Pituitary Carcinoma Research Articles

Efficacy and safety of temozolomide in the treatment of aggressive pituitary neuroendocrine tumours in Spain.

Current guidelines recommend temozolomide as the first-line chemotherapy for aggressive pituitary neuroendocrine tumours. However, no clinical trials have been conducted to date and clinical experience is quite limited. We retrospectively analyzed 28 patients (9 women and 19 men), aged 46.6+16.9, with aggressive pituitary tumours (4 pituitary carcinomas and 24 aggressive adenomas) treated with temozolomide in 10 Spanish pituitary reference centres. Four patients had Cushing's disease, 9 prolactinomas and 15 clinically non-functioning pituitary tumours (seven silent corticotroph, three silent somatotroph, one silent lactotroph, one silent gondotroph and three null-cell tumours). Median size at diagnosis was 10.5 cm3 (IQR 4.7-22.5), with cavernous sinus invasion in 88% and no metastases. Pre-temozolomide treatment, these data were 5.2 cm3 (IQR 1.9-12.3), 89.3% and 14.3% (2 intracranial and 2 spinal metastases). All patients had undergone surgery (1-5 surgeries), 25 (89.3%) had received radiotherapy (7 of them reirradiated) and 13(46.4%) had received cabergoline. One patient interrupted temozolomide prematurely. The remaining 27 patients received a median of 13 cycles (range 3-66) of 5 days every 28 days, with a mean initial dose of 265 ± 73 mg when administered alone and of 133 ± 15 mg when co-administered with radiotherapy. Eight patients (29.6%) had a significant reduction (>30%) in tumour volume and 14 (51.9%) attained tumour stabilization. After a median follow-up of 29 months (IQR 10-55), 8 out of these 22 showed disease progression. A longer progression-free survival was found in the five patients who received concomitant radiotherapy. Seven patients (25%) died (all of them because of tumour progression or complications of treatments) at 77 months (IQR 42-136) after diagnosis and 29 months (IQR 16-55) after the first dose of temozolomide. Adverse effects occurred in 18 patients (14 mild and 4 moderate or severe). In conclusion, temozolomide is an effective medical treatment for aggressive pitNET and pituitary carcinomas but is sometimes followed by tumour progression. Co-administration with radiotherapy may increase progression-free survival.

Historical Control Background Incidence of Spontaneous Neoplastic Lesions of Sprague-Dawley Rats in 104-Week Toxicity Studies.

Data collected from approximately 1800 male and 1800 female Sprague-Dawley (SD) rats used in 104-week carcinogenicity studies were archived in a historical control database at Labcorp Early Development, Inc, and the neoplastic microscopic observation data from these rats were retrospectively evaluated. Historical control data can provide useful information on the range and incidence of spontaneously occurring background neoplasms in the species and strain of the test animal used in different types of toxicity studies, including studies of differing lengths, delivery of test article, and test animal. Some of the most common malignant findings noted included fibrosarcoma of skin/subcutis and thyroid C-cell carcinoma in males (2.1% each) while mammary gland carcinoma and pituitary carcinoma (25% and 2.6%) were most common in females. Pituitary adenoma of pars distalis was found to be the most prevalent benign neoplasm in both males and females (56.4% and 77.1%). Fibroadenoma of mammary gland (35.6%) and thyroid C-cell adenoma (8.5%) were the second and third most common benign tumors in female SD rats. In males, the thyroid C-cell adenoma (10.9%) and benign pheochromocytoma (8.9%) were the second and third most common tumors.

Metastatic pituitary tumors: an institutional case series.

Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined. We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas. Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14). Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.

Aggressive pituitary adenoma and pituitary carcinoma

Anterior pituitary tumours, once considered benign neoplasms, may rarely have aggressive behaviour and can even metastasize. The current guideline of the European Society of Endocrinology defines aggressive pituitary adenomas as radiologically invasive tumours with an unusually rapid growth rate and frequent relapses despite the optimal use of standard therapies. Currently, there is not any single, well-defined pathological marker of malignancy. Pituitary carcinomas are thus clinically defined by the presence of craniospinal or distant metastases, typically developing several years after the first presentation. Histopathology may predict aggressive behaviour if the Ki67 index and mitotic rate are elevated and in case of positive p53 staining. These patients' short- and long-term therapy should be individualized and regularly discussed by a multidisciplinary pituitary team. Besides standard medical treatment administered in maximally tolerated doses, current recommendations suggest repeated surgery and radiotherapy. If this approach fails, the next choice of treatment is chemotherapy with temozolomide. After that, immune checkpoint inhibitors, bevacizumab, and peptide receptor radiotherapy are emerging therapies that should be used on a case-by-case basis. Orv Hetil. 2023; 164(30): 1167-1175.

Somatostatin Receptor-PET/CT/MRI of Head and Neck Neuroendocrine Tumors.

Due to its high sensitivity, somatostatin receptor-PET may detect smaller lesions and more extensive disease than contrast-enhanced MR imaging, while the superior spatial resolution of MR imaging enables lesions to be accurately localized. We compared results of somatostatin receptor-PET/MRI with those of MR imaging alone and assessed the added value of vertex-to-thigh imaging for head and neck neuroendocrine tumors. Somatostatin receptor-PET/CT was acquired as limited brain or head and neck imaging, with optional vertex-to-thigh imaging, following administration of 64CU/68GA DOTATATE. Somatostatin receptor-PET was fused with separately acquired contrast-enhanced MR imaging. DOTATATE activity was classified as comparable, more extensive, and/or showing additional lesions compared with MR imaging. Vertex-to-thigh findings were classified as positive or negative for metastatic disease or incidental. Thirty patients (with 13 meningiomas, 11 paragangliomas, 1 metastatic papillary thyroid carcinoma, 1 middle ear neuroendocrine adenoma, 1 external auditory canal mass, 1 pituitary carcinoma, 1 olfactory neuroblastoma, 1 orbital mass) were imaged. Five had no evidence of somatostatin receptor-positive lesions and were excluded. In 11/25, somatostatin receptor-PET/MRI and MR imaging were comparable. In 7/25, somatostatin receptor-PET/MRI showed more extensive disease, while in 9/25, somatostatin receptor-PET/MRI identified additional lesions. On vertex-to-thigh imaging, 1 of 17 patients was positive for metastatic disease, 8 of 17 were negative, and 8 of 17 demonstrated incidental findings. Somatostatin receptor-PET detected additional lesions and more extensive disease than contrast-enhanced MR imaging alone, while vertex-to-thigh imaging showed a low incidence of metastatic disease. Somatostatin receptor-PET/MRI enabled superior anatomic delineation of tumor burden, while any discrepancies were readily addressed. Somatostatin receptor-PET/MRI has the potential to play an important role in presurgical and radiation therapy planning of head and neck neuroendocrine tumors.

Phase II trial of pembrolizumab in patients with brain metastases.

2006 Background: Brain metastases are an increasing challenge in oncology due to increasing incidence and limited treatments. Recent studies suggest that brain metastases harbor a tumor microenvironment characterized by immunosuppressive phenotypes, which contribute to treatment resistance. Therefore, a logical therapeutic strategy for brain metastases is to evaluate immune-based strategies that augment T cell cytotoxicity. Methods: This study was designed as an open-label, single-stage, single-arm phase 2 clinical trial evaluating the intracranial efficacy of pembrolizumab, a PD-1 inhibitor, in patients with brain metastases of diverse histologies. The target accrual was 58 patients to achieve at least 52 evaluable patients (i.e., received at least one dose of pembrolizumab). The primary endpoint was intracranial benefit, defined as a best response of complete response, partial response, or stable disease by RANO criteria during treatment. The study design compared a null intracranial benefit rate of 10% against an alternative of 24%. If at least 8 patients among the total of 52 had intracranial benefit, the primary efficacy endpoint would be met and pembrolizumab would be considered worthy of further study in this patient population. This design has a type-I error of 10% and power of 89% (target type-II error of 15%). Results: In the 57 evaluable patients, median age was 53 (range 28-80) and 81% were female. Tumor histologies included breast (n = 35), non-small cell lung cancer (n = 7), melanoma (n = 2), small-cell lung cancer (n = 2), sarcoma (n = 2), ovarian (n = 1), pituitary carcinoma (n = 1), pituitary neuroendocrine tumor (n = 1), esophageal adenocarcinoma (n = 1), prostate (n = 1), renal cell carcinoma (n = 1), neuroendocrine carcinoma (n = 1), unknown primary (n = 1) and sinonasal adenocystic carcinoma (n = 1). For the patients with breast cancer, 16 patients had HER-2 positive disease, 17 patients had hormone receptor-positive disease, and 11 patients had the triple-negative subtype. The study met its primary endpoint and achieved an intracranial benefit rate of 42.1% (90% confidence interval [CI]: 31-54%). In addition, seven patients, who had either breast cancer, melanoma or sarcoma, had durable intracranial anti-tumor activity ( > 2 years). The extracranial benefit rate in patients with evaluable extracranial disease based on RECIST 1.1 criteria was 45% (18/40; 90% CI: 31-59%). Median overall survival was 8.0 months (90% CI: 5.5-8.7 months). Grade 4 toxicities at least possibly related to treatment were observed in 2 patients: cerebral edema (n = 2). Thirteen patients discontinued treatment for adverse events. Conclusions: Our study of pembrolizumab met overall primary endpoint for intracranial benefit in patients with brain metastases. These results suggest that PD-1 blockade may serve as the backbone of therapeutic strategies for a select group of patients with brain metastases and warrants further evaluation. Clinical trial information: NCT02886585 .

The Role of Immunotherapy in the Treatment of Rare Central Nervous System Tumors.

Establishing novel therapies for rare central nervous system (CNS) tumors is arduous due to challenges in conducting clinical trials in rare tumors. Immunotherapy treatment has been a rapidly developing field and has demonstrated improvements in outcomes for multiple types of solid malignancies. In rare CNS tumors, the role of immunotherapy is being explored. In this article, we review the preclinical and clinical data of various immunotherapy modalities in select rare CNS tumors, including atypical meningioma, aggressive pituitary adenoma, pituitary carcinoma, ependymoma, embryonal tumor, atypical teratoid/rhabdoid tumor, and meningeal solitary fibrous tumor. Among these tumor types, some studies have shown promise; however, ongoing clinical trials will be critical for defining and optimizing the role of immunotherapy for these patients.

Abstract #1393024: A Rare Case of ACTH-Producing Pituitary Carcinoma in Nelson’s Syndrome

A 55-year-old male with Nelson's Syndrome was originally diagnosed with Cushing’s disease 5 years prior after the identification of a 15 x 13 mm pituitary adenoma and ACTH 174 pg/mL. He had typical symptoms including proximal weakness, easy bruising, abdominal striae, weight gain, and atraumatic vertebral fractures. Pathology following TSRPT at that time showed an ACTH-producing tumor with MIB1 index 20%. He had initial improvement of his Cushing's stigmata but one year later developed proximal muscle weakness, hypokalemia requiring replacement, worsening diabetes, and weight gain. Repeat MRI was negative for new/recurring lesion. One and a half years after initial TSRPT, he started on ketoconazole 400 mg three times daily and cabergoline 1 mg TID as a repeat MRI showed a recurring pituitary lesion measuring 13 x 14 x 9 mm with corresponding ACTH level 159 pg/mL. He underwent radiotherapy with 20 Gy in one fraction and two months later underwent bilateral adrenalectomy with cessation of ketoconazole and cabergoline. Two years later, his ACTH level increased to 1,342 pg/mL and he underwent another fraction of radiotherapy of 20 Gy. A repeat MRI showed a decrease in the size of pituitary lesion. However, eight months later, his ACTH levels peaked at 45,510 pg/mL and he underwent a second TSRPT and a stereotactic radiosurgery series of 54 Gy in 30 fractions over three months. Surgical pathology showed a low-grade neuroendocrine neoplasm without any mitotic figures and an MIB-1 index 15% Two months following the SRS series, his ACTH levels peaked at 188,567 pg/mL. He presented to the ED for abdominal pain and CT Abdomen showed possible metastatic lesions in the liver, one of which was subsequently biopsied and positive for pituitary carcinoma. He is currently undergoing capecitabine chemotherapy and an SRS series to the liver with plans to add temozolomide upon completion of the SRS. A key learning point is to suspect metastatic disease with drastic ACTH increases. PET scan imaging is recommended in a patient with rapid or significant increase in ACTH level with or without progression of a lesion centrally. Additionally, although the original histology did not show carcinoma, the elevated MIB-1 index should raise the suspicion for malignant possibility and therefore, increased surveillance. Functional pituitary carcinoma has the twofold task of treating the excess hormone production and controlling the spread of metastatic disease. Given the rarity of this type of cancer, a multi-disciplinary approach best serves the patient including endocrinology, oncology, (neurological) surgery, and radiation oncology. More data and studies are needed to definitively assess efficacy of chemotherapeutics including capecitabine and temozolomide for these types of tumors.

526 Clinical Characteristics and Biomarkers of Aggressive Nonfunctional Pituitary Adenomas and Pituitary Carcinomas

INTRODUCTION: Nonfunctioning pituitary adenomas (NFPAs) are benign tumors of the pituitary gland. While surgery is the treatment of choice, a subset of aggressive NFPAs is associated with multiple recurrences and treatments. Pituitary carcinomas are a rare group of pituitary tumors, comprised of both functional and non-functional, which metastasize to other locations. METHODS: A retrospective review of 601 consecutive patients who underwent endoscopic transsphenoidal surgery between 2010 and 2018 at one institution was conducted. Among 209 NFPA patients, 29 patients had aggressive NFPAs, with ≥2 recurrences and ≥3 treatments. We used Infinium HumanMethylation450 BeadChip arrays along with R (R Core 2014) and Bioconductor for methylation analysis of patients with indolent NFPAs (n = 6), aggressive NFPAs (n = 8), pituitary carcinomas (n = 9), and normal pituitary glands (n=3). RESULTS: In multivariate analysis of clinical features, tumor volume and proliferative index were higher in aggressive NFPAs compared to indolent NFPAs. Although significantly different, these features were not specific to aggressive NFPAs. Methylation analysis showed no significant global methylation differences among all samples. However, we identified significant probe-wise differentiation in methylation of over 100 genes between indolent and aggressive NFPA groups. Heat map representation of the most significant differentially methylated genes demonstrated similarity in methylation patterns between the aggressive NFPA and pituitary carcinoma group, which were distinct from the indolent group. CONCLUSIONS: Tumor volume and proliferative index were significantly increased in the aggressive compared to the indolent group. In DNA methylation analyses, we identified numerous hypermethylated genes in the aggressive and pituitary carcinoma groups, which were distinct from the indolent group. DNA methylation may provide a useful predictive biomarker to identify aggressive NFPA types and potentially reveal common mechanistic links between aggressive NFPAs and pituitary carcinomas.

Initial pathology in aggressive pituitary tumours and carcinomas: 2b or not 2b?-that is the question.

Abstract From a cohort of 171 patients comprising 121 aggressive pituitary tumours (APT) and 50 pituitary carcinomas (PC), the clinicopathological or five-tiered classification based on tumour invasion and proliferation evaluated by at least 2 proliferative markers over the cut-offs (Ki-67 ≥3% or ≥10%, p53 positive or expressed in %, mitotic count >2%), could be applied on 43 tumours: 20 PC and 23 APT. At the initial surgery, 29/43 tumours (67.4%) were grade 2b (invasive and proliferative) of which 44.8% developed metastases during follow-up (PC, grade 3). Out of these 29 tumours, 55.1% had a Ki-67 ≥10%, and were classified grade 2b* (invasive and highly proliferative). There was one tumour grade 1b* (non-invasive and highly proliferative) which metastazed. Out of the 43 tumours, 30.2 % were grade 2a (invasive and non-proliferative). The sensitivity and the specificity of grade 2b for the diagnosis of APT at the initial surgery, were 68% and 90% respectively. The comparison of the high percentage (67.4%) of grade 2b tumours in this selected cohort of APT/PC with the low percentage (8.8%) in a surgical cohort of unselected tumours shows that the initial pathological diagnosis of grade 2b tumour may be considered, in the clinic, as representing a diagnosis of APT. In addition, a significant subgroup of tumours, which will develop metastases supports the proposal that an aggressive grade 2b tumour is “a tumour with malignant potential” or “a malignant tumour without metastases”. So, the clinician may take into account the pathological diagnosis, at the initial surgery, to propose a strict follow-up and to consider earlier use of radiotherapy and/or of temozolomide in the presence of tumours with aggressive behaviour.

Inhibition of VEGF receptors induces pituitary apoplexy: An experimental study in mice.

Anti-vascular endothelial growth factor (VEGF) therapy has been developed for the treatment of a variety of cancers. Although this therapy may be a promising alternative treatment for refractory pituitary adenomas and pituitary carcinomas, the effects of anti-VEGF agents on the pituitary gland are not yet well understood. Here, we found that mice administered with OSI-930, an inhibitor of receptor tyrosine kinases including VEGF receptor 1 and 2, frequently exhibited hemorrhage in the pituitary gland. This is the first report that anti-VEGF therapy can cause pituitary apoplexy. C57BL/6 mice were daily injected intraperitoneally with 100 mg/kg body weight of OSI-930 for one to six days. Pituitary glands were immunohistochemically examined. Four of six mice treated for three days and all of five mice treated for six days exhibited hemorrhage in the pituitary gland. In all cases, the hemorrhage occurred just around Rathke's cleft. In OSI-930-administered mice, the vascular coverage and branching were reduced in the anterior lobe, and capillary networks were also decreased in the intermediate lobe in a treatment-day dependent manner. Few blood vessels around Rathke's cleft of the intermediate lobe express VE-cadherin and are covered with platelet-derived growth factor receptor-β (PDGFR-β)-positive cells, which suggests that capillaries around Rathke's cleft of the intermediate lobe were VE-cadherin-negative and not covered with pericytes. The reduction of capillary plexus around Rathke's cleft was observed at the site where hemorrhage occurred, suggesting a causal relationship with the pathogenesis of pituitary hemorrhage. Our study demonstrates that anti-VEGF agents have a risk of pituitary apoplexy. Pituitary apoplexy should be kept in mind as an adverse effect of anti-VEGF therapy.

Aggressive Pituitary Tumors and Pituitary Carcinomas: From Pathology to Treatment.

Aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs) are heterogeneous with regard to clinical presentation, proliferative markers, clinical course, and response to therapy. Half of them show an aggressive course only many years after the first apparently benign presentation. APTs and PCs share several properties, but a Ki67 index greater than or equal to 10% and extensive p53 expression are more prevalent in PCs. Mutations in TP53 and ATRX are the most common genetic alterations; their detection might be of value for early identification of aggressiveness. Treatment requires a multimodal approach including surgery, radiotherapy, and drugs. Temozolomide is the recommended first-line chemotherapy, with response rates of about 40%. Immune checkpoint inhibitors have emerged as second-line treatment in PCs, with currently no evidence for a superior effect of dual therapy compared to monotherapy with PD-1 blockers. Bevacizumab has resulted in partial response (PR) in few patients; tyrosine kinase inhibitors and everolimus have generally not been useful. The effect of peptide receptor radionuclide therapy is limited as well. Management of APT/PC is challenging and should be discussed within an expert team with consideration of clinical and pathological findings, age, and general condition of the patient. Considering that APT/PCs are rare, new therapies should preferably be evaluated in shared standardized protocols. Prognostic and predictive markers to guide treatment decisions are needed and are the scope of ongoing research.

Pituitary Macroadenoma: A Case Report

Pituitary carcinoma is a rare form of malignancy that may be very difficult to diagnose and treat. Many cases were diagnosed by way of the autopsy. Delays in diagnosis often adversely impact patients' consequences. This case report emphasizes the need for timely identification and careful management of pituitary carcinoma. We report a medical staff nurse aged 29 years female presented with complaints of sudden severe headaches and was admitted to a local hospital. She was given symptomatic treatment. All blood investigations were normal. MRI with contrast revealed an isointense to a hypointense lesion in the pituitary fossa with an irregular central mass of necrosis. She was treated with surgery and radiation. Pituitary carcinoma is a very rare entity. Any rapidly increasing macroadenoma should be managed by a team including an endocrinologist, neurosurgeon, and oncologist. Keywords: Pituitary Macroadenoma; Diagnosis; Treatment; Pituitary Adenoma

Pituitary carcinoma: A rare presentation

Pituitary carcinoma (PC) is a very rare feature of pituitary tumors, which is defined by the presence of cerebrospinal and/or systemic metastases. These tumors pose a problem of diagnosis and management. Multimodal therapeutic strategy include surgery, radiotherapy and chemotherapy has improved the poor prognosis of these patients. We present the case of a 50-year-old patient, diagnosed with pituitary carcinoma, surgically recused, who received exclusive radiation therapy.

Natural history of pituitary carcinoma with metastasis to the cervical spine: illustrative case

Pituitary carcinoma is a rare tumor of the adenohypophysis with noncontiguous craniospinal dissemination and/or systemic metastases. Given the rarity of this malignancy, there is limited knowledge and consensus regarding its natural history, prognosis, and optimal treatment. The authors present the case of a 46-year-old woman initially treated with invasive prolactin-secreting pituitary macroadenoma who developed metastatic disease of the cervical spine 6 years later. The patient presented with acutely worsening compressive cervical myelopathy and required posterior cervical decompression, tumor resection, and instrumented arthrodesis for posterolateral fusion. This case underscores the importance of long-term monitoring of hormone levels and having a high clinical suspicion for metastatic disease to the spine in patients presenting with acute myelopathy or radiculopathy in the setting of previously treated invasive secreting pituitary adenoma.

Aggressive pituitary tumors and pituitary carcinomas: from pathology to treatment. Supplemental table 1.

Aggressive pituitary tumors and pituitary carcinomas: from pathology to treatment. Supplemental table 1.

Pituitary Carcinoma in Paediatric Age Group: A Rare Case Report

Abstract Pituitary Carcinoma is a rare neoplasm and presentation in paediatric age group is even rarer (1:1,000,000). In contrast to pituitary adenomas, pituitary carcinomas are more commonly non-functioning. Furthermore, due to the lack of specific markers, the diagnosis of pituitary carcinoma remains difficult prior to demonstration of metastasis. In view of the rarity of this disease, treatment is often difficult to plan. We present a case of seven years age old female who presented with left eye ptosis associated with squint, double vision and headache. Magnetic Resonance Imaging (MRI) Brain revealed large mass lesion in region of sella extending into suprasellar cistern and left parasellar region suggestive of Pituitary Macroadenoma. She underwent partial excision of tumour under neuro navigation. Histopathology suggestive of pituitary lesion with atypical feature. Block review showed pituitary carcinoma. We present here the details of this rare tumour.

Pituitary Carcinoma with Cerebral Spinal Fluid Dissemination Presenting with Spinal Cord Compression

Pituitary Carcinoma with Cerebral Spinal Fluid Dissemination Presenting with Spinal Cord Compression

GH Pituitary Carcinoma with Delayed Craniocervical Metastasis: a rare description and pertinent review

GH Pituitary Carcinoma with Delayed Craniocervical Metastasis: a rare description and pertinent review

New pathological classification and clinical implications of pituitary neuroendocrine tumors of the 2022 WHO version

In 2022, the World Health Organization proposed a new classification for pituitary adenomas. The major nomenclature change from the previous edition was the transition from"adenoma"to"pituitary neuroendocrine tumor"(PitNETs). The new classification provided the detailed histological subtypes of PitNETs for routine use of antibodies such as pituitary transcription factors (PIT1, TPIT, SF1, GATA3, and ERα) and hormones. The major PIT1, TPIT, and SF1 lineage-defined PitNETs types and subtypes featured distinct morphologic, molecular, and clinical differences. Unlike the 2017 WHO classification, the 2022 WHO version updated some concepts as follows: (1) Mammosomatotroph, acidophil stem cell tumors and mixed somatotroph/lactotroph tumor represented distinct PIT1-lineage PitNETs; (2) The diagnostic category of PIT1-positive plurihormonal tumor was replaced by the immature PIT1-lineage tumor and the mature plurihormonal PIT1-lineage tumor; (3) The term"metastatic PitNET"was advocated to replace the previous terminology"pituitary carcinoma". The new classification emphasizes the importance of pathological classification of PitNETs. Obviously, accurate pathological interpretation is the key to judge the clinical treatment pathway and prognosis of patients.