Hematopathology Flashcards
CD5+ small B cell lymphomas
CLL/SLL and Mantle Cell Lymphoma
Differentiate the two CD5+ small B cell lymphomas
CLL/SLL vs Mantle Cell Lymphoma
CD23 more likely positive in CLL/SLL (negative in MCL)
CYCLIND1 –> negative in CLL/SLL
*watch out for cyclinD1 (BLC1) in proliferation center of CLL –> SOX11 positive is ALWAYS mantle cell lymphoma
t(11;14) –> Mantle Cell
CD43 in a small B cell lymphoma
Positive –> CLL/SLL and Mantle cell and Marginal zone (majority)
Negative –> follicular
t(14;18) in a small B cell lymphoma
Follicular lymphoma
CD10+
BCL6+
B-cell markers positive (CD20, PAX5, CD79a)
t(11;14) in a small B cell lymphoma
Mantle Cell lymphoma
CyclinD1
Sox11 (most specific)
BCL1 (antibody for cyclin D1)
Classic Immunophenotype for CLL/SLL
CD5+
CD23+
CD200+
LEF1+
FMC7+
CD10-
CyclinD1- (except prolif centers)
Sox11-
BCL6-
CD5+
CLL/SLL
Mantle cell
Order CD10
order cyclinD1/sox11
order CD200
order LEF1
CD10+
Follicular lymphoma
*also Burkitt
CD5-
follicular lymphoma
marginal zone lymphoma
CD200+
think CLL/SLL
LEF-1
immediately think CLL/SLL
you see a nodular germinal center like area with CyclinD1 expression
CLL proliferation center vs. Mantle
order Sox11 (+ only in Mantle cell lymphoma)
t(14:18)(q32;q21) translocation
follicular lymphoma
BCL2 gene is recurrently rearranged in up to 95% of FL cases due to t(14;18))q32;q21).
Follicular Lymphoma characteristic translocation
t(14:18)(q32;q21) translocation
*not defining
FL is characterized genetically by a t(14:18)(q32;q21) translocation, with rearrangement of the BCL2 gene, in up to 95% of cases. This translocation can be detected by FISH on cytologic material in over 80% of cases,
What is characterized genetically by a t(14:18)(q32;q21) translocation, with rearrangement of the BCL2 gene, in up to 95% of cases. This translocation can be detected by FISH on cytologic material in over 80% of cases,
Follicular lymphoma
A green probe for igh (immunoglobulin heavy chain) at 14q32 and a red probe for bcl2 at 18q21 come together to give a yellow signal when there is a translocation.
FISH results for follicular lymphoma
What is Marginal Zone lymphoma?
Marginal zone lymphoma is an indolent, low-grade B-cell lymphoma that is divided into nodal and extranodal types. The extranodal type is synonymous with mucosa-associated lymphoid tissue (MALT) lymphoma and is more common than the nodal type, accounting for 7% to 8% of all B-cell lymphomas.
around 8% of all B-cell lymphomas…think predominantly extranodal
Marginal zone lymphoma is an indolent, low-grade B-cell lymphoma that is divided into nodal and extranodal types. The extranodal type is synonymous with mucosa-associated lymphoid tissue (MALT) lymphoma and is more common than the nodal type, accounting for 7% to 8% of all B-cell lymphomas.
MALT lymphoma is an extranodal manifestation of…
Marginal Zone Lymphoma
The two diagnoses are the same, just MALT is more accurately tied with the predominant extranodal manifestation of Marginal Zone Lymphoma
Where might you see FNA of marginal zone?
Although MALT lymphomas occur in a variety of sites, FNA cytologists typically only encounter them in specimens from the salivary gland, lung, lacrimal gland, thyroid, breast, and skin.
B cell lymphoma with a strong association with autoimmune disorders such as Hashimoto thyroiditis and Sjögren syndrome.
Marginal Zone Lymphoma
AKA - MALT lymphoma
*MALT = extranodal marginal zone
What is CLL/SLL?
Small lymphocytic lymphoma (SLL) comprises about 7% of non-Hodgkin lymphoma. 26 It is an indolent and typically incurable neoplasm of older adults. Disease is widespread (nodally and extranodally) at the time of diagnosis, usually including peripheral blood and bone marrow involvement (the latter perversely referred to by a different name: chronic lymphocytic leukemia (CLL)).
Which two B cell lymphomas are about equal in causing about 8% of all B-cell lymphomas?
CLL/SLL and Marginal Zone Lymphoma
CD5 should differentiate
CD5+ —> CLL/SLL
CD5- –> marginal zone
MLL rearrangement in ALL means what?
The t(4;11)(q21;q23) translocation and the associated MLL rearrangement are seen in ALL and the prognosis is very poor.
Is it a good thing that a pediatric bone marrow shows ALL with MLL rearrangement?
NO
The t(4;11)(q21;q23) translocation and the associated MLL rearrangement are seen in ALL and the prognosis is very poor.
What can (FISH) analysis was performed using a myeloid/lymphoid leukemia (MLL) gene dual-color break-apart probe tell you?
prognostic finding in ALL
t(4;11)(q21;q23) translocation
Chromosome changes most common in MDS
The chromosome changes frequently seen in MDS are del(5q)/monosomy 5, del(7q)/monosomy 7, del(20q)/monosomy 20, and trisomy 8.
Burkitt lymphoma has 3 associated rearragements…
t(8;14)(q24;q32),
t(8;22)(q24;q11),
t(2;8)(p11;q24)
characteristic chromosome translocations in BL.
Translocation defining of APL
APL is associated with chromosome translocation t(15;17)(q22;q21)
What drug/chemo treatment is associated with MLL rearranged leukemia later on?
Topoisomerase II inhibitors (etoposide) are associated with MLL rearrangement.
*methotrexate is often used to treat MLL leukemia
*MLL is mixed lineage leukemia, can happen in ALL or AML
*in AML, this rearrangement gives a monoblastic differentiation to AML
Which rearrangement in AML can lead to monoblastic differentiation?
MLL
t(4;11)(q21;q23) translocation and the associated MLL rearrangement
Bone marrow shows acute leukemia. FLOW:
Flow cytometric analysis of the marrow after exclusion of the CD45-negative to dim gate, showed a phenotype of CD19+, CD79a+, CD22+, CD10+, CD20–, CD34+ (partial), CD117–, HLA-DR+, CD43+, CD38+, CD52+, and TdT+.
Pre-B ALL
*look for hyperdiploidy status for a good prognosis
immunohistochemical staining for Bcl-6, and t(3;14)(q27;q32) translocation are characteristic ….
DLBCL.
DLBCL best IHC and FISH results for diagnosis
immunohistochemical staining for Bcl-6, and t(3;14)(q27;q32) translocation are characteristic of DLBCL.
The t(11;18) translocation involves the API2 and MALT1 genes and is mainly detected in…
gastric and pulmonary MALT lymphomas
Most important translocation MALT lymphomas of the GI tract
t(11;18)(q21;q21) –> API2 and MALT1 fusion
*confers resistance to h pylori eradication treatment
most common translocation in ALCL
anaplastic large cell lymphoma
*t(2;5)(p23;q35)
*CD30 positive, ALK positive probably (80%)
*EMA positive
*DDX with hodgkin, melanoma, DLBCL
adverse prognostic features of CLL
CD38 expression
ZAP 70 expression
germline (or ‘unmutated’) IGH –> mutated IGH is actually a GOOD thing in CLL/SLL
11q
17p
GOOD prognosis in CLL
mutated IGH
13q deletion
*remember number criteria for CLL
*greater than 5X10^9 for 3 months or more (otherwise monoclonal B lymphocytosis)
greater than 5X10^9 for 3 months or more (otherwise monoclonal B lymphocytosis)
numerical diagnostic criteria for CLL
characteristic t(14;18)(q32;q21)
Translocation characteristic for Follicular Lymphoma
*CD19+, CD20+, sIg+, CD10+, bcl-6 and bcl2+
*look for mum-1 and hans classification
*CD10+ bcl6+, mum1- is GC-type
adverse features of MDS
bad and worsening cytopenias
cytopenias spreading lineages
elevated blast count –> 2 in peripheral blood, 5-19 in bone marrow
Adverse: TP53, EZH2, RUNX1, ASXL1, ETV6, complex karyotype (greater than 3 abnormalities)
SF3B1
Ring sideroblasts
good prognosis type of MDS (single lineage dysplasia)
specific chromosomal deletion in MDS that comprises a specific diagnosis
isolated del(5q)
A CD34 negative, HLA-DR negative, CD117 positive, CD33 positive, and MPO positive immunophenotype…
is characteristic of acute promyelocytic leukemia.
phenotype best for acute promyelocytic leukemia
A CD34 negative, HLA-DR negative, CD117 positive, CD33 positive, and MPO positive
Myelomonocytic blasts phenotype
leukemic cells that are monoblasts and promonocytes characterized by delicate nuclear foldings, as well as abundant blue-gray cytoplasm.
*These cells express monocytic markers, such as CD11c, CD36, CD14, CD4 and CD64
*also myelomonocytic markers such as CD33 and CD13.
*NOTE: CD34 is often negative due to monocytic maturation of the acute leukemia.
Foldy and vacuolated blasts are CD11c positive, CD64 positive, CD36 positive, CD14 positive, CD4 positive, CD33 positive and CD13 positive
AML with monocytic differentiation
promyelomonocytic differentiation
monoblastic leukemia
CD19 positive, CD10 positive, CD34 positive, and cytoplasmic IgM positive immunophenotype
B-lymphoblastic leukemia/lymphoma
Hairy Cell leukemia phenotype
CD19 positive, CD20 positive, CD11c positive, CD25 positive, and CD103 positive immunophenotype
phenotype of NLPHL popcorn cells
CD20 positive, CD10 positive, Bcl-6 positive, and CD45 positive.
*they are B cells
*CD15 and CD3O negative as they are not classic HD
what benign architectural disruption event can be seen in LN with NLPHL in it or previously in it?
PTGC may be seen simultaneously in the same lymph node affected, or in previous or subsequent lymph node biopsies.
Most common places involved by hodgkin lymhomas
NLPHL: Cervical, axillary, and inguinal lymph nodes are most common sites of involvement.
Classic: Mediastinal
NEITHER: bone marrow (don’t click bone marrow)
CD20 positive, CD5 negative, CD25 positive, CD103 positive, Annexin A1 positive, tartrate resistant acid phosphatase positive, and CD123 positive immunophenotype is typical of….
Hairy cell leukemia
*interstitial infiltration by fried egg cells
*monocytopenia
*splenomagaly
t(8;14)
This translocation is typical of Burkitt lymphoma (BL) and can be seen in other aggressive B-cell lymphomas. BL is CD20 bright, CD10 positive, Bcl6 positive, CD43 positive, CD5 negative, and Bcl2 negative.
CD25 is also known as…
sIL-2 receptor
*look for this in HLH context
Fever
Splenomegaly
Cytopenias
Hypertriglyceridemia or Hypofibrinogemia
Serum ferritin ≥ 500 µg/L
Hemophagocytosis
Low or absent NK-cell activity
Soluble CD25 (sIL-2 receptor) > 2,400 U/mL
HLH criteria
Fever
Splenomegaly
Cytopenias
Hypertriglyceridemia or Hypofibrinogemia
Serum ferritin ≥ 500 µg/L
Hemophagocytosis
Low or absent NK-cell activity
Soluble CD25 (sIL-2 receptor) > 2,400 U/mL
t(14;18)(q32;q21) translocation involving the IGH and MALT1 genes
This translocation is mainly detected in MALT lymphoma arising in ocular adnexa/orbit and salivary gland lesions.
*look for association with chlamydia psittaci
*MOST COMMON DISTRACTOR in MALT lymphoma of stomach question, which wants you to pick t(11;18), conferring resistance to h pylori eradication
Small bowel MALT lymphoma…
campylobacter jejuni association
Small intestinal marginal zone lymphoma or immunoproliferative small intestinal disease (IPSID) is associated with
campylobacter jejuni
Chlamydia psittaci and lymphoma
Lacrimal gland or orbital marginal zone lymphomas are associated with Chlamydia psittaci.
*In addition to the infectious etiologies, patients with autoimmune conditions, such as Hashimoto thyroiditis and Sjögren syndrome, have a propensity for developing thyroid and salivary gland marginal zone lymphomas, respectively.
*t(5;11) most common translocation of malt lymphoma in eyes
WHAT lymphoma cells are cytotoxic T cells, usually of the gamma/delta (γδ) type, which express granzyme and TIA-1.
hepatosplenic T-cell lymphoma.
*The lymphoma cells are cytotoxic T cells, usually of the γδ type; however, a minority of cases appear to be of α/β type.
*CD3 positive, CD5 negative, CD4 negative, and CD8 negative/positive is the characteristic immunophenotype
t(11;14)(q13;q32) is characteristic of what?
Mantle cell lymphoma
cyclin D1 and immunoglobulin
poor prognostic indicators in myeloma
high serub beta-2 microglobulin
low serum albumin
high ki-67,
hypopoloidy
t(4;14)
t(14;16)
deletion of chromosomes 13 and 17
typical and less typical rearrangements for burkitt lymphoma
Burkitt lymphoma (BL).
* t(8;14) translocation between the immunoglobulin heavy chain and MYC genes is characteristically seen in BL.
*The MYC gene can also be rearranged in variant translocations, though less commonly, including t(2;8) and t(8;22) translocations with the kappa and lambda immunoglobulin light chain genes, respectively.
*NOTE: all about deregulation of the MYC gene
Biallelic CEBPA mutations in AML
Biallelic CEBPA mutations are also typically associated with a normal karyotype and are associated with favorable prognosis.
NPM1 mutation in AML
NPM1 mutations are typically associated with a normal karyotype and are associated with a favorable prognosis when concurrent FLT3 is unmutated (wild type).
KIT mutations in AML
KIT mutations are seen in AML with t(8;21)(q22;q22.1) and AML with inv 16(p13.1q22) or t(16;16)(p13.1;q22). In both entities, KIT mutations are associated with a worse prognosis.
*NOTEUnlike FLT3 mutation status, KIT mutation is not used in current risk stratification schemes.
EBV and PTLD
*Risk of developing a PTLD is related to the degree of immunosuppression and EBV status prior to transplantation. *A negative EBV status prior to transplantation carries a higher risk for developing PTLD.
EBV-negative lesions tend to develop later in the course of transplantation, are more common in adults, and are more likely to be of monomorphic type.
*The majority of PTLD are EBV-driven B-cell proliferations, which tend to develop earlier (early onset) after transplantation.
Lymphomatoid granulomatosis
Lymphomatoid granulomatosis is an Epstein-Barr virus-positive pulmonary lymphoma of B-cell origin.
*vasculocentric necrotic nodules.
*In addition to the lung, skin and the central nervous system can be involved.
Which Castelman Disease manifestation is HHV-8 associated?
*Unicentric HV-CD typically presents in young adults as localized lymphadenopathy and excision is typically curative
*Unicentric HV-CD is negative for HHV8
*multicentric Castleman disease, typically of PC-CD morphology, can be HHV8 positive or negative.
*HIV infection is highly associated with HHV8-positive MULTICENTRIC Castleman disease (MCD)
Two clinical associations with plasma cell variant of castleman’s disease
*HHV8 can be positive or negative in unicentric, non-HIV cases
*PC-CD can be associated with POEMS syndrome, which is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes
Expression of which marker by mast cells in patients with cutaneous mast cell infiltrates is indicative of systemic disease?
CD25
A CD3 positive, CD5 positive, CD7 negative, CD4 positive, CD8 negative, and CD25 positive phenotype is characteristic of…
adult T-cell leukemia/lymphoma (ATLL).
*HTLV-1, japan and caribbean
*median presentation of 58 years
*hypercalcemia
*flower cell
you see HLH and you should try and find…
Underlying malignancy
* T-cell lymphomas are the most common malignancy associated with HLH, in particular subcutaneous panniculitis-like T-cell lymphoma.
*T-cell large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma (ATLL), anaplastic large cell lymphoma, etc. have also been associated with HLH.
hyperdiploid karyotype in myeloma
Good prognosis
*A hyperdiploid karyotype is due to trisomies of the odd chromosomes (except chromosome 13), such as 3, 5, 7, 9, 11, 15, 19, and 21.
Del 17p in myeloma
poor prognosis
*also hypodiploid is poor prognosis
Monosomy 13 in myeloma
intermediate risk
near tetraploid in myeloma
poor prognosis
*only hyperdiploid is good
t(14;16) and t(14;20) are associated with what in myeloma?
High risk, poor prognosis
CD4 and CD8 double positive T cells
Thymic T cells
*could represent malignant phenotype, but wouldn’t scatter or spread on flow
CD34+/HLA-DR+/MPO+/dim CD19+
acute myeloid leukemia with t(8;21)
RARA fusions that don’t respond to ATRA in APL
cases with ZBTB16::RARA and STAT5B::RARA do not respond to treatment with ATRA.
t(6;9)(p23;q34); DEK::NUP214
Acute myeloid leukemia (AML) with t(6;9)(p23;q34); DEK::NUP214 is an AML with recurrent genetic abnormality in the 2016 WHO classification.
*commonly associated with basophilia, myelomonocytic differentiation, FLT3-ITD mutations
CD20+/CD103-/CD25-/cyclinD1-/AnnexinA1- with deletion 7q
Expected IP for splenic marginal zone lymphoma
*spleen, splenic hilar lymph nodes, and bone marrow.
*Bone marrow shows nodular interstitial and intrasinusoidal pattern of involvement.
CD20+/CD103+/CD25+/cyclinD1+/AnnexinA1+ with numerical abnormalities of chromosomes 5 and 7
Hairy cell leukemia
Intrasinusoidal growth of T-cells is characteristic of two neoplastic T-cell entities:
*T-cell large granular lymphocytic leukemia (T-LGLL) –> usually does not expand the sinusoids
*hepatosplenic T-cell lymphoma (not an answer choice in this question). –> usually expands sinusoids
SEC23B molecular abnormality
CDA II is the most common of the CDAs, and many binucleate erythroblasts are seen in the marrow.
*congenital dyserythropoietic anemia (CDA) Type II
TCL1A BAP FISH
T-cell prolymphocytic leukemia (T-PLL)
*Although most T-lymphoproliferative disorders demonstrate immunophenotypic aberrancy by loss of T-cell associated antigens, T-PLL is notorious for retaining expression of these antigens.
*While T-PLL is usually CD4 positive, it is not uncommon to see coexpression of both CD4 and CD8 (double positive) in almost 25% of cases.
inv(16) in AML
CBFB-MYH11
*POSITIVE: CD13, 33, 14, 4, 64
*monocytic and neutrophilic
AML with super granular cells and lots of eos
inv(16) - good prognosis
B-ALL with t(12;21)
good prognosis
*The t(12;21) juxtaposes the ETV6 gene on 12p13 to the RUNX1 gene on 21q22.
The classic Hodgkin lymphomas (CHLs) are …
The classic Hodgkin lymphomas (CHLs) are lymphocyte depleted, lymphocyte rich, mixed cellularity, and nodular sclerosis.
