Adenoid Cystic Carcinoma (ACC)

CLINICAL FEATURES

• Accounts for ~ 10% of all salivary neoplasms and 30% of minor salivary gland tumors;

• M:F=2:3, mean age of 54.5;

• The parotid gland is the single most common site(25%).  ACC of minor salivary gland origin occurs most frequently in the oral cavity (palate);

• Slow growing but clinical course is relentless and progressive; 50% metastasize, often silently to lung or bone;

• The cribriform pattern was also called cylindroma;

• Biphasic tumor: ductal and myoepithelial components, most of the tumor cells are abluminal type cells of myoepithelial differentiation;

• Frequent multiple local recurrence: solid pattern 100%, cribriform pattern 89%, tubular pattern 59%; frequent spread to the lungs and bones;

• Frequent nerve invasion due to expression of brain derived neutrotrophic factor;

GROSS FINDINGS

• Small, solid, poorly encapsulated and infiltrative; Firm and white to gray-white.

MICROSCOPIC FINDINGS

• Three growth patterns: cribriform, solid or tubular pattern; typically a mixture of these patterns.

  • Cribriform Pattern

    • Most common pattern, sieve-like or Swiss cheese-like appearance, islands of tumor cells contain several small, round pseudo-cystic structures;

    • Cystic structures: vary slightly in diameter, rarely very large; not true ductal or glandular lumen but are contiguous with the supporting connective tissue stroma; usually contain basophilic and/or eosinophilic hyalinized material;

    • Tumor cells: indistinct cell borders, variable amphophilic to clear cytoplasm;

    • Nuclei: rather uniform, round to oval, or angular and irregular; darkly basophilic to lightly basophilic with homogeneous chromatin; occasional small nucleoli.

  • Tubular Pattern

    • Scattered foci of nests that are separated from one another;

    • Tumor cells surround tiny lumens, which are much smaller than the pseudo-lumens of the pseudo-cysts;

    • More eosinophilic cytoplasm, larger N/C ratio, uniform round nuclei, occasional small nucleoli.

  • Solid Pattern

    • Least common pattern;

    • Solid tumor islands in variable sizes, round or lobulated;

    • Tumor cells are similar to those in other pattern, but many cells are larger, less angular, larger nuclei.

• Peripheral nerve invasion: hallmark of this tumor.

• Dedifferentiated tumors: irregular tumor islands, anaplastic cells with abundant cytoplasm and desmoplastic stroma.

• Grading

  • Low grade/grade I: tubular and cribriform patterns;

  • Intermediate grade/grade II: <30% solid;

  • High grade/grade III: >30% solid.

DIFFERENTIAL DIAGNOSES

• Polymorphous Low Grade Adenocarcinoma (PLGA)

  • Terminal duct carcinoma, primarily a tumor of the intraoral minor gland, very rare in major salivary glands;

  • Variable patterns: cribriform, hyalinized, cystic, sheet, glandular, tubular, canalicular, single-file cords;

  • Very uniform population of epithelial cells with round, vesicular to euchromatic nuclei and eosinophilic cytoplasm;

  • CD117 weak/negative.

  • Immunohistochemistry Stainings

    	PLGA	ACC
    CEA	+/−	+
    EMA	+	+
    S100	+	+/−
    Vimentin	+	−
    SMA	?	+
    MSA	+/−	+
    P53	+/−	+/−
    C-erB-2	−	+/−
    GFAP	−	?
    CD117	−/+	+

• Pleomorphic adenoma

  • Not invasive, no perineural invasion, squamous metaplasia and mesenchyme-like areas;

  • Plasmacytoid and spindle myoepithelial cells.

• Basaloid Squamous Cell Carcinoma

  • Predilection for the hypopharynx, base of the tongue, and supraglottic larynx;

  • Tumor cells: small, hyperchromatic; in solid lobules, adenomatoid pattern and cords.

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

• Cytokeratin

• CEA

• Alpha-1-antichymotrypsin

• S100

• CD117/c-kit

• SMA

ELECTRON MICROSCOPIC FINDINGS

• Pseudoglandular spaces, intercellular spaces, abundant basal lamina, true glandular lumina;

• Cells are intercalated ducts, myoepithelial, secretory and reserve cells

CYTOGENETIC STUDIES

• Loss of heterozygosity at 6q23-25 ( t[6;9][q21-24;p13-23] )

TREATMENT AND PROGNOSIS

• Treatment: radical surgery regardless of tumor differentiation

• Prognosis

  • 5-year survival 60%, 10-year 30%, 15-year 15%;

  • 15-year survival, solid 5%, cribriform 26%, tubular 39%;

  • Better prognosis: tumors of palate or parotid gland;

  • Poorer prognosis: dedifferentiated, p53+ tumors.

REFERENCES

• AFIP, tumor of the salivary glands, series 3;

• http://www.pathologyoutlines.com/salivaryglands.html#adenoidcystic

• Curr Opin Otolaryngol Head Neck Surg 12:127–132

• Bianchi B et al., Adenoid cystic carcinoma of intraoral minor salivary glands, Oral Oncol (2008)