Work

MON-091 Recurrent Cushing’s Disease With Malignant Transformation And Tumor Necrosis

Year: 2025

Type: article

Abstract: Disclosure: M.D. Figueiredo: None. T. Wolinsky: None. T.L. Beaumont: None. D. Piccioni: None. J.A. Hattangadi-Gluth: None. J. Chang: None. K.C. McCowen: None. Introduction: ACTH-secreting pituitary adenomas are typically benign, with a very low risk of malignant transformation. Pituitary carcinomas account for only 0.1% of all pituitary tumors. Contributing factors to malignant transformation may include genetic predisposition, specific mutations, aggressive tumor behavior, incomplete resection, and prior radiotherapy.Case Report: A 65-year-old woman was diagnosed with Cushing’s disease in 09/2021. MRI of the pituitary revealed a 4 cm, solid, heterogeneous, enhancing mass with suprasellar extension and invasion into both cavernous sinuses. She underwent transsphenoidal surgery (TSS), though a significant portion of the tumor was unresectable. Pathology showed a typical pituitary adenoma with a Ki-67 index of 1%. Rapid tumor regrowth led to a repeat TSS in 03/2022, during which all sellar tumor and part of the left cavernous sinus tumor were removed. Pathology revealed an atypical ACTH+ corticotroph adenoma with Ki-67 up to 10-15% and absent P53. Radiotherapy led to remission until 01/2024.In 2024, she experienced clinical and chemical relapse. MRI showed regrowth of a large sellar and left cavernous sinus mass with extension into the left middle cranial fossa. Multiple medical therapies had failed between the surgeries, thus a final TSS was performed in 10/2024. Pathology demonstrated severe cytologic atypia and high mitotic activity (Ki-67 80-90%), with features indistinguishable from a high-grade pleomorphic sarcoma or carcinoma. Staining for ACTH and T-Pit was negative.Ten days postoperatively, her urine free cortisol (UFC) was 2,880 mcg/d. Ten days later, she developed weakness and hypotension. Labs revealed UFC 7.2 mcg/d, ACTH 100 pg/mL, and cortisol 3 mcg/dL. Hydrocortisone replacement led to clinical improvement. She is currently receiving temozolomide and additional radiotherapy. NGS of the 2024 resection specimen revealed a number of mutations - CDKN2B loss, MUTYH variant, SMARCA2 deletion, and TP53 exon 7 variant. Discussion: This patient with recurrent Cushing’s disease exhibited dedifferentiation of a pituitary adenoma into a sarcoma-like tumor lacking neuroendocrine features. Radiation-induced sarcomas, though rare after pituitary radiotherapy, carry a poor prognosis. The rapid development of adrenal insufficiency despite elevated ACTH suggests tumor necrosis and secretion of immunoreactive but biologically inactive ACTH. Conclusion: Dedifferentiation of a pituitary ACTH-oma into a sarcoma is exceedingly rare and associated with a poor prognosis. Comprehensive analysis of all four pathology samples is ongoing to identify genetic alterations that may guide future therapies. Presentation: Monday, July 14, 2025

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvaf149.1421