True carcinosarcoma of the esophagus

Diseases of the Esophagus (2006) 19, 48 –52 © 2006 ISDE Case report Blackwell Publishing Asia True carcinosarcoma of the esophagus T. Iwaya,1 C. Maesawa,2 N. Uesugi,3 T. Kimura,2 S. Ogasawara,1 K. Ikeda,1 Y. Kimura,1 S. Mitomo,1 K. Ishida,1 N. Sato,4 K. Saito,1 T. Masuda2 Departments of Surgery I and 2Pathology, 3Division of Pathology, Central Clinical Laboratory, and 4Critical Care Medicine, Iwate Medical University School of Medicine, Morioka, Japan SUMMARY. Most esophageal carcinosarcomas are diagnosed as so-called carcinosarcoma, in which individual elements may be derived from a single common ancestor cell, and there have been a few reports describing true carcinosarcoma originating from two individual stem cells. We describe a case of esophageal carcinosarcoma exhibiting neoplastic osteoid formation. Immunoreactivity for vimentin and p53 was limited to only the sarcomatous component and was absent in the carcinomatous component. Furthermore, a point mutation in exon 7 of the p53 gene was observed only in the sarcomatous component. Both sarcoma and carcinoma cells distinctively metastasized to different lymph nodes. These observations led us to diagnose the esophageal tumor as a true carcinosarcoma. KEY WORDS: collision tumor, esophagus, osteosarcoma, p53, true carcinosarcoma. Here, we describe a case of true esophageal carcinosarcoma, in which the sarcomatous cells showed neoplastic osteoid formation. Both the sarcomatous and carcinomatous components distinctively metastasized to different lymph nodes. INTRODUCTION Carcinosarcomas are rare malignant neoplasms consisting of both carcinomatous and sarcomatous components. Two major explanations have been proposed for the pathogenesis of carcinosarcomas: the metaplastic and the collision concepts.1 The metaplastic concept is that individual elements may be derived from a single common ancestor cell (so-called carcinosarcoma), whereas the collision concept is that two individual stem cells may independently and simultaneously undergo malignant transformation (true carcinosarcoma).1 Immunohistochemical,2,3 ultrastructural4,5 and molecular genetic studies6–8 have demonstrated that the spindle sarcomatous cells originate from carcinoma cells, thus supporting the metaplastic concept. Esophageal carcinosarcomas comprise approximately 1–2% of all esophageal neoplasms,9 and the metaplastic concept has been the mainstream view for the pathogenesis of these tumors. Therefore, most esophageal carcinosarcomas are diagnosed as a so-called carcinosarcoma, and there have been a few reports describing true carcinosarcoma.10–13 CASE REPORT A 57-year-old man presented with dysphagia. Barium swallow esophagograms and endoscopic examination revealed a polypoid tumor 13 cm in diameter in the thoracic and abdominal esophagus. The tumor did not invade to the adjacent organs. Multiple biopsies of the tumor revealed it to be squamous cell carcinoma (SCC). The patient underwent esophagectomy with a gastric pull-up reconstruction, cervical anastomosis, and lymphadnectomy via abdominal, left cervical and right thoracotomy incisions, at the Department of Surgery I, Iwate Medical University School of Medicine, Morioka, Japan. The patient was discharged 1 month after surgery. One year later, the tumor recurrence was observed in the thorax. Despite radiotherapy, tumor growth could not be controlled and the patient died 3 months later. Macroscopically, the resected tumor, measuring 170 × 98 × 45 mm in size, was located in the thoracic and abdominal esophagus. The surface of the tumor Address correspondence to: Dr Takeshi Iwaya, Department of Surgery I, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Japan. Email: 48 1 True carcinosarcoma of the esophagus 49 Table 1 Results of immunohistochemical staining Cytokeratin EMA Vimentin Desmin α-SMA HHF 35 S-100 p53 c-Kit CD34 Carcinomatous component Sarcomatous component (+) (+) (–) (–) (–) (–) (–) (–) (–) (–) (–) (–) (+) (–) (–) (–) (–) (+) (–) (–) DISCUSSION Fig. 1 Macroscopic appearance of the tumor (upper, longitudinal section after fixation). (A–D) Microscopic features of the tumor indicated by squares with letters in the upper panel (HE, original magnification ×200). (a) The portion composed of both well differentiated SCC and spindle-shaped sarcomatous elements. (b) Transitional zone between carcinomatous and sarcomatous elements. (c) Sarcomatous component. (d) Osteosarcomatous portion. was erosive and necrotic (Fig. 1). Microscopically, the tumor consisted mainly of spindle-shaped cells that showed frequent mitoses (Fig. 1c). We found neoplastic osteoid formation by atypical cells in part of the sarcomatous component, showing the feature of osteosarcoma (Fig. 1d). The SCC component was observed in the basal part of the polypoid tumor (Fig. 1a), and features of SCC in situ were also seen around the polypoid lesion. A gradual transition between the sarcomatous and carcinomatous elements was evident (Fig. 1b). In an abdominal In most cases, it has been suggested that the sarcomatous element of esophageal carcinosarcoma generally results from differentiation of SCC cells into mesenchymal tumor cells. This is based on the facts that most carcinosarcomas contained a transitional zone with both carcinomatous and sarcomatous components,16 and that identical genetic alterations were observed in both components.6,7 For conventional microscopic diagnosis, existence of a transitional zone and/or genuine sarcomatous components is a key feature. In the present case, a transitional zone was observed, but it was confined to within extremely narrow limits. However, the sarcomatous component was partially characterized by specific differentiation toward osteosarcoma. Furthermore, the sarcomatous and SCC cells showed distinctive metastasis to different lymph nodes. These findings indicated that both types of cells were lymph node, well differentiated SCC was observed (Fig. 2a), and another metastatic node in the thorax was composed of only spindle-shaped sarcomatous cells (Fig. 2b). Immunohistochemically, the SCC cells were positive for cytokeratin (Fig. 3a) and epithelial membrane antigen. In contrast, the spindle-shaped tumor cells were immunoreactive for vimentin (Fig. 3b) and negative for epithelial or other mesenchymal markers. Furthermore, only the sarcomatous cells were positive for p53 (Fig. 4). Both components were negative for c-Kit or CD34. These immunohistochemical results are summarized in Table 1. We also examined p53 gene mutations (exons 5 to 8) using the microdissected materials obtained from the carcinomatous and sarcomatous components, by PCR-single-strand polymoprphism analysis followed by direct sequencing, as described previously.14,15 A shifted band was observed only in the sarcomatous component. Sequence analysis revealed that the sarcomatous component showed a transversion (C-to-A) at codon 256 in exon 7 of the p53 gene (Fig. 5). 50 D (...truncated)