Cancer Report

Cancer : Anaplasic large cell lymphoma (ALCL)
Summary
Cancer Name Anaplasic large cell lymphoma (ALCL)
Description Anaplasic large cell lymphoma can be classified into :
  • 1- primary systemic ALK+ ALCL
  • 2- primary systemic ALK- ALCL
  • 3- primary cutaneous ALCL. (see in paragraph Pathology)
    NOTE The 2 first categories are defined according to the involvement (or not) of ALK in fusion proteins with various partners (see below); ALK+ ALCL cases are sometimes called ALK lymphomas, or ALKomas
    ALK+ ALCL can be further divided into t(2;5) cases, with NPM1-ALK fusion protein which localises both in the cytoplasm and in the nucleus, and t(2;Var), involving various partners and ALK, and a cytoplasmic localization of the fusion protein; the latter are called "cytoplasm only" ALK+ ALCL. ALCL may also arise from transformation of another lymphoma mycosis fungoides, peripheral T-cell lymphoma, ...); these ALCL are called secondary ALCL, and they bear a poor prognosis
  •  
    Clinics and Pathology
    Epidemiology ALCL represent about 5% of non Hodgkin lymphomas (NHL) in adults, and 15 % of pediatric NHL (i.e. 20-30 % of large cell lymphomas in children). ALK+ ALCL represent 50 to 60 % of ALCL cases. ALK+ ALCL predominantly affect young male patients (most cases occur before the age of 40 yrs) , while ALK- ALCL is found in older patients (median age around 50 yrs) of both sex
    Pathology 3 main histopathological types are found;
  • the common type, characterized by large lymphoid cells with horseshoe shaped nuclei with many nucleoli, and large cytoplasm; may be ALK + or - ALCL
  • the small cell type, together with the above described cells, show small and medium sized cells; almost exclusively ALK+ cases
  • the lymphohistiocytic type also contains a number of reactive histiocytes, which, earlier, lead to the misdiagnosis of malignant histiocytosis; almost always ALK+ cases.
    All the 3 forms contain large cells, positive for CD30 (on the cell membrane and the golgi ); they are mostly epithelial membrane antigen (EMA) positive.
    most cases are T-cell cases (often cytotoxic T-cells), or may be null cases, the null cases often involving the T-cell; B-cell cases may belong to a different category; ALK+/IgA+ immunoblastic large B-cell lymphomas could exist.
    Aside are primary cutaneous anaplasic large cell lymphomas, a disease with indolent clinical course, negative for ALK, lacking the t(2;5) or variant translocations, close to the benign lymphomatoid papulosis
    NOTE: there are cases where the differential diagnosis between Hodgkin disease (HD) -where CD30 is also strongly expressed- and ALCL is difficult (cases previously called ALCL-HD like).
  • Prognosis ALK+ ALCL have a favourable prognosis, whichever the ALK parner is: 70% to 80 % 5 yr survival, while ALK- ALCL cases have a much poorer prognosis (5 yr survival in only 30% -40 %). ALK+ cases without NPM1 involvement
     
    Related Genes
    Gene Symbol TFG
    Description From cancer gene census of CGP: " 406 amino acids, 44 kDa; widely expressed "
     
    Gene Symbol ARHH
    Description From OMIM: "Genomic instability promotes tumorigenesis through defective chromosome segregation and DNA mismatch repair inactivation. By screening 18 loci for mutations, Pasqualucci et al. (2001) identified changes in the germline sequences of PIM1 (164960), MYC (190080), ARHH, and/or PAX5 (167414), in addition to BCL6, in a majority of diffuse large-cell lymphomas (DLCLs; see 601889). No mutations in PIM1, MYC, ARHH, and PAX5 were detected in germinal-center lymphocytes, naive B cells, or B-cell malignancies other than DLCLs. ARHH mutations, which were observed in 46% of DLCLs, resided within noncoding sequences, suggesting an effect on regulation of ARHH expression. FISH analysis indicated that hypermutation in these genes is not due to chromosomal translocation, as seen in Burkitt lymphoma (113970). Chromosomal translocation, however, may be an outcome of hypermutation. Specific features of the hypermutation process, including the predominance of single nucleotide substitutions with occasional deletions or duplications, a preference for transitions over transversions, and a specific motif targeting RGYW, were recognizable in each of the hypermutated loci"
     
    Gene Symbol ALK
    Description From manual review, cancer gene census of CGP 1620 amino acids; 177 kDa; glycoprotein (200 kDa mature protein) ; membrane associated tyrosine kinase receptor
     
    Gene Symbol MSN
    Description From cancer gene census of CGP: " 576 amino acids, 68 kDa; cytoskeleton protein; binds to the plasma membrane and interacts with actin. "
     
    Gene Symbol IGH
    Description From cancer gene census of CGP:
     
    Gene Symbol MYH9
    Description From cancer gene census of CGP: 1960 amino acids; 227 kDa; binds actin; protein of the cytoskeleton
     
    Gene Symbol ATIC
    Description From cancer gene census of CGP: " 591 amino acids, 64 kDa; bifunctional purine biosythesis:9th and 10th step of the de novo purine synthesis "
     
    Gene Symbol BCL2
    Description From manual review:
     
    Gene Symbol CARS
    Description From cancer gene census of CGP:
     
    Gene Symbol TOPORS
    Description From COSMIC:
     
    Gene Symbol PCSK7
    Description From cancer gene census of CGP:
     
    Gene Symbol TPM4
    Description From cancer gene census of CGP:
     
    Gene Symbol TPM3
    Description From cancer gene census of CGP: " 284 amino acids, 33 kDa; coilde coil structure; role in Calcium dependant actin-myosin interaction ALCL presents as an aggressive lymphoma with systemic signs"
     
    Gene Symbol PAFAH1B2
    Description From cancer gene census of CGP:
     
    Gene Symbol NPM1
    Description nuclear localisation; RNA binding nucleolar phosphoprotein involved in preribosomal assembly
     
    Gene Symbol JUNB
    Description From OMIM: "Mathas et al. (2002) found AP1 constitutively activated, with robust JUN (165160) and JUNB overexpression, in all cell lines derived from patients with classical Hodgkin lymphoma (236000) and anaplastic large cell lymphoma (ALCL), but not in other lymphoma types."
     
    Gene Symbol ALO17
    Description From cancer gene census of CGP: 1599 amino acids
     
    Gene Symbol CLTCL1
    Description From cancer gene census of CGP:
     
    Gene Symbol CLTC
    Description From cancer gene census of CGP: " 1675 amino acids, 191 kDa; Component of the vesicles matrix originated from the plasma membrane or the golgi "
     
    Gene Symbol JUN
    Description From OMIM: "Mathas et al. (2002) found AP1 constitutively activated, with robust JUN and JUNB overexpression, in all cell lines derived from patients with classical Hodgkin lymphoma (236000) and anaplastic large cell lymphoma (ALCL), but not in other lymphoma types. AP1 supported proliferation of Hodgkin cells, but suppressed apoptosis of ALCL cells. Mathas et al. (2002) noted that, whereas JUN is upregulated by an autoregulatory process, JUNB is under the control of nuclear factor kappa-B (NFKB; 164011). They found that AP1 and NFKB cooperate and stimulate expression of the cell cycle regulator cyclin D2 (123833), the protooncogene MET (164860), and the lymphocyte homing receptor CCR7 (600242), which are all strongly expressed in primary Hodgkin/Reed-Sternberg (HRS) cells."
     
    Gene Symbol HOXC4
    Description From manual review:
     
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    Source and Citation
    Source Atlas of Genetics and Cytogenetics in Oncology and Haematology
    Citation Huret JL . Anaplasic large cell lymphoma (ALCL). Atlas Genet Cytogenet Oncol Haematol. August 2001 .
    URL : http://AtlasGeneticsOncology.org/Anomalies/AnaplLargeCelLymphID2103.html
    URL http://AtlasGeneticsOncology.org/Anomalies/AnaplLargeCelLymphID2103.html