Spleen
Hematogenous neoplasms
Prolymphocytic leukemia

Author: Jaleh Mansouri, M.D. (see Authors page)

Revised: 7 March 2018, last major update January 2014

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Prolymphocytic leukemia spleen

See also: B cell prolymphocytic leukemia and T cell prolymphocytic leukemia
Cite this page: Mansouri, J. Prolymphocytic leukemia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/spleenprolymphocyticleukemia.html. Accessed August 17th, 2018.
Definition / general
  • Similar features as SLL / CLL, although 20% are T cell phenotype
  • B cell and T cell prolymphocytic leukemia are distinct clinical entities
  • B cell phenotype: neoplastic proliferation of B cell prolymphocytes in peripheral blood (must exceed > 55% of lymphoid cells), bone marrow and spleen
  • T cell phenotype: neoplastic proliferation of T cell prolymphocytes in peripheral blood, bone marrow, lymph nodes, spleen, liver and skin
Terminology
  • Excludes CLL with increased prolymphocytes and transformed CLL
Epidemiology
  • B cell phenotype: ~1% of lymphocytic leukemias, median age 65 - 69 years (M:F ~1)
  • T cell phenotype: ~2% of adult lymphocytic leukemias, median age 65 years (range, 30 - 94 years); may occur as secondary neoplasm in patients with ataxia telangiectasia due to mutations in ATM gene (see molecular / cytogenetics description below)
Sites
  • Peripheral blood, bone marrow, spleen
  • T cell phenotype may additionally involve lymph nodes, liver, skin (20%) (T cell prolymphocytic leukemia involving extramedullary sites, Am J Clin Pathol 2005;123:456)
Pathophysiology
  • B cell phenotype: mature B cell is postulated normal counterpart
  • T cell phenotype: mature postthymic T cell is postulated normal counterpart
Clinical features
Diagnosis
  • Made by morphological examination of peripheral blood and bone marrow, CBC, flow cytometry and cytogenetic / molecular studies including FISH
Laboratory
  • B cell phenotype: anemia and thrombocytopenia (50%) with lymphocytosis usually exceeding 100 x 109/L
  • T cell phenotype: anemia and thrombocytopenia with lymphocytosis usually exceeding 100 x 109/L and > 200 x 109/L in 50% of cases; serology for HTLV1 negative
Prognostic factors
  • B cell phenotype:
    • Median survival of 30 - 50 months
    • ZAP70 and CD38 expression, 17p deletions and immunoglobulin gene mutational status do not appear to be prognostic indicators
  • T cell phenotype:
    • Aggressive course with median survival of less than 12 months
    • High expression of TCL1 and AKT1 are poor prognostic indicators
Case reports
Treatment
  • B cell phenotype:
    • Combination therapy such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and rituximab
    • Nucleoside analogs such as fludarabine and cladribine; splenectomy for symptomatic improvement
  • T cell phenotype:
    • Alemtuzumab (anti-CD52 monoclonal antibody) may achieve favorable response
    • Autologous and allogeneic stem cell transplant as adjunctive treatment for patients in remission
Gross description
  • Massive splenomegaly
  • May have miliary pattern of lymphoma
Microscopic (histologic) description
  • Expansion of white pulp and infiltration of red pulp by prolymphocytes
  • Prolymphocytes have basophilic cytoplasm; larger nuclei than SLL / CLL with dispersed heterochromatin, often indented nuclei, with distinct vesicular nucleoli
  • Also paraimmunoblast type cells
  • Bone marrow: intertrabecular distribution of nodular or interstitial infiltrates
  • T cell phenotype: preferential involvement of splenic red pulp with invasion of splenic capsule and fibrous trabeculae; cutaneous involvement has dermal and perivascular infiltrates; lymph node involvement shows diffuse, paracortical infiltrate
Microscopic (histologic) images

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t(11;14)+ cases

t(11;14)- case

Peripheral smear images

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Perpiheral blood and bone marrow

May-Grünwald-Giemsa stains

Positive stains
Negative stains
  • B cell phenotype: CD5 (positive in 20 - 30% of cases), CD23 (positive in 10 - 20%)
  • T cell phenotype: B cell markers
Flow cytometry description
  • B cell phenotype:
    • Positive for CD19, CD20, CD79a, CD79b, FMC7, surface immunoglobulin
    • Occasionally CD38 and ZAP70
    • Negative for CD5 and CD23 in most cases
  • T cell phenotype:
    • Positive for CD2, CD3, CD7, CD52 (strong)
    • CD4+ and CD8- in 60%, CD4+ and CD8+ in 25%, CD4- and CD8+ in 15% of cases
    • Negative for TdT and CD1a (Am J Clin Pathol 2013;140:727)
Molecular / cytogenetics description
  • B cell phenotype
    • Molecular:
      • Clonal rearrangement of immunoglobulin genes with unmutated heavy chain genes (VH3 and VH4)
    • Cytogenetics:
      • Complex karyotypes with del(17p) in 50% of cases (associated with p53 mutation)
      • Deletions at 13q14 in 27% of cases
  • T cell phenotype
    • Molecular:
      • Clonal rearrangement of T cell receptor genes (TRB@ and TRG@)
    • Cytogenetics:
      • Inversion of chromosome 14 with breakpoints at q11 and q32 (most common)
      • Reciprocal tandem translocation t(14;14)(q11;q32) - juxtaposes TRA@ with TCL1A and TCL1B (oncogenes)
      • t(X;14)(q28;q11) - involves TCA@ and MTCP1 (oncogene)
      • Abnormalities involving chromosome 8 and 6
      • Deletions at 12p13, 11q23 (ATM gene locus) and 17p13.1 (p53 overexpression)
Differential diagnosis