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Background <p>Non-small cell lung carcinoma (NSCLC) with co-expression of thyroid transcription factor-1 and p40 is an extremely rare and diagnostically challenging subtype. These tumors exhibit both glandular and squamous features, which reflect a dual-lineage differentiation pattern.</p> Case presentation <p>A 78-year-old male with a history of smoking and alcohol consumption was found to have a solid nodule in the right peripheral lung on CT. Postoperative pathology confirmed that the solid nodule was poorly differentiated NSCLC with diffused and strong positivity for both thyroid transcription factor-1 and p40 by immunohistochemistry. Next-generation sequencing identified somatic mutations of <i>LRP1B</i> and <i>TP53</i>, along with copy number amplification of <i>TP63</i> and <i>SOX2</i> as well as copy number loss of <i>CDKN2A/B</i>.</p> Conclusions <p>NSCLC with co-expression of Thyroid Transcription Factor-1 and p40 is a rare and diagnostically challenging subtype, most frequently observed in older male patients with a history of smoking and predominantly arising in peripheral lung regions. The morphological, immunophenotypic and molecular features of these tumors suggest that they may originate from stem-like basal cells with dual-lineage differentiation. Literature review identified high-frequency alterations in <i>TP53</i>, <i>FGFR1</i>, <i>CDKN2A</i>, <i>EGFR</i>, <i>KRAS</i>, <i>MYC</i>, <i>NF1</i> and <i>AKT1</i>. Next-generation sequencing-based genomic profiling facilitate the diagnosis and treatment of such cases.</p>

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Non-small cell lung carcinoma with co-expression of thyroid transcription factor-1 and p40: a case report and literature review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月24日

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  • Chusheng Wei,
  • Yishan Wang,
  • Weijia Lu,
  • Bi-yun Lin,
  • Danhui Gan,
  • Yuanzhi Lu

摘要

Background

Non-small cell lung carcinoma (NSCLC) with co-expression of thyroid transcription factor-1 and p40 is an extremely rare and diagnostically challenging subtype. These tumors exhibit both glandular and squamous features, which reflect a dual-lineage differentiation pattern.

Case presentation

A 78-year-old male with a history of smoking and alcohol consumption was found to have a solid nodule in the right peripheral lung on CT. Postoperative pathology confirmed that the solid nodule was poorly differentiated NSCLC with diffused and strong positivity for both thyroid transcription factor-1 and p40 by immunohistochemistry. Next-generation sequencing identified somatic mutations of LRP1B and TP53, along with copy number amplification of TP63 and SOX2 as well as copy number loss of CDKN2A/B.

Conclusions

NSCLC with co-expression of Thyroid Transcription Factor-1 and p40 is a rare and diagnostically challenging subtype, most frequently observed in older male patients with a history of smoking and predominantly arising in peripheral lung regions. The morphological, immunophenotypic and molecular features of these tumors suggest that they may originate from stem-like basal cells with dual-lineage differentiation. Literature review identified high-frequency alterations in TP53, FGFR1, CDKN2A, EGFR, KRAS, MYC, NF1 and AKT1. Next-generation sequencing-based genomic profiling facilitate the diagnosis and treatment of such cases.