Hyaline Vascular Castleman Disease



Hyaline Vascular Castleman Disease


Pei Lin, MD





Key Facts


Clinical Issues



  • Young adults


  • Lymphadenopathy, localized


  • Excision is usually curative


Microscopic Pathology



  • Large follicles with regressed (involuted) germinal centers


  • 2 or more germinal centers per follicle (twinning)


  • Concentric rings of mantle zone lymphocytes (“onion skin”)


  • Hyaline-vascular (“lollipop”) follicles


  • Increased vascular proliferation in interfollicular zones


  • Plasma cells and immunoblasts are not abundant


Ancillary Tests



  • Polytypic B cells and normal T cells


  • Increased FDCs in germinal centers: CD21(±), CD23(±), CD35(±), &/or EGFR(±)


  • No evidence of monoclonal Ig or TCR gene rearrangements


  • No consistent cytogenetic or molecular abnormalities known


Top Differential Diagnoses



  • Castleman disease, plasma cell variant


  • Thymoma


  • Angioimmunoblastic T-cell lymphoma


  • HIV lymphadenitis


  • Castleman-like changes associated with various lymphomas






Regressed germinal centers image are surrounded by expanded mantle zones image in this case of Castleman disease, hyaline-vascular variant (HV-CD). Note the marked interfollicular blood vessel proliferation image.






Positive CT scan shows a 4.5 cm mass in the lower left paraspinal region image. The site of disease in this patient is unusual, but is otherwise consistent with unifocal HV-CD.


TERMINOLOGY



Abbreviations



  • Castleman disease, hyaline-vascular variant (HV-CD)


Synonyms



  • Angiofollicular lymph node hyperplasia


  • Giant lymph node hyperplasia


  • Angiomatous lymphoid hamartoma



Definitions



  • Typically unicentric and reactive lymphoproliferation of unknown etiology involving lymph nodes


ETIOLOGY/PATHOGENESIS


Unknown



  • Possible factors in pathogenesis



    • Dysregulation of vascular endothelial growth factor


    • Follicular dendritic cell (FDC) dysplasia may be precursor


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare


  • Age



    • Young adults (typically under 30 years of age)


    • Can also affect children


  • Gender



    • M = F


Presentation



  • Patients present with localized mass



    • Mass often detected incidentally


  • Rarely symptoms related to compression of adjacent tissues by enlarged lymph nodes


  • Lymphadenopathy, localized



    • Mediastinal or thoracic lymph nodes most commonly involved


    • Other sites: Cervical and retroperitoneal lymph nodes


    • Extranodal sites of involvement are rare


  • Patients may develop secondary amyloidosis



Treatment



  • Surgical approaches



    • Surgery to remove enlarged lymph nodes


  • Adjuvant therapy



    • Usually not necessary


    • Radiation therapy has been used to alleviate compression symptoms


Prognosis



  • Excellent


  • Surgical removal is usually curative; relapse can occur uncommonly


  • Malignant neoplasms can arise in association with HV-CD



    • Follicular dendritic cell sarcomas are most common


    • Vascular neoplasms


    • Secondary neoplasms in HV-CD are often low grade, but metastases have been reported


IMAGE FINDINGS


Radiographic Findings



  • Enlarged lymph node or group of lymph nodes, but any site can be involved



    • Mediastinal or thoracic lymph nodes most common


MICROSCOPIC PATHOLOGY


Histologic Features



  • Numerous follicles in cortex and medulla of lymph node


  • Obliteration of subcapsular sinuses



  • ≥ 2 germinal centers in a follicle a.k.a. twinning


  • Follicles typically large with regressed (or involuted) germinal centers



    • Germinal centers are composed mostly of FDCs with few lymphocytes


    • FDCs often hyperplastic and can show dysplasia


  • Many follicles show so-called lollipop features characterized by



    • Concentric rings of the mantle zone lymphocytes (onion-skin appearance)


    • Sclerotic blood vessels radially traversing into germinal center


  • Interfollicular or stromal component is also important



    • Increased number of high endothelial venules with hyalinized walls


    • Stromal component can predominate with only a few hyaline-vascular follicles


  • Clusters of plasmacytoid dendritic cells (plasmacytoid monocytes) can be prominent


  • Plasma cells and immunoblasts are not abundant in HV-CD



    • Much more common in plasma cell variant of CD (PC-CD)


ANCILLARY TESTS


Immunohistochemistry



  • Human herpesvirus 8 (HHV8) is absent


  • Polytypic B cells and T cells


  • Increased FDCs in involuted germinal centers often positive for CD21, CD23, CD35, or EGFR



    • Dysplastic FDCs often stain variably for FDC markers


  • Plasma cells are polytypic


Flow Cytometry



  • Polytypic B cells and T cells with normal immunophenotype


Cytogenetics



  • Rare cases reported with chromosomal translocations or other clonal abnormalities



    • No consistent cytogenetic findings


  • Del(12q13-15) resulted in intragenic HMGIC gene rearrangement in 1 case


PCR



  • No evidence of monoclonal immunoglobulin (Ig) or T-cell receptor (TCR) gene rearrangements


DIFFERENTIAL DIAGNOSIS


Castleman Disease, Plasma Cell Variant (PC-CD), HHV8(-)



  • PC-CD represents 10-20% of localized (unicentric) CD cases


  • Any lymph node group can be affected



    • Mediastinal involvement less common than HV-CD


  • Preserved overall lymph node architecture


  • Sheets of plasma cells in interfollicular areas



    • No cytologic atypia


  • Variable follicular hyperplasia with focal, less well-developed hyaline-vascular lesions


  • Lymph node sinuses not obliterated

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Hyaline Vascular Castleman Disease

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