Clinical analysis of 23 patients pathologically diagnosed with primary and secondary pulmonary enteric adenocarcinoma
Rare lung cancers often pose unique diagnostic challenges—especially when they mimic other diseases or spread from organs outside the lungs. A 2019 study by researchers from Fujian Medical University and the 900th Hospital of the Joint Logistic Support Force in China aimed to untangle one such puzzle: distinguishing between primary pulmonary enteric adenocarcinoma (P-PEAC), which starts in the lung, and secondary pulmonary enteric adenocarcinoma (S-PEAC), which spreads to the lung from another organ like the colon, rectum, or stomach.
The team reviewed data from 23 patients diagnosed with PEAC between January 2013 and December 2018: 15 with P-PEAC (cancer originating in the lung) and 8 with S-PEAC (cancer metastasizing to the lung from organs including the colon [2 cases], rectum [2], stomach [3], and bile duct [1]). All patients underwent biopsy, imaging (CT, PET-CT, or endoscopy), and molecular testing to confirm their diagnosis.
Demographics and Symptoms: Similar, But Not Specific
Both groups were comparable in age (average 59 for P-PEAC, 60 for S-PEAC) and gender (more men, but no statistically significant difference). Most patients—13 with P-PEAC and 3 with S-PEAC—reported symptoms like cough, chest tightness, fatigue, or hemoptysis (coughing up blood). Cough was the most common complaint, but it wasn’t unique to either type of PEAC—meaning it couldn’t help doctors tell them apart.
Tumor markers like carcinoembryonic antigen (CEA) and CA19-9 were elevated in over half of patients (71% of P-PEAC and 75% of S-PEAC for CEA), but these markers also failed to distinguish between primary and secondary disease. They simply signaled the presence of cancer, not its origin.
Imaging: Hard to Tell Apart
Most patients (12/15 P-PEAC, 6/8 S-PEAC) had single lung lesions, often in the left lung. Chest CT scans showed masses, nodules, or pneumonia-like infiltrates—but the patterns were too similar to reliably differentiate P-PEAC from S-PEAC. The team noted that S-PEAC (a metastatic cancer) typically causes scattered nodules in the lower lungs, but their small sample size (only 8 S-PEAC patients) limited further analysis of CT findings.
Key Clues: Immunohistochemistry and Molecular Testing
The biggest breakthroughs came from two advanced tools: immunohistochemistry (using protein markers to identify cell types) and molecular testing (looking for gene mutations linked to cancer growth).
Immunohistochemistry: Markers That Tell a Story
PEAC gets its name from “enteric” (gut-like) features, so the team tested for markers of enteric cells (CDX2, CK20, MUC2) and lung cells (CK7, thyroid transcription factor 1 [TTF-1], NapsinA). Here’s what they found:
- P-PEAC: Retained “lung identity”—47% were positive for TTF-1 (a lung-specific protein) and 93% for CK7. Enteric markers were weaker (36% CK20, 0% MUC2).
- S-PEAC: No lung markers (0% TTF-1) but strong enteric features (100% CK20, 83% MUC2).
- Villin: A surprise finding—100% of both P-PEAC and S-PEAC patients tested positive, suggesting it could be a universal marker for PEAC.
Molecular Testing: KRAS Mutations Stand Out
Compared to typical lung adenocarcinomas, P-PEAC patients had a higher rate of KRAS gene mutations—a known driver of cancer growth. The team analyzed published data (from PubMed and CBM databases) and found that P-PEAC patients had a 43% KRAS mutation rate (vs. 8-10% in Chinese lung cancer patients overall). In their own study, 3 of 15 P-PEAC patients had KRAS mutations (none of the S-PEAC patients did).
EGFR mutations—common in Asian lung cancer patients—were rare in P-PEAC (only 4% in published data), further distinguishing it from typical lung cancer.
Why This Matters for Diagnosis and Treatment
Accurately distinguishing P-PEAC from S-PEAC is critical:
- P-PEAC is treated like a primary lung cancer (surgery, chemotherapy, or targeted therapy if mutations are present).
- S-PEAC requires targeting the original tumor (e.g., colon cancer drugs for S-PEAC from the colon).
The study confirms that basic tests (symptoms, imaging, tumor markers) aren’t enough. Instead, immunohistochemistry (especially TTF-1 and CK20) and KRAS status are key to making the right call.
Limitations and Next Steps
The study’s small size (23 patients) limits how broadly its findings apply, but it’s a vital step forward for diagnosing this rare cancer. The authors call for larger studies to refine targeted therapies for P-PEAC—especially since KRAS mutations are common and EGFR (a common target in lung cancer) is not.
The study was published in the Chinese Medical Journal in 2019 by Lei Gu, Xu-Zhou Wang, Wen Wen, and colleagues from Fujian Medical University and the 900th Hospital of the Joint Logistic Support Force.
doi.org/10.1097/CM9.0000000000000266
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