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01-02-2012 | Original Article

Malignant pheochromocytoma: new malignancy criteria

Authors: Pierre de Wailly, Luigi Oragano, Francois Radé, Anthony Beaulieu, Vincent Arnault, Pierre Levillain, Jean Louis Kraimps

Published in: Langenbeck's Archives of Surgery | Issue 2/2012

Abstract

Purpose

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.

Zarnegar R, Kekebew E, Duh QY, Clark OH (2006) Malignant pheochromocytoma. Surg Oncol Clin N Am 15:555–571PubMedCrossRef

Bravo EL, Gifford RW Jr (1984) Pheochromocytoma: diagnosis, localization and management. New Engl J Med 311:1298–1303PubMedCrossRef

Thompson LD, Young WF, Kawashima A, Komminoth P, Tischler AS (2004) Malignant adrenal phaeochromocytoma. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) WHO classification of tumours: pathology and genetics—tumours of endocrine organs. IARC, Lyon, pp 147–150

Lack EE (1997) Tumours of the adrenal gland and extra-adrenal paraganglia. Armed Forces Institute of Pathology, Washington

Medeiros LJ, Wolf BC, Balogh K, Federman M (1985) Adrenal pheochromocytoma: a clinicopathologic review of 60 cases. Hum Pathol 16:580–589PubMedCrossRef

Ilias I, Pacak K (2008) A clinical overview of pheochromocytomas/paragangliomas and carcinoid tumors. Nucl Med Biol 35:27–34CrossRef

Fassnacht M, Kreissl MC, Weismann D, Allolio B (2009) New targets and therapeutic approaches for endocrine malignancies. Pharmacol Ther 123:117–141PubMedCrossRef

Linnoila RI, Keiser HR, Steinberg SM, Lack EE (1990) Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features. Hum Pathol 21:1168–1180PubMedCrossRef

Thompson LD (2002) Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol 26:551–566PubMedCrossRef

10.

Edström Elder E, Xu D, Höög A, Enberg U, Hou M, Pisa P et al (2003) KI-67 and hTERT expression can aid in the distinction between malignant and benign pheochromocytoma and paraganglioma. Mod Pathol 16:246–255PubMedCrossRef

11.

Strong VE, Kennedy T, Al-Ahmadie H, Tang L, Coleman J, Fong Y et al (2008) Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis. Surgery 143:759–768PubMedCrossRef

12.

Unger P, Hoffman K, Pertsemlidis D, Thung S, Wolfe D, Kaneko M (1991) S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas. Arch Pathol Lab Med 115:484–487PubMed

13.

Achilles E, Padberg BC, Holl K, Kloppel G, Schroder S (1991) Immunocytochemistry of paragangliomas—value of staining for S-100 protein and glial fibrillary acid protein in diagnosis and prognosis. Histopathology 18:453–458PubMedCrossRef

14.

Van der Harst E, Bruining HA, Jaap Bonjer H, van der Ham F, Dinjens WN, Lamberts SW et al (2000) Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases? J Pathol 191:175–180PubMedCrossRef

15.

Tavangar SM, Shojaee A, Moradi Tabriz H, Haghpanah V, Larijani B, Heshmat R et al (2010) Immunohistochemical expression of Ki-67, c-erbB-2, and c-kit antigens in benign and malignant pheochromocytoma. Pathol Res Pract 206:305–309PubMedCrossRef

16.

Kimura N, Watanabe T, Noshiro T, Shizawa S, Miura Y (2005) Histological grading of adrenal and extra-adrenal pheochromocytomas and relationship to prognosis: a clinicopathological analysis of 116 adrenal pheochromocytomas and 30 extra-adrenal sympathetic paragangliomas including 38 malignant tumors. Endocr Pathol 16:23–32PubMedCrossRef

17.

Grossman A, Pacak K, Sawka A, Lenders JW, Harlander D, Peaston RT et al (2006) Biochemical diagnosis and localization of phaeochromocytoma. Can we reach a consensus? Ann New York Acad Sci 1073:332–347CrossRef

18.

Clarke MR, Weyant RJ, Watson CG, Carty SE (1998) Prognostic markers in pheochromocytoma. Hum Pathol 29:522–526PubMedCrossRef

19.

Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G et al (2002) Germline mutation in non syndromic pheochromocytoma. New Engl J Med 346:1459–1466PubMedCrossRef

20.

John H, Ziegler WH, Hauri D, Jaeger P (1999) Phaeochromocylomas: can malignant potential be predicted? Urology 53:679–683PubMedCrossRef

21.

Lehnert H, Mundschenk J, Hahn K (2004) Malignant pheochromocytoma. Front Hormon Res 31:155–162CrossRef

22.

Ross EJ, Griffith DNW (1989) The clinical presentation of pheochromocytoma. Q J Med 71:485–496PubMed

23.

Kaltas GA, Besser GM, Grossman AB (2004) The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev 25:458–511CrossRef

24.

Anouar Y, Yon L, Guillemot J, Thouennon E, Barbier L, Gimenez-Roqueplo AP, Bertherat J et al (2006) Development of novel tools for the diagnosis and prognosis of phaeochromocltoma using peptide marker immunoassay and gene expression profiling approaches. Ann New York Acad Sci 1073:533–540CrossRef

25.

Wu D, Tischler AS, Lloyd RV, DeLellis RA, de Krijger R, van Nederveen F et al (2009) Observer variation in the application of the Pheochromocytoma of the Adrenal Gland Scaled Score. Am J Surg Pathol 33:599–608PubMedCrossRef

26.

Eisenhofer G, Bornstein SR, Brouwers FM, Cheung NK, Dahia PL, de Krijger RR et al (2004) Malignant pheochromocytoma: currents status and initiatives for future progress. Endocr Relat Canc 11:423–436CrossRef

27.

Pacak K, Eisenhofer G, Ahlman H, Bornstein SR, Gimenez-Roqueplo AP, Grossman AB et al (2007) Pheochromocytoma: recommendations for clinical practice from first international symposium. Nat Clin Pract Endocrinol Metabol 3:92–102CrossRef

28.

Khorram-Manesh A, Ahlman H, Nilsson O, Friberg P, Odén A, Stenström G et al (2005) Long-term outcome of a large series of patients surgically treated for pheochromocytoma. J Int Med 258:55–66CrossRef

29.

Glodny B, Winde G, Herwig R, Meier A, Kuhle C, Cromme S et al (2001) Clinical differences between benign and malignant pheochromocytomas. Endocr J 48:151–159PubMedCrossRef

30.

Brown HM, Komorowski RA, Wilson SD, Demeure MJ, Zhu YR (1999) Predicting metastasis of pheochromocytomas using DNA flow cytometry and immunohistochemical markers of cell proliferation: a positive correlation between MIB-1 staining and malignant tumor behavior. Cancer 86:1583–1589PubMedCrossRef

31.

Bryan J, Farmer J, Kessler LJ, Towensend RR, Nathanson KL (2003) Pheochromocytoma: the expanding genetic differential diagnosis. J Nat Can Institut 95:1196–1204CrossRef

32.

Lenders JW, Eisenhofer G, Mannelli M, Pacak K (2005) Pheochromocytoma. Lancet 366:665–675PubMedCrossRef

Title: Malignant pheochromocytoma: new malignancy criteria
Authors: Pierre de Wailly
Luigi Oragano
Francois Radé
Anthony Beaulieu
Vincent Arnault
Pierre Levillain
Jean Louis Kraimps
Publication date: 01-02-2012
Publisher: Springer-Verlag
Published in: Langenbeck's Archives of Surgery / Issue 2/2012
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-011-0850-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Malignant pheochromocytoma: new malignancy criteria

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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