Lymphoma In HIV : A Case-based Discussion
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1 Lymphoma In HIV : A Case-based Discussion Prof Dipanjan Bandyopadhyay Kolkata dipanjanbandyo@gmail.com
2
3 To begin with a case 51 male, CD4 61 Headache, nausea, recurrent seizures On ZLN past 3 months, poor compliance Confused, oriented only to persons, uncooperative for neurological exam Neck soft, plantar left up
4 On evaluation CBC, LFT, electrolytes, sugar, creatinine: N CSF Protein 225mg/dl, sugar 80mg/dl Cells 280, all lymphocytes Fungal elements: absent ADA < 5 VDRL, CRAg, IgG Toxoplasma: Negative
5 MRI White matter hyperintensities in the right periventricular location with significant perilesional edema
6 Points favoring PCNSL Multiple lesions Lesions on either side of the midline Periventricular location EBV PCR positivity Negative Toxoplasma serology On sustained CTX prophylaxis
7 AIDS & lymphoma AIDS definition in 1985 Late in the natural history Not more common in MSM or in Africa Risk higher by 100% in HIV 95% CD19, CD20 positive
8 Epidemiology of cancers in HIV RR of cancers in HIV infected populations Kaposi s sarcoma 545 NHL 24.6 Hodgkin s lymphoma 13.1 Anal cancer 8.2 Leukemia 2.4 Lung cancer 1.9 Source: JAIDS 2004; 36:861 HAART has reduced AIDS associated cancers by 75%
9 Pathogenesis of cancers in HIV Immunodeficiency hampers immune surveillance CCR5 mutants are more oncogenic Other pathogenetic viruses contribute Antigen stimulation, polyclonal B cell expansion Non-infectious risk factors like smoking, alcohol HAART prolongs life, increases cancers
10 AIDS defining cancers High grade B-cell NHL Kaposi s sarcoma Invasive cervical cancer
11 Non-AIDS defining malignancies Anal HD: mixed cellularity / lymphocytedepleted Lung tobacco Testicular seminoma Skin: basal, squamous cell, melanoma Multiple myeloma Leukemia, M4, M5 Leiomyosarcoma in pediatrics
12 Initiating ART
13 International Collaboration on HIV and Cancer : ARL Occurring specifically in PLHIV Occurring in other immunodeficient states as well Occurring in immunocompetent persons as well
14 Occurring specifically in HIV Primary Effusion Lymphoma Plasmablastic lymphoma of the oral cavity
15 Occurring in other immunodeficient states Polymorphic B cell lymphoma
16 Occurring also in immunocompetent persons Burkitt Lymphoma Classic With plasmacytoid differentiation Atypical Diffuse large B cell lymphoma Extra nodal marginal zone B cell lymphoma of mucosa associated lymphoma tissue (rare) Peripheral T cell Lymphoma Classic Hodgkin Lymphoma Centroblastic Immunoblastic
17 AIDS related NHL Diffuse proliferative pattern Cellular pleomorphism B cell origin High grade Malignant
18 AIDS related NHL Systemic 80% Primary CNS 20% High grade, diffuse forms B symptoms Sites: CNS, BM, GIT, Liver
19 Case 1 47 yr/male, diagnosed HIV 6 years back Not on HAART Fever, SOB, Rt. chest heaviness x 3 months Pallor, right pleural effusion CT thorax: mediastinal LN+, Rt. Pleural effusion CT guided biopsy 19
20 C1: Mediastinal lymphadenopathy
21 Case 2 46 yr HIV +ve male on ZLN past 18 months Decreasing urine output x 1 week Altered sensorium, oliguria anuria Firm pelvic mass Rapidly rising serum creatinine and K +
22 CT scan abdomen: C2 Large pelvic (? Retroperitoneal) mass Complete obstruction of both ureters Bilateral hydronephrosis PD: Obstructive renal failure
23 C2: CT Abdomen
24 C2: CT Abdomen
25 C2 CT guided biopsy Left ureteral stenting Hemodialysis Died on 8 th post admission day Biopsy findings post mortem
26 Case 3 53 yr/ male, on ZLE past 4 years Generalised lymphadenopathy Sudden onset double vision Pain in right eye Rapidly progressive painful proptosis (R)
27 C3
28 C3: CT scan brain and orbit Right retro-orbital mass causing compression of right optic nerve Excision biopsy from cervical LN
29 Case 4 55/M, chronic alcoholic, on TLE past 1 year Pain abdomen, fever and weight loss x 3m CT abdomen: Large (10 X 8 cm) suprarenal mass compressing the liver and encasing the great vessels Guided trucut biopsy
30 C4: CT Abdomen
31 Case 5 54 / M, on ART past 3 years, non-compliant Spastic paraplegia, slowly progressive x 2 wks Bowel and bladder involvement MR spine: soft tissue paravertebral mass causing compressive myelopathy (D10- D12) CT guided trucut biopsy
32 C5: MRI Spine
33 C1 C5: HPE Sheets of monomorphic large lymphoid cells with prominent nucleoli, scant to moderate deeply basophilic cytoplasm and frequent mitotic figures, suggestive of diffuse large B-cell lymphoma
34 C1 C5: HPE
35 C1 C5: IHC Plasma cell markers CD38, CD138/syndecan Positive in all 5 B-cell markers CD3, CD20, CD30 Negative in all 5 4 patients were positive for EBER
36 Immuno-phenotype of PBL Negative for B cell narkers CD45 CD20, CD79a, PAX5 Positive for Plasma cell markers Multiple myeloma oncogene (MUM1) CD138 (Syndecan-1) CD 38 EBV encoded RNA (EBER)
37 Histopathology CD20 Negative CD138 Positive MUM1/IRF4 Positive Ki67 Positive EBER Positive
38 Chemotherapy in ARL AIDS Malignancy Consortium Chemotherapy for HIV associated NHL in combination with HAART J Clinical Oncology 19: , 2001
39 Low dose m-bacod, every 28 days Day 1 Cyclophosph 300mg/m 2 Doxorubicin 25mg/m 2 Vincristine 1.4mg/m 2 Bleomycin 4U/m 2 Dexamethasone 3mg/m 2, On days 1 4 Day 15 CNS Prophylaxis Cytosine arabinoside 50mg IT on days 1, 8, 21 and 28 of first cycle Helmet field RT with known CNS involvement MTX 500 mg/m 2
40 EPOCH in ARL Etoposide* 200mg/m 2 Prednisone 60mg/m 2 PO Vincristine 1.6mg/m 2 Doxorubicin 4U/m 2 Cyclophosphamide 187 or 375 mg/m 2 IT MTX on D1 & D5 3 rd cycle onwards * Continuous infusion over 96 hours
41 PBL: Clinical outcomes
42 HIV related NHL: An European multicohort study. Antivir Ther. 2009; 14(8): Exposure to low CD4 cell counts is the main risk factor for developing NHL, but with similar CD4 cell nadirs, ART treated patients had a lower risk of NHL compared to patients not on ART
43
44 Primary effusion lymphoma Neoplastic serous effusion No identifiable tumor, no nodes Infection by HHV-8, EBV B cell GF, VEGF, viral IL6 (lymphoma growth factors) +ve 1 5 % of ARL cases, occurs as end stage HIV Median survival 6 months
45 ARL : Diagnosis Biopsy, FNAC BMA CSF CT, MRI Gallium 67 scans FDG PET
46 Poor prognostic markers Age > 35 Poor performance status Stage III or IV Extra-nodal sites Prior AIDS LDH CD4
47 Favorable prognostic factors Presence of polyclonality Absence of EBV in the tumor CD4 cell count of > 300 cells / mm 3
48 A concluding case 51 year male, CD4 101 Epigastric pain Vomiting Low grade fever 2 years 6 months 6 months Emaciation
49 Visible epigastric lump
50 GOO
51 Laparotomy
52 Extensive mesenteric nodes: NHL
53 HIV & Lymphoma HAART has changed ARL, cure remains low Virologic failure predisposes to ARL Aggressive, extra nodal, EBV related Cytopenia of chemotherapy Early diagnosis of HIV Beyond opportunistic infections
54
2012 by American Society of Hematology
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