title: [Clinicopathologic features of 66 cases of anaplastic lymphoma kinase positive and negative systemic anaplastic large cell lymphoma: a comparative study].
abstract: OBJECTIVE
  To study the clinicopathologic features of 66 cases of primary systemic anaplastic large cell lymphoma (ALCL), with emphasis on the differences between ALK-positive and ALK-negative cases.
  
  
  METHODS
  The clinical data of 66 cases of ALCL was analyzed. The histologic features were reviewed. Immunohistochemical study for CD30, ALK protein, epithelial membrane antigen, CD2, CD3, granzyme B and TIA-1 was carried out. In-situ hybridization for small mRNA of Epstein-Barr virus (EBER) was also performed. The chromosomal abnormalities were studied by fluorescence in-situ hybridization (FISH). The differences between ALK-positive and ALK-negative cases were statistically analyzed.
  
  
  RESULTS
  There were 48 cases of ALK-positive ALCL and 18 cases of ALK-negative ALCL. The patients with ALK-positive ALCL were younger than those with ALK-negative ALCL (P < 0.05), with the median age being 18 years and 36 years, respectively. Fever, especially hyperpyrexia, was more commonly observed in ALK-positive ALCL patients than in ALK-negative ALCL patients (33 cases versus 4 cases, P < 0.05). The overall survival rate and median duration of survival in patients with ALK-positive ALCL were higher and longer than those in patients with ALK-negative ALCL (80% versus 71%; 21 months versus 12.5 months, P > 0.05). There were however no significant differences in histology between ALK-positive ALCL and ALK-negative ALCL. Histologically, most cases showed diffuse growth pattern. Nodular pattern was demonstrated in a minority of cases. "Hallmark" cells were seen in most of the ALCL cases. Focal necrosis and myxomatous stroma were identified in a few cases. Most ALK-positive cases belonged to the common variant (35 cases). A small number represented lymphohistiocytic variant (8 cases). Small cell variant and sarcomatoid subtype were found only in few cases (3 cases and 2 cases, respectively).On the other hand, common variant (17 cases) constituted the majority of ALK-negative ALCL. Lymphohistiocytic variant was seen in only 1 case. Immunohistochemical study showed that ALK-positive ALCL always expressed CD30 and epithelial membrane antigen. ALK-positive ALCL more often expressed epithelial membrane antigen (100% versus 72%; P < 0.05) but less so for T-cell markers (including CD2, CD3, CD43 and CD45RO). Cytotoxic molecules were more commonly expressed in ALK-positive ALCL (P > 0.05). EBER was negative in all cases studied. FISH showed that in ALK-positive ALCL, 1 case had normal ALK gene, 1 had deletion and multicopy and 2 had deletion. On the other hand, 1 case of ALK-negative ALCL had normal ALK gene.
  
  
  CONCLUSIONS
  While there are no significant morphologic differences between ALK-positive ALCL and ALK-negative ALCL, the clinical features, immunophenotypes and genetic features of both groups vary. These differences are helpful in guiding the differential diagnosis.
authors.affiliation: Department of Pathology, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Xiao-ge
authors.initials: XG
authors.lastname: Zhou
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Gong
authors.forename: Ran
authors.initials: R
authors.lastname: Yu
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Zheng
authors.forename: Jian-lan
authors.initials: JL
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008305:Malignant Hyperthermia / Q000209:etiology; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D015996:Survival Rate; D055815:Young Adult
chemical_list: D017730:Ki-1 Antigen; D018396:Mucin-1; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases