Lymphoma In HIV : A Case-based Discussion

Transcription

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