Research Department, "Marius Nasta" Institute of Pneumophthisiology, 050159 Bucharest, Romania.
Pathology Department, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
Medicina (Kaunas). 2024 Jan 7;60(1):112. doi: 10.3390/medicina60010112.
Lung cancer is among the most common oncological diseases regarding incidence and mortality, with most of these having epithelial origins. Pathological reporting of these tumors is conducted according to the 5th edition of the World Health Organisation (WHO) classification of thoracic tumours. This study aims to draw the pathologist's attention to four rare, atypical microscopic aspects that some of the most common types of lung malignancies reveal upon standard evaluation (hematoxylin-eosin stain) that make histopathological diagnosis challenging: acantholytic, pseudoangiosarcomatous, signet ring cell, and clear cell features. Each of these aspects was exemplified by a case diagnosed in the pathology department of the "Marius Nasta" Institute. Furthermore, we analyzed the classification dynamics of different WHO editions and used PubMed to review articles written in English and published in the last eleven years on this subject. Pathologists should be familiar with these unusual aspects to avoid misdiagnoses and to ensure the correct classification of tumors, which is extremely important because these tumor phenotypes have been associated with specific molecular alterations and a worse clinical evolution. There is a need to clarify the histogenesis and associated genetic mutations, given the fact that the rarity of these tumor phenotypes makes their study difficult. Some authors consider these to be overlapping entities; however, we do not encourage this, as they may exhibit different prognoses and various molecular alterations with important therapeutic implications. The signet ring cell feature was associated with ALK rearrangement in lung adenocarcinoma; thus, these patients can benefit from tailored therapy with ALK-tyrosine kinase inhibitors (ALK-TKI). Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.
肺癌是发病率和死亡率最高的常见肿瘤之一，其中大多数起源于上皮细胞。这些肿瘤的病理报告是根据世界卫生组织（WHO）第 5 版胸部肿瘤分类进行的。本研究旨在提请病理学家注意四种罕见的、非典型的微观方面，一些最常见的肺癌恶性肿瘤在标准评估（苏木精-伊红染色）中揭示了这些方面，使得组织病理学诊断具有挑战性：棘层松解、假性血管肉瘤样、印戒细胞和透明细胞特征。每个方面都通过在“Marius Nasta”研究所的病理科诊断的一个病例进行了例证。此外，我们分析了不同 WHO 版本的分类动态，并使用 PubMed 回顾了过去十一年间就该主题发表的英文文章。病理学家应该熟悉这些不寻常的方面，以避免误诊并确保肿瘤的正确分类，这一点非常重要，因为这些肿瘤表型与特定的分子改变和更差的临床转归有关。鉴于这些肿瘤表型的罕见性，需要阐明其组织发生和相关的基因突变。一些作者认为这些是重叠的实体；然而，我们不鼓励这样做，因为它们可能表现出不同的预后和各种具有重要治疗意义的分子改变。肺腺癌中的印戒细胞特征与 ALK 重排相关；因此，这些患者可以受益于针对 ALK 酪氨酸激酶抑制剂（ALK-TKI）的靶向治疗。最近的研究将透明细胞形态与 FGFR3-TACC3 融合相关联，提示具有这种诊断的患者可能有资格接受 FGFR 抑制剂治疗。我们首次描述了肺腺癌中假性血管肉瘤样模式；据我们所知，到目前为止，这种方面仅在鳞状细胞癌中有所描述。
