Treatment of Signet Ring Cell Gastric Carcinoma
For localized signet ring cell gastric adenocarcinoma, surgery alone with D2 lymphadenectomy is the recommended initial treatment, as perioperative chemotherapy provides no survival benefit and is associated with worse outcomes in this specific histologic subtype. 1
Stage-Specific Treatment Algorithm
Very Early Disease (T1a, Intramucosal)
Endoscopic submucosal dissection (ESD) is NOT recommended for signet ring cell carcinoma, even for small early lesions. 1 These tumors are characteristically multifocal and occur throughout the stomach, making endoscopic or limited resection inappropriate despite meeting size criteria. 1
Surgical resection with D2 lymphadenectomy is required even for T1a lesions due to the multifocal nature of signet ring cell histology. 1
For pT1aN0 tumors after complete R0 resection, observation without additional adjuvant treatment is appropriate. 1
Localized Resectable Disease (Stage IB and Above)
Critical distinction: Unlike other gastric adenocarcinoma histologies, signet ring cell carcinoma should be treated with surgery alone rather than perioperative chemotherapy. 1
Surgical Principles
Complete R0 resection with D2 lymphadenectomy is essential, as negative margins are the most critical prognostic factor. 1
A minimum of 14 lymph nodes, optimally at least 25, should be examined pathologically. 2
Subtotal gastrectomy is appropriate for distal tumors; total gastrectomy is required for proximal lesions. 1
Splenectomy should not be performed unless the tumor directly invades the spleen, as it increases morbidity without oncologic benefit. 3
Laparoscopy with or without peritoneal washings should be performed preoperatively in all potentially resectable cases to exclude occult peritoneal metastases. 2
Hereditary Diffuse Gastric Cancer (CDH1 Germline Mutations)
For patients with CDH1 germline pathogenic variants, prophylactic total gastrectomy between ages 20-30 years is the only effective prevention strategy. 1
D1 lymphadenectomy is recommended as a pragmatic compromise for prophylactic procedures. 1
Baseline endoscopy is mandatory before prophylactic surgery to exclude established cancer requiring neoadjuvant treatment. 1
Metastatic or Unresectable Disease (Stage IV)
For unresectable or metastatic signet ring cell carcinoma, systemic chemotherapy is recommended despite poor response rates in this histology. 1
First-Line Chemotherapy Options
Docetaxel 75 mg/m² + cisplatin 75 mg/m² (day 1) + fluorouracil 750 mg/m²/day continuous infusion for 5 days, repeated every 3 weeks. 4
Alternative regimens include fluoropyrimidine-platinum combinations, though response rates remain poor in signet ring cell histology. 2, 1
HER2 testing must be performed, as trastuzumab plus chemotherapy is indicated for HER2-positive disease. 1
Supportive Care
Best supportive care alone is appropriate for patients with poor performance status. 1
Palliative chemotherapy should only be offered to patients with adequate performance status. 2
Critical Pitfalls to Avoid
Do not attempt endoscopic resection even for small, early-stage lesions that meet standard ESD criteria. 1 The multifocal nature of signet ring cell carcinoma makes this approach inappropriate regardless of lesion size or depth.
Do not use perioperative chemotherapy protocols (ECF/ECX regimens) that are standard for other gastric adenocarcinomas. 1 These provide no survival benefit and worsen outcomes in signet ring cell histology.
Do not proceed to surgery without staging laparoscopy in potentially resectable cases. 2 Imaging frequently misses peritoneal metastases that would change management.
Do not accept inadequate lymph node evaluation (fewer than 14 nodes examined). 2 This leads to understaging and suboptimal treatment planning.
Nuances in the Evidence
The evidence demonstrates a critical histology-specific treatment difference: while ESMO guidelines recommend perioperative chemotherapy (ECF regimen) for most gastric adenocarcinomas 2, the American College of Surgeons specifically recommends against this approach for signet ring cell histology due to lack of benefit and worse outcomes. 1 This represents an important exception to general gastric cancer treatment algorithms.
Early-stage signet ring cell carcinoma (T1a) has favorable prognosis with low lymph node metastasis rates (10.7%) and excellent 5-year survival (96.1%) after surgical resection. 5 However, the multifocal nature of these lesions precludes endoscopic management despite meeting traditional size and depth criteria. 1