Liquid biopsy perspectives in pleomorphic carcinoma of the lung: case report

Our plain-English summary of Liquid biopsy perspectives in pleomorphic carcinoma of the lung: case report, by T. Rossi, M. Cortesi, M. Zanoni, et al (Translational Lung Cancer Research, 2025).

The study

• Authors: T. Rossi, M. Cortesi, M. Zanoni, S. Bandini, C. Sbrighi, D. Angeli, V. Masciale, G. Grisendi, M. Costantini, F. Stella, P. Ulivi, B. Aramini
• Journal: Translational Lung Cancer Research
• Published: 2025;14(6):2324-2336
• Type of article: Case report
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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.

Cases Description: 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.

Conclusions: 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.

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In plain English

This case report described two men, aged 72 and 75, treated in Forlì, Italy, in 2022 for pleomorphic carcinoma, a rare non-small cell lung cancer. The article does not discuss asbestos. Mesothelioma appears only as a tumor that can be hard to tell apart from this cancer under the microscope. Before surgery, the authors tested each patient's blood for circulating tumor cells and extracellular vesicles (tiny particles released by cells). They also analyzed tumor tissue and compared some results with seven patients who had other lung cancer types. Both patients had clusters of tumor cells joined with white blood cells in the blood: 3 clusters in the first patient and 6 in the second. No common genetic alterations were seen between the two. In the first patient's vesicle sample, the strongest marker signals were for two platelet markers. The first patient had no recurrence at the time of writing. The second died of cancer that returned in the brain 10 months after surgery. The authors said that with only two patients the study was mainly descriptive, and they called for further studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of two patients (blood and tumor tissue laboratory analysis), with descriptive comparison to tumor samples from patients with other lung cancer types
• Who was studied: Two men, aged 72 and 75, who had lung lobectomy for pleomorphic carcinoma of the lung at the Thoracic Surgery Unit of the Morgagni Pierantoni Hospital, Forlì, Italy, in 2022. Comparison samples came from 7 sex- and age-matched patients: adenocarcinoma (n=3), squamous-cell carcinoma (n=2) and neuroendocrine tumors (n=2).
• Exposure: No asbestos or occupational exposure is reported or studied. Both patients were described as heavy smokers (80 packs/year and 120 packs/year, as printed).
• Main results:
  • In tumor tissue, case 2 had 1.44% epithelial cells compared with 18.56% in case 1, and 0.08% stem-type cells compared with 3.33% in case 1.
  • The median epithelial cell population in the two pleomorphic tissues (10%) was lower than in squamous (27.55%), neuroendocrine (82.7%) and adenocarcinoma (71.16%) samples.
  • Blood vesicle concentration was 1.37e+10 particles/mL (mean size 116.9 nm) in case 1 and 6.69e+11 particles/mL (mean size 145 nm) in case 2.
  • In case 1's vesicle sample, the highest measured marker signals were for the platelet-associated markers CD42a (normalized MFI 642.83) and CD41b (normalized MFI 512.09). No statistical comparison was performed.
  • CD3 (a T-cell marker) was absent on vesicles from the two pleomorphic carcinoma patients but present in the other lung cancer groups.
  • Clusters of circulating tumor cells joined with white blood cells were found before surgery: 3 in case 1 and 6 in case 2.
  • In case 2, the genetic changes in the clusters were linked to enrichment of mTOR-related pathways. No common alterations were seen between the two patients.
  • Case 1 was free from recurrence at the time of writing. Case 2 died from brain recurrence 10 months after surgery.
• The authors' conclusion: The authors concluded that the findings suggest immune-evasive properties in pleomorphic carcinoma, marked by platelet-related vesicle markers, specific circulating tumor cell features and genetic changes in pathways such as mTOR. They described the analysis as preliminary and called for further studies.
• Limitations the authors state:
  • Only two patients were studied, which limits statistical power and makes the study primarily descriptive.
  • No statistical comparison was performed because of the small number of cases.
  • Both patients had early-stage disease, so very few circulating tumor cells were detectable. The clustering also limited assessment of cell shape.

Topics

Medical terms in this study, explained in our Lexicon: Liquid Biopsy, Pleomorphic, Carcinoma, ctDNA, Sarcomatoid, Spindle Cell, Mesothelioma, Sarcoma.

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