Lymphoid Aggregates in Bone Marrow



Lymphoid Aggregates in Bone Marrow


Kaaren K. Reichard, MD









This is the typical appearance of a benign lymphoid aggregate in bone marrow; it is nodular, nonparatrabecular, well circumscribed, and composed of predominantly small mature lymphocytes.






Typical immunohistochemical findings in a benign lymphoid aggregate show a slight T-cell predominance (CD3, red) with a central collection of B cells (CD20, brown).


TERMINOLOGY


Abbreviations



  • Lymphoid aggregate (LA)


  • Bone marrow (BM)


Definitions



  • Focal collections of nonneoplastic lymphoid cells


  • Usually identified in BM clot and core biopsy sections


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Variety of systemic infections may be associated with benign LAs in bone marrow



    • Viral most common (e.g., HIV, Epstein-Barr virus)


Underlying Immune Disorders



  • Autoimmune disorders


  • Collagen vascular disease


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Increases with age


  • Age



    • More common in older individuals


  • Gender



    • Tends to be more common in females


Presentation



  • Asymptomatic


  • If symptomatic, relates to underlying disorder


Laboratory Tests



  • Performed for work-up of possible underlying etiology



    • Systemic infection


    • Autoimmune disorder


    • Neoplasia


Treatment



  • No treatment necessary for benign LAs per se


  • Treatment targeted toward underlying disease (e.g., infection, immune dysregulation)


Prognosis



  • Relates to underlying disease


MICROSCOPIC PATHOLOGY


Histologic Features



  • Small, round, well circumscribed, interstitial/nonparatrabecular


  • Morphologic variations



    • Large, polymorphous aggregates (e.g., HIV)


    • Occasional larger atypical or activated cells (e.g., infection, autoimmune disorder)


    • Associated germinal center (occasional)


    • Associated lipogranuloma (especially in elderly)


    • Associated histiocytes


Cytologic Features



  • Round or slightly irregular nuclear contours, mature, clumped chromatin, inconspicuous nucleoli, usually scant cytoplasm


Predominant Pattern/Injury Type



  • Circumscribed


  • Focal, nodular


  • Interstitial


  • Perivascular


Predominant Cell/Compartment Type



  • Lymphocyte


Bone Marrow Aspirate



  • May identify small, discrete collections of lymphocytes on scanning



  • Background marrow generally does not reveal increased, individually dispersed lymphocytes


Bone Marrow Clot Section/Core Biopsy



  • Discrete foci of predominantly small lymphocytes


  • Interstitial/nonparatrabecular distribution, perivascular, adjacent to dilated sinuses, or associated with a small, penetrating vessel


  • Morphologic variations



    • Large, poorly circumscribed, polymorphous infiltrates



      • Typical of human immunodeficiency virus infection


      • Often see admixed larger, atypical cells; may require distinction from lymphoid neoplasia


    • Occasional larger atypical or activated cells



      • Typical of infection or ongoing immune reaction


    • Associated germinal center



      • Uncommon overall


      • More evident in autoimmune disorders


    • Associated with lipogranuloma


    • Associated with small collections of epithelioid histiocytes


ANCILLARY TESTS


Immunohistochemistry



  • Cellular composition



    • Predominance of CD3(+) T cells with few admixed CD20(+) B cells or


    • Equal admixture of CD20(+) B cells and CD3(+) T cells


  • Cellular distribution



    • B cells tend to locate centrally surrounded by concentric rim of T cells


  • B-cell antigen expression



    • No aberrant detection of CD5, CD10, CD43



      • Normal germinal center cells may be CD10(+)


Flow Cytometry



  • Polyclonal B cells


  • Normal T-cell antigens and subsets


  • Caveat



    • Lymphoid aggregate cells may not be well represented in flow cytometric BM aspirate samples


Genetics



  • Nonclonal


DIFFERENTIAL DIAGNOSIS


Lymphomas/Chronic Leukemias with Nodular Pattern



  • General comments



    • Paratrabecular or intrasinusoidal pattern helps distinguish from benign LAs


    • B-cell disorders show B-cell predominance (CD20/CD19)


    • Reed-Sternberg cells in classical Hodgkin lymphoma


    • Aberrant antigen expression



      • CD5(+) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL)


      • CD10(+) in follicular lymphoma


      • Cyclin D1(+) in MCL


      • Light chain restriction by flow cytometry


    • Molecular studies



      • Clonal


      • Recurring genetic abnormalities in certain disorders [e.g., t(11;14)(q13;q32) in MCL]


  • After rituximab (anti-CD20) treatment



    • Post-therapy aggregates are T-cell predominant


    • Useful distinguishing features from benign LAs



      • Often paratrabecular


      • Often poorly circumscribed


    • CD79a and CD19 useful to identify residual neoplastic cells


Hematogones



  • Rarely cluster


  • Characteristic immunophenotypic profile



Metastatic Tumor



  • In addition to nodular collections, also tend to see sinusoidal involvement


  • Cells typically much larger than lymphocytes


  • Lymphoid markers are negative (e.g., CD20, CD3)


  • Express tumor-associated antigens


Erythroid Colonies



  • Foci of erythroid precursors (round, often dark nuclei) may mimic lymphoid aggregates



    • Often result of poor processing, sectioning, staining


  • Cells are negative for lymphoid markers; positive for hemoglobin A

Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Lymphoid Aggregates in Bone Marrow
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