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«IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 14, Issue 2 Ver. VII (Feb. 2015), PP 20-24 ...»

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IOSR Journal of Dental and Medical Sciences (IOSR-JDMS)

e-ISSN: 2279-0853, p-ISSN: 2279-0861.Volume 14, Issue 2 Ver. VII (Feb. 2015), PP 20-24

www.iosrjournals.org

Granular Cell Tumour near the Angle of Mouth on Buccal

Mucosa: Case Report and Review

Dr. C A Ashoka,Asst Professor,1 Dr. Uma Swaminathan, Prof,2

Dr Sharada P,Prof & Hod3, Dr. NagamaliniB R,Reader4,

1, Dept of dentistry,Mandya institute of medical sciences

2,3,4,Dept of oral pathology, AECS Maruthi Dental college,

I. Introduction Granular Cell Tumor (GCT) formerly known as Granular Cell Myoblastoma and Abrikosoff’s tumor is a rare neoplasm. It is a benign lesion affecting the mucous membrane of the upper aerodigestive tract. GCT is a tumor of uncertain origin that has been variably considered a true neoplasm, a degenerative metabolic process or a trauma induced proliferation. Most GCTs are benign, but approximately 10% have malignant behaviour.

Metastases to the regional lymph nodes and distant metastases have been observed. 1,2 We report a case of a GCT which presented as a nodular swelling of the buccal mucosa.

II. Case History A 35 yr old male patient reported with a growth in the oral cavity. On examination, a well defined sessile growth measuring 2x1cms on the left buccal mucosa near the commissure was seen. The growth was whitish pink in color with an irregular surface. No lymph nodes were palpable. The lesion was provisionally diagnosed as fibroma clinically.

The lesion was excised and biopsy specimen measuring 2x.8cms, grayish white in color, with firm consistency was sent to the lab in 10% formalin. The tissue was grossed as required and processed.

H&E under 4x magnification – Overlying epithelium showing pseudoepitheliomatous hyperplasia simulating squamous cell carcinoma Microscopic examination of H and E stained section showed over parakeratotic stratified squamous epithelium with pseudoepitheliomatous hyperplasia.

H&E under 10x magnification- Underlying connective tissue showing granular cells arranged in the form of ribbons separated by fibrous septa The underlying connective tissue showed numerous granular cells arranged in DOI: 10.9790/0853-14272024 www.iosrjournals.org 20 | Page Granular cell tumour near the angle of mouth on buccal mucosa: case report and review sheets and ribbons, separated by fibrous septa. The cells were round to oval in shape, with distinct borders, and eccentrically placed nucleus. The cytoplasm showed numerous eosinophilic granules.

H&E under 40x magnification showing granular cells infiltrating into the muscle.

The granular cells appeared to be invading the muscle in few areas. Moderate inflammatory infiltrate predominantly composed oflymphocytes, few blood vessels lined by endothelial cells and extravasated RBC’s were also seen. The granules showed a positive reaction to PAS stain and were immunohistochemically positive for S-100. Based on the findings, a histopathological diagnosis of Granular Cell Tumor was arrived at.

10x magnification- Granular cells showing positivity for S-100.

–  –  –

III. Discussion And Review Of Literature GCT was first described by Weber in 1854, and established as a clinical entity by Abrikossoff in 1926,who termed it as Granular Cell Myoblastoma. It has been known by several names which include Abrikosoffs tumor, Myoblastoma, Granular cell neurofibroma and Granular cell schwanomma.(5) Clinical Features GCT is an uncommon benign lesion affecting the mucous membrane of the upper aero- digestive tract.

Although GCT may appear in any site of the body 50% occur in the mouth, more precisely on the tongue.

Cutaneous lesions constitute about 30% of cases, out of which only 1-3% are malignant. Typically, it appears as a single sessile and asymptomatic nodule rarely greater than 3cms. It is common in the 4th to 6th decade of life and has a predilection for females (1,2 10). Oral lesions present as a papule or nodule less than 3cms in diameter. They are asymptomatic, slow growing and generally covered by an intact mucous membrane of normal appearance, but can also be verrucous or pseudo-ulcerated. The tumor typically appears as a solitary lesion, although multifocal tumours at the first presentation have been reported in 4-10% of cases(2). Basili John R et al described a polypoid granular cell tumor of the oral cavity(9).About 25% of GCTs present as multiple lesions and Luana et al reported multiple granular cell tumors of the tongue and parotid gland.(12). About 10of patients develop multiple lesions principally in the skin, soft tissues, breast and lungs. Sergio sargantiNito et al reported a multicentric granular cell tumour of ventral apical part of the tongue, lowerlip, groin. vulva, vagina and zygomatic process.(13)

–  –  –

Superficial lesions tend to protrude through the mucosa. But when more deeply located the tumor may simply be palpated as a firm mass. It is usually benign but sometimes it may be locally aggressive while 2% show metastases at a distant site. (5) Pathogenesis As with all lesions, the origin of GCT also has been a matter of debate since its description in 1926 by Alekeri Ivanovich Abrikosov a Russian pathologist (1875-1958). He classified GCT as having a myogenic origin and in 1970, Sequeria et al named it as Granular cell myoblastoma. Oliveria and Taube had doubts about the cell origin and preferred to consider it of mesenchymal origin. Reichler et al believed in a Schwann cell origin, as the tumour cell morphology was similar to its phagocytic form. (3) Many cell types have been implicated in its histogenesis, including muscle cells, Schwann cells, neuroendocrine cells, fibroblasts, neural sheath cells, undifferentiated mesenchymal cells and histiocytes. The histogenesis of GCTs has remained elusive despite a vast number of IHC and ultra structural studies. The diagnosis is mostly based on the histological findings and is confirmed by a positive IHC staining for S-100 and NSE. It also expresses Vimentin, PGP 9.5, NKI/C3 and CD68 while some markers such as Inhibin-α, Calretinin, Gelectin-3 and HBME show varying rates of staining.(3,4) A large body of evidence at the morphological, ultra structural and immunohistochemical levels has been accumulating during the past years in support of the theory that the cells of origin for GCTs is neural with a schwannian differentiation. However, more recent findings have cast doubt on the neural origin of these tumors(6).





The IHC profile of GCTs has undergone extensive analysis. They are positive for S100 protein which serves as sound evidence for their schwannian /neural origin. CD68, a marker of lysosomes mostly associated with macrophages, is also usually positive in GCTs and its presence is explained by the assumption that Schwann cells acquire lysosomes during phagocytosis of myelin, a phenomenon which is known to occur in peripheral nerves showing Wallerian degeneration as well as in traumatic neuroma. (6).

The belief that GCTs are of Schwann cell origin has been questioned in light of the observation that myelin and myelin forming cells are extremely rare in the neurohypophysis and in spite of this, tumors with similar morphological grounds and ultra structural features of typical GCT are found at this site. (6).

Also, with the considerable progression and interpretation of immunohistochemical stains over the last two decades, together with the improvement of technical laboratory procedures, it became clearer that positive immunoreactions to S100 and CD68 cannot fully support a neural origin of the granular cells in GCTs. The variety of cell types positive for these proteins, is wider than was originally thought. S100 protein has been identified in cells of non neural lineages such as macrophages, normal skeletal muscle cells and rhabdomyoma and granular cells in Ameloblastoma. (6).

It is also noted the GCTs showed positive staining for p75, NKI/C3 and PGP9.5. These immunostains are not tissue specific but are rather expressed in a very large variety of adult tissues and their neoplastic counterparts. (6).

In addition, with a positive immunoreaction to inhibin α, the granular cells of GCTs take on, an immunoprofile, that may be better explained in terms of a stress induced degenerative process or a metabolic disorder, that leads to the evolvement of aberrant and uncharacteristic proteins and also loss of the cellular proteins and organelles that were once the foot prints of the cell of origin. (6).

Cytoplasmic granularity, such as that seen in GCT is not a unique feature of this lesion. It has been observed in various extents in cells in a vast array of conditions such as reactive `lesions, odontogenic cysts and tumors and other benign and malignant tumors. Granular cells have also been experimentally induced following exposure to cyclophosphamide. (6).

Also, lesions which exhibit granular cells have been found to be of neural, smooth muscle, striated muscle, endothelial, primitive mesenchymal, histiocytic and epithelial differentiation, further emphasizing the ambiguity of the granular cells. (6).

When granular cells of different cell lineages were ultra structurally analyzed they generally revealed lysosomal granules and cytoplasmic filaments, similar or identical to those observed in conventional GCTs.

Collectively, these observations may indicate that on morphologic grounds, cytoplasmic granularity is not powerful enough to consider a GCT as being a distinct pathologic entity. Analogically, other cytoplasmic changes such as those recognized as clear, oncocytic, rhabdoid and signet cells which are not necessarily related to a specific cell of origin, are seen in many benign and malignant conditions and usually do not constitute a separate entity. (6).

Vered et al in their study noted the transition of striated muscle cells to granular cells as highlighted by Inhibin α staining results. This reflects the modification that striated muscle cells undergo and the process which gives them a granular morphology and an altered immunohistochemical phenotype that is completely unrelated to that of normal skeletal muscle. It was also found that similar modifications were seen in granular cells that DOI: 10.9790/0853-14272024 www.iosrjournals.org 22 | Page Granular cell tumour near the angle of mouth on buccal mucosa: case report and review seemed to evolve from peripheral nerve fibers. This further strengthens the assumption that the appearance of granular cell is not limited to one cell type, but is rather site dependent and that the cell of origin may differ according to its accessibility at any site. However, the tongue is rich in nerve fibers encased by Schwann cells that could also be the source for GCTs that cannot be morphologically distinguished from those of muscle cell origin following an event of metabolic stress. In contrast, in the subcutaneous tissues, which are devoid of striated muscle fibers, other mesenchymal tissues, eg. Nerve fibers, smooth muscles and endothelial cells, could give rise to GCTs given that they undergo granular cell changes induced by metabolic stress. (6).



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