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Nature of Granular Cells in Granular Cell Ameloblastoma

IMMUNOHISTOCHEMICAL STUDY

Objective: To judge the type of granular skin cells in granular cell ameloblastoma

Study Design: Muscle specimens of five patients with granular cell ameloblastoma were fixed in buffered formalin and later inserted in paraffin wax. Blocks were sliced into 3micron heavy parts for immunohistochemicalanalysis using a -panel of markers Disc68, Bcl2, S100, P53, Cytokeratin(AE1/AE3), vimentin and desmin

Results: All five situations were firmly positive for cytokeratin and Compact disc68. S100 was negative in three cases and showed minor positivity in two situations. Bcl2, P53, Vimentin and Desminwere negative in all the five cases.

Conclusions: This review reveals a heterogenous aspect of the granular skin cells, however further validation is required with a more substantial test size.

INTRODUCTION:

Ameloblastoma is a harmless odontogenic tumour usually located in the jaw bone [1]. It is considered to be the most typical odontogenic tumor. It is a tumor of the teeth enamel organ without creation of teeth enamel. Robinson has defined it as: Unicentric, nonfunctional, intermittent in development, anatomically benign and clinically persistent. The need for this tumor is based on its common event, locally invasive habit which causes proclaimed deformity and serious debilitation. They also illustrate increased recurrence rate after surgery. [2]It has a distinctive microscopic appearance seen as a the presence of peripheral columnar cells with hyperchromatic, reversely polarized nuclei, set up in a palisaded routine. [3]

Conventional sturdy or multicysticameloblastoma displays six microscopic subtypes namely follicular, plexiform, acanthomatous, granular cell, desmoplastic and basal cell ameloblastoma. [4]. The follicular and plexiform patterns are the most frequent. Less common histopathologic subtypes include the acanthomathous, granular cell, desmoplastic, and basal cell [1, 5] Granular cell ameloblastoma (GCA) is one of the uncommon histological variants of ameloblastomaaccounting for only 3. 5% of ameloblastomas. [5]

Granular cell ameloblastoma is characterized by nests of large, eosinophilic granular skin cells. [6] Aggressive behavior has been eliminated by many reports and claim that granular skin cells are only a transitional or matured phase in the life routine of ameloblastomas, starting with normal stellate reticulum-like skin cells, resulting in a development of granules and lastly resulting in degeneration and development of cystic areas. [7] Whether granular cell change in ameloblastoma is a degenerative process or a harbinger of a more competitive course is a matter of debate. [8] [Figure 1& 2]

Previous studies have completed ultrastructural, histochemical and immunohistochemical solutions to characterize the type of the granular cells, though the device involved is poorly understood.

The present research endeavors to do an immunohistochemical evaluation with a panel of markers to review the nature of granular cells in granular cell ameloblastoma. Because of its rarity accounting to 3. 5%, literature search discovered that majority of them were one circumstance studies. This review is the first of its kind to record antigenic characterization in five such instances with a variety of markers.

MATERIALS AND METHODS:

Case Selection:

Formalin-fixed paraffin-embedded structure blocks of granular cell ameloblastoma were retrieved from the archives of Department of Oral and Maxillofacial Pathology, SRM Dental care College, Chennai. The specialized medical data of the patients are stated in desk 1.

Immunohistochemical Evaluation:

Immunohistochemical evaluation was performed on 3 tissues sections on poly-L-Lysine coated slides (Biogenix Life Sciences Limited, CA, US). Pre-diluted ready to use main monoclonal mouse anti - Compact disk-68, anti - Bcl2, anti-S 100, anti-P53, anti-cytokeratin antibody (AE1/AE3), anti-Vimentin and anti-Desmin(Biogenix Life Sciences Small, CA, US)were used accompanied by thesuper hypersensitive polymer HRP diagnosis system(Biogenix Life Sciences Small, CA, US). Shaded reactions were developed by incubating with 3'3'-diaminobenzidine and eventually counterstained with Harris hematoxylin. Negative and positive controls were contained in all reactions. Existence of brown colored end product at the site of goal antigen was indicative of positive immunoreactivity. Analysis of theimmunoreactivity was predicated on staining depth and wereclassified asweak, moderate, and strong. Localization of favorably stained skin cells in peripheral ameloblast-like cells, central stellate reticulum like skin cells, and granular cells were also evaluated.

RESULTS:

Immunoreactivity of the markers found in the study are listed in desk 2. Disc-68expressed strong positivity in all the five instances. Positivity was noticed only in the granular skin cells. Cytokeratin (AE1/AE3) indicated strong positivity in every the five situations by staining peripheral cells, stellate reticulum like cells and granular cells. Bcl2, P53, Vimentin and Desminexhibited negative staining in all the five situations.

DISCUSSION:

Granular cell ameloblastoma accounts to 3. 5% of most ameloblastomas [11]. The lesion presents with marked transformation of thecytoplasm of the stellate reticulum like skin cells, so the cells take on an extremely coarse, granular, eosinophilic appearance. [5] GCA may be competitive histologic version among all the ameloblastoma. Granular cells have been explained in other odontogenic tumor, the granular cell ameloblastic fibromaand dental lesions, such as congenital epulis and granular cell tumor [12]

The nature of various dental granular cell lesions is unclear, and many theories have been suggested for the origin of granules, the principal ones are odontogenic, fibroblastic, histiocytic, myoblastic, and neurogenic. [13] Granular skin cells are also seen associated with the teeth enamel organ of developing tooth. [14]

The granular appearance has been ascribed to numerous lysosomes predicated on histochemical and electron microscopic results. Ultrastructurally, the osmiophilic interior structure of the lysosomes ranges considerably. [15] Many of these granules plan 1Ојm in size; giant granules of 30Ојm in diameter are hardly ever seen. They present with top features of finger-print-like membranous structures, myelin information, small contaminants, granules, vesicles, lattice set ups, and crystalloids. This variety may stand for different materials and levels of digestion of the lysosomal items. The myelin statistics suggest the occurrence of phospholipid in the granules. Therefore, it has been concluded by many writers that numerous lysosomes stand for increased cellular actions of the tumour ameloblasts to break down unwanted components [14, 16].

Considerable interest about the nature of granular skin cells in ameloblastoma ever since it was known has happened because of its reported aggressive behaviour however recent literature reviews speculate that the granular cell transformation in granular cell ameloblastoma may be associated with the aging sensation. [17, 18, 19]

The present review was completed in five conditions of granular cell ameloblastoma to ascertain the type of the granules using a -panel of markers Compact disc68, Bcl2, S100, P53, Cytokeratin (AE1/AE3), vimentin and desmin. Strong positivity for cytokeratin and Compact disc68was noted in every the conditions. S100 was negative in three instances and mildly positive in two circumstances. P53, Bcl 2, Vimentin and desmin were negative in all the five situations. [Stand 2]

The dynamics of granules in granular cell ameloblastoma in the previous studies have reported epithelial origin due to constant positivity with cytokeratin and negativity with other mesenchymal markers. [Shape 3] Occurrence of strong positivity with Compact disk68 in granular skin cells indicates the existence of lysosomal aggregates. [Number 4]

Negative appearance of antiapoptotic factors such as Bcl-2 and p53 proteins in granular cells indicate that there is increased apoptosis in the granular cells. This finding was like the report by Kumomoto et al who reported apoptosis in the granular cells [20]. Contradictory to earlier records is the existence of gentle positivity with S100 unlike other previously published studies. S100 is normally present in skin cells produced from the neural crest ( Schwann cells, and melanocytes), chondrocytes, adipocytes, myoepithelialcells, macrophages, Langerhans cells, dendritic cells, and keratinocytes. Mild positivity of S100 could be suggestive of transdifferentiation of the cells. Such heterogenous display of granular ameloblastomas evokes more interest to help expand ratify its true nature.

CONCLUSION:

The current immunohistochemicalpanel could be advanced further for a better understanding of the type of the granular cells in ameloblastomas. Further studies with an increase of number of cases could help reason out the antigenic heterogeneity of granular cell ameloblastoma.

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