Lymphoma spillover.pptx

An array of presentation of lymphoma spillover in the peripheral smear and bone marrow. All types of lymphomas are discussed along with a bouquet of HPE pictures

1. INTERESTING CASE DISCUSSION - HEMATOLOGY DR TAMIL NILA POST GRADUATE

2. Case History A 65 year old female came with complaints of generalised lymphadenopathy Peripheral smear and Bone Marrow Aspiration was done

3. Peripheral Smear RBC – Hypochromic microcytes, normochromic normocytes, few macrocytes & polychromatophils WBC count normal. Few activated lymphocytes DC: N – 64 L – 30% E – 04% M – 02% Platelets normal in number & morphology

4. Bone Marrow Partly diluted marrow Erythropoiesis – MNB, NB Maturation Leucopoiesis active Atypical Blastoid cells upto 25% Megakaryocytes seen

5. Past History – Lymph node biopsy Excision biopsy from the Nodes showed effacement of architecture showing diffuse monotonous proliferation of lymphocytes Lymphoproliferative disorder

6. Past history - Immunohistochemistry CD 20 – positive CD 15 – negative CD 30 – Negative CD 3 – Negative Non Hodgkin’s Lymphoma

7. Lymphoma spill over in the Bone marrow In Correlation with the clinical history

8. Lymphoma work up Biopsy of lymph node/ organ showing lymphoma IHC History of B symptoms Blood counts Peripheral smear Bone marrow aspirate & Biopsy LDH, β 2 macroglobulin Rule out tumour lysis syndrome Radiology Gallium scan Staging

9. INTERNATIONAL PROGNOSTIC INDEX Age LDH Performance status Stage No of Extranodal sites Bone Marrow involvement

10. Patterns of Bone Marrow involvement

11. Frequency of Bone Marrow Involvement Lymphoma Percentage Follicular Lymphoma (Grade 1) 30.4% DLBCL 16% Mantle cell Lymphoma 9.3% Low Grade B cell lymphoma, NOS 8.7% Follicular Lymphoma (Grade 2) 7.1% Mature T & NK Cell Lymphoma 6.4%

12. Bone marrow involvement in CLL/SLL B cell Prolymphocytic leukemia Splenic Marginal zone lymphoma Hairy cell leukemia Follicular Lymphoma Lymphoplasmacytic Leukemia Mantle cell lymphoma DLBCL Burkitt lymphoma Intravascular B cell Lymphoma T – LGL leukemia T cell Prolymphocytic Leukemia Angioimmunoblastic T cell Lymphoma Anaplastic large cell lymphoma Hepatosplenic T cell Lymphoma Adult T cell Leukemia T cell /Histiocyte rich large B cell lymphoma Classical Hodgkin’s Lymphoma

13. Peripheral smear – CLL/SLL Small cells Clumped chromatin Minimal cytoplasm Larger cells – Prolymphocytes Single Prominent nucleolus Atypical CLL Larger cells Open chromatin

14. Bone Marrow Aspirate Small inconspicuous lymphocytes Large transformed cells with prominent nucleoli Richter transformation

15. Bone Marrow Biopsy in CLL Nodular Pattern Interstitial

16. IHC Biphasic pattern CLL/SLL cells – weak CD 20 positive DLBCL – strong positive

17. Peripheral Smear - B cell prolymphocytic leukemia Prolymphocytes Medium sized or 2x lymphocyte Nucleus – open chromatin Regular nuclear membrane Prominent central nucleolus Elevated lymphocyte count Anemia Thrombocytopenia

18. Bone Marrow Biopsy & IHC Diffuse infiltration of B-PLL cells CD 20 positivity

19. Peripheral smear - Splenic marginal zone lymphoma Numerous lymphoid cells Cytoplasmic projections Polar villi present

20. Bone Marrow & IHC Lymphoma cells in sinusoids Vague interstitial small lymphoid infiltrate CD 20 immunohistochemical study

21. Peripheral Smear - Hairy cell leukemia Medium sized cells Cytoplasm – abundant pale blue Circumferential projections Fine hair-like Nucleus – oval Inconspicuous nucleoli

22. Bone Marrow - Hairy cell leukemia Dry tap- reticulin fibrosis Monomorphic lymphoid cell collection Usually Sinusoidal pattern Fried egg appearance – central nucleus Abundant cytoplasm Distinct cell boarders Suppressed erythropoiesis

23. IHC CD 20 CD 11c TRAP

24. Transcription factor – T Box (T-Bet) CD 123

25. BRAF V600E DBA44

26. Paratrabecular growth Buttock cells Lymphoglandular bodies Suppresses hematopoiesis 2 cell types Centrocyte Small Irregular Dark nuclei Centroblast Larger Vesicular chromatin Peripheral nucleoli Bone Marrow -Follicular lymphoma

27. IHC CD 20 CD 10 BCL 6 BCL 2

28. Bone marrow - Lymphoplasmacytic lymphoma Post follicular B cell committed to plasma cell differentiation Bone marrow involved in most cases Dilated sinus – eosinophilic plasma protein Dutcher Bodies + Hemosiderin laden macrophages

29. IHC Kappa light chain – positive Lambda – Negative CD 19+ CD 20+ CD 138 + CD 38 + Lymphoid Plasmacytic

30. Bone Marrow - Mantle cell Lymphoma Small – medium sized lymphoid cells Resembling centrocytes Cyclin D1 + IHC depends on stage of cell cycle CD 5 + (weak) Any Pattern on BM infiltration

31. Blastoid variant Blastoid cells in peripheral smear Large, open chromatin, deeply clefted nuclear contour High mitotic count – BM Cyclin D1 negative SOX 11 positive

32. Bone Marrow - Diffuse Large B cell Lymphoma BM involved in 1/4 th Centroblastic / immunoblastic/pleomorphic cells CD 20 + BCL 2 + (double expresser)

33. Burkitt lymphoma – Bone marrow Medium sized mature B cell lymphoma Mitotic figures Scattered macrophages Starry sky appearance (10x) Dark blue cytoplasm with clear lipid vacuoles Ki67 +

34. T – LGL leukemia – PS & BM T cell LGL >2000 cells/cu.mm Cytopenias BM – hypercellular Interstitial or within sinusoids CD3 + CD 8 +

35. Angioimmunoblastic T cell lymphoma Paratrabecular Hypercellular Numerous large atypical lymphoid cells Rich in Eosionophils IHC PD-1 + CD 10 + CXCL 3 + CD 20 +

36. Anaplastic large cell lymphoma Patchy & subtle Large, epitheloid , cohesive cell clusters Loss of multiple pan-T cell antigens “null” phenotype CD 30+

37. Hepatosplenic T cell lymphoma Patchy ill defined clusters Paratrabecular atypical lymphohistiocytic aggregates Pleomorphic large lymphoid cells IHC TIA – 1 + TCR Beta + CD 68 – Concurrent hemophagocytosis

38. Adult T cell leukemia Circulating lymphoma cells – clefted, polylobate – flower cells Diffuse interstitial involvement Large cohesive lymphoma cells Irregular nuclear contours IHC CD3 + CD 4 + CD 25 + TCR - beta

39. Intravascular large B cell lymphoma Large atypical lymphoid cells within vessels IHC CD 20 + Variants Asian - aggressive Western – limited to skin

40. Classical Hodgkin’s lymphoma Marked paucity of neoplastic cells in a predominantly inflammatory background Vaguely nodular infiltrate at BM Scattered RS cells Large mononuclear cells with eosinophilic nucleoli IHC CD 30 + PAX 5 + PD – L1

41. T Cell Histiocyte rich large B cell lymphoma Scattered epithelioid granulomas Very few large atypical lymphoid cells within the granulomas Mimics NLPHL IHC CD 20 + ve PD – 1 - ve OCT 2 nuclear immunostain

42. References Tejinder Singh Atlas and Textbook of Hematology AAP Atlas of Bone Marrow Pathology Bone Marrow Diagnosis – Kevin Gatter and David Brown Wintrobe’s Clinical Hematology Williams Hematology Malignant Lymphoid Diseases Bone marrow biopsy involvement by non-Hodgkin's lymphoma: frequency of lymphoma types, patterns, blood involvement, and discordance with other sites in 450 specimens, Daniel A Arber   1 ,  Tracy I George