title: Malignant pheochromocytoma: new malignancy criteria.
abstract: OBJECTIVE
  The pathological diagnosis of malignancy in pheochromocytomas remains a controversial issue. According to the WHO, malignancy is defined in the presence of metastasis. Multiparameter scoring systems such as PASS (Pheochromocytoma of Adrenal gland Scaled Score) have been used but remain controversial. The aim of this study was to search for new immunohistologic elements allowing determination of pheochromocytoma malignancy.
  
  
  METHODS
  Among 53 patients operated for pheochromocytoma between 1993 and 2009, we selected pheochromocytomas with proven metastasis, seven cases in group 1 (G1) and paired two others groups: group 2 (G2), patients who had "benign" pheochromocytoma with PASS ≥4 and group 3 (G3), patients who had "benign" pheochromocytoma with PASS <4. We retrospectively analysed PASS criteria, size, weight, tumour necrosis, Ki-67 and pS100 staining.
  
  
  RESULTS
  The size and weight of the lesion were directly and significantly correlated to malignancy in all three groups: respectively 9.7 cm and 292.0 g (G1), 6.2 cm and 83.8 g (G2) and 3.8 cm and 37.1 g (G3) (p < 0.005 for both). Tumour necrosis (TN) was present in all G1 (p < 0.005) and respectively at 0% and 37.5% in G2 and G3. Ki-67 is directly correlated to presence of TN (p < 0.005) and malignancy (G1 14.1%, G2 1.8%, G3 2.6%; p < 0.001). All G1 had a Ki-67 index >4%, although one G3 presented an 11% Ki-67 index. There was an inverse statistically significant correlation between the three groups in staining using pS100 (p < 0.01).
  
  
  CONCLUSIONS
  Size and weight of the pheochromocytoma are directly related to PASS and malignancy. The presence of tumour necrosis, Ki-67 index >4% and pS100 absence impose a close histopathological evaluation and follow-up with regard to cases presenting a high risk of malignancy/recurrence.
authors: Service de Chirurgie Digestive et Endocrinienne, CHU La Milétrie, 86021, Poitiers, France. jpdewailly@hotmail.fr
authors: Pierre
authors: P
authors: de Wailly
authors: Luigi
authors: L
authors: Oragano
authors: Francois
authors: F
authors: Radé
authors: Anthony
authors: A
authors: Beaulieu
authors: Vincent
authors: V
authors: Arnault
authors: Pierre
authors: P
authors: Levillain
authors: Jean Louis
authors: JL
authors: Kraimps
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000145:classification* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000315:Adrenalectomy / Q000379:methods; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood*; D001707:Biopsy, Needle; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010673:Pheochromocytoma / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D011300:Preoperative Care / Q000379:methods; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D047368:Tumor Burden; D014944:World Health Organization
chemical_list: D014408:Biomarkers, Tumor