Pituitary Carcinoma in a Patient with an SDHB Mutation

Nicola Tufton,Irene Hadjidemetriou,Naomi Fersht,Michael Powell,Stephanie E Baldeweg,Márta Korbonits,Mary N Dang,Federico Roncaroli,Leonardo Guasti,Maria Thom,Judit Dénes

doi:10.1007/s12022-017-9474-7

Abstract

We present the first case of pituitary carcinoma occurring in a patient with a succinate dehydrogenase subunit B (SDHB) mutation and history of paraganglioma. She was initially treated for a glomus tumour with external beam radiotherapy. Twenty-five years later, she was diagnosed with a non-functioning pituitary adenoma, having developed bitemporal hemianopia. Recurrence of the pituitary lesion (Ki-67 10% and p53 overexpressed) occurred 5 years after her transsphenoidal surgery, for which she underwent two further operations followed by radiotherapy. Histology showed large cells with vacuolated clear cytoplasm with positive immunostaining for steroidogenic factor 1 (SF1) and negative staining for pituitary hormones. Four years after the pituitary radiotherapy, two metastatic deposits were identified: a foramen magnum lesion and an intradural extra-medullary cervical lesion at the level of C3/C4. There was also significant growth of the primary pituitary lesion with associated visual deterioration. A biopsy of the foramen magnum lesion, demonstrating cells with vacuolated, clear cytoplasm and positive SF1 staining confirmed a pituitary carcinoma, for which she was commenced on temozolomide chemotherapy. There was dramatic clinical improvement after three cycles and reduction in the size of the lesions was observed following six cycles of temozolomide, and further shrinkage after 10 cycles. The plan is for a total of 12 cycles of temozolomide chemotherapy. SDH mutation-related pituitary tumours have an aggressive phenotype which, in this case, led to metastatic disease. SF1 immunostaining was helpful to identify the tissue origin of the metastatic deposit and to confirm the pituitary carcinoma.

Highlights

The co-occurrence of pituitary adenoma (PA) and paraganglioma is a rare event
We describe the first patient with an SDHB mutation who developed a paraganglioma and a clinically non-functioning gonadotroph carcinoma
Pituitary carcinomas rarely occur in genetic syndromes; examples of pituitary carcinoma patients with MEN1 mutations have been documented [15,16,17], whilst AIP, PRKAR1A, DICER1 and GPR101 mutations have not been associated with metastatic spread to date

Summary

Introduction

The co-occurrence of pituitary adenoma (PA) and paraganglioma is a rare event. Such association was first described in 1952 [1] but it is only recently that the underlying genetic mutations have been elucidated in some of the cases [2,3,4,5]. A biopsy of the foramen magnum lesion, demonstrating cells with vacuolated, clear cytoplasm and positive SF1 staining confirmed a pituitary carcinoma, for which she was commenced on temozolomide chemotherapy. SDH mutation-related pituitary tumours have an aggressive phenotype which, in this case, led to metastatic disease. SF1 immunostaining was helpful to identify the tissue origin of the metastatic deposit and to confirm the pituitary carcinoma.

Results

Conclusion