Case Report: Synchronous SCLC and minimally invasive adenocarcinoma in the same lobe: NGS-confirmed cross-histological molecular heterogeneity in an ultra-rare case

Vollständiger Abstract

Worum geht es in dieser Arbeit?

A 73-year-old male was diagnosed with synchronous multiple primary lung cancer (sMPLC) involving small cell lung cancer (SCLC) and minimally invasive adenocarcinoma in the right upper lobe—an ultra-rare entity accounting for only 2.0% of all lung cancers, with cross-histological (SCLC + adenocarcinoma) same-lobe presentation reported in fewer than 10 cases globally to date. Notably, the SCLC component exhibited striking aggressiveness and diagnostic mimicry: it initially presented as a 0.3cm tiny nodule with benign imaging features (clear borders, no lobulation), which was consistent with “low-risk nodule” criteria per clinical guidelines, yet rapidly progressed to 1.8cm×1.5cm×1cm within 1 year (a 31-fold volume increase). The patient underwent single-port video-assisted thoracoscopic right upper lobectomy combined with mediastinal lymph node dissection. Pathological examination confirmed: Nodule 1 (the progressed lesion) was peripheral SCLC with airway spread (Syn, CgA, CD56 positive); Nodule 2 (0.8cm×0.4cm×0.3cm) was peripheral minimally invasive adenocarcinoma with predominant lepidic growth pattern (TTF-1, Napsin A positive). No mediastinal lymph node metastasis was detected (Groups 2 + 4/7/10-14, 0/15). Next-generation sequencing (NGS) of mixed tissue from both lesions revealed an EGFR exon21 c.2573T>G mutation (p.L858R, 0.46%, OncoKB Level 1 sensitivity) and a TP53 exon8 c.820G>T mutation (p.V274F, 79.5%), with no RB1 mutation detected; although this is consistent with de novo SCLC, it is insufficient to exclude transformation given that 20–30% of confirmed T-SCLC cases lack RB1 mutations. Four cycles of postoperative etoposide plus cisplatin chemotherapy were well tolerated, with no severe adverse events. Eight-month follow-up showed no tumor progression; a slight elevation of progastrin-releasing peptide (ProGRP, 136.70ng/L) was considered a postoperative transient fluctuation. This case highlights the extreme rarity of same-lobe cross-histological synchronous SCLC and adenocarcinoma, as well as the “benign mimicry” and ultra-fast progression of small-volume SCLC—key pitfalls in preoperative diagnosis. Preoperative multimodal evaluation, postoperative immunohistochemistry, and NGS facilitate accurate diagnosis, while single-port thoracoscopy combined with platinum-based chemotherapy constitutes a safe and effective treatment strategy.