Kissing tumors; the concurrent diagnosis of leiomyosarcoma and squamous cell carcinoma of the esophagus

Background Esophageal leiomyosarcoma (LMS) is a rare tumor that constitutes less than 1% of all malignant esophageal tumors. Concurrent occurrence of esophageal leiomyosarcoma with squamous cell carcinoma (SCC) is even rarer than isolated leiomyosarcoma. Case presentation In this report, we present a case of concurrent leiomyosarcoma and SCC in a 64-year-old woman presenting with vomiting and solid dysphagia, which has not been properly diagnosed following several referrals and diagnostic modalities. At last Exploratory laparotomy with gastric pull-up was performed in addition to radical laryngectomy with partial resection of the esophagus and subtotal thyroidectomy. Pathologic evaluation of the surgical specimen showed concurrent LMS (5.2 × 4.5 × 3 cm) and SCC (1.5 × 0.6 × 0.6 cm) at the same anatomical level in the proximal esophagus. Conclusions This study proposes the importance of using ancillary diagnostic tests such as immunohistochemistry (IHC) to diagnose less common cases such as concurrent LMS and SCC.


Background
Esophageal carcinoma is the eighth most common cancer worldwide with a poor prognosis due to its overly aggressive nature [1]. The two typical esophageal carcinoma forms, accounting for 95% of esophageal malignancies, include squamous cell carcinoma (SCC), arising from the squamous epithelial adenocarcinoma, affecting columnar glandular cells. Less than 1-2% of esophageal cancers are sarcomas, while other carcinomas, like melanomas, leiomyosarcomas, carcinoids, and lymphomas account for less than 1% of esophageal malignancies [2]. Leiomyosarcoma (LMS) is a high-grade slow-growing smooth muscle connective tissue tumor with late metastasis observed in different organs, such as the gastrointestinal tract and uterus. [3]. There are few case reports of esophageal LMS [4,5]. There are even fewer cases reporting esophageal LMS with SCC, occurring/diagnosed simultaneously [6], or after esophageal SCC [7]. Some have also reported LMS and SCC's simultaneous incidence in the larynx [8] and oral cavity [9]. These reports refer to the possible concurrency of LMS and SCC in the upper aero-gastrointestinal tract. Nevertheless, the number of reported cases are very few, and there is much to be known in this regard. Here, we report a case of concurrent esophageal LMS and SCC anatomically located at the same level in a 64-year-old woman, presenting with vomiting and dysphagia, diagnosed and treated appropriately.

Case presentation
The patient was a 64-year-old woman with seven children brought to the hospital with severe vomiting and a history of solid dysphagia; she had the symptoms for three months and was referred to different physicians, left without definite diagnosis before admission to our center.. Patient's past medical history was unremarkable. Post-contrast computed tomography (CT) of the neck showed two lesions (kissing tumors) in the upper esophagus, causing the tracheal shift to the right side with no lymph node enlargement ( Fig. 1). Physical examination revealed no abnormalities, and the results of laboratory examinations were within the normal range. CT-guided fine-needle aspiration biopsy evaluation of the mass showed a few pleomorphic spindle malignant cells among inflammatory cells in a bloody background. Additional endoscopy of the esophagus, stomach, and duodenum was performed for the patient, which showed a large tumor in the cricopharyngeus causing stricture, while the stomach and duodenum were normal. (Fig. 2). The patient was scheduled for exploratory laparotomy with the exploration of cervical organs, resection of the pharynx, thyroid (partial), and esophagus and gastric pull up along with the insertion of a tracheostomy and bilateral chest tube, and cervical penrose.

Surgical procedure
The patient was laid in a supine position. After preparation and sterilization, the abdomen was opened by a high midline incision. The surgeon inserted his finger into the mediastinum to assess the presence of any tumors. Stomach was mobilized by harmonic ligasure, lesser sac was opened, short gastric and left gastric arteries were ligated, and gastric pedicle was made on the right gastroepiploic arteries and epigastric area. Then, the esophagus was dissected bluntly by the finger in the mediastinum through the hiatus's opening and continued upward. Adhesion to the carina was found and released meticulously. Next, the collar incision was made on the neck. Then, subtotal thyroidectomy was done, and the specimen was sent for pathologic evaluation. Trocar was introduced in the sheath over the spine, and the esophagus was gently dissected and pulled up. The esophagus' blunt dissection was also carried out from the above until two hands could reach each other via the upper and lower incisions. After the esophagus' full release, resection of pharynx, larynx, and esophagus was done, and specimens of the proximal esophagus were sent for further pathological evaluation. Then, anastomosis of the mouth floor to the stomach was performed with polydioxanone suture 3/0, and the neck wound was irrigated and closed after insertion of a Penrose drain. The posterior part of the trachea was then fixed to the skin with Vicryl 3/0, and tracheostomy tube size 7.5 was inserted. The abdomen was irrigated, and the fascia was closed with a nylon loop one and irrigated. The skin was closed by nylon 3/0. Bilateral chest tubes No. 24 were inserted into the 5th intercostal space with a depth of 10 cm and fixed with silk 0 dressing. The surgery lasted for five hours and thirty minutes, and the patient received two packed cells and 6500 cc normal saline and had 4000 cc urination and 450 cc bleeding.

Pathologic results
The gross pathological evaluation showed two separate grey cream masses with a smooth glistening surface at the cricopharyngeal level that made a stricture, as shown in Fig. 2. Microscopic evaluation showed malignant pleomorphic spindle cell neoplasm with high mitotic rate and many atypical mitoses in the larger  (Fig. 3) Immunohistochemistry (IHC) evaluation of the larger mass sections revealed negative results for P63, desmin, CD34, c-kit, DOG1, and cytokeratin (CK). It was diffusely positive for smooth muscle actin (SMA), S100, and also the high expression of proliferation index Ki67 to up to 15% was suggestive of malignant smooth muscle tumor. (Fig. 3) IHC evaluation of the smaller mass shows diffuse CK, P63 positivity (Fig. 3), and negative immunostaining for S100 and SMA was observed, which indicates the diagnosis of SCC. Tumors had no lymphovascular invasion, and the resection was curative with negative horizontal and vertical margins. Histopathological evaluation of the thyroid specimen shows nodular hyperplasia. Seven regional lymph nodes were free of metastasis.
The patient was discharged after ten days of hospital admission and was referred to the radio-oncologist. The patient underwent radiotherapy and was stable at six months' follow-up with no recurrence.

Discussion
We presented a case with concurrent LMS and SCC in the proximal esophagus without invasion to other organs. Fortunately, the patient was appropriately treated with a radical laryngectomy, partial resection of the esophagus, and subtotal thyroidectomy. The case presented in this study had undergone several diagnostic investigations, including ultrasound, endoscopy, FNA, and pathologic examinations, leaving the patient without a definite diagnosis. As the presence of a tumor was suspected, we performed exploratory laparotomy for the patient with the exploration of cervical organs, resection of the pharynx, thyroid (partial), and esophagus in addition to gastric pull up along with the insertion of a tracheostomy and bilateral chest tubes, and cervical Penrose. This intervention was chosen considering that simultaneous resection of other solid organs and esophagectomy is considered to increase the chance of survival [10]. The specimens' histopathologic results showed that all organs, other than the proximal esophagus, such as distal margins of the esophagus, tracheal margin, larynx, epiglottis, and nuchal cord were free of tumor, and there was no need for further resection.
LMS is a rare tumor of the esophagus, and there are few similar cases reported in the literature [4,5]. It is estimated that esophageal LMS accounts for about 0.5% of esophageal carcinomas [3]. Esophageal LMS concurrent with carcinoma is even rarer [6,9,[11][12][13][14][15][16]. The summary of such cases is presented in Table 1. To our knowledge, there are only eight cases of simultaneous LMS and SCC, of which three cases were in the esophagus [6,15,16]. In a study by Jang et al. [6], a 72-year-old male patient presenting with chest pain was diagnosed with polypoid LMS in mid esophagus combined with SCC, similar to our case. However, the diagnostic method and tumor progression differed, as they reported a rapidly growing LMS, although LMS is generally considered a tumor with a slow growth rate [17]. Nakao et al. [7] also reported a 52-year-old Japanese man who developed esophageal LMS without metastasis four years after undergoing subtotal esophagectomy following the diagnosis of a well-differentiated SCC of the lower esophagus. We must insist that the currently presented case's novelty is the concurrent diagnosis of two separate LMS and SCC masses at the same anatomical level of the esophagus. There have also been few case reports of concurrent LMS and SCC   [8,14] and oral cavity [9], that could propose a possible connection between LMS and SCC in the upper aerodigestive system. As esophagus LMS symptoms are not different from other esophageal carcinomas and patients present mainly with dysphagia and/or chest pain [4], more accurate diagnostic methods are required for diagnosis. In our case, several modalities such as ultrasound, endoscopy, and FNA could not result in a definitive diagnosis, and we had to perform exploratory surgery for resection of the organs suspected of tumor involvement. Jang and colleagues suggested using the Positron emission tomography/computed tomography scan as a useful tool in diagnosing esophageal LMS [6]. Nakao et al. [7] also performed IHC examination that showed positive SMA and vimentin and negative CK and S100, which is similar to the present study showing positive results for SMA and Ki67 expression in LMS.

Conclusion
By presenting this rare case of concurrent esophageal LMS and SCC, the authors aimed to highlight the concurrency of such a diagnosis that has a high probability of being misdiagnosed in a patient. We must also propose that such cases urge ancillary diagnostic tests such as IHC in the better evaluation of a patient's tumor and lead to a more definite and proper diagnosis.