Carcinosarcoma was first described by Virchow in 1865 as a rare malignant neoplasm composed of both carcinomatous and sarcomatous elements. The first case of esophageal carcinosarcoma was reported by Hansemann in 1904(7). The incidence of ECS is very low, Wu reported a large cohort study between 1973 and 2011 that esophageal sarcoma represented 0.2% of all esophageal malignant tumors and ECS makes up 42% of the esophageal sarcoma(8). One common morphological characteristic of the ECS is that they commonly form huge polypoid tumors with a pedicle attached to the wall of the esophagus, with or without ulceration. A study conducted by Chino indicated that abundant collagenous stroma positive for type IV collagen and laminin of the sarcomatous components contributes to the polypoid morphology of the tumor while the carcinomatous components of the tumor lead to the ulcerative pattern similar to ordinary squamous cell carcinomas(2, 9). Several hypotheses have been proposed regarding to the etiology of the esophageal carcinosarcoma. Lane initially used the term “pseudosarcoma” to describe neoplasms consisting of epithelial and mesenchymal components and suggested that the sarcomatoid components are fibroblastic proliferation stimulated by the adjacent carcinomatous components(10). Jun reported a case in which the sarcoma cells were different from the carcinoma cells morphologically and they did not express any epithelial markers, indicating that some ECS are results of simultaneous occurrence of a carcinoma and a sarcoma independently(11). Matsumoto concluded that ECS is derived from a single clone of a pure squamous cell carcinoma by conducting loss of heterozygosity analysis on six cases and found that an original clone of a pure squamous cell carcinoma acquired sarcomatous phenotype through a progressive accumulation of genetic divergency(12). To sum up, the sarcomatous components of the ECS may originate from fibroblastic proliferation stimulated by carcinomatous components, sarcomatous transformation independently, or from the same stem cell as the carcinomatous components.
ECS shares similar clinical manifestations with ESCC. Both of the two malignancies manifest dysphagia as the most frequent symptom and sometimes accompanied with chest pain, odynophagia, hematemesis and weight loss(13, 14). A statistical analysis conducted by Schizas revealed that the most common tumor location was middle esophagus (56.9%), the second common location was lower esophagus (23.5%) and the third common position was upper esophagus (19.6%). Middle-aged men with a history of smoking and/or alcohol abuse are most frequently victims to suffer ECS indicated by further investigations. Imaging examinations are crucial in the diagnosis and management of ECS. X-ray barium meal examination can reveal the location of the lesion while CT and PET play a pivotal role in detecting local invasions and lymphatic/distal metastasis to assist TNM staging(1). As for the case, X-ray barium meal examination and contrast-enhanced CT scan indicated the primary invasion of the neoplasm and guided the subsequent therapeutic plan. IHC analysis is the gold standard for the diagnosis of carcinosarcoma. There are various specific markers for the carcinomatous elements such as CEA, CD56 and synaptophysin. As for the sarcomatous components, desmin, SMA and vimentin are sensitive markers(1). The IHC analysis of the case showed that CK5/6, Ki-67 and P40 immunoactivity could be found in the carcinomatous components, indicating the squamous carcinomatous characteristics of the carcinomatous components with a malignant growth pattern. SMA and vimentin immunoactivity indicates the mesenchymal origin of the sarcomatous components. In light of the slight immunoactivity of SMA, the sarcomatous component is considered as undifferentiated pleomorphic sarcoma. Furthermore, no transitional zone that displays both CK5/6 and vimentin immunoactivity is observed and thus the sarcomatous component is not considered to be derived from the monoclonal origin as the carcinomatous component. Aside from these traditional diagnostic methods, Endoscopic ultrasonography (EUS) and serum levels of several cytokines have been applied to evaluate ECS by some scholars(15, 16).
Therapeutic management of primary ECS is decided by the location, pathological type, TNM grade and stage of the neoplasm. Endoscopic treatment might be managed on ECS with smaller size and is limited to the mucosa/submucosa layer without lymphatic node or distal metastasis. In addition, endoscopic treatment could also be considered as a choice in patients with poor health conditions, high risk of perioperative complications or contraindications of the major surgery(17, 18). Complete resection of the esophagus with lymphadenectomy of locoregional nodes is still recommended as the best potentially curative treatment. A multicenter European experience shows that 21 patients accepted transthoracic esophagectomy over 29 years with a 5-year OS and DFS rates of 35% and 33% with the total recurrence rate as 48%(5). Wu conducted a study that reported cancer data from 18 state and regional cancer registries and represents approximately 28 % of the US in 2015, indicating that surgery showed a significant OS advantage in adjusted and unadjusted survival analyses for ECS(8). As for the operation approach, Lv investigated the results of ten patients underwent uniport VATS esophageal operations and found that none of the ten patients conversed to open surgery and no serious complications occurred. He also concluded that operations of inferior esophageal cancer is relatively easier (19). Hasan reported an 18-patient investigation in which 15 patients with esophageal cancer who underwent uniport showed no perioperative complications and three patients had leaks. He concluded that intrathoracic esophagogastric anastomosis is a pivotal step to reduce perioperative leaks (20). Although uniport VATS esophageal operations provides benefits, it still has limitations like crowding of the instruments and the optic gets dirty easily which may increase the operation duration(21). On account of the position and invasion of the tumor, we conducted uniport VATS esophagectomy. The operation was success and the patient did not suffer any serious complications. It is well known that chemotherapy and radiotherapy are important in malignant tumor treatment, but there haven’t been any well recognized chemotherapy schemes due to the rarity of ECS. Xu recommend that chemoradiotherapy associated with endoscopic management could be considered as an alternative to surgery for a patient with ECS whenever surgery is not feasible(14). Kimura reported a case that ECS disappeared after palliative radiotherapy (45 Gy/15 fr) alone, speculating that the complete response is a result of an increase of the immune reaction against neoplasm antigen activated by irradiation. However, the indication for radiotherapy in the management of ECS should be considered carefully since standard treatment strategy had not been established(22).
For the prognosis of ECS compared to ESCC, there is still a controversy. Some scholars consider that ECS has a better prognosis than ESCC. Wang analyzed the clinical outcomes of 33 patients and found that the median OS for all the patients with esophageal carcinosarcoma was 43.5 months, and the 1-year, 3-year, and 5-year OS rates were 74%, 57%, and 48 %, better than that of ESCC in their center(3). Another multicenter analysis conducted by Zhang also revealed that ECS has a better prognosis with a 5-year OS of 43 months, higher than that for ESCC, which was 37.5 months(23). The reasons why ECS may has a better prognosis than ESCC includes its low-grade malignant potential and intraluminal growth pattern that can lead to early diagnosis and treatment(14). However, some scholars held the opposite opinion that ECS does not have a better prognosis than ESCC. Lyomasa conducted a twenty-case study in 1990 in which the clinical results of 20 carcinosarcoma patients are compared with that of 773 cases of squamous cell carcinoma, indicating that although the three-year survival rate of ECS is higher than that of squamous cell carcinoma, there is no significant different in five-year survival rate between the two neoplasms. Moreover, ECS manifests a higher frequency of lymph node recurrence and hematogenous metastasis(4). Sano also reported that hematogenous metastasis was more frequent in ECS than that of ESCC. Sano also found that more organ metastasizes consist of sarcomatous components(24). To sum up, as for the primary neoplasm behaviors, ECS have a better prognosis than ESCC owning to its lower local invasion tendency and exogenous growth pattern, which means that clinical symptoms occur earlier and thus early diagnosis and treatment is possible. However, ECS seems to have a higher lymphatic and hematogenous metastasis rate, which enlightens us that lymphadenectomy and pathological examination are necessary intraoperatively.