Abstract

We report an extremely rare case of leiomyosarcoma arising from a remnant esophagus. A 52-year-old Japanese man was referred to our hospital for treatment of a tumor arising from the remnant esophagus. Four years earlier, he underwent a subtotal esophagectomy for esophageal squamous cell carcinoma (well differentiated squamous cell carcinoma, T1N0M0 Stage I) located in the lower esophagus. After preoperative studies, partial esophagectomy with laryngeal preservation and reconstruction using a free graft from the jejunum were performed. Histopathological and immunohistochemical examination revealed leiomyosarcoma without metastasis. Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin and vimentin, but were negative for cytokeratin and S100. The deeply biopsied specimens are helpful for preoperative histological diagnosis. Mitotic activity has been considered an important criterion of malignancy. However, some cases with minimal mitosis in the tumor grow rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. We also provide a review of 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data between 1969 and 1999, including the present case, and discuss their clinicopathological features. Asynchronous occurrence of leiomyosarcoma and squamous cell carcinoma in the esophagus is most unusual and has never been reported. Patients with infiltrating type leiomyosarcoma measuring more than 5 cm in diameter tend to have a poor prognosis. Chemotherapy did not exhibit any survival benefits. In the present patient, no recurrence has been noted for 23 months after surgery.

Received May 28, 2001; accepted June 26, 2001.

INTRODUCTION

Leiomyosarcoma is a high-grade, smooth-muscle soft-tissue tumor that can occur in any tissue containing smooth muscle fibers. Leiomyosarcoma of the esophagus is a rare malignant tumor, accounting for less than l% of all malignant esophageal tumors (13). We report here an extremely rare case of leiomyosarcoma arising from remnant esophagus following squamous cell carcinoma in a 52-year-old man, treated by surgery. We also review previously reported Japanese cases to characterize the clinicopathological features of Japanese patients with this malignancy.

To the best of our knowledge, this patient is the first report of remnant esophageal leiomyosarcoma and only the fifth reported case of multiple malignancies of esophageal squamous cell carcinoma and leiomyosarcoma in the world (47).

CASE REPORT

A 52-year-old Japanese man was referred to our hospital in May 1999 for further examination and treatment of a tumor arising from remnant esophagus detected during postoperative follow-up. The patient had previously undergone subtotal esophagectomy for esophageal cancer (well differentiated squamous cell carcinoma, T1N0M0 Stage I) situated in the lower third of the esophagus and the alimentary tract was reconstructed through the retrosternal route in May 1995 (Fig. 1a). Histopathological examination of the resected specimen at that time showed a well-differentiated squamous cell carcinoma (Fig. 1b). Radiotherapy (45 Gy) was applied to the mediastinum area after surgery.

On admission, routine laboratory tests were within normal limits, including tumor markers such as squamous cell carcinoma antigen and carcinoembryonic antigen. Barium swallow showed a round, smooth mass in the upper esophagus (Fig. 2). Esophagoscopy demonstrated an intraluminal polypoid lesion in the remnant esophagus with ulceration, 13 cm from the upper gum margin (Fig. 3), which was a suspected leiomyosarcoma histopathologically. The tumor was too large to allow passage of the scope to the distal parts of the esophagus. Computed tomography (CT) confirmed thickening of the upper esophageal wall, but enlarged lymph nodes or liver metastasis were not detected. Magnetic resonance imaging showed the absence of any space occupying lesion in the liver.

Surgery was performed after obtaining informed consent. On opening the right hemithorax through the fifth intercostal space, a tumor was found on the posterior wall of the upper esophagus and adhesion around the esophago-gastrostomy was divided by blunt and sharp dissection in the left-lateral position. Reconstruction was done using the cervical approach without median sternotomy in a supine position. For the jejunal free graft preserving pharyngeal functions, left transverse cervical artery and internal jagular vein were applied as donor vessels. Macroscopically, the resected specimen included a nodular tumor measuring 2.4 × 3.0 cm in size in the upper portion of the remnant esophagus (Fig. 4). Histopathologically, the tumor consisted of pleomorphic spindle cells with oval and long oval nuclei without a component of carcinoma, compatible with leiomyosarcoma (Fig. 5a). Tumor invasion was limited to the tunica adventitia layer. Adjacent 24 lymph nodes did not contain any metastases.

Immunohistochemical examination showed that most tumor cells were positive for smooth muscle actin (Fig. 5b) and vimentin, but negative for cytokeratin and S100 (Fig. 5c). No adjuvant therapy was applied after surgery. The postoperative period was uneventful and the patient showed a smooth recovery. At the last follow-up visit to our department 23 months after surgery, the patient was well and free from any recurrence or distant metastasis.

DISCUSSION

Esophageal leiomyosarcoma is an extremely rare malignant neoplasm of the esophagus. Although there have been many case reports of esophageal leiomyosarcoma in the world (2,6,8), a review of the Japanese literature showed very few cases. Therefore analysis of the characteristics of the reported Japanese cases would be of interest and important.

We found 64 cases of esophageal leiomyosarcoma reported in the Japanese literature with available data using MEDLINE and IGAKU-CHUO-ZASSHI (in Japanese) between 1969 and 1999, including the present case. In squamous cell carcinoma, the most common esophageal malignancy in Japan, the male-to-female ratio of cases is usually 5:1. However, these cases with leiomyosarcoma of the esophagus included 41 males and 23 females. The age of patients ranged between 21 and 83 years (average: 48 years). Leiomyosarcoma was located in the upper third segment of the esophagus in eight (12.5%) cases, the middle third in 22 (34.4%) cases and in the lower third in 34 (53.1%) cases, indicating a higher incidence of this type of tumor in the lower third of the esophagus. This may be due to the anatomical feature of abundant smooth muscles in this area. Tumor size ranged between 2.5 and 24.0 cm (average: 8.8 cm).

Esophageal leiomyosarcomas are often divided into two types: the polypoid type, to which the present case belonged, and infiltrating type based on morphological and pathological findings (2). According to this classification, 48 cases were of the polypoid type, 11 cases of the infiltrating type and five cases of unknown type. Using the available data, the 1-year survival rate in the series of esophageal leiomyosarcoma was 77% among patients with polypoid lesions and 40% among those with infiltrating lesions. Based on our review, patients with polypoid lesions <5 cm in diameter tended to have a better prognosis. These characteristics are in agreement with previous studies demonstrating a better survival rate in patients with polypoid type than in those with the infiltrating type (2,911). Therefore, the prognosis of the present case, which was located in the upper third segment, was of polypoid type and was smaller than 5 cm, would be promising.

Surgical resection was performed in 53 patients, which included esophagectomy in 39 (61%) patients and enucleation in 14 (22%) patients. Eighteen patients underwent additional treatment, including chemotherapy in three, chemoradiotherapy in seven and radiotherapy alone in eight patients. However, the role of chemotherapy and radiotherapy is still controversial. In the literature, we found only two inoperable cases which showed complete tumor regression in response to radiotherapy alone. Chemotherapy did not exhibit any survival benefits. Radiotherapy or chemotherapy may be indicated in inoperable, recurrent or metastatic disease. Resection with esophagectomy should be the standard management for most patients with esophageal leiomyosarcoma. Curative resection was associated with a significant survival benefit (12). Metastases were recognized in the lungs (two cases), liver (nine cases) and lymph nodes (seven cases). However, no metastasis was reported in patients with tumors measuring <5 cm in diameter. Even though hepatic metastases were reported in some cases, aggressive hepatectomy might provide a good prognosis (13,14).

Overall, we conclude that patients with infiltrating type leiomyosarcoma measuring >5 cm in diameter tend to have a poor prognosis, based on a Japanese literature review. Furthermore, the clinicopathological features of Japanese patients are similar to those reported in other parts of the world.

It is important to be aware of the limitations of endoscopic specimens, particularly when the mucosa overlying the tumor mass is intact, as false-negative biopsy specimens may be obtained (15). Because the tumor grows subepithelially, an accurate histopathological diagnosis with a biopsied specimen is often precluded. Preoperative differentiation between leiomyoma and leiomyosarcoma is usually difficult. However, the large specimens with deep layers in our case make histological diagnosis more accurate. To differentiate leiomyomas from leiomyosarcomas, the following criteria suggestive of malignancy have been proposed (2). Accurate diagnosis according to histopathological evaluation includes the rate of mitosis, cellularity, nuclear pleomorphism and tumor necrosis (8). In particular, mitotic activity has been considered an important criteria of malignancy. However, two cases were reported to have minimal mitosis in the tumor, which grew rapidly and were associated with poor prognosis. Therefore, we advocate that the clinical behavior is the only true indication of malignancy. Evaluation following surgery provided the final diagnosis of leiomyosarcoma.

The present case showed asynchronous multiple esophageal malignancies. To our knowledge, only four cases of synchronous esophageal malignancies of carcinoma and leiomyosarcoma have been reported in the literature (47) (Table 1). Moreover, metachronous occurrence is extremely rare and has never been reported. This should be due to the lowest occurrence of leiomyosarcoma in the remnant cervical esophagus. Although the pathogenesis of esophageal leiomyosarcoma is not clear, irradiation for esophageal cancer might be one possible factor inducing this tumor. In our case, 4 years had elapsed between irradiation and identification of the leiomyosarcoma. However, there was no strong evidence for cancers to be induced by irradiation, because radiation-induced changes in the remnant esophagus around the cancer area were not severe. Moreover, there are no reported cases of esophageal leiomyosarcomas diagnosed after irradiation. Therefore, it is possible that these tumors represent sporadic primary esophageal tumors.

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For reprints and all correspondence: Yoshio Naomoto, First Department of Surgery, Okayama University Medical School, 2–5–1 Shikata-cho, Okayama 700-8558, Japan

Figure l. Resected specimen of the first esophageal cancer. (a) The tumor was located in the lower esophagus and measured 7.1 × 4.3 cm in size. (b) Histopathologically, it was diagnosed as well-differentiated squamous cell carcinoma with submucosal invasion (hematoxylin and eosin).

Figure l. Resected specimen of the first esophageal cancer. (a) The tumor was located in the lower esophagus and measured 7.1 × 4.3 cm in size. (b) Histopathologically, it was diagnosed as well-differentiated squamous cell carcinoma with submucosal invasion (hematoxylin and eosin).

Figure 2. Barium meal demonstrating a round, smooth mass in the upper esophagus.

Figure 2. Barium meal demonstrating a round, smooth mass in the upper esophagus.

Figure 3. Endoscopy revealed an intraluminal polypoid lesion in the remnant esophagus with ulceration.

Figure 3. Endoscopy revealed an intraluminal polypoid lesion in the remnant esophagus with ulceration.

Figure 4. Macroscopic features of the leiomyosarcoma. (a) The resected specimen included a nodular tumor measuring 2.4 × 3.0 cm in size in the remnant esophagus. (b) The loupe figure showed the tumor arising from the esophagus, but not from the stomach role.

Figure 4. Macroscopic features of the leiomyosarcoma. (a) The resected specimen included a nodular tumor measuring 2.4 × 3.0 cm in size in the remnant esophagus. (b) The loupe figure showed the tumor arising from the esophagus, but not from the stomach role.

Figure 5. Examination of the tumor. (a) Histopathological examination showing typical interlacing fascicles of pleomorphic spindle-shaped cells with abundant mitotic figures, consistent with the diagnosis of leiomyosarcoma (hematoxylin and eosin). Immunohistochemical staining showed that most tumor cells are positive for smooth muscle actin (b) but negative for cytokeratin (c).

Figure 5. Examination of the tumor. (a) Histopathological examination showing typical interlacing fascicles of pleomorphic spindle-shaped cells with abundant mitotic figures, consistent with the diagnosis of leiomyosarcoma (hematoxylin and eosin). Immunohistochemical staining showed that most tumor cells are positive for smooth muscle actin (b) but negative for cytokeratin (c).

Table 1.

Synchronous esophageal malignancies of carcinoma and leiomyosarcoma

Ref. Year Age (years) Gender Treatment Prognosis (months) 
1951 56 Female Esophagectomy 25, alive 
1961 54 Male Esophagectomy 7, died (brain metastasis) 
1965 71 Female Esophagectomy 1.6, died (operative death) 
1978 56 Male Esophagectomy 3, alive 
Ref. Year Age (years) Gender Treatment Prognosis (months) 
1951 56 Female Esophagectomy 25, alive 
1961 54 Male Esophagectomy 7, died (brain metastasis) 
1965 71 Female Esophagectomy 1.6, died (operative death) 
1978 56 Male Esophagectomy 3, alive 

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Author notes

Departments of 1Surgery I and 2Pathology, Okayama University Medical School, Okayama, Japan