Hematologic malignancies Flashcards
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
Positive: CD5, CD19, CD23
Negative: CD10, FMC7
Lymph node: Architecture: effacement, Pseudofollicles (proliferation centers)
Deletion of 13q14 >50% of CLL Trisomy chromosome 12 Deletion of 11q22 Deletion of 17p13 Absolute mature lymphocytosis of ≥5 × 109/L, sustained for at least 3 months Median 65 years, male predominance, M:F=2:1 asymptomatic (70% of cases) or only mildly symptomatic,
Folicular Lymphoma (FL)
75-90% t(14;18)(q32;q21), BCL2-IGH
B-cell markers positive: CD19+, CD20+
BCL2+ positive
Germinal center B-cell marker positive: CD10 and BCL6
Morphology of follicles: Poorly defined with scant or absence of mantle zone, starry-sky pattern, diffuse areas may be present,
Patterns of follicles: Closely packed, back to back, with effacement of the nodal architecture
Locations: mostly lymph nodes, also spleen, bone marrow
A lymphoma of germinal center B cells (centrocytes and centroblasts) with typically
at least a partially follicular pattern
mostly adults, median 60 years
male = female
Clinical presentations: more than 80% cases have widespread stage III or IV disease
at diagnosis, 40% have bone marrow involvement
,
Extranodal or intramedullary involvement
Mantle Cell Lymphoma (MCL)
Characteristic t(11;14)(q13;q32) BCL1-IGH
B-cell markers positive: CD19+, CD20+
Germinal center B-cell marker positive: CD10 and BCL6
Cyclin D1 (BCL1) positive
CD5 positive, CD23 negative
Architecture: effacement of lymph node
with a vaguely nodular, diffuse or mantle zone growth pattern;
Age: middle to older age, median age 60
M:F=2:1
Location: mostly lymph nodes, also spleen and bone marrow
Clinical presentations: most patients present with stage III or IV with lymphadenopathy, hepatosplenomegaly; >50% of cases with massive splenomegaly and marrow involvement
Burkitt ’s lymphoma (BL)
t(8;14)(q24;q32) MYC-IGH fusion
B-cell markers positive: CD19+, CD20+
High proliferation index, nearly 100% by Ki-67 staining
Negative: BCL2, CD5, CD23, TdT
A highly aggressive B-cell lymphoma, often presenting at extranodal sites or as a
leukemic form
.
4-7 years of age,
Endemic: jaw or abdomen, 95% EBV positive.
Sporadic: mostly in ileocecal area
Diffuse infiltration of monomorphic, medium-sized cells with starry sky pattern
Abundant basophilic cytoplasm. Some times “squared off” boarders deeply basophilic cytoplasm with lipid vacuoles
Plasma Cell Neoplasms
immunoglobulin-producing plasma cells that secrete a single class of immunoglobulin or a polypeptide subunit of a single immunoglobulin, which is usually detectable as a monoclonal protein (M protein)
Plasma Cell Myeloma (Multiple Myeloma)
originates from the marrow with disseminated marrow involvement in most cases.
Diagnostic Criteria: M protein in serum or urine no bottom limit, but >30g/L, IgG, >25g/L, IgA, or >1g/24 hours of urine
Bone marrow clonal plasma cells
hypercalcemia, renal insufficiency, anemia, bone lesions (CRAB)
> 50 years of age, median age at diagnosis ~ 68 years
frequent symptom: bone pain in the back or extremities due to lytic lesion
Rouleaux formation
Monoclonal Gammopathy of Undetermined Significance (MGUS)
presence of a monoclonal immunoglobulin in the serum or urine with no evidence of plasma cell myeloma
50-70 years old
Diagnostic criteria: M component less than myeloma levels, Marrow plasmacytosis <10%, no lytic bone lesions, mo myeloma-related symptoms
precursor lesion of plasma cell myeloma
Solitary plasmacytoma of bone
localized tumor of the bone, which is
composed of clonal plasma cells that are cytologically, immunophenotypically, and
genetically similar to those of plasma cell myeloma.
Diagnostic criteria: Single bone lesion consisting of monoclonal plasma cells,
No evidence of other bone lesions
Absence of renal failure, hypercalcemia, and anemia that could be attributable
to myeloma
Absent or low serum or urine M protein
Extraosseous Plasmacytoma
localized plasma cell tumors that arise in tissues outside of the bone marrow
median age 55
2/3 males 1/3 female
localized mass lesions in upper respiratory tract, including nasal passages, sinuses, oropharynx, and larynx.
nodular lymphocyte-predominant of Hodgkin’s lymphoma (NLPHL)
germinal center B-cell origin
indolent malignancy, representing a nodular proliferation comprising a minority of large neoplastic centroblasts with multilobated nuclei, popcorn or lymphocyte-predominant (LP)
Nodular sclerosis Classic Hodgkin Lymphoma (NSHL)
Most frequent subtype, accounts for 50-80% of all CHLs
Predominates in young adults, especially in females
Morphology:
Thickened lymph node capsule with broad bands of collagen
Nodular areas surrounded by broad bands of collagen
Lacunar cells: a type of HRS cells with polypoid nuclei and small nucleoli.
Background of small round lymphocytes (predominantly T-cells), eosinophils, plasma cells, and some neutrophils
above diagphragm
EBV+, 10-25%
Mixed cellularity CHL Classic Hodgkin Lymphoma
20-30% of CHLs
cellular composition is similar to that of NSHL
children and older patients
Frequently in stages III and IV and with B symptoms,
more often below or on
both sides of the diaphragm
Lack of broad bands of collagen seen in nodular sclerosis CHL
EBV+, ~ 75%
Lymphocyte rich CHL
5% of all CHLs
nodular growth pattern, with residual germinal centers or remnants of
residual germinal centers
rare HRS cells
Lymphocyte depleted CHL
1% of CHL
paucity of lymphocytes in this subtype
Numerous RS cells
Usually EBV+
Classis Hodgkin lymphoma
malignant cells usually represent only a small minority, between 0.1% and
2%, of the total cellular population of involved tissues
diagnosis identification of Reed-Sternberg (RS)
Mononuclear variants are called
Hodgkin cells
RS cells and variants express the CD30 and CD15,
CD45 negative
Acute lymphoblatic leukemia
nearly all ALL patients present with near
replacement of their marrow by lymphoblasts.
Lymphoblasts express TdT,
B-ALL with t(9;22)(q34;q11.2)
BCR-ABl1
CD19, CD22, and/or CD79a
25% of adult B-ALL
worse progrnosis
B-ALL with translocation 11q23
MLL
CD19, CD22, and/or CD79a
neonates and young infants
poor prognosis
B-ALL with t(12:22)(p13:q22)
ETV6-RUNX1
25% of cases of childhood B-ALL.
Favorable prognosis.
T-ALL
minority of ALL cases (25-30%)
T-ALL occur in adolescents and young adults
males over females
express CD2, CD3, CD7 , immature T cells express CD99 and CD1a
ACUTE MYELOID LEUKEMIA (AML)
65 years old. Rare in children and young adults
Diagnosis myeloblast accounting for 20% or more of nucleated cells in the marrow or peripheral blood.
Auer rods
CD117 (C-Kit) , myeloperoxidase, CD33, and
CD13
AML with t(8;21)(q22;q22)
RUNX1-RUNX1T1
Found in 5% AML cases
Fusion protein blocks the transcription of core binding protein needed for hemtapoieses —> block differentiation.
Relatively good prognosis.
AML with t(16;16)(p13.1;q22)
increased myeloblasts and increased moncytes (myelomoncytic leukemia)
mechanism involves core binding factor
Presence of translocation provides diagnosis regardless of blast count
relative good prognosis.
(CD64, CD14)
Acute promyelocytic leukemia
t(15:17)(q22,q12)
distinct subtype AML because abnormal promyelocyte predominate instead of blasts. Can be diagnosed by morphology alone.
5-10% of AML cases.
APL cells are hyperglanular obstructing the nucleus and may contain multiple Auer rods.
APL has fusion gene that invloves retinoic acid receptor alpha (RARA). RARA is needed for differentiation, but is malfanctioning in APL. Super-physiological doses of All-trans retinoic acid treatment helps to reactiave RARA.
Some cases of APL give rise to DIC.
