Table of ContentsDefinition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Peripheral smear description | Peripheral smear images | Positive stains | Negative stains | Flow cytometry description | Flow cytometry images | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Shi M, Jevremovic D. T cell prolymphocytic leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBTcellpro.html. Accessed June 12th, 2021.
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)
- 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
- T cell chronic lymphocytic leukemia (small cell variant of T cell prolymphocytic leukemia)
- Rare (2% of mature lymphocytic leukemias)
- Adults and elderly (> 30 years, median age 65 years)
- Widespread: peripheral blood, bone marrow, lymph nodes, spleen, liver, skin
- 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)
- Unknown at this time
- Higher risk in patients with ataxia-telangiectasia (germline ATM mutations)
- 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])
- 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)
- Increased peripheral blood lymphocytes, often > 100 k, increased lactate dehydrogenase (LDH) and beta2 microglobulin (Ann Oncol 2017;28:1554)
- Negative serology for HTLV-1
- Prominent hepatosplenomegaly and widespread lymphadenopathy; moderate to high FEV on PET scan
- 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)
- 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.
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
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
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
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.
- 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+
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 style 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: T cell prolymphocytic leukemia
Reference: T cell prolymphocytic leukemia
Board review style question #2