What is the diagnosis and treatment approach for signet ring cells found on a computed tomography (CT) scan of the thorax?

Signet Ring Cells on CT Thorax

When signet ring cells are identified on CT thorax, the primary concern is distinguishing primary pulmonary signet ring cell adenocarcinoma from metastatic disease, most commonly from gastric or colorectal origin, which requires immediate tissue diagnosis and comprehensive staging to guide treatment.

Diagnostic Approach

Radiologic Findings

The "signet ring sign" on CT thorax typically refers to bronchiectasis (enlarged bronchi appearing larger than accompanying vessels), not signet ring cell carcinoma 1. However, if the clinical context suggests malignancy with signet ring cell morphology:

• Primary lung signet ring cell adenocarcinoma presents as solid nodules or masses ranging 1.0-8 cm, occasionally with multiple nodules 2
• Most cases show solid lesions; cavitation is rare 2
• Multiple enlarged mediastinal and hilar lymph nodes are common 2

Critical Distinction: Primary vs Metastatic Disease

Tissue diagnosis is mandatory before proceeding with treatment, as signet ring cell morphology in the thorax most commonly represents metastatic disease from gastrointestinal primaries 1, 3.

Workup Algorithm:

1. Obtain tissue biopsy (CT-guided or bronchoscopic) for histology and immunohistochemistry 2, 3

2. Immunohistochemical panel to determine origin:

   • Primary lung origin: TTF-1 positive (100% sensitive), CK7 positive, napsin A positive, CK20 negative, CDX2 negative 2, 3
   • Gastric/GI origin: CK20 positive, CDX2 positive, TTF-1 negative 1, 4
   • Require minimum 50-100 viable tumor cells for adequate evaluation 1

3. If GI origin suspected, perform:

   • Upper endoscopy with gastric biopsies 1
   • Colonoscopy 5
   • CT chest/abdomen/pelvis for complete staging 1
   • Consider diagnostic laparoscopy if peritoneal metastases suspected (sensitivity 85%, specificity 100%) 1

4. Evaluate for poorly cohesive/diffuse gastric cancer:

   • Signet ring cell histology has highest CLDN18.2 positivity (48.3%) among gastric cancers 1
   • Peritoneal metastases common with gastric signet ring cell carcinoma 1

Treatment Based on Origin

Primary Lung Signet Ring Cell Adenocarcinoma

• Surgical resection (lobectomy) for stage I disease 2, 3
• Poor prognosis: 6/11 patients died within 1 year in one series 3
• Standard lung cancer staging and treatment protocols apply 2

Metastatic Gastric Signet Ring Cell Carcinoma

• Systemic chemotherapy is primary treatment for metastatic disease 1
• Consider CLDN18.2 testing for targeted therapy eligibility 1
• Peritoneal-directed therapies at specialized centers for peritoneal metastases 1

Metastatic Colorectal Signet Ring Cell Carcinoma

• Standard colorectal cancer protocols based on stage 5
• Test for microsatellite instability and BRAF V600E mutation (strong association) 5
• Adjuvant chemotherapy and radiation per standard guidelines 5

Critical Pitfalls to Avoid

• Do not assume metastatic disease without tissue confirmation - primary lung signet ring cell adenocarcinoma exists but is rare 2, 3
• Ensure adequate tissue sampling: minimum 50-100 viable tumor cells needed for immunohistochemistry 1
• Evaluate H&E-stained slides alongside immunostains to avoid mistaking signet ring cells for inflammatory cells 1
• Only membranous staining counts for biomarker assessment; cytoplasmic staining in signet ring cells can be misleading 1
• CT has low sensitivity (28-51%) for peritoneal metastases from gastric primaries; consider laparoscopy for definitive staging 1