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, β2 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 1/4th
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 AArber 1, Tracy I George