Mortara Umberto, Orlando Giulia, Volante Marco, Papotti Mauro, Duregon Eleonora
Pathology Unit, Città Della Salute E Della Scienza Hospital, Turin, Italy.
Department of Oncology, University of Turin, Orbassano, Turin, Italy.
Endocr Pathol. 2025 Jun 4;36(1):21. doi: 10.1007/s12022-025-09867-y.
The reticulin framework, composed mainly of type III collagen, is an essential structural component of biological tissues. Reticulin stains, particularly silver-based methods, enable detailed visualization of reticulin framework alterations, which have been proven to be quick, low-cost, and reliable solutions for highlighting quantitative and qualitative changes of reticulin framework and have been variably associated with neoplastic and non-neoplastic conditions. This review provides an updated overview of reticulin stain applications and reticulin framework assessment in endocrine and neuroendocrine neoplasms, including those of the pituitary, parathyroid, adrenal, and other neuroendocrine systems. In pituitary neuroendocrine tumors, reticulin framework loss serves as a distinguishing feature between normal and neoplastic adenohypophysis. Parathyroid neoplasms, including adenomas, atypical tumors, and carcinomas, exhibit varying degrees of reticulin framework disruption, which may aid in differential diagnosis. Similarly, in adrenocortical neoplasms, reticulin framework evaluation plays a crucial role in malignancy assessment, as defined in the reticulin algorithm, which incorporates reticulin framework alterations alongside three Weiss criteria: necrosis, high mitotic count (> 5/10 mm), and venous invasion. Moreover, specific reticulin framework patterns help to distinguish the different morphological subtypes of bilateral macronodular adrenocortical disease. Pheochromocytomas and paragangliomas display a range of reticulin framework patterns which might be related to the genetic background of the tumor. Finally, different neuroendocrine neoplasms exhibit variable reticulin framework integrity, with a more significant disruption observed in high-grade carcinomas. Advancements in digital pathology and artificial intelligence offer promising avenues for automated reticulin framework quantification, enhancing diagnostic precision and prognostic assessments. The integration of computational approaches may further improve the clinical utility of reticulin framework evaluation in endocrine pathology.
网状纤维框架主要由III型胶原蛋白组成，是生物组织的重要结构成分。网状纤维染色，特别是基于银的方法，能够详细观察网状纤维框架的改变，这些方法已被证明是突出网状纤维框架定量和定性变化的快速、低成本且可靠的解决方案，并与肿瘤性和非肿瘤性疾病存在不同程度的关联。本综述提供了网状纤维染色在内分泌和神经内分泌肿瘤中应用及网状纤维框架评估的最新概述，包括垂体、甲状旁腺、肾上腺及其他神经内分泌系统的肿瘤。在垂体神经内分泌肿瘤中，网状纤维框架缺失是正常腺垂体与肿瘤性腺垂体的一个区别特征。甲状旁腺肿瘤，包括腺瘤、非典型肿瘤和癌，表现出不同程度的网状纤维框架破坏，这可能有助于鉴别诊断。同样，在肾上腺皮质肿瘤中，网状纤维框架评估在恶性评估中起关键作用，如网状纤维算法所定义，该算法将网状纤维框架改变与三个Weiss标准（坏死、高有丝分裂计数（>5/10mm）和静脉侵犯）相结合。此外，特定的网状纤维框架模式有助于区分双侧大结节性肾上腺皮质疾病的不同形态亚型。嗜铬细胞瘤和副神经节瘤表现出一系列可能与肿瘤遗传背景相关的网状纤维框架模式。最后，不同的神经内分泌肿瘤表现出不同程度的网状纤维框架完整性，在高级别癌中观察到更明显的破坏。数字病理学和人工智能的进展为网状纤维框架的自动化定量提供了有前景的途径，提高了诊断准确性和预后评估。计算方法的整合可能进一步提高网状纤维框架评估在内分泌病理学中的临床应用价值。
