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Anaplastic Large Cell Lymphoma (ALCL)

Anaplastic Large Cell Lymphoma (ALCL). Objectives of this presentation Discuss morphologic variants of ALCL which have potential to be misdiagnosed with non-hematopoietic neoplasms Discuss the differential diagnosis with emphasis on the immunohistochemical profile and molecular testing

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Anaplastic Large Cell Lymphoma (ALCL)

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  1. Anaplastic Large Cell Lymphoma (ALCL) • Objectives of this presentation • Discuss morphologic variants of ALCL which have potential to be misdiagnosed with non-hematopoietic neoplasms • Discuss the differential diagnosis with emphasis on the immunohistochemical profile and molecular testing • Discuss prognosis based on morphologic variants and specific molecular ttranslocation with clinical outcomes

  2. ALCL T cell lymphoma of large lymphoid cells with pleomorphic, often horseshoe shaped nuclei and abundant cytoplasm with sinusoidal spread in lymph nodes, expressing CD30 with or without ALK and either T cell associated antigens or no lineage specific antigens • Nodal, localized or multiple • Extranodal (bone, GI, Lung, Skin) • High stage (children) • Aggressive but curable • ALCL accounts for approximately 3% of adult non-Hodgkin lymphoma and involves both lymph nodes and extra-nodal sites. • Extra-nodal ALCL has been found in the skin (21%), soft tissue (17%), bone (17%), lung (11%), and liver (8%). • Involvement of the breast is rare in primary ALCL.

  3. Differential Diagnosis • Sarcomatoid/ Anaplastic Carcinoma • Pleomorphic Sarcoma, Nos • Angiosarcoma • Malignant Melanoma • Histiocytic Sarcoma, NOS • Proximal Epithelioid Sarcoma • (Sarcomatoid) Hodgkin’s Lymphoma (LD) • Anaplastic Large Cell Lymphoma (ALCL)

  4. ALCL Morphology • Wide variety of morphologic variants • All may show hallmark cells in varying proportion • classical (60%) • giant-cell rich • lymphohistiocytic (10%) • small cell (5%) • Hodgkin-like (3%) • sarcomatoid (<1%) • mixed subtypes (15%) • Small cell variant renders itself to a wider differential including carcinoma and melanoma • The Sarcomatoid variant in extra-nodal sites (skin and soft tissue) morphologically overlaps with sarcomas and inflammatory myofibroblasticpseudotumor

  5. ALCL • 3% adults; 10-30% childhood lymphomas • Activated mature cytotoxic T cell : cell of origin • Primary systemic (CD30 +, ALK1 +, EMA+) • Primary Cutaneous (CD30 +, ALK1-, EMA -/+) • Expression of T cell antigens: 60% :CD30 positive with CD3 +/-, CD5 +/-, CD4 +/-, CD43 +/-CD7, CD8 negative and cytotoxic T cell antigen positive (granzyme B, TIA-1, perforin) • * CD99 shown to be +ve in 75% cases of ALCL • By Flow Cytometry show CD2 but can show myeloid marker (CD13, CD33) • Even “Null cell” (40%) type show T cell gene rearrangement by molecular analysis

  6. ALCL • ALK 1 positivity- good prognostic factor (2% of all NHL and 10% of childhood NHL) • Staining can be cytoplasmic, nuclear ( due to dysregulation of ALK kinase activity) and occassional membranous: ALK-1 antibody • Fusion of transmembrane protein ALK protein gene (2p23) with nucleophosmin NPM, nuclear transport protein resulting in t(2;5) (75%) (FISH more sensitive than RT-PCR or classical cytogenetics): ALK-1 antibody on FFPE tissue • Systemic ALCL- 5 year survival in ALK positive cases is 80% compared to less than 40% in ALK negative cases • ALK negative ALCL (older age group) demonstrates similar (poor) prognosis to peripheral T cell lymphoma, NOS • Relapses are common (30%) but sensitive to chemotherapy

  7. CD30 Expression: Always use in a panel • ALCL • Hodgkin’s Lymphoma • T and NK/T cell lymphomas • Large B cell Lymphoma • Lymphomatoid papulosis • Reactive Conditions • AML/ Granulocytic Sarcoma • Plasma cell neoplasms • Non-Hematological malignancies • Embryonal Carcinoma • Pancreatic Carcinoma • Malignant Melanoma • Mesothelioma

  8. ALK Expression in Tumors Other than ALCL • Cytoplasmic rather than nuclear staining • Occurs in • Inflammatory Myofibroblastic Tumor • Alveolar>Embryonal RMS • MPNST • Leiomyosarcoma and MFH (10% of cases) • Neuroblastoma • Rare Large B cell Lymphoma showing t(2; 17)

  9. Treatment and prognosis • ALCL (ALK+): CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), is the standard first-line treatment, with an overall response rate of 90% • Patients with ALK+ ALCL exhibit significantly better outcome than patients with ALK- ALCL; 5-year Overall survival of 70–80% (vs. 33–49% for ALK – ALCL) • BrentuximabVedotin (Anti CD30): Recurrent/ Relapsed ALCL

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