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Mature Lymphoid Neoplasms

28. Mature Lymphoid Neoplasms. Learning Objectives—Level I. At the end of this unit of study, the student should be able to: Describe the clinical presentation of patients with mature lymphoid neoplasms. Describe how the diagnosis of a lymphoid neoplasm is made. continued on next slide.

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Mature Lymphoid Neoplasms

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  1. 28 Mature Lymphoid Neoplasms

  2. Learning Objectives—Level I At the end of this unit of study, the student should be able to: • Describe the clinical presentation of patients with mature lymphoid neoplasms. • Describe how the diagnosis of a lymphoid neoplasm is made. continued on next slide

  3. Learning Objectives—Level I At the end of this unit of study, the student should be able to: • Differentiate among chronic lymphocytic leukemia (CLL), lymphoma, and plasma cell myeloma based on peripheral blood findings and ancillary studies. • Describe the histology of a normal lymph node. • Summarize the causes of lymphadenopathy. continued on next slide

  4. Learning Objectives—Level I At the end of this unit of study, the student should be able to: • Contrast the morphology of Hodgkin and non-Hodgkin lymphoma. • List and describe the chronic leukemic lymphoproliferative disorders. • Recognize and differentiate abnormal and normal lymphocytes on a stained peripheral blood smear and associate their presence with a clinical diagnosis. continued on next slide

  5. Learning Objectives—Level I At the end of this unit of study, the student should be able to: • Describe and apply a multidisciplinary approach to the classification and staging of lymphoid neoplasms. • Compare the laboratory and clinical findings of multiple myeloma and lymphoplasmacytic lymphoma. • Define monoclonal gammopathy.

  6. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Describe the use of immunophenotyping and genotyping in detecting clonality and list the characteristic results of the more common mature lymphoid neoplasms. • Contrast the features of low-grade and high-grade lymphoma. continued on next slide

  7. Learning Objectives – Level II At the end of this unit of study, the student should be able to: • Compare and contrast the laboratory features characteristic of the following non-Hodgkin lymphomas: • Small lymphocytic lymphoma • Follicular lymphoma • Mantle cell lymphoma • MALT lymphoma • Lymphoplasmacytic lymphoma continued on next slide

  8. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Compare and contrast the laboratory features characteristic of the following non-Hodgkin lymphomas: • Diffuse large B-cell lymphoma • Burkitt lymphoma • Anaplastic large cell lymphoma • Peripheral T-cell lymphoma continued on next slide

  9. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Compare and contrast the laboratory features characteristic of Hodgkin lymphoma (HL) subtypes. continued on next slide

  10. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Compare and contrast the clinical and laboratory features characteristic of the following chronic leukemic lymphoproliferative disorders: • Chronic lymphocytic leukemia (CLL) • B-prolymphocytic leukemia (B-PLL) • Hairy cell leukemia (HCL) • T-prolymphocytic leukemia (T-PLL) continued on next slide

  11. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Compare and contrast the clinical and laboratory features characteristic of the following chronic leukemic lymphoproliferative disorders: • Large granular lymphocyte leukemia (T-LGL) • Sézary syndrome continued on next slide

  12. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Compare and contrast the laboratory features characteristic of the following plasma cell disorders: • Plasmacytoma • Symptomatic plasma cell myeloma • Monoclonal gammopathy of undetermined significance continued on next slide

  13. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Recognize and identify the peripheral blood abnormalities associated with CLL, B-PLL, HCL, T-LGL, Sézary syndrome, plasma cell myeloma, and non-Hodgkin lymphoma. continued on next slide

  14. Learning Objectives—Level II At the end of this unit of study, the student should be able to: • Describe the etiology and pathogenesis of lymphoid neoplasms. • Differentiate reactive from malignant proliferations of lymphoid cells using clinical and laboratory data.

  15. Introduction • Mature lymphoid neoplasms • Heterogeneous group of disorders • Grouped by distribution of disease • Leukemia • Lymphoma • WHO classification groups them together • Probably represent different clinical manifestation of single disease

  16. Etiology and Pathogenesis • Genesis of lymphoid neoplasms is multi-step process • Acquired genetic factors • Alterations of • Proto-oncogenes • Tumor suppressor genes continued on next slide

  17. Etiology and Pathogenesis • Genesis of lymphoid neoplasms is multi-step process • Acquired genetic factors • Associated with development of mature lymphoid neoplasms • Translocation of BCL-2 gene leads to inhibition of apoptosis and lymphocyte accumulation within lymph node continued on next slide

  18. Etiology and Pathogenesis • Genesis of lymphoid neoplasms is multi-step process • Inherited genetic factors • Some immunodeficiency syndromes associated with ↑ incidence of malignant lymphoma continued on next slide

  19. Etiology and Pathogenesis • Genesis of lymphoid neoplasms is multi-step process • Environmental factors • EBV associated with development of neoplasms • African Burkitt lymphoma, lymphoma associated with HIV, Hodgkin lymphoma • Helicobacter pylori associated with • Non-Hodgkin lymphoma (MALT lymphoma-type)

  20. Diagnosis and Classification • Involves integration of clinical information with morphology, flow cytometry, molecular and chromosome analysis • Morphologic appearance • PB, BM, or tissue biopsy • Normal or reactive lymphocytes • Mixture of cells varying in size, shape and staining characteristics continued on next slide

  21. Diagnosis and Classification • Involves integration of clinical information • Morphologic appearance • Lymphoid neoplasms • Homogeneous (expansion of single cell type) • Occasionally may have abnormal or bizarre appearance continued on next slide

  22. Diagnosis and Classification • Involves integration of clinical information • Immunophenotyping, molecular diagnostics, cytogenetics • Used to detect clonality and abnormal lymphocytes • Presence of identical cells from single progenitor continued on next slide

  23. Diagnosis and Classification • Involves integration of clinical information • Presence of a population of cells with an abnormal phenotype (flow cytometry) • CD5– T-cells • Cytogenetic translocations • BCL-2 gene rearrangement

  24. Diagnosis and Classification • Classification performed to guide therapy and provide additional prognostic information • WHO • Classifies mature lymphoid neoplasms into distinct disease entities • With similar morphologic, phenotypic, and genotypic features

  25. Diagnosis and Classification • Most have expected clinical course and response to treatment. • Low-grade lymphoma: long indolent course • High-grade lymphoma: clinically aggressive • Kills patient rapidly if not treated continued on next slide

  26. Diagnosis and Classification • Most have expected clinical course and response to treatment. • Current therapeutic regimens more effective against high-grade than low-grade lymphoid neoplasms

  27. Table 28-1 WHO Classification of Selected Mature Lymphoid Neoplasms

  28. Diagnosis and Classification • Lower-grade lymphoma • Histologic sections demonstrate nodular growth pattern, smaller cells, lower mitotic activity, and absence of apoptosis • Higher-grade lymphoma • Diffuse growth pattern, larger cells, and more numerous mitoses and apoptotic bodies

  29. Diagnosis and Classification • Some subdivided into more prognostic groups • Follicular lymphoma divided into three grades defined by number of large cells • Some CLL with expression of CD38, ZAP-70 have more aggressive course • Diffuse large B-cell lymphoma • Germinal center type—better outcome • Non-germinal center type

  30. Diagnosis and Classification • Prognosis of patient related to: • Extent and distribution of the disease (stage) • Patients with widespread lymphoma usually have worse prognosis

  31. Diagnosis and Classification • Determination of stage usually involves: • Radiologic studies • PB examination • BM aspiration and biopsy • BM involvement = disseminated disease, stage IV

  32. Table 28-2 Ann Arbor Staging System for Malignant Lymphoma

  33. Mature B-Cell Neoplasms

  34. Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma • CLL and SLL seem to represent different clinical manifestations of one disease entity. • CLL presents with PB lymphocytosis • Can develop lymph node involvement • SLL presents with lymphadenopathy • Can develop PB and BM disease

  35. CLL/SLL • Often detected in asymptomatic patients as result of finding lymphocytosis on CBC

  36. CLL/SLL • Symptoms (if present) related to: • Cytopenias • Due to: • Leukemic infiltration of marrow • Hypersplenism • Poor nutritional status • Immune-mediated cell destruction

  37. CLL/SLL • Sustained absolute lymphocytosis • > 5 × 109/L • Cells morphologically • Small and mature with scant cytoplasm • Nuclei—round, clumped (block-type) chromatin • Nucleoli inconspicuous continued on next slide

  38. CLL/SLL • Sustained absolute lymphocytosis • Presence of smudge cells • Neoplastic cells fragile • Prolymphocytes < 10% of all lymphocytes

  39. Figure 28-1a Chronic lymphocytic leukemia. Small round lymphocytes with clumped chromatin, a larger prolymphocyte with a prominent nucleolus, and numerous smudge cells (arrows)(peripheral blood, Wright stain, 1000× magnification).

  40. CLL/SLL • Differentiate CLL from reactive lymphocytosis and other chronic leukemia lymphoproliferative disorders • CLL characterized T-cell CD5+, CD20 ±, monoclonal Ig ± • Mantle cell lymphoma (MCL) • Many features of CLL • CD23+, CD200+, lack of FMC-7 positivity

  41. CLL/SLL • Lymph node biopsy in CLL/SLL • Diffuse infiltrate of small, mature lymphs • Dense, regular clumped chromatin • Lack nucleoli • Contain aggregates of paler large cells (proliferative centers) • Abundant pale-staining cytoplasm • Prominent eosinophilic nucleoli

  42. Figure 28-1b Small lymphocytic lymphoma. The periphery of the image displays many small lymphocytes with round nuclei and clumped chromatin. The center of the image contains a vague nodule containing pale-staining larger cells (proliferation center) (lymph node biopsy, H&E stain, 50× magnification).

  43. CLL/SLL • CLL/SLL is heterogeneous disorder • Includes subset of patients with different prognostic markers • Important to identify for treatment and outcomes • CD38, ZAP-70, and the mutational status of Ig heavy chain gene variable region (VH) continued on next slide

  44. CLL/SLL • CLL/SLL is heterogeneous disorder • Chromosomal abnormalities 50% of cases • Del 13q14-23.1 most common, good prognosis • Trisomy 12, del 11q22.3-23.1, del 6q21-23, del17p13.1 (p53 alterations), 14q abnormalities • Associated with worse prognosis

  45. CLL/SLL • < 10% CLL/SLL patients transform to B-cell lymphoid neoplasm • Early stage CLL patients monitored for disease progression • Standard therapy • Chemotherapy • New small molecule inhibitors (e.g., ibrutinib) work inside cells to block enzymes responsible for cell signaling

  46. B-Cell Prolymphocytic Leukemia • Aggressive leukemic disorder • Often does not respond to treatment • Median survival 7.5 months • Arises de novo, rarely develops from CLL

  47. B-Cell Prolymphocytic Leukemia • B-cell PLL • Marked splenomegaly, minimal lymphadenopathy • Marked lymphocytosis (often > 300 × 109/L) • > 55% prolymphocytes • Large cells, moderate pale basophilic cytoplasm, single prominent nucleolus, moderate condensed chromatin

  48. Figure 28-2 Prolymphocytic leukemia. Numerous large lymphoid cells with prominent nucleoli (prolymphocytes) (peripheral blood, Wright stain, 1000× magnification).

  49. B-Cell Prolymphocytic Leukemia • Differentiate B-PLL from CLL • Variable CD5 expression • CD20 and sIg intense expression • FMC-7 positivity • CD23 negative continued on next slide

  50. B-Cell Prolymphocytic Leukemia • Differentiate B-PLL from CLL • No characteristic chromosome abnormality • Sometimes del(17p) resulting in inactivation of p53 gene • Poor prognosis

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