Pituitary Carcinoma in a Patient with an SDHB Mutation

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.

Keywords: Paraganglioma; Pituitary carcinoma; SDHB; Succinate dehydrogenase; Temozolomide.

Fig. 1

Histology of the recurrent pituitary lesion. The recurrent pituitary lesion shows acinar and lobular architecture and is composed mostly of large cells with clear, vacuolated cytoplasm reminiscent of physaliferous cells of chordoma (a—HE, ×40); tumour cells show nuclear expression of SF1 (b—immunoperoxidase, ×40, mouse anti-SF1 (sc-393,592) at dilution 1:100) top left insert shows SF1 nuclear expression in normal adrenal and lower right insert shows SF1 expression in FSH positive pituitary adenoma; up to 15% of neoplastic cells are positive for Ki-67 (c—immunoperoxidase, ×20, DAKO, monoclonal at dilution 1:200) and about 5% show strong nuclear expression of p53 (d—immunoperoxidase, ×20, DAKO, clone D07 at dilution 1:200). Ki-67 and p53 were quantified at the magnification of ×40 in the three fields showing the highest number of positive cells. The number of positive cells and the overall number of neoplastic cells was counted manually by tagging in each field, averaged and represented as a percentage of Ki-67 or p53 expressing cells against the whole number of neoplastic cells

Fig. 2

Radiological images of the pituitary lesion and metastatic deposits. a Sagittal section of MRI pituitary post gadolinium showing suprasellar mass and extra-axial metastatic deposit in the posterior fossa with extension into the left hypoglossal canal. b MRI axial sequence post gadolinium showing the intradural extra-medullary cervical metastatic deposit at the level C3/C4

Fig. 3

Histology of the metastatic deposit. Pathological features of the metastatic deposit are similar to the sellar recurrent tumour; neoplastic cells shows clear vacuolated cytoplasms; one mitosis is present in this field (a—HE, ×40); the immunoreactions for MGMT is negative in neoplastic cells; endothelial cells demonstrate normal nuclear expression (b—immunoperoxidase, ×20, Chemicon, monoclonal antibody at dilution 1:500); tumour cells show nuclear expression of MSH6 (c immunoperoxidase, ×20 using Roche clone 44 and antigen retrieval with CC1 and Optiview detection kit)