Dysphagia in a Man with Down's Syndrome

John C. Deutsch, M.D.
John M. Streitz, M.D.
Brad J. Davis, M.D.

 

Keywords

Dysphagia, Down’s Syndrome, verrucous carcinoma.

 

Introduction

A 51-year-old man with Down’s Syndrome presented with dysphagia, aspiration and a possible fistula. A diagnosis of verrucous squamous cell carcinoma was eventually made through an open biopsy.

 

Methods for Image Capture/Processing

Video was made using SVHS tape and digitally converted with Adobe Premiere software. Other images were captured using digital cameras and edited on Adobe Photoshop software.

 

Disclaimer

No experimental therapies were used. All procedures were performed after obtaining written or verbal permission from the subject's legal guardian.

 

Case/Body

A 51-year-old patient with Down’s syndrome presented with pneumonia. His symptoms failed to resolve with antibiotic therapy and further workup suggested the possibility of a tracheoesophageal fistula and he was transferred to a tertiary care facility.

He lived in a group home. His cognitive impairment from Down’s syndrome was significant, and he did not communicate verbally.

He had a 20 pound weight loss but otherwise had no obvious complaints.

His past history was significant for reflux disease and hypothyroidism. He had a previous cholecystectomy and appendectomy.

His only medication was levothyroxine, 125 mcg per day.

His exam revealed the stigmata of Down’s syndrome. There was no adenopathy. His lung exam revealed rhonchi.

Chest CT showed esophageal thickening through the distal 2/3 of the thorax. There was also significant mediastinal adenopathy.

Figure 1A
Figure 1B

Video Clip 1: Esophagoscopy.

An EGD with biopsy was done showing esophageal obstruction beginning at 25 cm from the incisors; the endoscope could not be passed further than 33 cm from the incisors. (Video 1).

Biopsies revealed hyperplastic squamous epithelium and fungal elements (Figures 2A and 2B).

An EUS with FNA was performed of the mediastinum with FNA showing non malignant squamous cells and admixed inflammation (Figure 3).

Figure 2A
Figure 2B
Figure 3

 

 

 



An Olympus ultrathin GIF XP 160 endoscope was used to traverse the overgrown mucosa. Passage of the endoscope and biopsies cleared a channel through the abnormal mucosa. The abnormality involved approximately 10 cm of the esophagus, from 35 cm to 25 cm from the incisors. A barium swallow done immediately after endoscopy demonstrated no evidence of an esophagopleural fistula. It was presumed the patient had been aspirating.

Since it was unclear if this was a reactive epithelial proliferation or a malignancy, the patient was treated with diflucan and antibiotics for 4 weeks, placed on a liquid diet, and brought back for reevaluation.

Although the patient appeared to have no symptoms related to esophageal obstruction while on the liquid diet, a follow-up EGD now showed essentially complete obstruction of the esophagus at 28 cm from the incisors. The ultrathin endoscope could only be advanced to 32 cm and a wire could not be guided into the stomach fluoroscopically. Multiple deep biopsies were again taken which returned benign tissue (Figures 4A and 4B).

Figure 4A
Figure 4B

 


A CT scan at that time (Figures 5A, 5B,and 5C) showed progression of the disease process.

Figure 5A
Figure 5B
Figure 5C



The patient was therefore taken to the OR where an open gastrostomy, mini-laparotomy, and intraoperative EGD were performed. At the time of surgery, the GE junction was found to be "rock" hard and impassible with a finger from the gastrostomy. The GE junction was then manipulated, and a stiff guidewire was forced endoscopically from the esophagus into the stomach. Savary dilation to 8 mm was accomplished, and a 15 cm long Ultraflex stent (Flange of 23 mm and diameter of 17 mm) was placed endoscopically, while the distal end was positioned manually from the gastrostomy just distal to the tumor.

The diaphragm was opened and intrathoracic biopsies of the esophagus were performed. Histology revealed invasive squamous cell carcinoma (Figures 6A and 6B).

Figure 6A
Figure 6B



The patient was completely palliated by the stent. A barium swallow done three days post operative showed good function (Figures 7A and 7B). A repeat EGD at 30 days showed no evidence of esophageal impairment.

Figure 7A
Figure 7B



Discussion

Verrucous carcinoma of the esophagus is a rare clinicopathologic entity (1-4). Verrucous carcinoma is a well-differentiated squamous cell carcinoma characterized by verrucous (papillary) architecture. Approximately 20 cases of esophageal verrucous carcinoma have been reported in the world literature (1), but there are also cases reported from essentially every other squamous covered site (5-10). The occurrence of verrucous cancer in subjects with Down's syndrome has not been previously reported.

Verrucous carcinoma generally has a predominantly pushing margin rather than an overtly infiltrative pattern characteristic of most squamous cell carcinomas. It is also characterized by minimal cytologic atypia and pronounced parakeratosis. The lack of marked cytologic atypia and overt infiltration often lends an appearance of reactive squamous hyperplasia with parakeratosis on superficial endoscopic biopsies as it did in this case (4). Verrucous carcinoma should be suspected in clinically large villiform lesions despite the lack of marked squamous atypia or obvious invasion. Clinicopathologic correlation is essential in ultimately making a diagnosis based on endoscopic biopsies since a diagnosis of malignancy can only be made if invasion is seen. This is problematic since the invasion occurs deep to the luminal overgrowth. As illustrated, endoscopic biopsies often fail to shown the diagnostic malignant component.

The case subject's initial biopsies demonstrated what appeared to be reactive squamous hyperplasia associated with colonization by fungal organisms consistent with Candida sp. Subsequent biopsies as well as EUS guided brushings and fine needle aspiration demonstrated cytologically bland squamous epithelium with only mild atypia. Histologically, these findings were favored as being reactive. However, given the clinical description of a mass, a low-grade squamous carcinoma was considered in the differential diagnosis. Ultimately an open biopsy of this mass demonstrated diagnostic material with focal unequivocal invasion by a well-differentiated squamous cell carcinoma consistent with a verrucous carcinoma of the esophagus.

It is important to confirm invasion when a papillary overgrowth is found, and cancer is suspected. One can not assume that the gross appearance is enough, as benign squamous proliferation can also occur. For example, a verrucous proliferation has been reported in infectious conditions such as blastomycosis (11). Furthermore, foreign bodies can cause a verrucous proliferation as is occasionally seen following esophageal stenting (12).

Summary

The reported outcomes in subjects with verrucous esophageal cancer suggests that this is a deadly disease, despite the bland histology. Approximately 2/3 of the reported subjects died of disease or direct complications of therapy. The follow up of reported survivors is short (three years or less) (1).
This interesting condition requires a high index of clinical suspicion and persistence in obtaining a definitive diagnosis.


References

1. Osborn NK, Keate RF, Trastek VF, Nguyen CC. Verrucous carcinoma of the esophagus: clinicopathophysiologic features and treatment of a rare entity. Dig Dis Sci. 2003 Mar;48(3):465-74.

2. Tajiri H, Muto M, Boku N, Ohtsu A, Yoshida S, Kawahara H. Verrucous carcinoma of the esophagus completely resected by endoscopy. Am J Gastroenterol. 2000 Apr;95(4):1076-7.

3. Garrard CL, Sheih WJ, Cohn RA, Sawyers JL. Verrucous carcinoma of the esophagus: surgical treatment for an often fatal disease. Am Surg. 1994 Aug;60(8):613-6.

4. Biemond P, ten Kate FJ, van Blankenstein M. Esophageal verrucous carcinoma: histologically a low-grade malignancy but clinically a fatal disease. J Clin Gastroenterol. 1991 Feb;13(1):102-7.

5. Yorganci A, Serinsoz E, Ensari A, Sertcelik A, Ortac F. A case report of multicentric verrucous carcinoma of the female genital tract. Gynecol Oncol. 2003 Aug;90(2):478-81.

6. Heinzerling LM, Kempf W, Kamarashev J, Hafner J, Nestle FO. Treatment of verrucous carcinoma with imiquimod and CO2 laser ablation. Dermatology. 2003;207(1):119-22.

7. Suda Y, Hanamure Y, Kasano F, Kashima N. Nippon Verrucous carcinoma of the nasal cavity: a case report. Jibiinkoka Gakkai Kaiho. 2003 Feb;106(2):156-9.

8. Michelman FA, Filho AC, Moraes AM. Verrucous carcinoma of the penis treated with cryosurgery. J Urol. 2002 Sep;168(3):1096-7.

9. Palascak R, Game X, Milcent S, Camparo P, Berlizot P, Houlgatte A Verrucous epidermoid carcinoma of the bladder unrelated to schistosomiasis. Prog Urol. 2001 Sep;11(4):695-9.

10. Yoshimura Y, Mishima K, Obara S, Nariai Y, Yoshimura H, Mikami T. Treatment modalities for oral verrucous carcinomas and their outcomes: contribution of radiotherapy and chemotherapy. Int J Clin Oncol. 2001 Aug;6(4):192-200.

11. Khandekar A, Moser D, Fidler WJ. Blastomycosis of the esophagus. Ann Thorac Surg. 1980 Jul;30(1):76-9

12. Karras PJ, Barawi M, Webb B, Michalos A. Squamous cell papillomatosis of esophagus following placement of a self-expanding metal stent. Dig Dis Sci. 1999 Mar;44(3):457-61.

 




Editorial Board:
Manoop S. Bhutani, M.D.
Galveston, TX
William R. Brugge, M.D.
Boston, MA
Peter R. McNally, D.O.
Denver, CO
Iqbal S. Sandhu, M.D.
Salt Lake City, UT
Thomas J. Savides, M.D.
San Diego, CA

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