title: Large cell calcifying Sertoli cell tumor: a clinicopathologic study of 1 malignant and 3 benign tumors using histomorphology, immunohistochemistry, ultrastructure, comparative genomic hybridization, and polymerase chain reaction analysis of the PRKAR1A gene.
abstract: Four cases of large cell calcifying Sertoli cell tumor, 3 benign and 1 malignant, with no clinical signs of Carney complex or Peutz-Jeghers syndrome are reported with results of histologic, immunohistochemical, ultrastructural, and comparative genomic hybridization studies. Analysis of PRKAR1A gene was performed on 2 cases. The age range of the patients was 19 to 54 years. The patient with a malignant large cell calcifying Sertoli cell tumor died of disease 4 years after surgery. Patients with benign tumors have had an uneventful follow-up for 1 and 3 years. All tumors were well circumscribed, unencapsulated, and composed of solid sheets, irregular cords, tubular structures, and nests in a fibrous and/or myxoid stroma with cellular atypia in the malignant case. All tumors showed diffuse immunoreactivity for inhibin, vimentin, calretinin, and S100 protein. Focal positivity for cytokeratin (AE1/AE3) was noticed in 1 case. Tumors were negative for CAM 5.2, Mic-2, Melan-A laminin, placental alkaline phosphatase, and alpha-fetoprotein. The proliferation index was 5% and 10% for 2 of the benign tumors and 30% for the malignant tumor. Comparative genomic hybridization was performed in 2 cases. There was no evidence of any major chromosomal changes. In one case, no PRKAR1A gene mutation was found. In the other case, a heterozygous shift mutation c.65_84dup was found, despite the absence of other clinical signs of Carney complex or Peutz-Jeghers syndrome. Although the combination of large cell calcifying Sertoli cell tumor and PRKAR1A mutation fulfills the criteria for establishing a diagnosis of Carney complex, the clinical relevance of finding a PRKAR1A gene mutation in a patient without any clinical signs of Carney complex or Peutz-Jeghers syndrome remains to be established.
authors.affiliation: Department of Pathology, National University Health System, Singapore 119074, Singapore. fredrikpetersson@live.se
authors.forename: Fredrik
authors.initials: F
authors.lastname: Petersson
authors.forename: Stela
authors.initials: S
authors.lastname: Bulimbasic
authors.forename: Radek
authors.initials: R
authors.lastname: Sima
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.forename: Milan
authors.initials: M
authors.lastname: Hora
authors.forename: Hugo Dominguez
authors.initials: HD
authors.lastname: Malagon
authors.forename: Josef
authors.initials: J
authors.lastname: Matoska
authors.forename: Ondrej
authors.initials: O
authors.lastname: Hes
mesh_terms: D000328:Adult; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D055028:Comparative Genomic Hybridization; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012707:Sertoli Cell Tumor / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D055815:Young Adult
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human