Abstract

Transformation of a poorly differentiated squamous cell carcinoma (SCC) of the esophagus into a “carcinosarcoma” of the pleura and lung has never been reported and its histogenetic origin is still debated. A 48-year-old man was admitted due to progressive dysphagia and a weight loss of 5 kilograms within 2 months. Upper gastrointestinal panendoscopic biopsy revealed poorly differentiated SCC of thoracic esophagus, upper third, T4N1M1a, stage IVa. He received concurrent chemoradiotherapy (CCRT). About 9 months later, rapid progression of lung metastases and pleural effusion were found. According to the histopathological and immunohistochemical stain results, carcinosarcoma was diagnosed. Palliative therapy was given and the patient eventually died of the disease 9 months after SCC of the thoracic esophagus was diagnosed and one month after carcinosarcoma of the pleura and lung were confirmed.

The incidence of esophageal squamous cell carcinoma (SCC) shows marked variation, with half of all esophageal SCC in the world occurring in China.¹ Carcinosarcoma of the esophagus is regarded as a rare malignant neoplasm composed of both carcinomatous and sarcomatous elements. Case reports introducing the pathological characteristics of this tumor have increased recently, and it is gradually becoming accepted that the spindle-shaped cells in the sarcomatous component are of squamous epithelial cell origin and that this category of tumor is one of the special types of SCC. However, there are no reports of these two types combined, so the true incidence and precise prognosis of carcinosarcoma remain unknown.²

In previous reports, there are no significant differences in age, sex, symptoms, or location between the carcinosarcoma and SCC of esophagus. Carcinosarcoma had the following morphological characteristics: 75% cases were of the elevated type, with large tumor size in 80% of cases, the depth of invasion was limited to the esophageal wall, compared with the frequency of lymph node recurrence, hematogenous (lung and/or liver) metastasis was higher for carcinosarcoma. Although the three-year survival rate was higher for carcinosarcoma (62.8%), there was no significant difference in the five-year survival rate between them.² We present the first case of transformation of a poorly differentiated SCC of the esophagus into a “carcinosarcoma” of the pleura and lung.

Case

A 48-year-old man was admitted to our hospital with a 2-month history of progressive dysphagia and weight loss of 5 kilograms in 2 months. Past history included hepatitis C virus and alcohol-related cirrhosis of the liver complicated with esophageal varices, which were ligated 2 years previously. Splenomegaly, thrombocytopenia and coagulopathy had been noted for 5 years. He reported a 20 pack-year history of smoking, having stopped using tobacco one year previously. Physical examination revealed tumor marker levels that were all within normal limits: SCC antigen, 1 ng/mL and carcinoembryonic antigen (CEA) 3 ng/mL. Upper gastrointestinal series revealed a segmental filling defect about 9.5 cm in length with mucosa destruction over the esophagus at the level above the carina, consistent with esophageal carcinoma. The CT scan of the chest showed a large, lobulated soft-tissue mass about 6.4×3.3×3.3 cm over the esophagus, from a level near the thoracic inlet to a level about 0.5 cm above the carina. Enlarged nodes in the surrounding region of the esophageal tumor were suggestive of esophageal carcinoma with cervical lymph nodal metastasis. Endoscopic examination revealed a ulcerative mass at 22 to 27 cm from the incisors. Analysis of the biopsy specimen showed the tumor to be a poorly differentiated SCC. On the basis of an imaging study and biopsy findings, a poorly differentiated SCC of the thoracic esophagus, upper third, T4N1M1a, stage IVa, was confirmed.

The patient underwent chemotherapy (weekly cisplatin) and radiation therapy (66 Gy) for 2 months. After treatment, a follow-up CT scan of the chest revealed significant resolution. Because of progressive dysphagia, he received a percutaneous esophagogastrostomy, bur still choked easily when drinking liquids. He had been admitted to our hospital twice due to aspiration pneumonia. He received regular follow-up at the outpatient department. The image did not reveal lung parenchyma mass or pleural effusion 1-2 months before the last admission.

Two weeks prior to the admission, progressive shortness of breath and nocturnal cough were noted. Physical examination revealed decreased breathing sounds over the left lung field. Chest x-ray showed massive left pleural effusion (Figure 1). A CT scan of the chest showed a huge lobulated soft-tissue density mass over the esophagus, from the cervical level to near the carina, with mediastinal extension. Lobulated soft-tissue density masses around 9 cm in size were in the left lung parenchyma and numerous soft-tissue density tumors were over the left pleura. There werre bilateral pleural effusions and multiple enlarged nodes in the surrounding region of the esophageal tumor and neck, and pulmonary, pleural and multiple lymph node metastases were highly suspected (Figure 2).
Diagnostic sono-guiding pleural biopsy and thoracentesis revealed a malignant anaplastic tumor accompanied by a solid tumor nest with bizarre nuclei and prominent nucleoli. The tumor cells were immunohistochemically positive for vimentin, but negative for cytokeratin (Figure 3). According to the histopathological and immunohistochemical stain results, carcinosarcoma was diagnosed. Because of declining performance status, chemoradiation therapy was withdrawn and palliative therapy was given. He eventually died of disease progression under hospice care 9 months after SCC of the thoracic esophagus was diagnosed and one month after carcinosarcoma of the pleura and lung were confirmed.

Discussion

Our patient had been diagnosed with primary poorly differentiated SCC of the esophagus and had received concurrent chemoradiotherapy (CCRT) for 2 months. He had developed secondary carcinosarcoma of the pleura and lung 5 months later. Using the phrase ‘transformation of SCC of esophagus into a “carcinosarcoma” in a search of MEDLINE on the PubMed website, we found no cases of this type.
The most widely accepted hypothesis on the histogenesis of carcinosarcoma is that it originates from stem cells, which are present in almost all tissues and may generate different cellular lineages by the multi-step process of differentiation. The role of stem cells in tumorigenesis has been clearly demonstrated in a number of carcinogenic models.^3-5 Recent studies have supported a “monoclonal hypothesis”, which proposes an origin from a single totipotential stem cell that differentiates along distinct epithelial and mesenchymal pathways.⁶ Concordance of positive p53 staining in both the epithelial and sarcomatous components of carcinosarcomas has been adduced in support of the monoclonal hypothesis.⁷

Most cancers result from the interaction of genetics and environment. Environmental factors could explain 95% of all cancer, and radiotherapy and chemotherapy are the most established causes of second malignant neoplasm.⁸ The patient received CCRT, which may be an inducible factor for the transformation from SCC into carcinosarcoma. However, this was also a case of esophageal tumor: the initial biopsy showed SCC and the lung metastasis showed carcinosarcoma. Although it may be SCC that transformed to carcinosarcoma, the likely explanation is that this was a carcinosarcoma from the start. The initial biopsy was small and was interpreted as SCC. Carcinosarcoma would have been confirmed initially by the resection of the esophagus, but resection of the esophagus was not indicated in this case, which was in the terminal stages of esophageal cancer.

Several previous reports refer to a good prognosis with carcinosarcoma.^9-13 However, the prognosis of carcinosarcoma at present is not as favorable as previously reported. Esophageal carcinosarcoma may become symptomatic earlier than SCC, thus aiding detection and diagnosis, but it is not associated with a better long-term prognosis because of its rapid growth.¹⁴ Limited invasion, high resectability and a good prognosis with a 3-year survival rate were noted. On the other hand, the 5-year survival rate may be influenced by a relatively high possibility of hematogenous metastasis of the carcinosarcoma in the late period.² The true incidence and prognosis of esophageal carcinoma is still uncertain due to the rarity of reported cases. Our case of secondary carcinosarcoma had distinguishing characteristics, including a large recurrent esophagus tumor, adjacent lymph node metastasis, and rapid hematogenous metastasis to the lung and pleura. In conclusion, we think this case is interesting because carcinosarcoma rarely arises from an SCC of the esophagus with progressive metastases to lung and pleura. To our knowledge, this is the first report of this nature.

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