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Lymphoma & other HIV-related malignancies

Lymphoma & other HIV-related malignancies

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Lymphoma & other HIV-related malignancies

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

  2. 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)

  3. 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

  4. 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

  5. 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

  6. NHL Overview

  7. 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

  8. 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

  9. 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

  10. 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

  11. Physical Exam • Lymph Nodes • HEENT • 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

  12. 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)

  13. 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

  14. Tissue is the Issue • When to biopsy a Lymph Node? 4 NegPositive Tenderness Generalized Pruritus Size < 1cm Supraclavicular Hard Courtesy of Lee Berkowitz

  15. 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

  16. References • 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. http://www.med.unc.edu/medicine/web/10.2.07%20Lymphoma%20Berkowitz.ppt. Oct 2007