A 75 years old female with a history of headache, lower back pain, and left lower limb numbness
Ibrahim Robadi M.D., Peter L. Perrotta M.D.
A 75 year-old female was transferred from an outside facility with a history of headache, lower back pain and left lower limb numbness. She denied any history of fever, chills or night sweats. Her initial CBC revealed leukocytosis with white cell count of 280 x103/uL, anemia with hemoglobin of 7.4 g/dl and thrombocytopenia with a platelet count of 58 x103/uL. There was also absolute lymphocytosis (260 x 103 lymphocytes/uL). A CT scan of the abdomen showed massive splenomegaly (spleen size 21x17x9 cm) but without definitive lymphadenopathy. Peripheral blood smears showed atypical lymphocytosis (1A). Bone marrow biopsy (A2-A3) and flow cytometry were performed. Immunohistochemistry was positive for CD20 (1C) and negative for CD3, CD1, and PAX5.
Flow cytometry revealed a kappa-restricted B-cell population with the following immunophenotype: CD19, CD20, CD22, CD5, CD23, (dim), FMC-7 (dim), and Kappa surface immunoglobulin. The cells were negative for CD38,CD10, CD11c, CD25, and CD34.
Cytogenetic testing revealed a 17p13 deletion in 90% of interphases analyzed.
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B-cell prolymphocytic leukemia (B-PLL) is rare lymphocytic disorder first identified in the early 1970s that has characteristic features which can overlap with other mature B-cell leukemias and lymphomas.1 By definition, more than 55% PLL in the peripheral blood are required for making the diagnosis. Patients have high white cell counts, splenomegaly and no or minimal lymphadenopathy. Generally, patients with B-PLL are elderly and tend to have a poor prognosis with a median survival of 3 years due to the aggressive clinical course.2
Patients mostly present with B-symptoms and rapidly rising white cell counts (>100 × 109 /L), splenomegaly, thrombocytopenia and anemia. Lymphadenopathy is not prominent if it is present.
In the peripheral blood, >55% of the total lymphocytes are prolymphocytes, which are characterized by scant basophilic cytoplasm, round-oval nuclei with condensed chromatin, and a single larger nucleolus.3 Bone marrow exam shows interstitial, nodular, diffuse, or patchy pattern of the lymphoid aggregates. Lymph nodes may display a patchy, vaguely nodular or diffuse pattern which most of the time are not diagnostic and appear similar to prolymphocyte seen in smaller numbers in B-CLL.
The presence of a monoclonal B-cell population that expresses CD19, CD20, CD22, CD79a, PAX5, FMC7 and surface immunoglobulin (IgM or IgM/IgD) is typical of PLL. Cyclin D1, CD10, and BCL6 are negative.4 Most importantly, immunotyping will rule out CLL (CD5+, CD23+, kappa/lambda light chain, and FMC7- ). However, up to 30% of the B-PLL may express CD5 and these cases may be difficult to differentiate from MCL in a leukemic phase.
Due to the rarity of the disease, only few studies have been reported. Using FISH, 17p deletions (TP53), 13q14 deletions, and monoallelic 11q23 deletions can be seen in PLL. Immunoglobulin heavy chain genes in B-PLL are clonally rearranged, in which cases B-PLL are derived from mutated and unmutated progenitor cells. However, 50% of cases have mutated IGHV genes. Translocations (e.g., t(11;14)) have been found in 20% of cases and these are now classified as leukemic-phase mantel cell lymphoma). It was previously thought these cases represented B-PLL due to the prolymphocytic morphology of the lymphoid cells.5
Prognosis and therapy of B-PLL
As mentioned above, B-PLL was originally described as a variant of CLL. However, it is now considered as a distinct clinicopathological entity in the current WHO classification. Typical cases of B-PLL have an aggressive clinical course and the median survival is only 3-4 years.4 B-PLL is most commonly treated with combination regimens used for treating CLL such as fludarabine, cyclophosphamide, and rituximab.6
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- Hercher C, Robain M, Davi F, et al. A multicentric study of 41 cases of B-prolymphocytic leukemia: Two evolutive forms: The groupe français d'hématologie cellulaire. Leuk Lymphoma. 2001;42(5):981-987.
- Pawson R, Dyer MJ, Barge R, et al. Treatment of T-cell prolymphocytic leukemia with human CD52 antibody. J Clin Oncol. 1997;15(7):2667-2672.
- Stein H, Warnke R, Chan W, et al. Diffuse large B-cell lymphoma, not otherwise specified. WHO classification of tumours of haematopoietic and lymphoid tissues. 2008;2:233-237.
- Pittman S, Catovsky D. Chromosome abnormalities in B-cell prolymphocytic leukemia: A study of nine cases. Cancer Genet Cytogenet. 1983;9(4):355-365.
- Shvidel L, Shtalrid M, Bassous L, Klepfish A, Vorst E, Berrebi A. B-cell prolymphocytic leukemia: A survey of 35 patients emphasizing heterogeneity, prognostic factors and evidence for a group with an indolent course. Leuk Lymphoma. 1999;33(1-2):169-179.