Clinical Characteristics And Prognosis Of Micropapillary Pattern In Lung Adenocarcinoma

Objective: The clinical data and prognosis of 20 cases of pulmonary adenocarcinoma with micropapillary pattern hospitalized in oncology department of General Hospital from April 2013 to December 2018 were retrospectively analyzed.The purpose of this study was to understand the clinical characteristics and prognosis of MPPAC,and to provide reference for future clinical diagnosis and treatment.Method: According to the new classification standard of lung adenocarcinoma published by IASLC/ATS/ERS on February 2011,MPPAC patients were screened out from ADC patients admitted to our department in recent 6 years.The clinical and prognostic characteristics of MPPAC were summarized and analyzed by reviewing clinical records,imaging data,gene detection,telephone follow-up and outpatient review.Result:1?The average age of MPPAC patients was 61.5 years old,and 85% of them were 50-65 years old.Males,non-smokers and symptomatic onset accounted for 55% respectively.The onset symptoms were mostly cough and sputum.No specific tumor markers,preoperative CEA elevation(1-6.39 times)was the most common in 63.64%(7/11);There were also increases in NSE and CYFRA21-1(1-3 times)accounting for 33.33%(3/9)respectively,and no increase in SCC(0/9).2?On imaging,peripheral MPPAC accounted for 80%(16/20),predominantly in the right lung(14/20),and there was no significant difference in the incidence of lung lobe tumors,while left lung MPPAC was most common in the upper lobe(5/6).The imaging manifestations were nonspecific,mostly solid masses,with lobulation,burr,pleural traction,and enhanced CT.3?In the organizational structure of MPPAC,57.89%(10/20)of the three structural types were mixed,and no ADC with five structural types or only MPP structure was found.MPP structure was most often mixed with acinar structure(16/20).In immunohistochemistry,the most common positive markers were CK7,NapsinA,TIF-1,KI-67;the negative markers were P40,CgA,Syn.MPPAC has the characteristics of high recurrence,high pleural metastasis and high lymph node metastasis.The 3-year recurrence rate is 100%(14/14),visceral pleural metastasis rate is 38.89%(7/18),lymph node metastasis rate is 83.33%(15/18).Postoperative recurrence of MPPAC was found in 1-2 organs.Lung(78.57%)was the most common,followed by bone,pleura and brain.No adrenal involvement was found.The stage of pT was smaller and pN was larger.The most common stage of pT2,pN2 and PIIIA were 55.56%(10/18),72.22%(13/18)and 55.56%(10/18),respectively.In addition,there were 7 patients with MPPAC who had different stages before and after operation,mainly N stages.One patient had CN0?PN2,and four patients had CN1?PN2.4?Among 19 MPPAC patients who underwent gene testing,15 had genetic abnormalities,of which 5 had mutations of more than 2 genes(among them,there was a co-mutation of EGFR Exon 20 and 21,and a co-mutation of EGFR Exon 18 and KRAS Exon 4.);In this study,the mutation rates of EGFR,KRAS,ALK,MET,RET and ROS-1 genes were 47.37%(9/19),21.05%(4/19),12.5%(2/16),14.29%(2/14),7.15%(1/14)and 6.67%(1/15)respectively.Exon 19,21 mutations in EGFR and Exon 2 mutations in KRAS were the most common mutations in 3 cases respectively.No abnormalities of ERBB-2 and BRAF genes have been found.5?Nineteen MPPAC patients in this study were able to perform DFS analysis with a median DFS of 17.27 months.The recurrence rates in one year,two years and three years were 21.05%(4/19),62.5%(10/16)and 100%(14/14)respectively.Univariate analysis showed that there was no significant difference in DFS between patients with age > 65 and < 65,tumors > 3cm and < 3cm(P=0.92,P=0.30).Although DFS in males was better than that in females and those with negative pleural metastasis were better than those with positive pleural metastasis,the difference was not significant(P=0.32,P=0.2),while DFS in smokers was significantly better than that in non-smokers(P=0.027).the wild type of EGFR was significantly better than the mutant type(the median DFS was 21.59 VS 10.72 months;P=0.001).In addition,it was found that there was a negative correlation between post-operative stage and DFS.The median DFS: I + II > II I a > II I B + IV(20.3 months > 17.42 months > 16.97 months).Multivariate analysis showed that EGFR gene status(HR,0.024;95% CI.0.001-0.620;P = 0.027)was an independent factor affecting DFS.The median OS of MPPAC patients was 30.5 months.The median OS of I + II,II I A and II I B + IV patients was 43.33 months,33.24 months and 17.26 months respectively.Because 73.68% of patients did not reach the end point,OS and its influencing factors were not analyzed.Conclusion:1?MPPAC was predominant in males,non-smokers and patients aged less than 65 years(mainly 50-65 years old).The importance of physical examination should be emphasized.At present,there are no specific tumor markers.Peripheral lung cancer is the most common type in imaging,mainly in the right lung;Postoperative paraffin sections are the gold standard for the diagnosis of MPPAC.2?MPPAC has the characteristics of high recurrence,high pleural metastasis and high lymph node metastasis.It has no specific immunohistochemical markers The stages were characterized by smaller pT and larger pN.Postoperative recurrence of MPPAC is manifested by 1-2 kinds of organ involvement.Lung(78.57%)is the most common,followed by bone,pleura and brain.Therefore,the examination of related organs should be improved when patients are reexamined.3?At present,the understanding of MPPAC is insufficient.We should study the malignant mechanism of MPP;the effect of different adjuvant therapy after operation;the clinical,pathological characteristics and prognosis of lung adenocarcinoma with different MPP proportions in order to bring the best diagnosis and treatment to patients.