title: Follicular-derived neoplasms: morphometric and genetic differences.
abstract: BACKGROUND
  The distinction between follicular adenomas (FAs) and well differentiated follicular and papillary carcinomas is often a demanding task and sometimes only intuitive.
  
  
  OBJECTIVE
  We report an histomorphological evaluation of follicular neoplasms [FAs, follicular carcinomas (FCs), and follicular variant of papillary carcinomas (FVPTCs)], supported by a qualitative and quantitative image analysis and by a molecular characterization.
  
  
  METHODS
  Tumor fibrosis and haemorrhage, neoplastic capsule thickness, follicle diameter, number of neoplastic cells, nuclear diameter of neoplastic cells, vessels density, vessels area and intratumoral distribution were evaluated. Ras and BRAF mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements were analyzed. Correlations with clinico-pathological features have been studied.
  
  
  RESULTS
  We found that FAs had a more extensive intratumoral haemorrhage, while malignant neoplasms were characterized by an evident fibrosis, higher cellularity and larger size. FVPTCs had higher nuclear diameter; cells count was higher in the minimally invasive follicular thyroid carcinomas, as well as a thickener neoplastic capsule. The CD34 stain showed a higher microvessel density in the FVPTCs group. A higher peripheral vessels distribution was observed only in malignant neoplasms. We observed overall Ras mutations in 2.4% of adenomas, in 41.5% of FVPTCs, and in 44.8% of FCs. It is outstanding that there is a marked difference in the Ras mutation distribution between the benign and malignant tumors in our series.
  
  
  CONCLUSIONS
  We found that genotyping of Ras gene family together with an accurate analysis of selected morphological features could help in the differential diagnosis of follicular-derived thyroid neoplasms.
authors.affiliation: Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Università di Pisa, Via Paradisa 2, 56124 Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Proietti
authors.forename: C
authors.initials: C
authors.lastname: Sartori
authors.forename: N
authors.initials: N
authors.lastname: Borrelli
authors.forename: R
authors.initials: R
authors.lastname: Giannini
authors.forename: G
authors.initials: G
authors.lastname: Materazzi
authors.forename: P
authors.initials: P
authors.lastname: Leocata
authors.forename: R
authors.initials: R
authors.lastname: Elisei
authors.forename: P
authors.initials: P
authors.lastname: Vitti
authors.forename: P
authors.initials: P
authors.lastname: Miccoli
authors.forename: F
authors.initials: F
authors.lastname: Basolo
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology*; D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D011905:Genes, ras / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*
chemical_list: D048493:Proto-Oncogene Proteins B-raf