TY - JOUR
T1 - High-Grade Progression, Sarcomatous Transformation, and/or Metastasis of Pituitary Neuroendocrine Neoplasms (PitNENs)
T2 - The UCSF Experience
AU - Terry, Merryl
AU - Nguyen, Minh P.
AU - Tang, Vivian
AU - Guney, Ekin
AU - Bharani, Krishna L.
AU - Dahiya, Sonika
AU - Choutka, Ondrej
AU - Borys, Ewa
AU - Reis, Gerald
AU - Blevins, Lewis
AU - Aghi, Manish K.
AU - Kunwar, Sandeep
AU - DeGroot, John
AU - Raleigh, David R.
AU - Pekmezci, Melike
AU - Bollen, Andrew W.
AU - Cha, Soonmee
AU - Joseph, Nancy M.
AU - Perry, Arie
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Pituitary neuroendocrine tumors (PitNET) that metastasize comprise ~ 0.2% of adenohypophyseal tumors are aggressive and are challenging to treat. However, many non-metastatic tumors are also aggressive. Herein, we review 21 specimens from 13 patients at UCSF with metastatic PitNETs (CSF or systemic, N = 7 patients), high-grade pituitary neuroendocrine neoplasms (HG-PitNEN, N = 4 patients), and/or PitNETs with sarcomatous transformation (PitNET-ST, N = 5 patients). We subtyped cases using the World Health Organization (WHO) and International Agency for Research on Cancer (IARC) criteria for neuroendocrine neoplasms (NENs). Lineage subtypes included acidophil stem cell, null cell, thyrotroph, corticotroph, lactotroph, and gonadotroph tumors. The median Ki-67 labeling index was 25% (range 5–70%). Lack of p16 was seen in 3 cases, with overexpression in 2. Strong diffuse p53 immunopositivity was present in 3 specimens from 2 patients. Loss of Rb expression was seen in 2 cases, with ATRX loss in one. Molecular analysis in 4 tumors variably revealed TERT alterations, homozygous CDKN2A deletion, aneuploidy, and mutations in PTEN, TP53, PDGFRB, and/or PIK3CA. Eight patients (62%) died of disease, 4 were alive at the last follow-up, and 1 was lost to the follow-up. All primary tumors had worrisome features, including aggressive lineage subtype, high mitotic count, and/or high Ki-67 indices. Additional evidence of high-grade progression included immunohistochemical loss of neuroendocrine, transcription factor, and/or hormone markers. We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.
AB - Pituitary neuroendocrine tumors (PitNET) that metastasize comprise ~ 0.2% of adenohypophyseal tumors are aggressive and are challenging to treat. However, many non-metastatic tumors are also aggressive. Herein, we review 21 specimens from 13 patients at UCSF with metastatic PitNETs (CSF or systemic, N = 7 patients), high-grade pituitary neuroendocrine neoplasms (HG-PitNEN, N = 4 patients), and/or PitNETs with sarcomatous transformation (PitNET-ST, N = 5 patients). We subtyped cases using the World Health Organization (WHO) and International Agency for Research on Cancer (IARC) criteria for neuroendocrine neoplasms (NENs). Lineage subtypes included acidophil stem cell, null cell, thyrotroph, corticotroph, lactotroph, and gonadotroph tumors. The median Ki-67 labeling index was 25% (range 5–70%). Lack of p16 was seen in 3 cases, with overexpression in 2. Strong diffuse p53 immunopositivity was present in 3 specimens from 2 patients. Loss of Rb expression was seen in 2 cases, with ATRX loss in one. Molecular analysis in 4 tumors variably revealed TERT alterations, homozygous CDKN2A deletion, aneuploidy, and mutations in PTEN, TP53, PDGFRB, and/or PIK3CA. Eight patients (62%) died of disease, 4 were alive at the last follow-up, and 1 was lost to the follow-up. All primary tumors had worrisome features, including aggressive lineage subtype, high mitotic count, and/or high Ki-67 indices. Additional evidence of high-grade progression included immunohistochemical loss of neuroendocrine, transcription factor, and/or hormone markers. We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.
KW - Grading
KW - Metastasis
KW - Neuroendocrine neoplasms
KW - Pituitary carcinoma
KW - Pituitary neuroendocrine carcinoma
KW - Pituitary neuroendocrine tumor
KW - Pituitary sarcoma
UR - http://www.scopus.com/inward/record.url?scp=85206362154&partnerID=8YFLogxK
U2 - 10.1007/s12022-024-09829-w
DO - 10.1007/s12022-024-09829-w
M3 - Article
C2 - 39388031
AN - SCOPUS:85206362154
SN - 1046-3976
VL - 35
SP - 338
EP - 348
JO - Endocrine Pathology
JF - Endocrine Pathology
IS - 4
ER -