Moderately to poorly differentiated adenocarcinoma invading a leiomyoma: A case report

Abstract

BACKGROUND

Gastric collision tumors, where neoplasms of different origins coexist, are exceptionally rare. A specific challenge arises when gastric adenocarcinoma directly infiltrates a pre-existing benign mesenchymal tumor. This study aims to evaluate the effectiveness and safety of endoscopic treatment for gastric collision tumors.

CASE SUMMARY

A 59-year-old male presented with a three-year history of recurrent abdominal bloating. Gastroscopy revealed a well-defined, 1.2 cm submucosal bulge in the gastric body, with a central depression. Endoscopic ultrasound showed a heterogeneous, hypoechoic mass originating from the muscularis propria. The patient underwent endoscopic submucosal dissection. Histopathological examination of the complete endoscopic submucosal dissection specimen revealed moderately-to-poorly differentiated adenocarcinoma infiltrating into a spindle cell neoplasm. Immunohistochemistry was crucial for confirmation: The carcinomatous component was positive for cytokeratin-pan, while the spindle cells were positive for smooth muscle actin and desmin, and negative for CD117 and discovered on gastrointestinal stromal tumor-1, confirming a leiomyoma. The final diagnosis was a collision tumor of gastric adenocarcinoma and leiomyoma.

CONCLUSION

This case highlights the critical value of a multimodal diagnostic approach: Endoscopic ultrasound can suggest the possibility of a complex lesion, but only comprehensive histology and immunohistochemistry on the completely excised specimen can establish the diagnosis. Recognizing this rare pathological entity is essential for accurate diagnosis and appropriate clinical management.

Key Words: Submucosal tumor; Gastric leiomyoma; Gastric adenocarcinoma; Overlying; Collision tumor; Immunohistochemistry; Endoscopic submucosal dissection; Case report

Core Tip: Gastric collision tumors featuring adenocarcinoma invading leiomyoma are extremely rare, posing diagnostic and therapeutic challenges. This case describes a 59-year-old male with recurrent abdominal bloating, diagnosed via a multimodal approach: Gastroscopy, endoscopic ultrasound, contrast-enhanced computed tomography, histopathology, and immunohistochemistry. Immunohistochemistry (smooth muscle actin, desmin positivity for leiomyoma; cytokeratin-pan positivity for adenocarcinoma) was pivotal for definitive diagnosis. Endoscopic submucosal dissection (ESD) achieved en bloc resection with uneventful recovery and no recurrence at 8-month follow-up. Notably, the benign leiomyoma may have constrained malignant invasion, facilitating ESD feasibility. This report underscores the necessity of comprehensive diagnostics and supports ESD as a minimally invasive option for localized lesions, warranting further research on the tumor-stroma interaction.

INTRODUCTION

Submucosal tumors (SMTs) are a rare subgroup of gastrointestinal malignancies, accounting for approximately 1% to 2% of all such neoplasms[1-3]. Histologically, gastric SMTs encompass a spectrum of entities, including gastrointestinal stromal tumors (GISTs), leiomyomas, leiomyosarcomas, and schwannomas. Preoperative diagnostic accuracy remains a clinical challenge. This frequently necessitates surgical resection, which serves not only a therapeutic purpose but also provides definitive pathological confirmation[1,4-7].

We report a case of a gastric leiomyoma, a benign smooth muscle tumor constituting about 2.5% of gastric neoplasms[8,9], coexisting with an adenocarcinoma. The lesion presented macroscopically as an ulcerated SMT. The coexistence of an epithelial lesion with a subepithelial tumor, such as a leiomyoma, is highly uncommon. In this case, an accurate diagnosis was established through a combination of endoscopic ultrasound, thoracic imaging, and endoscopic histopathological evaluation.

CASE PRESENTATION

Chief complaints

A 59-year-old Chinese male presented with intermittent abdominal bloating. that had been occurring for 3 years.

History of present illness

The symptoms began insidiously three years prior as postprandial bloating, which the patient did not initially address. He reported no alarm symptoms such as melena, nausea, or vomiting. Recently, his bowel movement frequency increased from once every 2-3 days to daily, but the stools remained formed and yellow. He sought medical attention due to the persistent bloating.

History of past illness

His medical history was negative for tumors or related diseases, and there was no family history of cancer.

Personal and family history

The patient and family histories were negative.

Physical examination

The patient with no other positive signs.

Laboratory examinations

Laboratory tests upon admission revealed several abnormalities, including elevated tumor markers, dyslipidemia, and signs of systemic inflammation (Table 1).

Table 1 Tumor markers.

Marker	Status	Result	Unit	Reference range
Tumor markers
CYFRA21-1	↑	3.95	ng/mL	0.10-3.30
Lipid profile
TC	↑	6.21	mmol/L	< 5.18
TG	↑	1.72	mmol/L	0.56-1.70
HDL-C	↓	1.01	mmol/L	> 1.04
LDL-C	↑	4.44	mmol/L	< 3.37
Apo B	↑	1.46	g/L	0.6-1.4
sdLDL	↑	1.82	mmol/L	0.25-1.17
Inflammation and others
ALB	↓	39.6	g/L	40.0-55.0
Hs-CRP	↑	3.68	mg/L	< 1.00
Serolog
HBcAb	Positive	4.12	IU/mL	0-0.35

TC: Total cholesterol; TG: Triglyceride; HDL-C: High-density lipoprotein; LDL-C: Low-density lipoprotein; Apo B: Apolipoprotein B; sdLDL: Small dense low-density lipoprotein; ALB: Albumin; Hs-CRP: High-sensitivity C-reactive protein; HBcAb: Hepatitis B core antibody.

Imaging examinations

We have improved the electronic gastroscopy, endoscopic ultrasound and enhanced computed tomography (CT) and other related examinations (Figures 1 and 2).

Figure 1 Endoscopic findings. A and B: Visible under white light: A hemispherical mucosal elevation is observed on the posterior wall of the gastric body, measuring approximately 1.5 cm × 2.0 cm in diameter. The surface is depressed with ulceration, covered by a white coating, and the surrounding mucosa appears congested and edematous; C and D: Endoscopic ultrasound findings: The gastric body lesion was hypoechoic, ellipsoid-like, with a still homogeneous internal echo and partially visible hypoechoic, and the size of the slice was about 1.0 cm × 1.0 cm, with a still clear border, originating in the intrinsic muscularis propria layer.

Figure 2 Enhanced gastric computed tomography. The posterior wall of the lower gastric body shows focal nodular thickening measuring approximately 16 mm × 8 mm. On contrast-enhanced imaging, the lesion demonstrates progressive, marked enhancement with heterogeneous filling. The lesion protrudes into the gastric lumen with localized surface indentation. The serosal margin of the lesion appears smooth. No significant perigastric lymphadenopathy is noted. A: Non-contrast; B: Arterial phase; C: Venous phase; D: Delayed phase. Arrow: Location of the lesion.

FINAL DIAGNOSIS

Ulcerative adenocarcinoma of the stomach accompanied by submucosal leiomyoma (Figure 3).

Figure 3 Hematoxylin and eosin staining was performed on the tumor tissue. A and B: The structure of the gastric mucosal glands was disordered, presenting a sieve-like fusion-like change. The glandular epithelial cells are significantly abnormal, manifested as enlarged nuclei, increased nucleoplasmic ratio, disordered cell arrangement, and loss of polarity; C and D: The cancer cells are arranged in an irregular glandular and nest-like pattern, with obvious cell atypia and distinct mitotic signs. The tumor infiltrated into the submucosa and invaded the surrounding leiomyoma tissue. The measured depth of infiltration was approximately 4.26 mm.

TREATMENT

The submucosal bulge, along with the overlying mucosal lesion, was resected en bloc via endoscopic submucosal dissection (ESD). The postoperative course was uneventful, and the patient was discharged on the 11^th postoperative day. Follow-up endoscopy conducted at 8 months revealed no signs of recurrence, and the patient remained asymptomatic (Figure 4, Table 2).

Figure 4 Intraoperative and postoperative images of endoscopic submucosal dissection. A: White-light; B: Peeling along the submucosa; C: Specimen fixation; D: Postoperative wound.

Table 2 Immunohistochemistry.

Marker	Result	Clinical significance
Panel A: Mesenchymal tumor differentiation
SMA	Positive	Supports leiomyoma origin
Desmin	Positive	Supports leiomyoma origin
CD117 (KIT)	Focally positive	Helps rule out GIST
DOG-1	Negative	Helps rule out GIST
SDHB	Intact	Rules out SDH-deficient GIST
CD34	Negative/intact vascular staining	Not typical for GIST in this context/no evidence of lymphovascular invasion identified
S-100	Negative/nerves highlighted	Helps rule out schwannoma/no perineural invasion identified
Panel B: Epithelial tumor characterization
CK7	Positive	Consistent with gastric origin
CK20	Rarely positive	Common profile for gastric adenocarcinoma
Mucin-2	Negative	Suggests intestinal-type differentiation
Mucin 5AC	Focally positive	Suggests gastric/gastrointestinal differentiation
Mucin 6	Rarely positive	Suggests gastric differentiation
CDX-2	Positive	Supports intestinal-type differentiation
Panel C: Proliferation and tumor suppressor markers
Ki-67	1%-5% +/80% (in hotspot regions)	Indicates a high proliferative index
P53	90% positive, located in the cell nucleus. Positive tumor cells account for approximately 85%	Suggests underlying TP53 gene mutation
Her-2	(1+) negative, positive tumor cells account for approximately 10%	May have implications for targeted therapy
MSH-6	(+) located in the cell nucleus. Positive tumor cells account for approximately 10%	The mismatch repair function is missing
MlH-1	(+) located in the cell nucleus. Positive tumor cells account for approximately 95%	Prompt to save the mismatch repair function

SMA: Smooth muscle actin; KIT: Proto-oncogene receptor tyrosine kinase; DOG-1: Discovered on gastrointestinal stromal tumor-1; SDHB: Succinate dehydrogenase B; CK: Cytokeratin; CDX-2: Caudal-type homeobox 2; MSH-6: MutS homolog 6; MlH-1: MutL homolog 1; GIST: Gastrointestinal stromal tumors; SDH: Succinate dehydrogenase.

OUTCOME AND FOLLOW-UP

The postoperative course was uneventful, and the patient was discharged on the 11^th postoperative day. Follow-up endoscopy conducted at 8 months revealed no signs of recurrence, and the patient remained asymptomatic.

DISCUSSION

This case clearly demonstrates that histomorphology alone is insufficient for diagnosing gastric mesenchymal tumors. Immunohistochemistry is not merely an ancillary tool but a fundamental component of the diagnostic workflow. Our experience emphasizes that strictly adhering to a standardized immunohistochemistry (IHC) protocol in clinical practice is crucial. This helps avoid misdiagnosis, guides appropriate surgical intervention, and ultimately optimizes patient outcomes. For future cases, when imaging suggests a mesenchymal tumor, the threshold for performing IHC on biopsy samples should be low to prevent diagnostic and therapeutic pitfalls.

Beyond the initiating carcinogenic mechanism, the proliferating mesenchymal cells within the leiomyoma component play a crucial and active role in tumor biology[10]. Far from being a passive presence, the leiomyoma significantly influences the local microenvironment, immune landscape, and epithelial cell behavior.

First, these mesenchymal cells construct a supportive stromal framework and regulate the extracellular matrix. This provides not only structural integrity but also releases biochemical signals that promote tumor growth and development[11-13].

Furthermore, mesenchymal cells create an immunosuppressive microenvironment by releasing factors like interleukin-10 and transforming growth factor β. This suppresses anti-tumor immune responses and promotes immune evasion, thereby enhancing tumor survival and invasive potential[14]. They also drive fibrosis and tissue remodeling, a process closely associated with the activation of smooth muscle cells within the leiomyoma. This fibrotic response alters tissue architecture, creating a stiffened stroma that fosters a microenvironment conducive to sustained tumor progression and immune evasion[15,16]. Finally, signals from mesenchymal cells can induce epithelial-mesenchymal transition in the adenocarcinoma cells. This fundamental mechanism, which confers a mesenchymal-like phenotype, significantly enhances the cells’ invasive and metastatic capabilities[17,18].

The synchronous occurrence of gastric tumors with different histological types, while gaining increasing recognition, remains a rare phenomenon. Most reported cases involve combinations of gastric adenocarcinoma with neuroendocrine tumors or low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. In contrast, the collision between adenocarcinoma and a mesenchymal tumor, particularly a leiomyoma, is exceedingly rare.

To our knowledge, only one previous case of a true collision tumor composed of gastric adenocarcinoma and leiomyoma has been documented in the English literature[10]. In previous cases, the same examination of biopsy samples showed moderately differentiated adenocarcinoma. The lesion was located at the junction of the esophagus and stomach, so a total gastrectomy and D2 lymph node dissection were performed. The surgical trauma is huge and the recovery time is long. However, in this case, the lesion was located in the body of the stomach. The diagnosis of adenocarcinoma before the surgery had not been confirmed, and the enhanced gastric CT did not show enlarged lymph nodes. So we adopted the ESD surgical method, which is less invasive, has a shorter recovery time and lower cost for the patient.

Critically, the diagnosis of a collision tumor in this case is well-supported by pathological evidence. According to established definitions, a collision tumor is characterized by two morphologically distinct tumor cell populations growing in a “side-by-side” or “overlapping” manner, yet remaining separate from each other[19]. This stands in clear contrast to a composite tumor, where the two tumor components are intimately intermixed without a clear boundary[20]. Distinguishing between these entities can be particularly challenging when both tumors originate from epithelial tissue. However, in our case, the two neoplasms had different origins: The adenocarcinoma was epithelial, and the spindle cell lesion was mesenchymal. Furthermore, histological examination revealed a clear “stacked” spatial relationship between them. This distinct histological separation, coupled with the unique immunophenotypic profile confirming the leiomyoma, strongly supports its classification as a collision tumor.

Preoperatively distinguishing gastric leiomyomas from GISTs remains a significant clinical challenge[21]. As demonstrated in this case, imaging studies alone cannot provide a definitive diagnosis. This diagnostic dilemma carries serious clinical consequences due to the markedly different management strategies for these two tumor types: Leiomyomas are typically benign and may only require conservative resection or surveillance, whereas GISTs possess malignant potential and necessitate complete surgical excision, often supplemented with tyrosine kinase inhibitor therapy for high-risk lesions[22]. Failure to differentiate them preoperatively can lead to overtreatment of benign conditions or, more concerningly, undertreatment of a potentially aggressive malignancy.

In this context, IHC serves as the indispensable gold standard for precise diagnosis. A specific panel of markers provides confirmatory evidence: The vast majority of GISTs (approximately 95%) show strong positivity for KIT (CD117) and/or discovered on GIST-1 (DOG1), with about 70% also expressing CD34. In contrast, leiomyomas are typically negative for these markers. The diagnostic value of this marker panel is particularly evident in rare KIT-negative GISTs. In such cases, diagnosis relies on combining DOG1 and CD34 staining results, supplemented by molecular testing for KIT and PDGFRA gene mutations[23].

The IHC profile in our patient was definitive: The tumor cells showed diffuse positivity for the smooth muscle-specific markers smooth muscle actin (97.2%) and desmin (94.5%), while exhibiting only focal positivity for CD117 and negativity for DOG1 and CD34. This immunophenotype is characteristic of a leiomyoma and effectively rules out a GIST. Furthermore, the observed high proliferation index (Ki67 ≈ 80% in hot spots) and strong p53 positivity (≈ 90%) strongly support the diagnosis of a gastric smooth muscle tumor coexisting with adenocarcinoma.

CONCLUSION

In this case, the benign nature of the gastric leiomyoma was adequately confirmed before surgery. Contrast-enhanced CT revealed a well-defined lesion with an intact adjacent serosal surface and no local lymph node enlargement. Endoscopic ultrasound further verified its origin from the muscularis propria and suggested it was readily separable. These features were crucial for determining the treatment strategy, which ultimately led to the successful en bloc resection of both the submucosal leiomyoma and the overlying moderately-to-poorly differentiated adenocarcinoma via ESD. However, once malignant tumors infiltrate the surrounding tissues or metastasize to the surrounding lymph nodes, etc., we will no longer be able to use ESD to treat the tumors, which greatly limits the application of ESD in such patients.

This case prompts an intriguing hypothesis: Did the underlying leiomyoma exert a protective, constraining effect on the overlying adenocarcinoma? This concept is supported by literature on esophageal leiomyomas, where dense benign stromal tissue has been found to act as a physical barrier, hindering the lateral spread and deep invasion of concurrent squamous cell carcinoma[24,25]. By analogy, we speculate that the gastric leiomyoma in our case may have served a similar function. Its well-demarcated, densely structured smooth muscle proliferation might have mechanically constrained the cancer cells, preventing deep invasion into the gastric wall. This confining effect likely facilitated the success of the ESD procedure by localizing the lesion and may contribute to a favorable prognosis by potentially reducing the risk of deep invasion and subsequent metastasis. To test this hypothesis, further clinicopathological studies are urgently needed to investigate the association between the presence of underlying benign mesenchymal tumors in gastric cancer patients and the depth of tumor invasion, as well as survival outcomes.