Neoplastic White Blood Cell Disorders

Amy S. Gewirtz, MD

Lymphomas
Hodgkin Lymphoma Non-Hodgkin lymphoma Malignant proliferation of lymphoid tissue May spread to involve solid tissue, bone marrow and blood

Leukemias
Acute Chronic Myeloid Lymphoid Malignant cells of the bone marrow that are also present in the blood May spread to involve solid tissue, typically liver and spleen

Hodgkin Lymphoma

A lymphoma of a distinctive cell

type (Reed-Sternberg cell). Arises in a single lymph node or chain of nodes and spreads contiguously. Curable in many cases with chemotherapy and/or radiotherapy.

Hodgkin Lymphoma
Clinical Features

Bimodal age distribution: 20-30 years

old and >50 years old. Painless lymphadenopathy involving a limited group of lymph nodes (cervical, supraclavicular, mediastinal common sites) Splenomegaly Fever, weight loss, night sweats (B symptoms) Bone marrow involvement

Hodgkin Lymphoma
Clinical Features

Diagnosis requires identification of

Reed-Sternberg cells in appropriate background. Four different types are recognized each with their own clinical presentations, histologic features and prognosis.

Reed-Sternberg Cell
Large cell with mirror image nuclei and prominent nucleoli This is the malignant cell of Hodgkins disease Cell of origin appears to be the B lymphocyte Epstein-Barr virus genome can be present

Hodgkin Lymphoma
Reed-Sternberg cells Variable inflammatory cell background

Lymphocytes, plasma cells, eosinophils

Hodgkin Lymphoma
Clinical Spread

Spread of disease is
predictable: lymph nodes spleen liver bone marrow Staging is used to determine treatment and prognosis.

Cancer Staging
Evaluation of tumor burden Low stage

Localized involvement Typically no B symptoms Wide spread disease with distant site or bone marrow involvement

High Stage

Hodgkin Lymphoma
Clinical Staging Stage Characteristics
I Tumor in one anatomic region or two contiguous anatomic regions on the same side of the diaphragm II Tumor in more than two anatomic regions or two noncontiguous regions on the same side of the diaphragm III Tumor on both sides of the diaphragm not extending beyond lymph nodes, spleen or Waldeyers ring IV Tumor in bone marrow, lung, etc.- any organ site outside of the lymph nodes, spleen or Waldeyers ring B symptoms: Fever, night sweats, weight loss

Treatment
Based primarily on stage Low stage

Radiotherapy Radiotherapy plus chemotherapy

High Stage

Low, but definite risk of development of secondary treatment related acute leukemia

Hodgkin Lymphoma
Clinical Course

Lymph node biopsy is required for

diagnosis. Younger patients with favorable histology present with low stage disease. Stage III and IV disease more likely to have B symptoms 5 year survival rate in Stage I and IIa is 90% 5 year survival rate in Stage IV is 60-70%.

Non-Hodgkin Lymphoma

Neoplastic, clonal expansion of

lymphocytes originating in lymph nodes or extranodal lymphoid tissue that are arrested at a certain stage of development with unregulated cell proliferation Most (85%) are of B cell origin Remainder are primarily of T cell origin Incidence rises steadily after age 40.

Non-Hodgkin Lymphoma
Clinical Findings

Painless lymph node enlargement. Systemic symptoms in 30% of patients. Immune abnormalities frequent. Splenomegaly May involve GI tract, bones, central nervous system Peripheral blood involvement more common in small cell types.

Non-Hodgkin Lymphoma
Classification

World Health Organization Recognizes distinct clinicopathologic

entities Numerous subtypes with great morphologic diversity Based on morphologic, immunophenotypic and molecular features

Classification
Growth pattern

Nodular vs diffuse Small vs large

Cell size

Cytogenetic, immunologic and molecular abnormalities Nodular does better than diffuse Small does better than large

Staging
Localized disease - low stage Numerous sites of involvement or bone marrow involvement - high stage Prognosis based more on classification than stage

Cell type and proliferation indices

Treatment
Chemotherapy Possible Radiation therapy Bone marrow transplantation

Classification of Leukemias
Acute

Rapid onset with blasts in the blood Myeloid and lymphoid cells affected Indolent onset and tends to involve more mature cells Myeloid and lymphoid cells affected

Chronic

Leukemia Classification
Acute Leukemia
Rapidly fatal Survival in months Mostly blasts

Feature
Course

Chronic Leukemia
Indolent Survival in years Mostly mature cells Typically increased Blasts not usually increased

Blood

White cell count Typically increased Bone marrow >20% blasts

Acute Lymphoblastic Leukemia

Clonal proliferation of a primitive lymphoid cell Both B and T cell types exist Increased white blood cell count often accompanied by thrombocytopenia More common in children May have lymphadenopathy and splenomegaly

Acute Lymphoblastic Leukemia

Prognosis related to cytogenetics Children have good prognosis Adults often have bad prognostic indicators Chemotherapy is mainstay of treatment with bone marrow transplantation considered at relapse

Acute Myelogenous Leukemia

Clonal proliferation of primitive myeloid cell Several subtypes exist based on morphology, cytochemistry, immunophenotype and cytogenetics Increased white blood cell count often accompanied by anemia and thrombocytopenia More common in adults

Acute Myelogenous Leukemia

Myeloperoxidase is present in the cytoplasm Auer rods may be present Chemotherapy is the mainstay of treatment While 70% of patients may have a remission, many relapse Prognosis is influenced by cytogenetics

Chronic Lymphocytic Leukemia

Clonal proliferation of mature lymphocyte, typically a B cell The B cells are immunologically incompetent Monoclonal expression of surface immunoglobulin - either kappa or lambda Most common in adults over 60

Chronic Lymphocytic Leukemia

Increased white cell count with lymphocytosis Often presents with splenomegaly and lymphadenopathy Anemia and thrombocytopenia eventually develop as disease progresses All cases eventually terminate into a higher grade process - either acute leukemia or high grade lymphoma Chemotherapy is the mainstay of treatment

Chronic Myelogenous Leukemia

Clonal proliferation of immature granulocytes, this is a stem cell disorder Marked increase in white blood cell count with eosinophilia and or basophilia, left shifted granulocytes May have thrombocytosis and anemia Splenomegaly is typically present

Chronic Myelogenous Leukemia

Disease defining cytogenetic abnormality; t(9;22) Molecular fusion of bcr and abl genes All cases eventually terminate into acute leukemia - either myeloid or lymphoid Chemotherapy is the mainstay of treatment

Overview of Leukemias
Abnormal cells suppress growth of normal cells Infiltration of body organs by abnormal cells Immune dysfunction

Plasma Cell Proliferations

Multiple Myeloma

A clonal proliferation of monoclonal

plasma cells. Monoclonal heavy and or light chain production IgG is most common A disease of late middle age to elderly.

Clonal Origin of Myeloma

kappa

Monoclonal (Multiple Myeloma)

lambda

Polyclonal (Reactive)

Multiple Myeloma
Clinical Features

Serum monoclonal protein Bone marrow infiltration by plasma cells Multiple osteolytic bone lesions Polyclonal hypogammaglobulinemia Bence-Jones proteinuria Hypercalcemia Renal failure Infections

Multiple Myeloma
Blood and Marrow Features

Circulating plasma cells in blood is

uncommon RBC show rouleaux Marrow plasma cell infiltrates in single cells and sheets

Multiple Myeloma
Diagnostic Criteria
1. >30% marrow plasmacytosis 2. Monoclonal gammopathy >3.5 g/dL of IgG >2.0 g/dL of IgA or >1 g/daykappa or lambda light chains in urine without other significant proteinuria A. 10-30% marrow plasmacytosis B. Monoclonal gammopathy with values less than 3 above C. Lytic bone lesions D. Suppressed normal immunoglobulins Dx: C, or D; 1 + B, C, or D; 2 + A, B, C; or 2 + A, B, D.

Multiple Myeloma
Prognosis and Treatment

Prognosis is variable, but generally

poor. Indolent form: survival for years Typical form: median survival 3 years Chemotherapy Radiotherapy Bone Marrow Transplant