New Challenges for the Practicing Surgical Pathologist in the Diagnosis and Management of Breast Lesions

FigureThe increasing numbers of breast core biopsies that are being performed for mammographic calcifications has presented surgical pathologists in recent years with a broadening spectrum of abnormal breast lesions. We are now frequently seeing lesions that had previously been considered rare, and some of these entities can present diagnostic and management challenges. Although columnar lesions have been recognized since the 1940s,1 they are now receiving greater scrutiny owing to their increasing frequency in breast core biopsies. The literature is particularly confusing in this area because there has been no uniformly accepted terminology for these lesions and little is known about their biologic potential. In his article, Dr. Schnitt has described in detail the histologic features of a spectrum of lesions showing columnar change and has clarified the many overlapping terms that have been applied to such cases. It is hoped that this will facilitate a uniform approach to their diagnosis. Dr. Schnitt's comprehensive review summarizes what is known about the behavior of columnar cell lesions and addresses several practical considerations when reporting such cases. Lobular carcinoma in situ (LCIS) showing classic morphology is generally easily differentiated from ductal carcinoma in situ (DCIS), even on breast core biopsies. However, as Jacobs outlines, there are several recently recognized variants of LCIS that can present diagnostic challenges, including the “pleomorphic” variant. This variant is often accompanied by foci of intraluminal comedo-type necrosis and calcifications, but retains the cytologic features of LCIS and is uniformly negative for E-cadherin. The paucity of clinical outcome data for variants of LCIS makes it difficult to determine the most appropriate management strategy. Nevertheless, Jacobs provides a pragmatic approach to the management of these lesions when diagnosed on core biopsy. Clinically validated morphologic criteria are available for differentiating atypical ductal hyperplasia (ADH) from minute examples of low-grade DCIS,2,3 and these criteria can also be applied to core biopsies. However, as a result of limitations of sampling, ductal carcinoma in situ or even invasive carcinoma might be present in the subsequent excision. Because of this, the traditional approach is to recommend local excision if ADH is diagnosed on core biopsy. Page et al. challenge this view by presenting some preliminary data suggesting that there might be a subset of ADH that could be followed conservatively. They discuss a probabilistic approach to reporting ADH on core biopsy and emphasize the importance of close communication between the pathologist and radiologist in managing these lesions. The development and adoption of new diagnostic and therapeutic procedures for women with breast disease further highlights the importance of the team approach to the diagnosis and management of breast lesions. Since its introduction in the mid-1990s, sentinel lymph node biopsy (SLNB) has been rapidly embraced by the surgical community. Its widespread adoption has brought several important and difficult issues to the forefront. These issues have implications for the pathologist as well as for our colleagues in surgery and oncology. The article by Weaver focuses on the issues that have direct relevance for the pathologist in terms of handling SLNBs and reporting those that have micrometastatic disease. He makes the important distinction between micrometastases and occult metastases and indicates that many studies of occult metastases include both micro- and macro-metastatic disease. In discussing the processing of sentinel lymph nodes, Weaver highlights the statistical principles of node sampling. He notes that the performance of serial sectioning of the sentinel lymph node at 2-mm intervals is a method likely to detect all clinically relevant nodal metastases. A consensus panel of the College of American Pathologists has recommended this approach.4 The article by Warr and Miller focuses on the clinical dilemma created for the treating physician when isolated, cytokeratin-positive cells are detected in SLNB performed on women with DCIS only. As their case report highlights, the finding of a few isolated cytokeratin-positive cells in a sentinel lymph node from a patient with DCIS can cause substantial anxiety for the patient, despite the fact that such a finding is of no proven prognostic significance. In some instances, it could possibly lead to needless treatment of the patient with systemic therapy. Although the results from the ongoing clinical trials will clarify many of the issues raised by SLNB, these results will not be available in the near future. In the interim, the sixth edition of the American Joint Committee on Cancer manual has recommended that patients with isolated tumor cells or tumor cell clusters up to 0.2 mm in greatest dimension are classified as lymph node-negative (pN0) for staging and treatment purposes.5 Ductal lavage is a new technique that could potentially play a role as an adjunct to other methods of risk assessment in helping women and their physicians make decisions regarding chemoprevention. It is also being investigated as a method of serially assessing chemotherapeutic effects in women treated with neoadjuvant therapy and as a method of detecting occult cancers. However, as Dr. Sneige has emphasized, there are no data as yet to support its use as a method for occult cancer detection. If this technique does extend our ability to detect early lesions, the challenge will be to ensure that the morbidity associated with detection and subsequent treatment is less than the potential morbidity of the lesion being detected. Undoubtedly, further research is needed to determine how best to incorporate this technique into the management of high-risk women. A well-defined high-risk group that requires better surveillance procedures is the group of women with known BRCA1/2 gene mutations. The risk of developing breast cancer for these women has been reported as high as 80% by 70 years of age,6 although population-based studies suggest that it might be closer to 40%.7 Numerous studies have reported the pathologic features of tumors arising in such individuals. Although a distinct histologic phenotype for BRCA2-associated tumors has not emerged, Dr. Lakhani highlights the specific tumor phenotype that occurs in BRCA1 carriers. These tumors are characteristically of high histologic grade with high proliferation rates and pushing margins and are frequently negative for estrogen (ER) and progesterone (PR) receptors. Despite this phenotype of high-grade ER and PR negativity, data suggest that HER2 protein overexpression might not be important in the pathogenesis of such tumors.8,9 This finding, if confirmed by others, could have important treatment implications for this group of individuals. Also, the recognition of a distinct morphologic and immunophenotype for BRCA1-associated tumors could lead to wider use of these characteristics in genetic screening. I want to express my sincere thanks to all the contributors to this issue of Pathology Case Reviews. I hope these articles will prove useful to you as you encounter these breast lesions in your daily practice. Frances P. O'Malley MB, FRCPC Department of Pathology and Laboratory Medicine Mount Sinai Hospital Toronto, Ontario, Canada

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