Clinicopathological analysis of 19 cases of mixed gangliocytoma-pituitary neuroendocrine tumors

Abstract Mixed gangliocytoma-pituitary neuroendocrine tumors (PitNETs) occurring in the sellar region are extremely rare neoplasms. To improve the understanding of these tumors and guide clinical diagnosis, a comprehensive retrospective study analyzing clinical manifestations and pathological morphology in 19 cases of sellar mixed gangliocytoma-PitNETs was conducted. A total of 19 mixed gangliocytoma-PitNETs patients from Huashan Hospital, Fudan University (January 2013 – September 2025) were enrolled. Clinical manifestations, radiological characteristics, histological features, immunohistochemical and molecular analyses were systematically evaluated. This tumor is more common in women, and the cohort comprised 17 females and 2 males, aged 28–70 years (mean 45.3 ± 12.1). Acromegaly was the most common clinical presentation (6/19, 31.59%). Preoperative endocrine testing revealed elevated Insulin-like Growth Factor-1 (IGF-1) levels in the majority of patients (12/19, 63.16%). MRI demonstrated round or oval-shaped mass lesions with marked contrast enhancement. Histologically, PitNETs components exhibited diffuse sheets of small, uniform round-to-ovoid cells, accompanied by focal large gangliocyte-like cells. Immunohistochemistry revealed Pit-1 positive in all 19 cases and CAM5.2 highlights fibrous bodies in 18 cases while 1 case perinuclear positive. According to the 2022 WHO criteria, 18 cases (18/19, 94.74%) diagnosed as high-risk sparse granular somatotroph PitNETs and 1 case (1/19, 5.26%) diagnosed as dense granular somatotroph PitNETs. Molecular analyses of GNAS R201 and BRAF V600E mutations in 19 cases showed wild-type. All patients underwent transsphenoidal surgery (TSS). Postoperative follow-up (mean 67.2 ± 36.0 months, range 3–129) revealed no tumor recurrence. For PitNETs with gangliocytic components, histopathological evaluation must rigorously assess adenoma lineages, given their frequent association with high-risk Pit-1-lineage tumors.