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Keywords
Adenoid cystic carcinoma (ACC), advanced endoscopy, dysphagia, endosonographic ultrasound, esophagus, EUS, EUS-FNA, fine needle aspiration, rare esophageal carcinoma.
Introduction
Adenoid cystic carcinoma is typically a salivary gland tumor. However, it can present in the esophagus. We present the use of endoscopic ultrasound (EUS) and EUS-fine needle aspiration (FNA) in the management of such a case.
Methods for Image Capture/Processing
The Olympus UM-20 echoendoscope and the Pentax FG324A linear array echoendoscope were used
during this procedure.
Case/Body
A 60-year-old male presented with three weeks of solid dysphagia. He denied problems with swallowing liquids, weight loss, or chest pain. The patient had a distant history of smoking and denied any alcohol consumption. There were no relevant findings on physical exam or laboratory tests.
Initial evaluation of his dysphagia was by upper GI x-ray, which showed a possible deformity of the mid-esophagus (Figure 1). This was followed by an upper endoscopy, which revealed a large, smooth, submucosal mass of the upper esophagus from 18 cm to 28 cm (Figure 2). The mucosa over the mass was intact and appeared normal. Chest CT showed a paraesophageal mass starting at approximately the same level as the arch of the aorta (Figure 3). The patient was then referred for endosonography to further delineate the lesion.
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Figure 1 |
Figure 2 |
Figure 3 |
On radial endosonographic evaluation (Figures 4A-4D), the lesion was an isoechoic submucosal solid mass measuring up to 3.2 cm x 2.4 cm in largest cross-sectional diameter (Figure 4A). It appeared to be primarily located in the third endosonographic layer (submucosa) of the esophageal wall (Figure 4B). The mass was in the right wall of the esophagus, adjacent to the azygous arch (Figure 4C). Incidentally, the patient was also noted to have gallstones.
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Figure 4A |
Figure 4B |
Figure 4C |
Figure 4D |
EUS-guided FNA of the submucosal mass revealed a basaloid neoplasm with myoepithelial differentiation (Figures 5A and 5B). The specimen was strongly positive for smooth muscle actin, but staining for S100 was weakly focally positive. The groups of basaloid cells were noted to have hyperchromatic, oval, focally angulated nuclei with rare mitotic canalicular and gland-like structures. The histological differential diagnosis included adenoid cystic carcinoma, squamous cell carcinoma variant, adenoma, or myoepithelioma. Surgical resection was required for symptomatic relief and definitive diagnosis.
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Figure 5A |
Figure 5B |
An Ivor Lewis esophagectomy, cholecystectomy, and Heineke-Mikulicz pyloroplasty were performed to remove the mass and gallbladder, noted to have gallstones on EUS. Although he was asymptomatic from his gallstones, a prophylactic cholecystectomy was performed as part of the tumor resection because of the patient's age, comorbidities of diabetes mellitis, congestive heart failure, and atrial fibrillation. Eight more lymph nodes were noted in dissection of the removed section of esophagus. Grossly, the tumor appeared well-circumscribed and confined to the esophageal wall without extension through the mucosa. Microscopically, the tumor extended through the muscle layers, and, in one section, showed involvement with an external serosal margin (Figure 6A). The tumor had cribriform nests with occasional trabeculae (Figure 6B). No lymphatic or vascular invasion was identified (Figure 6C). The cells were basaloid in appearance, containing small hyperchromatic nuclei with fine chromatin and occasional chromocenters and nucleoli. Eosinophilic cytoplasm was noted to be scant, and scattered apoptotic cells and mitoses were noted (Figure 6D). All margins of the whole specimen were noted to be clear of malignancy. All lymph nodes were found negative for tumor. Because the tumor was composed mostly of cribriform formations rather than of solid components, and, due to the low appearance of mitoses and nuclear atypia, the histological diagnosis was adenoid cystic carcinoma. Oncology consultation for adjuvant therapy of the patient’s adenoid cystic carcinoma recommended no further therapy.
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Figure 6A |
Figure 6B |
Figure 6C |
Figure 6D |
Discussion
Squamous cell carcinomas and adenocarcinomas are the most common esophageal cancers. The less common esophageal malignancies include adenoid cystic, carcinoid, carcinosarcoma, choriocarcinoma, mucoepidermoid, and small cell carcinoma, representing less than 1% of esophageal carcinomas. Adenoid cystic carcinoma of the esophagus has a reported prevalence of 0.07% to 0.8% with approximately 60 reported cases (5,6). This rare cancer of the esophagus has occurred in persons aged 36 to 83 with a mean age prevalence in the early to mid-60s and occurs in men 2.5 to 4.3 times more commonly than in women. A history of tobacco use is not uncommon as well. About half of the reported cases had diffuse metastasis on presentation, usually to the lymph nodes, liver, lung, or brain. Adenoid cystic carcinomas are more commonly found in the salivary glands. At this site, they predominate in women and have a relatively less aggressive course than its extrasalivary manifestations, such as the uterine cervix, lung, anorectal junction, oropharynx, respiratory tract, and mammary gland. In the great majority of cases reviewed, adenoid cystic carcinoma of the esophagus occurred in the middle third to lower third of the esophagus, which is a similar distribution to the origin of squamous cell carcinoma of the esophagus (5,6,7,9).
This report represents the first description of the endosonographic evaluation of one of these rare tumors. The most common submucosal tumor of the esophagus is the gastrointestinal stromal tumor (11). By endosonography, these are typically hypoechoic and originate from the fourth layer (muscularis propria) of the esophagus. On the other hand, this case demonstrates that ACC of the esophagus was isoechoic and primarily submucosal. Other esophageal tumors that may have this appearance also include rare neoplasms such as granular cell tumors and carcinoids (12). Cytologic analysis by EUS-FNA could definitely rule out these other possibilities and was thus helpful in narrowing the differential diagnosis.
Epstein et al. suggest that there are histological differences between the more common origin of this type of carcinoma and its less frequently seen manifestations. A cribiform pattern is present in both, but more solid and basaloid areas were present in the esophageal site. Plus, a greater degree of nuclear pleomorphism, increased number of mitoses, and more direct continuity with the overlying squamous mucosa exist in the esophageal version of adenoid cystic carcinoma (2,6). Kitada et al. describes this rare tumor as having a proliferation of myoepithelial cells and duct lining cells within the cysts with the interstitium containing hyaline materials (3). Epstein et al. goes on to suggest that these features along with its demographics make the tumor more like squamous carcinoma of the esophagus. These similarities to squamous cell carcinoma of the esophagus may explain the aggressive nature of adenoid cystic carcinoma in this extrasalivary location (2,6).
The literature has consistently shown that the basaloid cells of adenoid cystic carcinomas stain with some positivity for keratin, muscle actin, and S-100 protein like myoepithelium.
Tsubochi et al. found that cytokeratin (CK) subtypes as well as other immunohistochemical markers were useful in differentiating the difficult to histologically distinguish basaloid squamous cell, adenoid cystic, and mucoepidermoid carcinomas. Adenoid cystic was immunopositive for CK8 and CK14, basaloid squamous cell was immunopositive for CK14, CK17, and CK19, and mucoepidermoid was positive for CK8, CK14, CK17, and CK19. Adenoid cystic carcinoma was also found to have increased E-cadherin and α-catenin staining, decreased nuclear p53 protein positivity, be non-CEA reactive, and had no CA19-9 immunoreactivity detected (4,9,10).
The histological origin of these tumors is in dispute. The submucosal glands of the esophagus, the neck of the duct of the submucosal glands, the overlying squamous epithelium, or tracheobronchial rests have all been suggested as possibilities. The tumor is known to show coexistence of numerous histological types of cells. Kitada et al. narrows this debate to the origin being from either the esophageal gland or the epithelium, suggesting that the first is more likely with this rare tumor being S-100 positive (1,2,6-9).
Most patients with adenoid cystic carcinoma of the esophagus present with dysphagia, but other presentations include retrosternal chest pain, nausea and vomiting, and post prandial epigastric fullness. Cases had a duration of symptoms averaging three months before presentation (2,7,8). Reviews of previous cases have shown that on occasion the preliminary biopsies suggested different diagnoses, but adenoid cystic carcinoma only in a minority of cases. It was only after excision that definitive diagnosis could be made (9). Lieberman et al. suggests that the rare carcinomas of the esophagus, excluding small-cell, have survival rates similar to squamous cell and adenocarcinoma (5). Unlike the favorable five-year survival rate of adenoid cystic carcinoma of the salivary glands of 60-70%, the esophageal location has a survival rate of 5-10%. The median survival time is approximately nine months by some reports. Surgical resection, radiation, and chemotherapy have all been used for treatment with no consistent effect on survival, but esophagectomy is generally recommended for most of the rare variants of esophageal cancer. Lin et al. concludes that prognosis depends mostly on tumor staging and resectability (2,5,6,7). It seems further studies are needed to delineate which mode or combination of treatment has the best survival rate. In the case presented, surgery proved to at least provide symptomatic relief.
References
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9. Morisaki Y, Yoshizumi Y, Hiroyasu S, Shibata H, Terahata S, Tamai S, Sugiura Y, Shima S, Tanaka S. Adenoid Cystic Carcinoma of the Esophagus: Report of a Case and Review of the Japanese Literature. Surg Today 1996;26:1006-9. <Related link>
10. Tsubochi H, Suzuki T, Suzuki S, Ohashi Y, Ishibashi S, Moriya T, Fujimura S, Sasano H. Immunohistochemical Study of Basaloid Squamous Cell Carcinoma, Adenoid Cystic and Mucoepidermoid Carcinoma in the Upper Aerodigestive Tract. Anticancer Res 2000;20:1205-12. <Related link>
11.
Chak A. Stromal Tumors. In VHJOE (Volume 1, Issue 4) [electronic journal]. Aurora, CO, 2002. Available at http://www.vhjoe.com/Volume1Issue4/1-4-6.htm; INTERNET.
12. Palazzo L, Landi B, Cellier C, Cuillerier E, Roseau G, Barbier JP. Endosonographic Features Predictive of Benign and Malignant Gastrointestinal Stromal Cell Tumors. Gut 2000;46:88-92.
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