluation (see Imaging Studies and Procedures). In primary effusion lymphoma, diagnosis can also be obtained from malignant cells with human herpesvirus 8 (HHV-8) in effusion or ascites samples.

Treatment & Management

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Media Gallery

Burkitt lymphoma under low magnification showing sheets of atypical mononuclear cells. Scattered macrophages can be seen (as demonstrated by the green arrows) giving rise to classical "starry-sky" pattern.
Burkitt lymphoma under high magnification showing sheets of atypical mononuclear cells. The cells are intermediate to large in size with scant cytoplasm, round to irregular nuclear contour, smudged chromatin and some with nucleoli. Mitosis and apoptosis are frequent with scattered macrophages giving focal "starry-sky" pattern. Green arrows = macrophages; yellow arrows = mitosis.
Diffuse large B cell lymphoma under low magnification showing diffuse proliferation of large atypical lymphoid cells in this lymph node specimen.
Diffuse large B cell lymphoma under high power showing cells that have moderate to abundant cytoplasm, round to irregular nuclear contour, vesicular nuclear chromatin and one to multiple nucleoli. Scattered small mature lymphocytes are seen. Green arrows = atypical lymphocytes; yellow arrows = small lymphocytes.

of 4

Table 1: Incidence and relative risk of AIDS-related lymphoma subtypes

Lymphoma subtype	Incidence (% of HIV-related lymphomas)	Relative risk (compared with the general population)
DLBCL, immunoblastic variant	64	652
Burkitt lymphoma	21	260
Indolent B-cell lymphoma	< 10	15
T-cell lymphoma	3	15
Hodgkin lymphoma	< 10	15-30
Primary CNS lymphoma	2-6	1000
Plasmablastic lymphoma	3	>1000
Primary effusion lymphoma	< 1	>1000

Table 2: Common chemotherapeutic options for initial treatment of AIDS-related DLBCL

Chemotherapy	Outcomes (complete remission rate %)	Indication
CHOP	63^[39]	Most patients with advanced-stage disease; addition of rituximab recommended for CD20+ disease when CD4 count over 50 /μL
Dose-adjusted EPOCH	74^[40]	Patients with a high proliferation index or plasmabatic histology; addition of rituximab recommended for CD20+ disease when CD4 count > 50 /μL
CDE	45^[41]
CDE = cyclophosphamide, doxorubicin, etoposide; CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; EPOCH = etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (hydroxydaunorubicin)

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Author

Christina Poh, MD Clinical Assistant Professor of Medicine, Division of Medical Oncology (Lymphoma), University of Washington School of Medicine

Christina Poh, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, American Society of Hematology, Hemostasis and Thrombosis Research Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Incyte Morphosys<br/>Received research grant from: Incyte Morphosys.

Coauthor(s)

Joseph M Tuscano, MD Associate Chief, Department of Hematology/Oncology/Internal Medicine, Veterans Administration Northern California System of Clinics; Professor, Department of Internal Medicine, Division of Hematology/Oncology, University of California, Davis, School of Medicine

Joseph M Tuscano, MD is a member of the following medical societies: American Association of Immunologists, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Mudassar Zia, MD Assistant Professor of Medicine, University of Missouri-Kansas City School of Medicine

Mudassar Zia, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Hesham M Taha, MD, FACP, MRCP(UK) Attending Physician, Department of Internal Medicine, Division of Hematology/Oncology, Nassau University Medical Center

Hesham M Taha, MD, FACP, MRCP(UK) is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology, Royal College of Physicians, American Society of Clinical Oncology, Royal College of Physicians and Surgeons of Glasgow

Disclosure: Nothing to disclose.

Muhammad A Mir, MD, FACP Assistant Professor of Medicine (Hematology, Blood/Marrow Transplant) Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Muhammad A Mir, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Acknowledgements

Adnan A Jabbar, MD, PhD Adjunct Clinical Assistant Professor, Department of Medicine, New York College of Osteopathic Medicine of NY Institute of Technology; Fellow, Hematology and Medical Oncology, Emory University

Adnan A Jabbar, MD, PhD is a member of the following medical societies: American College of Physicians, American Medical Association, Chicago Medical Society, and Sigma Xi

Disclosure: Nothing to disclose.

Hesham M Taha, MD, FACP, MRCP(UK) Attending Physician, Department of Internal Medicine, Division of Hematology/Oncology, Nassau University Medical Center

Hesham M Taha, MD, FACP, MRCP(UK) is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, Royal College of Physicians, and Royal College of Physicians and Surgeons of Glasgow

Disclosure: Nothing to disclose.

Acknowledgments

Medscape Reference and the previous authors would like to thank the following physicians for their valuable contributions to this article: Roshan Patel, MD, Department of Pathology, Westchester Medical Center-NYMC and Kyle Bradley, MD, Department of Pathology, Emory University School of Medicine.