Hairy Cell Leukemia Variant



Hairy Cell Leukemia Variant


Roberto N. Miranda, MD










Hairy cell leukemia variant (HCL-v) shows a diffuse infiltrate throughout splenic red pulp cords and sinuses, with complete obliteration of white pulp nodules.






HCL-v shows a diffuse red pulp infiltrate of small to intermediately sized lymphocytes with small nucleoli image and indistinct cytoplasm. Cords and sinuses are inapparent due to lymphocyte density.


TERMINOLOGY


Abbreviations



  • Hairy cell leukemia variant (HCL-v)


Synonyms



  • Splenic B-cell lymphoma with villous lymphocytes



    • Also used for splenic marginal zone lymphoma (SMZL)


  • Prolymphocytic variant of hairy cell leukemia (HCL); term is obsolete


Definitions



  • Mature small B-cell neoplasm that primarily involves peripheral blood, bone marrow, and spleen


  • Resembles classical HCL but has atypical laboratory, morphologic, or immunophenotypic features


  • Provisional entity in 2008 WHO classification


ETIOLOGY/PATHOGENESIS


Environmental Exposure



  • No known association with exposure to carcinogens, viral infections, or radiation


Cell of Origin



  • Activated mature memory B cell


CLINICAL ISSUES


Epidemiology



  • Incidence



    • HCL-v is less frequent than classical HCL, < 0.4% of all lymphoid leukemias


    • HCL-v may be more frequent in Asian countries (Japanese form of HCL-v)


  • Age



    • Predominantly affects elderly people



      • Median: 71 years


  • Gender



    • M:F = 1.6:1


Presentation



  • Splenomegaly (85%)


  • Hepatomegaly (20%)


  • Lymphadenopathy (15%)


Laboratory Tests



  • Leukocytosis (> 10 × 109/L) in 90%, with lymphocytosis and normal monocyte count



    • Median leukocyte count: 34 × 109/L


  • Thrombocytopenia (< 100 × 109/L) in 40%


  • Anemia (Hgb < 10 g/L) in 30%


Treatment



  • Partial response with purine analogues in 50% of patients



    • Pentostatin or cladribine


  • Interferon-α is not effective


  • Splenectomy is good palliative alternative for symptomatic anemia, thrombocytopenia, or abdominal pain



    • Usually partial response; median duration of 4 years


Prognosis



  • Indolent clinical course; median survival: 9 years


  • Morbidity related to splenomegaly, hypersplenism, and cytopenias


  • Histologic transformation of disease in 6%



    • B-symptoms, marked lymphocytosis, or lymphadenopathy may indicate transformation


    • Poor prognosis


MACROSCOPIC FEATURES


General Features



  • Splenomegaly with diffuse effacement



MICROSCOPIC PATHOLOGY


Histologic Features



  • Spleen



    • Diffuse infiltration of red pulp cords and sinusoids



      • Dilated sinusoids with abundant lymphocytes


      • Red blood cell lakes may be noted


    • Atrophy or complete effacement of white pulp


  • Liver



    • Infiltration in portal tracts and within sinusoids


  • Bone marrow



    • Interstitial and nodular lymphocytic distribution; occasional intrasinusoidal pattern


Cytologic Features



  • Peripheral blood smear



    • Circulating HCL-v cells easily identified



      • Some authors require 20-30% of villous lymphocytes for diagnosis


    • Cytoplasm is abundant, bluish to basophilic



      • Cytoplasmic projections around part of cell circumference


    • Round to oval nuclei with distinct nucleoli


  • Spleen and other tissue sites



    • Intermediate size lymphocytes with scant to moderately abundant indistinct cytoplasm


    • Variation in nuclear features; most commonly round with distinct, eccentric nucleoli


    • “Fried egg” or “honeycomb” appearance uncommon


  • Histologic transformation is characterized by large cells or cells with blastic chromatin



    • High mitotic rate


Predominant Pattern/Injury Type



  • Lymphoid, diffuse


Predominant Cell/Compartment Type



  • Lymphocytosis


ANCILLARY TESTS


Immunohistochemistry



  • B-cell antigens(+), DBA.44/CD76(+)


  • Tartrate-resistant acid phosphatase (TRAP)



    • Immunohistochemistry can be positive


    • Cytochemistry usually negative or weakly positive


  • CD123(−), annexin-A1(−), HC2(−), CD10(−), Bcl-6(−)


Flow Cytometry



  • Mature B cells with strong surface immunoglobulin (Ig)



    • Usually IgG, sometimes IgM and IgD are coexpressed


  • CD11c(+), CD22(+), CD79b([+] ˜ 20%), CD103([+] ˜ 70%), FMC7(+)


  • CD5(−), CD10(−), CD23(−), CD25(−), CD27(−/+)


Cytogenetics



  • No specific changes


  • Some cases show complex karyotypes



    • Involving 8q24/MYC, 14q32/IgH, and del(17p)/p53


Molecular Genetics



  • Monoclonal IgH and Ig light chain gene rearrangements


  • HCL-v cells carry MYC transcripts; associated with resistance to interferon-α therapy


  • P53 gene deleted in subset of cases is common



    • Higher risk of histologic transformation


DIFFERENTIAL DIAGNOSIS


Hairy Cell Leukemia (HCL), Classical



  • Patients present with pancytopenia and monocytopenia


  • Few leukemic HCL cells in blood smear


  • “Fried egg” appearance in tissue sections


  • CD25(+), CD123(+), annexin-A1(+), HC2(+)


  • T-bet(+), c-MAF(+)



Splenic Diffuse Red Pulp Small B-cell Lymphoma (SDRP SBCL)



  • Provisional entity in 2008 WHO Classification


  • Mature B-cell small lymphocytes with diffuse pattern involving red pulp and sinuses


  • Cytologically display central round nuclei with indistinct nucleoli; occasional cytoplasmic projections


  • Less degree of lymphocytosis; more IgM/IgD expression than HCL-v


  • Appears to have substantial overlap with HCL-v


Splenic Marginal Zone Lymphoma (SMZL)/Splenic Lymphoma with Villous Lymphocytes (SLVL)



  • Prominent nodular involvement of white pulp with secondary red pulp involvement



    • White pulp has biphasic histologic appearance


  • Neoplastic lymphocytes of intermediate size with moderately abundant cytoplasm


  • In blood smear: Cells have polar cytoplasmic projections (villous lymphocytes)


  • IgM(+), IgD(+/−), CD11c(+), CD79b(+)


  • CD5(−/+), CD10(−), CD23(−/+), CD43(−), CD103(−), annexin-A1(−)


B-cell Prolymphocytic Leukemia (B-PLL)



  • Aggressive disease with marked peripheral blood lymphocytosis



    • Intermediate size lymphocytes with prominent central nucleoli


    • Cells lack cytoplasmic villous projections


  • Marked splenomegaly



    • Prominent nodular white pulp with secondary red pulp involvement


    • Nucleoli are difficult to appreciate in tissue sections without 1,000x (oil) magnification


  • IgM(+), IgD(+/−), B-cell antigens(+), CD5(+/−), CD79b(+), CD10(−)


Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)



  • Prominent nodular involvement of white pulp with secondary red pulp involvement



    • White pulp has monophasic appearance


  • Small, round lymphocytes, prolymphocytes, and paraimmunoblasts


  • IgM(+), IgD(+/−), CD5(+), CD23(+), CD10(−), CD22(−), CD79b(−/+)


Mantle Cell Lymphoma (MCL)



  • Prominent nodular involvement of white pulp with secondary red pulp involvement



    • White pulp has monophasic appearance


  • Monotonous tumor cell population; no large cells (in typical cases)


  • IgM(+), IgD(+), CD5(+); Cyclin-D1(+, bright), CD23(−/+), CD10(−), DBA.44/CD76(−)


DIAGNOSTIC CHECKLIST


Clinically Relevant Pathologic Features



  • Leukocytosis and lymphocytosis common


Pathologic Interpretation Pearls



  • Spleen: Diffuse expansion of red pulp cords and sinuses with effacement of white pulp


  • Blood: Small cells with distinct nucleoli and cytoplasmic projections


  • CD11c(+), CD22(+), CD103(+/−), CD25(−), and TRAP cytochemistry(−)



SELECTED REFERENCES

1. Dong HY et al: Immunophenotypic analysis of CD103+ B-lymphoproliferative disorders: hairy cell leukemia and its mimics. Am J Clin Pathol. 131(4):586-95, 2009

2. Hashimoto Y et al: Hairy Cell Leukemia-Related Disorders Consistently Show Low CD27 Expression. Pathol Oncol Res. Epub ahead of print, 2009

3. Petit B et al: Among 157 marginal zone lymphomas, DBA.44(CD76) expression is restricted to tumour cells infiltrating the red pulp of the spleen with a diffuse architectural pattern. Histopathology. 54(5):626-31, 2009

4. Cannon T et al: Hairy cell leukemia: current concepts. Cancer Invest. 26(8):860-5, 2008

5. Matutes E et al: Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia. 22(3):487-95, 2008

6. Traverse-Glehen A et al: Splenic red pulp lymphoma with numerous basophilic villous lymphocytes: a distinct clinicopathologic and molecular entity? Blood. 111(4):2253-60, 2008

7. Razaq M et al: Hairy cell leukemia variant transforming into aggressive lymphoma with prostatic involvement in a patient with polycythemia vera. Leuk Lymphoma. 47(4):754-7, 2006

8. Cessna MH et al: Hairy cell leukemia variant: fact or fiction. Am J Clin Pathol. 123(1):132-8, 2005

9. Del Giudice I et al: The diagnostic value of CD123 in B-cell disorders with hairy or villous lymphocytes. Haematologica. 89(3):303-8, 2004

10. Kansal R et al: Histopathologic features of splenic small B-cell lymphomas. A study of 42 cases with a definitive diagnosis by the World Health Organization classification. Am J Clin Pathol. 120(3):335-47, 2003

11. Matutes E et al: The variant form of hairy-cell leukaemia. Best Pract Res Clin Haematol. 16(1):41-56, 2003

12. Mollejo M et al: Splenic small B-cell lymphoma with predominant red pulp involvement: a diffuse variant of splenic marginal zone lymphoma? Histopathology. 40(1):22-30, 2002

13. Matutes E et al: The natural history and clinico-pathological features of the variant form of hairy cell leukemia. Leukemia. 15(1):184-6, 2001

14. Sun T et al: Relationship between hairy cell leukemia variant and splenic lymphoma with villous lymphocytes: presentation of a new concept. Am J Hematol. 51(4):282-8, 1996

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Hairy Cell Leukemia Variant
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