NAME OF PROCEDURE
- 88305 – Level IV – Breast, Biopsy not requiring microscopic evaluation of surgical margins
- 88307 – Level V – Breast, Excision of lesion, requiring microscopic evaluation of surgical margins
Breast Cancer Prognostic Profile
- Estrogen Receptor Studies
- Progesterone Receptor Studies
- HER2/neu overexpression
Suspected tumor tissue
Routine surgical pathology
Breast cancer prognostic profile I, HER2/neu overexpression and estrogen/ progesterone receptor studies will be ordered if necessary and are performed using formalin-fixed, paraffin embedded (FFPE) tissue. Fresh tissue is not required.
Plastic container with lid, containing 10% neutral buffered formalin
Label with patient’s name, date, time of collection and type of specimen.
A copy of the radiograph should accompany a needle localization excisional biopsy specimen.
Laboratories should communicate the following fixation guidelines to clinical services:
- Specimens should be immersed in fixative within 1 hour of the biopsy or resection procedure.
- If delivery of a resection specimen to the pathology department is delayed (e.g. specimens from remote sites), the tumor should be bisected prior to immersion in fixative. In such cases, it is important that the surgeon ensure that the identity of the resection margins is retained in the bisected specimen; alternatively, the margins may be separately submitted.
- The time of removal of the tissue and the time of immersion of the tissue in fixative should be recorded and submitted to the laboratory.
Communication may be through memoranda, website, phone, face-to-face meetings, or other means. The laboratory should consider monitoring compliance and contacting clients when these guidelines are not met.
Information on time of fixation may be obtained by appropriate questions on the laboratory’s requisition form.
CAUSES FOR REJECTION
Specimen container not properly labeled
Specimen not placed in formalin
Complete a <Anatomical Pathology Requisition>.
- Specimens subject to these tests should be fixed in 10% neutral buffered formalin for at least 6 hours, up to a maximum of 48 hours for HER2 testing and 72 hours for estrogen receptor and progesterone receptor testing.
- The volume of formalin should be at least 10 times the volume of the specimen.
- Decalcification solutions with strong acids should not be used.
- For cases with negative HER2 results by IHC that were fixed outside these limits, consideration should be given to performing confirmatory analysis by in-situ hybridization.
For IHC stained slides, positive cases are those with strong and complete membrane staining in greater than 30% of invasive cancer cells (Score 3). Negative cases are defined as those with no staining (Score 0) or weak, incomplete membrane staining in any proportion of cells (Score 1). Equivocal or indeterminate cases are those cases with complete membrane staining that is either non-uniform or weak in intensity but with obvious circumferential distribution in at least 10% of cells. Careful attention should be paid to the recommended exclusion criteria for performing or interpreting HER2 assays (e.g. artifactual distortion of tissue; strong membrane staining of normal ducts).
HER2 gene amplification by in situ hybridization (e.g. FISH, CISH, SISH) results are reported using the ASCO/CAP scoring criteria.
For HER2 gene status determined by in-situ hybridization, positive (amplified) cases are those with ratios of HER2 to CEP17 of > 2.2. Negative cases are defined as those with ratios of <1.8. Equivocal cases are those with a ratio of 1.8 to 2.2. For test systems without an internal control probe, positive (amplified) cases are those with an average HER2 gene copy number > six signals/nucleus, negative cases are those with < four signals/nucleus, and equivocal cases are those with an average HER2 gene copy number of four to six signals/nucleus. Careful attention should be paid to the recommended exclusion criteria for performing or interpreting in situ hybridization for HER2 (e.g. signal obscured by background; for FISH, difficulty in defining areas of invasive carcinoma under UV light).
Surgical pathologists need clinical details, especially tumor location, particularly for a lesion in the environs of the nipple which may include florid papillomatosis of the nipple. History of prior biopsy may explain fibroplasia which might be mistaken for tumor desmoplasia. History of trauma, current or recent pregnancy may be extremely relevant. Information regarding type of specimen, admitting diagnosis, and pertinent clinical history (i.e. age, clinical impression, past diagnosis, radiographic findings, and history of radiation or chemotherapy) is essential to interpretation and should be noted on the requisition.
Send radiograph with specimen when available
Results interpreted by pathologist:
- Confirm the presence of calcific structures identified in mammograms and specimen radiographs and characterize them.
- Specimen radiograph is commonly performed to confirm that the biopsied tissue contains calcific structures, but it cannot provide a diagnostic explanation for them.
- Diagnosis of carcinoma of the breast and other disease entities and evaluation of the specimen for appropriate patient.
Since many women presently request breast-conserving surgical procedures, breast tumor specimen handling has recently changed from the time of its surgical removal through dissection on the surgical pathology bench.
The pathologist determines the size of the specimen and of the tumor and its relationship to resection margins. Specimen orientation is desirable for direction of potential further surgery; therefore, it is sometimes necessary for the surgeon to provide markers (superior, inferior, lateral, medial, deep, superficial) in a combination appropriate for the setting of a given neoplasm. Coating of the specimen surfaces with india ink by the pathologist is desirable in many instances of lumpectomy and of re-excision specimens. It does not interfere with receptor assays. Sections can then be taken to provide margin evaluation by light microscopy. Estrogen and Progesterone receptors are enhanced with application of DNA flow cytometry.
DNA ploidy with S-phase fraction support projection of prognosis are useful for therapeutic decision making. Patient with diploid or tetraploid tumors statistically tend to have a better prognosis. Aneuploidy and high S-phase fraction are associated with absent steroid receptors. DNA studies can be done on formalin fixed paraffin embedded (FFPE) tissue blocks.