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Background

This is a rare variant of leukemia, usually seen in elderly men. The classic clinical presentation is a patient with splenomegaly without lymphadenopathy. These patients have an aggressive clinical course with an overall poor prognosis. These leukemias must be distinguished from cases of B-cell chronic lymphocytic leukemia which may undergo prolymphocytoid transformation.

OUTLINE

Epidemiology  
Pathogenesis  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
SYNONYMS B-cell prolymphocytic leukemia
B-PLL
INCIDENCE Rare
AGE RANGE-MEDIAN 6th-7th decade
SEX (M:F)
Males favored

PATHOGENESIS CHARACTERIZATION
t(11;14)(q13;q32) 20% of cases
Trisomy 12 <10%

LABORATORY/
RADIOLOGIC
 
SERUM BETA MICROGLOBULIN  
An indolent case of T-prolymphocytic leukemia with t(3;22)(q21;q11.2) and elevated serum beta2-microglobulin.

Moid F, Day E, Schneider MA, Goldstein K, DePalma L.

Department of Pathology, George Washington University Hospital, Washington, DC 20037, USA.

Arch Pathol Lab Med. 2005 Sep;129(9):1164-7. Abstract quote  

We report a novel case of T-prolymphocytic leukemia, small cell variant, associated with complex cytogenetic findings including t(3;22)(q21;11.2) and elevated serum beta2-microglobulin.

The diagnosis is based on morphologic, immunophenotypic, cytogenetic, and molecular analysis of peripheral blood and bone marrow. In contrast to most reported cases of T-prolymphocytic leukemia, this patient did not present with lymphadenopathy or organomegaly. Moreover, only a moderate leukocytosis (25.3 x 10(3)/microL) was evident at presentation.

In the absence of any specific treatment, the patient is doing well, with a stable white blood cell count 12 months following presentation. Further investigation may be warranted to determine whether the unusual cytogenetic findings and elevated serum beta2-microglobulin are associated with the indolent clinical course in this patient.

 

CLINICAL VARIANTS CHARACTERIZATION
EXTRAMEDULLARY  
Peripheral T-cell lymphoma with a "follicular" pattern and the perifollicular sinus phenotype.

Jiang L, Jones D, Medeiros LJ, Orduz YR, Bueso-Ramos CE.

Department of Pathology and Laboratory Medicine, the University of Texas-Houston Medical School.
Am J Clin Pathol. 2005 Mar;123(3):448-55. Abstract quote  

We report a case of peripheral T-cell lymphoma (PTCL) with an exclusively "follicular" pattern at one lymph node site and a diffuse pattern at a second lymph node site. Molecular studies confirmed the clonal identity of the tumor at both sites.

In the lymph node showing a follicular pattern, the tumor cells appeared to infiltrate follicles where the perifollicular sinuses remained patent. The infiltrated follicles retained nonneoplastic B cells and a follicular dendritic cell network. By contrast, in the lymph node showing diffuse involvement, intranodal sinuses were no longer identifiable and there was no evidence of tumor cells infiltrating follicles. The tumor immunophenotype was influenced by the pattern: the follicular component was positive and the diffuse component was negative for bcl-6 and CD31.

We suggest that the follicular growth pattern in this case of PTCL arose secondarily to tumor spread via the perifollicular sinus.
SPLEEN  
Histopathology of the spleen in T-cell large granular lymphocyte leukemia and T-cell prolymphocytic leukemia: a comparative review.

Osuji N, Matutes E, Catovsky D, Lampert I, Wotherspoon A.

Section of Haemato-Oncology, Royal Marsden Hospital Foundation Trust/Institute of Cancer Research, London UK.
Am J Surg Pathol. 2005 Jul;29(7):935-41. Abstract quote  

We review retrospectively the spleen histology in 8 patients with T-cell large granular lymphocyte (LGL) leukemia and 4 with T-cell prolymphocytic leukemia (T-PLL) to identify characteristic patterns of involvement and to distinguish such patterns from those described in other low grade B- and T-cell malignancies.

Moderate splenic enlargement with red pulp expansion due to lymphocytic infiltration was characteristic of LGL leukemia. Abnormal lymphocytes expressed cytotoxic granule proteins and were consistently CD45RO and CD5 negative in contrast to normal red pulp T cells. This infiltration respected anatomic boundaries with encroachment but no invasion of white pulp areas. Unlike in hairy cell leukemia, the main differential diagnosis for red pulp lymphocytosis, the white pulp was not only preserved in T-cell LGL leukemia but showed germinal center hyperplasia with expansion of the mantle zones.

By comparison, T-PLL spleens showed marked red pulp lymphoid infiltration by medium-sized cells with irregular nuclei and prominent eosinophilic nucleoli. T-PLL lymphocytes, unlike LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp areas. T-cell prolymphocytes did not express cytotoxic granule proteins or NK-cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+, CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-. Expression of CD4 and CD8 in these cells mirrored that of circulating T-PLL cells.

These observations on the morphologic and immunohistochemical appearances of the spleen in T-cell LGL leukemia and T-PLL may aid diagnosis of these uncommon T-cell disorders, particularly T-cell LGL leukemia, where presentation may be cryptic and where unique pathognomonic features, are absent.

 

HISTOLOGICAL TYPES CHARACTERIZATION
Prolymphocyte

Large cells with moderate pale blue cytoplasm

Oval to round nuclei with smooth nuclear contours and large central nucleolus

Peripheral smear Usually >100x10*9/L
Bone marrow Interstitial or diffuse, usually extensive involvement
>55% prolymphocytes
VARIANTS  

Mature B-Cell Leukemias With More Than 55% Prolymphocytes A Heterogeneous Group That Includes an Unusual Variant of Mantle Cell Lymphoma

Ellen Schlette, etal.

Am J Clin Pathol 2001;115:571-581 Abstract quote

We studied 20 cases of mature B-cell leukemia with more than 55% prolymphocytes in peripheral blood or bone marrow, fulfilling the French-American-British criteria for B-cell prolymphocytic leukemia (PLL). Cases segregated into 3 groups: de novo PLL, 6; PLL occurring in patients with a previous well-established diagnosis of chronic lymphocytic leukemia (PLL-HxCLL), 10; and t(11;14)(q13;q32)-positive neoplasms, 4. All cases expressed monotypic immunoglobulin light chain, and most were positive for CD5. All t(11;14)-positive neoplasms were CD23 and uniquely positive for cyclin D1. Cytogenetic abnormalities were present in 19; in all 19, the karyotype was complex, indicating clonal evolution and genomic instability. The most frequent cytogenetic abnormality in de novo PLL involved chromosome 7 in 4 cases. Trisomy 12 or add(12p) was present in 4 cases of PLL-HxCLL.

We conclude that mature B-cell leukemias with more than 55% prolymphocytes are a heterogeneous group that includes t(11;14)-positive neoplasms, which we suggest are best classified as mantle cell lymphoma. We also suggest that prolymphocytic morphologic features are a common end-stage of transformation for several B-cell neoplasms.

 

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER
CHARACTERIZATION
Prolymphocytes CD5 +/-
CD19, CD20 positive
Bright Ig
FMC-7 Antibody positive
CD10 negative

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
Mantle cell lymphoma in leukemic phase CD5+
CD10-
CD23-
CLL in prolymphocytic transformation Trisomy 12 in 15%
Peripheral smear with WBC count of <30x10*9/L in 2/3 of patients


Mature B-cell leukemias with more than 55% prolymphocytes: report of 2 cases with Burkitt lymphoma-type chromosomal translocations involving c-myc.

Merchant S, Schlette E, Sanger W, Lai R, Medeiros LJ.

Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Arch Pathol Lab Med 2003 Mar;127(3):305-9 Abstract quote

CONTEXT: The molecular genetic events involved in the pathogenesis of mature B-cell leukemias with more than 55% prolymphocytes are not well characterized. We have encountered 2 such cases in which conventional cytogenetic analysis identified Burkitt lymphoma-type chromosomal translocations involving 8q24.

OBJECTIVE: To assess these 2 cases for involvement of the c-myc gene using fluorescence in situ hybridization analysis with probes specific for the c-myc and immunoglobulin heavy-chain (IgH) genes.

RESULTS: In both cases, conventional cytogenetic analysis demonstrated complex karyotypes, including chromosomal translocations involving 8q24. In case 1, a case of de novo prolymphocytic leukemia, the t(8;14)(q24;q32) was detected. In case 2, a case of chronic lymphocytic leukemia in prolymphocytoid transformation, the t(8;22)(q24;q11) was identified. Fluorescence in situ hybridization studies showed c-myc/IgH fusion signals in case 1, proving the presence of the t(8;14). Split c-myc signals without fusion to IgH were observed in case 2, proving c-myc gene rearrangement and consistent with the t(8;22).

CONCLUSION: These results suggest that c-myc gene alterations may be involved in the pathogenesis of a subset of mature B-cell leukemias with more than 55% prolymphocytes.

Hairy cell leukemia variant

TRAP+
CD11c+
CD25+
CD103+

CD5 and 23-

Splenic lymphoma with villous lymphocytes CD5-
CD10-/+
CD23 and 25 -
T-cell prolymphocytic leukemia T cell phenotype

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
5 Year Survival Usually die within 48 months of diagnosis
Treatment Chemotherapy

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Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.


Commonly Used Terms

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Commonly Used Terms
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Last Updated September 8, 2005

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