Progressive Transformation of Germinal Centers



Progressive Transformation of Germinal Centers


Pei Lin, MD





Key Facts


Terminology



  • Progressive transformation of germinal centers (PTGC)


Clinical Issues



  • Young adults most commonly affected


  • Asymptomatic localized lymphadenopathy in most patients



    • Cervical lymph nodes in ˜ 50%


  • Generalized lymphadenopathy occurs in subset of patients


  • Can be incidental finding in patients with lymphoma



    • NLPHL most common


  • PTGC usually resolves spontaneously



    • Can recur


  • PTGC not associated with HIV


Microscopic Pathology



  • Scattered large follicles in otherwise reactive lymph node with follicular hyperplasia


  • Mantle zone cells migrate into and disrupt hyperplastic germinal centers


  • Each affected follicle at different stage of PTGC (asynchronous)


Top Differential Diagnoses



  • Nodular lymphocyte-predominant Hodgkin lymphoma


  • Lymphocyte-rich classical Hodgkin lymphoma, nodular variant


  • Follicular lymphoma, floral variant


  • HIV-associated lymphadenopathy






The PTGC follicle image is 4-5x larger than normal reactive follicles image. Note the expanded mantle zone image of the PTGC follicle.






High-power magnification shows the center of a PTGC follicle. Centroblasts and centrocytes are intermixed with small mature lymphocytes from the mantle zone. However, LP cells are not present.


TERMINOLOGY



Abbreviations



  • Progressive transformation of germinal centers (PTGC)


Synonyms



  • Progressively transformed germinal centers


  • Progressively transformed follicular centers



Definitions



  • Reactive hyperplasia of follicles characterized by



    • Large follicles with hyperplastic germinal centers


    • Disruption of germinal centers due to infiltration by mantle zone B cells


    • Affected follicles typically are at different stages of dissolution


ETIOLOGY/PATHOGENESIS


Unknown



  • Viral cause suspected


CLINICAL ISSUES


Presentation



  • PTGC can occur at any age but is common in young adults



    • Median age: 28 years


    • ˜ 20% of cases occur in children


  • M > F


  • PTGC usually involves peripheral lymph nodes



    • Cervical lymph nodes are most commonly involved (50% of cases)


    • Axillary and inguinal lymph nodes less common


  • PTGC can be the predominant change in lymph nodes prompting biopsy


  • Patients with PTGC can present ± symptoms



    • Most frequent presentation is asymptomatic and localized lymphadenopathy


    • Generalized lymphadenopathy can occur in subset of patients



      • Adolescents who present with viral-like illness


      • Patients with autoimmune diseases


    • PTGC can be incidental finding in patients with lymphoma



    • PTGC can be detected at initial diagnosis or after therapy


    • Interval between PTGC and lymphoma can be > 10 years


    • PTGC also rarely can precede diagnosis of lymphoma


  • PTGC usually spontaneously resolves but can recur



    • Same or different lymph nodes


    • Recurrence occurs more often in children than in adults


  • PTGC is not associated with HIV infection



Treatment



  • Observation


Prognosis



  • Excellent


IMAGE FINDINGS


Radiographic Findings



  • Lymphadenopathy in subset of patients


MICROSCOPIC PATHOLOGY


Histologic Features



  • Follicles with PTGC are usually large



    • 4-5x larger than normal reactive secondary follicles


  • PTGC is usually focal; involves only a few follicles in lymph node


  • Process of PTGC appears to proceed in stages



    • Initially germinal centers become hyperplastic



      • “Starry sky” pattern can occur but is unusual



    • 2-3 germinal centers per follicle fuse together


    • Mantle zone B cells infiltrate and disrupt germinal centers


    • Eventually germinal centers disappear



    • Centroblasts and follicular dendritic cells are scattered among small mantle zone B cells


  • Follicles involved by PTGC appear to be at different stages (i.e., asynchronous)


  • PTGC is almost always accompanied by follicular hyperplasia



    • Interfollicular hyperplasia often present


  • PTGC follicles can show Castleman-like changes (uncommon)


  • Clusters of epithelioid cells can surround PTGC follicles



    • More common in pediatric cases


  • PTGC can coexist with Hodgkin or non-Hodgkin lymphoma



    • Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is most common



      • No data to support PTGC as precursor of NLPHL


    • Other lymphoma types uncommonly associated with PTGC



      • Classical Hodgkin lymphoma (nodular sclerosis or mixed cellularity)


      • Plasma cell myeloma


    • PTGC may involve same lymph node involved by lymphoma or different lymph node


  • In generalized cases of PTGC, histologic findings are more florid



    • Rarely associated with lymphoma


Cytologic Features



  • Mixed population of small and large lymphocytes



    • Small round lymphocytes are mantle zone B cells and reactive T cells


    • Germinal center centrocytes and centroblasts


  • No LP cells; no Hodgkin-Reed-Sternberg (HRS) cells


  • No plasma cells, neutrophils, or eosinophils


ANCILLARY TESTS


Immunohistochemistry



  • Preserved B-cell and T-cell compartments of lymph node



    • Prominent follicular pattern


  • In PTGC follicles



    • Germinal centers



      • B-cell antigens (±), T-cell antigens (-)


      • CD10(±), Bcl-6(±), Bcl-2(-)


      • Disruption of follicular dendritic cells that are CD21(±), CD23(±)


    • Mantle zones



    • B-cell antigens (±), T-cell antigens (-)


    • IgD(±), Bcl-2(±)


    • CD10(-), Bcl-6(-)


  • T cells are relatively few in PTGC follicles


Flow Cytometry



  • No evidence of monoclonal B-cell population

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Progressive Transformation of Germinal Centers

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