<B>Ductal Carcinoma in Situ </B>

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Ductal Carcinoma in Situ

Etiology:

• Unknown

Pathogenesis:

• BRCA1 either inherited or somatically mutated with loss of heterozygosity may remove suppression of cell growth by gene product
• Gene product is a granin (same family as chromogranin seen in neurosecretory granules
• Bound to RNA polymerase II holoenzyme with impact on transcription
• Other pathogenetic mechanisms not known.

Epidemiology:

• Increasing age
• More frequent in women of low parity with first child after 30
• Increased in obesity
• Increased in women with history of atypical hyperplasia
• Increased in women with history of breast carcinoma
• Increased in women with mother or sibling with breast cancer
• Increased in women with mutations in BRCA1 or BRCA2 genes

General Gross Description:

• May be associated with microcalcifications within the lumens
• Gross findings may be of fibrocystic change
• May form mass
• In comedo variant cysts(dilated ducts) filled with granular, yellow white material
• May be associated with invasive carcinoma

General Microscopic Description:

• Several varieties including papillary (delicate fibrovascular cores covered with atypical cells), cribriform (multiple lumens within a single duct), solid, micropapillary (tiny epithelial papillae) and comedo (around necrotic center)
• All show loss of typical bilayer epithelium
• All show enlarged round to oval nuclei with nucleoli; comedo variety typically shows nuclear pleomorphism, hyperchromasia, large nucleoli and mitotic activity
• All show loss of polarity towards lumen
• All types may show intraluminal microcalcifications

Clinical Correlations:

• Increased risk of breast cancer 10 fold
• Lesions are generally extirpated surgically with clear margins

References:
• Cotran RS, Kumar V, Robbins SL. Robbins Pathologic Basis of Disease 5th edition. W.B. Saunders, Philadelphia, 1994, pp.1099-1108. • Scully, R.; et.al. Proc. Nat.Acad. Sci. 94: 5605-5610, 1997.