Peripheral T Cell and Lymphoblastic malignancies

Question 1

Peripheral T-cell and NK-cell Neoplasms in general

Answer 1

Higher % in Asia

Much more aggressive neoplasms than B-cell neoplasms

(Much worse prognosis than B-cell neoplasms)

Occur Predominately in extranodal sites
Diagnosis via flow cytometry marker studies
Exhibit T-cell surface CD markers
Lack TdT
May or may not express CD4 and/or CD8

Question 2

Peripheral T-cell Lymphoma, Unspecified

Answer 2

Present with lymphadenopathy and sometimes systemic signs (pruritis, fever, and weight loss)

** T-cell lymphomas associated with lymph nodes

Significantly worse prognosis than comparable B-cell

**Survival under 1 year with treatment

CD2, CD3, CD5, αβ or γδ T-cell receptors, +/- CD4 or CD8

Question 3

Anaplastic Large Cell Lymphoma

Answer 3

ALK+ [anaplastic lymphoma kinase (ALK) gene

Results in fusion protein which activates tyrosine kinase (JAK/STAT)

Excellent response to treatment when ALK+

ALK-
Usually in older adults
poor prognosis ~other peripheral T-cell lymphomas

Markers – CD30, +/- ALK

histology: “hallmark” cells (horseshoe shape), ALK fusion protein

Question 4

Adult T-cell Leukemia/Lymphoma

Answer 4

• Only in adults infected with human T-cell leukemia virus Type 1 (HTLV-1)

Endemic in Southern Japan, West Africa & ** Caribbean

Hepatosplenomegaly, lymphadenopathy, skin lesions, lymphocytosis, hypercalcemia
Rapidly progressive; fatal within months
Median survival 8 months

Characteristic cloverleaf nucleii
High levels of CD 25

Question 5

Mycosis Fungoides

Answer 5

CD4+ T-cell lymphoma of the skin

• Sezary syndrome is variant in which skin involvement is manifest as a generalized exfoliative erythroderma

Leukemic phase with Sezary cell (cerebriform nuclei) seen in Sezary syndrome and 25% of plaque
→Survival less than 3 years

“My Fun Seizures!”

Question 6

Large Granular Lymphocytic Leukemia

Answer 6

Associated with rheumatologic disorders
** Felty syndrome in some (rheumatoid arthritis,
splenomegaly and neutropenia)

Lymphocytes with abundant blue cytoplasm containing scattered azurophilic granules
Rare disorder
Variants
CD3+ T-cell (indolent)
CD56+ NK cell (aggressive)
Neutropenia & anemia despite scant marrow involvement
Involves splenic red pulp and hepatic sinusoids (hepatomegaly)

Question 7

Felty syndrome

Answer 7

rheumatoid arthritis,

splenomegaly and neutropenia

Question 8

Extranodal NK/T-cell Lymphoma

Answer 8

• • Clinically presents as sinonasal lymphoma…..aggressive neoplasm poorly responsive to chemotherapy
• • EBV related

Tumor cells typically surround and invade small vessels

Most CD56+ NK cell
Sometimes midline skin
or testes involved

P.K.A. lethal midline granuloma, midline malignant reticulocytosis and angiocentric lymphoma

Question 9

Most common acute leukemia associated with Down Syndrome

Answer 9

Lymphoblastic Neoplasms

Question 10

Lymphoblastic Neoplasms IN GENERAL

Answer 10

Terminology: Neoplasms also known as
“Acute Lymphoblastic Leukemia”
US Epidemiology:
Together 80 % of childhood leukemias
Twice as common in Caucasians as in blacks
Slightly more common in Hispanic population
Slightly more common in males than females

Most common acute leukemia associated with Down Syndrome !!!!

Question 11

Lymphoblastic Neoplasms Body Location and Morphology

Answer 11

B-cell precursor neoplasms present in young kids (peak 3 y.o.) with extensive bone marrow involvement with peripheral blood “leukemic phase”
Occasionally present as “lymphoma” with mass in lymph nodes

T-cell precursor neoplasms tend to present in adolescent males as lymphoma with thymic involvement and possible leukemia

May be aleukemic

Question 12

Acute lymphoblastic leukemia histology

Answer 12

PAS+ / Myeloperoxidase -

Question 13

Lymphoblastic Neoplasms Immunophenotype:

Answer 13

+ TdT (terminal deoxynucleotidyltransferase)

B-cell type (Maturation arrested before surface expression of Ig)
CD19, PAX5

T-cell type (arrested at early stages of development)
+ CD1, CD2, CD5, CD7

Special stains: PAS+ /Myeloperoxidase -

Cytogenetics and Molecular Genetics:
~ 90% patients have structural changes in chromosomes of B-cell leukemic cells with hyperdiploidy most common, some hypodiploidy and some expressing Philadelphia chromosome (t9:22)

Question 14

70% T-ALLs have what gain of function mutation?

Answer 14

NOTCH1

Question 15

Lymphoblastic Neoplasms Clinical Features

Answer 15

Abrupt and stormy onset
	Classic Symptoms Leukemia: Depressed marrow function (bone marrow replaced by leukemic cells)
			Fatigue (anemia)
			Infection & fever (neutropenia)
			Bleeding (thrombocytopenia)
	Generalized Lymphadenopathy
	Bone pain and tenderness
	Splenomegaly and Hepatomegaly
	CNS Symptoms - meningeal involvement (headache, vomiting) and nerve palsies 
	Testicular involvement

Question 16

Lymphoblastic Neoplasms Prognosis:

Answer 16

95 % childhood B-cell ALL achieves remission & 3/4 considered cured

Bad Prognosis Factors:
(1) Age less than 2 years (increased incidence of MLL gene mutations)
(2) Presentation in adolescence or adulthood
(3) Peripheral blast count > 100,000 cells/ul
(4) Presence of unfavorable cytogenetic aberrations
Philadelphia chromosome t(9;22)
Rearrangements of MLL (mixed lineage leukemia) gene