HIVor AIDS –ASSOCIATED LYMPHOMAS H.A. MWAKYOMA, MD

CURRENT FACTS HIV patients have increased incidence of certain tumours Kaposis sarcoma Non-hodgkin lymphoma Cervical cancer Scc conjuctiva Ano rectal carcinoma Leiomyosarcoma in children

AIDS Defining Malignancies (ADMs KS Lymphoma: PCNSL, Immunoblastic, Burkitt’s, Primary Effusion Cervical carcinoma

Non-Hodgkin lymphoma Recognised as part of AIDS in 1982 Characteristically aggressive and often involve extra nodal sites Some HIV individuals are more prone to develop lymphoma than others

Aetiology and pathogenesis Lymphomas develop against a background of chronic antigenic stimulation and most are of B-cell origin Cytokenes stimulate expansion once malignant transformaton has occurred(IL-6, TNF-beta and IL-10) Chemokines produced by HIV infected macrophages and monocytes produce autocrine stimulation of the abnormal clone

Clinico-pathological categories of HIV related lymphomas Diffuse large cell lymphoma(DLCL) Large non cleaved (LNCCL) ebv 40% Immunoblastic plasmacytoid (IBPL) 90% Burkitt’s lymphoma (BL) ebv 30% Primary lymphomas of the central nervous system(PCNSL) ebv 100% Primary effusion lymphomas (PEL) ebv 90%, HHV-8 100%

Clinico-pathological categories of HIV related lymphomas Degree and duration of HIV affects type of lymphoma that developes: Primary CNS lymphomas are associated with profound immunosuppression and occur late in the course of HIV The other types may occur early Extranodal lymphomas more common in AIDS patients

NHL 70-90% High grade B cell lymphomas (large B cell, immunoblastic, Burktt’s—c-myc translocation) PCNSL—15% (Primary Central Nervous System Lymphoma) Primary Effusion Lymphoma (“Body Cavity Lymphoma”)—rare

NHL Present at more advanced stage, extranodal disease (GI tract common), bone marrow, liver and lung, CNS, 80% Stage 4 disease at presentation More often with “B” sx—night sweats, fever, weight loss Incidence inversely related to CD4 count but can occur at any CD4 Diagnosis same as in non-HIV pt but higher rate of asymptomatic CNS involvement FNA usually not adequate, need excisional BX

AETIOLOGY -NHL Immunodeficiency Infectious agents(other than HIV) congenital Acquired Autoimmune Infectious agents(other than HIV) H.pylori EBV HTLV-1 HHV8-kaposi sarcoma related

BURKITT`S LYMPHOMA

BURKITT`S LYMPHOMA Highly aggressive type of NHL -B cell type Accounts for approx. 40% of childhood lymphomas Two types Endemic - associated with EBV(95%) Frequent involvement of jaw and other facial bones Sporadic Extensive intra abdominal and bone marrow involvement common Histologically - starry sky appearance

BL- CLINICAL PRESENTATION Abdomen is the most common presenting site in sporadic cases . Typically seen in boys of 5 – 10 years age group Exploratory laparotomy is indicated for diagnosis Head and neck region is common site in endemic cases Less common sites-epidural mass, skin nodules,bone and bone marrow

Primary Effusion Lymphoma Rare HHV-8 Serous effusions (pleural, peritoneal, pericardial, joint effusions) with malignant lymphocytes No mass lesions Very poor prognosis

PEL Primary effussion lymphomas (body cavity lymphomas) Pleural effusion or ascitis without evidence of bulk disease Thickening of pleural or peritoneal membranes with no evidence of tumour masses Symptoms are from accumulation of fluid Dyspnoea, chest or abdominal discomfort

PCNSL Primary CNS 75% develop in known AIDS patients 50% have CD4 of less than 50/dl Symptoms similar to SOL (headache, change in consciousness, focal neurological symptoms, visual disturbances) Rapid onset and therefore difficult to differentiate from infection

PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA NHL arising in and confined to the CNS Incidence: 0.5-1%of all intracerebral neoplasms 1.9-6% HIV pt Immunodeficient state, renal transplantation Common in 6th to 7th decade

PCNSL EBV 100-1000x higher than general population CD4<100, usually <50 Dx: LP +EBV, MRI with homogeneous, sometimes ring enhancing lesions, often peri-ventricular, often +mass effect, Prognosis: poor in pre-HAART era, overall still very poor

PCNSL-Clinical Presentation Disseminated lesion , Brain (Common) Eye (20%) , Leptomeninges (7%) Spinal Cord Clinical Stage – Stage I E Pathology – Intermediate Malignant type Investigations – CSF study Ophthalmic exam with slit lamp CXR, CT- Abd, Cranial/spinal MRI with Gadolinium Stereotactic biopsy

Hodgkin’s Lymphoma and HIV Usually advanced stage at time of diagnosis (stage 3,4) More extra-nodal involvement—bone marrow, liver Worse prognostic cell type—mixed cellularity histologic subtype (nodular sclerosis most common in non-HIV) Worse overall prognosis Better outcomes in era of HAART