Journal of Histopathology and Cytopathology
Official Journal of Bangladesh Academy of Pathology
Vol 10, No 1, January 2026
Editorial
Pathologic Evaluation of Breast Carcinoma after Neoadjuvant Therapy: The Need for Standardized Reporting
*Anjum R
Breast cancer management has evolved with widespread use of neoadjuvant chemotherapy, shifting pathology from mainly diagnosis to critical assessment of treatment response. Clear, structured reporting of post-therapy specimens is essential for accurate staging, informed adjuvant decisions, and reliable prognostic insight.
Variability in post-neoadjuvant pathologic reporting has important clinical implications. Inconsistent assessment of residual disease may lead to discordant staging, uncertainty in defining pathologic complete response, and challenges in selecting optimal adjuvant systemic therapy or radiotherapy. Although existing frameworks such as the Residual Cancer Burden (RCB) system, the AJCC 8th edition staging system, and the College of American Pathologists (CAP) protocols provide a structured approach, several practical gray zones persist. These include interpretation of fibrosis-dominant tumor beds, scattered residual tumor cells, lymphovascular invasion without a residual invasive mass, and treated lymph nodes.
Elements to be Included in Pathology Report after Neoadjuvent Therapy
Gross evaluation must document whether residual tumor is identified, the quadrant or location of the tumor, the presence of multifocality, the size of the residual invasive component in millimeters, and whether a biopsy clip or marker has been found. This typically requires slicing the specimen into thin (≤5-mm) sections and smallspecimens may be entirely submitted, while larger ones are sampled commonly one block per centimeter of pretreatment tumor or a minimum of 10 blocks.
Microscopic assessment begins with the histologic diagnosis, typically invasive carcinoma of no special type, followed by assignment of histologic grade using tubule formation, nuclear grade, and mitotic activity. The dimensions of the residual tumor bed and the size of the largest residual invasive focus should be recorded, along with the estimated percentage of residual tumor cellularity. Key ancillary features such as lymphovascular invasion and the presence or absence of ductal carcinoma in situ should be documented. When DCIS is present, its total extent, architectural pattern (cribriform, micropapillary, solid, or papillary), nuclear grade, and the presence of necrosis (focal or comedo) should be described. Measurement of the overall tumor size including DCIS may also be required depending on the response system applied. Retesting ER, PR, and HER2 after NACT is optional . Margin assessment should specify whether invasive carcinoma or DCIS is present at or close to the margins and provide the exact distance to the closest margin. Tumor bed involvement at the margin should also be noted, even in the absence of viable tumor cells.
Lymph node reporting must include the number of sentinel and axillary lymph nodes examined, the number involved by macrometastasis and the size of the largest metastatic focus, the number of micrometastases, and the presence of isolated tumor cells. Any lymph nodes showing treatment-related changes such as fibrosis or histiocytic aggregates without viable tumor should be recorded. The presence or absence of extracapsular extension should also be included.
Challenges in the Pathologic Examination after Neoadjuvant Chemotherapy
Gross identification of the tumor bed is often challenging. Microscopically, tumor beds show irregular fibrous stroma with variable edema, myxoid change, inflammation, calcification, and loss of normal lobular structures. Residual carcinoma frequently exhibits reduced cellularity, cytoplasmic vacuolization, nuclear atypia, and decreased mitotic activity. Stromal retraction around tumor nests is common and should not be misinterpreted as lymphovascular invasion. Single residual tumor cells may be difficult to distinguish from inflammatory cells. Residual DCIS embedded in fibrosis can mimic invasive carcinoma, LVI-only residual disease may occur and should not be mistaken for DCIS.
Single residual tumor cells should be documented as residual invasive carcinoma and included in tumor bed assessment rather than dismissed as treatment effect. Lymphovascular invasion as the only residual disease represents persistent viable tumor and should be reported and not equated with pathologic complete response. Residual DCIS embedded within fibrosis may mimic invasive carcinoma and should be carefully distinguished using architectural features and, when necessary, myoepithelial immunohistochemistry.
Chemotherapy can cause nodal atrophy and fibrosis, making lymph nodes difficult to detect grossly. Submission of fibrotic tissue can improve nodal yield. Nodes completely cleared of metastasis may show only fibrous scars or macrophage aggregates; these should be documented as evidence of treated metastasis.
Clinically meaningful changes have been reported in a minority of cases – ER, and HER2. Changes in Ki-67 after treatment can help assess partial response and guide adjuvant therapy decisions.
Challenges With the Current RCB, CAP and AJCC Systems and Suggested Revisions
The I-SPY 2 trial Pathology Working Group compiled and compared reporting practices across sites and discuss the issues and controversies related to therapy and provided their recommendations.
A common difficulty with the RCB system is the requirement to separately estimate the percentage of the tumor bed occupied by invasive carcinoma and the percentage of cancer that is in situ. Uncertainty also arises regarding when DCIS extends beyond the invasive component or when classic LCIS is present – the working group recommends simplifying the calculator to reduce confusion and potential errors.
The AJCC currently bases post therapy tumor size on the largest contiguous invasive focus and applies the “m” modifier when multiple foci are present. Pathology working group suggest limiting the m modifier to clearly multifocal or multicentric tumors. Current AJCC guidance states that lymphovascular tumor emboli without residual invasive carcinoma in the breast do not qualify as pCR; however, no specific ypT category is provided for this scenario. A designation such as ypT(LVI), accompanied by a comment describing the extent of lymphatic or vascular involvement, would improve clarity.
Partial response to presurgical therapy in the invasive carcinoma, complete response to presurgical therapy is proposed to be included. In lymph nodes, ypN category is based on the longest extent of metastatic carcinoma, fibrous scarring that extends beyond residual tumor cells is not included. Partial response to presurgical therapy in metastatic carcinoma, no residual metastasis, fibrous scarring or histiocytic aggregates related to prior lymph node metastasis with pathologic complete response are suggested to be included.
References
- Park CK, Jung WH, Koo JS. Pathologic Evaluation of Breast Cancer after Neoadjuvant Therapy. J Pathol Transl Med. 2016 May;50(3):173-80. doi: 10.4132/jptm.2016.02.02. Epub 2016 Apr 11. PMID: 27068026; PMCID: PMC4876080.
- Sahoo S, Krings G, Chen YY, Carter JM, Chen B, Guo H, Hibshoosh H, Reisenbichler E, Fan F, Wei S, Khazai L, Balassanian R, Klein ME, Shad S, Venters SJ, Borowsky AD, Symmans WF, Ocal IT. Standardizing Pathologic Evaluation of Breast Carcinoma After Neoadjuvant Chemotherapy. Arch Pathol Lab Med. 2022 May 1;147(5):591-603. doi: 10.5858/arpa.2022-0021-EP. PMID: 35976643.
- College of American Pathologists. CAP Cancer Protocol: Breast Protocol Template. Version 2024. Available from: https://www.cap.org/protocols-and-guidelines.
- Giuliano AE, Connolly JL, Edge SB, et al. Breast Cancer. In: Amin MB, Edge SB, Greene FL, et al., editors. AJCC Cancer Staging Manual. 8th ed. Chicago, IL: American Joint Committee on Cancer; 2017:587-636.
*Dr. Rahat Anjum, Associate consultant, Department of Histopathology and Cytopathology, Apollo Imperial Hospitals, Chittagong. anjum.r.dr@gmail.com
DOI: https://www.doi.org/10.69950/jhc.2026.10.1.1
[Journal of Histopathology and Cytopathology, 2026 Jan; 10 (1):1-3]
