Rossi Tania, Cortesi Michela, Zanoni Michele, Bandini Sara, Sbrighi Camilla, Angeli Davide, Masciale Valentina, Grisendi Giulia, Costantini Matteo, Stella Franco, Ulivi Paola, Aramini Beatrice
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
Transl Lung Cancer Res. 2025 Jun 30;14(6):2324-2336. doi: 10.21037/tlcr-2024-1275. Epub 2025 Jun 19.
Liquid biopsy has recently made it possible to use minimally invasive testing to examine tumor-derived material released into peripheral blood, including circulating tumor cells (CTCs), extracellular vesicles (EVs), and circulating tumor deoxyribonucleic acid (ctDNA). Lung pleomorphic carcinoma (PC) is an extremely rare and severe form of cancer. Although resection tissues are the basis for PC diagnosis in everyday practice, tiny biopsies and cytologic specimens might potentially raise suspicions. Because PC may show varied expression of conventional carcinoma markers, it can be particularly challenging to differentiate sarcomatoid (i.e., spindle cell or giant cell) components from other tumor forms, such as sarcomatoid mesothelioma and other sarcomas. We think that defining a more specific context to better understand patient prognosis may be aided by the discovery of blood molecular markers in PC.
We present two cases of patients underwent major lung resection at our center with a diagnosis of PC of the lung; specifically, according with 8th TNM edition, case 1 showed a final pathological stage pathological tumor-node-metastasis (pTNM): pT1cN0G3LV0R0, and case 2 showed a stage pTNM: pT3N0G3LV0R0. Patients were both discharged after surgery with no postoperative complications. Oncologists suggested a 5-year clinical and radiological follow-up, however case 1 patient is free from recurrence at the moment, while case 2 patient died for brain recurrence 10 months after surgery. Immediately after surgical resection, patient's specimens were sent to the pathology unit. The pathologist, without affecting the accuracy of histological diagnosis, selected representative tissue samples and sent them at 4 ℃ in specific media, to Bioscience Laboratory, IRCCS IRST "Dino Amadori" for tissue analysis. Additionally, blood samples collected before surgery were sent for the characterization of CTCs and EVs.
To better characterize the potential relationship between the presence of CTCs, EVs and high grade of malignancy and any subsequent connection to death and/or recurrence, we think that liquid biopsy, which involves the identification and characterization of tumor-derived elements, may serve as future approach and tool not only in NSCLC but also in each specific histotype as for lung PC.
液体活检最近使得通过微创检测来检查释放到外周血中的肿瘤衍生物质成为可能，这些物质包括循环肿瘤细胞（CTC）、细胞外囊泡（EV）和循环肿瘤脱氧核糖核酸（ctDNA）。肺多形性癌（PC）是一种极其罕见且严重的癌症形式。虽然在日常实践中切除组织是PC诊断的基础，但微小活检和细胞学标本可能会引发怀疑。由于PC可能表现出传统癌标志物的不同表达，因此将肉瘤样（即梭形细胞或巨细胞）成分与其他肿瘤形式（如肉瘤样间皮瘤和其他肉瘤）区分开来可能特别具有挑战性。我们认为，发现PC中的血液分子标志物可能有助于定义一个更具体的背景，以更好地了解患者的预后。
我们展示了两例在我们中心接受肺大切除术并被诊断为肺PC的患者；具体而言，根据第8版TNM分期，病例1的最终病理分期为病理肿瘤-淋巴结-转移（pTNM）：pT1cN0G3LV0R0，病例2的分期为pTNM：pT3N0G3LV0R0。两名患者术后均顺利出院，无术后并发症。肿瘤学家建议进行5年的临床和影像学随访，然而病例1的患者目前无复发，而病例2的患者在术后10个月因脑转移死亡。手术切除后，立即将患者的标本送往病理科。病理学家在不影响组织学诊断准确性的情况下，选择代表性组织样本，并在4℃下用特定培养基将其送往IRCCS IRST“迪诺·阿马多里”生物科学实验室进行组织分析。此外，术前采集的血样被送去进行CTC和EV的特征分析。
为了更好地表征CTC、EV的存在与高恶性程度之间的潜在关系以及与任何后续死亡和/或复发的联系，我们认为，涉及肿瘤衍生成分鉴定和表征的液体活检不仅可作为未来非小细胞肺癌（NSCLC）的方法和工具，也可用于肺PC等每种特定组织学类型。
