Clinical Analysis of 23 Patients Pathologically Diagnosed with Primary and Secondary Pulmonary Enteric Adenocarcinoma
Primary pulmonary enteric adenocarcinoma (P-PEAC) is a rare variant of lung adenocarcinoma, classified under invasive mucinous adenocarcinoma, colloid adenocarcinoma, and fetal adenocarcinoma by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This type of lung adenocarcinoma is often confused with secondary pulmonary enteric adenocarcinoma (S-PEAC), which manifests as pulmonary infiltration. To address this confusion, a retrospective study was conducted to investigate the differences in clinical manifestations, imaging presentations, immunohistochemical staining, and molecular pathological characteristics between P-PEAC and S-PEAC.
The study reviewed data from inpatients diagnosed with PEAC at the 900th Hospital of the Joint Logistic Support Force, People’s Liberation Army, Fujian, China, between January 2013 and December 2018. A total of 23 patients were included, comprising 15 P-PEAC patients and eight S-PEAC patients. All patients underwent histological and immunopathological examinations to confirm their diagnoses. The P-PEAC patients were divided into two groups based on clinical tumor-node-metastasis (TNM) staging: early stage (I/II) and late stage (III/IV). The primary tumors of the eight S-PEAC patients were identified through physical examinations, including computed tomography (CT), fluorodeoxyglucose-positron emission tomography, or fiber-optic gastrointestinal endoscopy. The primary tumors included colon cancer (two cases), rectal cancer (two cases), gastric cancer (three cases), and cholangiocarcinoma (one case). By the end of the study on January 10, 2019, six patients had died, and six were lost to follow-up, with follow-up periods ranging from 8 to 56 months.
The age of P-PEAC patients (nine males and six females) ranged from 44 to 72 years, with a mean age of 59 ± 8 years. The age of S-PEAC patients (six males and two females) ranged from 41 to 76 years, with a mean age of 60 ± 11 years. There was no significant difference in gender (P = 0.495) or age of onset (P = 0.793) between the two groups. Among the P-PEAC patients, 13 had at least one clinical symptom, including cough, expectoration, hemoptysis, chest tightness, chest pain, dyspnea, fever, night sweats, throat discomfort, headache, fatigue, and enlargement of cervical lymph nodes. Among the S-PEAC patients, three had similar symptoms. Cough was the most common symptom but was not specific to either group. The positive rates of tumor markers carcinoembryonic antigen (CEA), CA19-9, and CA-125 were 71% (10/14), 50% (5/10), and 50% (5/10) in P-PEAC patients, and 75% (6/8), 67% (4/6), and 33% (2/6) in S-PEAC patients, respectively. Although CEA and CA19-9 levels were elevated in more than half of the patients, there was no significant difference between the two groups (CEA, P = 0.683; CA19-9, P = 0.547).
Lung lesions in most patients were predominantly single and distributed in the left lung (10/18), whether P-PEAC (12/15) or S-PEAC (6/8). Chest CT imaging revealed a variety of lesions, including masses (11/15 in P-PEAC vs. 3/8 in S-PEAC), nodules (3/15 in P-PEAC vs. 4/8 in S-PEAC), and limiting or diffuse pneumonic infiltrates. The imaging differences between the two diseases were minimal. S-PEAC is essentially a metastatic pulmonary cancer characterized by scattered nodules distributed in the basal lung area on chest CT imaging. When the number of pulmonary metastases is few, nodules are usually located in the peripheral lung field. However, with only eight cases available, the study provided limited insight into the distributions and shapes of chest CT imaging in S-PEAC patients.
P-PEAC shares some morphologic and immunohistochemical appearances with pulmonary adenocarcinoma and S-PEAC, making the differential diagnosis challenging. Histologic subtyping can be used to distinguish P-PEAC from S-PEAC, which is essentially intrapulmonary metastasis. For immunohistochemistry, P-PEAC expresses at least one of the enteric differentiation markers, including Caudal Type Homeobox 2 (CDX2), cytokeratin (CK) 20, and mucin 2 (MUC2), with lung adenocarcinoma markers (such as CK7 and thyroid transcription factor 1 [TTF-1]) being consistently positive in almost half the cases. In this study, the expression rates of CK20, MUC2, CDX2, Villin, CK7, TTF-1, and NapsinA were summarized as follows: 36%, 0%, 89%, 100%, 93%, 47%, and 39% in P-PEAC, and 100%, 83%, 100%, 100%, 50%, 0%, and 33% in S-PEAC. The results suggested that Villin also serves as a common marker for PEAC.
The study found that the positive rate of KRAS mutations in P-PEAC patients was higher compared to usual lung adenocarcinoma, based on data from published cases on P-PEAC up to December 31, 2018. Specifically, the positive rates of EGFR mutations and KRAS mutations in P-PEAC patients were 4% and 43%, respectively. Similar to EGFR mutations (6% vs. 2%), KRAS mutations (22% vs. 60%) were also different between Asian and non-Asian P-PEAC patients. EGFR and KRAS mutations have been identified as driver genes of non-small cell lung cancer, with varying rates among different ethnic populations. The EGFR mutation rate is as high as 30% to 40% in Asians and 10% to 20% in non-Asians, while the KRAS mutation rate is 20% to 30% in Europe and America, 8% to 10% in Asians, and 8.3% in China. However, regardless of ethnicity, the KRAS mutation rate in P-PEAC was much higher, and the EGFR mutation rate was much lower compared to usual lung adenocarcinoma. The higher KRAS mutation rate, especially in non-Asian P-PEAC patients, might suggest unique biological properties and the potential for KRAS-targeted inhibitor treatment. To further clarify the patients’ data, the ADx-ARMS KRAS assay was used to detect KRAS mutation status in tumor tissue samples. All eight S-PEAC patients tested negative for KRAS mutations, while three of the 15 P-PEAC patients tested positive (3/15). The mutations included codon 12 G12D (35G > A) in exon 2, codon 13 G13D (38G > A) in exon 2, codon 61 (Q61L/Q61R/Q61H) in exon 3, and codon 61 (182A > T/182A > G/183A > C/183A > T) in exon 3. The positive rate of KRAS mutations in this study was 13%, which is higher than the reported data for the Chinese population (8%).
In conclusion, P-PEAC is a rare type of lung adenocarcinoma that is difficult to differentiate from S-PEAC. A deeper understanding of the differences between primary and secondary PEAC can aid doctors in making accurate differential diagnoses. In addition to medical history, clinical manifestations, laboratory tests, physical examinations, and histopathology, immunohistochemistry and KRAS mutation status serve as important identifying points. Further studies are required to improve our understanding of driver gene mutations and their implications for targeted therapy and standard chemotherapy regimens.
doi.org/10.1097/CM9.0000000000000266
Was this helpful?
0 / 0