"Rare Primary Pulmonary Sarcomatoid Carcinoma with Isolated Pancreas Metastasis: Case Report and Literature Review"

Sarcomatoid change is an uncommon phenomenon (accounts for approximately 0.4%) in non-small cell lung cancer (NSCLC) which is characterized by poorly differentiated neoplasm containing sarcoma or sarcomatoid components [1-3], its pathological diagnosis include five subtypes (pleomorphic carcinoma, spindle cell carcinoma, carcinosarcoma, giant cell carcinoma and pulmonary blastom) and require high-quality sampling of the tumor [4]. Since pulmonary sarcomatoid carcinoma (PSC) is generally a form of highly aggressive malignancy in NSCLC, it is no wonder that it has an extremely poor prognosis [1]. Previous studies have shown ARTICLE INFO ABSTRACT


Introduction
Pulmonary sarcomatoid carcinoma (PSC) is a very rare subtype of non-small cell lung cancer (NSCLC) and has an extremely poor prognosis with 5-year overall survival rate ranging from 10% to 21%, and it accounts for approximately 0.4% of all pulmonary malignancies. Compared with other types of NSCLC, PSC is more prone to invasion and distant metastasis, and the most common metastatic sites are bone, adrenal gland and brain. The incidence of pancreatic metastasis of malignant tumors is uncommon clinically, and the occurrence of PSC with pancreatic metastasis is even rarer. Here, we describe a case of PSC with isolated pancreas metastasis that was initially considered as acute pancreatitis. After multidisciplinary discussion, the patient underwent stateof-the-art Da Vinci robotic surgery and simultaneous resection of the pancreatic and pulmonary masses followed by multiple cycles of chemotherapy. Soon after, the patient progressed and the treatment was changed to immunotherapy combined with antiangiogenesis therapy. Since the patient developed an acute episode of immunological enteritis, the therapeutic schedule was adjusted to maintenance therapy with Anlotinib subsequently, and we now estimate that the patient's subsequent survival time is relatively short.
Abbreviations: PSC: Pulmonary Sarcomatoid Carcinoma; NSCLC: Non-Small Cell Lung Cancer; CT: Computed Tomography; PET: Positron Emission Tomography that patients with PSC respond poorly to platinum based standard regimens and develop easily to chemotherapeutic resistance [2,5], and thus it is absolutely essential to explore and work out a more effective therapeutic strategy. Here, we reported a 59-year-old patient who was admitted for attacks of acute pancreatitis and was diagnosed with PSC with isolated pancreas metastasis, an even rarer malignance. Then, we reviewed the literature available and hope to seek out safer and more effective treatment strategies which can improve the prognosis of PSC patients.

Case Description
A 59-year-old male, an active smoker with a 40-year history of tobacco smoking (an average of 40 cigarettes per day), presented to a hospital in Xuzhou on November 26, 2020, he complained of persistent epigastric pain for half a day after heavy drinking. The patient denied any previous history of respiratory or digestive disease and malignancies. The results of hematological examination showed a mild leukocytosis and hyperamylasemia (130U/L; reference range: 30-110U/L), therefore, the patient was initially thought to had acute pancreatitis. However, According to the images of chest and abdomen computed tomography (CT), a lesion (46mm × 31mm) in the right lower lung lobe was detected; a cystic lesion was existed in the body of pancreas, and cystadenocarcinoma remained to be ruled out. In order to further clarify the patient's condition and diagnosis, the patient then underwent positron emission tomography (PET)/CT. As shown in Figure 1, the two nodules which located in the inferior lobe of right lung and the body of pancreas had significantly increased fluorodeoxyglucose metabolism and were considered to be malignant lesions. Then, the patient underwent the CT-guided percutaneous pulmonary nodules puncture biopsy, and the pathological diagnosis was poorly differentiated lung adenocarcinoma.   The patient's therapeutic process has been summarized as shown in Figure 4B, and we now estimate that the patient's subsequent survival time is relatively short.

Discussion
Pancreatic metastasis of lung cancer is rare, its frequency was mainly related to the histological types and small cell lung carcinoma has the highest incidence which was followed by lung adenocarcinoma [6], while the morbidity of PSC with pancreatic metastasis was extremely low. In this study, we reported a patient who suffered from PSC with isolated pancreas metastasis, after simultaneous resection of the pulmonary and pancreatic masses by state-of-the-art Da Vinci robotic surgery, the patient underwent multiple cycles of chemotherapy, immunotherapy and antiangiogenesis therapy, and he has survived for more than 11 months.
Due to the highly malignant and aggressive characteristics of this tumor, the vast majority of patients with PSC are tended to presented at advanced stage at the time of diagnosis, thus losing the opportunity of surgical resection, therefore, effective systemic treatments are of great importance. It is widely known that the determination of effective therapeutic strategies should be based on well-defined molecular mechanisms of tumorigenesis and cancer progression, whereas little was known about PSC's molecular pathogenesis now because of its rarity and heterogeneous morphology [2].
In order to describe the mutational profile of sarcomatoid and PI3KCA, and the EGFR mutations were almost always rare mutations (89%) [7], and this result had been confirmed by Terra SB, et al. [8]. The above finding suggested that testing for targetable mutations should be considered for patients with PSC, because a subpopulation may benefit from some molecular targeted antitumor drugs which have been approved for clinical use. Another promising new therapeutic strategy of PSC is the use of immune checkpoint inhibitors, because several studies had illustrated that PD-L1 was overexpressed in PSC [9][10][11]. Moreover, Pecuchet N, et al. demonstrated that, compared with the PSCs with APOBEC enzyme and homologous recombination deficiency, the PSC patients with tobacco-associated signatures had a higher rate of PD-L1 overexpression and a poorer overall survival [12]. The growing body of studies regarding the molecular mechanisms of PSC support that the malignant tumor is not only morphologically diverse, but also quite genetically diverse. Hence, the discovery and description of genetic events might provide novel treatment choices for PSCs, and potentially improve the patients' prognosis and bring PSC into the era of targeted therapy and immunotherapy.

Conclusion
In this study, we described an extremely rare case of PSC with isolated pancreas metastasis which was presented as acute pancreatitis initially. For PSC patients with isolated metastasis, if the patient's physical condition permit, surgical resection of the lesions could be considered and thus obtain high-quality tissue specimens for gene detection, which would provide a stronger basis for the selection of subsequent systemic therapy strategies including gene targeting treatment and immunotherapy.

Data Availability Statement
The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.

Ethics Statement
The study involving human participant was reviewed and approved by the ethics committee of the Affiliated Hospital of Xuzhou Medical University. The patient provided his written informed consent to participate in this study.

Conflict of Interest
The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.