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Mediastinal granular cell tumor in a 16-year-old boy: A surgical and pathologic

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perspective.

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Lacey M. Winchester, 1 Yana Puckett, 2 Jose Greenspon, 2 Carole A. Vogler1

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Departments of 1 Pathology and 2 Pediatric Surgery, Saint Louis University and

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Cardinal Glennon Children’s Medical Center, St. Louis, Missouri

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ABSTRACT

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occurs most commonly in the subcutaneous tissues of the trunk, breast, and

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extremities of adults. Congenital gingival lesions comprise the majority of the pediatric

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granular cell tumors. Granular cell tumors are generally small and asymptomatic, and

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while 1 in 10 patients have multiple tumors, recurrence and malignancy are very rare.

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Mediastinal granular cell tumors have been reported, most occurring in young adult or

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middle-aged women. We present a case of a 16-year-old asymptomatic boy with a

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large mediastinal granular cell tumor incidentally identified after a motor vehicle

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accident, and we review the intraoperative, microscopic, and ultrastructural features

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of this tumor. Both the patient’s age and anatomical location are unusual for this

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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

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INTRODUCTION

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Granular cell tumor (GCT) is a benign neuroectodermal tumor that occurs most

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commonly in the subcutaneous tissues of the trunk and extremities. It is also seen in

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many other sites including breast, GI tract, tongue, and lung. The vast majority of these

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lesions occur after age 30 years, and the incidence in women is twice that in men [1,2].

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In the pediatric population, GCT is most frequently encountered as congenital epulis, a

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submucosal gingival lesion; pediatric breast GCTs have also been reported [3].

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Wherever they arise, GCTs are typically small (3 cm or less), slow-growing,

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asymptomatic nodules. The local recurrence rate for benign lesions is less than 5%.

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Malignant GCTs are rare, accounting for approximately 2% of cases [4]. However, with

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malignant lesions, risk of local recurrence—as well as mortality from disease—is as

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high as 30% [5].

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CASE REPORT

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We present the case of a16-year-old African-American male previously well boy who

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was involved in a severe motor vehicle accident. As the patient had complaints

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concerning for acute thoracic vertebral injury, a computed tomography scan of his

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chest was obtained, which revealed the incidental finding of a 6.5 x 4.5 cm x 4 cm mass

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occupying the left posterior mediastinum, extending caudally from the apex of the

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pleural cavity to the level of the T2-T3 vertebrae. Small, finger-like extensions toward

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the T2 and T3 nerve roots were identified on magnetic resonance imaging (Figure 1).

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The radiographic differential diagnosis included ganglioneuroma and schwannoma.

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There was no family history of tumor syndromes or other hereditary disorders. The

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patient continued to have upper paraspinal tenderness after the motor vehicle

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collision, but this was felt to be unrelated to the mass. Surgery was scheduled to

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achieve a tissue diagnosis.

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Approximately 4 weeks after initial presentation, a left video-assisted thoracoscopic

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surgery was performed to dissect the tumor from the left upper posterior chest. The

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tumor was extremely indurated, with a consistency most resembling bone. The mass

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was densely adherent to the medial chest wall, paraspinal muscles, left vertebral

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column, and descending aorta and was intimate with sympathetic ganglia. The

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surrounding parietal pleura was incised and blunt dissection was used to free the

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mass. The incision nearest his axilla was enlarged to retrieve the specimen. The patient

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developed a postoperative Horner’s syndrome. On clinic follow-up six weeks

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postoperatively, the ptosis and meiosis had resolved, though the patient continues to

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have some anhidrosis of the left face.

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PATHOLOGIC FEATURES

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The tumor was received in two portions—a 5.7 x 4.5 x 3.8 cm encapsulated ovoid mass

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and a 2.1 x 1.8 x 1.4 cm irregular fragment. The cut surface of the larger specimen was

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solid and yellow-white to pink (Figure 2). Microscopically, the tumor was composed of

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interlacing sheets and fascicles of irregular, polygonal cells with abundant granular,

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eosinophilic cytoplasm and round to ovoid nuclei with occasional nucleoli and no

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significant mitotic activity. The microscopic interface between tumor cells and

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surrounding tissue mimicked that seen on imaging—an infiltrative, poorly demarcated

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zone of granular cells with surrounding dense fibrous connective tissue. The smaller

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tissue fragment received was a sympathetic ganglion infiltrated by the GCT, with

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abundant neurons admixed with tumor cells. The tumor cells’ cytoplasm contained

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several large eosinophilic globules with clear halos. These, as well as the finer

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cytoplasmic granules, were positive for acid phosphatase and for PAS (diastase-

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resistant). (Figure 3 A-D) Immunohistochemical staining for S-100 was uniformly and

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strongly (3+) positive; CD68 highlighted the cytoplasmic granularity throughout the

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tumor. (Figure 3 E-F) Inhibin staining showed variable immunoreactivity. Calretinin,

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glial fibrillary acid protein (GFAP), and synaptophysin were negative in lesional cells.

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Electron microscopy demonstrated the classic ultrastructural appearance of abundant

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phagolysosomes of various sizes and appearances packing the tumor cells’ cytoplasm.

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(Figure 3 G)

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DISCUSSION

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Granular cell tumor is well described and fairly readily recognized, but its histogenesis

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has been argued. GCTs were initially described by Abrikossoff in 1926 [6] as “granular

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cell myoblastomas” due to their abundant eosinophilic cytoplasm mimicking immature

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rhabdoid cells, but ultrastructural and immunohistochemical techniques have since

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established that they exhibit features of Schwann cell differentiation [7]. However, the

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exact origin of granular cell tumor remains debated; some believe it represents a

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Schwann cell neoplasm with degenerative changes [4]. In the case of mediastinal GCT,

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the neural origin of the tumors may relate to the recurrent observation of nerve

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involvement by these benign lesions. Rather than the invasion and destruction of

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nerves frequently observed in malignant tumors, the presence of GCT tissue around

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nerves likely represents sampling of a site of tumor origin.

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Machida et al. reported seven patients with posterior mediastinal GCTs, with nerve

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involvement in three [8]. Others have described superior mediastinal GCTs associated

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with sympathetic nerves [9-12]. Malignant mediastinal GCTs have also been described.

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[13-14] Japan,

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sites for mediastinal GCTs, and these patients are frequently younger than the middle-

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aged cohort described in reference texts. [9-17] Three of the seven cases in Machida’s

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report [8] were less than 21 years old. Symptoms may include cough, chest pain, and

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wheezing, but many GCTs are incidental findings, as in this case [8]. In some cases,

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mediastinal masses have been identified as one of multiple GCTs [15,16].

South Korea and Malaysia are the most frequently reported geographic

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The differential diagnosis in a case such as ours can be broad. While a benign GCT can

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be readily recognized on H&E, it is important to keep in mind that a host of tumor

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types can have “granular cell” subtypes, and that other entities such as thymoma,

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lymphoma, and neurogenic tumors (such as schwannoma or neurofibroma) are more

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common in the mediastinum than a GCT.[17]

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Congenital epulis is considered a varian of GCT. Clinically, it occurs exclusively in

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infants and is typically located on the dental ridge. Morphologically, it has prominent

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vascularity, and does not show immunostaining for S100 protein. Ultrastructurally,

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both GCT and epulis contain phagolysosomes, although they are described as more

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uniform in epulis than in GCT [18].

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There are no specific radiographic findings in GCT and definitive diagnosis rests on

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pathologic findings. In this particular specimen, the presence of neurons scattered

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between groups of polygonal to spindled cells allowed for the consideration of a

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ganglioneuroma. However, the paucity of ganglion cells in the remainder of the tumor

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and the results of ancillary studies confirmed the final diagnosis of GCT.

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This case poses several dilemmas. First, while GCT is generally benign, clear resection

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margins are recommended to reduce the risk of local recurrence [17]. In this case, a

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complete local excision was the only option as the tumor was adherent to numerous

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vital structures. The patient thus has a risk of local recurrence and he will require close

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radiographic follow-up. Moreover, this case reinforces the need to consider GCT in the

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differential diagnosis of mediastinal lesions in children.

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Immunohistochemistry and electron microscopy are helpful ancillary techniques that

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can confirm the diagnosis in particularly challenging cases. Mediastinal GCTs can be

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technically difficult to resect due to their predilection for the posterior mediastinum,

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adjacent great vessels and sympathetic nervous system structures. They can, however,

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be resected with minimal postoperative sequelae, and are very rarely recurrent.

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Mediastinal Granular Cell Tumor in a 16-Year-Old Boy: A Surgical and Pathologic Perspective.

Granular cell tumor is a benign tumor of likely neural or neuroectodermal origin that occurs most commonly in the subcutaneous tissues of the trunk, b...
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