Case 229 - Discussion

Uploaded: 2008-05-20, Updated: 2008-05-23

Adenoid Cystic Carcinoma (ACC)

The Key Features

  • Most ACCs arise in the minor salivary glands (60%), especially oral cavity (palate);

  • Slow growing but clinical course is relentless and progressive;

  • Frequent peripheral nerve invasion;

  • Three growth patterns: cribriform, solid or tubular pattern;

  • CD117+.


  • 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;


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


  • 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.


  • 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.


  • Cytokeratin

  • CEA

  • Alpha-1-antichymotrypsin

  • S100

  • CD117/c-kit

  • SMA


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

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


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


  • 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.


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

  • Curr Opin Otolaryngol Head Neck Surg 12:127132

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