Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type



Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type


Sa A. Wang, MD










Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). This field shows a diffuse infiltrate replacing the dermis with sparing of the epidermis image.






The lymphoma cells in PCDLBCL-LT are large and strikingly round with centrally located nucleoli (immunoblasts).


TERMINOLOGY


Abbreviations



  • Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT)


Synonyms



  • Primary cutaneous large B-cell lymphoma, leg type


  • Primary cutaneous diffuse large B-cell lymphoma


Definitions



  • Primary cutaneous diffuse large B-cell lymphoma composed exclusively of large transformed B cells



    • Often occurs in lower leg(s) but can arise at other skin sites


ETIOLOGY/PATHOGENESIS


Cell of Origin



  • Peripheral B cell of post-germinal center cell origin



    • Immunophenotype: IRF-4/MUM1(+), FOXP1(+)


    • High frequency of somatic mutations of IgH variable (V)-region genes


Possible Role of Antigen Selection



  • Preferential use of certain IgH V gene segments



    • Suggests that antigen stimulation may be involved in pathogenesis


Role of Molecular Abnormalities



  • Number of genetic rearrangements and deletions reported


  • No abnormality consistently present


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare



      • 4% of all cutaneous lymphomas


      • 20% of primary cutaneous B-cell lymphomas


  • Age



    • Elderly patients; median age: 7th decade


  • Gender



    • More common in women



      • Male to female ratio: 1:1.6; as high as 1:4 in some studies


Site



  • Most cases arise in skin of lower leg; 1 or both legs



    • ˜ 85% of all cases


  • Subset of cases arise in skin of other sites (trunk, arms, head and neck)



    • ˜ 15% of cases


    • Similar morphologic and immunophenotypic characteristics


  • Single or multiple lesions at time of presentation



    • Some patients have dissemination at initial diagnosis


Presentation



  • Red or blue-red lesions on skin



    • Plaque, verrucous plaques, or deep plaques


    • Nodular, tumoral lesions


    • Often associated with ulcer


    • Multiple lesions are common


  • B symptoms in 10-20% of patients


Treatment



  • Anthracycline-containing systemic chemotherapy plus rituximab (R-CHOP)


  • Radiotherapy has role for localized lesions in elderly patients


Prognosis



  • Relapse is common


  • 40-50% 5-year survival rate



    • Factors adversely correlated with prognosis



      • Older age



      • Multiple lesions at presentation


      • Inactivation of CDKN2A


    • Factors not correlated with prognosis



      • Duration of lesions before diagnosis


      • Gender, B symptoms, performance status or serum lactate dehydrogenase level


      • Bcl-2 or IRF-4/MUM1 expression


MICROSCOPIC PATHOLOGY


Histologic Features



  • Diffuse pattern of involvement in dermis



    • Infiltrate can be deep


  • Cohesive, monotonous sheets of large cells



    • Centroblasts or immunoblasts


    • Often very round nuclei


  • Mitotic figures numerous


  • Few small reactive T cells in background


  • No centrocytes (or small B cells) present


  • No epidermotropism


ANCILLARY TESTS


Immunohistochemistry



  • Pan-B-cell antigens(+)


  • Cytoplasmic IgM(+), IgD(+/−)


  • Bcl-2(+), IRF-4/MUM1(+), FOXP1(+)


  • Bcl-6(+), CD10(−)


  • No follicular dendritic cell (FDC) meshworks



    • CD21(−), CD23(−), CD35(−)


  • T-cell antigens(−), LMP1(−), HHV8(−)


In Situ Hybridization



  • FISH often shows rearrangements of MYC, BCL-6, or IgH genes


  • No evidence of IgH-BCL-2/t(14;18) or BCL-2 rearrangements


  • EBER(−)


Array CGH



  • Amplification of 18q21.31-33 involving BCL-2 and MALT1 genes


Molecular Genetics



  • Monoclonal IgH gene rearrangements


  • No evidence of IgH-BCL-2/t(14;18)


Gene Expression Profiling



  • Profile is consistent with activated B-cell phenotype


DIFFERENTIAL DIAGNOSIS


Primary Cutaneous Follicle Center Cell Lymphoma (PCFCL)

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type
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