Non-invasive breast carcinoma

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Non-invasive breast carcinoma is a type of breast cancer and a common entity... since the introduction of radiologic breast screening.

Viewed simplistically, it can neatly be divided into the discussion of two entities:

  1. Ductal carcinoma in situ (DCIS).
  2. Lobular carcinoma in situ (LCIS).

Invasive breast cancer is dealt with in the article invasive breast cancer.

Ductal neoplasia

Overview

This category includes:

  1. Atypical ductal hyperplasia (ADH).
  2. Ductal carcinoma in situ (DCIS).

The difference between ADH and DCIS is:

  1. The degree of nuclear atypia; high grade is DCIS.
  2. The extent; small lesions are ADH, large lesions (low-grade) DCIS.

Is it ductal neoplasia?

FEHUT versus ADH versus DCIS

  • Breast duct lumen with too many cells; this is common problem is breast pathology.[1]
    • The general DDx for this scenario is: EHUT versus ADH versus DCIS.

Notes:

  • EHUT = epithelial hyperplasia of the usual type, AKA florid epithelial hyperplasia of the usual type (FEHUT).
  • ADH = atypical ductal hyperplasia.
  • DCIS = ductal carcinoma in situ.

Tabular comparison - histomorphology

Comparison of EHUT, ADH and DCIS (memory device: CLEAN = cell uniformity, luminal spaces, extent/size, arch., nuclei):

EHUT ADH DCIS
Cellular composition varied focal uniformity uniform
Lumina slits/irregular spaces;
cells haphazardly
arranged around lumen		 irregular spaces, no slits circular "punched-out";
cells side-by-side +
equally spaced @ interface
Extent usually lobulocentric limited extent extensive
Architecture irregular/swirling DCIS-like DCIS architecture (solid,
cribriform, papillary, micropapillary)
Nuclei (intranuclear
spacing)		 variable hyperchromatic
& uniform		 evenly spaced

Treatment - implications:

  • EHUT - nothing; EHUT is benign.
  • ADH - simple excision, i.e. lumpectomy.
  • DCIS - excision (lumpectomy) + radiation.
  • Invasive ductal carcinoma - excision with sentinel lymph node biopsy (for staging)[2] and radiation.
  • Positive sentinel node - systemic chemotherapy. (???)

IHC

Usual ductal hyperplasia (AKA FEHUT) vs. ADH/DCIS:[3][4]

  • FEHUT: ER-low/CK5-high profile.
  • ADH/DCIS: ER-high/CK5-low.

Where:

  • ER-high = diffuse strong staining in >90% of cells.
  • CK5-high = mosaic pattern of staining in >20% of cells
  • CK5-low = absent or staining in <20% of cells.

Atypical ductal hyperplasia

  • Abbreviated ADH.

General

  • Molecular studies have shown it is the same thing as low-grade DCIS; thus, some have called for abolition of the term.[5]
  • ADH is considered an indication for a lumpectomy.[6]
    • Two large studies suggest the conversion of an ADH on core biopsy to breast cancer on surgical excision, known as "up-grading", is approximately 30%.[7][8]

Epidemiology:

  • Relative risk of breast cancer, based on a median follow-up of 8 years, in a case control study of US registered nurses, is 3.7.[9]

Microscopic

Features:

  • Cytologic and architectural featurs same as low-grade DCIS.
  • Limited extent - either:[10]
    1. < Two complete ducts.
    2. < 2 mm.

Images:

Ductal carcinoma in situ

  • Abbreviated DCIS.

General

  • Diagnosis based on nuclear abnormalities and architecture.
  • It is typically picked-up during radiologic screening.

Microscopic

Features:

  • Architectural changes:
    • Equal spacing of cells - "cookie cutter" look.
    • Cells line-up along lumen/glandular spaces - form "Roman briges".
    • Architecture suggestive of DCIS - see Subtypes of DCIS.
  • Nuclear changes:
    • Nuclear enlargement - at least 2-3x size of RBC - key feature.
      • Compared to RBCs to grade DCIS - see Grading DCIS.
        • Compare sizes of nuclei if you cannot find RBCs.
    • Nuclear pleomorphism - important feature.
  • +/-Mitoses.

Note:

  • Apocrine changes of cytoplasm -- nuclei should be ~4x RBC for low grade, 5x RBC for high grade.[11]

Subtypes of DCIS

Subtypes are based on architecture:

  • Solid.
    • No spaces between cells.
  • Cribriform.
    • Honeycomb-like appearance: circular holes.
    • "Cookie cutter" appearance/"punched-out" appearance/"Roman bridges" -- cells surround the circular holes.
  • Papillary.
    • Papillae with fibrovascular cores.
  • Micropapillary.
    • Small papillae without fibrovascular cores.
    • Have "drum stick" shape.

NOTE: comedonecrosis - used to be considered a separate subtype -- essentially solid type DCIS with necrosis.

Grading DCIS

Graded 1-3 (low-high)[12] - compare lesional nuclei to one another.

  • Grade 1:
    • Nuclei 2-3x size of RBC.
    • No necrosis.
  • Grade 2:
    • Nuclei 2-3x size of RBC.
    • +/-Necrosis.
  • Grade 3:
    • Nuclei >3x size of RBC.
    • Necrosis usually present.

Notes:

  • It is often hard to find RBCs when you want 'em. DCIS is pleomorphic.
  • If no RBCs are present to compare with compare the nuclei to one another.
  • If you see nuclei >3x larger than their neigbour you're ready to call DCIS Grade 3.

Size criteria for low-grade DCIS

ADH is diagnosed if the lesion is small - specifically:[13][14]

  1. < Two membrane-bound spaces.
  2. < 2 mm extent.

The treatment is similar; ADH and DCIS are both excised.

The differences are:

  • DCIS is cancer, i.e. this has life insurance implications.
  • Radiation treatment - DCIS is irradiated; ADH does not get radiation.

Micrometastasis in DCIS

Micrometastasis in DCIS - not significant.[15][16]

Lobular neoplasia

Overview

Includes:

  1. Atypical lobular hyperplasia (ALH).
  2. Lobular carcinoma in situ (LCIS).
  • These entities (ALH, LCIS) are near identical from a histomorphologic perspective.
  • The difference is extent of involvement:
    • ALH <50% of terminal duct lobular unit (TDLU) is involved.
    • LCIS >=50% of TDLU is involved.

Atypical lobular hyperplasia

  • Abbreviated ALH.

Microscopic

See LCIS.

Lobular carcinoma in situ

  • Abbreviated LCIS.

General

  • Management is currently some matter of debate.
  • Not detected radiologically - it is an incidental pathologic finding.

Microscopic

Features:[17][18]

  • Cells distend the duct.
  • Dyscohesive - distinct cell border visible.
  • Clear cytoplasm (focally); may have signet ring cell-like appearance.
  • Eccentrically placed round nucleus,
    • Usually minimal atypia, relatively small ~1-2x size lymphocyte.
    • +/-Nucleolus.


Memory device ABCDE:

  • Atypia minimal.
  • Borders of cells distinct.
  • Clear cytoplasm.
  • Distend duct.
  • Eccentric nucleus.

Subclassification[18]

  • Non-PLCIS.
    • Type A.
      • Nucleus 1-1.5x lymphocyte.
      • No nucleolus.
    • Type B.
      • Nucleus ~2x lymphocyte.
      • Nucleolus present.
  • PLCIS (pleomorphic lobular carcinoma in situ).

Main DDx:

  • Low-grade DCIS.

See also

References

  1. ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 167-8. ISBN 978-0443066801.
  2. ↑ Sentinel Lymph Node Biopsy: What Breast Cancer Patients Need to Know. cancernews.com. URL: http://www.cancernews.com/data/Article/202.asp. Accessed on: 9 October 2009.
  3. ↑ Rabban, JT.; Koerner, FC.; Lerwill, MF. (Jul 2006). "Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: a potentially difficult distinction resolved by cytokeratin 5/6.". Hum Pathol 37 (7): 787-93. doi:10.1016/j.humpath.2006.02.016. PMID 16784976.
  4. ↑ Grin, A.; O'Malley, FP.; Mulligan, AM. (Nov 2009). "Cytokeratin 5 and estrogen receptor immunohistochemistry as a useful adjunct in identifying atypical papillary lesions on breast needle core biopsy.". Am J Surg Pathol 33 (11): 1615-23. doi:10.1097/PAS.0b013e3181aec446. PMID 19675450.
  5. ↑ Ghofrani, M.; Tapia, B.; Tavassoli, FA. (Dec 2006). "Discrepancies in the diagnosis of intraductal proliferative lesions of the breast and its management implications: results of a multinational survey.". Virchows Arch 449 (6): 609-16. doi:10.1007/s00428-006-0245-y. PMID 17058097.
  6. ↑ Liberman L, Cohen MA, Dershaw DD, Abramson AF, Hann LE, Rosen PP (May 1995). "Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy". AJR Am J Roentgenol 164 (5): 1111–3. PMID 7717215. http://www.ajronline.org/cgi/pmidlookup?view=long&pmid=7717215.
  7. ↑ Deshaies, I.; Provencher, L.; Jacob, S.; Côté, G.; Robert, J.; Desbiens, C.; Poirier, B.; Hogue, JC. et al. (Feb 2011). "Factors associated with upgrading to malignancy at surgery of atypical ductal hyperplasia diagnosed on core biopsy.". Breast 20 (1): 50-5. doi:10.1016/j.breast.2010.06.004. PMID 20619647.
  8. ↑ Margenthaler, JA.; Duke, D.; Monsees, BS.; Barton, PT.; Clark, C.; Dietz, JR. (Oct 2006). "Correlation between core biopsy and excisional biopsy in breast high-risk lesions.". Am J Surg 192 (4): 534-7. doi:10.1016/j.amjsurg.2006.06.003. PMID 16978969.
  9. ↑ London, SJ.; Connolly, JL.; Schnitt, SJ.; Colditz, GA. (Feb 1992). "A prospective study of benign breast disease and the risk of breast cancer.". JAMA 267 (7): 941-4. PMID 1734106.
  10. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 258. ISBN 978-0470519035.
  11. ↑ URL: http://surgpathcriteria.stanford.edu/breast/dcis/apocrinedcis.html. Accessed on: 4 August 2011.
  12. ↑ URL: http://surgpathcriteria.stanford.edu/breast/dcis/. Accessed on: 4 August 2011.
  13. ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 168. ISBN 978-0443066801.
  14. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 258. ISBN 978-0470519035.
  15. ↑ Lara, JF.; Young, SM.; Velilla, RE.; Santoro, EJ.; Templeton, SF. (Nov 2003). "The relevance of occult axillary micrometastasis in ductal carcinoma in situ: a clinicopathologic study with long-term follow-up.". Cancer 98 (10): 2105-13. doi:10.1002/cncr.11761. PMID 14601079.
  16. ↑ Broekhuizen, LN.; Wijsman, JH.; Peterse, JL.; Rutgers, EJ. (Jun 2006). "The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast.". Eur J Surg Oncol 32 (5): 502-6. doi:10.1016/j.ejso.2006.02.006. PMID 16569492.
  17. ↑ Weedman Molavi, Diana (2008). The Practice of Surgical Pathology: A Beginner's Guide to the Diagnostic Process (1st ed.). Springer. pp. 188. ISBN 978-0387744858.
  18. ↑ 18.0 18.1 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 170. ISBN 978-0443066801.
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