Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive system (1). The histological appearance of GISTs is mainly characterized by spindle-shaped cells (2). Morphologically, epithelioid cells, palisaded–vacuolated cells, and sclerotic patterns may also be present (2). GISTs generally express positive indicators such as CD117 and DOG1 according to immunohistochemistry (IHC) staining (3).

Small cell carcinoma is a type of neuroendocrine carcinoma. When small cell carcinoma occurs in the lung, it can also be known as small cell lung cancer (SCLC). SCLC accounts for approximately 15% of all lung cancers (4). In SCLC, finely granular nuclear chromatin, absent nucleoli, and common fusiform shapes are histologically found, and the nuclear/cytoplasmic ratio is generally high (5). In terms of IHC staining, SCLC is usually positive for thyroid transcription factor-1 (TTF-1), cytokeratin (CK), and synaptophysin (Syn) (6, 7).

SCLC commonly metastasizes to the brain, bones, liver, and adrenal glands (8), but the metastasis of SCLC to other solid tumors is not commonly reported. GISTs have been reported to accompany SCLC (9). However, small cell carcinoma infiltrating GISTs has not been found.

SCLC often metastasizes to the bone and the brain in advanced stages (10). Metastasis to other sites is rare. Only a few studies have reported GISTs with neuroendocrine carcinoma components. Phan et al. (9) reported on a patient with pancreatic GIST and limited-stage SCLC. However, this patient’s GIST and SCLC occurred in two different lesion tissues. Our patient suffered from advanced-stage SCLC. The pathological features of our patient corroborate the aggressiveness of small cell carcinoma: it may invade less malignant tumors. A patient with simultaneous poorly differentiated neuroendocrine carcinoma and GIST of the stomach was identified by Ding et al. (11). These authors explained this phenomenon by the fact that GISTs and neuroendocrine tumors (NETs) have some commonalities in their immunoreactivity profiles, which could indicate a common oncogenic mechanism for neuroendocrine cancer and GISTs (11). Their cases had a histological pattern typical of GIST. Moreover, the expression of IHC in the neuroendocrine carcinoma was similar to that of our patient. The difference was that, in their cases, the neuroendocrine carcinoma did not invade the GIST. Our case likely presented metastasis from the primary tumor in the left lung, which led to the GIST being infiltrated by small cell carcinoma.

The literature shows that GIST and neuroendocrine carcinoma have some common immunophenotypes. CD117 and DOG1 positivity is commonly used clinically to aid in the diagnosis of GIST (12). However, Akintola-Ogunremi et al. (13) demonstrated that CD117 is expressed in some neuroendocrine carcinomas and has potential therapeutic implications. Marando et al. (14) reported a statistically significant correlation between DOG1 expression and neuroendocrine tumors of the gastrointestinal tract. This evidence may suggest that it is not a coincidence that our case of GIST was infiltrated by small cell neuroendocrine carcinoma. GISTs could also coexist with a single well-differentiated, sporadic, small NET (15).

The metastasis and infiltration of SCLC into the GIST in our patient may not have been coincidental. Thus, the potential underlying mechanism was explored based on previous studies. An in vivo experiment on SCLC showed that tumors are generally composed of phenotypically distinct cells characterized by neuroendocrine or mesenchymal markers, and these cells have a common origin (16). The biological behavior of tumor cells is affected by the crosstalk between mesenchymal and neuroendocrine cells. Mesenchymal cells can confer metastatic capacity on neuroendocrine cells (16). GISTs are tumors derived from mesenchymal cells. This might represent a potential connection. Genetically, GIST and SCLC share some commonly mutated genes, such as FGFR1 and KIT (17, 18). The diseases also share abnormal expression of some molecules in common pathways such as PI3K/AKT and MAPK (19–21).

Moreover, SCLC is highly vascularized, and angiogenesis greatly contributes to its metastatic process (22). Small cell carcinomas could metastasize via the bloodstream with a tumor-homing effect and are more likely to grow in the setting of gastrointestinal mesenchymal tumors. Epithelial-to-mesenchymal transition (EMT) could also play an important role in the metastasis of small cell carcinoma. A study of drug responses in small cell carcinoma revealed that it partly exhibits features of EMT (23). In this process, small cell carcinomas may express chemokines that target the GIST. The molecular and cellular mechanisms of small cell carcinoma homing and EMT in specific environments are poorly understood.

Exploring these mechanisms could lead to the design of better treatments for patients with poorly differentiated small cell carcinoma. However, our case is an isolated one. Our findings do not rule out the possibility that these tumors occurred coincidentally. More experiments are needed to ascertain the link between the two diseases. The patient had been treated with chemotherapy for SCLC for several months prior to undergoing resection of the GIST. This may have led to necrosis in the area infiltrated by the small cell carcinoma in the GIST, causing the GIST to rupture. Hence, the small cell carcinoma infiltrating area became a range of necrosis in the resection specimens. It is difficult to explore the mechanisms in resection specimens.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by Ethics Committee of the Second Affiliated Hospital of Dalian Medical University. The studies were conducted in accordance with the local legislation and institutional requirements. The human samples used in this study were acquired from a by-product of routine care or industry. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

YZ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Writing – original draft, Writing – review & editing. LS: Supervision, Validation, Visualization, Writing – review & editing. LL: Conceptualization, Resources, Validation, Writing – review & editing. SL: Conceptualization, Resources, Validation, Writing – review & editing. QW: Conceptualization, Methodology, Project administration, Resources, Supervision, Validation, Writing – review & editing.