Granular Cell Tumor of the Proximal Esophagus

A Rare Disease

HERM.ANUS D. VUYK, MD,' GORDON B. SNOW, MD, PHD,* RAMMOHAN M. TIWARI, MS, FRCS, PHD,' DICK VAN VELZEN, MD,t AND ROELOF W. VELDHUIZEN, MD, PHDt

In 1926, Abrikossoff described a tumor, usually benign, which only rarely appears in the esophagus. In a 40-year-old woman, the authors found a multicentric granular cell tumor which was localized in the cervical esophagus and in the subcutaneous tissues over the right scapula; it was removed surgically. Granular cell tumors causing stenosis of the upper esophagus have been described only four times in the literature. Characteristics and treatment are discussed.

Cancer 55445-449, 1985.

RANULAR CELL TUMOR (granular cell myoblas- G toma) is a rare and usually benign tumor which is predominantly found in the head and neck region, espe- cially in the tongue. Since Abrikossof described the basic histolalgic features of this entity in 1926, there have been more than 1,000 cases reported. Because this rare tumor usually presents as a nonspecific painless mass, a correct diagnalsis before surgical excision or biopsy is seldom made. The histogenesis and etiology are still disputed, but a rieurogenic derivation is generally favored.

The primary location of Abrikossof's tumor in the esophaLgus is rare. So far only 36 cases have been de- scribed in the l i t e r a t ~ r e . ~ - ~ Virtually all cases presented as small, well-localized lesions, with a plaque-like ap- pearance not larger than approximately 1 cm in diame- ter. The lesion usually runs a benign course and is fre- quently diagnosed as a chance finding at autopsy.

This, report presents a patient with a constricting gran- ular cell tumor of the proximal esophagus, which has been described only four times in the world literature.

Case Report A 40,-year-old white woman had been complaining of swal-

lowing difficulties caused by an obstruction high "in the neck" for the last 10 years. During the last month, swallowing had become progressively difficult, and as a result she could not take solid food anymore and could barely drink liquids. She had lost 10 kg of weight during the last few months.

From the *Department of Otolaryngology and the TInstitute of Pa- thology, Free University Hospital, Amsterdam, the Netherlands.

Address for reprints: H. D. Vuyk, MD, Department ofOtolaryngol- ogy, Free University Hospital, de Boelelaan 1 117, 1081 HV Amster- dam, the Netherlands.

Accepted for publication January 13, 1984.

As a child she had suffered from meningitis, which had caused bilateral deafness.

Recently oesophagoscopy had been performed elsewhere. Because of extreme stenosis, even a small size scope could not be passed. There was no evidence of mucosal ulceration. After dilatation a nasogastric feeding tube was inserted. The patient was referred to our department for additional evaluation and treatment,

On general examination the only abnormality found was a nonsymptomatic subcutaneous nodule over the right scapula. All laboratory data were within normal limits. She was not anemic and total serum iron was normal.

On indirect laryngoscopy, stasis of saliva in both piriform sinuses was found. The vocal cords had a normal appearance and were mobile on phonation. X-ray examination of a bar- ium swallow demonstrated a stricture extending approxi- mately 4 cm in the upper esophagus (Fig. 1). Computed tomog- raphy (CT) scanning demonstrated a tumor in the proximal part of the esophageal wall, encircling the feeding tube, causing an increase of soft tissue between the larynx and the cervical spine (Fig. 2). The tumor appeared to have well-defined edges and caused a tracheal impression.

A tracheoesophagoscopy was performed. Just below the esophageal introitus, a severe firm circular stenosis was found with intact overlying mucosa. A deep biopsy was taken. Begin- ning about 0.5 cm below the glottis, a forward bulging of the dorsal tracheal wall was seen. A needle aspiration biopsy from the posterior tracheal wall was taken. No histologic or cytologic diagnosis could be made from the material obtained.

Therefore an exploration of the neck was camed out. A vertical incision was made along the anterior border of the right sternomastoid muscle. The omohyoid muscle was di- vided and the right laryngeal nerve was identified. An inci- sional biopsy was taken from a whitish, 4-cm tumor in the wall of the esophagus. On histopathologic examination, a diagnosis ofgranular cell tumor was made. Surgical excision was consid- ered to be the best treatment for this condition. After careful dissection of the esophagus from the trachea and identification

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446 CANCER January 15 1985 Vol. 55

FIG. 1. X-ray of upper esophagus with contrast. Notice fusiform stenosis over approximately 4 cm. Anteroposterior direction.

of both recurrent laryngeal nerves, the segment of the esopha- gus containing the tumor was resected (Fig. 3). This was fol- lowed by reconstruction of the cervical esophagus using a pec-

FIG. 2. Computerized tomography scan of the upper esophageal region. Ventral side ofbody is up. Transversal section, approximately 1 cm below lower rim of cricoid. Notice trachea being impressed from the rear by thickening of esophageal wall, most prominent ventrally. Feeding tube is in place.

FIG. 3. Resection specimen after fixation, viewed from posterior. Inset: A slice with encircling tumor most conspicuous in ventral part is shown.

toralis major myocutaneous flap. Subsequently the subcuta- neous nodule on the back was excised and an elective tra- cheostomy was carried out.

The postoperative course was uneventful. After 8 weeks the nasogastric feeding tube could be removed and decanulation performed. A minor stenosis ofthe upper anastomosis between the hypopharynx and the myocutaneous flap required a few dilatations.

Currently, 3 years postoperatively, a stenosis of the recon- structed cervical esophagus earlier needed repeated dilatations. Both vocal cords show a certain degree ofreduced mobility not causing any airway obstruction.

Histopathologic Examination

As demonstrated in Figure 4, histopathologic exami- nation of the incisional biopsy showed a diffuse growth of cells with a large pale cytoplasm with rather mono- morphous nuclei between relatively unaffected muscu- lar cells. The thorough nature of these tumor cells is inconspicuous at low magnification with hematoxylin and eosin stain. The cytoplasm of these cells demon- strated periodic acid-Schiff (PAS) positivity also after diastase digestion in a granular pattern. Formalin-fixed and paraffin-embedded material showed positive reac-

No. 2 GRANULAR CELL TUMOR OF ESOPHAGUS . Vuyk et ai. 447

FIG. 4. Hematoxylin and eosin- stained section of incisional biopsy specimen. Between fibroblasts, cells with large cytoplasm and oval, some- what dark-staining nuclei are present (X 200). Inset: The granular nature of the cytoplasm is shown, but it still re- mains difficult to recognize the specific cell type with H&E stain (X 650).

tion with a fat stain (Sudan black, oil, red, 0), this possi- bly is due to the presence of structural lipids. Diagnosis was facilitated by semithin sections stained with tolui- dine blue demonstrating strikingly green granules caused by metachromatical staining of the neutral fat component of the inclusions (Fig. 5) . No mitotic figures were seen.

At the subcellular level, evidence was found for Schwilnn’s cell origin of the tumor cells. Basement membrane-like material and extensive coiling of tumor cells around collagen and among themselves were seen. Angdate body cells were found between granular cells

(Fig. 6). Various author^^*^ described these angulate body cells and considered them to be evidence of Schwann’s cell origin. The cytoplasmic granules thought to be lyso- soma1 in origin demonstrated the typical myelin-like fig- ures also mentioned by other authors (Fig. 6, Inset A). Close relation with preexistent axons was noted (Fig. 6, Inset B).

The resection specimen (Fig. 3) demonstrated a dif- fuse thickening of the wall of the esophagus most promi- nent in the ventral part. Histopathologic examination of the resection specimen revealed the same characteristics as described in the incisional biopsy. The caudal resec-

FIG. 5 . Toluidine blue-stained, Eppone- embedded semithin section of the inci- sional biopsy specimen. Cytoplasmic granules staining blue and metachromati- cal green become very conspicuous (X 500).

448 CANCER January 15 1985 VOl. 55

FIG. 6. Electron microscopic image of tumor cells, osmium fixation with glutaraldehyde 2% in cacodylate buffer, lead citrate and uranyl acetate poststaining. In the center, a group of tumor cells is seen (G). The cytoplasm is filled with granular structures. Tumor cell cytoplasm is present between the bundles of collagen (CB) (X 300). Inset A (top): Typical myelin figures in granules with the features of lysosomes (X 2500). Inset B (bottom): In some areas, the tumor cells had close relations to preexistent nerve fibers (X2500).

tion margin contained nests of tumor cells which were intimately associated with nerve bundles. The subcuta- neous nodule demonstrated a similar proliferation of granular cells.

Discussion

Of all the reported granular cell tumors, two thirds of the cases have occurred in women,’-1° mostly between the third and sixth decade. Blacks are more commonly affected.8J2

The incidence of multicentricity is estimated to be between 5% and 1 4%.8J0J2J3 The most common sites are the tongue (40%), the skin and subcutaneous tissue (30%), the breast (1 5%), the respiratory tract (lo%), and the gastrointestinal tract (5940-6%).~ The esophagus is a rare site for granular cell tumor. A 2% incidence is quoted.s

Only 36 patients have been reported with granular cell tumor of the esophag~s .~-~ Only 50% of these patients

had related symptoms. Seventy-three percent of these patients were women. In 40% the granular cell tumor was found in the upper esophagus, whereas in 25% (8 cases) there was multicentricity, in 10% ( 3 cases) the second or other lesions were found in the skin or subcu- taneous tissues. In the gastrointestinal tract the tumor often presents as a submucous, polypoid yellowish mass which sometimes can be removed through the endo- scope. Establishing the diagnosis with fiberoptic instru- ments is difficult and dangerous because of epithelial hyperplasia which is often present in the superficial biopsy and which can be mistaken for carcinoma. In our case, no atypical hyperplasia of the epithelium of the esophagus was present. In addition to routine x-ray ex- amination of the esophagus, CT scan of the esophagus was helpful in assessing the spread of the lesion, the images being directly comparable to the sections of the resection specimen.

Granular cell tumors causing stenosis of the upper esophagus are very rare indeed and have been observed

No. 2 GRANULAR CELL TUMOR OF ESOPHAGUS VUJk et d. 449

only in four patients. In two cases14*15 alocal excision was performed, whereas one patient l 6 died after an esopha- geal bypass operation. Obiditsch-Mayer et al. l7 de- scribed the lethal outcome of a malignant granular cell tumor in the proximal esophagus of a 20-year-old woman with cervical lymph node metastasis.

Currently, only 26 examples of malignancy in all cases of reported granular cell tumor are to be found in litera- ture, comprising about 2% of all reported granular cell tumors. Cellular pleomorphism, mitotic activity, or ul- trastructural findings cannot be used as criteria of malig- nant potential or recurrence risk. In our patient, the growtlh of the lesion seemed to be very slow in view of the 10-year history of complaints. A lethal course however, is related to rapid growth, large size, and invasion into adjacent tissues. Wide local excision is a treatment of choice and gives a low recurrence rate. There are several reports of inadequate removal of these tumors without recurrence even after years of follow-up.sJoJ

Although in our case the tumor is fairly large and demonstrated a diffuse, infiltrating growth pattern, causing stenosis and obstruction, the uniform cell pat- tern, the absence of mitotic activity as well as the long history suggests that the tumor is benign. The associated skin lesion in our patient may well be considered to be a form of multicentricity. Despite its rarity, granular cell tumor of the esophagus should be taken into considera- tion in patients with upper esophageal tumors, especially in patients with an associated skin or tongue mass.

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