Hematologic Malignancies VI: T-cell and NK-cell lymphomas Flashcards
T or F. T-cell and NK-cell malignancies are relatively poorly understood in comparison to B-cell malignancies.
T.
While B-cell malignancies which appear to derive from well differentiated cells are in general less aggressive, no such correlation is seen with T-cell malignancies
While B-cell malignancies which appear to derive from well differentiated cells are in general less aggressive, no such correlation is seen with T-cell malignancies
There are no simple recurrent themes in T cell malignancies, unlike B-clel malignancies.
Most do NOT involve translocation of an oncogene to a T-cell receptor promoter (No simple analogy to B-cell lymphomas)
Many show complex karyotypes
Only a few have been genetically defined
What is one useful genetic tool in diagnosing T cell diagnosing
TCR Clonality can often be demonstrated by PCR-based studies of the T-cell receptor gene.
does not apply to NK cells
T or F. Clinical presentation of T-cell malignancies is highly variable
T.
What organs are affected in ALK+ (ALK gene fuses to one of several partners) Anaplastic large cell lymphoma? Most to least
- *lymph nodes
- liver, soft tissues
- bone marrow and cortex
- skin
- peripheral blood
What organs are affected in Angio-immunoblastic T-cell lymphoma? Most to least
- lymph nodes
- skin, bone marrow, spleen, GI tract
What organs are affected in Mycosis fungicides? Most to least
- skin
- lymph nodes, spleen, liver
some peripheral blood involvement (Sezary)
Mycosis fungicides immunophenotype?
its immunophenotype approximates that of a helper T-cell, i.e. it expresses CD4 and – usually – other T-cell antigens like CD3.
so they are CD3/4/and 5+
But it tends to not express the complete package of 4 or 5 normal T-cell antigens – and identifying T-cells that lack one or more of them is one of the ways in which we make this diagnosis.
What is Sezary syndrome?
A subset of mycosis fungoides – specifically, the term applies to those MF cases in which there is significant peripheral blood involvement.
How does mycosis fungoides present clinically?
Patchy, flat red skin lesions that can progress to thick, psoriasis-like or ulcerated lesions;
can involve bloodstream (“Sezary Syndrome”), usually in elderly patients
Normal counterpart of mycosis fungicides?
CD4+ T cells
Morphology of mycosis fungicides?
- Cytology: normal size lymphocytes with indented nuclei
- Tissue: Bland looking lymphocytes that invade the epidermis in clusters (called “Pautrier micro-abscesses”, although they really are not abscesses)
- Bloodstream: bland lymphocytes with “cerebriform” nuclei
Genetic cause of mycosis fungoides?
clonal re-arrangement of T-cell receptor gene
The Paltrier micro-abscesses seen in mycosis fungoides are also common in what?
Nothing BUT It can be hard to distinguish this kind of lesion from some kind of chronic inflammatory/reactive condition.
In the latter, though, the T-cells present will (on molecular analysis) usually contain a variety of re-arranged T-cell receptor genes. In MF, as in other T-cell malignancies, one clone is predominant – so just one rearranged form of the T-cell receptor will be present. We often have to analyze this in order to be sure of the diagnosis.
What is Peripheral T-cell lymphoma NOS?
Currently make up about 30% of T-cell lymphomas
garbage category of “not otherwise specified”
Clinical symptoms of Peripheral T-cell lymphoma NOS?
Diffuse lymphadenopathy
B symptoms (fever, night sweats, weight loss)
paraneoplastic features
eosinophilia
pruritis
hemolytic anemia eosinophilia
Normal counterpart in Peripheral T-cell lymphoma NOS?
unclear
Involved sites in Peripheral T-cell lymphoma NOS?
just about anywhere but usually NOT blood stream
Diagnosis of Peripheral T-cell lymphoma NOS depends on what?
the pathologist’s basic microscopic skills.
If the normal architecture is effaced, AND a collection of cells showing similar histologic characteristics are present, AND those cells don’t show the cohesive, gland-forming architecture typical of a carcinoma, we look into whether this could be a T-cell lymphoma.
In the cases shown, most pathologists can pick out a population of cells that is just too uniform for normal paracortex.
Usually lymph themes of Peripheral T-cell lymphoma NOS?
expanded paracortex and effacement of normal architecture
BUT clusters of “epithelia histiocytes” usually seen near the cortex (paracortical) is possible
Some T-cell malignancies also show a proliferation of cells with large amount of eosinophilic cytoplasm, a cohesive kind of clustering, and normal looking nuclei These “epitheiiod histiocytes” are a clue to the presence of a T-cell malignancy, particularly if they are more prominent near the capsule of the node.
Some T-cell malignancies also show a proliferation of cells with large amount of eosinophilic cytoplasm, a cohesive kind of clustering, and normal looking nuclei These “epitheiiod histiocytes” are a clue to the presence of a T-cell malignancy, particularly if they are more prominent near the capsule of the node.
Immunophenotyping usually completes the diagnosis of Peripheral T-cell lymphoma NOS. What will it look like?
What’s expected: CD3, 5, 7, and 4 or 8
What’s usually seen: Loss of one or more of the above
Variants:
“Double positives” (CD4+, CD8+)
unexpected markers:
1) CD20 (B-cell marker)
2) CD56 (macrophage /monocyte marker)
3) CD30 (R/S cell marker)
Genetics of Peripheral T-cell lymphoma NOS?
Complex karyotype:
Multiple chromosomal gains and losses
Multiple chromosomal deletions
No pattern has emerged
