Lymphomas & Plasma Cell Neoplasms Flashcards
BCL6 and CD10
Markers of germinal B cells (and derived lymphomas)
CD20
B-cell specific marker positive in both mantle zone and germinal center B cells
CD3
T-cell specific marker positive in paracortical T cells
Chronic lymphocytic leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) - Definition
Both characterized by lymphocytosis of monoclonal B cells with mature immunophenotype
Peripheral lymphocytosis > 5 x 10^9 / L over 3 months
CLL is a liquid presentation originating in the bone marrow
SLL is a solid presentation usually presenting in a lymph node
CLL & SLL - Immunophenotype
Positive for B cell markers CD19, CD23 and T cell marker CD5
Weakly positive for CD20 and sIg (mature B cell markers)
Negative for CD10 (expressed on germinal B cells)
CLL & SLL - Epidemiology
CLL is the most common leukemia in the Western world and accounts for 30% of all leukemias
SLL accounts for 7% of Non-Hodgkin Lymphoma
Median age of diagnosis - 65 years, most elderly patients with CLL are asymptomatic
Follicular Lymphoma - Epidemiology
40% of adult lymphomas in the US; 20% worldwide
Median age of diagnosis - 60 years
Stages III and IV are common at diagnosis; however, patients are often asymptomatic except for lymphadenopathy
Follicular Lymphoma - Immunophenotype, and Cytogenetics
Lymphoma of germinal B cell origin
B cell marker positive - CD19, CD20
Germinal B cell marker positive - BCL6, CD10
Positive for BCL2, which is negative in normal, reactive germinal center B cells
t(14;18) causes constitutive expression of BCL2 under the IGH promotor; BCL2 functions to suppress apoptosis and is normally down-regulated in normal germinal center B cells, allowing cells to die during selection
Mantle Cell Lymphoma - Epidemiology
Comprises 3-10% of Non Hodgkin Lymphoma
Median age of diagnosis = 60 years
Presentation in stages III and IV with hepatosplenomegaly and marrow involvement is common; moderately aggressive disease
Mantle Cell Lymphoma - Immunophenotype & Cytogenetics
B cell marker positive (CD19, CD20)
Positive for CD5 but negative for CD23 (differentiates from CLL/SLL)
Negative for germinal center B-cell markers (CD10, BCL6)
Positive for cyclin D1 (BCL1) - specific for Mantle Cell Lymphoma
t(11;14) induces constitutive activation of the BCL1 gene under the IGH promotoer, leading to over-expression of cyclin D1 and unchecked progression through the cell cycle
Burkitt’s Lymphoma (BL) - 3 Types
Endemic BL - typically seen throughout equatorial Africa in children 4-7 years old; often presents in the jaw or abdomen; 95% EBV+
Sporadic BL - typically seen in children or young adults; often presents in the ileocecal area; 30% EBV +
Immunodeficiency-associated BL - primarily seen in HIV+ patients; 25-40% EBV+
Burkitt’s Lymphoma - Immunophenotype & Cytogenetics
Positive for B cell markers (CD19, CD20)
Positive for germinal B-cell markers (CD10, BCL6)
Positive for MYC
t(8;14) causes constitutive activation of the MYC transcription factor under the IGH promoter
Plasma Cell Neoplasms - Definition
A clonal proliferation of plasma cells that secrete a singe class of Ig or a polypeptide subunit of a single Ig, detectable as a monoclonal protein (M protein) on serum or urine electrophoresis
Plasma Cell Myeloma (PCM, Multiple Myeloma) - Definition & Diagnosis
A bone-marow based plasma cell neoplasm associated with M protein in the serum or urine;
Diagnosed based on:
M protein present in serum or urine (most often IgG, IgA)
Monoclonal plasma cells present in the bone marrow, usually > 10% nucleated cells in the marrow
Related organ or tissue impairment: hypercalcemia, renal insufficiency, anemia, bone lesions (CRAB)
Rouleaux formation (stacked or linked RBCs) may be present on peripheral smear when M protein is significantly elevated
Monoclonal Gammopathy of Undetermined Significance (MGUS) - Definition and Diagnosis
Describes the presence of a monoclonal Ig in the serum or urine of a patient without other evidence of plasma cell myeloma or other disease known to produce monoclonal immunoglobulins
Diagnosis is based on:
Presence of M protein at less than myeloma levels
Marrow plasmacytosis < 10%
No lytic bone lesions or other myeloma-related symptoms (CRAB)
*MGUS is a precursor lesion of PCM with a malignant transformation rate of 1.5%/year
Solitary plasmacytoma of bone - definition & diagnosis
A localized tumor of the bone composed of clonal plasma cells
Diagnosis is based on:
Presence of a single bone lesion consisting of monoclonal plasma cells
Absence of PCM-related symptoms (CRAB)
Absent or low serum or urine M protein
Extraosseous plasmacytoma
Localized plasma cell tumors arising in tissues outside of the bone marrow, most often in the upper respiratory system
Hodgkin’s Lymphoma - 5 sub types
Classical Hodgkin's Lymphoma Nodular Sclerosis Hodgkin's Lymphoma Lymphocyte-rich Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte-depleted Hodgkin's lymphoma
Reed-Sternberg (RS) cells
Diagnostic for Classical Hodgkin’s Lymphoma
Morphology:
Large
Multiple nuclei or single, multi-lobated nuclei
Single large, eosinophilic nucleolus
Ample cytoplasm
Classical Hodgkin’s Lymphoma
Germinal B cell lymphoma
Diagnosis is based on the identification of Reed-Sternberg cells; malignant cells represent only <2% of total cellular population
CHL - Immunophenotype
Positive for CD30 and CD15
Negative for CD10 and BCL6 (usually positive in germinal center B cells)
Nodular Sclerosis Classic Hodgkin Lymphoma
Most common subtype of CHL; accounts for 50-80% of all CHLs
Predominates in young adults
Morphology includes a thickened lymph node capsule and nodular areas of lymph node surrounded by broad bands of collagen
Lacunar cells present - large tumor cells surrounded by a prominent clear space, an artifact of formalin fixation
Positive for CD15 and CD30
Mixed Cellularity CHL
Second most frequent sub-type of CHL, 20-30%
Frequently seen in stages III and IV with B symptoms (fever, fatigue, night sweats)
Lack of broad bands of collagen seen in nodular sclerosis CHL
75% EBV+
Lymphocyte Rich CHL
Accounts for 5% of CHLs
Frequently presents in stages III and IV with presence of B symptoms; lack of broad bands of collagen seen in nodular sclerosis CHL
Classic RS cells very rare
Most favorable prognosis
Lymphocyte-depleted CHLs
Rarest subtype of CHL - 1%
Numerous scarce RS cells, scarce lymphocytes
