There are no histopathological, immunohistochemical, or ultrastructural features to reliably differentiate PC from PA. Microscopically, PC usually appear as well- differentiated neuro endocrine tumours akin to benign PA. While histological features of hypercellularity, nuclear pleomorphism, necrosis, haemorrhage, or invasion may be present in PC, they are also common in PA. Neuronal metaplasia has been reported in PC but is rare. Metastatic deposits often have more atypical cytological features compared to the primary pituitary tumour. Mitoses are more frequently seen in PC compared with PA, although there are cases of PC without significant mitoses. In one study, mitoses were present in 3.9% of non- invasive PA, 21.4% of invasive PA and 66% of PC, while in the large European Society of Endocrinology (ESE) survey cohort of APT a raised mitotic count (>2 mitoses/ 10 high powered field (HPF)) was found in 90% of PC compared with 63% of APT.

The neuroendocrine origin of PC can be confirmed on immunohistochemical analysis with expression of markers such as chromogranin A and synaptophysin. Pituitary hormone ex pression does not differentiate PC from PA but is important to determine tumour subtype. Tumour subclassification, utilizing immunohistochemical analysis of transcription factors and low- molecular- weight cytokeratin, can assist in identifying a tumour with an increased potential for more aggressive be haviour (Table 1). Clinically non- functioning but immunohistochemically classified Pit-1 positive plurihormonal adenomas (previously termed silent subtype 3 PA) are particularly recognized for their inherently aggressive behaviour. Cytokeratin staining identifies the fibrous bodies of a sparsely granulated somatotroph adenoma and also hyaline changes of Crooke’s cell adenomas. Ultrastructural evaluation is no longer necessary in the routine classification of pituitary tumours.

Table1. Pituitary tumour subtypes with potential for aggressive behaviour

Measurement of Ki67, using the MIB- 1 antibody, provides an assessment of the number of cells in the S- phase of the cell cycle, and is an important marker of the rate of cellular proliferation. Metastatic deposits frequently exhibit higher Ki67 indices than the primary pituitary tumour. Higher Ki67 indices have been correlated with invasive adenomas, risk of recurrence and malignant behaviour. The mean Ki67 in one series was 1.37% for non- invasive PA compared with 4.66% for invasive adenomas and 11.91% for PC. Similarly, in the ESE survey cohort 46% of APT and PC were found to have a Ki67 ≥ 10%. A threshold Ki67 ≥ 3% has commonly been used as a marker associated with an increased risk of tumour recurrence while a Ki67 ≥ 10% is considered by some authors to indicate a malignant pituitary tumour. However, there is substantial variability in Ki67 reported among PC from 0% to 34%. This may result from tumour heterogeneity as well as differences in interpretation of Ki67 labelling.

Used in isolation, the Ki67 measurement has limited prognostic potential [39, 40]. Increased expression of p53 has been reported in 100% of a cohort of PC compared with 7.1% of PA, while in other studies p53 expression has progressively increased during the progression from adenoma to carcinoma. It has also been found to be absent in PC and considerable debate exists over its reliability. The combination of Ki67 >3% and extensive p53 immunoreactivity has been associated with an increased recurrence rate of PA in some studies, but not in others. In the 2004 WHO classification of pituitary tumours, an ‘atypical pituitary adenoma’ was defined by the presence of Ki67 >3%, p53 overexpression, and increased mitotic rate, however this category was abandoned in the 2017 WHO classification given the lack of clinical validation as a prognostic tool. Nevertheless, measurement of Ki67, along with p53 immunostaining and evaluation of mitotic count, remain recommended in the assessment of an APT. The utility of these proliferative markers may be most useful in determining risk of recurrence for invasive PA. This formed the basis for a clinicopathological grading classification system in which invasive and proliferative PA demonstrated a 12- fold increased risk of tumour progression compared with non- invasive, non- proliferative PA.

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اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية ينظّم ختمة قرآنية رمضانية لطلبة العلوم الدينية الأفارقة في النجف

شعبة الخطابة تقيم مجلسا للوعظ والإرشاد في الصحن الشريف تزامناً مع حلول شهر رمضان المبارك

قسم التطوير يختتم دورة إعداد المدربين لملاكات مديرية تربية كربلاء

ضمن فعاليات ملتقى النورين.. المجمع العلمي يطلق الختمة القرآنية الرمضانية المرتّلة في بابل

المزيد

الآخبار الصحية

مفاجأة.. تحسين القدرة على التحمل لا يعتمد العضلات فقط

المرتفعات والأكسجين.. دراسة "مبشرة" لمرضى السكري

علماء يبتكرون "آلية" تتوقع موعد ظهور أعراض الزهايمر

ماذا يحدث لجسمك عند التوقف عن تناول الخضراوات والفواكه؟

المزيد

الآخبار التكنلوجية

رصد "القرش النائم" في أحد أقسى الأماكن على وجه الأرض

أسماك أعماق البحر تكشف نظاما بصريا يتجاوز "المألوف"

زوكربيرغ أمام القضاء في قضية إدمان المراهقين

"علي بابا" تكشف عن نموذج جديد للذكاء الاصطناعي

المزيد

مواضيع ذات صلة

Pituitary incidentaloma

Clinical Presentation and Diagnosis of Pituitary carcinomas

Aetiopathogenesis and Pathology of Thyrotropinomas

Cancer and The Environment

Cytogenetic Changes in Cancer

Telomerase as an Oncogene

Activation of Oncogenes by Chromosome Translocation or Fusions

Imaging of the Pituitary: Adenomas

T pit Family of tumours

Pit- 1 Family of tumours

Pituitary Adenomas

Molecular Mechanisms of Carcinogenesis