Hematologic Malignancies VI: T-cell and NK-cell lymphomas

Question 1

T or F. T-cell and NK-cell malignancies are relatively poorly understood in comparison to B-cell malignancies.

Answer 1

T.

Question 2

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

Answer 2

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

Question 3

There are no simple recurrent themes in T cell malignancies, unlike B-clel malignancies.

Answer 3

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

Question 4

What is one useful genetic tool in diagnosing T cell diagnosing

Answer 4

TCR Clonality can often be demonstrated by PCR-based studies of the T-cell receptor gene.

does not apply to NK cells

Question 5

T or F. Clinical presentation of T-cell malignancies is highly variable

Answer 5

T.

Question 6

What organs are affected in ALK+ (ALK gene fuses to one of several partners) Anaplastic large cell lymphoma? Most to least

Answer 6

• *lymph nodes
• liver, soft tissues
• bone marrow and cortex
• skin
• peripheral blood

Question 7

What organs are affected in Angio-immunoblastic T-cell lymphoma? Most to least

Answer 7

• lymph nodes

- skin, bone marrow, spleen, GI tract

Question 8

What organs are affected in Mycosis fungicides? Most to least

Answer 8

• skin
• lymph nodes, spleen, liver

some peripheral blood involvement (Sezary)

Question 9

Mycosis fungicides immunophenotype?

Answer 9

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.

Question 10

What is Sezary syndrome?

Answer 10

A subset of mycosis fungoides – specifically, the term applies to those MF cases in which there is significant peripheral blood involvement.

Question 11

How does mycosis fungoides present clinically?

Answer 11

Patchy, flat red skin lesions that can progress to thick, psoriasis-like or ulcerated lesions;

can involve bloodstream (“Sezary Syndrome”), usually in elderly patients

Question 12

Normal counterpart of mycosis fungicides?

Answer 12

CD4+ T cells

Question 13

Morphology of mycosis fungicides?

Answer 13

• 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

Question 14

Genetic cause of mycosis fungoides?

Answer 14

clonal re-arrangement of T-cell receptor gene

Question 15

The Paltrier micro-abscesses seen in mycosis fungoides are also common in what?

Answer 15

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.

Question 16

What is Peripheral T-cell lymphoma NOS?

Answer 16

Currently make up about 30% of T-cell lymphomas

garbage category of “not otherwise specified”

Question 17

Clinical symptoms of Peripheral T-cell lymphoma NOS?

Answer 17

Diffuse lymphadenopathy

B symptoms (fever, night sweats, weight loss)

paraneoplastic features
eosinophilia
pruritis
hemolytic anemia eosinophilia

Question 18

Normal counterpart in Peripheral T-cell lymphoma NOS?

Answer 18

unclear

Question 19

Involved sites in Peripheral T-cell lymphoma NOS?

Answer 19

just about anywhere but usually NOT blood stream

Question 20

Diagnosis of Peripheral T-cell lymphoma NOS depends on what?

Answer 20

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.

Question 21

Usually lymph themes of Peripheral T-cell lymphoma NOS?

Answer 21

expanded paracortex and effacement of normal architecture

BUT clusters of “epithelia histiocytes” usually seen near the cortex (paracortical) is possible

Question 22

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.

Answer 22

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.

Question 23

Immunophenotyping usually completes the diagnosis of Peripheral T-cell lymphoma NOS. What will it look like?

Answer 23

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)

Question 24

Genetics of Peripheral T-cell lymphoma NOS?

Answer 24

Complex karyotype:
Multiple chromosomal gains and losses
Multiple chromosomal deletions
No pattern has emerged

Question 25

Clinical course of Peripheral T-cell lymphoma NOS?

Answer 25

aggressive with 5 yr survival 20-30%

Question 26

What is Angioimmunoblastic T-cell lymphoma (AITL)? Original cell type?

Answer 26

This is one of the better characterized T-cell lymphomas. The immunophenotype of these cells corrresponds to a particular class of normal mature T-cells, the T-follicular helper cells.

not on exam

Question 27

Clinical presentation of AITL?

Answer 27

Rapidly progressive critical illness

• Diffuse lymphadenopathy
• Hepatosplenomegaly
• Skin rash
• cold autoimmune hemolytic anemia
• Evidence of immunocompromise

These usually present to us with widespread, rapidly progressing disease.

Question 28

Normal counterpart in AITL?

Answer 28

follicular T-helper cells

Question 29

Involved sites in AITL?

Answer 29

lymph nodes
spleen, liver
bone marrow
skin

Question 30

Lymph node morphology in AITL?

Answer 30

normal/reactive lymph node

involvement of multiple superficial lymph nodes

What we typically see is “effacement of normal architecture”, although occasional germinal centers are typically still present.

The node is enlarged by an expansion of the paracortex.

Unfortunately, the paracortex in reactive/ infectious conditions shows a great deal of variation in cell content, and it normally contains occasional lymphoid cells with large nuclei and prominent nucleol (“immunoblasts”).

So finding those “angry looking” features at high power is not helpful. What we do see in this case is an unusual expansion of small paracortical vessels, often with a dense eosinophilic material thickening their walls, and a larger number of immunoblasts than is typical of reactive conditions

Question 31

Immunophenotype of AITL?

Answer 31

Immunostains:

• Excess CD10+ cells in paracortex (B cells are not usually common in the paracortex!!!)
• Residual FDC networks (CD21+)

Flow: CD3+, CD4+, CD10+

Question 32

Follicular dendritic cels (FDC) present antigens to B and T cells in germinal centers, and their processes form a kind of meshwork within the GCs. In most cases, if the GC’s are gone, an immunostain for the FDC’s (CD21) shows that they are gone too. In the case of AILT, they are suprisingly NOT absent; ghosts of germinal centers can be identified, another key clue to a diagnosis of AILT.

Answer 32

Follicular dendritic cels (FDC) present antigens to B and T cells in germinal centers, and their processes form a kind of meshwork within the GCs. In most cases, if the GC’s are gone, an immunostain for the FDC’s (CD21) shows that they are gone too. In the case of AILT, they are suprisingly NOT absent; ghosts of germinal centers can be identified, another key clue to a diagnosis of AILT.

Question 33

Finally, flow cytometry can anil down the diagnosis by showing a large population of CD10+ T-cells. In normal and reactive nodes this population is too small to be clearly identified by this method.

Answer 33

Finally, flow cytometry can anil down the diagnosis by showing a large population of CD10+ T-cells. In normal and reactive nodes this population is too small to be clearly identified by this method.

Question 34

Genetics of AITL?

Answer 34

Complex karyotype:
Multiple chromosomal gains and losses
Multiple chromosomal deletions
No pattern has emerged

Question 35

Clinical course of AITL?

Answer 35

Aggressive

Median survival less than 3 years

The prognosis is poor, and standard chemotherapeutic agents have a high morbidity rate in AILT because their immunocompromising side effects are compounded by the immunocompromise inherent to the disease itself.