Primary Cutaneous Anaplastic Large Cell Lymphoma



Primary Cutaneous Anaplastic Large Cell Lymphoma


Aaron Auerbach, MD, PhD





Key Facts


Terminology



  • One of the primary cutaneous CD30(+) T-cell lymphoproliferative disorders



    • T-cell lymphoma of atypical, usually large CD30(+) cells, without evidence of mycosis fungoides


Clinical Issues



  • Solitary or localized nodules that can regress but frequently occur


  • Can involve regional lymph nodes


  • Treated with skin-targeted therapy for low-stage disease, chemotherapy for systemic disease


  • Good prognosis, ˜ 90% 10-year survival


Microscopic Pathology



  • Polymorphic background infiltrate not prominent


  • Diffuse sheets of large T cells in the dermis ± subcutis


  • Hallmark cells with multiple nuclei (horseshoe-shaped), helpful if present


Ancillary Tests



  • Immunohistochemistry: CD30(+), CD15(−), CD3(+), cytotoxic markers(+), EMA(−), ALK(−), CLA(+)


  • Molecular: No ALK gene translocations on chromosome 2


Top Differential Diagnoses



  • Systemic ALCL with cutaneous involvement



    • EMA(+), ALK(+) and ALK gene translocations, unlike primary cutaneous ALCL


  • Lymphomatoid papulosis (LyP)



    • Groups of papules that regress and recur


    • Wedge-shaped and prominent polymorphous background infiltrate







This is a solitary raised nonulcerated tumor nodule on the forehead of a man diagnosed with primary cutaneous anaplastic large cell lymphoma. (Courtesy R. Willemze, MD.)






Histologic section of cutaneous ALCL shows large atypical cells with abundant cytoplasm and irregular multilobated nuclei image, admixed with a background of small inflammatory cells.


TERMINOLOGY


Abbreviations



  • Primary cutaneous anaplastic large cell lymphoma (PCALCL)


Synonyms



  • Regressing atypical histiocytosis


  • Primary cutaneous large cell T-cell lymphoma, CD30(+)


Definitions



  • CD30(+) T-cell lymphoma consisting of atypical, usually large cells, without evidence of mycosis fungoides



    • One of the primary cutaneous CD30(+) T-cell lymphoproliferative disorders, including lymphomatoid papulosis (LyP) and borderline lesions


ETIOLOGY/PATHOGENESIS


Idiopathic



  • Viral infection, chronic antigen stimulation, and immunosuppression may play a role


  • Mechanism may involve CD30/TRAF1 upregulation of NF-κB


CLINICAL ISSUES


Epidemiology



  • Incidence



    • 2nd most common cutaneous T-cell lymphoma after mycosis fungoides



      • 0.1-0.2 per 100,000 people


      • 20% of systemic ALCL cases involve skin


  • Age



    • Median age: 60s, but can occur in children


  • Gender



    • Male:female = 2-3:1


Site



  • Often trunk, face, and extremities


Presentation



  • Solitary or localized nodules, tumors, or papules



    • ± ulceration


    • Multifocal ˜ 20%


  • Usually no symptoms other than mass effect


Natural History



  • Partial or complete spontaneous regression (40%), but frequently recur


  • Extracutaneous dissemination ˜ 10%



    • Usually to regional lymph nodes


Treatment



  • Adjuvant therapy



    • Radiation for localized nodules


    • Methotrexate for multifocal lesions


    • Chemotherapy for systemic disease


Prognosis



  • Better than most T-cell lymphomas



    • ˜ 90% 10-year survival


    • Age < 60 years and spontaneous regression are good prognostic indicators


    • Systemic disease is poor prognostic indicator



      • Multifocal skin lesions and local lymph node involvement do not yield worse prognosis


MICROSCOPIC PATHOLOGY


Histologic Features



  • Diffuse sheets of large T cells in the dermis ± subcutis



    • Infrequent epidermotropism ± ulceration


    • Can involve lymphatic spaces


  • Tumor cells



    • Large anaplastic, pleomorphic, or immunoblastic appearance



    • Anaplastic cells with roundish shapes ± abundant cytoplasm



      • Small cell and histiocyte-rich variants are rare


    • Mitotic figures


    • Hallmark cells with multiple nuclei (horseshoe-shaped), often not seen, but helpful if present


  • Polymorphic background infiltrate (eosinophils and plasma cells) uncommon, unlike LyP



    • Exceptions



      • Ulcerating ALCL has polymorphic infiltrate, fewer CD30(+) cells, and epidermal hyperplasia


      • Neutrophil-rich (pyogenic ALCL) shows clusters of neutrophils with only scattered CD30(+) cells


ANCILLARY TESTS


Immunohistochemistry



  • CD30(+) (> 75% of tumor cells), CD15(−)


  • T-cell antigens expressed (CD2[+], CD3[+], CD5[+], CD7[+])



    • But can show loss of T-cell antigens



      • CD7 most common


  • CD4(+)/CD8(−)



    • CD8(+) and CD4(−)/CD8(−) rarely


  • Cytotoxic markers positive



    • Granzyme-B, perforin, TIA


  • EMA(−) and ALK(−) in PCALCL



    • Usually EMA(+) and ALK(+) in systemic ALCL


    • ALK(+) skin tumor likely indicates secondary cutaneous ALCL


  • Cutaneous lymphocyte antigen (CLA[+]) and HOXC5(+) in PCALCL



    • But CLA(−) in systemic ALCL


  • Negative for B-cell markers (CD20 and CD79)



    • Rarely positive for pax-5


Cytogenetics



  • No specific findings


Molecular Genetics



  • Clonal T-cell receptor gene rearrangement ˜ 90%


  • No translocations of ALK gene on chromosome 2p23


DIFFERENTIAL DIAGNOSIS


Systemic ALCL with Cutaneous Involvement



  • Similar morphologic features and overlapping phenotype with PCALCL


  • Separate disease from PCALCL, with different molecular findings and prognosis



    • Primary tumor in extracutaneous site that secondarily involves skin


  • Differences from PCALCL



    • Systemic ALCL also found in extracutaneous sites


    • Typically EMA(+) and ALK(+), unlike PCALCL


    • Translocations involving ALK gene


    • Less favorable prognosis (especially ALK[-] systemic ALCL)


Lymphomatoid Papulosis (LyP)

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Primary Cutaneous Anaplastic Large Cell Lymphoma

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