Abstract
BackgroundPituitary carcinomas are rare but aggressive and require maximally coordinated multimodal therapies. For refractory tumors, unresponsive to temozolomide (TMZ), therapeutic options are limited. Immune checkpoint inhibitors (ICI) may be considered for treatment as illustrated in the present case report.CaseWe report a patient with ACTH-secreting pituitary carcinoma, progressive after multiple lines of therapy including chemotherapy with TMZ, who demonstrated disease stabilization by a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) ICI therapy.DiscussionManagement of pituitary carcinoma beyond TMZ remains ill-defined and relies on case reports. TMZ creates, due to hypermutation, more immunogenic tumors and subsequently potential candidates for ICI therapy. This case report adds support to the possible role of ICI in the treatment of pituitary carcinoma.ConclusionICI therapy could be a promising treatment option for pituitary carcinoma, considering the mechanisms of TMZ-induced hypermutation with increased immunogenicity, pituitary expression of CTLA-4 and PD-L1, and the frequent occurrence of hypophysitis as a side effect of ICI therapy.
Highlights
Pituitary carcinomas are rare but aggressive and require maximally coordinated multimodal therapies
Metastases were detected in the posterior fossa, left cerebellum and cervical drop metastases at the level of the dens and the third cervical vertebra (Fig. 1). These findings confirmed the evolution toward corticotroph pituitary carcinoma, possibly in the context of Nelson's syndrome given the rapid progression after the bilateral adrenalectomy
Management guidelines beyond TMZ rely on case reports. This is the second case of a patient with ACTH-secreting pituitary carcinoma, refractory to TMZ chemotherapy, treated with Immune checkpoint inhibitors (ICI)
Summary
Pituitary carcinomas are rare, accounting for 0.1% of pituitary tumors [1]. Cerebrospinal and/or distant metastases are present by definition. Metastases were detected in the posterior fossa, left cerebellum and cervical drop metastases at the level of the dens and the third cervical vertebra (Fig. 1) These findings confirmed the evolution toward corticotroph pituitary carcinoma, possibly in the context of Nelson's syndrome given the rapid progression after the bilateral adrenalectomy. Ketoconazole (800 mg/ day) was restarted and TMZ therapy was continued for a total of nine cycles (April 2019), when clinical progressive disease was suspected with the development of right oculomotor and abducens nerve palsies and increasing 08:00 h ACTH (419.9 ng/L) and cortisol (208 μg/L). Radiological disease stabilization is observed when comparing MRI obtained after the last TMZ cycle with follow-up imaging one year after the initiation of ICI (Fig. 1). His CD is still under control with 800 mg of ketoconazole daily
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