How to Classify and Define Pituitary Tumors: Recent Advances and Current Controversies

Abstract

Pituitary tumors are very complex and heterogeneous and have a very wide range of proliferative and aggressive behaviors, and how to define and classify these tumors remains controversial. This review summarizes the epidemiology and progress in the classification and definition of pituitary tumors, as well as controversial issues. Based on the results of radiologic and autopsy studies, the prevalence of pituitary tumors has recently increased significantly. However, the majority of pituitary tumors are incidentally discovered and asymptomatic, and such tumors are called pituitary incidentalomas. Most of these incidentalomas do not induce symptoms, remain stable in size, and do not need treatment. The recent revised classification strategies mainly depend on immunohistochemistry (IHC) to detect pituitary hormones and pituitary transcription factors; therefore, the accuracy of diagnosing pituitary tumors has improved. Although new classification strategies and definitions for pituitary tumors have been presented, there are still some controversies. The term pituitary neuroendocrine tumor (PitNET) was proposed by the International Pituitary Pathology Club, and this terminology can encompass the unpredictable malignant behavior seen in the subset of aggressive pituitary adenomas (PAs). However, some endocrinologists who oppose this change in terminology have argued that the use of tumor in the terminology is misleading, as it gives PAs a harmful connotation when the majority are not aggressive. Such terminology may add new ambiguity to the origin of PAs and unnecessary anxiety and frustration for the majority of patients with benign PAs. The classification of aggressive PAs mainly relies on subjective judgment of clinical behavior and lacks objective biomarkers and unified diagnostic criteria. However, the term “refractory” could more accurately represent the characteristics of these tumors, including their clinical behaviors, radiological features, and pathologic characteristics. Moreover, the diagnostic criteria for refractory PAs are stricter, more objective, and more accurate than those for aggressive PAs. Early identification of patients with these tumors through recognition and increased awareness of the definition of refractory PAs will encourage the early use of aggressive therapeutic strategies.

Pituitary Tumours

“…Pituitary adenomas are broadly classified as functioning or non-functioning adenomas based on hypersecretion of specific hormones [42][43][44][45][46][47].…”

“…Significant changes affecting the diagnosis of pituitary adenomas (PA) were introduced, and simultaneously panels of experts have also proposed replacing the term PA for Pituitary neuroendocrine tumour (Pit NET) [42][43][44][45][46][47].…”

The Application of Artificial Intelligence and Machine Learning in Pituitary Adenomas

“…Some PAs are microadenomas (<10 mm) but secrete excess hormones, whereas others are invasive giant PAs (≥40 mm), leading to mass effects but without excessive hormone secretion. Some PAs are asymptomatic and remain stable with long-term follow-up, but others have obvious clinical symptoms at initial diagnosis and need to be treated in a timely manner ( 2 ). A subset of PAs is responsive to surgery, medical therapy, and radiotherapy, while others do not respond to these treatments.…”

Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications

“…In addition, pathology proliferation markers (Ki-67 expression: ≥3%, mitotic count n > 2) taken alone are not reliable markers of malignancy [12,13]. In fact, only the rare pituitary tumours with distant metastases can be named "pituitary carcinomas", indicating truly malignant behaviour [14,15].…”