Adenoid cystic carcinoma

ADENOID CYSTIC CARCINOMA

• It is a malignant epithelial tumour of modified myoepithelial (abluminal) & ductal (luminal) differentiated cells.

• General features:

  • Adenoid cystic carcinoma is the 4 ^th most common carcinoma of salivary glands

  • Incidence is 10% of all salivary gland carcinomas

  • 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.

  • Sex – shows female predominance

  • Age- Peak incidence is in the sixth decade. But can occur at any age.

• Clinical features:

  • Painless slow growing tumours

  • Later produce tenderness & facial nerve paralysis

  • Palatal tumours produce intra oral mucosal ulceration.

• Gross findings:

  • They are poorly circumscribed tumours

  • Cut surface is grey white and are firm in consistency

• Microscopic findings:

  • Tumor cells are relatively uniform and have variety of patterns

  • 3 growth patterns which are found are –

    • Cribriform (most common)

    • Tubular pattern

    • Solid pattern

• Cribriform pattern

  • Sieve like or Swiss cheese like appearance showing islands or sheets of tumour cells having small circular, pseudo cystic structures

  • Cyst like spaces are not true gland lumens but are contiguous with the supporting connective tissue stroma of tumour .They contain accumulation of

    • Eosinophilic,hyalinized basal lamina (PAS positive)

    • Basophilic amorphous glycoasaminoglycans (Alcian blue positive)

    • Both

  • True glandular lumens lined by ductal epithelial cells are also seen.

  • 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.

  • Nuclear cytoplasmic ratio is 1:1.

• Tubular pattern:

  • This is composed of ducts lined by ductal cells which are surrounded myoepithelial cells.

  • Myoepithelial differentiation is easily identified by angular nuclei and clear cytoplasm.

  • Cells are arranged in small nests separated by the stroma.

  • In some cases stroma is hyalinized and tumour cells are arranged in thin strands –trabecular pattern.

• Solid pattern:

  • Tumour cells are arranged as lobulated aggregate with minimum or absence of stroma.

  • Necrosis, cellular pleomorphism and mitotic figures can be seen in these variant.

• Dedifferentiated adenoid cystic carcinoma

  • 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.

• Immuno histochemical findings:

  • Ductal cells react more intensely than myoepithelial cells with pancytokeratin immunostains.

  • Tumour cells are reactive for

    • CK7

    • CK14

    • CK17

    • CK19

  • Keratin, Vimentin, Muscle specific actin & Myosin are positive with cells showing myoepithelial differentiation

  • Myoepithelial differentiated cells also express P 63, Smooth Muscle Actin, Smooth Muscle Myosin heavy chains & Calponin.

  • Other IHC markers which are positive in ACC are-

    • EGFR

    • Fibroblast growth factors & its receptor

    • TGF-α

    • Hyakeronan

• Molecular & cytogenetic findings:

  • 30% of tumors shows translations involving chromosome 9p13-23.

  • Deletion or methylation of p16INK4a localised to 9p21 is more frequent.

  • Other chromosomal abnormalities noted are

    • loss in chromosome 12q12-q13

    • Allelic losses at 1p, 2p, 6q, 17p, 19q & 20P

    • loss of heterozygosity at 6q23-25.

    • Over expressed genes in this tumor include-SOX4, AP-2α, AP-2ᵞ, & NGFI-A binding protein 1

• Differential diagnosis:

  • Polymorphous Low Grade Adenocarcinoma

  • Basal cell adenoma

  • Basal cell adenocarcinoma

  • Basaloid squamous cell carcinoma

• 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.

• 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	++	+	+/-	–

• Epithelial myoepithelial carcinoma also have dual population but lacks cribriform pattern.

• Pleomorphic adenoma –

  • Myxochondroid areas, plasmacytoid & spindle shaped myoepithelial cells are seen in PA but absent in ACC

  • In ACC tumor cells are usually well demarcated from the surrounding stroma where as in PA myoepithelial cells blend into the myxochondroid areas.

• Treatment & prognosis:

  • Prognosis of tumor depends upon the patterns of tumor cell and are graded as high grade & low grade

  • Szan etal grading system

    • High grade – >30% of solid areas in tumor

    • Low grade -<30% of solid areas

  • Perineural invasion is associated with poorer survival higher recurrence rate & greater incidence of metastatsis.

  • Tumor size – greater than 4cm was unfavourable prognosis

  • Regional Lymphnode metastasis or distant metastasis – poor prognostic factors

  • Tumor stage –independent prognostic factor

  • Proliferation index by immunostaining with ki-67- is an important prognostic factor.

  • Treatment – wide to radical surgical excision along with adjunct radiotherapy is rcommended

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.