Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic analysis of 51 cases

Background Pulmonary sarcomatoid carcinoma is a diagnostically challenging group of tumors. It’s a rare histologic subtype of non-small cell lung cancer.There are five subgroups of pulmonary sarcomatoid carcinoma, they are identified as pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. We explored the clinicopathologic features and prognostic factors of this tumor. Methods We analyzed retrospectively the clinicopathological data of 51 patients with pulmonary sarcomatoid carcinoma who were treated in the First Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital and Henan People Hospital from January 2005 to December 2012. The correlation between prognosis and age, sex, smoking history, tumor size, TNM staging, and treatment modality was analyzed by the statistical software SPSS 17.0. The survival analysis was conducted using the Kaplan-Meier method. The factors influencing survival were analyzed using univariate (Log-rank) and multivariate (Cox) models. Results The overall survival rates at 1, 2, 3 and 5 years were 45.5%, 35.8%, 28.2% and 20.1%, respectively. Cox univariate analyses revealed that age, tumor size, T stage, M stage, surgery or not, and postoperative chemotherapy or not, were prognostic factors. Cox multivariate analysis found that tumor size and M stage were independent prognostic factors for PSC. Conclusions Due to its rarity and the lack of large-scale clinical trial evidence, few studies about PSC have been reported, its clinical and pathological characteristics remain unclear, and its preoperative diagnosis and investigation of novel treatment approaches are imperative. In our study, the main factors affecting the prognosis of tumor size and M staging are the crucial prognostic factors for PSC. Surgical resection and postoperative adjuvant chemotherapy might result in better prognosis.


Background
Sarcomatoid carcinoma can occur throughout the body; however, primary sarcomatoid carcinoma in the lung is very rare, accounting for 0.1% to 0.4% of all lung malignancies [1]. Pulmonary sarcomatoid carcinoma (PSC) is a rare histologic subtype of non-small cell lung cancer (NSCLC) [2]. PSC is defined as poorly differentiated nonsmall cell carcinoma that contains a component of sarcoma or sarcoma-like elements according to the 2004 World Health Organization [3].
PSC generally runs an aggressive clinical course and may cause major difficulties in the diagnosis; its rapid preoperative diagnosis is very difficult because of its heterogeneity [4]. The prognosis remains controversial. Although some insist that the prognosis of PSC is less favorable than other NSCLC among postoperative patients [1,5,6], others see no difference between PSC and other NSCLC [7,8].
This study discusses the clinicopathological features and prognostic factors for 51 cases of pulmonary sarcomatoid carcinoma. This retrospective analysis of clinical data, treatment methods and survival rates may yield clues to appropriate diagnostic and therapeutic strategies for this aggressive 'miniature monster'.

Methods
Ethical approval: Any experimental research were performed with the approval of ethics committee. Research carried out on humans were in compliance with the Helsinki Declaration,

Results
1. Pathological results: Of the patients, 3 of 9 cases that were biopsied using a fiber endoscope were confirmed by pathological examination, and 12 of 18 cases were confirmed by computed tomography  (Figure 1a-f ) showed that prognosis of the patients was influenced by age, tumor size, T stage, metastatic status, surgery or not, and postoperative chemotherapy or not (P <0.05, Table 1). However, multivariate analysis showed that tumor size (P = 0.005) and metastatic status (P = 0.032) are independent prognostic factors ( Table 2).

Discussion
PSC occurs mostly in men in their sixth and seventh decades, except for the pulmonary blastoma subtype, which occurs equally in men and women and frequently in the fourth decade [9,10]. It shows prevalence among male smokers, with an average age at presentation of 60 years and who have a history of moderate to heavy tobacco   [7,11,12]. In this group, the male to female ratio was 5.4:1 and 63.0% (29/46) of the patients have a history of smoking; however, the smoking history did not have a significant influence on the prognosis (P = 0.430). Compared to other histologic subtypes, PSC behaves in an aggressive way. In the major published series of PSC, no specific signs or symptoms have been found when compared with other typical NSCLC [11][12][13][14][15]. The preoperative diagnosis of PSC is very difficult. Although PSC may sometimes be diagnosed on cytological preparations, surgical or biopsy specimens are necessary to obtain a definitive diagnosis because of the heterogeneity of PSC. In this group, the preoperative misdiagnosis rate was 70.6% (36/51). Someone raised [16], A modified vimentin histologic score (M-VHS) could be an effective diagnostic tool for this cancer, as to whether can be applied to clinical needs further large-scale studies. Some reports [10,[16][17][18] show that positron emission tomography (PET) uptake is much higher in sarcomatoid carcinoma than in other NSCLC (P <0.0001), which means a PET scan may effectively identify PSC, but further confirmation still depends on pathological diagnosis.
The average survival of patients with PSC was 13.3 months in our study, which is slightly longer than the 11 months that is reported in other published series [12]. It is possible that multimodality therapeutic approach may also have contributed to a better prognosis for advanced patients. The 1-, 2-, 3-and 5-year overall survival rates in this group were 45.5%, 35.8%, 28.2% and 20.1%, respectively. Multivariate analysis of prognostic factors revealed that the main factors affecting prognosis are tumor size and M staging.
The treatment principle for pulmonary sarcomatoid carcinoma is similar with other non-small cell lung cancer. In this study, surgery or not (P = 0.005) and postoperative chemotherapy or not (P = 0.029) both have significant impact on prognosis on a statistical level. Early surgery is the preferred treatment for PSC, for which the postoperative adjuvant chemotherapy can be performed. Given the current status of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in treatment of NSCLC, could be considered for treatment of PSC? Until now, innovative treatments such as monoclonal antibodies, which are target epidermal growth factor receptor mutations, have shown no definitive effect on the outcome [17][18][19]. It needs more large population clinical studies to prove whether EGFR-TKI can bring the Gospel for patients with PSC or not. Tsao AS and his colleague show that PDGFR-b has a higher expression and an increase of gene copy number in PSC compared with other NSCLC, which suggests that perhaps PDGFR-b would become a new therapeutic target [20]. These studies suggest a new research direction for PSC treatment.
The study presents several limitations that must be considered when interpreting the results. First, the population in this study was small because the disease is rare. Second, this study includes a wide variety of patients. Some patients underwent curative resection, while some did not because of advanced disease. Some patients underwent chemotherapy, while some did not because of economic conditions. Third, the study includes only eight female patients. Future studies with larger patient population must re-evaluate the influence of gender so that we can obtain statistical power.

Conclusions
In summary, many patients are easily misdiagnosed before accepting surgery, so an accurate preoperative histological diagnosis is imperative. Limited experience in diagnosis, treatment and prognosis of PSC still exists because the disease is rare and because there is a lack of large-scale clinical trial evidence. Because further research in diagnosis and treatment is urgent, we hope that the reports about PSC will gradually increase in order to facilitate clinical doctors to manage the disease and benefit the patients.

Consent
Written informed consent was obtained from the patient for the publication of this report and any accompanying images.