Lymphoid Neoplasm

1. Lymphoid Neoplasm Nirwansyah Parampasi Department of Pathology Untad

3. Neoplastic proliferations of white cells • Lymphoid Neoplasms • Myeloid Neoplasms - Acute myelogenous leukemia - Myelodysplastic syndromes - Chronic myeloproliferative disorders • Histiocytosis  Langerhans cell hitiocytosis

4. Lymphoid Neoplasmsclose to immune regulatory system • Lymphoid neoplasm are tumors of the immune system  disrupt normal immune regulatory mechanisms • Evidences: susceptibility to infection, autoimmune diseases

5. Lymphoid Neoplasmsclose to immune regulatory system • Patients with inherited or acquired immunodeficiency are at high risk of developing certain lymphoid neoplasm, particularly these associated with EBV infection

6. Lymphoid Neoplasms • All lymphoid neoplasms are derived from single transformed cell  monoclonal • Divided into 2 big groups: - Non Hodgkins Lymphoma(NHL) - Hodgkins Lymphoma (HL)

7. Lymphoid Neoplasms • NHLs often present as involvement of a particular tissue site • Sensitive molecular assay usually show that the tumor is widely disseminated at the time of diagnosis  only systemic therapy are curative

8. Lymphoid Neoplasms • HLs are often presents at a single site  spreads methodically to contiguous lymph nodes group • Early course tumors may be cured with local therapy alone

9. Lymphoid Neoplasms • HL spreads in orderly fashion, and as a result STAGING is of importance in determining therapy • The spread of NHL is less predictable  most patients are assumed to have systemic disease at the time of diagnosis  staging in particular NHL provides useful prognosis information, but generally not important in guiding therapy

10. E T I O L O G Y • Chromosomal translocation: Chronic Meylocytic Lymphoma (CML), Burkitt lymphoma • Inherited genetic factors: Bloom syndrome, Fanconi anemia, ataxia telangiectasia, Down syndrome • Viruses: HTLV-1, EBV, KSHV, HHV-8 • Environmental agents: Helicobacter pylorii (gastric B-cell lymphoma), gluten-sensitive enteropathy (T-cell lymphoma), HIV (B-cell lymphoma) • Iatrogenic factors: radiotherapy & chemotherapy  mutagenic effect

11. Lymphoid Neoplasms Certain relevant principles must be emphasized • Can be suspected from the clinical features, but histological examination of lymph nodes and other involved tissue is required for diagnosis • The vast majority of lymphoid neoplasm (80% - 85%) are of B-cell origin; most of the remainder being T-cell tumors; only rarely are tumors of NK origin encountered • Two basic forms of B-cell lymphoma: follicular & diffuse type

12. The WHO Classification of theLymphoid Neoplasms • Precursor B-cell Neoplasms: neoplasms of immature B-cells • Peripheral B-cell Neoplasms: neoplasms of mature B-cells • Precursor T-cell Neoplasms: neoplasms of immature T-cells • Peripheral T-cell and NK-cell Neoplasms: neoplasms of mature T-cell and NK-cell • Hodgkin Lymphoma: neoplasms of Reed-Sternberg cells and variants

13. Origin of Lymphoid Neoplasms CLP: common lymphoid precursor; BLB: pre-B lymphoblast; NBC: naive B-cell; MC: mantle B-cell; GC: germinal center B-cell; MZ: marginal zone B-cell; DN: CD4/CD8 double negative pre-T cell; DP: CD4/CD8 double positive pre-T cell; PTC: peripheral T-cell

15. Precursor B & T cell neoplasms • Acute lymphoblastic Leukemia (ALL): contain of immature cells, precursor B / T cells (lymphoblast) • 85% arising from precursor B cell  childhood acute leukemia • The less common, from precursor T cell  adolescent males lymphoma

16. Precursor B & T cells neoplasms • There is overlap in the clinical behaviour of B & T-ALL. • B-ALL uncommonly presents as a mass in the skin/ bone and T-ALL presents with leukemic picture • ALL must be distinguished from CML due to differing response to chemotherapy

17. The Classification of theLymphoid Neoplasms WHOPrecursor B-cell NeoplasmsDiagnosis: precursor B lymphoblastic leukemia/lymphoma • Asal: sel B prekursor sumsum tulang mengekspresikan TdT • tidakmengandung Ig permukaan • Genotipa: • translokasi kromosom t(12;21), • CBFα dan ETV6 rearrangement • Klinis:agresif • predominan pada anak-anak, • gejala : pansitopeni

18. The WHO Classification of theLymphoid NeoplasmsIII. Precursor T-cell NeoplasmsDiagnosis: precursor T lymphoblastic leukemia/lymphoma • Asal: prekursor sel T, sering dari timus • Mengekspresikan TdT • Genotipa: • Translokasi kromosom, lokus reseptor sel T • Paling sering rearrangement TAL1

19. Acute lymphoblastic leukemia / lymphoma • Originate from B-cell or T-cell, mostly from T-cell • Can be differed by B-cell marker CD22 • The nuclear chromatin is delicate and finely stippled, • and nucleoli are either absent or inconspicuous

20. The WHO Classification of theLymphoid NeoplasmsII. Peripheral B-cell Neoplasms • CLL / small lymphocytic lymphoma • B-cell prolymphocytic leukemia • Lymphoplasmacytic lymphoma • Splenic and nodal marginal zone lymphoma • Extranodal marginal zone lymphoma • Mantel cell lymphoma • Follicular lymphoma • Marginal zone lymphoma • Hairy cell leukemia • Plasmacytoma / plasma cell myeloma • Diffuse large B-cell lymphoma • Burkitt lymphoma

21. II. Peripheral B-cell Neoplasms Small Lymphocytic LeukemiaSmall Lymphocytic Lymphoma • The two indistinguishable disorders: - morphologically, phenotypically - genotypically differing in the degree of peripheral blood lymphocytosis • Proliferation center: loose aggregates of pro-lymphocyte  pathognomonic • Tumor cells usually infiltrate the splenic white and red pulp, and the hepatic portal tract, although the extent of involvement varies widely.

22. II. Peripheral B-cell Neoplasms Small Lymphocytic LeukemiaSmall Lymphocytic Lymphoma Diffuse effacement of nodal architecture The majority of the tumor cells are small round lymphocytes. Arrow: pro-lymphocyte

23. II. Peripheral B-cell Neoplasms Follicular Lymphoma • The most common form of NHL in the USA (45% of adult lymphomas) • Usually present in the middle age and afflicts males and females equally • Less common in Europe, and rare in Asian population • The tumor cells closely resemble normal germinal center B-cells

24. II. Peripheral B-cell Neoplasms Follicular Lymphoma • In most cases, at low magnification, a predominantly nodular or nodular and diffuse growth pattern is observed • Involvement: bone marrow (85%), spleen, liver • Te overall median survival is 7 to 9 years, is not improved by aggressive therapy

25. II. Peripheral B-cell Neoplasms Follicular Lymphoma • Two principle cells are observed in varying proportion: (1) small cell with irregular or cleaved nuclear contour and scant cytoplasm  centrocyte (2) larger cells with open nuclear chromatin, several nucleoli, and modest amount of cytoplasm  centroblast

26. Follicular Lymphoma (spleen) Prominent nodules represent white pulp follicles expanded by follicular lymphoma cells

27. Follicular Lymphoma Malignant lymph follicles are marked by Bcl-2 positive

28. Follicular Lymphoma Small lymphoid cells with condensed chromatin and irregular or cleaved nuclear outline (centrocyte), mixed with a population of larger cells with nucleoli (centroblast)

29. Mantle cell lymphoma Neoplastic lymphoid cells surround a small, atrophic germinal center  exhibiting mantle zone pattern of growth Homogenous population of small lymphoid cells with somewhat irregular nuclear outlines, condensed chromatin, and scant cytoplasm.

31. II. Peripheral B-cell Neoplasms Diffuse large B-cell lymphoma(DLBCL) • Slight male predominance • Average age about 60 years • 5% of childhood lymphoma • Clinically present with a rapidly enlarging, often asymptomatic mass, at a single nodal or extranodal site

32. Diffuse large B-cell lymphoma Spleen: typical isolated large mass

33. Diffuse large B-cell Lymphoma Tumor cells show prominent nucleoli

34. Diffuse large B-cell lymphoma Tumor cells with large nuclei, open chromatin, and prominent nucleoli

35. II. Peripheral B-cell Neoplasms Burkitt lymphoma • Categories: (1) African (endemic) Burkitt lymphoma, (2) sporadic (non-endemic), (3) a subset of aggressive lymphoma occuring in individual with HIV infection • Responds well to short-term, high dose chemotherapy (children & young adults) • Clinical feature Both endemic & non-endemic are found largely in children and young adults (30%) • Most tumor manifests at extra-nodal sites

36. Burkitt lymphoma Low power: many tingible body macrophages  Starry sky appearance Monotonous appearance, tumor cells with multiple small nucleoli and high mitotic index (typical)

37. Burkitt Lymphoma Several starry sky macrophages was shown (arrows)

38. II. Peripheral B-cell Neoplasms Multiple myeloma of the skull The sharply punched-out bone lesions are most obvious in the calvarium

39. Multiple myeloma (bone aspirate) Normal marrow cells are replaced by plasma cells

40. Lymphoplasmacytic lymphoma Bone marrow biopsy: various degrees of plasma cell differentiation Mast cell

41. The WHO Classification of theLymphoid NeoplasmsIV. Peripheral T&NK-cell Neoplasms • T-cell prolymhocytic leukemia • Large granular lymhocytic leukemia • Mycosis fungoides / Sezary syndrome • Peripheral T-cell lymphoma, unspecified • Anaplastic large cell lymphoma • Angioimmunoblastic T-cell lymphoma • Enteropathy-associated T-cell lymphoma • Panniculitis-like T-cell lymphoma • Hepatosplenic γδ T-cell lymphoma • Adult T-cell leukemia/Lymphoma • NK/T-cell lymphoma, nasal type • NK-cell leukemia

42. IV. Peripheral T&NK-cell LymphomaPeripheral T-cell lymphoma • T-cell lymphoma without specific defining features fall collectively into the category of “unspecified” • Account for approximately half of all T-cell lymphoma in the western world • As a group they are aggressive malignant with low 5-yrs • They may be nodal or extra nodal • Variable expression  most nodal expressing CD4+ • They may be associated with eosinophilia

43. IV. Peripheral T&NK-cell LymphomaPeripheral T-cell lymphoma A spectrum of small, intermediate, and large lymphoid cells, many with irregular nuclear contours.

44. IV. Peripheral T&NK-cell LymphomaAnaplastic large cell lymphoma mitosis

45. Anaplastic large cell lymphoma “Hallmark” cells with horseshoe-like or “embryo –like” nuclei and abundant cytoplasma lie near the center of the field. IHC: ALK protein

46. IV. The WHO Classification of theLymphoid NeoplasmsV. Hodgkin Lymphoma • Classical subtype Nodular sclerosis Mixed cellularity Lymphocyte-rich Lymphocyte depletion • Lymphocyte pre-dominance

47. V. Hodgkin Lymphoma:KLINIS • Manifes sebagai benjolan periferal, tidak sakit, mengenai satu atau lebih limfonodi • Penyebaran dapat diperkirakan (lewat saluran limfe aferen dan eferen) • Pada penyebaran lanjut makin sulit diprediksi karena mulai ada penyebaran hematogen • Simtom konstitusional (40%): demam ringan (kadang siklik), berkeringat malam, penurunan berat badan (10% dari bb), pruritus, sakit pada daerah tumor sesudah minum alkohol

48. V. Hodgkin Lymphoma:KLINIS • Karakteristik: defisiensi fungsi sel T • Disfungsi imunitas ini dapat diperberat dengan pemberian obat-obat imunosupresan • Pada 50% kasus ditemukan limfositopeni absolut • Imunitas humoral masih ada sampai akhir

49. Urut-urutan frekwensi lokasi • Cervical & mediastinal (anterior – nodular sclerosis type) • Axillar, inguinal, retroperitoneal • Antecubital, Popliteal, mesenterik

50. Lymphocyte predomi- Nant, (paling lembut). Umur <35th. L:P=4:1 V. Hodgkin Lymphoma Mixed cellularity, dekade 4-5. Cure rate 75% Lymphocyte rich Lymphocyte depleted. Paling agresif. Nodular sclerosis. Paling banyak, dengan prognosis baik. Cure rate 80-85%