Chapter 13: Peripheral T-Cell and NK-Cell Neoplasms Flashcards
These categories include a heterogeneous group of neoplasms having phenotypes resembling
mature T cells or NK cells.
Peripheral T-cell tumors make up about 5% to 10% of NHLs in the United States and Europe, but are more common in Asia.
NK-cell tumors are rare in the West,
but also more common in the Far East.
Only the most common diagnoses and those of
particular pathogenetic interest will be discussed.
- Peripheral T-Cell Lymphoma, Unspecified
- Anaplastic Large-Cell Lymphoma (ALK Positive)
- Adult T-Cell Leukemia/Lymphoma
- Mycosis Fungoides/Sézary Syndrome
- Large Granular Lymphocytic Leukemia
- Extranodal NK/T-Cell Lymphoma
What is Peripheral T-Cell Lymphoma, Unspecified?
Although the WHO classification includes a number of distinct peripheral T-cell neoplasms,
many of these lymphomas are not easily categorized and are lumped into a “wastebasket”
diagnosis, peripheral T-cell lymphoma, unspecified .
- As might be expected, no morphologic
- feature is pathognomonic, but certain findings are characteristic.
- These tumors efface lymphnodes diffusely and are typically composed of a pleomorphic mixture of variably sized malignant T cells ( Fig. 13-22 ).
- There is often a prominent infiltrate of reactive cells, such as eosinophils and macrophages, probably attracted by tumor-derived cytokines.
- Brisk neoangiogenesis mayalso be seen.
FIGURE 13-22 Peripheral T-cell lymphoma, unspecified (lymph node). A spectrum of small,
intermediate, and large lymphoid cells, many with irregular nuclear contours, is visible.
What is required in the diagnosis of Peripheral T-Cell Lymphoma, Unspecified?
The diagnosis requires immunophenotyping.
By definition, all peripheral T-cell lymphomas have
a mature T-cell phenotype.
What is the immunophenotype of Peripheral T cell Lymphoma, unspecified?
They usually express CD2, CD3, CD5, and either αβ or γδ T-cell receptors.
Some also express CD4 or CD8; such tumors are t aken to be of helper or cytotoxic
T-cell origin, respectively.
However, many tumors have phenotypes that do not resemble any known normal T cell.
In difficult cases where the differential diagnosis lies between lymphoma and a florid reactive process, what analysis can be used to confirm the presence of clona T-cell receptor rearrangements?
DNA analysis
What are the clinical features of Peripheral T-Cell Lymphoma, Unspecified?
Most patients present with generalized lymphadenopathy, sometimes accompanied by
eosinophilia, pruritus, fever, and weight loss.
What is the prognosis of Peripheral T-cell Lymphoma, unspecified?
Although cures of peripheral T-cell lymphoma have
been reported,these tumorshave a significantly worse prognosisthan comparably aggressive
mature B-cell neoplasms(e.g., diffuse large B-cell lymphoma).
What is Anaplastic Large-Cell Lymphoma (ALK Positive)?
This uncommon entity is defined by the presence of rearrangements in the ALK gene on
chromosome 2p23.
These rearrangements break the ALK locus and lead to the formation of chimeric genes encoding ALK fusion proteins, constitutively active tyrosine kinases that trigger a number of signaling pathways, including the JAK/STAT pathway
What is the composition of Anaplastic Large-Cell Lymphoma (ALK Positive)?
As the name implies, this tumor is typically composed of large anaplastic cells, some containing horseshoe-shaped nuclei and voluminous cytoplasm (so-called hallmark cells) ( Fig. 13-23A ).
The tumor cells often cluster about venules and infiltrate lymphoid sinuses, mimicking the
appearance of metastatic carcinoma.
ALK is not expressed in normal lymphocytes or other
lymphomas;thus, thedetection of ALK protein in tumor cells ( Fig. 13-23B ) is a reliable
indicator of an ALK gene rearrangement.
What are hallmark cells?
As the name implies, this tumor is typically composed of large anaplastic cells, some containing horseshoe-shaped nuclei and voluminous cytoplasm (so-called hallmark cells) ( Fig. 13-23A ).
How does the ALK mimick the
appearance of metastatic carcinoma?
The tumor cells often cluster about venules and infiltrate lymphoid sinuses,
Why is detection of ALK protein in tumor cells ( Fig. 13-23B ) is a reliable
indicator of an ALK gene rearrangement.
ALK is not expressed in normal lymphocytes or other
lymphomas; thus, the detection of ALK protein in tumor cells ( Fig. 13-23B ) is a reliable
indicator of an ALK gene rearrangement.
FIGURE 13-23 Anaplastic large-cell lymphoma.
- A, Several “hallmark” cells with horseshoelike or “embryoid” nuclei and abundant cytoplasm lie near the center of the field.
- B, Immunohistochemical stain demonstrating the presence of ALK fusion protein.
T-cell lymphomas with ALK rearrangements tend to occur in what age?
children or young adults,
Why does ALK carry a very good prognosis(unlike other aggressive peripheral T-cell neoplasms)?
frequently involve soft tissues,
What is the cure rate with chemotherapy in ALK?
75% to 80%.
Inhibitors of ALK
are under development and offer an excellent opportunity for the development of a selective,
targeted therapy
.
