Things every pathologist should know about Ductal Carcinoma in-situ (DCIS)

General

  • Clonal proliferation of epithelial cells that is limited to the duct (intact basement membrane; maintains myoepithelial layer).

  • There is NO invasion into the surrounding tissues.

  • DCIS constitutes ~15-30% of all cancers in women receiving screening for breast cancer.

  • Bilateral in 10-20% of cases..

  • Excision is curative in more than 95% of cases. If untreated, risk for development of cancer is 1% per year.

  • Cancer risk

  • 8-10x increased risk of developing cancer

  • Has a loss of 16q and 17p

Clinical picture

  • Ill-defined lump on palpation, but most often found incidentally on mammography (due to dystrophic calcifications in response to focal necrosis)

Microcalcifications associated with DCIS:

  • Irregular clusters, linear, or branching patterns of microcalcifications represent about 20% chance of malignancy and should be biopsied or resected.

  • Radiographs of resection specimens help pathologists to sample the areas of greatest concern more heavily.

  • If possible, the entire lesional area should be submitted.

  • Mention that histopathologic correlation with the specimen radiograph was performed in the pathologist’s comment section of the report.

  • Clinicians & radiologists want to correlate the abnormal clinical picture/imaging findings to pathology. If the requisition sheet says there should be calcifications present but you don’t see any, consider X-raying the block to make sure calcifications are present and get deeper levels. If you still can’t find any calcs, MENTION IT! They may have missed the lesion and need to go back!



Histologic patterns in DCIS:


Cribriform/Noncomedo DCIS

  • Uniform, well demarcated secondary lumens (Formed by sharp radial distribution of tumor cells)

  • Referred to as “cookie cutter” or “punched out” lesions

  • Sharp, well demarcated margins


Micropapillary (& Papillary type) DCIS

  • Micropapillary DCIS has fingertip-like papillary projections into lumen (they do NOT have a fibrovascular core)

  • Typically have very narrow base with broadened, bulging tips that connect to each other forming “Roman bridges”.

  • Intervening epithelium is usually flat

  • Low grade nuclei (unusual cases with high grade nuclei, frequent mitosis and necrosis)

Solid DCIS

  • Cells fill and expand the duct lumina, but still confined by basement membrane

Comedo DCIS

  • Uncommon, but generally good prognosis even if there is microinvasion (<1mm)

  • Basically, is just solid DCIS that has central necrosis +/- calcifications

  • Necrosis is what causes the “cheesy material” from the ducts with pressure (similar to comedone)

  • Prominent periductal fibrosis with minimal chronic inflammation


  • Other patterns of DCIS (not pictured):

  • Clinging

  • Pagetoid

NUCLEAR GRADING OF DCIS


Van Nuys System

  • Classification system for DCIS primarily based on the nuclear grade, presence of necrosis, size and margin status.

  • If a focus of DCIS is ER positive, attenuation of estrogen effect (by receptor blockade or by inhibition of aromatase enzyme involved in estrogen production) is used to reduce local recurrence.

  • “Clear margins” not clearly defined. However, a margin of 1 cm (10 mm) appears to be adequate for DCIS and likely obviates the need for radiation therapy in most cases.


LOW GRADE DCIS

  • Uniform, round, hyperchromatic nuclei that are relatively evenly spaced

  • Still surrounded/confined by basement membrane

  • +/- microcalcifications

  • Increased monomorphic cells entirely filling the duct in specific architectural pattern

  1. Mild increase in nuclear to cytoplasmic ratio

  2. Well-defined cell membranes

  3. Minimal hyperchromatism; homogeneous chromatin distribution

  4. Minimal pleomorphism

  5. Inconspicuous nucleoli

  6. No intermingled myoepithelial cells present within the cellular proliferation

Criteria to diagnose low grade DCIS:

  • More than one focus of these (low grade) atypical glands should be identified to call it DCIS or >2 mm in size. (If only a single focus, consider calling it ADH instead)

  • Both the characteristic low grade nuclear morphology and an architectural pattern are needed.

  • Requires some degree of geographical extent per pathologist’s interpretation. Commonly used opinions:

  1. See >1 minute focus of low grade DCIS be present

  2. Total extent of the process be 2 mm or more

  3. 3 or more ducts involved





HIGH GRADE DCIS

  • Compelling nuclear atypia

  • Often has central necrosis (but not reqd to make the diagnosis)

  • Still can form architectural patterns (comedo, solid, micropapillary etc) +/- microcalcifications

  • No quantitation requirements needed to make this diagnosis.

  • If you see nuclear atypia or central necrosis, CALL IT HIGH GRADE!

  • Make sure to look for signs of invasion!



Criteria to diagnose high grade DCIS:

  • The diagnosis of high grade DCIS can be done in a single duct of any size. If you see nuclear atypia, it automatically makes it high grade!

  • Neither the architecture of the intraductal proliferation nor the amount need to be considered in the diagnosis of high grade-intraductal carcinoma

DCIS vs. Invasive Carcinoma

  • If there is a questionable focus of invasive-appearaning cancer adjacent to DCIS, lean away from calling it invasive. It may just be a tangential section through the DCIS.

  • An intact basement membrane or myoepithelial cell layer favors non-invasive.

  • Remember that some invasive carcinomas still retain ME cells and that ME cell layer is discontinuous and may not stain in in all benign lesions.

  • If definite invasive component extends <1 mm into the stroma, the term “microinvasion” can be used.

DCIS SUMMARY:


What to mention when signing out DCIS:

  • Histologic pattern (Cribriform, micropapillary, solid, comedo)

  • Nuclear features (Low vs. high grade)

  • Necrosis (Focal/central vs. Extensive)

  • Microcalcifications (CaPO4; can form on secretory material/cell membranes with regular repeating structure)


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These posts contain high yield information collected from various educational resources including textbooks, journal articles, educational websites and more. They are intended for educational use only and should NOT be taken as medical advice. I strongly believe the spreading of knowledge and depth of learned information should be encouraged in today's society rather than coveted. Membership is required to view these posts  and should be used solely for educational purposes only.