Breast biopsy or excision

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Author: Mikael Häggström [notes 1]

Fixation

Generally 10% neutral buffered formalin. Fresh breast specimens should be put in formalin within one hour.[notes 2] Breast specimens should be immersed in formalin for 6-72 hours.[1]

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))
Other legend

<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
[[Comments]]
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Gross processing

Selection and trimming

For excision (also called lumpectomy):

  • Determine total specimen size. ((Weight the specimen[2]))
  • Ink margins. If sample orientations are marked, use different colors for different directions.[2]
  • Palpate the specimen for masses. If felt, estimate the greatest dimension.[notes 3] Compare with radiography if available.[2] Confirm the presence of any known biopsy clips, either visibly or by post-operative radiography (in order to confirm that the specimen includes the region of interest).
Cut a lumpectomy in the direction that gives the shortest distance from margin to margin. If a lumpectomy is uneven as shown, cut so that the first and last slice become wedge shaped (because these will later be cut further, perpendicularly to the margin), avoiding a wedge-shape for remaining slices.
  • Serially section the specimen.
  • When performing triage of fresh lumpectomies, generally make slices 1.1 to 1.5 cm thick. When laid down and flattened, this is generally thin enough to allow for fixation over at least 6 hours, and thick enough to be further cut into 2 or 3 slices after fixation; Note the direction of up/down on each such thick slice so that the relative orientation of the thinner slices thereof is maintained. Slices with solid tumors are cut somewhat thinner since they won't flatten as much when laid down.
  • When selecting tissue for submission after fixation, make 3-4 mm thick slices.[2]
  • Inspect for any grossly visible lesions. If found, measure at least the greatest dimension of the lesion on the slice where it appears largest. (Also compare the greatest gross measurement (including any palpated one) with the greatest measurement at previous imaging, and note if it confers a staging discrepancy between imaging and gross dimensions, with cutoffs at 0.1 cm, 0.5 cm, 1.0 cm, 2.0 cm, and 5 cm.)
Re-excisions

Tissue selection

Further serially section each of the two end sections into perpendicular sections, so that the distance between the surgical margin and any tumor involvement can be measured. If they are visibly involved as pictured, sections can be selectively taken from there. If end sections are not grossly involved, submit one perpendicular section, (every other perpendicular section), ((or the entire end sections)).
  • For lumpectomies, submit:[2]
  • Entire specimen if it can fit in 3-5 slices.
  • If larger:
  • For relatively well demarcated tumors: 1 slice per cm of tumor (minimum of 3 slices of tumor), including both center and periphery of tumor, including closest distance to the surgical margin if possible.
  • For diffuse or even invisible tumors such as often is the case for DCIS and ILC, either still submit whole, or use X-ray to guide what tissue to submit.
  • Additional suspicious areas, including those indicated by radiography.
  • ((Representative sections of margins in each direction.))

Breast specimens where breast cancer is possible should generally not be decalcified even when containing small calcifications, to preserve the ability to perform immunohistochemistry.

See also: General notes on gross processing

Gross report

  • Size of original tissue sample, preferably in 3 dimensions.
  • Description of inking
  • Tumor properties, at least:
  • Size in 3 dimensions.[2]
  • Distance from margins[2]
  • Consistency[2]
  • (Description of sectioning and submissions.)
  • ((Time of procurement and time of placement in formalin.[notes 2]))

Example:

(The specimen is received fresh and consists of) an irregular fragment of yellow tan fibrofatty tissue measuring 4.0 x 2.8 x 2.0 cm. (The specimen is oriented with two sutures and) the surgical margins are inked as follows: superior-blue, inferior-green, medial-red, lateral-yellow, anterior-orange, and posterior-black. {{A radioactive seed is embedded in the tissue.}} The tissue is serially sectioned {{to reveal a tan-gray, spiculated, indurated mass measuring _cm in greatest dimension. The mass is located _cm from the nearest (<<superior, inferior etc>>) margin. (The specimen is entirely submitted in sequential sections from medial to lateral in 10 cassettes. The medial and lateral margins are submitted as perpendicular sections.) The specimen was procured at _AM/PM on _/_/2020. The specimen was placed in formalin at _AM/PM on _/_/2020.

Staining

Usually H&E staining.

Routine immunohistochemistry usually include estrogen and progesterone receptors (ER, PR) and HER2.[3]

Microscopic evaluation

If tumor is found, determine:

  • Tumor size
  • Malignancy
  • Distance from excision margin

Malignancy

The most important is to classify a sample as either of the following:

  • Benign
  • Carcinoma in situ
  • Invasive cancer

Most common types

Women seeking evaluation of a breast lump[4]
Finding Relative
incidence
Histopathology Image
Fibrocystic breast changes 40% Sclerosing adenosis (pictured), with an increase in glandular elements in addition to stromal proliferation that distorts and compresses glands.[5] Histopathology of sclerosing adenosis of the breast.jpg
Radial scar, seen as a fibroelastic stroma and entrapped glands radiating outward. Measure the size of these.[notes 4] Histopathology of a radial scar of the breast.jpg
No disease 30%
Fibroadenoma 7% Proliferation of both stromal and epithelial components,[notes 5] arranged into either a pericanalicular pattern (stromal proliferation around epithelial structures), or an intracanalicular pattern (stromal proliferation compressing the epithelial structures into clefts). Fibroadenomas characteristically display hypovascular stroma compared to malignant tumors.[6][7][8] Furthermore, the epithelial proliferation appears in a single terminal ductal unit and has duct-like spaces surrounded by a fibroblastic stroma. The basement membrane is intact.[9] Micrograph of a fibroadenoma.jpg
Atypical ductal hyperplasia 7%[10] Epithelial proliferations which are not qualitatively or quantitatively abnormal enough to be classified as ductal carcinoma in situ.[10] Micrograph of atypical ductal hyperplasia.jpg
Other benign mammary dysplasias and neoplasms 5% Including:
  • Flat epithelial atypia: variably dilated acini lined by one to several layers of epithelial cells with low-grade cytologic atypia, usually columnar.[11]
  • Columnar cell change: Terminal duct lobular unit with epithelium exhibiting tall cells with oval or elongated nuclei orientated perpendicularly to the basement membrane.[12]
Histopathology of flat epithelial atypia and columnar cell change.jpg
Intraductal papilloma: unremarkable epithelial cells lining fibrovascular cores. Histopathology of intraductal papilloma.jpg
Breast cancer (in situ or invasive) 10% See next section.

Breast cancer types

Breast cancer types, with relative incidences and prognoses.
Cancer type Histopathology Image
Invasive ductal carcinoma (IDC) Carcinomatous cells are seen below the basement membrane of lactiferous ducts. Otherwise, there are no specific histologic characteristics, essentially making it a diagnosis of exclusion.[13] Invasive ductal carcinoma, with occasional entrapped normal ducts.jpg
Ductal carcinoma in situ (DCIS) Malignant epithelial cells confined to the ductal system of the breast, without invasion through the basement membrane.[14] DCIS - Intraductal carcinoma of the breast.jpg
Invasive lobular carcinoma (ILC) The "classic" pattern is round or ovoid cells with little cytoplasm in a single-file infiltrating pattern, sometimes concentrically giving a targetoid pattern. Classic Invasive Lobular Carcinoma of the Breast (6813147194).jpg
Lobular carcinoma in situ (LCIS)
  • Monomorphic, loosely cohesive, slightly enlarged and evenly spaced cells that fill acini.[15]

Cells have indistinct cell borders, pale cytoplasm, and uniform small nuclei with evenly distributed chromatin and inconspicuous nucleoli.[15]

Histopathology of lobular carcinoma in situ.jpg
Further information: Evaluation of tumors

If tumor is not found

Check the imaging indication, and look for abnormalities that may explain the diagnostic findings:

  • Dense stromal fibrosis for radiodense areas.
  • Calcifications if found on X-ray.

If still not found, note their absence, since it indicates that the biopsy may have missed the target of interest.

Microscopy report

A normal biopsy may be reported as follows

(Fibrofatty tissue with benign ducts and lobules.) Negative for (atypia and) malignancy.

More detailed reports are given at the disease-related articles.

See also: General notes on reporting

Notes

  1. For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.
  2. 2.0 2.1 An increased cold ischemia time (time from procurement to time in formalin) negatively effects the utility of immunohistochemistry.
    - Khoury, Thaer (2018). "Delay to Formalin Fixation (Cold Ischemia Time) Effect on Breast Cancer Molecules ". American Journal of Clinical Pathology 149 (4): 275–292. doi:10.1093/ajcp/aqx164. ISSN 0002-9173. 
  3. A palpated greatest dimension before cutting is still superior to trying to align cut pieces together or mathematically adding the thicknesses of involved slices.
  4. Size is a major factor in whether to fully excise radial scars, at an approximate cutoff at around 1 cm.
  5. The proliferation of two histological components is called "biplasia", from Latin bis (“twice”) and -plasia (“formation”), or "biphasic proliferation"

Main page

References

  1. . Recommendations for HER2 Testing in Breast Cancer: ASCO – CAP Clinical Practice Guideline Update. College of American Pathologists (2013-10-17).
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Monika Roychowdhury. Grossing (histologic sampling) of breast lesions. Pathologyoutlines.com. Topic Completed: 1 August 2012. Revised: 19 September 2019
  3. "Immunohistochemical detection of estrogen and progesterone receptor and HER2 expression in breast carcinomas: comparison of cell block and tissue block preparations ". Int J Clin Exp Pathol 2 (5): 476–80. 2009. PMID 19294006. 
  4. Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. p. 739. ISBN 978-1-4160-2973-1. 
  5. Jaya Ruth Asirvatham, M.B.B.S., Julie M. Jorns, M.D.. Breast - Fibrocystic changes - Sclerosing adenosis. Pathology Outlines. Topic Completed: 1 January 2015. Minor changes: 31 December 2020
  6. Tavassoli, F.A., ed (2003). World Health Organization Classification of Tumours: Pathology & Genetics: Tumours of the breast and female genital organs . Lyon: IARC Press. ISBN 978-92-832-2412-9. 
  7. Jaya Ruth Asirvatham, M.B.B.S., Carlos C. Diez Freire, M.D., Cansu Karakas, M.D., Belinda Lategan, M.D., Nat Pernick, M.D., Emily S. Reisenbichler, M.D., Monika Roychowdhury, M.D., Mary Ann Gimenez Sanders, M.D, Ph.D., Gary Tozbikian, M.D., Hind Warzecha, M.D. Senior Authors: Julie M. Jorns, M.D., Shahla Masood. Breast nonmalignant, Fibroepithelial neoplasms, Fibroadenoma. Retrieved on 2019-11-04. Revised: 31 October 2019
  8. Rosen, PP. (2009). Rosen's Breast Pathology (3rd ed.). ISBN 978-0-7817-7137-5. 
  9. . Fibroadenoma of the breast.
  10. 10.0 10.1 David J. Myers; Andrew L. Walls.. Atypical Breast Hyperplasia. StatPearls, National Center for Biotechnology Information. Last Update: February 15, 2019.
  11. Schnitt, Stuart J (2003). "The diagnosis and management of pre-invasive breast disease: Flat epithelial atypia – classification, pathologic features and clinical significance ". Breast Cancer Research 5 (5). doi:10.1186/bcr625. ISSN 1465-542X. 
  12. Logullo, Angela Flavia; Nimir, Cristiane (2019). "Columnar cell lesions of the breast: a practical review for the pathologist ". Surgical and Experimental Pathology 2 (1). doi:10.1186/s42047-018-0027-2. ISSN 2520-8454. 
  13. Peter Abdelmessieh. Breast Cancer Histology. Medscape. Retrieved on 2019-10-04. Updated: May 24, 2018
  14. Siziopikou, Kalliopi P. (2013). "Ductal Carcinoma In Situ of the Breast: Current Concepts and Future Directions ". Archives of Pathology & Laboratory Medicine 137 (4): 462–466. doi:10.5858/arpa.2012-0078-RA. ISSN 0003-9985. 
  15. 15.0 15.1 Sucheta Srivastava. Breast - Noninvasive lobular neoplasia - LCIS classic. Topic Completed: 1 September 2017. Minor changes: 21 June 2020
  16. Nassar, Lara; Baassiri, Amro; Salah, Fatima; Barakat, Andrew; Najem, Elie; Boulos, Fouad; Berjawi, Ghina (2019). "Stromal Fibrosis of the Breast: A Spectrum of Benign to Malignant Imaging Appearances ". Radiology Research and Practice 2019: 1–6. doi:10.1155/2019/5045908. ISSN 2090-1941.