What is the prognosis and treatment approach for a young adult with no significant past medical history diagnosed with signet cell colon cancer?

Signet Ring Cell Colon Cancer: Highly Aggressive with Poor Prognosis

Signet ring cell carcinoma (SRCC) of the colon is an exceptionally aggressive malignancy with dismal outcomes, particularly in young adults, who paradoxically experience worse survival than older patients despite younger age typically being protective in conventional colon cancer. 1, 2

Disease Characteristics and Aggressiveness

Epidemiology and Presentation

• SRCC accounts for less than 1% of all colorectal cancers but is disproportionately more common in adolescents and young adults (AYA) compared to older populations 3, 4, 2
• The incidence is rising in the AYA population despite overall declining colorectal cancer rates in older adults 3, 4
• Patients typically present with advanced disease at diagnosis, with stage IV disease being common even in young patients 3, 4, 5
• Right-sided colon involvement is more frequent, and peritoneal carcinomatosis is a characteristic metastatic pattern 6, 5, 2

Histologic Features Associated with Poor Prognosis

• Higher incidence of mucinous histology and signet ring cells in young adults with colon cancer 6
• More frequent microsatellite instability (MSI) in this population, though this does not translate to better outcomes in SRCC 6
• SRCC demonstrates distinct clinical behavior with unconventional histologic characteristics compared to standard adenocarcinoma 3, 4

Prognosis: Exceptionally Poor

Survival Data

• Five-year overall survival ranges from 0% to 46%, representing one of the worst prognoses among colorectal cancer subtypes 2
• Stage-corrected outcomes are significantly worse than both mucinous and standard adenocarcinoma 2
• Younger patients (≤35 years) with SRCC paradoxically have WORSE survival than older patients (HR 1.411,95% CI 1.032-1.929, P=0.031), which is the opposite of conventional colon cancer where youth is protective 1

Factors Contributing to Poor Prognosis

• Higher percentage of stage III and N2 nodal disease in patients ≤35 years 1
• Advanced stage at presentation is the rule rather than exception 3, 4, 5
• Lower rates of curative resection (21%-82%) compared to other histological types 2
• Frequent peritoneal involvement limits surgical options 5, 2

Treatment Approach

Diagnostic Workup

• Systematic exploratory laparoscopy should be considered to determine the presence of peritoneal metastases, as imaging may underestimate peritoneal disease 2
• Comprehensive staging with CT chest/abdomen is essential 6
• Mismatch repair (MMR) testing should be performed on all young patients with colon cancer, as higher prevalence of Lynch syndrome exists in early-onset colorectal cancer, though MSI-H status in SRCC does not confer the same favorable prognosis 6

Surgical Management

• Surgery remains the mainstay of treatment when feasible, though curative resection rates are disappointingly low 2
• Standard oncologic resection principles apply: adequate lymphadenectomy is mandatory 7
• Extended surgical resections are NOT recommended based on young age alone—clearing colonoscopy should be performed to avoid unnecessary extensive resection 6
• For peritoneal metastases, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) should only be offered to highly selected patients, as routine HIPEC is not recommended for colorectal peritoneal metastases 6

Systemic Therapy

• Aggressive adjuvant chemotherapy is commonly administered to young adults with colorectal cancer, though evidence for survival benefit specifically in this population is lacking 6
• Standard regimens include FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil) as demonstrated in the case reports 5
• For metastatic disease, doublet or triplet chemotherapy should be offered based on performance status 6
• If MSI-H/dMMR is confirmed, pembrolizumab immunotherapy is recommended in the first-line metastatic setting 6
• For MSS/pMMR left-sided tumors with RAS wild-type, chemotherapy plus anti-EGFR therapy is recommended 6
• For MSS/pMMR right-sided tumors with RAS wild-type, chemotherapy plus anti-VEGF therapy is preferred 6

Critical Pitfalls to Avoid

• Do not assume younger age confers better prognosis in SRCC—the opposite is true 1
• Rule out metastatic gastric signet ring cell carcinoma, as this is the main differential diagnosis and requires different management 5, 2
• Do not perform extended colectomy based solely on young age without clear indication 6
• Do not routinely offer HIPEC for peritoneal disease—highly selective use only 6

Surveillance and Long-Term Management

• Intensive surveillance during the first 2-3 years is critical, as this is when most recurrences occur and when curative salvage is most feasible 8
• Continue post-treatment surveillance indefinitely—do not discharge young patients from follow-up 6
• Screen for Lynch syndrome and other hereditary cancer syndromes, as these require specialized surveillance protocols 6

Special Considerations for Young Adults

Association with Inflammatory Bowel Disease

• SRCC can arise in the setting of ulcerative colitis, adding complexity to management 5
• When ulcerative colitis is present, follow disease-specific surveillance guidelines 6

Psychosocial and Practical Concerns

• Address insurance security, as young adults risk losing coverage (aging out of parents' insurance, employment changes) 6
• Consider fertility preservation discussions before initiating chemotherapy 6
• Assess need for child care and transportation assistance 6

The bottom line: Signet ring cell colon cancer in young adults is a devastating diagnosis with 5-year survival often below 50%, advanced stage at presentation, and paradoxically worse outcomes in the youngest patients. Aggressive multimodal therapy with surgery when feasible and systemic chemotherapy is warranted, but expectations must be realistic given the dismal prognosis. 1, 2