Mediastinal granular cell tumor in a 16-year-old boy: A surgical and pathologic
Lacey M. Winchester, 1 Yana Puckett, 2 Jose Greenspon, 2 Carole A. Vogler1
Departments of 1 Pathology and 2 Pediatric Surgery, Saint Louis University and
Cardinal Glennon Children’s Medical Center, St. Louis, Missouri
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occurs most commonly in the subcutaneous tissues of the trunk, breast, and
extremities of adults. Congenital gingival lesions comprise the majority of the pediatric
granular cell tumors. Granular cell tumors are generally small and asymptomatic, and
while 1 in 10 patients have multiple tumors, recurrence and malignancy are very rare.
Mediastinal granular cell tumors have been reported, most occurring in young adult or
middle-aged women. We present a case of a 16-year-old asymptomatic boy with a
large mediastinal granular cell tumor incidentally identified after a motor vehicle
accident, and we review the intraoperative, microscopic, and ultrastructural features
of this tumor. Both the patient’s age and anatomical location are unusual for this
tumor, which presented technical and diagnostic challenges to the patient care team.
Granular cell tumor is a benign tumor of likely neural or neuroectodermal origin that
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Key words: granular cell tumor, mediastinum, thoracic pathology
Granular cell tumor (GCT) is a benign neuroectodermal tumor that occurs most
commonly in the subcutaneous tissues of the trunk and extremities. It is also seen in
many other sites including breast, GI tract, tongue, and lung. The vast majority of these
lesions occur after age 30 years, and the incidence in women is twice that in men [1,2].
In the pediatric population, GCT is most frequently encountered as congenital epulis, a
submucosal gingival lesion; pediatric breast GCTs have also been reported .
Wherever they arise, GCTs are typically small (3 cm or less), slow-growing,
asymptomatic nodules. The local recurrence rate for benign lesions is less than 5%.
Malignant GCTs are rare, accounting for approximately 2% of cases . However, with
malignant lesions, risk of local recurrence—as well as mortality from disease—is as
high as 30% .
We present the case of a16-year-old African-American male previously well boy who
was involved in a severe motor vehicle accident. As the patient had complaints
concerning for acute thoracic vertebral injury, a computed tomography scan of his
chest was obtained, which revealed the incidental finding of a 6.5 x 4.5 cm x 4 cm mass
occupying the left posterior mediastinum, extending caudally from the apex of the
pleural cavity to the level of the T2-T3 vertebrae. Small, finger-like extensions toward
the T2 and T3 nerve roots were identified on magnetic resonance imaging (Figure 1).
The radiographic differential diagnosis included ganglioneuroma and schwannoma.
There was no family history of tumor syndromes or other hereditary disorders. The
patient continued to have upper paraspinal tenderness after the motor vehicle
collision, but this was felt to be unrelated to the mass. Surgery was scheduled to
achieve a tissue diagnosis.
Approximately 4 weeks after initial presentation, a left video-assisted thoracoscopic
surgery was performed to dissect the tumor from the left upper posterior chest. The
tumor was extremely indurated, with a consistency most resembling bone. The mass
was densely adherent to the medial chest wall, paraspinal muscles, left vertebral
column, and descending aorta and was intimate with sympathetic ganglia. The
surrounding parietal pleura was incised and blunt dissection was used to free the
mass. The incision nearest his axilla was enlarged to retrieve the specimen. The patient
developed a postoperative Horner’s syndrome. On clinic follow-up six weeks
postoperatively, the ptosis and meiosis had resolved, though the patient continues to
have some anhidrosis of the left face.
The tumor was received in two portions—a 5.7 x 4.5 x 3.8 cm encapsulated ovoid mass
and a 2.1 x 1.8 x 1.4 cm irregular fragment. The cut surface of the larger specimen was
solid and yellow-white to pink (Figure 2). Microscopically, the tumor was composed of
interlacing sheets and fascicles of irregular, polygonal cells with abundant granular,
eosinophilic cytoplasm and round to ovoid nuclei with occasional nucleoli and no
significant mitotic activity. The microscopic interface between tumor cells and
surrounding tissue mimicked that seen on imaging—an infiltrative, poorly demarcated
zone of granular cells with surrounding dense fibrous connective tissue. The smaller
tissue fragment received was a sympathetic ganglion infiltrated by the GCT, with
abundant neurons admixed with tumor cells. The tumor cells’ cytoplasm contained
several large eosinophilic globules with clear halos. These, as well as the finer
cytoplasmic granules, were positive for acid phosphatase and for PAS (diastase-
resistant). (Figure 3 A-D) Immunohistochemical staining for S-100 was uniformly and
strongly (3+) positive; CD68 highlighted the cytoplasmic granularity throughout the
tumor. (Figure 3 E-F) Inhibin staining showed variable immunoreactivity. Calretinin,
glial fibrillary acid protein (GFAP), and synaptophysin were negative in lesional cells.
Electron microscopy demonstrated the classic ultrastructural appearance of abundant
phagolysosomes of various sizes and appearances packing the tumor cells’ cytoplasm.
(Figure 3 G)
Granular cell tumor is well described and fairly readily recognized, but its histogenesis
has been argued. GCTs were initially described by Abrikossoff in 1926  as “granular
cell myoblastomas” due to their abundant eosinophilic cytoplasm mimicking immature
rhabdoid cells, but ultrastructural and immunohistochemical techniques have since
established that they exhibit features of Schwann cell differentiation . However, the
exact origin of granular cell tumor remains debated; some believe it represents a
Schwann cell neoplasm with degenerative changes . In the case of mediastinal GCT,
the neural origin of the tumors may relate to the recurrent observation of nerve
involvement by these benign lesions. Rather than the invasion and destruction of
nerves frequently observed in malignant tumors, the presence of GCT tissue around
nerves likely represents sampling of a site of tumor origin.
Machida et al. reported seven patients with posterior mediastinal GCTs, with nerve
involvement in three . Others have described superior mediastinal GCTs associated
with sympathetic nerves [9-12]. Malignant mediastinal GCTs have also been described.
sites for mediastinal GCTs, and these patients are frequently younger than the middle-
aged cohort described in reference texts. [9-17] Three of the seven cases in Machida’s
report  were less than 21 years old. Symptoms may include cough, chest pain, and
wheezing, but many GCTs are incidental findings, as in this case . In some cases,
mediastinal masses have been identified as one of multiple GCTs [15,16].
South Korea and Malaysia are the most frequently reported geographic
The differential diagnosis in a case such as ours can be broad. While a benign GCT can
be readily recognized on H&E, it is important to keep in mind that a host of tumor
types can have “granular cell” subtypes, and that other entities such as thymoma,
lymphoma, and neurogenic tumors (such as schwannoma or neurofibroma) are more
common in the mediastinum than a GCT.
Congenital epulis is considered a varian of GCT. Clinically, it occurs exclusively in
infants and is typically located on the dental ridge. Morphologically, it has prominent
vascularity, and does not show immunostaining for S100 protein. Ultrastructurally,
both GCT and epulis contain phagolysosomes, although they are described as more
uniform in epulis than in GCT .
There are no specific radiographic findings in GCT and definitive diagnosis rests on
pathologic findings. In this particular specimen, the presence of neurons scattered
between groups of polygonal to spindled cells allowed for the consideration of a
ganglioneuroma. However, the paucity of ganglion cells in the remainder of the tumor
and the results of ancillary studies confirmed the final diagnosis of GCT.
This case poses several dilemmas. First, while GCT is generally benign, clear resection
margins are recommended to reduce the risk of local recurrence . In this case, a
complete local excision was the only option as the tumor was adherent to numerous
vital structures. The patient thus has a risk of local recurrence and he will require close
radiographic follow-up. Moreover, this case reinforces the need to consider GCT in the
differential diagnosis of mediastinal lesions in children.
Immunohistochemistry and electron microscopy are helpful ancillary techniques that
can confirm the diagnosis in particularly challenging cases. Mediastinal GCTs can be
technically difficult to resect due to their predilection for the posterior mediastinum,
adjacent great vessels and sympathetic nervous system structures. They can, however,
be resected with minimal postoperative sequelae, and are very rarely recurrent.
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