- Email: [email protected]
Adenocarcinoma of the upper esophagus
Clinics and Research in Hepatology and Gastroenterology (2011) 35, 418—419
CASE REPORT
Adenocarcinoma of the upper esophagus A. Bard a, T. Coton a,∗, C. De Biasi b, M. Guisset a a b
Service de pathologie digestive, HIA Laveran, BP 60149, 13384 Marseille cedex 13, France Laboratoire d’anatomopathologie, hôpital d’instruction des armées Lavéran, BP 60149, 13384 Marseille cedex 13, France
Available online 26 February 2011
Summary Glandular heterotopia of the upper esophagus is a congenital abnormality that is frequently discovered during upper digestive tract endoscopy (in 0.26—4.9% of cases), but usually with no malignant potential. Indeed, adenocarcinoma of the upper esophagus related to such lesions is a rare entity. We report here the 27th observation of this rare type of tumor in an 87-year-old man complaining of cervical dysphagia. This adenocarcinoma had developed from an area of gastric heterotopia 3 cm below the upper sphincter of the esophagus. The treatment regimen was based on exclusive radiochemotherapy, which led to a complete endoscopic response at the end of treatment. The patient’s symptom-free survival was six months and overall survival was 17 months from diagnosis. This case of a rare tumor of the upper esophagus raises the question of whether the detection and surveillance of this type of heterotopia would be useful and, thus, to be recommended. © 2011 Elsevier Masson SAS. All rights reserved.
Observation Although glandular heteropia in the upper esophagus is frequently discovered during examination of the upper digestive tract by endoscopy, it is usually a benign finding. Nevertheless, 26 cases of esophageal adenocarcinoma have been reported at this location [1], and this is another report of such an observation. A 87-year-old man was hospitalized on May 4th, 2009 with upper esophageal dysphagia to solids, lasting for four months, with odynophagia and cough. The patient was a retired teacher and former smoker, with a history of high blood pressure, coronary heart disease treated by coronary bypass in 2000, colon adenocarcinoma surgically cured since
∗
Corresponding author. Fax: +33-491-617023. E-mail address: [email protected] (T. Coton).
1999, L3—L4 laminectomy for lumbar spinal stenosis, a right hip prosthesis and bladder carcinoma in 2007 that recurred in 2009. His clinical examination was normal. Blood analyses showed normocytic anemia (hemoglobin at 10.5 g/dL) with no deficiency, and a moderate inflammatory syndrome (Creactive protein [CRP]: 30 mg/L). ENT examination and bronchoscopy were also normal. On the other hand, upper digestive tract endoscopy revealed a budding, halfcircumferential lesion located 18—26 cm from the dental arcades. Pathological analyses concluded that the lesion was a moderately differentiated adenocarcinoma, expressing cytokeratin (CK) 20 (no immunostaining for chomogranin, synaptophysin, CD56/neural cell adhesion molecule [NCAM], CK5/6, CK7 or thyroid transcription factor-1 [TTF1]), with no underlying Barrett’s esophagus. The tumor was classified as usT3 N1 by echoendoscopy, and cervical, thoracic, abdominal and pelvic computed tomography (CT) found no metastases.
2210-7401/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.clinre.2011.01.010
Adenocarcinoma of the upper esophagus Because the patient was elderly and had coexisting uncontrolled neoplasia, exclusive radiochemotherapy was proposed, according to the following protocol: bifractionated radiotherapy of 42 Gy in five sequences of five days for five weeks (with one week of rest), following a conformational three-dimensional (3D) technique using image-guided radiotherapy (IGRT), and concomitant chemotherapy using cisplatin alone, because of the patient’s history of coronary heart disease and elderly age (infusions of 7 mg/m2 over three days each week, for 10 weeks). At the end of treatment, the patient was symptom-free and showed a complete endoscopic response. Six months later, a recurrent upper dysphagia to solids revealed local recurrence of the adenocarcinoma as a halfcircumferential, ulcerovegetating tumor, lying 22—25 cm the wings of the nose on upper digestive endoscopy; this was confirmed by histopathology. Palliative treatment, involving the insertion of an esophageal cervical endoprosthesis that had initially been refused by the patient, was carried out in August 2010. The patient died in October 2010, 17 months after the initial diagnosis.
419 of the upper esophagus are difficult, although a limited resection after neoadjuvant treatment may be attempted [1,10]. In cases of superficial tumor, endoscopic resection can be proposed and completed, if necessary, by chemotherapy. Those two options were not chosen in our patient, aged 87 with a second progressive neoplasia. However, exclusive radiochemotherapy was selected, which allowed him six months of symptom-free survival with optimal digestive comfort. Death occurred 17 months after the initial diagnosis. In conclusion, given the consensus recommendation to perform careful and complete esophageal examination during upper digestive tract endoscopy, should systematic biopsies also be carried out when areas of glandular heterotopia are found in the upper esophagus? Von Rahden et al. [1] proposed that patients with low-grade dysplastic lesions within areas of heterotopia must be followed, and that those with high-grade dysplasia must be treated as for Barrett’s esophagus. This would also mean that biopsies must be practised at least once in patients with lesions in areas of gastric heterotopia in the upper esophagus. However, at present, discussion of this issue remains open.
Discussion In contrast to lower esophageal adenocarcinoma, carcinoma of the upper esophagus is a rare tumor that, to our knowledge, has only been previously reported in 26 published cases. This type of tumor develops in areas of congenital glandular heterotopia (incomplete replacement of original glandular mucosa during embryogenesis) of gastric type in the upper esophagus, although degeneration appears to be rare [1]. Indeed, finding lesions of glandular metaplasia in the upper esophagus (inlet patch) [2] usually occurs during endoscopy (in 0.26—1.1% of cases) [2,3], and their prevalence is likely to be underestimated because their location—–just under the upper sphincter of the esophagus— –favors their being missed when the endoscope is quickly withdrawn, as evidenced by a prevalence rate that is six to ten times higher (2.6—4.9%) with experienced operators [4,5]. The lesions may be found single with variable sizes up to 30 mm, in pairs (‘‘kissing’’) or multiple [6,7], and can involve corporeal, transitional and antral gastric metaplasia (20.5%, 28.2% and 18%, respectively) [3]. In that series intestinal metaplasia was found in 12.8% of cases, but no cases of dysplasia. Also, they are often associated with gastritis, esophagitis or endobrachyesophagus. Colonization by Helicobacter pylori is not unusual and was also associated in the stomach in 18.7% of cases [8]. Such lesions are more often clinically latent but can, nevertheless, cause stenosis, hemorrhage, fistula and perforation [4]. For this reason, von Rahden et al. [9] proposed a histoclinical classification (heterotopic gastric mucosa [HGM] I to V: symptom-free to adenocarcinoma, respectively). The 26 previously reported cases of upper esophageal carcinoma showed that areas of heterotopia can degenerate. In our patient, endoscopy and immunostaining (CK20+ /CK7−) led to the suspicion of possible heteropia of the gastric mucosa in the upper esophagus, although a CK20+ /CK7+ profile would have been more typical. The locations of these lesions make this type of cancer difficult to treat, and their rarity does not allow any standardized recommendations. Indeed, surgical approaches
Conflict of interest statement The authors declare no conflict of interest for this work.
References [1] Von Rahden BH, Stein HJ, Becker SK, Siewert RJ. Esophageal adenocarcinomas in heterotopic gastric mucosa: review and report of a case with complete response to neoadjuvant radiochimiotherapy. Dig Surg 2005;22:107—12. [2] Tang P, Mckinley MJ, Sporrer M, Kahn E. Inlet patch: prevalence, histologic type and association with esophagitis, Barrett esophagus and antritis. Arch Pathol Lab Med 2004;128:444—7. [3] Song ZY, Huang KD, Peng JP, Sun AW, Zhang YY, Zhao ZG. Clinical analysis of 39 cases of heterotopic gastric mucosa in the upper esophagus. Zhonghua Yi Xue Za Zhi 2005;85:244—7. [4] Azar C, Jamali F, Tamim H, Abdul-Baki H, Soweid A. Prevalence of endoscopically identified heterotopic gastric mucosa in the proximal esophagus: endoscopist dependent? J Clin Gastroenterol 2007;41:468—71. [5] Jacobs E, Dehou MF. Heterotopic gastric mucosa in the upper esophagus: a prospective study of 33 cases and review of literature. Endoscopy 1997;29:710—5. [6] Maconi G, Pace F, Vago L, Carsana L, Bargiggia S, Bianchi Porro G. Prevalence and clinical features of heterotopic gastric mucosa in the upper esophagus (inlet patch). Eur J Gastroenterol Hepatol 2000;12:745—9. [7] Akbayir N, Alkim C, Erdem L, Sökmen HM, Sungun A, Basak T, et al. Heterotopic gastric mucosa in the cervical esophagus (inlet patch): endoscopic prevalence, histological and clinical characteristics. J Gastroenterol Hepatol 2004;19:891—6. [8] Borhan-Manesh F, Farnum JB. Study of Helicobacter pylori colonization of patches of heterotopic gastric mucosa (HGM) at the upper esophagus. Dig Dis Sci 1993;38:142—6. [9] Von Rahden BH, Stein HJ, Becker K, Liebermann-Meffert D, Siewert JR. Heterotopic gastric mucosa of the esophagus: literature review and proposal of a clinicopathologic classification. Am J Gastroenterol 2004;99:543—51. [10] Alrawi SJ, Winston J, Tan D, Gibbs J, Loree TR, Hicks W, et al. Primary adenocarcinoma of cervical esophagus. J Exp Clin Cancer Res 2005;24:325—30.
CASE REPORT
Adenocarcinoma of the upper esophagus A. Bard a, T. Coton a,∗, C. De Biasi b, M. Guisset a a b
Service de pathologie digestive, HIA Laveran, BP 60149, 13384 Marseille cedex 13, France Laboratoire d’anatomopathologie, hôpital d’instruction des armées Lavéran, BP 60149, 13384 Marseille cedex 13, France
Available online 26 February 2011
Summary Glandular heterotopia of the upper esophagus is a congenital abnormality that is frequently discovered during upper digestive tract endoscopy (in 0.26—4.9% of cases), but usually with no malignant potential. Indeed, adenocarcinoma of the upper esophagus related to such lesions is a rare entity. We report here the 27th observation of this rare type of tumor in an 87-year-old man complaining of cervical dysphagia. This adenocarcinoma had developed from an area of gastric heterotopia 3 cm below the upper sphincter of the esophagus. The treatment regimen was based on exclusive radiochemotherapy, which led to a complete endoscopic response at the end of treatment. The patient’s symptom-free survival was six months and overall survival was 17 months from diagnosis. This case of a rare tumor of the upper esophagus raises the question of whether the detection and surveillance of this type of heterotopia would be useful and, thus, to be recommended. © 2011 Elsevier Masson SAS. All rights reserved.
Observation Although glandular heteropia in the upper esophagus is frequently discovered during examination of the upper digestive tract by endoscopy, it is usually a benign finding. Nevertheless, 26 cases of esophageal adenocarcinoma have been reported at this location [1], and this is another report of such an observation. A 87-year-old man was hospitalized on May 4th, 2009 with upper esophageal dysphagia to solids, lasting for four months, with odynophagia and cough. The patient was a retired teacher and former smoker, with a history of high blood pressure, coronary heart disease treated by coronary bypass in 2000, colon adenocarcinoma surgically cured since
∗
Corresponding author. Fax: +33-491-617023. E-mail address: [email protected] (T. Coton).
1999, L3—L4 laminectomy for lumbar spinal stenosis, a right hip prosthesis and bladder carcinoma in 2007 that recurred in 2009. His clinical examination was normal. Blood analyses showed normocytic anemia (hemoglobin at 10.5 g/dL) with no deficiency, and a moderate inflammatory syndrome (Creactive protein [CRP]: 30 mg/L). ENT examination and bronchoscopy were also normal. On the other hand, upper digestive tract endoscopy revealed a budding, halfcircumferential lesion located 18—26 cm from the dental arcades. Pathological analyses concluded that the lesion was a moderately differentiated adenocarcinoma, expressing cytokeratin (CK) 20 (no immunostaining for chomogranin, synaptophysin, CD56/neural cell adhesion molecule [NCAM], CK5/6, CK7 or thyroid transcription factor-1 [TTF1]), with no underlying Barrett’s esophagus. The tumor was classified as usT3 N1 by echoendoscopy, and cervical, thoracic, abdominal and pelvic computed tomography (CT) found no metastases.
2210-7401/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.clinre.2011.01.010
Adenocarcinoma of the upper esophagus Because the patient was elderly and had coexisting uncontrolled neoplasia, exclusive radiochemotherapy was proposed, according to the following protocol: bifractionated radiotherapy of 42 Gy in five sequences of five days for five weeks (with one week of rest), following a conformational three-dimensional (3D) technique using image-guided radiotherapy (IGRT), and concomitant chemotherapy using cisplatin alone, because of the patient’s history of coronary heart disease and elderly age (infusions of 7 mg/m2 over three days each week, for 10 weeks). At the end of treatment, the patient was symptom-free and showed a complete endoscopic response. Six months later, a recurrent upper dysphagia to solids revealed local recurrence of the adenocarcinoma as a halfcircumferential, ulcerovegetating tumor, lying 22—25 cm the wings of the nose on upper digestive endoscopy; this was confirmed by histopathology. Palliative treatment, involving the insertion of an esophageal cervical endoprosthesis that had initially been refused by the patient, was carried out in August 2010. The patient died in October 2010, 17 months after the initial diagnosis.
419 of the upper esophagus are difficult, although a limited resection after neoadjuvant treatment may be attempted [1,10]. In cases of superficial tumor, endoscopic resection can be proposed and completed, if necessary, by chemotherapy. Those two options were not chosen in our patient, aged 87 with a second progressive neoplasia. However, exclusive radiochemotherapy was selected, which allowed him six months of symptom-free survival with optimal digestive comfort. Death occurred 17 months after the initial diagnosis. In conclusion, given the consensus recommendation to perform careful and complete esophageal examination during upper digestive tract endoscopy, should systematic biopsies also be carried out when areas of glandular heterotopia are found in the upper esophagus? Von Rahden et al. [1] proposed that patients with low-grade dysplastic lesions within areas of heterotopia must be followed, and that those with high-grade dysplasia must be treated as for Barrett’s esophagus. This would also mean that biopsies must be practised at least once in patients with lesions in areas of gastric heterotopia in the upper esophagus. However, at present, discussion of this issue remains open.
Discussion In contrast to lower esophageal adenocarcinoma, carcinoma of the upper esophagus is a rare tumor that, to our knowledge, has only been previously reported in 26 published cases. This type of tumor develops in areas of congenital glandular heterotopia (incomplete replacement of original glandular mucosa during embryogenesis) of gastric type in the upper esophagus, although degeneration appears to be rare [1]. Indeed, finding lesions of glandular metaplasia in the upper esophagus (inlet patch) [2] usually occurs during endoscopy (in 0.26—1.1% of cases) [2,3], and their prevalence is likely to be underestimated because their location—–just under the upper sphincter of the esophagus— –favors their being missed when the endoscope is quickly withdrawn, as evidenced by a prevalence rate that is six to ten times higher (2.6—4.9%) with experienced operators [4,5]. The lesions may be found single with variable sizes up to 30 mm, in pairs (‘‘kissing’’) or multiple [6,7], and can involve corporeal, transitional and antral gastric metaplasia (20.5%, 28.2% and 18%, respectively) [3]. In that series intestinal metaplasia was found in 12.8% of cases, but no cases of dysplasia. Also, they are often associated with gastritis, esophagitis or endobrachyesophagus. Colonization by Helicobacter pylori is not unusual and was also associated in the stomach in 18.7% of cases [8]. Such lesions are more often clinically latent but can, nevertheless, cause stenosis, hemorrhage, fistula and perforation [4]. For this reason, von Rahden et al. [9] proposed a histoclinical classification (heterotopic gastric mucosa [HGM] I to V: symptom-free to adenocarcinoma, respectively). The 26 previously reported cases of upper esophageal carcinoma showed that areas of heterotopia can degenerate. In our patient, endoscopy and immunostaining (CK20+ /CK7−) led to the suspicion of possible heteropia of the gastric mucosa in the upper esophagus, although a CK20+ /CK7+ profile would have been more typical. The locations of these lesions make this type of cancer difficult to treat, and their rarity does not allow any standardized recommendations. Indeed, surgical approaches
Conflict of interest statement The authors declare no conflict of interest for this work.
References [1] Von Rahden BH, Stein HJ, Becker SK, Siewert RJ. Esophageal adenocarcinomas in heterotopic gastric mucosa: review and report of a case with complete response to neoadjuvant radiochimiotherapy. Dig Surg 2005;22:107—12. [2] Tang P, Mckinley MJ, Sporrer M, Kahn E. Inlet patch: prevalence, histologic type and association with esophagitis, Barrett esophagus and antritis. Arch Pathol Lab Med 2004;128:444—7. [3] Song ZY, Huang KD, Peng JP, Sun AW, Zhang YY, Zhao ZG. Clinical analysis of 39 cases of heterotopic gastric mucosa in the upper esophagus. Zhonghua Yi Xue Za Zhi 2005;85:244—7. [4] Azar C, Jamali F, Tamim H, Abdul-Baki H, Soweid A. Prevalence of endoscopically identified heterotopic gastric mucosa in the proximal esophagus: endoscopist dependent? J Clin Gastroenterol 2007;41:468—71. [5] Jacobs E, Dehou MF. Heterotopic gastric mucosa in the upper esophagus: a prospective study of 33 cases and review of literature. Endoscopy 1997;29:710—5. [6] Maconi G, Pace F, Vago L, Carsana L, Bargiggia S, Bianchi Porro G. Prevalence and clinical features of heterotopic gastric mucosa in the upper esophagus (inlet patch). Eur J Gastroenterol Hepatol 2000;12:745—9. [7] Akbayir N, Alkim C, Erdem L, Sökmen HM, Sungun A, Basak T, et al. Heterotopic gastric mucosa in the cervical esophagus (inlet patch): endoscopic prevalence, histological and clinical characteristics. J Gastroenterol Hepatol 2004;19:891—6. [8] Borhan-Manesh F, Farnum JB. Study of Helicobacter pylori colonization of patches of heterotopic gastric mucosa (HGM) at the upper esophagus. Dig Dis Sci 1993;38:142—6. [9] Von Rahden BH, Stein HJ, Becker K, Liebermann-Meffert D, Siewert JR. Heterotopic gastric mucosa of the esophagus: literature review and proposal of a clinicopathologic classification. Am J Gastroenterol 2004;99:543—51. [10] Alrawi SJ, Winston J, Tan D, Gibbs J, Loree TR, Hicks W, et al. Primary adenocarcinoma of cervical esophagus. J Exp Clin Cancer Res 2005;24:325—30.