Background: Breast pathology reporting, especially for breast cancer, has evolved through the years, from terse succinct diagnostic conclusions with scant histological details to the current comprehensive reporting guidelines issued by major pathology colleges and bodies, including the International Collaboration on Cancer Reporting. Pathology elements included in reporting guidelines are evidence based and contribute significantly to individualised and personalised patient management. Summary: This article is based on the lively interactive question and answer session that followed the breast pathology segment in the symposium jointly organised by the British Association of Urological Pathology, British Association of Gynaecological Pathologists, British Society of Gastroenterology and the Association of Breast Pathology, in November 2022, titled “Personalised histopathology reporting for personalised medicine.” Key Messages: The breast pathology session emphasised the clinical utility of breast pathology data items, incorporating a case-based approach by highlighting the relevance of pathology information in various clinical scenarios. This review included clinico-pathological discussion points on florid lobular carcinoma in situ, atypical apocrine adenosis, post-neoadjuvant chemotherapy reporting, atypical ductal hyperplasia presenting at the margin, flat epithelial atypia versus columnar cell change, papilloma on core needle biopsy, margin status, mucocele-like lesion, total duct excision/microdochectomy specimen, and anterior and nipple margins in skin-sparing mastectomy. Effective communication and regular involvement of pathologists in breast multidisciplinary tumour boards are crucial.

Pathology reports are crucial for patient management. With increasing information on tumour classification and prognosis, the relevance and importance of reporting elements, particularly for cancer, need to be emphasised. Various international bodies and pathology organisations have devised synoptic reporting datasets that can be applied to daily diagnostic practice, in order to ensure complete and comprehensive pathology reports for clinical utility. Amid the backdrop of standardised datasets for pathology reporting is the push towards an individualised or personalised approach that addresses the specific significance of various pathology parameters for the patient, for whom the pathology report is being formulated and crafted.

In November 2022, a symposium webinar to discuss this subject was jointly organised by the British Association of Urological Pathology, British Association of Gynaecological Pathologists, British Society of Gastroenterology and the Association of Breast Pathology, titled “Personalised histopathology reporting for personalised medicine” [1]. Among the goals was to emphasise the role of the pathologist in multidisciplinary care through informed and accurate reporting of pathology data. This report summarises the discussion, arranged in a topical manner that ensued after the didactic lectures, which reflect recurrent challenges and questions faced by practising pathologists in daily practice. It is hoped that the discussion will also assist decision making at the multidisciplinary tumour boards.

A diagnosis on core biopsy of a fibroadenoma (FA) is reliable and accurate, when there is appropriate clinicoradiological correlation. A 3-centre study presented at the US and Canadian Academy of Pathology (USCAP) in 2014 described a large 3-centre series of FAs diagnosed on core biopsy that found a very low incidence of subsequent phyllodes tumours (PTs), at 0.38% [2]. Most of these PTs were benign. Heterogeneity with FA-like areas was concluded as the likely reason for the discrepancies [3]. Unfortunately, no pathologic features on core needle biopsy (CNB) appeared to be prospectively predictive of PT at excision [3]. Presence of suspicious imaging features at the time of CNB or on follow-up should prompt consideration for surgical excision [3]. It was determined that the diagnosis of FA on CNB is reliable and safe when there is adequate imaging correlation and follow-up.

For core biopsies of cellular fibroepithelial lesions, there have been multiple studies that have suggested various histological findings to be helpful: increased stromal cellularity, mitoses, stromal overgrowth, tissue fragmentation, adipose infiltration, ill-defined borders, heterogeneity, subepithelial condensation, nuclear pleomorphism, immunohistochemical findings of elevated Ki67, and topoisomerase 2 alpha indices, with recent inclusion of tumour size more than 2 cm and the clinical factor of age thresholds of 40 and 50 years [4‒10]. Presence of these features, in conjunction with clinicoradiological findings, may lead to a recommendation for surgical excision.

The duration of follow-up needed after a patient is diagnosed with PT depends on the tumour grade [11]. A patient diagnosed with malignant PT would be referred for oncologic management, and usually treated based on sarcoma therapy principles, with follow-up by the oncology clinic [11]. For those with borderline PT, some institutions may consider radiotherapy after resection [11, 12]. For benign PT, there is no firm recommendation for clinical follow-up [13].

A survey conducted in the United Kingdom (UK) [14] and an international cross-sectional survey in sixteen countries across four continents [11] found a wide variation in follow-up practices for resected PT, and urged for evidence-based national guidelines to inform best practice. A 5-year follow-up period for all PTs is preferred among surgeons and oncologists in the international cross-sectional survey [11].

From the clinical standpoint, follow-up duration should be based on when recurrences are likely to occur. In a large series of 605 cases of PT, the mean and median times to recurrence were 29.8 and 24.6 months, respectively, suggesting that a follow-up period of 3 years may be prudent [15]. However, the study did not stratify the periods to recurrence according to PT grade. A more individualised follow-up strategy may be informed by the Singapore nomogram which predicts recurrence-free likelihoods of patients diagnosed with PT [15], https://nomogramtool.solis.sg/. While there are no established follow-up protocols of patients diagnosed with PTs, it is understood that there is ongoing effort by the Association of Breast Surgery UK to provide guidelines soon.

Florid Lobular Carcinoma in situ

Florid lobular carcinoma in situ (LCIS) is regarded as a subtype of LCIS, defined as classic LCIS that forms a confluent mass-like architecture, with little to no intervening stroma between markedly distended acini of involved lobules, and/or a size threshold of expanded acini or ducts filling an area equivalent to 40–50 cells in diameter (shown in Fig. 1) [16]. The management of florid LCIS continues to be debated as data on its natural history remains limited. The WHO editorial board recommends excision for florid LCIS discovered on CNB, and for margin status to be reported on excisions containing florid LCIS to inform further management decisions [16‒18].

Fig. 1.

Scanning magnification of LCIS shows crowded distended duct spaces filled with a uniform epithelial population. The epithelial cells show discohesion (inset), with E-cadherin immunohistochemistry being negative (not shown). The background of radial scar is also present.

Fig. 1.

Scanning magnification of LCIS shows crowded distended duct spaces filled with a uniform epithelial population. The epithelial cells show discohesion (inset), with E-cadherin immunohistochemistry being negative (not shown). The background of radial scar is also present.

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Atypical Apocrine Adenosis

The management of atypical apocrine adenosis is somewhat controversial for several reasons. Firstly, the diagnosis of what constitutes “atypical” apocrine adenosis is not universally agreed upon, especially since apocrine cells often possess some degree of nuclear atypia regarded as of inherent nature (shown in Fig. 2). The WHO 2019 tumour classification refers to ≥3-fold variation in nuclear size with nucleolar enlargement [16], though no further information on management implication is provided. Secondly, whether architectural atypia, which may also be encountered in apocrine lesions [19], should be included within the definition of atypical apocrine adenosis, is unresolved. HER2 immunohistochemistry can sometimes be helpful in the stratification of atypical apocrine proliferations [19]. Weak membranous staining can be seen in atypical apocrine lesions, but strong expression is supportive of a malignant apocrine process, though this must not be interpreted in isolation [19, 20].

Fig. 2.

Apocrine adenosis shows apocrine cells in adenosis (inset). Apocrine cells show vesicular nuclear enlargement and distinct nucleoli, though the degree of atypia needed for considering “atypical” apocrine adenosis may be debatable.

Fig. 2.

Apocrine adenosis shows apocrine cells in adenosis (inset). Apocrine cells show vesicular nuclear enlargement and distinct nucleoli, though the degree of atypia needed for considering “atypical” apocrine adenosis may be debatable.

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Thirdly, how atypical apocrine adenosis on core biopsy influences management, and whether patients need “high risk” imaging surveillance if the same alterations are discovered on excision specimens akin to atypical hyperplasia, are uncertain. Studies conducted have produced variable results, with some concluding that atypical apocrine adenosis is an uncommon core biopsy diagnosis that may not require surgical excision [21, 22], while others recommend excision as high upgrade rates of 20% and 25% have been encountered [23, 24].

Pragmatically, a triple approach for collective management is critical when atypical apocrine adenosis is observed as the worst lesion on core biopsy material. Pathologically, it is useful to examine deeper levels to assess if there are additional abnormal histological findings such as mitoses and necrosis which may weigh towards the need for excision [25]. For atypical apocrine adenosis on excision specimens, there is no uniform recommendation, with authors describing both nil as well as increased risk for cancer development [26, 27], respectively.

The tumour node metastasis system of the UICC is recommended [28] for staging of post-neoadjuvant-treated breast cancer specimens. For post-treatment specimens, classification of T, N, and M by pathology examination uses a lower case “yp” prefix (ypT, ypN, ypM). Measurement of residual tumour (ypT) is based on the largest contiguous invasive tumour focus without intervening areas of fibrosis, which may differ from the dimensions used for calculating the residual cancer burden (RCB) [29].

If there are multiple primary tumours, the suffix “m” is used in parentheses, e.g., ypT(m) NM. Nodal stage post-neoadjuvant therapy (ypN) correlates with survival outcomes and is also important for cancer registries for monitoring the population demographics of breast cancer. The number of lymph nodes with metastases for UICC8/AJCC9 staging includes the number of lymph nodes with macrometastases and with micrometastases, provided one macrometastasis is present [30, 31].

The number of lymph nodes with metastases that informs the UICC8/AJCC9 staging may be different than that for calculating RCB. For RCB, the number of lymph nodes with ITCs and micrometastases is included regardless of the presence of a lymph node with macrometastases. Likewise, the RCPath guidelines state that all lymph nodes that contain tumour are regarded as positive [32].

In cases where there is no residual invasive disease detected in the breast (ypT0/ypTis or ypT0) and no evidence of metastatic disease in sampled lymph nodes (ypN0), indicating pathologic complete response (pCR), this needs to be stated in the report as a mandated parameter (core element) according to the ICCR guideline [29]. It is important to note that the presence of only lymphovascular invasion without any residual tumour deposit does not qualify as pCR [29]. The presence of ductal carcinoma in situ (DCIS) precluding pCR is still a matter of debate. Absence of viable carcinoma cells, with only necrotic tumour cells or mucin present, is also considered as pCR [29].

Repeat testing of biomarkers such as ER, PR, and HER2 is currently non-mandatory according to the ICCR guideline [29]. Nevertheless, the guideline suggests considering repeat immunohistochemical testing for ER, PR, and HER2 in two scenarios: (1) when there is a significant amount of residual disease in the breast or lymph nodes and (2) when the carcinoma exhibits different histomorphology compared to the pre-treatment tumour. The US College of American Pathologists (CAP) [33] also suggests repeating biomarker testing in cases showing negative results on the pre-treatment specimen, as positive conversion may occur in a subset of carcinomas due to tumoural heterogeneity and limited tissue sampling prior to treatment. Subsequent positive results may be of benefit for patient treatment. The ICCR guideline [29, 34] provides a recommended reporting format for biomarkers, and a summary of these recommendations is presented in Table 1.

Table 1.

Summary of clinico-pathologic discussion points related to pathology findings and reporting

IssuesPathologic consideration
Florid LCIS ‐ Reporting margin status in the excisional specimen is recommended 
Atypical apocrine adenosis ‐ Note of sinister features, such as atypical mitosis and necrosis on CNB, is recommended to support the need for excision 
‐ Strong HER2 IHC expression may be useful as a diagnostic adjunct to corroborate a malignant apocrine process 
Post-neoadjuvant chemotherapy reporting ‐ Cancer staging based on the tumour node metastasis system of the UICC is recommended to be reported with the prefix “yp.” 
‐ Measurement of residual tumour (ypT) is based on the largest contiguous invasive tumour focus without intervening fibrosis 
‐ The number of lymph nodes with metastases 
 ‐ For UICC8/AJCC9 staging, the number of lymph nodes with macrometastases and with micrometastases, provided one macrometastasis is present, is included. Lymph nodes with ITCs are not counted as positive lymph nodes (30, 31) 
 ‐ For RCB and RCPath guideline, the number of lymph nodes with ITCs and micrometastases are included as positive lymph nodes (32) 
‐ pCR should be reported with specified definition (29) 
 ‐ pCR (ypT0 ypN0/cN0) 
 ‐ pCR (ypTis ypN0/cN0): residual DCIS 
 ‐ Not pCR: residual invasive cancer or presence of lymphovascular invasion only or ITCs only (ypN0(i+)) 
‐ Post-treatment biomarkers can be reported with the template provided in the ICCR datasets (29) 
 ‐ ER and PR: antibody clone, specify 
  • Positive 
   • Percentage of cells with nuclear positivity 
   • Intensity of staining (weak/moderate/strong) 
  • Negative (less than 1% nuclear positivity) 
   • Internal control cells: present and stain as expected or absent 
  • Cannot be determined 
   • Internal control cells present; no immunoreactivity of either tumour cells or internal controls 
 ‐ HER2: antibody clone, specify 
  • By immunohistochemistry (IHC) 
   • Negative (score 0) 
   • Negative (score 1+) 
   • Equivocal (score 2+) 
   • Positive (score 3+) 
   • Percentage of cells with uniform, intense, complete membrane staining 
  • By in situ hybridisation 
   • Negative (not amplified) 
   • Positive (amplified) 
  • Number of observers 
  • Number of invasive tumour cells 
  • Probe assay 
  • HER2/CEP17 ratio and average number of HER2 and CEP17 signals per cell 
  • Aneusomy (if present) 
  • Heterogeneous signals (if present): percentage of cells with amplified HER2 signals 
ADH presenting at the margin ‐ Reporting of margins is recommended if the “ADH” focus is contiguous with low-grade DCIS, as it likely represents a contiguous clonal process with DCIS. 
‐ Isolated ADH, which does not transect the margin, is not an indication for additional surgery 
FEA versus CCC ‐ Strict criteria, as follows, are recommended for the core biopsy diagnosis of FEA as its presence may warrant excision 
 - CCCs with low-grade epithelial atypia showing monotonous appearance and a darker appearance (due to higher nuclear-cytoplasmic ratios) 
 - Rigidity to luminal spaces rimmed by a smooth to flat-lining of epithelial cells devoid of architectural atypia 
 - Rounded enlarged vesicular to hyperchromatic nuclei and visible nucleoli, accompanied by scant cytoplasm and frequent apical snouts 
Anterior and nipple margins in skin-sparing mastectomy ‐ Close or involved margins, including anterior and nipple margins, should be reported for consideration of irradiation of positive margins 
Papilloma on CNB ‐ Papilloma should be classified as B3 due to intralesional heterogeneity and sampling issues 
‐ An exception is when a small duct papilloma is confined within the diameter of the tissue core, which can be classified in the B2 category 
Margin status ‐ The word “incomplete or complete excision” should be avoided for reporting 
‐ “Involved or not involved margin” is preferable 
MLL ‐ Extracellular mucin should be closely evaluated and documented in the report as it may raise the possibility of a mucinous carcinoma 
‐ ADH associated with MLLs should be noted due to the significantly higher risk of upgrade in the subsequent resection 
Total duct excision/microdochectomy specimen ‐ Common pathologic findings are duct ectasia, papilloma, or DCIS. In the absence of any pathology, the MDT should review the indications and radiologic correlation to ensure that any pathology has not been missed 
IssuesPathologic consideration
Florid LCIS ‐ Reporting margin status in the excisional specimen is recommended 
Atypical apocrine adenosis ‐ Note of sinister features, such as atypical mitosis and necrosis on CNB, is recommended to support the need for excision 
‐ Strong HER2 IHC expression may be useful as a diagnostic adjunct to corroborate a malignant apocrine process 
Post-neoadjuvant chemotherapy reporting ‐ Cancer staging based on the tumour node metastasis system of the UICC is recommended to be reported with the prefix “yp.” 
‐ Measurement of residual tumour (ypT) is based on the largest contiguous invasive tumour focus without intervening fibrosis 
‐ The number of lymph nodes with metastases 
 ‐ For UICC8/AJCC9 staging, the number of lymph nodes with macrometastases and with micrometastases, provided one macrometastasis is present, is included. Lymph nodes with ITCs are not counted as positive lymph nodes (30, 31) 
 ‐ For RCB and RCPath guideline, the number of lymph nodes with ITCs and micrometastases are included as positive lymph nodes (32) 
‐ pCR should be reported with specified definition (29) 
 ‐ pCR (ypT0 ypN0/cN0) 
 ‐ pCR (ypTis ypN0/cN0): residual DCIS 
 ‐ Not pCR: residual invasive cancer or presence of lymphovascular invasion only or ITCs only (ypN0(i+)) 
‐ Post-treatment biomarkers can be reported with the template provided in the ICCR datasets (29) 
 ‐ ER and PR: antibody clone, specify 
  • Positive 
   • Percentage of cells with nuclear positivity 
   • Intensity of staining (weak/moderate/strong) 
  • Negative (less than 1% nuclear positivity) 
   • Internal control cells: present and stain as expected or absent 
  • Cannot be determined 
   • Internal control cells present; no immunoreactivity of either tumour cells or internal controls 
 ‐ HER2: antibody clone, specify 
  • By immunohistochemistry (IHC) 
   • Negative (score 0) 
   • Negative (score 1+) 
   • Equivocal (score 2+) 
   • Positive (score 3+) 
   • Percentage of cells with uniform, intense, complete membrane staining 
  • By in situ hybridisation 
   • Negative (not amplified) 
   • Positive (amplified) 
  • Number of observers 
  • Number of invasive tumour cells 
  • Probe assay 
  • HER2/CEP17 ratio and average number of HER2 and CEP17 signals per cell 
  • Aneusomy (if present) 
  • Heterogeneous signals (if present): percentage of cells with amplified HER2 signals 
ADH presenting at the margin ‐ Reporting of margins is recommended if the “ADH” focus is contiguous with low-grade DCIS, as it likely represents a contiguous clonal process with DCIS. 
‐ Isolated ADH, which does not transect the margin, is not an indication for additional surgery 
FEA versus CCC ‐ Strict criteria, as follows, are recommended for the core biopsy diagnosis of FEA as its presence may warrant excision 
 - CCCs with low-grade epithelial atypia showing monotonous appearance and a darker appearance (due to higher nuclear-cytoplasmic ratios) 
 - Rigidity to luminal spaces rimmed by a smooth to flat-lining of epithelial cells devoid of architectural atypia 
 - Rounded enlarged vesicular to hyperchromatic nuclei and visible nucleoli, accompanied by scant cytoplasm and frequent apical snouts 
Anterior and nipple margins in skin-sparing mastectomy ‐ Close or involved margins, including anterior and nipple margins, should be reported for consideration of irradiation of positive margins 
Papilloma on CNB ‐ Papilloma should be classified as B3 due to intralesional heterogeneity and sampling issues 
‐ An exception is when a small duct papilloma is confined within the diameter of the tissue core, which can be classified in the B2 category 
Margin status ‐ The word “incomplete or complete excision” should be avoided for reporting 
‐ “Involved or not involved margin” is preferable 
MLL ‐ Extracellular mucin should be closely evaluated and documented in the report as it may raise the possibility of a mucinous carcinoma 
‐ ADH associated with MLLs should be noted due to the significantly higher risk of upgrade in the subsequent resection 
Total duct excision/microdochectomy specimen ‐ Common pathologic findings are duct ectasia, papilloma, or DCIS. In the absence of any pathology, the MDT should review the indications and radiologic correlation to ensure that any pathology has not been missed 

Nipple-sparing mastectomies are increasingly performed for preservation of the nipple, providing improved psychological and cosmetic outcomes [35]. Intraoperative subareolar frozen section (shown in Fig. 3) assessment may obviate returns to the operating room and save costs [36]. The concordance between the frozen section and subsequent paraffin histology ranges from 92.1% to 95% [35, 37]. Even for breast carcinoma presenting with nipple discharge, nipple preservation is regarded as oncologically safe if there are negative margins which may be assessed intraoperatively [38].

Fig. 3.

Frozen section paraffin of a nipple margin shows DCIS, leading to removal of the nipple which was initially intended for preservation.

Fig. 3.

Frozen section paraffin of a nipple margin shows DCIS, leading to removal of the nipple which was initially intended for preservation.

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While fine-needle aspiration cytology (FNAC) has been largely supplanted by core needle biopsy in the assessment of breast lesions in many institutions, there remain complementary roles that FNAC can play in the diagnostic workup of patients with breast abnormalities. The recent introduction of the International Academy of Cytology Yokohama system for reporting of FNAC standardises and reiterates a clinically useful system for categorising FNAC of breast lesions, guiding management and follow-up approaches [39]. In many countries, FNAC continues to be an effective and cost-efficient tool for diagnosis and management of breast cancer, including nipple cytology where it is highly related to DCIS with HER2 overexpression [40]. The role of nipple cytology in investigating nipple discharge, however, is not universally accepted. In the UK, the Association of Breast Surgery guidelines state that nipple cytology is not recommended as it is a poor predictor of histological diagnosis [41]. Nevertheless, FNAC is a reliable method for follow-up surveillance of breast cancer patients, with high accuracy in diagnostic evaluation of recurrent ipsilateral, contralateral, and extramammary lesions [42].

In particular, FNAC has an important role in assessing the axilla, with a review finding an almost 100% specificity and a sensitivity of 40–90% in FNAC of the axilla, with a positive result reducing necessity of a second axillary procedure by up to 20% [43]. It is also suggested that patients with 3 or more abnormal lymph nodes on ultrasound and positive axillary cytology were more likely to have 3 or more positive lymph nodes compared to those with false-negative results [44].

Another situation where cytology has a key role is in the investigation of a suspected case of breast implant-associated anaplastic large cell lymphoma. Apart for routine cytology, ancillary tests such as immunohistochemistry as well as flow cytometry are carried out on samples taken for cytology [45].

There is relatively scant data on the impact of atypical ductal hyperplasia (ADH) found at the surgical margins of lumpectomy specimens. A study from 2008 reported that ADH at the margin of a lumpectomy specimen is associated with a high rate of residual ADH and cancer and advocated re-excision [46]. Another report opined that ADH at the margin of breast conservation surgical specimens is subject to interobserver variability, proposing that re-excision be considered especially if associated with low-grade DCIS [47]. Yet another study suggested that atypical hyperplasia (including both atypical lobular and ADH) found at margins during breast conserving surgery does not increase the risk of subsequently developing an ipsilateral recurrence [48]; however, the implication of ALH versus ADH at margins cannot be equated.

Discussion of such cases at the breast multidisciplinary tumour board is helpful to determine further management. If ADH is found in the immediate vicinity of DCIS, it is likely that it represents a contiguous clonal process and may benefit from additional surgery [47]. However, if ADH is an isolated finding away from any adjacent DCIS and is not transected, it is reasonable not to pursue further surgery.

Columnar cell change (CCC) refers to the presence of columnar cells lining the ducts and lobules, often associated with calcifications which may be radiologically detected. When there are several layers of columnar cells lining the ducts and ductules, the term columnar cell hyperplasia is used [16]. These are collectively called columnar cell lesions.

Flat epithelial atypia (FEA) is defined as low-grade cytological atypia in columnar cell lesions (shown in Fig. 4). The histological identification of FEA is challenging. What constitutes sufficient cytologic atypia to meet criteria for FEA can be subject to interobserver differences [49]. The agreement of FEA diagnosis among pathologists is 71.4%, compared with the 87.5% agreement rate for the diagnosis of columnar cell lesions without atypia [49]. When the higher limit of cytologic atypia for FEA is exceeded, beyond which clinging type DCIS is diagnosed, can also be variable [50].

Fig. 4.

FEA at low magnification shows ducts lined by epithelial cells that appear “dark” due to the increased nuclear-cytoplasmic ratios. Apical cytoplasmic snouts can be observed (arrowheads), better appreciated at higher magnification (inset) where low-grade nuclear atypia is also evident.

Fig. 4.

FEA at low magnification shows ducts lined by epithelial cells that appear “dark” due to the increased nuclear-cytoplasmic ratios. Apical cytoplasmic snouts can be observed (arrowheads), better appreciated at higher magnification (inset) where low-grade nuclear atypia is also evident.

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Histologic clues to the presence of FEA are ducts and ductules with CCC harbouring a monotonous appearance, with rigidity to luminal spaces rimmed by a smooth to flat lining of epithelial cells [49, 50]. These affected ducts and ductules have a somewhat darker appearance at low magnification due to the nuclear enlargement and increased nuclear-cytoplasmic ratios [49, 50]. At higher magnification, apical snouts are often seen, with rounded enlarged vesicular to hyperchromatic nuclei and visible nucleoli, accompanied by scant cytoplasm [50].

In the context of a core biopsy, the importance of distinguishing CCC from FEA lies in the discussion around subsequent management. The estimated risk of upgrade to carcinoma of FEA diagnosed on CNB varies among studies ranging from 4 to 10% [51‒54] while the estimated risk of upgrade to ADH is 18.6–30% [52, 53], leading to proposals by some authors for routine excision. Presence of FEA in a core biopsy performed for a large area of calcifications may warrant further excision in case of upgrade to a worse lesion. In cases where core needle biopsy (CNB) targeted calcifications ≥15 mm, Grabenstetter et al. [54] observed upgrading to invasive carcinoma in two FEAs. No upgrade lesions were found in cases with <15 mm of calcifications in the resection specimen. The authors suggested considering surgical excision when the biopsy target is a lesion that exceeds 10–15 mm and is not completely removed during CNB [54]. However, the routine need for additional surgery when FEA is found as the worst lesion on core biopsy is uncertain [16], with radiological-pathological correlation and multidisciplinary discussion required for decision [55].

Historically, margin distances are not necessarily reported in a mastectomy specimen as there is no further tissue to excise in a mastectomy. However, with the increase in skin-sparing mastectomy and varying mastectomy flap thickness, several studies have demonstrated the risk of residual tumour in the skin flap. With a skin flap thickness of >5 mm, residual benign breast tissue was identified in the skin flap in approximately 60% of cases. Additionally, in the group of flap thickness >5 mm, residual carcinoma was detected in 9.5% of cases [56]. Another study showed a strong association between positive anterior margin and residual carcinoma in the additional anterior margin [57]. There is increasing evidence that margin involvement in a mastectomy (posterior margin or anterior margin in a skin-sparing mastectomy) is associated with a 3-fold increased risk of local recurrence [58]. Hence, it is important to report their status, which is also being advocated by newer guidelines [32].

Involved or close margins should be discussed at the multidisciplinary tumour board (MDT) as there could be potential treatment implications in terms of chest wall radiotherapy (not routine in mastectomy patients) in these patients. In a nipple-sparing mastectomy, the “nipple margin” is a true margin, and presence of tumour at this margin, albeit with a low frequency of 4.5% [59], may necessitate surgical excision of the nipple.

Yes, the pathologist is a core member of the MDT. The essential role of a pathologist within a multidisciplinary team (MDT) involves presenting and clarifying the pathology findings, discussing diagnoses in the clinicoradiological context (triple assessment) [60], providing input on questions posed by the surgeon and oncologist, opinion on molecular applications [61]. Moreover, the MDT serves as a collaborative platform where the latest developments and service requirements can be shared and updated [62]. With the development of precision medicine, pathologists are increasingly taking on a significant role in shaping treatment recommendations such as providing the information of prognostic and predictive factors for breast cancer patients, underscoring their vital contribution to patient management.

It is important that all B1 (normal histology) cases are discussed at the MDT so that triple assessment (clinical and radiological correlation) can take place to explain the normal findings on histology. The risk with excluding B1 cases from the MDT is that the patient may be discharged as having no abnormality but in reality, the biopsy may not be representative of the underlying abnormality and a sinister lesion could be missed. A study highlighted the importance of radio-pathologic correlation where there was a change in histologic category of breast biopsies from B1 to B5 or B3/4 in 53% and 10%, respectively, for cases which were re-biopsied due to discordance between radiological and histological findings [63].

It is possible, however, to have a protocol where certain benign cases (B2) are not discussed at the MDT by some form of pre-MDT triage process. This should be based on a strict pre-agreed template and agreed by all specialities represented at the MDT, e.g., benign radiology suggestive of a FA and wide bore needle shows a FA (B2).

Managing microinvasion on core biopsy is tricky. Some pathologists do not advocate using the term “microinvasion” on a core biopsy due to the limited nature of sampling. Instead, they prefer to state that “a small focus of invasion measuring less than 1 mm is present.” Other pathologists however report microinvasion using the definition as it exists for post-operative specimens (invasive focus not more than 1 mm). The RCPath guidelines recommend using the term microinvasion, applying current criteria but advocating further assessment in terms of examining further levels.

In invasive carcinomas, an axillary staging procedure (such as sentinel lymph node [SLN]) will be done. However, in microinvasive carcinomas, SLN procedure is not always necessary as these are treated as “in-situ” carcinomas [64]. This is yet another example of a situation where thorough MDT discussion is necessary to correlate with radiological and clinical suspicion of invasion. If frank invasion is suspected, it may be prudent to repeat the core biopsy or consider SLN biopsy.

The use of datasets enables pathologists to report breast specimens in an accurate and consistent manner which complies with national and international standards [17, 18, 29, 65‒68]. Datasets also ensure that key prognostic and predictive breast pathology elements are not missed, which in turn allow clinicians to provide high-quality care for their patients. Datasets have an additional benefit in that they standardise reporting of breast pathology in terms of data items that need to be reported across the world allowing cancer registries/data information systems to collect data and monitor trends in breast disease and breast cancer both within and between countries.

However, datasets and guidelines cannot anticipate every clinical scenario. Hence, it may also occasionally be important to deviate from the datasets based on clinical utility and scenarios and particularly for pathologists to be aware of these scenarios. The RCPath UK recognises this need and states, “It may rarely be necessary or even desirable to depart from the guidelines in interests of specific patients and special circumstances” [32].

Papillary lesions are classified as B3 (lesion of uncertain malignant potential) on a core biopsy due to the intralesional heterogeneity often seen in papillary lesions as well as the limited nature of a core biopsy that may miss areas of concern [69]. The only situation where a B2 (benign) diagnosis may be considered is when a small benign papilloma is seen that is contained within the diameter of the core, sometimes referred to as a micropapilloma [69].

The pathology report should not categorically comment on completeness of resection but state whether margins are involved or not (as well as give the distance in mm). The decision regarding completeness of surgery and the need to perform further resection should be taken by the MDT. A report saying incomplete excision implies further surgery is necessary. This approach aligns with different guidelines and accommodates different recommendations of distances required for completeness of excision such as tumour on inked margin versus 1–2 mm clearance [70].

The management of mucocele-like lesions (MLLs) depends on multiple factors, including whether it is found on core biopsy or on excision, and if there is an associated atypical epithelial proliferation [71‒73]. MLLs are accompanied by calcifications in 93% of cases [74] which represent the radiological target for assessment. If a MLL is small and benign on core biopsy, and the radiological calcifications are completely removed, it may not be necessary for further excision as the rate of upgrade on subsequent excision is low (3–4%) [72, 73, 75‒77]. If the calcifications extend over a significant area on imaging, MDT discussion is needed to determine if excision is needed [78, 79]. MLLs associated with atypical epithelial hyperplasia are frequently subjected to excision due to the risk of lesional upgrade reported in up to 15–20% for patients with MLL-associated atypia [76, 80, 81]. MLLs with DCIS or invasive carcinoma are managed accordingly.

It is important to closely evaluate the extracellular mucinous areas to exclude the possibility of a focus of invasive mucinous carcinoma [73, 82]. MLLs on excision specimens, if completely excised and without epithelial atypia, do not require additional specimen management strategies.

With regard to localisation method, most of these lesions have a solid component that is biopsied. It is fairly easy to place a localising seed into this area to facilitate excision. There is no evidence in the literature for any of the seed techniques to suggest that these lesions have a higher failure rate for localisation.

In the UK, the surgical practice is not to ask for frozen section on post-neoadjuvant specimens as it is better to get a definite and more reliable answer on optimally fixed specimens. However, elsewhere touch 1preparations or frozen sections are optional and may be used for intraoperative margin assessment [83].

Many breast surgeons in the private sector setting in Singapore employ intraoperative frozen section evaluation for margins and SLNs even in the post-neoadjuvant setting, to avoid returns to the operating theatre and to facilitate shorter hospital stays. While frozen section analysis is regarded as accurate for margin and sentinel node assessment [84, 85], data on its accuracy in the post-neoadjuvant setting are relatively scant. Investigations on intraoperative frozen section analysis of sentinel lymph node biopsy (SLNB) in breast cancer cases following neoadjuvant chemotherapy have demonstrated comparable sensitivity, specificity, and accuracy when compared to non-neoadjuvant cohorts [86‒90]. Despite the high overall accuracy in the post-neoadjuvant setting, ranging from 80 to 90% [86‒90], there exists a considerable false-negative rate in the intraoperative assessment of SLNs in node-positive, neoadjuvant-treated breast cancer cases, reported to be between 5 and 40% [90‒93].

The most consistent factors associated with false-negative results are the presence of a small volume of metastasis, micrometastasis, and isolated tumour cells [90, 91]. Wong et al. [90] noted a reduction in the false-negative rate from 28.1% to 20.7% when cases displaying isolated tumour cells in SLNs were excluded. Technical limitations of frozen section analysis and tissue sampling may contribute to false negativity, with metastatic foci being exclusively identified on permanent sections in 89% of cases [93]. Moreover, treatment-related changes, such as fibrosis leading to the loss of nodal architecture and lymphohistiocytic inflammatory reactions, pose challenges in SLNB evaluation, particularly when small tumour foci are deposited in the tumour bed [90]. Given the substantial false negative rates and the diagnostic complexities associated with frozen section analysis, intraoperative consultation of SLNB in post-neoadjuvant-treated breast carcinomas may not be routinely applied in some laboratory practices.

Axillary dissection remains the standard treatment for cases with SLN metastases in the post-neoadjuvant setting, irrespective of metastatic carcinoma size [94, 95]. Consequently, any missed small metastases during frozen section analysis may have clinical consequence. A recommended approach involves multidisciplinary evaluation for determining axillary lymph node management in individual patients with node-positive breast cancer after neoadjuvant chemotherapy [96].

Single/total duct excision should be performed for bloody nipple discharge. Single duct excision can be performed if the bleeding duct can be accurately identified at the time of surgery. The specimen for the duct excision usually shows pathology like duct ectasia, papilloma or DCIS, with the majority disclosing pathological lesions [97, 98]. In the absence of any pathology, the MDT should review the indications and the operation notes to ensure that the pathology has not been missed. The clinicopathologic discussion points with specific considerations for pathologic findings and reporting are summarised in Table 1.

As affirmed during the open discussion of the breast pathology segment of the symposium, practising pathologists continue to face challenges and questions in routine diagnostic reporting of breast specimens. The forum highlighted issues that benefited from dialogue and clarification, reiterating that common problems in diagnostic breast pathology may not always have a single answer but require several perspectives that can be best addressed at the multidisciplinary setting.

We thank Ms. Nur Diyana from Luma Medical Centre (Pathology) for administrative assistance with the manuscript and Dr. Murali Varma for the support for this breast pathology segment in the symposium.

The authors have no conflicts of interest to declare.

The authors did not receive financial support for the write-up of this article.

Dr. Rahul Deb, Dr. Natthawadee Laokulrath, Dr. Leena Chagla, and Prof. Puay Hoon Tan wrote, revised and provided input to the manuscript.

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