ADR. Annals of Dental Research. Journal homepage: http// Adenoid Cystic Carcinoma - A Case Report

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1 A d e n o i d C y s t i c C a r c i n o m a : P a g e 36 ADR 3(2), 36-41, 2014 Annals of Dental Research ADR Journal homepage: http// Adenoid Cystic Carcinoma - A Case Report Multani Rupinder Kaur *,a, Shahi Prinka b, Singh Jaspreet c a Department of Oral Pathology, Rayat Bahra Dental College and Hospital, Punjab, India b Department of Pedodontics and Preventive Dentistry, MMU-CDSR, Mullana, India c Private Practitioner * Corresponding author, rupin678@gmail.com Article history Received: 25 October 2013 Accepted: 18 January 2014 Available Online: 31 January 2014 Keywords Carcinoma; Adenoid; Salivary gland. Abstract Adenoid Cystic Carcinoma is the fifth most common salivary gland neoplasm which occurs relatively frequently in oral accessory salivary glands particularly palate. The cellular make-up of adenoid cystic carcinoma is strongly suggestive of an origin from the pluripotential stem cells. Adenoid cystic carcinoma cells have a known propensity for perineural invasion which lead to a high incidence of local recurrence and a great difficulty in the curative resection of adenoid cystic carcinoma HATAM: Publishers. All rights Reserved Introduction Adenoid Cystic Carcinoma is the fifth most common salivary gland neoplasm which occurs relatively frequently in oral accessory salivary glands particularly palate. This was first described by Theoder Billroth as Cylindroma. In 1953, Foote and Frazell proposed the term Adenoid Cystic Carcinoma. 1 Case Report A 37 yrs old patient reported to the Department of Oral Pathology with the chief complaint of pain and discomfort in the left back cheek region in the left buccal mucosa. There was associated symptom of pain and discomfort over the anterior border of masseter. The history dates back to 7-10 days with gradual onset.past Medical history of

2 A d e n o i d C y s t i c C a r c i n o m a : P a g e 37 parotitis 8 yrs back for which antibiotics were taken. Clinical investigations MRI Neck was done which showed parotid, submandibular & sublingual gland of normal size and shape. There was enhanced soft tissue thickening seen involving left posterior buccal space which extends posteriorly to the retromolar trigone region and abuts left masseter muscle. Sialogram Parotid gland showed well visualized entire parotid duct system with no abnormalities. On intra oral examination Nodular mass was seen in left buccal mucosa irt 16, 17, 18. 1cm X 1.5cm in superioinferior & anterioposterior dimension with normal apearing overlying mucosa. The growth is nodular with firm consistency. There was induration present over parotid duct opening. Submandibular lymph node were palpable. An excisional biopsy was done and three soft tissue bits were received measuring 1 cm X 0.8cm, 0.8cmX 0.2cm, 0.4cmX0.2cm. Provisional diagnosis of Buccal Lymph Node was given. Histopathological findings Submitted H&E stained section shows tumor cells in the form of islands in cribriform and tubular structures. Cribriform patterns consists of islands of basaloid epithelial cells with hyperchromatic nuclei and contains multiple cylindrical cystic spaces. These cystic spaces consists of eosinophilic material. Tumor islands are surrounded by hyalinized material. The whole of tumor island is surrounded by fibrous capsule. Small islands of tumor cells are present within muscle. PAS positive Diastase resistant epithelial mucin is seen in cystic spaces. Alcian blue at ph i.e. strongly sulfated mucin are seen within cystic spaces. Figure 2: H&E stained section shows multiple cystic spaces(x10). Inset shows individual cystic spaces lined by hyperchromatic cells (X40). Figure 1: Three soft tissue bits creamish brown in colour measuring 1cmX0.8cm, 0.8cmX0.2cm, 0.4X0.2cm. Figure 3: PAS positive epithelial mucin is seen within the cystic spaces. X40.

3 A d e n o i d C y s t i c C a r c i n o m a : P a g e 38 Discussion Adenoid Cystic Carcinoma clinically presents as swelling and mass. It is slow growing with pain and tenderness. If parotid gland is involved paralysis of facial nerve occurs. It occurs predominantly in the parotid and submandibular gland. Palate is the most common intra oral site followed by tongue and buccal mucosa. Histopathology reveals that the tumour is composed of isomorphic cells characterized by dark, deeply staining basophilic nuclei and scanty cytoplasm that are arranged in various morphologic patterns. Depending on the relative prominence of these morphologic patterns, it is seen to exist in (1) Cribriform pattern with arrangement of tumour cells in the so called Swiss cheese configuration. The cells are arranged in nests of variable size and shape that contain many circular or ovoid spaces. The spaces may contain either a faintly basophilic mucinous substance or hyalinized eosinophilic zones. (2) Tubular type shows single ductal structures formed by layers of isomorphic cells. (3) Solid type with arrangement of isomorphic cells in nests or sheets of varying size and shape. 2 Friborsky used alcian blue, electronmicroscopy and polarization optics and concluded that the acellular material was composed of mucopolysaccharides and periodic fibrils of the collagenous type. Eneroth and associates found only hyaline material and aperiodic fibrils, implying that the substance represented an overproduction of basement membrane-like material by the tumor cells. They concluded that this excessive production of material in the cribriform-cylindromatous type tumors was a reflection of an immunologic response and accounted for a better prognosis as compared to the solid adenoid cystic carcinoma. 2 Chen histochemically and ultrastructurally studied the nature of the material contained within the cyst-like tumor spaces. He found the material PAS-positive and diastase resistant. It was alcian blue, toludine blue and mucicarmine- positive, suggesting an acid mucopolysaccharide nature. Ultrastructurally, three zones were easily recognizable :(1) a juxtacellular zone consisting of a network of replicated basal lamina; (2) an intermediate zone of stellate granules; and (3) a central zone of aperiodic filaments and collagen fibers. He concluded that mucoid material present in the cyst-like spaces was identical to that produced by mucous-secretory acinar cells, and, therefore, was of epithelial origin. Bloom et al found that the material at the periphery of the pseudocyst to be composed of concentric, multiple basal laminae of different thicknesses and varied patterns. The material consisted of a replicated basal lamina-like substance next to the epithelial neoplastic cells. Towards the center, the material was composed of stellate granules, aperiodic fibrils and collagen fibers. 3 The cellular make-up of adenoid cystic carcinoma is strongly suggestive of an origin from the pluripotential reserve/stem cells which normally reside at the acinar intercalated junctions and in the intercalated ducts proper. 4,5 The combination of luminal and myoepithelial /basal cells which resembles normal ductoacinar unit is replicated in the

4 A d e n o i d C y s t i c C a r c i n o m a : P a g e 39 tubular variant whereas there is preferential differentiation of myoepithelial/basal cells in the solid form of this tumour. The production of excess basal lamina and glycosaminoglycans in association with the myoepithelial/basal cell component is responsible for development of the cribriform variant. 2 The role and the extent of participation by the myoepithelium in the histogenesis of adenoid cystic carcinoma is controversial. Hubner et al suggested that adenoid cystic carcinoma originated from the myoepithelial cells which in addition to myofibrils, contained large amounts of rough endoplasmic reticulum, indicating an intensive synthesis of proteins. They further claimed that the acellular hyaline material was the product of myoepithelium and not of fibroblasts. 2 Bruce and Wertheimer noted histochemically that the tumor cells in adenoid cystic carcinoma failed to display the high levels of alkaline phosphatase and ATPase activities that were normal characteristics of myoepithelium. 3 Tandler identified myoepithelial-like cells in association with the ductal lumina, but was not convinced of their role as histogenetic precursors. Since squamous metaplasia is a frequent finding in the tumor cells, the cytofilaments could have been of tonofilament rather than myofilament type, the two being indistinguishable. 4 The extent of myoepithelial cell presence in adenoid cystic carcinoma varies from one tumor to another. They are commonly associated with the acinar-intercalated units and tubular-ductal structures and not with the solid areas of tumors. The observed myoepithelial cells are similar in location and ultrastructural features to their normal counterparts. It seems that myoepithelial cells are from two different sources: (1) the original acinar intercalated ducts (2) the proliferation and cytodifferentiation of pluripotential reserve/stem cells. A dual origin of adenoid cystic carcinoma, partly from a population of acinar and ductal cells and partly from myoepithelium, has been suggested. 5 Kleinsasser et al proposed that, histogenetically, adenoid cystic carcinoma corresponded to a primitive fetal salivary gland bud, just developing adenoid and basket cells, a concept was fully supported. It is proposed that salivary gland tumors correspond to different stages of a developing gland. Adenoid cystic carcinoma recapitulates the terminal tubule complex stage of development with predominant differentiation of the analage along the intercalated duct cell line. 6 Chen and Gnepp studied expression of CEA, EMA, antikeratin (54kd), S100, MSA, laminin, type IV collagen in adenoid cystic carcinoma and normal salivary gland tissue. In a normal salivary gland, CEA and EMA were positive in acini, intercalated duct, and striated duct. Anti keratin antibody was demonstrated in intercalated duct & striated duct. The myoepithelial cells were positive for S-100 and MSA. In adenoid cystic carcinoma the luminal cells demonstrated CEA, EMA, antikeratin and S-100 clearly resembling ductal expression pattern. The non luminal cells /pseudocystic lining cells expressed

5 A d e n o i d C y s t i c C a r c i n o m a : P a g e 40 MSA, S-100 resembling myoepithelial cells. Anti Laminin & anti IV collagen antibody was seen only in pseudocysts in cribriform pattern and absent in tubular type. 7 Adenoid cystic carcinoma cells have a known propensity for perineural invasion. They are regularly found to encircle nerve sheaths and invade neural tissue directly. This leads to a high incidence of local recurrence and causes great difficulty in the curative resection of adenoid cystic carcinoma. The fundamental hypothesis was the inference that perineural invasion of adenoid cystic carcinoma cells may be analogous to that of schwann cells along embryonic nerves. Both S-100 and GFAP are defined as schwann cell markers in studies. 8 Although these two immunohistochemical markers may react to a variety of tissues, only Schwann cells and glial cells react to both of them. S-100 and GFAP were present in most Adenoid cystic carcinoma cells. Salivary Adenoid cystic carcinoma originates from two kinds of gland cell: myoepithelial cells and canula endothelial cells. Immunoelectron microscopy showed that the ultrastructures of S-100 and GFAP positive cells fit the characteristics of myoepithelial cells. Besides, double immunolabelling of S100 and the myoepithelial cell marker maspin proved the co-expression of these two markers. The results provided additional evidence that schwann cell differentiation occurs in modified myoepithelial cells of adenoid cystic carcinoma. It was demonstrated that a strong correlation between schwann cell differentiation and perineural invasion and it proves that Schwann cell differentiation occurs in modified myoepithelial cells of adenoid cystic carcinoma. It is therefore speculated that schwann cell differentiation of modified myoepithelial cells may be the histological base of perineural invasion of Adenoid Cystic Carcinoma. 9 The gene expression profile of adenoid cystic carcinoma has been studied by oligonucleotide array. The most overexpressed genes encode for basement membrane and extracellular matrix proteins of myoepithelial differentiation (e.g. laminin-b1, versican, biglycan and type IV collagen-a1). The most underexpressed genes are those encoding for proteins of acinar-type differentiation (e.g. amylase, carbonic anhydrase and salivary proline-rich proteins). Loss of heterozygosity in chromosome 6q23-25 has been found in 76% of cases of adenoid cystic carcinoma. 10 Oncogenes like CD117, HER2, mdm2,sox4 have been implicated in tumorogenesis of Adenoid Cystic Carcinoma. 11 Treatment & Prognosis The treatment of the Adenoid Cystic Carcinoma is chiefly surgical. The five year survival rate is 75% which gradually decreases to 20% at 10 years & 10% at 15 years. The overall prognosis depends upon several factors. Histologically, solid pattern has worse prognosis than cribriform patterns. Clinically size greater than 4 cm, surgical margins which are not clear are associated with worse prognosis. 12 Conclusion The cellular make-up of adenoid cystic carcinoma is strongly suggestive of an origin from the pluripotential reserve/stem cells.

6 A d e n o i d C y s t i c C a r c i n o m a : P a g e 41 Adenoid cystic carcinoma cells have a known propensity for perineural invasion which lead to a high incidence of local recurrence and a great difficulty in the curative resection of adenoid cystic carcinoma. With the advent of genetic studies, a better understanding of the molecular histogenesis is achieved, which further helps in deciding the treatment modalities and prognosis of Adenoid Cystic Carcinoma. References 1. Ellis, Auclair, Gnepp: Surgical pathology of salivary glands. Philadelphia WB Saunders Company 1991; pp Hubner G, Klein HJ, Kleinsasser, Schiefer HG. Role of myoepithelial cells in the development of salivary gland tumors. Cancer 1971; 27: Eversole LR. Histogenic classification of salivary gland tumours. Arch Pathol 1971; 92: Batsakis JG. Salivary gland neoplasia: An outcome of modified morphogenesis and cytodifferentiation. Oral Surg 1980; 49 (3): Tandler B. Ultrastructure of adenoid cystic carcinoma of salivary gland origin. Lab Invest 1971; 24: Chaudhry AP, Cutler L, Leifer C, Satchidanand S, Labay GR, Yamane G. Histogenesis of acinic cell carcinoma of the major and minor salivary glands. An ultastrucutral study. Jornal Oral Pathol 1986; 148: Chaudhry AP, Leifer C, Cutler LS, Satchidanand S, Labay GR, Yamane G. Histogenesis of Adnoid Cystic Carcinoma of the salivary glands. Light and electon microscopic study. Cancer 1986; 58: Chen JC, Gnepp DR, Bedrossian CW. Adenoid cystic carcinoma of the salivary glands: An immunohistochemical analysis. Oral Surg Oral Med Oral Pathol 1988; 65: Luo XL, Sun MY, Lu CT, Zhou ZH. The role of Schwann cell differentiation in perineural invasion of adenoid cystic and mucoepidermoid carcinoma of the salivary glands. Int J Oral Maxillofac Surgery 2006; 35: Cheuk W, Chan JKC. Advances in surgical pathology. Histopath 2007; Elledge R. Current concepts in research related to oncogenes implicated in salivary gland tumourigenesis: a review of the literature. Oral Dis 2009; 15: Marx RE, Stern D. Oral & Maxillofacial pathology A rationale for diagnosis & treatment.2003;