Lymphoma & related disorders

Mature B cell neoplasms

Small B cell lymphomas with a circulating component

Prolymphocytic leukemia



Topic Completed: 22 June 2021

Minor changes: 22 June 2021

Copyright: 2001-2021, PathologyOutlines.com, Inc.

PubMed Search: B cell prolymphocytic leukemia[TI]


Richard K. Wood, M.D.
Dietrich Werner, M.D.
Page views in 2020: 3,110
Page views in 2021 to date: 4,178
Cite this page: Wood RK, Shawwa A, Werner D. Prolymphocytic leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomaprolymphocyticleukemia.html. Accessed December 3rd, 2021.
Definition / general
  • Rare aggressive mature B cell neoplasm that represents less than ~1% of all leukemias
  • Characterized by the presence of large lymphoid cells (prolymphocytes) accounting for at least 55% of total circulating cells in the peripheral blood
  • Prolymphocytes are defined as large cells (> 2 erythrocytes) with clumped chromatin (but more open than in chronic lymphocytic leukemia [CLL]), a large single prominent vesicular nucleolus and abundant cytoplasm (Br J Haematol 2016;174:767)
Essential features
  • Aggressive B cell neoplasm defined by large prolymphocytes accounting for 55% of total circulating cells in the peripheral blood
  • Main sites of involvement are peripheral blood, spleen and bone marrow
  • Marked absolute lymphocytosis (usually > 100 x 109/L)
  • Poor prognosis in general; the degree of treatment response is dictated by anemia, degree of lymphocytosis and molecular prognostic markers
Terminology
  • Prolymphocytic leukemia, B cell type (B-PLL)
ICD coding
  • ICD-O: 9833/3 - Prolymphocytic leukemia, B cell type
Epidemiology
Sites
  • Sites of involvement are peripheral blood, bone marrow and typically the spleen
Pathophysiology
Etiology
  • Very rare malignancy; no specific etiology or causal lesion associated with it
Clinical features
  • Peripheral blood lymphocytosis usually > 100 x 109/L
  • Patients often present with constitutional symptoms and massive splenomegaly
  • Lymphadenopathy is typically absent or mild (Semin Oncol 2006;33:257)
Diagnosis
  • Peripheral blood: CBC count, morphology review and flow cytometry
  • Bone marrow biopsy: morphology, flow cytometry and immunohistochemistry studies
  • Molecular and cytogenetic analysis have prognostic significance but are not necessary for a diagnosis
Laboratory
  • Additional laboratory findings to the presence of marked absolute lymphocytosis in the CBC include anemia and thrombocytopenia; these are present ~50% of the time
Radiology description
  • No specific radiology findings
Prognostic factors
Case reports
Treatment
  • Rare cases that present as indolent disease and are asymptomatic can be followed with a watch and wait approach without immediate treatment; however, cases often progress rapidly and will require close monitoring
  • Chemotherapy is the treatment indicated; in the absence of 17p deletion or TP53 mutation, rituximab in association to FC (fludarabine, cyclophosphamide) or bendamustine is the recommended first line therapy (Hematology Am Soc Hematol Educ Program 2015;2015:361)
  • Chemotherapy for poor prognosis cases is different; in del(17p) or TP53 mutated tumors, treatment with alemtuzumab or more recently ibrutinib are used (Hematology Am Soc Hematol Educ Program 2015;2015:361, Br J Haematol 2017;179:501)
Microscopic (histologic) description
  • Bone marrow involvement shows neoplastic infiltrates with a mixed nodular, interstitial or diffuse patterns composed of medium to large lymphoid cells
  • Spleen shows expanded white pulp with red pulp infiltration by medium to large neoplastic cells with ample cytoplasm, round or irregular nuclei and a central large, eosinophilic nucleolus
  • Lymph node involvement when present shows diffuse or nodular infiltration by neoplastic lymphoid cells without proliferation centers
Microscopic (histologic) images

Contributed by Richard K. Wood, M.D. and Dietrich Werner, M.D.

Bone marrow involvement

CD20 positivity in bone marrow

CD79a positivity in bone marrow

Cyclin D1 negativity in bone marrow

Peripheral smear description
  • Marked absolute lymphocytosis with at least a 55% prolymphocyte count out of total circulating cells
  • Prolymphocytes:
    • Medium to large sized lymphoid cells with round or occasionally indented nuclei
    • Moderately condensed to open chromatin
    • Single large prominent central nucleolus
    • Moderate amount of basophilic cytoplasm
    • Reference: Br J Haematol 1974;27:7
Peripheral smear images

Contributed by Allam Shawwa, M.D.

Prolymphocytes in peripheral blood

Prolymphocytes in peripheral blood

Positive stains
Negative stains
Flow cytometry description
Flow cytometry images

Case #120

CD19 and CD20

Kappa and lambda

FMC7 and CD22

Molecular / cytogenetics description
Sample pathology report
  • Bone marrow, right posterior iliac crest, biopsy, aspirate and clot section:
    • B cell prolymphocytic leukemia (B-PLL) (see comment)
    • Comment: This is a 79 year old man presenting with an elevated CBC count of 153 x 109/L and an absolute lymphocyte count of 124 x 109/L. A manual peripheral blood smear count shows a prolymphocyte count of 74%.
  • Bone marrow aspirate:
    • Quality of specimen: particulate
    • Cellularity: hypercellular
    • Approx. M:E ratio: 4:1
    • Erythropoiesis: normoblastic and decreased
    • Granulopoiesis: all stages of maturation present and decreased
    • Megakaryocytopoiesis: normal
    • Lymphocytes: increased with two monomorphic populations noted. The first is characterized by medium sized cells with prominent central nucleoli and abundant cytoplasm. The second consists of small lymphocytes with densely packed chromatin and minimal cytoplasm.
    • Plasma cells: normal; not increased
  • Bone marrow aspirate differential:
    • Metamyelocytes: 3%
    • Bands: 7%
    • Seg. neutrophils: 10%
    • Eosinophils: 1%
    • Lymphocytes: 72%
    • Monocytes: 2%
    • Erythroblasts: 8%
    • Total cells counted: 500
  • Bone marrow biopsy:
    • A trephine biopsy with a length of 1.5 cm is submitted. The sample is adequate for examination. The specimen is hypercellular at approximately 70% cellularity. Trilineage hematopoiesis is decreased. Megakaryopoiesis is nondysplastic. Granulopoiesis is decreased but still shows a normal range of maturation and geographic distribution. There is a diffuse, interstitial and nodular infiltrate of lymphocytes consisting of two discrete populations. The first shows medium to large sized cells with prominent nucleoli and vesicular chromatin while the second consists of small, monomorphic lymphocytes with densely packed chromatin.
  • Ancillary testing:
    • Immunohistochemical evaluation of the larger cell population shows expression of CD20, CD19 and CD79a while CD5 and CD23 are not expressed. The population of smaller cells expresses CD20, CD19, CD5 and CD23. Both populations are negative for expression of CD3, SOX11 and cyclin D1.
    • The flow cytometry report shows two neoplastic cell populations surface light chain kappa restricted. The first larger population represents 69% of the sample and is positive for CD19, CD20 bright and kappa bright and is negative for CD5, CD10 and CD23. A second smaller population in 18% of the sample is positive for CD19, CD20 dim, CD5, CD23 and kappa dim.
    • Molecular and cytogenetic studies demonstrated deletion of 17p13. Translocation (11;14)(q13;q32) was not detected.
Differential diagnosis
  • Mantle cell lymphoma:
    • Usually contains t(11;14)(q13;q32) translocation between IGH and CCND1 with positive expression of cyclin D1 and SOX11
  • T cell prolymphocytic leukemia:
    • Neoplastic cells show cytoplasmic projections on peripheral smear
    • Marrow involvement shows perivascular or diffuse patterns
    • Expresses T cell markers CD2, CD3, CD7, TCR, TCL1 and is negative for B cell markers
  • Chronic lymphocytic leukemia with increased prolymphocytes:
    • Small, monomorphic lymphocytes with tightly condensed chromatin with fewer than 55% prolymphocytes
    • Nearly all cases express CD5 and CD23
    • Bone marrow involvement shows proliferation centers with background small, monomorphic lymphocytes
  • Hairy cell leukemia variant:
    • May lack CD25 but typically expresses CD103
    • Typically demonstrate the characteristic cytoplasmic projections of HCL
  • Splenic marginal zone lymphoma:
    • Neoplastic cells show characteristic short polar villi and do not have prominent nucleoli
    • Splenic involvement by MZL shows prominent marginal zone
    • Marrow involvement may show follicular arrangement with surrounding marginal zone B cells
    • Molecular analysis shows in some cases NOTCH2 and NFκB mutations (not reported in B-PLL)
  • Follicular lymphoma:
    • Typically follicular pattern and often involving lymph nodes
    • Expresses CD10
  • Lymphoplasmacytic lymphoma:
    • Plasmacytoid appearance of neoplastic cells often accompanied by rouleaux
    • MYD88 mutation in > 90% of cases
Board review style question #1

You review the peripheral blood smear of a 74 year old man with a high WBC count of 117 x 109/L, anemia and thrombocytopenia. The majority of the cells (75%) have the appearance shown in the above image. Flow cytometry shows that these cells have the following immunophenotype: CD20+, CD19+, FMC7+, CD200+ and CD10-, CD5-, CD23-. What is your diagnosis?

  1. Acute myeloid leukemia
  2. B cell prolymphocytic leukemia
  3. Chronic lymphocytic leukemia
  4. Mantle zone lymphoma
  5. Splenic marginal zone lymphoma
Board review style answer #1
B. B cell prolymphocytic leukemia

Comment Here

Reference: Prolymphocytic leukemia
Board review style question #2
Which of the following findings is the required criteria for a diagnosis of B cell prolymphocytic leukemia?

  1. Anemia
  2. Bone marrow involvement
  3. Deletion of 17p13
  4. Lymphocytosis over 100 x 109/L
  5. Medium to large sized lymphocytes with central, large nucleoli that are greater than 55% of the total WBC
Board review style answer #2
E. Medium to large sized lymphocytes with central, large nucleoli that are greater than 55% of the total WBC

Comment Here

Reference: Prolymphocytic leukemia
Back to top
Image 01 Image 02