T cell prolymphocytic leukemia

Lymphoma & related disorders

Mature T/NK cell disorders

T/NK cell disorders with a leukemic component

Authors: Min Shi, M.D., Ph.D., Dragan Jevremovic, M.D., Ph.D.

Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.

Topic Completed: 18 October 2019

Minor changes: 13 December 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: T cell prolymphocytic leukemia [title] pathology

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Table of Contents

Cite this page: Shi M, Jevremovic D. T cell prolymphocytic leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBTcellpro.html. Accessed August 7th, 2020.

Definition / general

Aggressive T cell leukemia, composed of small to medium sized mature T cells, usually with high white blood cell (WBC) count and widespread organ involvement (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised Edition, 2017)

Essential features

Aggressive leukemia of mature T cells
High white blood cell count (lymphocytosis)
Usually CD4+
Usually TCL1 positive by immunophenotyping and TCL1 rearranged by FISH
Difficult to treat, poor prognosis

Terminology

T cell chronic lymphocytic leukemia (small cell variant of T cell prolymphocytic leukemia)

ICD coding

ICD-0: 9834/3 - T cell prolymphocytic leukemia
ICD-10: C91.6 - prolymphocytic leukemia of T cell type

Epidemiology

Rare (2% of mature lymphocytic leukemias)
Adults and elderly (> 30 years, median age 65 years)

Sites

Widespread: peripheral blood, bone marrow, lymph nodes, spleen, liver, skin

Pathophysiology

Combination of overexpression of TCL1 family of proteins (which stimulate AKT / protein kinase B driven proliferation) and functional deficit of ATM protein (Nat Commun 2018;9:697)

Etiology

Unknown at this time
Higher risk in patients with ataxia-telangiectasia (germline ATM mutations)

Clinical features

High tumor burden with high white blood cell count (median 50 - 60 k), bone marrow involvement (in 100% of patients) with cytopenias, hepatosplenomegaly, lymphadenopathy, skin and mucosal lesions, other organ involvement / dysfunction (Am J Hematol 2017;92:441)
Prominent constitutional symptoms
20 - 30% present with inactive disease; progress to active disease within 1 - 2 years (criteria for progression: lymphocyte doubling time (LDT) of less than 6 months or lymphocyte count increase by > 50% in 2 months) (Blood 2019 Jul 10 [Epub ahead of print])

Diagnosis

Peripheral blood: morphology + flow cytometry variable fluorescent in situ hybridization (FISH)*
Bone marrow or solid tissue biopsy (lymph node, spleen, liver, skin, other): morphology + phenotyping (immunohistochemistry or flow cytometry) variable FISH*
*FISH not necessary if TCL1 overexpression in neoplastic T cells can be shown by IHC or flow (J Clin Pathol 2018;71:309)

Laboratory

Increased peripheral blood lymphocytes, often > 100 k, increased lactate dehydrogenase (LDH) and beta2 microglobulin (Ann Oncol 2017;28:1554)
Negative serology for HTLV-1

Radiology description

Prominent hepatosplenomegaly and widespread lymphadenopathy; moderate to high FEV on PET scan

Prognostic factors

Overall poor prognosis; median survival with active disease 1 - 2 years
Worse prognosis: pleural effusion, high LDH (> 1668 IU/l), low hemoglobin (< 9.3 g/dl), complex karyotype (Ann Oncol 2017;28:1554, Am J Hematol 2017;92:441)

Case reports

59 year old man with the history of renal transplant (J Med Case Rep 2019;13:223)
64 year old man with TCL-1-positive hematogones after T cell prolymphocytic leukemia therapy (Hum Pathol 2017;65:175)
68 year old man with heart failure (Blood 2017;130:691)
60 plus woman with a history of chronic myeloid leukemia (CML) (J Clin Pathol 2019;72:511)
75 year old man with unusual phenotype of T cell prolymphocytic leukemia (Blood 2018;132:111)

Treatment

Only for active disease
Standard treatment: alemtuzumab (anti-CD52) variable allogeneic bone marrow transplant
Experimental therapies with BCL2, JAK3 or HDAC inhibitors (Blood 2019 Jul 10 [Epub ahead of print])

Microscopic (histologic) description

Perivascular and diffuse tissue infiltrates of uniform small to medium sized lymphocytes
Red pulp involvement in the spleen

Microscopic (histologic) images

Contributed by Min Shi, M.D., Ph.D. and Dragan Jevremovic, M.D. Ph.D.

Diffuse bone marrow involvement

CD3 positivity in bone marrow

Splenic red pulp infiltrate

TCL1A staining in spleen

Monotonous paracortical lymphoid infiltrate

Intermediate size atypical lymphocyte

Monotonous T cell infiltrate

TCL1A positivity

Uniform strong TCL1A staining

Peripheral smear description

Lymphocytosis with small to medium sized lymphocytes with cytoplasmic projections, clumped chromatin and variably prominent central nucleolus
Small cell variant in 25% of cases: smaller cells without obvious nucleolus
Cerebriform variant in 5% of cases

Peripheral smear images

Contributed by Min Shi, M.D., Ph.D. and Dragan Jevremovic, M.D. Ph.D.

Cerebriform variant

Prolymphocytes in peripheral blood

Small cell variant

Positive stains

Usually CD2, CD3, CD5, CD7, CD52, TCR αβ, TCL1
TCL1 immunohistochemistry has better sensitivity than FISH for TCL1 rearrangement (J Clin Pathol 2018;71:309)
Usually CD4+ CD8- (see flow cytometry)

Negative stains

TdT, CD1a, CD16, CD30

Flow cytometry description

Mature CD3 positive T cells, usually express pan T markers CD2, CD5 and CD7; positive for CD52
CD4+ CD8- in 60%; CD4+ CD8+ in 25%; CD4- CD8+ in 15%

Flow cytometry images

Contributed by Min Shi, M.D., Ph.D. and Dragan Jevremovic, M.D. Ph.D.

T-PLL flow cytometry

Molecular / cytogenetics description

Clonal T cell receptor gene rearrangements (TRB@ and TRG@)
FISH is commonly used for diagnosis; T cell receptor locus rearranged with the TCL1 family of genes:
- TCL1A/B rearrangement: inv(14)(q11;q32) in 80%, t(14;14)(q11;q32) in 10%
- Rarely MTCP1 rearrangement t(X;14)(q28;q11)
- Rarely negative for TCL1A/B or MTCP1 rearrangements (Blood 2019 Jul 10 [Epub ahead of print])
Complex karyotype in 70 - 80%; abnormalities of chromosomes 6, 8, 12p, 17p
Mutations in ATM gene on 11q23 in 80-90%
Other mutations / alterations: TP53, JAK-STAT pathway genes IL2RG, JAK1, JAK3, STAT5B (Blood 2014;124:1460)

Molecular / cytogenetics images

Contributed by Min Shi, M.D., Ph.D. and Dragan Jevremovic, M.D. Ph.D.

FISH for TCL1A separation

Sample pathology report

Peripheral blood, bone marrow aspirate and biopsy, iliac crest: T cell prolymphocytic leukemia, extensively involving peripheral blood and bone marrow, with decreased trilineage hematopoiesis.
Peripheral blood
- CBC - HGB 11.2 g/dL; RBC 3.55 x10(12)/L; MCV 97.2 fL; RDW 15.2 %; WBC 470.0 x10(9)/L;PLT 111 x10(9)/L
- Cell % of total cells: neutrophils 4, lymphocytes 95, monocytes 1.
- Peripheral Smear: Lymphocytosis; small to intermediate lymphocytes with mature chromatin, prominent nucleoli, eccentric nuclei and moderate amounts of basophilic cytoplasm.
Bone marrow aspirate and biopsy
- Aspirate quality: Cellular.
- Biopsy quality: Adequate.
- M:E Ratio: Normal, 3:1
- Cellularity: Hypercellular, 90%.
- Erythroid precursors: Markedly decreased quantity. Normal morphology.
- Myeloid precursors: Markedly decreased quantity. Normal morphology. Blasts not increased.
- Megakaryocytes: Markedly decreased quantity. Normal morphology and distribution.
- Lymphocytes: Abnormal (diffuse) infiltrates of small to intermediate sized cells present (90% of the total marrow cellularity).
- Plasma cells: Not increased.
Ancillary studies
- Flow cytometry, bone marrow:
- Blasts: Not increased by CD45 / side scatter and CD34.
- B cells: No monotypic; normal expression pattern of CD19, CD10, surface kappa and lambda.
- T cells/NK cells: Distinct T cell population.
- Express: CD4, CD2, CD3, CD5, CD7.
- Do not express: CD8, CD16, TCR-gamma/delta, CD1a, nTdT, cMPO, cCD79a, cCD22.
- Estimated size: 95% gated lymphoid events; 87% total analyzed events
- T cell lymphoma FISH, bone marrow: The result is abnormal and indicates 88.5% of nuclei had a rearrangement involving TCL1A. This observation may indicate a clone with inv(14) or t(14;14), which are common rearrangements in T cell prolymphocytic leukemia.

Differential diagnosis

Sézary syndrome: clinical presentation (erythroderma); TCL1-, usually CD7-
Adult T cell leukemia / lymphoma (ATLL): morphology (flower cells); TCL1-; HTLV-1+, CD25+, CCR4+, FOXP3+
T lymphoblastic leukemia / lymphoma (T-ALL): TCL1-; immature phenotype with TdT+, CD1a+
T large granular lymphocytic leukemia (T-LGLL): clinical presentation (indolent disease with cytopenias); morphology (large granular lymphocytes); TCL1-; usually CD8+, CD16+, CD57+

Additional references

Blood 2004;104:328, Blood 2017;130:2499, Blood 2008;111:328

Board review style question #1

What is the most common phenotype of T prolymphocytic leukemia

CD3+ CD4+ CD5+ CD7+ CD8-
CD3+ CD4+ CD5+ CD7- CD8- CD26-
CD3+ CD4- CD7- CD8+ CD16+
CD3- CD4+ CD8+ TdT+
CD3- CD19+ CD20+ CD5+ CD23+

Board review answer #1

A. The most common phenotype of T cell prolymphocytic leukemia is that of a mature CD4+ T cells expressing pan T cell antigens, including CD7. Answer B is a common phenotype for Sézary syndrome. Answer C is a common phenotype for T cell large granulocytic lymphocyte leukemia. Answer D is a common phenotype for T lymphoblastic leukemia/lymphoma. Answer E. is a common B phenotype for CLL/SLL.

Reference: Lymphoma and plasma cell neoplasms - T cell prolymphocytic leukemia

Lymphoma and plasma cell neoplasms - T cell prolymphocytic leukemia

Board review style question #2

Which genetic abnormality is used to define T prolymphocytic leukemia?

17p (TP53) deletion
CCND1 rearrangement
MYC rearrangement
TCL1 rearrangement
TP53 mutations

Board review answer #2

D. TCL1 rearrangement on chromosome 14 is the most common genomic alteration which results in the overexpression of TCL1 protein and drives proliferation of neoplastic cells in T prolymphocytic leukemia.

Reference: Lymphoma and plasma cell neoplasms - T cell prolymphocytic leukemia

Lymphoma and plasma cell neoplasms - T cell prolymphocytic leukemia