A Rare Case of Squamous Gastric Carcinoma

A 67-year-old man presented to the hospital with progressive shortness of breath for 4 days, which worsened with exertion and was relieved by rest. He also noted one episode of dark vomitus and one episode of melena a few days prior to admission.

History. The patient had a past medical history of hypertension and atrial fibrillation. He denied any change in weight, nausea, abdominal pain, and night sweats. He was not taking any anticoagulants. His family history was non-contributory. He smoked for greater than 30 pack-years and denied alcohol or illicit drug use.

On physical examination, he had marked conjunctival pallor and an irregularly irregular pulse. The rest of the examination was unremarkable, including no palpable abdominal mass, abdominal distension, or lymphadenopathy.

Diagnostic testing. Laboratory studies revealed a hemoglobin of 4.3 g/dL. His anemia was normochromic, normocytic, and without anisocytosis. An abdomen computed tomography (CT) scan with intravenous and oral contrast revealed a 10 cm mass along the lesser curvature of the stomach involving the pancreatic body and tail with encasement of the splenic artery with no perigastric varices (Figure 1). The patient was then transfused with four units of packed red blood cells.

Figure 1. CT of the abdomen showing a 10 cm mass along the lesser curvature of the stomach (red arrow) involving the pancreatic body and tail with encasement of the splenic artery in transverse (A) and coronal plan (B).

An endoscopic examination showed a large, cratered ulcer in the gastric cardia and body of the stomach, which was biopsied (Figure 2). No active bleeding was observed at the time of the examination.

Figure 2. Endoscopy showing a large, cratered ulcer (white arrow) in the gastric cardia and body of the stomach.

Helicobacter pylori returned negative. Pathology results of the biopsy revealed a grade 3 squamous cell gastric carcinoma (Figure 3). Immunohistochemistry staining of the tumor showed CK7+, p63+, b72.3-, MOC31-, CK20-, and CDX2-, consistent with squamous cell gastric carcinoma. The tumor was negative for HER2/neu and PDL-1. Serum tumor markers were collected: carcinoembryonic antigen was 2.8 ng/mL, alpha fetoprotein was 4.9 ng/mL, cancer antigen 125 was 156 units/mL, and cancer antigen 19-9 was 171 units/mL.

Figure 3. The biopsy of ulcerative lesion revealing gastric squamous cell carcinoma.

The patient was initially stabilized and discharged with follow-up with an oncology specialist for treatment, but he was re-admitted a week later due to recurrent hematemesis. At that time, he was transferred to the intensive care unit and a CT angiography of the abdomen showed that the tumor had vessels arising from the common hepatic, left gastric, and splenic arteries. The patient underwent interventional radiology specialist-guided embolization of the left gastric artery resulting in cessation of bleeding. Due to the rarity of this tumor type and location, a repeat endoscopy and biopsy was performed during this readmission, confirming the diagnosis of squamous cell gastric cancer.

A positron emission tomography (PET) scan did not reveal any lymphadenopathy or metastases and the patient was diagnosed at Stage IVA.

Differential diagnosis. Another possible diagnosis that was initially considered was adenocarcinoma of the stomach, which is the more common type of gastric cancer. This differential diagnosis prompted a repeat biopsy of the gastric ulcer. The repeat pathology results revealed that this was the incorrect diagnosis.

Treatment and management. He underwent 10 fractions of 3000 cGy palliative radiation to prevent further gastrointestinal bleeding. The patient was then started on 14 cycles of FOLFOX chemotherapy (fluorouracil 400 mg/m², leucovorin 400 mg/m², and oxaliplatin 85 mg/m²) which was well tolerated.

A repeat CT scan 9 months later showed complete response to neo-adjuvant chemotherapy (Figure 4). The patient underwent surgical resection with an exploratory laparotomy, total gastrectomy with Roux-en-Y esophagojejunostomy, and placement of a jejunostomy tube. Additionally, four negative lymph nodes were resected. The patient did not undergo pancreatic resection.

Figure 4. CT of abdomen pre- and post-chemotherapy. Image (A) shows the tumor prior to treatment (arrow). Image (B) shows marked improvement with apparent resolution of previous gastric tumor after completing FOLFOX chemotherapy and radiation treatment.

Outcome and follow-up. The final pathology report confirmed a complete response to chemotherapy with a benign pancreatic margin and no invasive carcinoma seen in the stomach. The patient is currently in complete remission.

Discussion. Gastric cancer is one of the most common malignancies worldwide, with adenocarcinomas responsible for more than 90% of gastric cancer cases.¹ Primary squamous cell carcinoma is a rare histologic type of stomach cancer with an estimated worldwide incidence of 0.2% of all gastric malignancies, and an estimated 5-year survival rate of 13% to 32%.^2,3 GSCC was first reported by Rörig in 1895⁴ and fewer than 100 cases have been reported in the English literature by 2015.¹ The most common clinical symptoms include non-specific abdominal pain and weight loss.⁵ A recent review of 21 GSCC cases found that 14.4% of patients presented with severe anemia, similar to our patient.⁶ Approximately 47.2% of cases of primary squamous cell carcinoma are diagnosed at stage IV.^2,5 The recent study by Dong and colleagues found that 5-year overall survival for patients diagnosed in stages I, II, III, and IV was estimated to be 80.0%, 67.5%, 39.7%, and 6.0%, respectively.⁷ Compared with patients diagnosed with adenocarcinoma, patients with GSCC were found to have a decreased median survival time.^5,8

Due to the rarity of this type of gastric cancer, there is a paucity of consensus regarding definitive treatment. In a report by Meng and colleagues, multiple systemic chemotherapy treatments including FOLFOX, DOF, and XELOX have been used, with none showing definite efficacy against disease recurrence.⁸ There are a few case reports showing patients who have complete response to chemotherapy; however, different treatment regimens were used.^9,10 Wakabayashi and colleagues found that the majority of patients in the literature were treated with adjuvant chemotherapy and had poor response to treatment.³ Other studies suggest that there is a potentially increased favorable outcome in patients treated with neoadjuvant chemotherapy. However, the current data is not significant.^10–12 Additionally, the use of radiation therapy has not been standardized. Indeed, research shows that it has been used in about one-third of cases of GSSC (both in the adjuvant and neoadjuvant setting) making it difficult to assess its efficacy.² GSCC tumors have been shown to be less sensitive to chemotherapy and radiotherapy compared with adenocarcinoma, therefore these treatments are more often used in a palliative setting rather than curative.

As these tumors tend to respond poorly to chemotherapy, current first-line treatment is surgical resection.^3,5 Current optimal surgical treatment is radical subtotal gastrectomy with Roux-en-Y reconstruction and D2 lymphadenectomy.⁷ There is ongoing discussion about the improved prognosis of surgical resection. For example, Dong and colleagues found that the 5-year overall survival rate is significantly higher in patients who receive surgical resection in single variate analysis but not a significant difference in multivariate analysis, suggesting that physical condition of the patient and selection bias plays a stronger role in prognosis.⁷ Further study into the best treatment regimen for these patients is needed, which is a challenge given the rarity of this cancer.

Our patient presents with a case of primary squamous cell carcinoma, which has responded well to FOLFOX chemotherapy and radiation treatment with appearance of near complete resolution of the tumor on repeat CT scan 9 months later. Additionally, subsequent surgical resection has showed no visible remaining disease. This positive response to treatment may indicate a good prognosis for our patient, as a similar case presented by Yanagisawa and colleagues showed that the patient had no further recurrence.⁹

Conclusion. GSCC is exceedingly rare and presents unique challenges to treatment. Current data suggest that undergoing surgical resection of the tumor is the best treatment option with no specific chemotherapy or radiation therapy regimen identified to improve prognosis. Our patient, however, had complete tumor response to neoadjuvant FOLFOX chemotherapy and palliative radiation and subsequent surgical resection with no visible disease, suggesting a possible improved 5-year overall survival rate. The rarity of the type of cancer and excellent response to neoadjuvant chemotherapy highlights the importance of still considering chemotherapy as an adjunct to definitive surgical resection as it can improve outcomes.