A Unique Metastatic Spread of Lung Adenocarcinoma to the Stomach: A Case Report and Literature Review.

1.
Introduction
Lung cancer is an aggressive tumor, with approximately 50 % of patients showing metastasis at diagnosis. The most common sites for extrapulmonary metastases include the liver, bones, brain, and adrenal glands. Gastrointestinal metastasis is primarily seen in case reports, with clinical incidence ranging from 0.3 % to 1.77 %, while autopsy studies report higher rates of 11.9 %–13.7 %. Specifically, stomach metastasis occurs in 0.19 %–5.1 % of cases, with autopsy findings indicating a higher incidence of 2 %–14 %.1,2 Peng et al.3 report that approximately 20 individuals have developed stomach metastases from SCLC. Because of the rarity of this occurrence, it has not been extensively studied, and its clinical features may be overlooked or misinterpreted. Small cell lung cancer (SCLC) more frequently causes metastases compared to non-small cell lung cancer (NSCLC). While uncommon, gastrointestinal metastases from SCLC can lead to complications such as bleeding, obstruction, or perforation.4 The mechanisms of stomach metastasis remain unclear, but it is believed to primarily occur through the hematogenous and lymphatic pathways of lung cancer. The endoscopic appearance of these metastatic lesions is typically a single ulcerated lesion in the stomach corpus. Diagnosis relies on immunohistochemistry combined with biopsies or EUS-FNA/B. There is no standard treatment for gastric metastases from lung cancer (GMLC); care is tailored to the patient’s condition and pathology. Treatment options include surgery, targeted therapies, chemotherapy (with or without radiation), and supportive care2.

2.
Case report
A 60-year-old Caucasian female with a history of prediabetes, anxiety, hiatal hernia, neuropathy, arthritis, and a 42-pack-year smoking history with a normal annual low-dose CT scan obtained 8 months ago presented to urgent care with three weeks of worsening right shoulder and right-sided chest pain. She also reported chronic dysphagia and finger paresthesia but denied any fever, fatigue, or weight loss. Medications included famotidine, pantoprazole, and gabapentin. Her vitals were temperature 37.1, heart rate 80, blood pressure 120/70, respiratory rate 14, and saturation 96 % on room air. Her BMI was 37.36. She had diminished breath sounds and crackles in the right upper lung on physical examination. Laboratory data showed a white blood cell count of 10,200 cells/μL (reference range 4000–11,000 cells/μL), hemoglobin of 10.2 g/dL (12–16 g/dL), hematocrit of 37 % (36–46 %), platelets of 160,000 μL (150,000–450,000 μL), sodium of 140 mEq/L (135–145 mEq/L), potassium of 4 mEq/L (3.5–5.2 mEq/L), blood urea nitrogen of 29 (6–24 mg/dL), and creatinine of 1.10 (0.6–1.1 mg/dL). Chest X-ray showed a right apical mass with a possible lytic rib lesion. CT chest obtained by primary physician revealed a 7.1 × 5.9 × 6.7 cm right upper lobe RUL mass, mildly enlarged right peri-bronchial nodes, and bilateral pulmonary nodules. She was referred to oncology for further evaluation.
The patient was diagnosed with poorly differentiated, high-grade NSCLC via EBUS-guided biopsy of a right lung mass. Initial pathology suggested a breast origin, but negative mammograms ruled this out, and IHC results (CK7, GATA3, p40 positive; ER, PR, HER2 negative) supported a diagnosis of GATA3-positive lung cancer. The patient was not able to complete the full PET scan. It was obtained till the middle of the chest and did not reveal any metastasis. The brain MRI was unremarkable, too. Tumor board recommended concurrent chemoradiation, initiated with carboplatin/paclitaxel and radiotherapy, followed by cisplatin/etoposide. While on chemotherapy patient had a complete PET scan that showed no overt evidence of metastatic disease. Repeat CT chest, abdomen, and pelvis was obtained 5 months after the initial diagnosis that showed partial response in the RUL mass and radiation pneumonitis; treated with prednisone. Chemotherapy was discontinued due to neutropenia, and radiation was continued.
The patient was then started on durvalumab. He completed 6 cycles of durvulamab, which was after 9 months of initial diagnosis, when repeat CT showed stable disease with no new metastases. A subsequent PET/CT (as in Fig. 1) revealed new FDG-avid gastric lesions. EGD confirmed a malignant gastric ulcer, consistent with metastatic NSCLC. IHC and Tempus testing (comprehensive genomic profiling) supported pulmonary origin, with high PD-L1 expression (90 %, CPS 80), intact MMR, and no targetable mutations.
The patient received palliative gastric radiation (9/10 fractions) and then 6 cycles of chemoimmunotherapy (carboplatin, paclitaxel, pembrolizumab), followed by pembrolizumab maintenance. After 9 maintenance cycles, ctDNA was <0.25 %, and PET/CT (as in Fig. 2) showed no evidence of disease. She remains on maintenance immunotherapy, with no current evidence of disease.

3.
Discussion
Gastric metastasis from non-small cell lung cancer (NSCLC) is an uncommon clinical scenario, with limited data available on its incidence, clinical presentation, and management. According to a systematic review and pooled analysis by Tang et al., the occurrence of gastric metastasis from primary lung cancer is extremely uncommon, with lung adenocarcinoma being the most frequent histological type associated with such metastases.2 Another retrospective study by Taira et al. reported that among 2066 patients with lung cancer, only 0.33 % were diagnosed with gastrointestinal metastasis, and of these, a subset had gastric metastases. 5 Additionally, a retrospective review of 8159 lung cancer patients by Lee et al. found that only 0.26 % developed gastrointestinal metastases, including the stomach.6
The most common primary lung cancer histology associated with gastric metastasis is adenocarcinoma, followed by squamous cell carcinoma and small cell lung cancer.1 Common symptoms include epigastric pain, gastrointestinal bleeding (melena and hematemesis), nausea, and vomiting. Epigastric pain is the most common symptom, reported in 35.8 %–45.5 % of cases. Gastrointestinal bleeding, such as melena (22.7 %) and hematemesis (9.1 %) is frequently observed.7 In some instances, patients may be asymptomatic, and the gastric metastases are discovered incidentally during routine follow-up imaging or evaluations for other conditions. In our case, the initial PET scan showed no evidence of metastatic disease or gastric involvement. However, a follow-up PET scan after initial chemotherapy and immunotherapy revealed abnormal uptake in the gastric region, which was later confirmed through endoscopy. Notably, the patient remained asymptomatic, with no gastrointestinal symptoms.
Endoscopy is the primary diagnostic tool, which can reveal characteristic lesions such as polypoid masses, nodules, or ulcerative lesions in the stomach. Targeted biopsies of suspicious gastric lesions identified during endoscopy are essential.8 Immunohistochemical staining helps confirm the metastatic nature of the lesions from the primary lung tumor. Common markers include TTF-1, CD56, and CgA for small cell lung cancer, and other specific markers depending on the histological type of the primary tumor.9 Positron Emission Tomography (PET) scans are valuable for detecting hypermetabolic nodules in the stomach, which may indicate metastatic disease.
The metastasis of NSCLC to the stomach is driven by multiple mechanisms, including the CXCL12- CXCR4 chemokine axis, which facilitates tumor cell migration. Epithelial-mesenchymal transition (EMT), metabolic reprogramming, and tumor microenvironment interactions further support invasion and survival. Additionally, immune evasion mechanisms enable NSCLC cells to escape immune surveillance and establish gastric metastases.10
Chemotherapy remains a cornerstone in the management of metastatic NSCLC. Regimens such as carboplatin and gemcitabine have been used successfully in cases with gastric metastasis, as in Ohashi et al., where a patient achieved long-term survival following this regimen. Another case reported by Catalano et al. showed a complete response to gemcitabine monotherapy after surgical resection of gastric metastasis.11,12
For patients with specific genetic mutations, targeted therapies can be highly effective. For instance, patients with EGFR mutations may benefit from EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib or osimertinib. Liu et al. reported a case where a patient with EGFR-mutant NSCLC and gastric metastasis responded to osimertinib and subsequent chemotherapy.13 Surgical resection of gastric metastasis can be considered in selected patients, particularly those with solitary metastasis and good performance status.6
Literature specifically addressing the use of immunotherapy in NSCLC with gastric metastasis is limited. However, immunotherapy plays a major role in advanced metastatic NSCLC, with several agents demonstrating efficacy in improving patient outcomes. For patients with high PD-L1 expression (≥50 %), PD-1/PD-L1 monotherapy, particularly pembrolizumab, is recommended as a first-line treatment due to significant survival benefits. For those with lower PD-L1 expression (1 %–49 %), a combination of platinum-based chemotherapy and immunotherapy is preferred, as evidenced by the KEYNOTE-189 trial showing improved survival with Pembrolizumab plus chemotherapy.14 For unresectable Stage III NSCLC, durvalumab is recommended as consolidation therapy after cCRT, significantly improving PFS and OS per the PACIFIC trial. In metastatic NSCLC, the POSEIDON trial supports durvalumab with tremelimumab and chemotherapy for better outcomes.15,16
Prognosis for patients with gastric metastasis from NSCLC is generally poor, with median survival times ranging from a few months to just over a year, depending on the extent of metastasis and the treatment modalities employed. According to Tang et al., the median overall survival time is approximately 11 months, with a median survival time of 4.5 months after the diagnosis of metastatic cancer.2 These figures highlight the aggressive nature of NSCLC with gastric metastases and the poor prognosis associated with this condition.

4.
Conclusion
Gastric metastasis from NSCLC is uncommon (<0.5 %) and typically silent, hindering early detection. Prognosis is poor, with a median survival of only a few months. Careful monitoring in advanced cases is crucial to detect unusual metastatic sites. Tailored approaches, including surgery and systemic therapy, may help manage symptoms and prolong survival. Additional research is needed to inform future diagnostic and therapeutic strategies.