Dysphagia, Down’s Syndrome, verrucous
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.
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permission from the subject's legal guardian.
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
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.
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.
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
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).
A CT scan at that time (Figures 5A, 5B,and 5C) showed progression
of the disease process.
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).
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.
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).
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.
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