Fine needle aspiration cytology in the diagnosis and management of children and adolescents with Ewing sarcoma and peripheral primitive neuroectodermal tumor.

PURPOSE: The utility of fine needle aspiration cytology (FNAC) in conjunction with immunocytochemistry in the diagnosis of Ewing sarcoma and peripheral primitive neuroectodermal tumor, the Ewing family of tumors (EFT), is retrospectively described. PATIENTS AND METHODS: During a 10-year period 24 children and adolescents were diagnosed at Karolinska Hospital to have EFT of bone or soft tissue using FNAC. Criteria for diagnosis was based on cytomorphology combined with immunocytochemistry. The median age was 14.1 years (range 0.7-20.2). FNAC was performed within a median time of 1 day after referral. RESULTS: Forty aspiration procedures were performed, 24 at primary work up in 23 patients and 16 at suspected relapses in 10 patients. A primary cytologic diagnosis of EFT was obtained in 22 of 23 cases. In nine cases with primary disease there was no histologic confirmation. Two tumors were on FNAC diagnosed as neuroblastoma versus EFT, and EFT, respectively. Histopathology on resected tumor tissue from these patients showed EFT and small cell osteosarcoma, respectively. Suspected relapse was found to be positive at five and negative at 11 occasions. Immunocytochemistry was positive for CD45 (LCA) in 0/12, for desmin in 2/21, for MIC2 in 15/15, for NB84 in 1/3, for NFP in 7/7, for NSE in 12/18, for S-100 in 4/11 and for vimentin in 18/19. CONCLUSIONS: The results show that FNAC together with immunocytochemistry is a rapid, physically atraumatic and accurate method in diagnosing both primary EFT of bone and soft tissue as well as relapses.

The use of fine-needle aspiration cytology in the molecular characterization of neuroblastoma in children.

BACKGROUND: The utility of fine-needle aspiration (FNA) material in the molecular characterization of a group of neuroblastic tumors (NT) in children is presented. METHODS: A recent study showed a high accuracy rate for FNA cytology (FNAC) in combination with immunostaining as a diagnostic method in 26 children with NT. In the current study FNA smears from 18 children were analyzed, either at the time of diagnosis or retrospectively, on available stored smears for cellular DNA content (DNA ploidy) by means of image cytometry (ICM) and 1p deletion and N-myc amplification by interphase fluorescent in situ hybridization (FISH). RESULTS: A total 62 analyses (DNA ploidy, 20 analyses; chromosome 1 or 2 number, 11 analyses; 1p deletion, 16 analyses; and N-myc, 15 analyses) resulted in clear information in 60 cases, whereas 2 tests for N-myc amplification failed. The results were compared with each other and with cytometric DNA analyses on tumor touch imprints (n = 12) and N-myc analyses on material from surgical specimens (Southern blot analysis, n = 12). The results were concordant in all but seven analyses (all with clear informative results) in six children. These discrepancies may be explained as an effect of either chemotherapy or tumor heterogeneity. CONCLUSIONS: FNA is a fast and noninvasive diagnostic technique that yields sufficient material for the molecular characterization of neuroblastic tumors by means of FISH and ICM. Such analyses are of prognostic significance because they predict tumor behavior and response to therapy according to International Neuroblastoma Staging System/International Neuroblastoma Risk Groups criteria. In the majority of cases it also is possible to obtain material for storage and future investigations.

The clinical use of fine needle aspiration cytology for diagnosis and management of children with neuroblastic tumours.

This study presents the results of fine needle aspiration cytology in a series of 26 consecutive children with neuroblastic tumours. The cytological spectrum varied from undifferentiated small tumour cells to mature ganglion cells in a fibrillar background. In 24 children with neuroblastic tumours at onset the cytological diagnosis was correct in 21 cases, whereas two aspirates yielded nondiagnostic necrotic material and a fibrillar material without tumour cells, respectively. One necrotic lymph node aspirate was initially incorrectly diagnosed as lymphoma, but the diagnosis was later revised to neuroblastoma. Suspected signs of disease progression or relapses were confirmed (n = 9) or ruled out (n = 1) using aspiration cytology. The diagnostic accuracy in the complete series was 97% (31/32) in cases with adequate smears. Immunocytochemistry confirmed the cytological diagnosis in 14 of 15 cases and was decisive in one. Elevated catecholamine metabolites in urine was detected in all children with a cytological diagnosis of neuroblastoma. General anaesthesia was only performed when coincidental invasive investigations (n = 13) were to be carried out or if the aspiration was intrathoracic (n = 6). It is concluded that aspiration cytology in conjunction with immunocytochemistry offers a safe, rapid and accurate diagnostic method which may be useful, together with analyses of catecholamine metabolites in urine, in the clinical management of children with neuroblastic tumours.

Haemoglobin Köln as de novo mutations in Sweden: diagnosis by PCR and specific enzymatic cleavage.

Three independent cases of chronic haemolytic anaemia in Sweden have recently been demonstrated to be due to the unstable haemoglobin variant Hb Köln. The patients, all of whom have partially compensated chronic haemolytic anaemia, presented with aggravated haemolysis during acute infections in childhood. In one case, acute B19 parvovirus infection induced an aplastic crisis. The substitutions all seem to have occurred as de novo mutations. Diagnosis was based on haemoglobin instability testing and isoelectric focusing of haemoglobin dimers. The final identification procedure for the substitutions included extraction of DNA from whole blood, polymerase chain reaction (PCR) amplification of parts of the beta-globin gene and nucleotide sequencing of the resulting material, or studies of restriction length polymorphisms (RFLPs) using the restriction endonucleases Mae II or Nla III. The use of PCR-RFLP is recommended as a valuable tool for diagnosing Hb Köln.