Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

SF1-positive adenohypophyseal hormone-immunonegative gonadotroph adenoma is the most prevalent histological subtype of gonadotroph adenomas (#553)

Yeung-Ae Park 1 2 3 , Michael Christie 4 , James King 5 6 , Angeline Shen 1 2 , Christopher J Yates 1 2
  1. Department of Diabetes and Endocrinology, Royal Melbourne Hospital, Parkville, Victoria, Australia
  2. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
  3. Endocrinology & Diabetes Units, Monash Health, Melbourne, Victoria, Australia
  4. Department of Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  5. Department of Neurosurgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  6. Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia

Aim: Steroidogenic factor 1 (SF1) transcription factor (TF) immunohistochemistry (IHC) increased the detection of gonadotroph adenomas in the adenohypophyseal hormone-immunonegative pituitary tumours.1, 2 Our group recently reclassified 91% of null cell adenomas as SF1-lineage pituitary tumours following retrospective application of TF IHC.2 Heterogeneity of gonadotroph adenoma has been suggested between the luteinising hormone (LH)-/follicular-stimulating hormone (FSH)+, LH+/FSH- and FSH+/LH+ histological subtypes.3 However, prior studies did not include the SF1+/LH-/FSH- subtype. We aimed to evaluate the prevalence of histological subtypes of SF1-positive gonadotroph adenomas.

Methods: In a retrospective observational study, inpatients diagnosed with gonadotroph adenomas were identified between 1st January 2021 and 3rd July 2024 at the Royal Melbourne Hospital and Melbourne Private Hospital, Victoria, through ICD codes (35.2 and 44.3) and an established pituitary database. Patients without available histopathology reports were excluded. Gonadotroph adenomas were defined by pituitary tumours with positive SF1 and negative T-box transcription factor (TPIT) and pituitary-specific positive transcription factor 1 (PIT1) IHC. The prevalence of gonadotroph adenoma histological subtypes was investigated.

Results: A total of 70 patients with gonadotroph adenomas were included. Four with prior gonadotroph adenoma diagnoses based on adenohypophyseal hormone-immunopositivity without TF IHC (1 LH+/FSH+ and 3 LH-/FSH+ pituitary adenomas) were excluded. The most prevalent histological subtype was SF1+/LH-/FSH- gonadotroph adenomas (81.4%), followed by SF1+/LH-/FSH+ (7.1%), SF1+/LH+/FSH- (5.7%) and SF1+/LH+/FSH+ (5.7%) gonadotroph adenomas (Table 1).

Conclusion: We report the prevalence of histological subtypes of gonadotroph adenomas, which comprise the majority of the resected pituitary tumours at our centre. SF1+/LH-/FSH- gonadotroph adenomas are the most prevalent histological subtype of gonadotroph adenomas. The clinical importance of SF1 has been highlighted as a predictor of recurrence of gonadotroph adenomas,4 yet the clinical significance of histological subtypes involving SF1 is unknown. Studies are warranted to further explore the relationship between qualitative/quantitative IHC subtypes and clinical patterns of disease.

  1. Nishioka H, Inoshita N, Mete O, Asa SL, Hayashi K, Takeshita A, et al. The Complementary Role of Transcription Factors in the Accurate Diagnosis of Clinically Nonfunctioning Pituitary Adenomas. Endocr Pathol. 2015;26(4):349-55.
  2. Park Y, Christie M, King J, Shen A, Yates C. Prevalence of non-functioning pituitary adenoma subtypes at a Melbourne quaternary centre and underdiagnosis of gonadotroph adenomas [Conference presentation]. Australia and New Zealand Pituitary Alliance; Gold Coast, Queensland, Australia.2024.
  3. Ilie MD, Vasiljevic A, Louvet C, Jouanneau E, Raverot G. Gonadotroph Tumors Show Subtype Differences that Might Have Implications for Therapy. Cancers. 2020;12(4):1012.
  4. Hickman RA, Bruce JN, Otten M, Khandji AG, Flowers XE, Siegelin M, et al. Gonadotroph tumours with a low SF-1 labelling index are more likely to recur and are associated with enrichment of the PI3K-AKT pathway. Neuropathol Appl Neurobiol. 2021;47(3):415-27.