ADENOID CYSTIC CARCINOMA
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It is a malignant epithelial tumour of modified myoepithelial (abluminal) & ductal (luminal) differentiated cells.
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General features:
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Adenoid cystic carcinoma is the 4 th most common carcinoma of salivary glands
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Incidence is 10% of all salivary gland carcinomas
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Site – most common is parotid, can occur in minor salivary glands among which more common is palate. It is also common tumour among sublingual gland tumours.
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Sex – shows female predominance
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Age- Peak incidence is in the sixth decade. But can occur at any age.
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Clinical features:
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Painless slow growing tumours
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Later produce tenderness & facial nerve paralysis
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Palatal tumours produce intra oral mucosal ulceration.
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Gross findings:
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They are poorly circumscribed tumours
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Cut surface is grey white and are firm in consistency
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Microscopic findings:
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Tumor cells are relatively uniform and have variety of patterns
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3 growth patterns which are found are –
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Cribriform (most common)
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Tubular pattern
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Solid pattern
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Cribriform pattern
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Sieve like or Swiss cheese like appearance showing islands or sheets of tumour cells having small circular, pseudo cystic structures
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Cyst like spaces are not true gland lumens but are contiguous with the supporting connective tissue stroma of tumour .They contain accumulation of
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Eosinophilic,hyalinized basal lamina (PAS positive)
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Basophilic amorphous glycoasaminoglycans (Alcian blue positive)
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Both
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True glandular lumens lined by ductal epithelial cells are also seen.
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Tumour cells with myoepithelial differentiation have indistinct cell borders and eosinophilic to clear cytoplasm and have round or oval to angular nuclei. These cells surround the pseudo luminal spaces.
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Nuclear cytoplasmic ratio is 1:1.
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Tubular pattern:
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This is composed of ducts lined by ductal cells which are surrounded myoepithelial cells.
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Myoepithelial differentiation is easily identified by angular nuclei and clear cytoplasm.
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Cells are arranged in small nests separated by the stroma.
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In some cases stroma is hyalinized and tumour cells are arranged in thin strands –trabecular pattern.
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Solid pattern:
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Tumour cells are arranged as lobulated aggregate with minimum or absence of stroma.
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Necrosis, cellular pleomorphism and mitotic figures can be seen in these variant.
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Dedifferentiated adenoid cystic carcinoma
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In this type conventional adenoid cystic carcinoma is seen along with poorly differentiated adenocarcinoma or high grade undifferentiated carcinoma. There are aggressive neoplasms with poor prognosis.
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Immuno histochemical findings:
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Ductal cells react more intensely than myoepithelial cells with pancytokeratin immunostains.
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Tumour cells are reactive for
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CK7
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CK14
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CK17
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CK19
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Keratin, Vimentin, Muscle specific actin & Myosin are positive with cells showing myoepithelial differentiation
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Myoepithelial differentiated cells also express P 63, Smooth Muscle Actin, Smooth Muscle Myosin heavy chains & Calponin.
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Other IHC markers which are positive in ACC are-
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EGFR
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Fibroblast growth factors & its receptor
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TGF-α
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Hyakeronan
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Molecular & cytogenetic findings:
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30% of tumors shows translations involving chromosome 9p13-23.
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Deletion or methylation of p16INK4a localised to 9p21 is more frequent.
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Other chromosomal abnormalities noted are
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loss in chromosome 12q12-q13
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Allelic losses at 1p, 2p, 6q, 17p, 19q & 20P
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loss of heterozygosity at 6q23-25.
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Over expressed genes in this tumor include-SOX4, AP-2α, AP-2ᵞ, & NGFI-A binding protein 1
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Differential diagnosis:
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Polymorphous Low Grade Adenocarcinoma
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Basal cell adenoma
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Basal cell adenocarcinoma
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Basaloid squamous cell carcinoma
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PLGA (polymorphous low grade adenocarcinoma) – PLGA lacks angular nuclei of ACC. Dual population of ductal & myoepithelial cells is absent. Mitoto figures & cellular pleomorphism is rare.
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Differential Diagnosis of basoloid neoplasms
Features |
Basal cell adenoma |
Basal adenocarcinoma |
Basaloid squamous cell carcinoma |
Acc solid type |
Mitosis >3/10HPF |
Very rare (-) |
Can be seen (+/-) |
Always present (++) |
Usually present (+) |
perineural Invasion |
– |
present |
++ |
++ |
Necrosis |
– |
Occasionally(-/+) |
++ |
+ |
Angular nuclei |
– |
– |
– |
++ |
Squamous differentiation |
-/+ |
-/+ |
++ |
– |
Peripheral palisaded nuclei |
++ |
+ |
+/- |
– |
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Epithelial myoepithelial carcinoma also have dual population but lacks cribriform pattern.
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Pleomorphic adenoma –
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Myxochondroid areas, plasmacytoid & spindle shaped myoepithelial cells are seen in PA but absent in ACC
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In ACC tumor cells are usually well demarcated from the surrounding stroma where as in PA myoepithelial cells blend into the myxochondroid areas.
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Treatment & prognosis:
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Prognosis of tumor depends upon the patterns of tumor cell and are graded as high grade & low grade
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Szan etal grading system
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High grade – >30% of solid areas in tumor
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Low grade -<30% of solid areas
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Perineural invasion is associated with poorer survival higher recurrence rate & greater incidence of metastatsis.
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Tumor size – greater than 4cm was unfavourable prognosis
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Regional Lymphnode metastasis or distant metastasis – poor prognostic factors
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Tumor stage –independent prognostic factor
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Proliferation index by immunostaining with ki-67- is an important prognostic factor.
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Treatment – wide to radical surgical excision along with adjunct radiotherapy is rcommended
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References
Gary L. Ellis, Paul L.Auclair. Malignant epithelial neoplasm. Adenoid cystic carcinoma. In:Tumors of the salivary Glands.AFIP Atlas of Tumor pathology.Series 4.2008;pp 225-245.