A contemporary, multi-institutional analysis of transcription factor lineage in pituitary adenomas; comparative study of neuro-imaging, histopathology, and clinical outcomes

Sunday, May 5, 2024

2:33 PM – 2:35 PM CT

Location: S405a

Presenting Author(s)

Jeffrey J. Feng, MS

Medical Student
Keck School of Medicine of USC
Hacienda Heights, CA, US

Co-Author(s)

IB

Ilaria Bove, MD

Junior Assistant Professor
Division of Neurosurgery, Universita degli studi Federico II di Napoli
Monte San Biagio, Italy
RB

Robert G. Briggs, MD

Resident
Department of Neurological Surgery, Keck School of Medicine of USC
Los Angeles, California, United States
JC

John D. Carmichael, MD

Associate Professor, Clinical Chief
Department of Endocrinology, Keck School of Medicine of USC
Loma Linda, California, United States
AC

Ana V. Castro, MD, PhD

Staff Scientist
Department of Neurosurgery, Henry Ford Health, United States
Stephanie K. Cheok, MD (she/her/hers)

Assistant Professor
Department of Neurosurgery, Medical College of Wisconsin
Milwaukee, WI, US
David J. Cote, MD, PhD

Resident
Department of Neurological Surgery, Keck School of Medicine of USC
Los Angeles, California, United States
NG

Norman E. Garrett, III, BS

Clinical Research Coordinator
Department of Neurological Surgery, Keck School of Medicine of USC, United States
CH

Craig M. Horbinski, MD, PhD

Professor, Director
Department of Neuropathology, Northwestern Feinberg School of Medicine, United States
KH

Kyle M. Hurth, MD, PhD

Associate Professor, Medical Director of Immunohistochemistry Lab
Department of Pathology, Keck School of Medicine of USC, United States
Edward R. Laws, Jr., MD (he/him/his)

Professor
Department of Neurosurgery, Brigham and Women's Hospital
Boston, Massachusetts, United States
Andrew S. Little, MD

Neurosurgeon
Barrow Neurological Institute
Phoenix, AZ, US
AM

Anna J. Matthew, MD

Assistant Professor
Department of Pathology, Division of Neuropathology, Keck School of Medicine of USC, United States
DP

Dhiraj Pangal, MD

Resident
Department of Neurosurgery, Stanford Medicine
Los Angeles, California, United States
JR

Jacob J. Ruzevick, MD

Assistant Professor
Department of Neurological Surgery, University of Washington
Seattle, Washington, United States
Ishan Shah, BS

Medical Student
Department of Neurological Surgery, Keck School of Medicine of USC, Los Angeles, California, United States
MS

Mark S. Shiroishi, MD

Assistant Professor
Department of Radiology, Division of Neuroradiology, Keck School of Medicine of USC
Los Angeles, California, United States
BS

Ben A. Strickland, MD

Assistant Professor
Department of Neurosurgery, MUSC Health
Los Angeles, California, United States
Gabriel Zada, MD

Neurosurgeon
University of Southern California
Los Angeles, CA, US
YZ

Yana Zavros, PhD

Professor, Associate Head of Research
Cellular and Molecular Medicine, The University of Arizona College of Medicine Tucson, United States

Disclosure(s):

Jeffrey J. Feng, MS: No financial relationships to disclose

Stephanie K. Cheok, MD: No financial relationships to disclose

Andrew S. Little, MD: No financial relationships to disclose

Gabriel Zada, MD: Stryker Corp: Consultant (Ongoing)

Introduction: Pituitary adenomas (PAs), which often present with endocrinopathy and/or visual symptoms, were historically classified by functional status and histopathological staining of anterior pituitary hormones. In 2017, the World Health Organization (WHO) revised the classification of PAs, establishing cell lineages identified by the transcription factors (TFs) PIT1, TPIT, and SF1. The clinical behavior of PA subtypes based on TF typing, including growth patterns, treatment response, and recurrence rates remains a knowledge gap. We aimed to assess clinical presentation and outcomes according to TF lineage in a contemporary series of PAs.

Methods: A retrospective multicenter clinical study of patients undergoing resection of PAs between October 2005 and August 2021 was performed. Included tumors underwent immunohistochemical staining for WHO-defined transcription factors (TPIT, PIT1, and SF1). Clinical data including demographics, tumor characteristics, extent of resection, and outcomes pertaining to tumor control and hormonal remission were assessed.

Results: A total of 238 patients were included, with the following distribution of PAs: Nonfunctional (n=152, 63.9%), GH-secreting causing acromegaly (n=56, 23.5%), ACTH-secreting causing Cushing’s disease (n=28, 11.8%) and prolactinomas (n=2, 0.8%). The most common TF cellular lineages were SF1 (n=106, 44.5%), TPIT (n=52, 21.8%), and PIT1 (n=49, 20.6%). Twenty-three (9.7%) were positive for two TFs, and 8 (3.4%) had no TF staining (null cell). Suprasellar extension was highest in TF null cell and SF1 PAs (p < 0.001). Cavernous sinus invasion was highest in TF null cell, PIT1, and TPIT PAs (p=0.002). Although no significant differences in progression-free survival (PFS) were noted across various PA TF subtypes, among nonfunctional PAs median PFS for SF1, PIT1, and TPIT PAs was 106, 26, and 47 months, respectively (p=0.01). Nonfunctional PIT1 PAs had a significantly shorter PFS compared to functional PIT1 tumors (p=0.002).

Conclusion : The modern WHO diagnosis of PAs incorporates pituitary TF staining in an effort to standardize classification according to PA cell lineage. TF designation is associated with major clinical and endocrine variables including PA extension, extrasellar growth patterns, Ki-67 labeling index, and likely progression-free survival among particular PA subtypes.