Risk Stratification in Paragangliomas with PASS (Pheochromocytoma of the Adrenal Gland Scaled Score) and Immunohistochemical Markers

Abstract

Introduction: Paragangliomas (PGLs) are rare tumours that arise in sympathetic and parasympathetic paraganglia and are derived from neural crest cells. Presence of metastasis is the only absolute criterion for malignancy. There is no single histo-morphological feature indicating malignant potential and multiple parameters have been proposed to prognosticate the individual case. This includes studies conducted using Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Immunohistochemical (IHC) markers.

Aim: We have studied ten cases of paraganglioma and attempted to correlate the prognosis with multiple clinicopathological variables.

Materials and methods: This study was done in a tertiary care general hospital over a period of five years. Available clinical records and histopathology slides of all patients were reviewed. Using Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), we divided the cases into two groups-tumours showing high risk behaviour (PASS≥4) and tumours showing benign behaviour (PASS<4). IHC analysis was done using synaptophysin, chromogranin, S100 and Ki67. We correlated S100 immunoreactivity and Ki67 proliferative index with PASS score. Both PASS score and IHC markers were also correlated with clinical outcome.

Results: There were six Pheochromocytomas (PHC) and four Paragangliomas (PGL). Two paragangliomas were retroperitoneal and one each was located in ear (HNPGL) and broad ligament. PASS score was ≥4 in five cases and <4 in five cases. Out of five cases in which PASS was ≥4, three cases showed clinical evidence of malignancy and two cases were benign. All the cases in which PASS was <4 were clinically benign. S100 immunoreactivity was grade 1 in two cases, grade 2 in six cases and grade 3 in two cases. The cases in which S100 immunoreactivity was grade 1 were malignant. One case in which S100 was grade 2 was clinically malignant. Ki67 labeling index was raised (>3%) in two cases, which were malignant correlated with malignant PASS score.

Conclusion: We conclude that the following clinicopathological parameters should be taken into account for risk assessment of malignant behaviour of paragangliomas- location, size, PASS score, S100 immunoreactivity and Ki67 labeling index.

Keywords: PASS score pheochromocytoma; Paraganglioma; S100 immunoreactivity.

Figures

[Table/Fig-3]:

a-Gross photograph of pheochromocytoma with dichromate reaction. Photomicrographs of pheochromocytoma showing: b - capsular invasion (H and e; x100), c - chromogranin immunoreactivity (x100), d- synaptophysin immunoreactivity x(100), e- grade 2 S100 immunoreactivity (x400), f- Ki67 labeling index (8%) (x400). RP = Retroperitoneal; Gr = grade; B = Benign; M = malignant; HG =Hyaline globules.

[Table/Fig-4]:

Phtotomicrograph of pheochromocytoma showing S100 immunoreactivity: a=grade 1, b= grade 2, c= grade 3 (x400).