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Review
Pragmatic guide to the macroscopic evaluation of breast specimens
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  1. Yaileen D Guzmán-Arocho,
  2. Laura C Collins
  1. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
  1. Correspondence to Dr Laura C Collins, Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA; lcollins{at}bidmc.harvard.edu

Abstract

The pathological assessment of a breast surgical specimen starts with macroscopic evaluation, arguably one of the most critical steps, as only a small percentage of the tissue is examined microscopically. To properly evaluate and select tissue sections from breast specimens, it is essential to correlate radiological findings, prior biopsies, procedures and treatment with the gross findings. Owing to its fatty nature, breast tissue requires special attention for proper fixation to ensure appropriate microscopic evaluation and performance of ancillary studies. In addition, knowledge of the information necessary for patient management will ensure that these data are collected during the macroscopic evaluation, and appropriate sections are taken to obtain the information needed from the microscopic evaluation. Herein, we present a review of the macroscopic evaluation of different breast specimen types, including processing requirements, challenges and recommendations.

  • Breast Neoplasms
  • Methods
  • Tissue Fixation

https://doi.org/10.1136/jcp-2023-208833

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    Introduction

    The first step in the pathological assessment of a surgical specimen is macroscopic evaluation. To properly evaluate and select tissue sections from breast specimens, it is critical to correlate radiological findings, prior biopsies, procedures and treatment with the gross findings. Owing to its fatty nature, breast tissue requires special attention for proper fixation to ensure appropriate microscopic evaluation and performance of ancillary studies.

    Herein, we present a review of the macroscopic evaluation of different breast specimen types, including the processing requirements, challenges and recommendations. It is essential to discuss with the clinical team the factors that may impact local practice and establish standard operating procedures to facilitate the macroscopic evaluation of breast specimens in each practice setting.

    General principles

    Radiological correlation

    Evaluation of a palpable breast lesion typically requires physical examination, imaging and pathological evaluation using core needle biopsy or fine-needle aspiration. Although palpable lesions can be sampled without imaging guidance, most patients are referred for mammographic or ultrasound studies. Additionally, multiple international breast screening guidelines recommend mammography as a screening tool for average-risk women, and most agree on screening among women aged 40 or 50–74 years, to identify lesions in asymptomatic patients; these include non-palpable masses, microcalcifications, asymmetries and architectural distortions.1 Thus, imaging findings are invariably available when a breast specimen is received in pathology. Review of imaging findings and their correlation with macroscopic and microscopic findings is a critical step in evaluating all breast specimens to establish radiological–pathological concordance.

    Radiologists often deploy biopsy clips at the time of the procedure to mark the targeted location.2 Traditionally, a wire has been used to localise the targeted area during breast-conserving surgery.3 4 More recently, wire-free localisation devices have been employed, such as the SAVI SCOUT,5 Magseed6 and LOCalizer.7 Knowledge of the presence of a biopsy clip and/or localisation device will increase the likelihood that these are retrieved during macroscopic evaluation, and their presence should be recorded in the pathology report. Identifying the biopsy clip and/or localisation device also ensures that the targeted lesion is recognised, identified and has been removed. It is important to confirm from the imaging report the appropriate placement of the biopsy clip, as this can shift after deployment and/or prior to surgery.

    Type of procedures

    The first specimen received in pathology from a beast lesion typically is a core needle biopsy or fine-needle aspiration. High-risk lesions, defined in this setting as those likely to be upgraded to a worse lesion, require surgical management: either an excisional biopsy, partial mastectomy or lumpectomy, or sometimes mastectomy (with or without lymph node sampling/axillary contents). The type of surgery is selected based on multiple factors such as lesion size, location, prior procedures, medical history and patient preference. Other procedures include lymph node sampling when there is a known invasive carcinoma, re-excision of surgical margins for positive or close resection margins, prophylactic mastectomy in individuals with a genetic predisposition to breast cancer, chest contouring surgery for gender-affirming care, and reconstructive and plastic procedures.

    Tissue fixation and biomarker testing

    Ancillary testing for oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) is recommended for all newly diagnosed invasive breast carcinomas, recurrent tumours and metastatic tumours to guide treatment, such as endocrine therapy and HER2-targeted therapy.8–12 In addition, ER should be performed for all newly diagnosed ductal carcinomas in situ (DCISs). The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines recommend a cold ischaemia time of less than 1 hour for breast tissue undergoing ER, PR and HER2 testing (ie, the time from removal of tissue from the body to formalin fixation). Breast specimens must be fixed in 10% neutral phosphate-buffered formalin for 6–72 hours before processing.13–16 All breast tissue specimens, including biopsies and subsequent surgical specimens, should be placed in formalin as soon as possible (<1 hour). Certain circumstances require consideration for repeat ER, PR and HER2 testing on surgical specimens, for example, small biopsy samples that are insufficient for accurate assessment of the assays, discordant morphology or grade between biopsy and resection, triple-negative tumours, postneoadjuvant therapy specimens and unexpected findings (eg, upgrade to invasive carcinoma), hence the need for prompt fixation in every case. The ASCO/CAP guideline mandates recording of variables that can affect ancillary testing of breast tissue specimens; for this reason, the pathology report must include the time and date the tissue is removed from the patient, the time and date the tissue is placed in formalin, and the duration of formalin fixation.13–16

    Report requirements

    In addition to the diagnosis, the pathology report must include the information needed for patient management, including predictive and prognostic factors. Multiple organisations, including the International Collaboration on Cancer Reporting,17 the CAP,18 the Royal College of Pathologists,19 the Korean Society of Pathologists,20 the Royal College of Pathologists of Australasia21 and the College of Pathologists of Sri Lanka,22 have developed guidelines and templates for reporting breast specimens. A synoptic report provides a comprehensive summary of the relevant findings, and its use improves consistency in reports and decreases the misinterpretation or omission of data.23–26 The synoptic report should include the type of procedure, location (laterality and tumour site), histological type, tumour grade, size, focality, local extent (skin, nipple or skeletal muscle involvement), lymphatic or vascular involvement, margin status (distant to each margin for invasive carcinoma and DCIS and extent of involvement for positive margins), ancillary studies, pathological tumor, node, metastasis (pTNM) staging classification, data on DCIS (extent, architectural patterns, nuclear grade and margins), information on lymph node evaluation (number of lymph nodes involved each with macrometastases, micrometastases, isolated tumour cells, size of the largest deposit and presence of extranodal extension) and any additional diagnostic findings on microscopic evaluation.

    An awareness of these requirements is imperative when performing the macroscopic evaluation to ensure incorporation of relevant factors into the macroscopic description. The macroscopic description must include a description of all the grossly identified lesions, including measurement in three dimensions, proximity to margins and relationship to one another. Notably, the pT category is determined based on the size of the largest invasive component27; therefore, recording the macroscopic dimensions of the lesions is critical. However, the macroscopic dimensions must be correlated with the imaging and microscopic dimensions to properly stage the tumour. Documenting the absence of macroscopic findings is also essential, as only the sampled areas undergo microscopic evaluation.

    Specimen photographs and diagrams

    Specimen photographs and diagrams are helpful in documenting macroscopic findings, particularly in complicated cases, such as those with multiple lesions or postneoadjuvant therapy. A photograph of the serially sliced specimen can be used to map the lesions and where the sections are taken to correlate with the microscopic findings, determine the extent of the disease and guide the submission of additional tissue when needed.

    Macroscopy

    Core needle biopsies

    Core needle biopsy specimens are commonly received in pathology. All the tissue received should be submitted for evaluation. The gross description should include the number of cores received and the range of measurements. Limiting the number of cores in each cassette to two can be considered so as to have multiple tissue blocks for ancillary studies. There are no guidelines for the number of levels to be obtained from each block of breast core needle biopsy specimens; two to three levels upfront should be sufficient in most cases. For core needle biopsies targeting calcifications, radiologists should obtain specimen radiographs to confirm acquisition of the calcifications and to separate cores with calcifications from those without, which can then be submitted in different blocks.28 The pathologist should have access to the specimen radiograph to correlate the calcifications identified on imaging with the microscopic findings. If no calcifications are observed in the initial sections, additional levels can be targeted to the blocks that have cores with calcifications. If the cores were not separated upfront, a radiograph of the tissue blocks could be obtained to determine which ones contain calcifications. Radiological–pathological correlation is essential, and an additional set of levels should be obtained when there is discordance (eg, no correlate for a mass-forming lesion).

    Specimen inking

    Specimens oriented by the surgeon should be inked in multiple colours to preserve the specimen orientation after sectioning and to facilitate microscopic margin assessment. Clarification from the surgeon should be obtained prior to sectioning the specimen if there is a query regarding specimen orientation. After inking, the specimen should be dried, then dipped or sprayed with a mordant solution (eg, acetic acid) to properly fix the ink and limit ink tracking into the tissue. The colour that represents each margin should be documented in the macroscopic description. The establishment of a local inking protocol is recommended to facilitate consistency.

    Excisional biopsy, lumpectomy and partial mastectomy specimens

    On excisional biopsy, lumpectomy and partial mastectomy specimens, surgeons typically use two sutures to orient the specimen: often a short suture to designate the superior aspect and a long suture to designate the lateral aspect. The combination of laterality and two sutures is sufficient to orient the specimens; however, some surgeons use an additional suture to designate the anterior aspect of the specimen as well. Oriented specimens should be inked in six colours corresponding to the superior, inferior, lateral, medial, anterior (superficial) and posterior (deep) margins (figure 1). Even when additional shave margins are obtained, if the primary specimen is oriented, it is advisable to ink in six colours in case additional lesions are identified in the shave margins, or fewer than six shave margins are submitted. Inking the specimen may help correlate with the primary specimen if, for example, there is a question of multifocality versus direct extension of the tumour in the shaved margin. For unoriented specimens, it is advisable to ink the entire specimen in one colour, even when a benign diagnosis is expected based on the core biopsy. Incidental findings such as DCIS and invasive carcinoma might be encountered requiring margin assessment.

    Figure 1
    Figure 1

    Excision specimen inked in multiple colours.

    The specimen should be serially sectioned perpendicular to the long axis into thin (4 mm) slices. Except for the end sections, each slice should include representation of four margins. The end sections are sliced perpendicular to the inked surface to allow for proper measurement of the distance of any tumour from that margin. Include in the gross description the number of slices, the size of the lesions in three dimensions, the distance of each lesion to each of the six margins, which slices are involved by the lesion, and which slices have biopsy site changes and contain the biopsy clip and/or localisation device, all of which facilitate correlation with microscopic findings and will be helpful in cases where additional sections are needed. If multiple lesions are identified, the distance between them should be included in the gross description. Most breast excisions are preceded by a core needle biopsy, and it is critical to correlate the macroscopic findings with the biopsy diagnosis to ensure that the target has been resected. Documentation of biopsy site changes should always be included in the report; this is essential when no residual lesion is identified. Photographic examples of excision specimens are shown in figure 2, including invasive carcinoma (figure 2A), fibroadenoma (figure 2B) and grossly unremarkable tissue (figure 2C).

    Figure 2
    Figure 2

    Excision specimens. (A) A well-demarcated lesion and biopsy cavity in a case of invasive carcinoma. (B) A homogeneous mass consistent with fibroadenoma. (C) No gross lesions were identified (location of the biopsy clip and SAVI SCOUT is highlighted).

    Mastectomy specimens

    Typically, the surgeon will have placed one suture in the axillary tail to orient the mastectomy specimen. The posterior (deep) margin should be inked in one colour. The anterior margin (superficial/subcutaneous) could be inked with a different colour in skin-sparing mastectomies. In nipple-sparing mastectomies, the nipple margin is usually marked with a suture by the surgeon and should be inked with a different colour. Mastectomy specimens should be weighed and are usually measured to include the dimensions of the entire specimen, skin, nipple, areola and axillary tail (if present). Prior to formalin fixation, serially sectioning (‘breadloafing’) of the mastectomy specimen into thin (4 mm) slices from the posterior (deep) surface should be performed, usually keeping the specimen intact at the anterior (skin) surface.

    Again, it is necessary to correlate radiological findings, prior biopsy findings and prior procedures with the gross findings. It is crucial to identify the targeted lesion(s), biopsy site changes/biopsy clips, and areas of prior surgery, concerning lesions by imaging, and to evaluate the remaining tissue for incidental findings. Measure the grossly identifiable tumour and/or biopsy cavity in three dimensions and indicate the location (quadrant and slice numbers) and distance to the anterior, deep/posterior and nipple (in nipple-sparing mastectomies) margins. As mentioned for excision specimens, these macroscopic descriptions are beneficial in cases that require submission of additional sections to facilitate identification of the correct location.

    In most cases, there is no nipple involvement by DCIS or invasive carcinoma, and when present, it is typically caused by direct extension of the tumour.29 Thus, in nipple-sparing mastectomies, the nipple margin should be shaved and submitted en face for margin evaluation, allowing assessment of the entire surface. In order to be able to measure the distance of any tumour present to the nipple margin, some practices prefer to submit perpendicular sections, particularly if the tumour is grossly close to the nipple margin.30 31 Costal cartilage can be obtained during reconstructive procedures, and gross examination is considered adequate for evaluation if no grossly identifiable lesions are observed. Figure 3 illustrates mastectomy specimens with invasive carcinoma (figure 3A), surgical cavity (figure 3B) and tumour bed in a postneoadjuvant specimen (figure 3C).

    Figure 3
    Figure 3

    Mastectomy specimens. (A) The spiculated mass was consistent with invasive carcinoma. (B) prior surgery cavity. (C) Tumour bed in a postneoadjuvant specimen.

    Additionally submitted margins and margin re-excision specimens

    Some surgeons submit separate shave margins from each aspect of the lumpectomy cavity at the time of initial surgery.32 A margin is considered positive for invasive carcinoma if there is a tumour at the inked surface.33 The adequate margin for DCIS is 2 mm.34 A positive margin for invasive carcinoma or a close margin for DCIS may require re-excision either with a targeted or global re-excision.

    For individually submitted oriented margins, the surface designated as the true margin by the surgeon should be inked in one colour. The specimen is sectioned perpendicular to the inked surface, followed by careful evaluation for gross lesions. Grossly apparent lesions are described in the report, and the size and distance to the closest margin are recorded. For grossly unremarkable specimens, one section per centimetre of tissue is sufficient. If the entire specimen can be submitted in a few blocks, it can be submitted in its entirety. Any grossly identifiable lesion should be included in the representative sections, including sampling of the closest gross margin.

    For a global re-excision, the surgeon re-excises around the entire surgical cavity providing a single specimen. If oriented, the specimen is inked in six colours, similar to the oriented excision specimens. The specimen is sectioned at thin intervals; if a grossly apparent tumour is identified, the procedure for invasive carcinoma described previously is followed. If no grossly apparent tumour is identified, one section per centimetre is submitted, including representation from each margin. In addition, a few sections from the biopsy site and skin should be included, if present.

    Invasive carcinoma

    The macroscopic evaluation of breast specimens with known invasive carcinoma aims to confirm the grade, histological type and tumour size; to identify the presence of lymphovascular invasion; and to determine the margin status. If the tumour is grossly homogeneous, representative sections to document the greatest cross-sectional size (as a single section when feasible) and margin status are considered adequate. It is vital to correlate tumour size with preoperative imaging and clinical findings and consider that the residual tumour might be smaller in some cases because of prior biopsy. At least one section per margin should be sampled to include representation of each margin in relation to the tumour and certainly the closest, grossly apparent margins. The breast parenchyma adjacent to the tumour should be included to assess for lymphovascular invasion. If multiple tumours are identified, the distance between each lesion is described, and a section of intervening breast parenchyma should be obtained. If the tumours are close, a section that includes both tumours should be submitted. Tumours separated by at least 5 mm are considered separate foci.27

    Any additional lesions identified on gross inspection should be represented in the samples submitted for histological evaluation. All areas of concern must be identified and sampled, including all biopsy sites and any suspicious imaging findings. For mastectomy specimens, sections of the skin, nipple and random unremarkable fibrous tissue from each quadrant are generally included. The axillary tail should be evaluated for the presence of lymph nodes.

    Postneoadjuvant chemotherapy specimens

    Specimens obtained after neoadjuvant treatment are processed as described in the previous section for invasive carcinoma. The goal is to detect and quantify residual disease and assess response to therapy. There may be grossly evident tumour in patients with a poor response to therapy. Identifying and measuring the tumour bed, which appears grossly as an area of fibrosis, is critical for evaluating these specimens. Biopsy clips are sometimes used before the initiation of chemotherapy to mark the borders of the tumour, which is helpful in the identification of the tumour bed. Owing to the complexity of these specimens, creating a diagram or using gross photographs to map the tumour bed and where sections are taken is encouraged.

    The international multidisciplinary working group on evaluating and reporting postneoadjuvant specimens recommends submitting one block per centimetre of the original tumour size or at least 10 tissue blocks.35–37 For larger tumours, the recommendation is to submit five blocks per 1–2 cm based on the pretreatment tumour size, up to 25 blocks.

    Notably, for tumour staging in postneoadjuvant specimens, the American Joint Committee on Cancer (AJCC) specifies measuring the largest contiguous focus of residual carcinoma without including areas of fibrosis within the tumour bed.27 The most used method for reporting residual tumour in this setting is the MD Anderson Residual Cancer Burden score, which requires measurement of the largest two dimensions of the residual carcinoma present (referred to as the residual tumour bed, which is to be distinguished from the tumour bed as applied to the area of the original tumour).38

    DCIS and atypical lesions

    For atypical lesions, such as atypical ductal hyperplasia, papillomas with atypia and atypia involving sclerosing lesions, the objective is to determine if there is a worse lesion in the excised specimen. If feasible, the entire specimen should be subjected to microscopic evaluation. For larger specimens, representative sections should be submitted from the fibrous tissue to include the biopsy site. Margin evaluation becomes relevant when DCIS or invasive carcinoma is identified; in such cases, additional sections of the margins can be submitted.

    Similarly, specimens with a biopsy diagnosis of DCIS require more extensive sampling of the fibrous parenchyma to determine the presence of an invasive component. For excisions, the entire specimen or all/most of the fibrous parenchyma should be subjected to a microscopic evaluation. If the entire fibrous tissue is submitted, it should be recorded in the gross description. For mastectomy specimens with a diagnosis of DCIS, sampling should be guided by the extent of the disease on the imaging studies and must include the biopsy site and margins. A diagram mapping where the sections are obtained helps determine the extent of DCIS by correlating with the microscopic findings.

    Excisions for pleomorphic lobular carcinoma in situ (LCIS) and florid LCIS are handled similarly to DCIS, to include evaluation of the specimen margins. Extensive sampling of fibrous tissue is also required in specimens from patients with Paget disease without a known underlying carcinoma and in patients with proven metastatic carcinoma in the axillary lymph node without a documented invasive carcinoma in the breast parenchyma.

    Excisions for benign lesions and excisions without prior biopsy

    In certain circumstances, such as palpable, large, radiologically detected lesions or in symptomatic patients, benign lesions, including radial scar/complex sclerosing lesions and benign intraductal papillomas, are excised (see next section for fibroadenomas). As always, it is critical to ensure that the target lesion has been sampled. In these cases, representative sections to confirm the diagnosis are considered adequate, and submission of the entire specimen is not required. When a lesion is not grossly identifiable, sections should be obtained from the fibrous parenchyma (avoiding areas of the grossly fatty component) and areas with biopsy site changes.

    Sampling for cases with unknown pathology (no prior biopsy) should be determined based on clinical, radiological and gross findings. In the absence of gross lesions, 10 tissue blocks of fibrous parenchyma are considered sufficient for initial evaluation.39 If there are known calcifications without prior biopsy, a radiograph of the sliced specimen can be obtained to identify the location of the calcifications. All the areas of calcifications should be submitted for microscopic evaluation, along with representative sections from adjacent tissue slices.40 In cases of clinically suspected papilloma for which a duct excision has been performed, opening the specimen along the duct can help identify an intraductal mass; this is facilitated by the surgeon designating the proximal end of nipple duct with a suture. In any of the scenarios in this section, when an atypical lesion is identified, additional sections of fibrous tissue should be submitted to rule out an upgrade to DCIS or invasive cancer. If reasonable, all the remaining fibrous tissue can be submitted.

    Excisions for fibroepithelial lesions

    For known fibroadenomas, a representative section or two is sufficient in the grossly concordant specimen. One section per centimetre can be considered for fibroepithelial lesions, if a phyllodes tumour (or fibroepithelial lesion with increased stromal cellularity) is suspected on prior core needle biopsy or macroscopic evaluation. In this situation, it is important to include representation of the border of the lesion in relation to adjacent breast tissue and specimen margins. CAP guidelines recommend reporting margins for phyllodes tumours, and a margin is considered positive when there is ink on the phyllodes tumour. A surgical margin of ≥1 cm is still recommended for borderline and malignant phyllodes tumours.8 In contrast, re-excision for a benign phyllodes tumour with a positive margin is no longer required. Of note, a synoptic report is now available for recording pertinent features of phyllodes tumour.

    Gender-affirming surgery

    Transgender men (female-to-male) and masculine-centred gender non-conforming individuals may undergo chest contouring surgery (mastectomy). Although not a requirement for surgery, many of these patients have been receiving testosterone therapy at the time of surgery.41 Careful gross evaluation should be performed, and representative sections of any grossly evident lesions should be obtained. The rate of incidental atypical lesions (atypical ductal hyperplasia and atypical lobular hyperplasia) and carcinomas in this population is <3%.42–45 Based on the low risk of identifying high-risk lesions in these individuals, in the absence of gross findings, multiple groups recommend submitting just two to four tissue blocks per breast.42 43 Sections should focus on sampling the fibrous tissue; when present, sampling of the nipple and/or skin may be included.

    Reduction mammoplasty

    Typically, breast tissue from reduction mammoplasty specimens is received as multiple tissue fragments. The fragments should be weighed in toto; each fragment should be sectioned into thin slices and evaluated for gross lesions which, if identified, should be sampled for microscopic evaluation. A few representative sections of fibrous tissue are sufficient in the absence of gross lesions. The incidence of atypical lesions and carcinoma among cisgender women undergoing reduction mammoplasties ranges between 7.0% and 8.7%,43 46 and incidental invasive carcinoma is seen in <0.5% of the cases.47–49 Some groups suggest submitting more sections in older women because of the higher likelihood of identifying significant findings.48

    Risk-reducing mastectomy for known genetic predisposition

    Women carrying pathogenic variants that increase the risk of breast cancer, such as BRCA1/2, may undergo bilateral mastectomy, which reduces their risk of developing breast cancer by >90%.50 The combined incidence of carcinoma in situ and invasive carcinoma in risk-reducing mastectomy specimens has been reported to be up to 11%, whereas that of invasive carcinoma alone is <3%.51 52

    A thorough gross evaluation should be performed; any lesion must be described; and sections must be submitted for microscopic evaluation. Representative sections of the fibrous parenchyma are generally submitted from each quadrant in grossly unremarkable specimens. Nipple sampling is included in the representative sections submitted when present.

    Lymph nodes

    Lymph node status is typically assessed by sentinel lymph node excision in patients with known invasive carcinoma and in patients undergoing mastectomy for extensive DCIS in case of an upgrade to invasive carcinoma. Following sentinel lymph node excision, axillary lymph node dissection is considered based on the number of positive sentinel lymph nodes, the presence and extent of extracapsular extension and tumour stage.53 Upfront axillary lymph node dissection may be performed in patients who do not undergo sentinel lymph node excision in the presence of biopsy-proven metastasis, inflammatory breast cancer or advanced breast cancer.8

    Axillary dissection specimens require dissection of the fat to identify the lymph nodes, and all identifiable lymph nodes should be evaluated microscopically. The number of lymph nodes that should be excised during axillary dissection has not yet been established; however, the identification of at least 10 lymph nodes is suggested. If fewer than 10 lymph nodes are found, the remaining adipose tissue can be submitted for evaluation, if feasible.

    Sentinel and non-sentinel lymph nodes should be sectioned parallel to the long axis at 2 mm intervals and submitted in their entirety to identify any macrometastases, which have significant prognostic implications.54 Representative sections can be submitted for grossly positive lymph nodes and must include the largest dimension of the metastatic tumour. When submitting lymph nodes, the number of lymph nodes submitted in each cassette must be recorded to facilitate the proper count of lymph nodes at the time of microscopic evaluation. For sentinel lymph nodes, only one level is required,55 though many laboratories still obtain three levels of each block.56 A single level is adequate for non-sentinel lymph nodes. The upfront routine use of keratin immunostains for evaluation of lymph nodes is not recommended.57 58 Instead, keratin immunostains should be considered in selected cases, such as to confirm or refute foci of histological concern or in cases of low-grade invasive lobular carcinoma, which can be exceedingly subtle.

    Following neoadjuvant systemic therapy, the sectioning and processing of lymph nodes are performed as outlined previously. These lymph nodes might shrink in size after therapy, raising the need to submit more fibroadipose tissue for microscopic examination. It is essential to identify previously biopsied lymph nodes, document biopsy site changes and record the retrieval of biopsy clips. Uninvolved lymph nodes are evaluated in their entirety to document the presence or absence of metastases and evidence of treatment effect. Keratin immunostains are recommended to evaluate apparently negative lymph nodes with treatment effect to assess for the presence of micrometastases or isolated tumour cells, which have greater significance in this setting.59

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    Footnotes

    • Handling editor Runjan Chetty.

    • Twitter @guzmanarocho

    • Contributors Both authors contributed to the preparation, writing and review of this article.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; internally peer reviewed.