Blood and BM Path Chapter 28 - Chronic Lymphoid Leukemias Flashcards
Characteristic B-CLL immunophenotype
CD19+CD5+CD23+
Most common leukemia in the Western world
CLL
Morphologic features of CLL cells
- Generally low-grade lymphocytic appearance and low-grade nuclear features
- Smudge cells are often seen on peripheral smear
- Plasmacytoid morphology and clefted/irregular nucleated cells may be observed
- May be up to 10% prolymphocytes (If <55% prolymphocytes, consider ALL)
Smudge cells
Occur commonly in CLL/SLL due to poor cytoskeletal integrity in these cells – sometimes up to 75% of lesional cells!
However, adding albumin to your preparation before making your slide can help reduce the number of smudge cells and improve morphology
Richter’s syndrome / Richter transformation
Clinco-pathological transformation of CLL into an aggressive lymphoma – most commonly DLBCL
SLL pathologic features
Pseudofollicular pattern
Who has a worse prognosis? Patients with IGHV loci that have undergone somatic hypermutation, or those with IGHV loci which have not?
Patients without evidence of somatic hypermutation have a worse prognosis
B-PLL
B-prolymphocytic leukemia
An uncommon cause of chronic leukemia, affecting primarily elderly individuals (median age 70). Rate of progression to ALL is more rapid than CLL (with worse prognosis), and an M protein is more often present.
Prolymphocytes must exceed 55% of peripheral blood cells to make the diagnosis. Anemia and thrombocytopenia are common.
Morphology: Medium-sized cells with prominent nucleoli and vesicular chromatin quality.
Immunophenotype: IgM and/or IgD +, CD19+, CD5- and CD23-. Additionally CD20+, CD22+, CD79a+, and FMC7+. Often CD11c+. (If CD5 is seen, leukemic MCL is more likely)
Cytogenetics: No specific characteristic aberration, but often have complex karyotypes. TP53 abnormalities, 11q22-23 deletion, and 13q14 deletion are common.
T-PLL
T-prolymphocytic leukemia
An uncommon cause of chronic leukemia, affecting primarily individuals in middle-late old age. 1/3 of patients have skin involvement with pruritic rash or generalized erythroderma. Prognosis is very poor (<1 year), however some patients have been cured with anti-CD52 and HSC transplant.
Prolymphocytes must exceed 55% of peripheral blood cells to make the diagnosis. Anemia is common.
Morphology: Medium-to-small sized lymphoid cells with irregular nuclear contours, some with prominent medium-sized nucleoli. Cytoplasm is slightly basophilic and may be blebbed. In 5% of cases, cerebriform nuclei may be seen.
Immunophenotype: CD7+, cCD3+ (though may be surface CD3-). TCL1+ in most cases. CD25 negative of very weak. NK cell markers, CD1a, and TdT negative.
Cytogenetics: TCR beta or gamma is rearranged in all cases of T-PLL. Inv(14)(q11q32) is observed in 80% of cases. In a minority of cases, t(14;14)(q11q32) may occur instead. Both result in disordered TCL1 at the TCR alpha/delta locus. Complex karyotypes are common.
Chronic large granular lymphocytic leukemia may be derived from. . .
. . .from CD8 T cells or NK cells
T-LGL leukemia
May be T cell type or NK cell type. More common in individuals of Asian descent.
Often accompanied by neutropenia, anemia, thrombocytopenia.
Morphology: Medium-sized cells with abundant, weakly basophilic cytoplasm and prominent azurophilic granules. Bone marow should be evaluated with CD3, CD8, and CD57 stains.
Immunophenotype:
- T cell subtype: Usually CD3+CD8+TCRa/b+, but may be dual CD4/CD8 expressing or non-CD4/CD8 expressing – never CD8-CD4+. CD57, CD45RA, and CD62L are usually positive in leukemic clones.
- NK cell subtype: CD3-CD56+ and/or CD16+. Can be further characterized by KIR / CD158 studies. 1/3 of NK-LGLs will be monoclonal by KIR, the other 2/3 will have undetectable KIR. Either of these findings is aberrant.
Cytogenetics:
- T cell subtype: del(6q)
- NK cell subtype: Normal karyotype
KIRs in flow cytometry
Killer Ig-like receptor, one of the inhibitory receptors of NK cell that recognizes MHC class I (the other is NKG2A). The CD code is CD158.
An important marker for NK cell clonality
There are three subtpyes: CD158a, CD158b, CD158e.
Aggressive NK cell leukemia
Very rare, EBV-related leukemia of NK cells with morphology similar to T or NK-LGL leukemias, but with a more severe acute presentation. Has a predilection for affecting those of Asian descent. Rare EBV-independent cases are seen without ancestral preference.
Ultimately STAT3-mediated transcription of myc drives proliferation in both EBV-related and non-EBV-related cases.
Morphology: Resemble LGLs, but have additional cytologic atypia with a high N/C ratio, basophilic cytoplasm, and a visible nucleolus.
Immunophenotype: Classically CD2+, CD16+, CD56+ with loss of CD7 and variable CD8 and CD57.
Cytogenetics: del(6q) and del(11q) have been described.
Sezary syndrome and Mycosis Fungoides
SS involves skin and blood, MF is limited to the skin. Both are T cell lymphoma/leukemias that tend to occur in older individuals and may progress to ALCL.
Morphology: Sezary cells may be small or large, but both will have lobulated or cerebriform nuclei. Flower-shaped nuclei may sometimes be seen. Some Sezary cells have a ring of glycogen-filled vacuoles within their cytoplasm (“rosary bead” sign). In skin, they may be present at and obscure the DEJ.
Immunophenotype: Classically CD2, CD3, CD4, and CD5 positive. CD7 positive in 50% of cases. CD8 and CD25 are typically negative (if expressed, CD25 is weak). Recent studies suggest that Sezary cells have a memory T-cell like immunoprofile: CD4+CD27+CD26-CD45RA-. CD27 is usually positive in Sezary and negative in benign inflammatory erythroderma.
Cytogenetics:
- Sezary: TCR is usually rearranged. Losses on chromosomes 10 and 17 are common. Gain on chromosome 8 involving the MYC region is common.
- MF: Gain of 7q, loss of 5q and 9p.
Adult T cell leukemia/lymphoma (ATLL)
Occurs exclusively in carriers of HTLV-1. Endemic in Japan and the West Indies. ~95% of cases will not progress to lymphoma/leukemia and will remain asymptomatic carriers.
90% of cases present as leukemia, 10% as lymphoma. Opportunistic infections are common.
Morphology: Very pleomorphic atypical lymphocytes with moderate cytoplasm and nucleoli. Flower-shaped nuclear lobation is common. Some resemble Sezary cells.
Immunophenotyping: Usually exhibit the phenotype of activated CD4+ memory T cells, CD2, CD5, CD25, CD45RO, CD29, TCR alpha/beta, HLA-DR. Usually lack CD7 and CD26 and have an unusually low expression of CD3 for T cells.
Cytogenetics: Highly complex and variable. Gain of 3 or 3p is more common in the acute subset. Mutation or deletion of P53, p15INK4B, or p16INK4A is observed in 50% of cases.
Possible cytogenetic abnormalities in CLL
Possible mutations in CLL
Note that none of these are specific for CLL/SLL
