Granular cell tumors of the esophagus are rare neoplasms and their diagnosis is mainly based on histopathologic examination of endoscopic biopsies. With the development of endoscopic techniques, there has been a marked increase in local treatment modalities for early esophageal neoplasms. In this case report, we describe the removal of a granular cell tumor by the endoscopic submucosal dissection technique, and briefly discuss the literature on clinicopathologic aspects and management of granular cell tumors

A Giacobbe

AI Abrikossoff

Akira Sugawara

DS Coutinho

DU Kim

EE Lack

H Makuuchi

H Yamamoto

Hiroto Muroi

Hiroyuki Kato

Hiroyuki Kuwano

I Yasuda

JC Fanburg-Smith

JH Voskuil

JR Gibbons

JR Goldblum

K Saito

Kichiro Otsuka

Kinro Sasaki

L Rezende De

Makoto Sohda

Masahiro Tsubaki

Masanobu Nakajima

Miyako Tsumuraya

MJ Johnston

S Hülagü

S Okahara

SD Cohle

Shinichi Onodera

T Toyanaga

Tatsuya Miyazaki

Yasushi Domeki

English

PubMed

Crossref

Esophagus

Esophageal granular cell tumor successfully resected by endoscopic submucosal dissection

Springer - Publisher Connector

CASE REPORT
Esophageal granular cell tumor successfully resected
by endoscopic submucosal dissection
Masanobu Nakajima • Hiroyuki Kato • Hiroto Muroi • Akira Sugawara •
Miyako Tsumuraya • Kichiro Otsuka • Yasushi Domeki • Shinichi Onodera •
Kinro Sasaki • Masahiro Tsubaki • Makoto Sohda • Tatsuya Miyazaki •
Hiroyuki Kuwano
Received: 22 March 2011 / Accepted: 28 June 2011 / Published online: 14 July 2011
 The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract Granular cell tumors of the esophagus are rare
neoplasms and their diagnosis is mainly based on histo-
pathologic examination of endoscopic biopsies. With the
development of endoscopic techniques, there has been a
marked increase in local treatment modalities for early
esophageal neoplasms. In this case report, we describe the
removal of a granular cell tumor by the endoscopic sub-
mucosal dissection technique, and briefly discuss the lit-
erature on clinicopathologic aspects and management of
granular cell tumors.
Keywords Biopsy  Esophageal neoplasms 
Granular cell tumor  Surgical endoscopy
Introduction
Granular cell tumors (GCT) are relatively infrequent
lesions that were initially described by Abrikossoff [1] as
part of a series of 5 tumors of the tongue, which he termed
myoblastoma. In 1931, he described the first case of this
kind of neoplasm located in the esophagus [2] and since
then approximately 200 cases of GCT have been docu-
mented [3].
In the esophagus, the lesion is generally restricted to the
submucosal layer, although occasionally it can also affect
the mucosal layers and muscularis propria of the organ.
Histologically, different cell types, for example histiocytes,
fibroblasts, or intestinal mesenchymal cells, have been
reported to be the source of this tumor. However, the most
widely accepted theory was that it was of myogenic origin,
hence its former name of ‘‘granular cell myoblastoma’’.
Since 1950 and with the introduction of histochemical
techniques, it has clearly been shown that it is of neuro-
genic origin, arising from the Schwann cells [2] which, in
the esophagus, form part of the submucosal neuronal
plexus. There are many cases of endoscopic mucosal
resection (EMR) as treatment for GCTs. However, to our
knowledge, there are few reports of endoscopic submuco-
sal dissection (ESD) [4]. This article reports a case of a
GCT in the esophagus which was resected by ESD.
Case report
A 51-year-old man received an endoscopic examination
after an esophageal lesion was found in an upper gastro-
intestinal (GI) X-ray series health examination. At the time
of diagnosis he was completely asymptomatic and his
blood tests were normal. Endoscopy identified an elevated
yellow lesion, located 37 cm distal from the incisor teeth
with a submucosal aspect and a depression in the center,
measuring approximately 12 mm, which was rounded and
coated with normal mucosa. Iodine staining showed a
minimally unstained top of the tumor (Fig. 1). Endoscopic
ultrasonography (EUS) using a 20 MHz catheter probe and
the water filling method identified a submucosal tumor
M. Nakajima (&)  H. Kato  H. Muroi  A. Sugawara 
M. Tsumuraya  K. Otsuka  Y. Domeki  S. Onodera 
K. Sasaki  M. Tsubaki
Department of Surgery I, Dokkyo Medical University,
880 Kitakobayashi, Mibu, Shimotsuga-gun,
Tochigi 321-0293, Japan
e-mail: mnakajim@dokkyomed.ac.jp
M. Sohda  T. Miyazaki  H. Kuwano
Department of General Surgical Science (Surgery I),
Gunma University, Graduate School of Medicine,
Maebashi 371-8511, Japan
123
Esophagus (2011) 8:203–207
DOI 10.1007/s10388-011-0283-7
with a diameter of 10 mm. It was solid and the border was
unclear but the bottom of the tumor was demarcated from
the adjacent normal muscle layer, and was therefore con-
firmed to be located in the submucosal layer. The tumor
was hypoechoic, but was hyperechoic compared with the
adjacent muscle layer (Fig. 2). No mediastinal adenopa-
thies were identified. Histological analysis of tissue
obtained with standard endoscopic forceps revealed stroma
infiltrated by cells with eosinophilic cytoplasm of granular
aspect whose central nuclei showed no evidence of atypia
or mitotic figures (Fig. 3). The squamous surface epithe-
lium showed pseudoepitheliomatous hyperplasia. On the
basis of these histopathological findings, the lesion was
diagnosed as a GCT. An upper GI X-ray series showed an
elevated lesion with slight depression at the lower esoph-
agus (Fig. 4). A computed tomography scan of the chest
and abdomen revealed the solid mass in the distal esoph-
agus but no additional pathology.
The patient subsequently underwent an ESD using
sodium hyaluronate, a small-caliber tip transparent hood
(ST hood; Fujifilm, Japan) and a water jet short needle
knife (Flush knife; Fujifilm) according to the method
developed by Toyonaga [5]. The ESD procedure was car-
ried out using a single-channel upper GI endoscope
(Olympus, Japan) and a high-frequency generator with an
Fig. 1 Upper gastrointestinal endoscopy. a An elevated yellow lesion
located 37 cm distal from the incisor teeth, with a submucosal aspect
and a depression in the center, was identified. It was round and mostly
coated with normal mucosa. b Lugol staining showed minimal
unstained top of the tumor
Fig. 2 Endoscopic ultrasonography showing a tumor which was
solid, hypoechoic, with a diameter of 10 mm (T). This tumor was
located in the submucosal layer (white arrow) and demarcated from
the muscle layer (black arrow)
Fig. 3 The histological analysis revealed stroma infiltrated by cells
with eosinophilic cytoplasm of granular appearance whose central
nuclei showed no evidence of atypia or mitotic figures
204 Esophagus (2011) 8:203–207
123
automatically controlled system (Endocut mode; ICC200;
ERBE Elektromedizin, Germany). An ST hood was fitted
on the tip of the endoscope to obtain a constant view and to
create tension on the connective tissue for dissection. Lugol
staining was performed to mark the margins of the lesion.
With use of the Flush knife, dots were placed about 3 mm
outside the margins at 2 mm intervals. Following an initial
injection of 2 mL saline, a submucosal fluid cushion was
created using a solution prepared with a mixture of hyal-
uronic acid, saline, indigo carmine, and epinephrine.
Approximately 2 mL of the solution at a time was injected
into the submucosal layer, and repeated until the mucosa
was elevated. After lifting the lesion, the mucosa was
gently cut with the Flush knife, using the Endocut mode.
En-bloc resection with tumor-free lateral/basal margins
was accomplished (Fig. 5). To control minor bleeding,
hemostatic forceps were used in soft coagulation mode.
The resected specimen contained a massive tumor of
11 9 7 mm, with eosinophilic cytoplasm with a granular
appearance located from the lamina propria mucosae to the
submucosal layer (Fig. 6). The patient was discharged after
1 week without any complications. This method enabled
Fig. 5 Endoscopic submucosal dissection. a Lower esophagus where
the tumor and mucosa were removed. b Macroscopically, the surgical
margin of resected lesion was free from tumor cells
Fig. 4 An upper gastrointestinal X-ray series showed an elevated
lesion with slight depression at the lower esophagus (arrow)
Fig. 6 The resected specimen contained an 11 9 7 mm tumor with
eosinophilic cytoplasm with a granular appearance located from just
below the squamous epithelium to the lamina propria mucosae
Esophagus (2011) 8:203–207 205
123
submucosal incision under direct visualization, and thus
enabled precise determination of both the lateral and ver-
tical margins to be resected. Microscopically, the surgical
margin was free from tumor cells. Follow-up endoscopy
6 weeks after removal of tumor showed scar tissue from
mucosal dissection; no masses or nodules were detected.
Discussion
Although GCTs are uncommon tumors in the GI tract,
nearly one-third occur in the esophagus [6, 7], the most
common site of origin of GI GCTs. Most esophageal GCTs
are found incidentally during endoscopy of the upper GI
performed for other reasons. Although a GCT is usually
asymptomatic, when the tumor is larger than 1 cm, it may
cause dysphagia [3].
A GCT has a characteristic appearance on endoscopy.
The tumor usually appears as a yellowish-white, firm,
sessile submucosal mass. Differential diagnosis should
include an esophageal cyst, epithelial lesions, for example
glycogenic acanthosis, an inflammatory polyp, squamous
papilloma, and other submucosal tumors, for example lei-
omyoma, lipoma, and hamartoma [4].
GCTs were originally considered to be of myogenic
origin, but electron microscopic and immunohistochemical
studies confirmed the Schwann-cell origin of the tumors.
Histologically, these tumors consist of polygonal and
fusiform cells in compact ‘‘nests’’ [8]. Cells have small
dark nuclei and abundant, fine, granular eosinophilic acid-
Schiff-positive, diastase-resistant cytoplasm [9]. GCTs of
the skin, larynx, and esophagus are known to induce
pseudoepitheliomatous hyperplasia in the malpighian epi-
thelium. This feature may simulate a primary squamous
cell carcinoma [7, 10].
Although the natural history of the tumor is unclear,
most esophageal GCTs have a benign clinical course.
However, approximately 1.5–2.7% of all cases reported in
the literature were regarded as malignant variants. The
infiltrative growth pattern and the presence of metastases
are important features in differentiating between malignant
and benign tumors because they may be of very similar
appearance histologically. Malignant lesions are usually
larger than 4 cm, with evidence of rapid recent growth,
tend to recur locally after resection, and may have subtle
histologic features, for example nuclear pleomorphism,
increased nuclear size, tumor cell necrosis, large nucleoli,
mitotic figures (2 or more/10 high power fields), and tumor
cell spindling [11].
The optimum treatment for GCTs remains controversial,
but the current treatment options are a conservative
approach with regular endoscopic follow-up for tumors
\10 mm in diameter without evidence of malignant
change [12], and surgical excision for tumors [20 mm in
diameter, benign GCTs causing symptoms, or when
malignancy is suspected [13]. If no malignant changes are
detected in the removed specimen, additional treatment or
follow-up is not considered necessary [3]. EMR was
recently reported to be an effective treatment, and EUS is
thought to be most useful for deciding if a tumor meets the
criteria for endoscopic removal, including small size
(\20 mm) and non-attachment to the muscle layer [14, 15].
In a series of 650 esophageal mucosal cancers removed
with EMR, Makuuchi [16] reported an incidence of com-
plications of 4.8% (perforation 0.7%, bleeding 3.1%,
stricture 1.6%).
ESD for esophageal pathology has recently been estab-
lished, and the affected mucosa is incised and removed
using a variety of endoscopic electrosurgical knives. Using
ESD, a wider range of the mucosa can be resected in one
piece more reliably using an endoscope. Takahashi et al.
[17] reported that the incidence of complications was not
significantly different between ESD and EMR—perfora-
tion 2.6%, mediastinal emphysema 4.3%, pneumonia 2.6%,
and stenosis 17.2%. In our case, after submucosal injection
of sodium hyaluronate to maintain sufficient thickening of
the submucosal tissue, dissection of the mucosa and sub-
mucosa with a Flush knife was performed by the method
developed by Toyonaga [5]. We preferred ESD for its more
accurate resection than conventional EMR, and sodium
hyaluronate solution for its ability to maintain submucosal
elevation for a longer time [18]. Additional esophagectomy
with lymph node dissection was not required, because no
submucosal invasion or vessel permeation was seen in the
endoscopically resected specimen.
Endoscopic resection is less invasive and, for smaller
tumors, results in fewer complications than esophagec-
tomy; on the other hand there is a case report of EMR of a
malignant GCT with a diameter of 10 mm [17]. With
regard to GCTs from 10 to 20 mm in diameter, we believe
endoscopic resection (EMR or ESD) may be preferable, as
described elsewhere [19, 20].
Concerning esophageal GCTs exceeding 20 mm,
esophagectomy had been performed until quite recently.
However, esophagectomy is the therapeutic option with the
highest mortality [21]. Because ESD has been established
as safer and less invasive therapy, it is expected to be the
best therapeutic option for mucosal or submucosal esoph-
ageal GCTs exceeding 20 mm.
In summary, GCTs of the esophagus are rare neoplasms.
Endoscopic biopsies are the mainstay of diagnosis. Endo-
scopic and endosonographic evaluation of the lesion
defines the location and extent of the tumor and its suit-
ability for endoscopic treatment. ESD is a safe and accurate
procedure for identified cases.
206 Esophagus (2011) 8:203–207
123
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https://link.springer.com/content/pdf/10.1007%2Fs10388-011-0283-7.pdf

Esophageal granular cell tumor successfully resected by endoscopic submucosal dissection

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