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. An introduction to the breast is found in the breast pathology article.

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: FEHUT versus ADH versus DCIS.

Notes:

Tabular comparison - histomorphology

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

FEHUT ADH DCIS
Cell spacing varied, streaming 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 variable, no nucleolus hyperchromatic
& uniform, usu. no nucleolus		 evenly spaced +/-nucleolus

Treatment - implications:

  • FEHUT - nothing; FEHUT 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 feature of low-grade DCIS.
    • Cell spacing ~ equal.
    • Lumina round.
    • Architecture - classically cribriform or solid; may be micropapillary or papillary.
    • Small nuclei.
      • Small indistinct nucleoli.
  • Limited extent (diagnostic size cutoffs) - either:[10]
    1. < Two complete ducts.
    2. < 2 mm.

DDx:

Note:

  • High-grade DCIS is not in the DDx of ADH.

Images:

IHC

  • CK5 <20% +ve.
  • ER +ve - diffusely.
    • Heterogenous in EHUT.

Ductal carcinoma in situ

  • Abbreviated DCIS.

General

  • Diagnosis based on nuclear abnormalities and/or architecture.
    • Low-grade DCIS does not have a malignant cytology.
  • 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 -- several sets of criteria exist -- any of the following:
    1. Nuclei should be ~4x RBC for low grade, 5x RBC for high grade.[11]
    2. Nuclear enlargement of 3x +/- nucleolar enlargement.[12]
    3. Multiple nucleoli + nuclear size variation.[12]

Subtypes of DCIS

The subtypes are based on architecture.

Note:

  • Comedonecrosis used to be considered a separate subtype. Necrosis is seen most often in the context of solid ductal carcinoma in situ.
Solid ductal carcinoma in situ

Features:

  • No spaces between cells.

DDx:

Cribriform ductal carcinoma in situ

Features:

  • Honeycomb-like appearance: circular holes.
  • "Cookie cutter" appearance/"punched-out" appearance/"Roman bridges" -- cells surround the circular holes.
Papillary ductal carcinoma in situ

Features:

  • Papillae with fibrovascular cores.
Micropapillary ductal carcinoma in situ

Features:

  • Small papillae without fibrovascular cores.
  • Have "drum stick" shape.

Grading DCIS

Graded 1-3 (low-high)[13] - 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:[14][15]

  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.[16][17]

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.

General

  • May occur with ductal involvement by cells of atypical lobular hyperplasia (abbreviated DIALH).[18]
    • ALH with DIALH has a risk of developing breast cancer that is similar to LCIS.

Microscopic

Features:

  • Extent criterium: <50% of terminal duct lobular unit (TDLU) is involved.
  • See LCIS for details.

IHC

  • E-cadherin -ve or incomplete membrane staining.

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[19][20] - memory device ABCDEF:

  • Atypia minimal - usually.
    • Relatively small ~1-2x size lymphocyte.
  • Borders of cells distinct/visible - dyscohesive.
  • Clear cytoplasm (focal).
    • May have a signet ring cell-like appearance.
  • Distend duct.
  • Eccentric nucleus, usu. round.
  • Filled ducts.
    • No luminal spaces - key feature.
      • Partially filled ducts are not LCIS.

Images:

Subclassification[20]

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

DDx:

IHC

  • E-cadherin -ve or incomplete membrane staining.

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. ↑ 12.0 12.1 O'Malley, FP.; Bane, A. (Jan 2008). "An update on apocrine lesions of the breast.". Histopathology 52 (1): 3-10. doi:10.1111/j.1365-2559.2007.02888.x. PMID 18171412.
  13. ↑ URL: http://surgpathcriteria.stanford.edu/breast/dcis/. Accessed on: 4 August 2011.
  14. ↑ 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.
  15. ↑ Tadrous, Paul.J. Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum (1st ed.). Wiley. pp. 258. ISBN 978-0470519035.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ Page, DL.; Dupont, WD.; Rogers, LW. (Feb 1988). "Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk.". Hum Pathol 19 (2): 201-7. PMID 3343034.
  19. ↑ 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.
  20. ↑ 20.0 20.1 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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