Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Peripheral smear images | Positive stains | Negative stains | Flow cytometry description | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Mansouri J. Prolymphocytic leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/spleenprolymphocyticleukemia.html. Accessed August 8th, 2020.
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
- B cell phenotype: splenomegaly, B symptoms (Wikipedia: B Symptoms [Accessed 7 March 2018]), with minimal lymphadenopathy
- T cell phenotype: hepatosplenomegaly and lymphadenopathy, occasionally with pleural effusions
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
- 32 year old man with prolymphocytes in pleural fluid (Acta Cytol 2008;52:251)
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
Images hosted on other servers:
t(11;14)+ cases
t(11;14)- case
Peripheral smear images
Images hosted on other servers:
Perpiheral blood and bone marrow
May-Grünwald-Giemsa stains
Positive stains
- B cell phenotype: B cell antigens and surface immunoglobulin (see flow cytometry description below)
- T cell phenotype: α naphthyl acetate esterase, acid phosphatase (dot-like pattern in Golgi region), TCL1 (useful in monitoring for residual disease after therapy)
Negative stains
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
- Molecular:
- 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)
- Molecular:
Differential diagnosis
- Blastoid variants of mantle cell and splenic marginal zone lymphoma
- Prolymphocytic transformation of SLL / CLL
- Splenomegalic variant of mantle cell lymphoma with t(11;14) (Br J Haematol 2004;125:330)
- T cell large granular lymphocyte leukemia (Am J Surg Pathol 2005;29:935)
