MethodsIt was an cohort study involving 78 patients with pathologically confirmed PPMA who were treated in the First Affiliated Hospital with Nanjing Medical University from January 2009 to December 2019 and selected by non-random sampling method.The clinical data, treatment course and follow-up results were collected.Follow-up ended on December 31, 2021.Kaplan-Meier method (Log-Rank test) was used for plotting survival curves.Multiple Cox regression model was used to analyze the independent risk factors affecting the survival of PPMA.
ResultsA total of 78 patients with the mean age of onset of (60.1±11.8) years were recruited.Most patients (67.9%, 53/78) did not have smoking history.Forty-eight patients (61.5%) had primary lung tumor-related symptoms, including cough, expectoration, chest tightness, dyspnea, chest pain and fever.Chest CT scans showed peripheral type and central type in 59 cases (75.6%) and 19 cases (24.4%), respectively.There were 54 cases (69.2%) and 24 cases (30.8%) of nodular type and pneumonia type, respectively.Tumor markers associated with lung cancer increased in 69.7% (46/66) patients.Stratified by tumor staging, there were 31 cases (39.7%) of stage Ⅰ, 14 cases (17.9%) of stage Ⅱ, 16 cases (20.5%) of stage Ⅲ and 17 cases (21.8%) of stage Ⅳ.Immunohistochemical tests were performed in 35 patients, including 31 with positive cytokeratin 7 (CK7), 17 with positive thyroid transcription factor 1 (TTF-1), 12 with positive Napsin A and 8 with positive Villin.PPMA-related driver gene mutations were mainly KRAS mutations (15/46, 31.3%).Radical surgery was performed in 55 (70.5%) patients.By the end of follow-up, 31 cases (39.7%) died and 47 cases (60.3%) survived.The median follow-up time was 40.5 months.The median overall survival time of was 96.0 months, and the 1-, 3-, 5-, 7-year cumulative survival rate was 86%, 71%, 62%, and 52%, respectively.Distant metastasis occurred in 26 cases (33.3%), of which, bone metastasis (16 cases) was the most common.All stage Ⅰ PPMA patients underwent radical resection and no relapse reported.There were significant differences in sex, age, smoking history, symptoms associated with primary lung tumor, tumor markers (carcinoembryonic antigen [CEA], cytokeratin fragment antigen 21-1 [CYFRA21-1]), radiologic features and the tumor, node, metastasis (TNM) staging in PPMA patients with different survival status (P<0.05).Multiple Cox regression model analysis was conducted with survival outcome as the dependent variable, while sex, age, smoking history, symptoms, CEA, CYFRA21-1, imaging findings and TNM staging as covariates.The results showed that symptoms associated with primary lung tumor, elevated CEA, elevated CYFRA21-1, pneumonitis and TNM staging were independent risk factors affecting the survival of PPMA patients.
ConclusionsPPMA is more common in the middle-aged and elderly people.The clinical manifestations are non-specific, while the chest CT manifestations are mainly peripheral type and nodular type.KRAS mutations are the frequent driving gene mutations in PPMA patients.Primary lung tumor related symptoms, elevated CEA, elevated CYFRA2-1, pneumonia type and TNM staging are independent factors affecting the prognosis of PPMA patients.
