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Lymphoma & other HIV-related malignancies. AM report 9/30/2009 Darrell Laudate. Non-AIDS defining malignancies & HIV.

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Lymphoma other hiv related malignancies

Lymphoma & other HIV-related malignancies

AM report 9/30/2009

Darrell Laudate

Non aids defining malignancies hiv
Non-AIDS defining malignancies & HIV

  • As patients have survived longer with AIDS, the frequency of non-AIDS-defining malignancies has increased compared to the non-HIV-infected population, and cancer deaths have accounted for an increasing fraction of the deaths in HIV-infected individuals.

    • probably reflects a true increased prevalence, combined with greater screening, more frequent detection of incidental lesions, better reporting, and longer survival in the HIV-infected population 1

  • The usual suspects: Lung, Breast, , Prostate, Testicular, Bladder, Renal, Colorectal

  • Also , HCC, Skin (BCC, SCC, Melanomas), Head & Neck SCC, Conjunctival Ca, Hematologic Malignancies (Hodgkins, Plasma Cell disorder, AML)

Aids defining malignancies
AIDS defining Malignancies

  • Kaposi's Sarcoma

  • Invasive Cervical Cancer (as well as malignancies of the anogenital tract, including the anus, vulva, penis, and perianal skin)

  • NHL 

  • Primary CNS Lymphoma

Role of hiv in malignancy
Role of HIV in Malignancy

  • not generally considered oncogenic, a direct pathogenic role for HIV infection has been suggested by the following observations:

    • Components of the HIV viral genome have been incorporated into the fur gene complex on chromosome 15 in some cases of HIV-associated non-B cell malignant lymphomas.2

    • The HIV tat gene protein product appears to be a growth factor for KS. 

  • Other viruses including EBV, HPV, HHV-8, HBV, & HCV

Role of haart
Role of HAART

  • HAART causes both an immunologic response (manifested by a sustained elevations in CD4 lymphocyte counts) and a virologic response (nearly complete suppression of HIV viral replication).  

  • Both of these responses are important in achieving at least partial immune restoration, and thus decreasing the incidence of opportunistic infections, reducing the risk of developing NHL or KS, and prolonging survival. 

  • Since the widespread introduction of HAART, the incidence of KS and NHL has declined in HIV-infected patients, and is inversely proportional to the CD4 lymphocyte count.3

Who real classification of lymphoid neoplasms

B-Cell Neoplasms

Precursor B-cell neoplasm

Precursor B-lymphoblastic leukemia/lymphoma

(precursor B-acute lymphoblastic leukemia)

Mature (peripheral) B-neoplasms

B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma

B-cell prolymphocytic leukemia

Lymphoplasmacytic lymphoma‡

Splenic marginal zone B-cell lymphoma

(+ villous lymphocytes)*

Hairy cell leukemia

Plasma cell myeloma/plasmacytoma

Extranodal marginal zone B-cell lymphoma of MALT type

Nodal marginal zone B-cell lymphoma

(+ monocytoid B cells)*

Follicular lymphoma

Mantle cell lymphoma

Diffuse large B-cell lymphoma

Mediastinal large B-cell lymphoma

Primary effusion lymphoma†

Burkitt’s lymphoma/Burkitt cell leukemia§

T and NK-Cell Neoplasms

Precursor T-cell neoplasm

Precursor T-lymphoblastic leukemia/lymphoma

(precursor T-acute lymphoblastic leukemia

‡ Formerly known as lymphoplasmacytoid lymphoma or immunocytoma

II Entities formally grouped under the heading large granular lymphocyte

leukemia of T- and NK-cell types

* Provisional entities in the REAL classification

Mature (peripheral) T neoplasms

T-cell chronic lymphocytic leukemia / small

lymphocytic lymphoma

T-cell prolymphocytic leukemia

T-cell granular lymphocytic leukemiaII

Aggressive NK leukemia

Adult T-cell lymphoma/leukemia (HTLV-1+)

Extranodal NK/T-cell lymphoma, nasal type#

Enteropathy-like T-cell lymphoma**

Hepatosplenic γδ T-cell lymphoma*

Subcutaneous panniculitis-like T-cell lymphoma*

Mycosis fungoides/Sézary syndrome

Anaplastic large cell lymphoma, T/null cell,

primary cutaneous type

Peripheral T-cell lymphoma, not otherwise characterized

Angioimmunoblastic T-cell lymphoma

Anaplastic large cell lymphoma, T/null cell,

primary systemic type

Hodgkin’s Lymphoma (Hodgkin’s Disease)

Nodular lymphocyte predominance Hodgkin’s lymphoma

Classic Hodgkin’s lymphoma

Nodular sclerosis Hodgkin’s lymphoma (grades 1 and 2)

Lymphocyte-rich classic Hodgkin’s lymphoma

Mixed cellularity Hodgkin’s lymphoma

Lymphocyte depletion Hodgkin’s lymphoma

† Not described in REAL classification

§ Includes the so-called Burkitt-like lymphomas

** Formerly known as intestinal T-cell lymphoma

# Formerly know as angiocentric lymphoma

WHO/REAL Classification of Lymphoid Neoplasms

When to suspect lymphoma
When to suspect Lymphoma

  • Suspicious PMH

    • Positive family history

    • Radiation, chemotherapy, immunosuppressive agents

    • Infectious agents

      • HIV, HTLV-1, EBV, HCV, HBV

    • Connective tissue diseases

      • SLE, RA, Sjogren’s

    • Immunodeficiency's

    • Cryoglobulinemia

    • IBD treated with Azathioprine

  • Unexplained “B” symptoms

  • Lymphadenopathy

Hiv and nhl

  • AIDS-related lymphoma is generally divided into three type:

    • Systemic non-Hodgkin lymphoma (most common)

    • Primary CNS lymphoma

    • Primary effusion ("body cavity") lymphomas

  • HIV immunosuppression and coinfection with EBV seem to drive B cell clonal expansion

  • 70% of lymphomas in HIV have mutations resulting in deregulation of BCL-6 proto-oncogene

  • Diffuse lymph node involvement is considered much less common

  • Marrow involvement 30% of time

    • thus consider marrow biopsy if no other sites

  • 80% present with Stage IV disease

Clinical presentation
Clinical Presentation

  • “B” symptoms

    • more common in patients with aggressive and highly aggressive histologies (47%), especially in those with hepatic and extranodal involvement.

    • In contrast, less than 25% of patients with indolent lymphomas have B symptoms

  • Systemic complaints of fatigue, malaise, and pruritus occur less frequently in fewer than 10%

  • Bone pain or gastrointestinal symptoms may indicate extranodal involvement in these areas  

  • > 2/3 of patients with NHL present with peripheral LAD

  • CNS involvement

    • lethargy, focal neurologic symptoms, seizures, or paralysis

    • Rare - spinal cord compression, meningitis

Physical exam
Physical Exam

  • Lymph Nodes


    • Waldeyer’s Ring involvement in NHL>HL

    • CNS Lymphomas can affect cranial nerves

  • Chest

    • SVC Syndrome, pleural effusions

  • Abd/pelvis

    • Retroperitoneal, mesenteric, pelvic nodes in NHL>HL

    • If large enough, leads to nausea, early satiety, anorexia

  • GU

    • Testicular masses (men >60yo NHL is #1 malignancy of testes)

  • CNS

Labs imaging

  • CBC w/ differential and smear for evaluation Unexplained anemia, thrombocytopenia, or leukopenia due to extensive bone marrow infiltration or hypersplenism from splenic involvement

  • Renal and hepatic function, including LDH

  • Hypercalcemia (present in 15% but not usually symptomatic)

  • Hyperuricemia causing symptoms of gout or nephrolithiasis are unusual at presentation

    • certainly a concern following treatment of a rapidly proliferative NHL

  • Testing for HIV, HBV, and HCV (in select patients)

  • CXR

    • Mediastinal involvement, SVC compression, effusions

    • Intrathoracic involvement HL>NHL, but parenchymal involvement NHL>HL

  • CT Abd/Pelvis

    • Particularly for Staging

  • BM Biopsy often considered especially when biopsy would be otherwise difficult to obtain

  • Lumbar puncture (if CNS involvement suspected)

Ann arbor staging
Ann Arbor Staging

I. 1 nodal group

II. 2 nodal groups on the same side of the diaphragm

III. Disease above and below the diaphragm

IV. (Extranodal) Disease in other organs

Tissue is the issue
Tissue is the Issue

  • When to biopsy a Lymph Node? 4


    Tenderness Generalized Pruritus

    Size < 1cm Supraclavicular


    Courtesy of Lee Berkowitz

Fna vs excisional biopsy
FNA vs Excisional Biopsy

  • Accurate histopathologic evaluation of sufficient neoplastic tissue, preferably an intact lymph node, is critical. Although a tissue diagnosis can be suggested by fine needle aspiration (FNA), an excisional biopsy is often required in order to confirm the FNA findings of “lymphoma”5

  • Only an excisional biopsy of an intact node consistently allows sufficient tissue for histologic, immunologic, molecular biologic assessment, and classification

  • If no peripheral lymph nodes accessible for biopsy, consider CT guided biopsy vs laproscopic evaluation


  • Pantanowitz et al. Evolving spectrum and incidence of non-AIDS-defining malignancies. Curr Opin HIV AIDS 2008; 4:27.

  • Shiramizu et al. Identification of a common clonal human immunodeficiency virus integration site in human immunodeficiency virus-associated lymphomas.; Cancer Res 1994 Apr 15;54(8):2069-72

  • Biggar et al. AIDS-related cancer and severity of immunosuppression in persons with AIDS. J Natl Cancer Inst. 2007 Jun 20;99(12):962-72. Epub 2007 Jun 12

  • Vasilakopoulos et al. Application of a Prediction Rule to Select which Patients Presenting with Lymphadenopathy Should Undergo a Lymph Node Biopsy. Medicine 79(5) 2000:338 – 47.

  • Hehn et al. Utility of fine-needle aspiration as a diagnostic technique in lymphoma. J Clin Oncol 2004 Aug 1;22(15):3046-52.

  • Berkowitz. Lymphoma for the Internist ppt. Oct 2007