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.

 

Adenoid cystic carcinoma: Tumor cells arranged in lobules separated by fibrous septa. Tumor cells show cribriform pattern of arrangement (H&E,X50)

 

Adenoid cystic carcinoma: Sieve like appearance showing islands or sheets of tumor cells having pseudolumens (H&E,X100)

 

Adenoid cystic carcinoma

Adenoid cystic carcinoma: Sieve like appearance showing islands or sheets of tumor cells having pseudolumens. Perineural invasion is present (right side) (H&E,X100)

 

Adenoid cystic carcinoma

Adenoid cystic carcinoma: Tumor cells arranged in Sieve like pattern with pseudolumens (H&E,X200)

 

 

Adenoid Cystic carcinoma: Cyst like spaces containing eosinophilic hyalinized basal lamina material which is contagious with the connective tissue stroma of tumor (H&E,X100)

 

Adenoid cystic carcinoma: Tumor shows hyalinized stroma separating the lobules of tumor cells (H&E,X100)

 

Adenoid cystic carcinoma: Hyalinized stroma showing cords of tumor cells (H&E,X100)

 

Adenoid cystic carcinoma: Pseudolumens showing eosinophilic basal lamina like material which is contiguous with connective tissue stroma of tumor (H&E,X100)

 

Adenoid cystic carcinoma: Tumor cells arranged in glandular pattern and cribriform pattern with pseudolumens showing basophilic material. Interstitial stroma shows congested blood vessels (H&E,X100)

 

Adenoid cystic carcinoma: Tumor cells arranged in glandular pattern and cribriform pattern with pseudolumens showing basophilic material. Interstitial stroma shows congested blood vessels (H&E,X100)

 

Adenoid cystic carcinoma: Pseudolumens with basal lamina material contiguous with connective tissue stroma (H&E,X400)

 

Adenoid cystic carcinoma: Tumor cells arranged in tubular pattern with double layered lining epithelial cells surrounding the tubular luimens (H&E,X100)

 

Adenoid cystic carcinoma: True glandular lumens lined by epithelial cells (H&E,X400)

 

Adenoid cystic carcinoma: True glandular lumens lined by epithelial cells (H&E,X400)

 

Adenoid cystic carcinoma: Tumor cells arranged in tubular pattern with double layered lining epithelial cells surrounding the tubular luimens (H&E,X400)

 

Adenoid cystic carcinoma: Tumor cells arranged in Sieve like pattern with pseudolumens (H&E,X200)

 

Adenoid cystic carcinoma: Tumor cells arranged in solid sheets and tubular pattern (H&E,X100)

 

Adenoid cystic carcinoma: Tumor cells arranged in sieve like pattern. Cells have indistinct borders with eosinophilic to clear cytoplasm and have round or oval to angular nuclei. Pseudolumens have basophilic material (H&E,X400)

 

Adenoid cystic carcinoma: Circumscribed tumor with pseudocapsule (right below) and tumor cells arranged in lobules with sieve like pattern (H&E,X50)

 

Adenoid cystic carcinoma: Tumor cells arranged in lobules with sieve like pattern. (H&E,X50)

 

Adenoid Cystic carcinoma: Cyst like spaces containing eosinophilic hyalinized basal lamina material which is contagious with the connective tissue stroma of tumor (H&E,X100)

 

Adenoid Cystic carcinoma: Cyst like spaces containing eosinophilic hyalinized basal lamina material which is contagious with the connective tissue stroma of tumor (H&E,X100)

 

Adenoid cystic carcinoma: Circumscribed tumor (left) with pseudocapsule and adjacent salivary gland parenchyma (H&E,X50)

 

Adenoid cystic carcinoma: Tumor cells arranged in cribriform pattern with perineural invasion (centre) (H&E,X100)

 

Adenoid cystic carcinoma: Tumor cells arranged in cribriform pattern with perineural invasion (centre) (H&E,X400)

 

Adenoid cystic carcinoma: Tumor cells arranged in cribriform pattern with perineural invasion (centre) (H&E,X100)