Other malignant lymphoproliferative disorders

1. Other malignant lymphoproliferative disorders The lymphomas and plasma cell problems

2. Malignant lymphoprolifrative disorders • How do you tell the difference between a neoplastic cell and an atypical lymphocyte? • Neoplastic cells are “clonal” so they all look the SAME! • Atypical lymphocytes as seen in infections will be variable. They WILL NOT all look the same.

3. Malignant lymphoprolifrative disorders • What is the difference between a leukemia and a lymphoma? • In leukemias the neoplastic cell originates in the bone marrow and the neoplastic cells are found predominantly in the bone marrow and peripheral blood. • In lymphomas, the neoplastic cell originates in the lymph nodes or spleen and causes the development of a solid tumor. • Some lymphomas have a “leukemic phase” where the neoplastic cells are found in the peripheral blood. • They may be difficult to differentiate from a leukemia.

4. Malignant lymphoprolifrative disorders • Lymphomas • Lymphomas are divided into 2 major categories: Hodgkins lymphoma and non-Hodgkins lymphoma • Hodgkins lymphoma: • Can occur at any age with peak incidences at 20-30 and over 50. • Patients present to the doctor with symptoms of lymphadenopathy and may have fever, night sweats, weight loss and malaise • Diagnosis depends upon finding the Reed-Sternberg (RS) cell (something a pathologist must identify) • Are divided into 2 basic types based on the histopathology of the involved lymph nodes

5. Malignant lymphoprolifrative disorders • Nodular lymphocyte predominance – occasional or rare RS cell seen; rare, but has a good prognosis • Classic Hodgkins lymphoma which is further subdivided into: Nodular sclerosis - bands of collagen are seen in the lymph nodes. There are mature appearing lymphocytes (T helper cells) associated with varying numbers of granulocytes, macrophages and eosinophils. Numerous RS cells are seen. This is the most common form of the disease. Mixed cellularity – the lymph nodes contain proliferating lymphocytes, histiocytes, plasma cells, and eosinophils. There are a moderate number of RS cells Lymphocyte depleted – there are few lymphocytes and a predominance of RS cells Lymphocyte rich – there are numerous small T lymphocytes and occasional RS cells

6. Malignant lymphoprolifrative disorders Extranodal Hodgkins lymphoma – involves tumors in bone marrow, liver, or spleen • Lab features – normochromic, normocytic anemia with transitory increase in lymphocytes, monocytes, eosinophils, and sometimes platlets • Prognosis depends upon • The clinical stage of the disease (see next slide) • The histiologic type of the disease – in general, the prognosis is better the higher the number of lymphocytes and the lower the number of RS cells • Treatment • Combination chemotherapy • Radiation • A combination of chemotherapy and radiation • Cure rates are 80% or more, particularly if diagnosis occurs in an early stage of the disease.

7. Clinical staging of lymphomas

8. Malignant lymphoprolifrative disorders • Non-Hodgkins lymphoma (malignant lymphoma) • Many are associated with specific chromosomal translocations • Can be grouped morphologically by cell size into • Small • Intermediate • Large • Can be grouped functionally into • B cell • T cell • Null cell

9. Malignant lymphoprolifrative disorders • Can be grouped based on cell maturity into • Well differentiated • Poorly differentiated • Can be grouped based on how aggressive the disease is into • Low grade • Intermediate grade • High grade

10. Lymphomas - classification

11. Malignant lymphoprolifrative disorders • Prognosis – • Prognosis worsens generally with increased cell size • Prognosis worsens with decreased differentiation of the malignant cell • Low grade lymphomas have a better prognosis than high grade lymphomas

12. Malignant lymphoprolifrative disorders • Multiple myeloma (plasma cell myeloma) • This is usually seen in older adults • When the patient is first diagnosed the following are usually seen: • Multiple bone lesions with bone marrow infiltration of malignant cells • Monoclonal gamopathy (usually IgG or IgA) • Generalized hypogammaglobulinemia • Bence Jones proteinuria • What does this all mean? • A single immunoglobulin(antibody) is produced in excess = monoclonal gamopathy

13. Malignant lymphoprolifrative disorders • Synthesis of normal immunoglobulins is suppressed = generalized hypogammaglobulinemia • There is an overproduction of light chains resulting in light chains being found in the urine = Bence Jones proteinuria • A common complication is renal impairment • On a peripheral smear, rouleaux is the hallmark of the disease and occasional circulating plasma cells may be seen

14. Malignant lymphoprolifrative disorders • Waldenstrom’s macroglobulinemia • This is a plasma cell dyscrasia (abnormality) in which a monoclonal IgM is secreted. • Soft tissue involvement rather than bone marrow involvement is seen • Patients have problems with hyperviscosity of the blood.

15. Malignant lymphoprolifrative disorders • Heavy chain disease • This results from an overproduction of abnormal heavy chains. • Clinically the patients present with symptoms typical of malignant lymphoma.