ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's lymphoma: report of 10 cases.

Centre de Physiopathologie de Toulouse-Purpan, Department of Oncogenesis and Signalling in Hematopoietic Cells and Laboratory of Pathology, Hôpital Purpan, Centre Hospitalier Universitaire, University of Toulouse, Toulouse, France.
American Journal of Surgical Pathology (Impact Factor: 4.59). 03/2006; 30(2):223-9. DOI: 10.1097/01.pas.0000179123.66748.c2
Source: PubMed

ABSTRACT Anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) are recognized as biologically distinct entities. However, occasionally, these two entities may share some morphologic features responsible for diagnostic difficulties. In the last 10 years, we have collected 380 cases of ALK-positive ALCL of which 10 cases were originally diagnosed as nodular sclerosis classic HL (NSHL) on conventional histopathological examination. After immunostaining, these cases proved to be ALK-positive ALCL mimicking HL (so-called Hodgkin-like ALCL). These cases account for 2.6% of our cases of ALK-positive ALCL (10 of 380 cases). Median age was 11 years (3-92 years) with a female predominance (male/female ratio, 3:7). Characteristically, these lesions showed thick nodular fibrosing bands highly suggestive of NSHL. Neoplastic cells were scarce in 6 cases, whereas in the 4 remaining cases, sheets of tumor cells were also present. A perivascular and a sinusoidal growth pattern was observed in various degrees in all cases. Few binucleated Reed-Sternberg-like cells were present in every case in a background of small lymphocytes. Inflammatory cells (ie, granulocytes, eosinophils, and histiocytes) were rare. Neoplastic cells were positive for CD30 (10 of 10 cases), ALK protein (10 of 10 cases), epithelial membrane antigen (EMA) (9 of 9 cases), CD43 (6 of 9 cases), and perforin (8 of 8 cases), but negative for CD15 (10 of 10 cases), CD20 (10 of 10 cases), Pax5/BSAP (6 of 6 cases), and EBV (8 of 8 cases). In addition, in 7 cases, neoplastic cells were of T-phenotype, whereas the 3 remaining cases were considered to be of null/undetermined phenotype. Although rare, Hodgkin-like ALCL may mimic NSHL, and it is advisable to include EMA in the first line panel and to ask for ALK staining in EMA-positive, CD15-negative lesions with morphologic features suggestive of NSHL.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive (ALK+ ALCL) is an aggressive CD30-positive T-cell lymphoma that exhibits a chromosomal translocation involving the ALK gene and the expression of ALK protein. No particular risk factor has been clearly identified for ALCL. ALK+ ALCL shows a broad morphologic spectrum, but all cases contain a variable proportion of cells with eccentric, horseshoe- or kidney-shaped nuclei often with an eosinophilic region near the nucleus (hallmark cells). Five morphologic patterns can be recognized. ALK+ ALCL occurs in young subjects (median age ∼35 years), with male predominance, and frequently presents at an advanced stage, with systemic symptoms and extranodal involvement. Near 40% of patients are low risk according to the International Prognostic Index (IPI). Overall, the prognosis of ALK+ ALCL is remarkably better than other T-cell lymphomas. The IPI and the PIT scores in general predict survival in patients with ALK+ ALCL. Standard first-line treatment for ALK+ ALCL consists of doxorubicin-containing polychemotherapy, which is associated with an overall response rate of ∼90%, a 5-year relapse-free survival of ∼60%, and a 5-year overall survival of 70%. Excellent results have been reported with a variety of anthracycline-based chemotherapy regimens including CHOP, CHOEP or MACOP-B. Consolidative high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) has also been evaluated in patients in first remission with favourable results, however, superiority to standard chemotherapy is unproven and this approach remains investigational. Following universally accepted guidelines for the treatment of failed aggressive lymphomas, HDC/ASCT can effectively salvage a proportion of patients with relapsed or refractory ALK+ ALCL. Recently, the development of novel therapies targeting CD30 and ALK appear promising.
    Critical reviews in oncology/hematology 03/2012; 83(2):293-302. DOI:10.1016/j.critrevonc.2012.02.005 · 4.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nonhodgkin malignant lymphomas (NHL) represent a heterogeneous group of immune system cells-monoclonal tumors (lymphocytes and histiocytes). NHL can be divided phenotypically in T cell lymphomas and B cell lymphomas. T cell NHL are recognized only by three decades. They have an incidence of 12-15% and represent a heterogeneous group from clinical, evolutional and hystophenotypical point of view, which raises many problems of diagnosis and therapy. Rezumat: Limfoamele maligne nonhodgkin (LMNH) reprezintă un grup heterogen de tumori monoclonale al celulelor sistemului imunitar (limfocite şi histiocite). LMNH se împart din punct de vedere fenotipic în limfoame de tip T şi de tip B. LMNH de tip T sunt recunoscute doar de 3 decenii. Au o incidenţă de 12-15% şi reprezintă un grup heterogen din punct de vedere clinic, evolutiv şi histofenotipic ceea ce ridică numeroase probleme de diagnostic şi de conduită terapeutică.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The authors revise the concept of anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.
    Advances in Hematology 01/2010; 2010:345053. DOI:10.1155/2010/345053


Available from