Orbital Metastasis of Pituitary Growth Hormone Secreting Carcinoma-Causing Lateral Gaze Palsy: Case Report, Pathology Review, and Review of the Literature

Background and Importance: Although pituitary adenoma is one of the most common intracranial tumors, metastatic pituitary carcinoma is extremely rare. Commonalities in reported cases include subtotal resection at presentation, treatment with radiation therapy, and delayed metastatic progression. Controversy exists over pathologic descriptions in these lesions.

Case Report: We report the case of a 52-year-old gentleman initially diagnosed with acromegaly and pituitary tumor in 1996. He underwent three subtotal resections and five rounds of stereotactic radiosurgery over 14 years at two other hospitals. He presented to us with left eye lateral gaze palsy and was found to have an orbital metastasis with involvement of the left lateral rectus and lateral orbital wall. He underwent a left orbital craniotomy via eyebrow incision for resection of this lesion. Pathologic evaluation of this lesion showed a markedly elevated Ki67 level of 30%, higher than even most previously described cases of pituitary carcinoma.

Discussion: We reviewed all cases of pituitary carcinoma with clear clinical descriptions from 1990–2011. We found 45/46 (98%) reported adult cases had previous radiation exposure prior to transformation. Eight patients underwent stereotactic radiosurgery (mean: 1.13 doses) prior to transformation. 40 patients underwent external radiation therapy (mean, 1.11 doses). The mean delay from radiotherapy to metastatic transformation was 5.96 years.

Although the distinction between atypical adenoma and carcinoma had classically been based on presence of distal metastases, our review found some pathologic correlation as well. Mitoses are present in 3.9% of noninvasive adenomas, 21.4% of atypical adenomas, and 66% of carcinomas. The mean Ki-67 labeling index in noninvasive adenomas, atypical adenomas, and carcinomas was 1.37%, 4.66%, and 11.91%, respectively.

Conclusion: Although overall incidence of metastatic transformation of a pituitary adenoma after radiotherapy appears to be low, it appears to be a possible complication, and it could be more likely in patients receiving multiple doses of radiotherapy. Metastatic progression appears to be significantly delayed from radiation treatment, and correlated with subtotal resection of adenoma. These patients may also have more aggressive pathologic characteristics of their lesions.