18 - Immunoproliferative Disorders Flashcards
1
Q
Immunoproliferative Disorders
A
- Mature B-cell derived clonal disorders which may be
associated with production of monoclonal antibodies - Chronic lymphocytic leukemia
- Hairy cell leukemia
- Waldenström macroglobulinemia
- Plasma cell disorders
- Amyloidosis
- Involve lymph nodes, spleen, bone marrow, and
extranodal sites
2
Q
B-Cell Chronic Lymphocytic Leukemia
A
- Most common lymphoproliferative disorder in US
- Peak incidence at age 65 (male > female)
- Painless, generalized lymphadenopathy
- Frequent bone marrow/blood involvement
- Synonymous with small lymphocytic lymphoma
- Chronic, indolent clinical course
3
Q
B-Cell Chronic Lymphocytic Leukemia
* Morphology
A
- Small, round mature lymphocytes with smudge cells
- Absolute lymphocytosis in blood
- Diffuse nodal effacement with pseudofollicles
- Diffuse white pulp expansion in the spleen
- Bone marrow infiltration
4
Q
B-Cell Chronic Lymphocytic Leukemia
* Immunophenotyping
A
- Immunophenotyping
- B-cell markers (CD19, CD20, CD22)
- Aberrant co-expression of CD5 and CD23
- Surface light chain restriction
- Molecular phenotypes
- Naïve B cells (lack IgH rearrangement)
- Post-germinal center B cells (IgH rearrangement)
- Cytogenetics
- Trisomy 12
- 13q deletions (RB gene)
5
Q
B-Cell Chronic Lymphocytic Leukemia - Clinical
A
- Indolent, slowly progressive, but incurable
- Varying cytopenias with bone marrow infiltration
- Warm antibody autoimmune hemolytic anemia
(spherocytes, positive direct Coombs test) - Transformation to prolymphocytic leukemia or large B
cell lymphoma (Richter syndrome) - Conservative therapy
6
Q
Hairy Cell Leukemia
A
- Uncommon lymphoproliferative disorder
- Middle-aged/elderly males
- Lymphadenopathy not common
- Frequent splenic/bone marrow/blood involvement
- Post-germinal center, late-activated memory B cell
- Chronic, indolent clinical course
7
Q
Hairy Cell Leukemia
Morphology
A
- Small, mature lymphocytes with more abundant
cytoplasm and surface hair-like projections - Associated cytopenias (splenomegaly and marrow
involvement) - Diffuse red pulp involvement of the spleen
- Diffuse bone marrow infiltration (“fried egg”) with
reticulin fibrosis (dry tap)
8
Q
Hairy Cell Leukemia
Immunophenotyping
A
- B-cell markers (CD19, CD20, CD22)
- Aberrant co-expression of CD11c/CD25/CD103
- Surface light chain restriction
- Tartrate-resistant acid phosphatase (TRAP) activity
- Annexin A1 upregulation
Cytogenetics - no specific abnormalities
Molecular - BRAF gene point mutation (V600E)
9
Q
Hairy Cell Leukemia - Clinical
A
- Indolent clinical course
- Symptoms due to splenomegaly (abdominal fullness),
cytopenias - Impaired immunity (infection risk)
- Excellent, long-term response to single agent therapy
(deoxycoformycin or 2-chlordeoxyadenosine)
10
Q
Plasma Cell Disorders
A
- Clonal proliferation of plasma cells
- Production of monoclonal immunoglobulins (M protein)
- Previous radiation exposure or chronic antigenic
stimulation - Occur almost exclusively in adults
11
Q
Plasma Cell Myeloma
A
- Fairly common (10% of hematologic malignancies)
- Peak incidence in 6th-7
th decade
- More common in African-Americans
- Evidence of end-organ dysfunction (CRAB symptoms)
- hyperCalcemia, Renal failure, Anemia, lytic Bone
lesions
12
Q
Plasma Cell Myeloma
Morphology
A
- Bone marrow infiltration by plasma cells (mature or
immature), often >30% - May involve extramedullary sites
- May develop leukemic phase (advanced disease)
- Associated cytopenias
- Osteolytic bone lesions on x-ray
13
Q
Plasma Cell Myeloma - immunodetection
A
- Monoclonal protein on serum/urine electrophoresis
(IgG > light chain only/IgA, IgD/IgE/non-secretory rare) - Hypergammaglobulinemia (except light chain)
- Bence Jones protein (free light chains) in urine
- Immunoparesis of normal immunoglobulins
- CD38/CD138 – positive (lack B-cell markers)
- Hypercalcemia (bone lesions)
- Rouleaux formation
14
Q
Plasma Cell Myeloma - Clinical
A
- Variable clinical progression (median survival 3-4 years)
- Progressive renal disease (tubular damage)
- Progressive cytopenias (plasma cell leukemia)
- Infection risk (most common cause of death)
- Bone pain, pathologic fracture
- Amyloidosis (lambda more common)
- β2
-microglobulin levels to assess tumor burden - Treat with chemotherapy, autologous stem cell
transplantation
15
Q
Monoclonal Gammopathy of Undetermined
Significance (MGUS)
A
- Older patients (age >50)
- Small monoclonal spike (<3.0 g/dL)
- Low numbers of plasma cells (<10%)
- No CRAB symptoms
- Monitor for progression (1% per year)
16
A
- Median age – 65 years
- Light chain amyloid (lambda > kappa)
- Variable plasma cells (20% overt myeloma)
- Symptoms due to organ infiltration
- Amorphous eosinophilic deposits, Congo red positive,
apple green birefringence - Rapidly progressive – median survival 2 years
17
Q
Other Plasma Cell Disorders
A
- Plasmacytoma - localized bone lesion (70% progress)
- Smoldering myeloma – no symptoms (50% progress)
- POEMS (osteosclerotic myeloma) – Polyneuropathy,
Organomegaly, Endocrinopathy, Myeloma protein,
Skin changes - TEMPI syndrome - Telangiectasias, Erythrocytosis with
elevated erythropoietin, Monoclonal gammopathy,
Perinephric fluid collections, Intrapulmonary shunting
18
Q
Waldenström Macroglobulinemia
A
- Indolent lymphoproliferative disorder
- Peak incidence – 6th-7th decades
- Monoclonal IgM protein (macroglobulin)
- Bone marrow infiltration, but no lytic bone
lesions/hypercalcemia - Lymph node involvement (synonymous with
lymphoplasmacytic lymphoma)
19
Q
Waldenström Macroglobulinemia
Morphology and immunodetection
A
- Mixture of small mature B lymphocytes, plasma
cells, and plasmacytoid lymphocytes (all clonal) - Dutcher bodies (pseudonuclear inclusions)
- Increased mast cells
- Express B-cell markers (but lack CD5, CD10, and
CD23) and show surface light chain restriction
20
Q
Waldenström Macroglobulinemia - Clinical
A
- Indolent clinical progression –median survival 5-10
years, but considered incurable - Distinct from myeloma
- Hyperviscosity syndrome – therapeutic plasmapheresis
- Treat like an indolent B-cell lymphoma
