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Advances in Anatomic Pathology:
doi: 10.1097/PAP.0b013e31821698cc
Review Articles

Borderline Breast Lesions: Diagnostic Challenges and Clinical Implications

Masood, Shahla MD; Rosa, Marilin MD

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Department of Pathology & Laboratory Medicine, College of Medicine, University of Florida, Jacksonville, FL

Disclosure: No funding was received for this study from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); and other(s).

Reprints: Shahla Masood, MD, Department of Pathology & Laboratory Medicine, College of Medicine, University of Florida, Jacksonville, 655 W. 8th Street, Jacksonville, FL 32209 (e-mail: shahla.masood@jax.ufl.edu).

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Abstract

Breast cancer remains a global public health problem and is currently the most polarized cancer in the world. Attention to this disease, public awareness, and advances in breast imaging have made a positive impact on breast cancer screening and detection. The growing use of image-detected biopsies has led to increased diagnosis of ductal carcinoma in situ and high-risk proliferative breast lesions. This progress, however, has created a challenge for pathologists. In lieu of the fact that these entities are difficult to diagnose even in tissue sections taken from surgically excised lesions, pathologist are now expected to diagnose them in small and often fragmented tissue/cellular samples obtained from image-guided biopsies. In addition, some proliferative lesions are associated with an increased risk of finding neighboring malignancy when diagnosed on minimally invasive procedures. Therefore, classifying these lesions in small biopsies is difficult and risky. Some of the most challenging areas in diagnostic pathology includes the differentiation between atypical ductal hyperplasia and low-grade ductal carcinoma in situ, lobular neoplasia versus solid low-grade ductal carcinoma in situ, the correct interpretation of papillary lesions with atypia, and classifying the spectrum of columnar cell changes. Although these issues have been recognized for years, consensus criteria and uniform terminology for the diagnosis of these problematic lesions are far from being achieved. The purpose of this study is to review these “borderline” proliferative lesions in an effort to clarify some criteria and prompt the most needed discussion for consensus.

Breast cancer is a multifactorial disease.1 Several risks factors for breast cancer have already been identified. These factors include inherited germ line mutations such as BRCA 1 and BRCA 2 or personal and family history of previous in situ or invasive breast cancer, previous diagnosis of atypical lesions, lifestyle factors such as diet, age at menarche, and age at first live birth, among others. A positive family history doubles the risk of subsequent development of cancer in women whose biopsies show morphologic features of proliferative breast disease with atypia or atypical ductal hyperplasia.2–4

In 1998, “The Tamoxifen for prevention of breast cancer: report of the National Surgical Adjunct Breast and Bowel Project P-1 study,” showed the value of tamoxifen as a chemotherapeutic agent in women from high-risk groups.5 This study showed that administration of tamoxifen reduced the risk of invasive and noninvasive breast cancer by almost 50%. In addition, breast cancer risk was reduced in women with a history of lobular carcinoma in situ (LCIS) by 56% and atypical hyperplasia by 86%. Since then, tamoxifen is recommended for many women with increased risks for breast cancer. This report was a victory for those interested in the concept of chemoprevention. It also generated significant enthusiasm among high-risk individuals. This study, however, also highlighted the side effects of tamoxifen which includes a 3-fold increased relative risk of pulmonary embolism and 2.5-fold increased relative risk of endometrial cancer. In addition, in patients over the age of 50 years, a 1.8-fold increased relative risk of stroke was reported.5

The abovementioned facts emphasize the importance of accurate risks assessment to better stratify patients who may benefit from risk reduction modalities.6,7 Considering the significance of diagnosing atypical hyperplasia in individualized risk assessment and follow-up management, pathologists carry a major responsibility in this process. The association between breast biopsy for so-called “fibrocystic disease” and increased incidence of breast cancer in these patients has been recognized since 1981.8 Since then, attempts have been made to classify the spectrum of fibrocystic disease into reproducible and prognostically relevant categories. These efforts have resulted in introducing the new terminology of nonproliferative breast disease, proliferative breast disease without atypia, and proliferative breast disease with atypia (atypical ductal hyperplasia), and in an effort for defining specific morphologic changes associated with each category (Table 1).9–12 In the 1986 College of American Pathologists Consensus meeting about fibrocystic disease, it was suggested that nonproliferative breast disease carries no increased risk, proliferative breast disease without atypia has slightly increased risk (1.5 to 2 times) and proliferative breast disease with atypia has moderately increased risk (4 to 5 times) for subsequent development of breast cancer compared with general female population.10 Patients who have carcinoma in situ have 8 to 10 times the risk of ultimate development of breast cancer (Table 2).13–15

Table 1
Table 1
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Table 2
Table 2
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MORPHOLOGIC RISK FACTORS

Intraductal Proliferative Lesions of the Breast

The spectrum of proliferative changes in the breast includes usual ductal hyperplasia, atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS). DCIS is a clonal expansion of monomorphic epithelial cells within the ductal system and is a risk factor for breast cancer development.1 However, the heterogenous nature of DCIS regarding its presentation, morphologic, and biological features makes the risk prediction for progression to invasive carcinoma quite variable. On the basis of nuclear grade, presence or absence of necrosis, and architectural pattern, DCIS is stratified into different grades and types.16 Low-grade DCIS and high-grade DCIS represent 2 genetically distinct entities that lead to different forms of invasive cancer. High-grade lesions are associated with rapid growth and progression to invasive cancer and are easier to diagnose.16 In contrast, low nuclear grade lesions remain indolent and when they progress to invasive carcinoma the tumor is frequently of low grade and well differentiated. In addition, it has been also proposed that ADH and low-grade DCIS are more closely related to lobular carcinoma than to high-grade DCIS. These findings challenge the current concept of separating DCIS from LCIS and the relationship between low-grade DCIS and ADH.17,18

Despite significant emphasis on the study of atypical proliferative changes in breast pathology, distinction of ADH versus low nuclear grade DCIS, and sometimes usual ductal hyperplasia versus ADH, remains a diagnostic challenge. ADH has been defined as an entity that has some of, but not all the features of DCIS.19,20 Morphologically, ADH are small and focal lesions formed by a somewhat monotonous and uniform population of small-to-medium sized round, cuboidal, or polygonal cells which are regularly arranged. Rosette-like patterns may be seen and slit-like spaces are common. Rarely, mitosis and small areas of necrosis can be found. Quantitative measures such as morphologic changes of DCIS seen in <2 separate duct spaces or in <2 mm in maximum dimension are the current used criteria for separation between ADH and low nuclear grade DCIS (Figs. 1A, B).19,21 However, these morphologic and quantitative measures are quite subjective and somewhat arbitrary. They have been based on retrospective analysis of tissue sections of surgically excised lesions with no biological validation. In addition, technical issues further challenge the application of quantitative criteria, which can be subject to the variability of tissue sampling and processing of the specimen. The value of adherence to arbitrary quantitative measures has been questioned by several investigators who have used their own criteria.22,23 Currently, there is no consensus about the criteria that should be adopted to distinguish between ADH and low nuclear grade DCIS.24 Difficult cases are often sent for consultation to expert breast pathologists. However, there is difficulty in achieving a reasonable level of agreement about the diagnosis of these entities even among them. This issue is best shown by the article written by Dr Rosai in 1991 highlighting the seriousness of lack of concordance or consistency in diagnosis of atypical proliferative lesions of the breast.25 In another study by Schnitt et al,26 a fair level of agreement among pathologist was achieved using standarized criteria (Table 3). These studies highlight the importance of sufficient training for pathologists in these difficult areas.

Table 3
Table 3
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Figure 1
Figure 1
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Lobular Neoplasia

Intraepithelial proliferation of lobular type originates from the terminal duct lobular unit of the breast. They are characterized by a uniform and loosely cohesive proliferation of cells with minimal cytologic atypia and lack of cellular cohesion, with or without pagetoid pattern of extension to the ductal system (Fig. 1C).1,27,28 Atypical intraepithelial lobular proliferations include atypical lobular hyperplasia and LCIS. In 1978, Haagensen et al29 proposed the term “lobular neoplasia” after concluding that the term “lobular carcinoma in situ” was inaccurate because these lesions not always progress to invasive carcinoma and often regress after menopause. Currently, the term lobular neoplasia (LN) is widely used and this lesion is considered a morphologic risk factor and a nonobligated precursor of invasive carcinoma of either ductal or lobular type, in either breast.1

LN is considered as an incidental finding in breast biopsies performed for other reasons. It is usually not associated with microcalcifications, except the pleomorphic variant,1,27 therefore mammography is not considered a very useful tool for its detection.27,30 The incidence of LCIS/LN has been increasing in women of all ages, having more than doubled over the past 25 years.31 LN is reported in approximately 0.5% to 4% of otherwise benign breast biopsies1; however, being the lesion of incidental finding, its true incidence is unknown.28 In addition, LN is multicentric in up to 85% of the cases and often bilateral.1,32

In the majority of cases, LN is easily diagnosed as such in excisional biopsies; however the diagnosis may be extremely challenging when dealing with small amounts of tissue obtained by core needle or fine needle aspiration biopsy. In addition, LN may exhibit different morphologic patterns, and it may also involve other benign and proliferative lesions such as radial scar, papillomas, and sclerosing adenosis causing significant diagnostic problems.1,33 In addition, other intraepithelial proliferations such as low nuclear grade solid DCIS may be difficult to distinguish from LN. To accurately diagnose difficult cases E-cadherin immunostain, which is typically negative in lobular proliferations, is of pivotal value distinguishing lobular from ductal proliferations (Figs. 1D, E).1,27,32–34

Controversy still exists on the follow-up of patients diagnosed with LN on core needle biopsy. Some investigators recommend excisional biopsy in these cases, as on surgical excision LN is associated with a more serious lesion in a significant number of cases.28,31,35,36 Other investigators advocate for close follow-up and recommend excision only when radiology/pathology discordance is found.37–39 However, the close follow-up approach is only possible when patients are evaluated by a multidisciplinary team of breast disease experts and might not be possible in all settings.

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Columnar Cell Changes

Intraepithelial lesions with columnar cell morphology have puzzled pathologists for many years.40–44 These lesions are characterized by the presence of columnar epithelial cells lining the terminal duct lobular units of the breast. Other morphologic features of columnar cell changes include the presence of elongated nuclei, intraluminal secretions, and variable presence of cytoplasmic protrusions “snouts” in the luminal surface of the cells.41,45–47 Columnar cell change in its simple form is characterized by only 2 cell layers, composed by 1 layer of columnar epithelium and 1 layer of myoepithelial cells. When more than 1 layer of epithelial cells is present, the term columnar cell hyperplasia is used (Figs. 1F, G).45,46 Accordingly, atypical columnar cell changes have been named as flat epithelial atypia versus columnar cell hyperplasia with atypia using the same morphologic criteria.45,46 Flat epithelial atypia is characterized by loss of polarity in the epithelial cells, nuclear hyperchromasia, round-to-oval instead of elongated nuclei, variable presence of nucleoli, mitotic figures, and increased nuclear-to-cytoplasmic ratio (Figs. 1H, I).1,41,43–46 According to the degree of these cytologic or architectural changes, these lesion can be classified as low grade and high grade.44 Columnar cell hyperplasia with mild atypia is characterized by the presence of minimal micropapillary growth in an otherwise typical columnar cell hyperplasia. When more complex architectural pattern such as widespread micropapillae, rigid cellular bridges, “roman bridges,” and moderate-to-marked cytologic atypia is present, these lesions are similar and difficult to distinguish from high-grade in situ carcinomas.45,46 Although these lesions are currently well recognized, confusion still exists among pathologists regarding terminology.1,41,43–47 Several names and classifications have been used during the last years challenging uniformity among pathology reports and compromising a clear understanding of the true significance of these lesions. Although still the disagreement in terminology continues, it is clear that columnar cell lesions with atypia are seen in association with ADH, low nuclear grade DCIS, LN, and low-grade invasive carcinomas such as tubular, tubulolobular, and lobular carcinomas.42,46,48–50 Indeed some investigators have referred to these associations as low nuclear grade neoplasia family.51,52 Despite these associations, the risk of developing subsequent carcinoma after the diagnosis of columnar cell changes with atypia is still not clear and more comprehensive studies are needed in this area.46 In our practice we recommend surgical excisional biopsy for all lesions with atypia to evaluate the entire lesion in an effort to accurately classify the extent and seriousness of the disease, and to rule out the presence of associated carcinoma.

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Atypical Papillary Lesions

Papillary lesions remain as one of the most challenging areas in breast pathology.53–56 As a general hallmark, papillomas are composed of 2 layers of cells, 1 ductal epithelial cell layer and 1 myoepithelial cell layer, supported by a fibrovascular core. Papillary lesions range from benign to malignant with a broad range of diagnostic terminology used by different investigators.45,53–57 Although the number of lesions that belong to this group is large, in general papillary lesions include intraductal papillomas, atypical papillomas, intracystic papillary carcinomas, and invasive papillary carcinoma. In benign lesions a continuous myoepithelial cell layer is generally present.45,53,54 In malignant lesions, on the other hand, the myoepithelial cell layer is normally absent.45,54–56 However, diagnosing the spectrum between these 2 diagnostic ends, namely atypical papillomas and DCIS arising within a papilloma, is sometimes challenging, especially when dealing with small samples such as those obtained by fine needle aspiration biopsy or core needle biopsy.53,58 ADH and DCIS can be found populating a lesion otherwise recognized as a benign papilloma.54 To differentiate ADH from low-grade DCIS within a papilloma, Page et al59 used criteria based on the extent of the abnormal population. Accordingly, ADH is diagnosed if the extent of the atypical population within the papilloma is ≤3 mm and DCIS is diagnosed if the lesion is >3 mm in size.54 Tavassoli60 on the other hand, use the term “atypical papilloma” when less than a third of the papilloma shows atypical features, and the term “carcinoma arising in a papilloma” when more than a third but <90% of the papilloma is involved (Figs. 2A, B). As no consensus has been reached, these diagnostic criteria are interchangeably used by diagnostic surgical pathologists adding more subjectivity to the area. In addition, other proliferative lesions or even invasive carcinoma can be present in the periphery of papillary lesions, and therefore they may be missed during core needle biopsy sampling (Fig. 2C).53,54,61 The reported incidence of finding a more advanced lesion (ADH, DCIS, and invasive carcinoma) on follow-up excisional biopsy after the diagnosis of benign papilloma on core needle biopsy ranges in the literature from 0% to 25%.53 In addition, some lesions diagnosed as papillary on fine needle aspiration biopsy turn out to be nonpapillary on excision.62,63 Therefore, some investigators recommend surgical excision on all papillary lesions diagnosed in minimally invasive procedures.53,61,64,65 Nevertheless, there is no universal agreement and other investigators recommend excision only when atypia is present.66–68 This ongoing debate is fueled by the lack of studies including large number of cases, possible bias in some of the published studies, and the broad range of terminology and diagnostic criteria used by pathologists when dealing with these lesions. In our practice we recommend complete excision of all papillary lesions with a rim of normal breast tissue for diagnostic and therapeutic purposes.

Figure 2
Figure 2
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Radial Sclerosing Lesions

Radial sclerosing lesions (RSLs) are proliferative changes showing a stellate configuration radiologically and histologically.45 As many other proliferative breast lesions, RSLs have received several names in the past.45 Some investigators use the term radial scars when measuring <1 cm, and complex sclerosing lesions if the lesion measures >1 cm.69–71 Dr Rosen prefers the term RSLs as it describes the mammographic and histopathologic appearance of the lesion and it is sufficiently nonspecific to encompass the many histologic variants included in this category.45

RSLs have a radiologic and gross pathology appearance similar to invasive carcinoma.45,69 Histologically, RSLs are characterized by a central fibroelastotic core with the epithelial component radiating outward, giving the lesions it characteristic stellate appearance.45,72 The presence of compressed glands in the center of the lesion gives sometimes the impression of invasive carcinoma. In addition, RSL are often associated with several nonproliferative, proliferative, atypical, and malignant lesions such as microcysts, ductal hyperplasias, adenosis, DCIS, LN, and invasive carcinoma (Figs. 2D–F).45,72 DCIS associated with RSL is often of low or intermediate grade and invasive carcinomas are generally of grade 1 or 2.45,69,73

Manfrin et al73 suggested that radial scars represent a natural model of carcinogenesis starting from a proliferative lesion in patients below 50 years of age, with progressive transformation into atypical and later carcinoma over the years. In their study, analyzing 117 cases of radial scars, the incidence of associated carcinoma and atypical hyperplasia was 32% and 21%, respectively. This risk of malignancy has been also associated to the size of the lesion, meaning that lesions >1 cm in size have an increased risk in comparison with smaller lesions.73,74 In different studies analyzing the presence of DCIS or invasive carcinoma on follow-up of cases diagnosed as radial scar on core needle biopsy, a variable underestimation rates, ranging from 0% to 40% have been found. Therefore, many investigators believe that the diagnosis of radial scar on core needle biopsy does not exclude the presence of a more advanced disease.69,72,75 In their study of 157 cases of nonpalpable radial scar lesions diagnosed by core needle biopsy, Brenner et al76 found carcinoma on follow-up excision in 4% of lesions without associated atypia and in 28% of lesions with associated atypical hyperplasia at percutaneous biopsy. They concluded that core needle biopsy is likely to be a reliable method of diagnosing radial scar when associated atypical hyperplasia is not found, when the biopsy consists of >12 samples, and when there is concordance between radiologic and pathologic findings. They added that if these conditions are not met, excisional biopsy is required. However, these conditions are not feasible in all setting as the extent of sampling performed during biopsy will be subject to operator's criteria and radiologic features of the lesion. In their study, a small subset of patients in which radial scar was not associated with atypia, was found to have malignancy on follow-up.

It is important to add that, in published studies, selection criteria, terminology, the extent of core needle biopsy sampling, and even the way biopsies were processed may vary.72–74,76,77 Therefore, the diagnosis of RSL on minimally invasive procedures is extremely challenging, variable, and may be prone to errors and inaccuracy. Accordingly, the follow-up of these lesions remains a controversial area and a definitive consensus seems to be difficult to reach.

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Atypical Apocrine Proliferations

The majority of apocrine changes seen in breast are easily classified as benign or malignant.78–80 A small group of apocrine proliferations pose diagnostic problems when some but not all morphologic features of malignancy are present. This includes atypical apocrine hyperplasia and low nuclear grade apocrine DCIS.

Different criteria and nomenclature have been used to classify atypical apocrine proliferations.78–83 These criteria are primarily based on architectural changes, nuclear changes, and extent of the disease (Figs. 2F–H). Different experts emphasize on one feature over the others. According to different investigators, the definition of nuclear atypia includes a 3-fold nuclear enlargement with the presence of prominent nucleolus, or the presence of multiple small nucleoli in apocrine cells showing variability in nuclear size.82 Tavassoli and Norris83 used architecture and nuclear characteristics in addition to the 2-mm size criterion for the diagnosis of apocrine in situ carcinoma. In contrast, O'Malley et al81 do not use architectural pattern in their classification. They use size of the lesion and nuclear changes to define atypia. In their study, nuclear characteristics were divided into 3 groups (usual apocrine, borderline A and B, and noncomedo DCIS). Lesions with cytologic features of DCIS involving the majority of the cells were called apocrine DCIS. The borderline category (called “borderline DCIS”) was defined as lesions measuring between 4 and 8 mm showing borderline cytologic features in the majority of cells. Lesions >8 mm in size were designated as borderline DCIS when only a minority of cells showed the borderline cytologic features. In contrast, Tavassoli and Norris83 required only 1 duct or ductule lined by a markedly atypical apocrine proliferation when necrosis is present. In the absence of necrosis, if the epithelium has a solid, irregular cribriform, or micro-papillary pattern, they applied the 2 mm criteria for DCIS. O'Malley et al81 classified lesions >8 mm that consisted mainly of borderline nuclei and lesions showing nuclear abnormalities characterized by irregular nuclear membrane, coarse chromatin pattern, and multiple nucleoli as apocrine DCIS. Conversely, Durham and Fechner80 diagnose solid apocrine DCIS when ducts are completely filled by apocrine epithelium containing cells with 3-fold nuclear size variability and irregular nuclear contours.

Once the diagnosis of apocrine DCIS is established, grading these lesions is another challenging area. In 1997, the Consensus Conference on the classification of DCIS recognized apocrine DCIS as an especial type of DCIS. The panel described apocrine DCIS as “no so easily classified”; but no further recommendations about diagnostic criteria or grading were made.84 However, it is important to grade cases of apocrine DCIS. Tavassoli and Norris83 divided apocrine DCIS into 3 types: comedo (necrotic type), noncomedo, and papillary types. In their classification, comedo apocrine DCIS corresponded to high-grade DCIS, noncomedo apocrine DCIS corresponded to low-grade DCIS if nuclear atypia was subtle, or to intermediate-grade DCIS in cases of severe atypia. Leal et al85 stratified their cases into low, intermediate, and high histologic grade according to nuclear grade and the presence of comedo-type necrosis. Nuclear grade 3 was defined as presence of necrosis and similar features of high nuclear grade nonapocrine DCIS and at least 10% of the nuclei retained a single large nucleolus and the vesicular chromatin pattern. Low histologic grade apocrine DCIS was characterized as nuclear grade 1or 2 without necrosis, and intermediate histologic grade apocrine DCIS were those cases not classified as low or high histologic grade (Fig. 2I).

Another potential diagnostic problem arises when evaluating proliferative lesions involved by apocrine change. Complex sclerosing lesions involved by atypical apocrine proliferations may show an infiltrative pattern difficult to distinguish from invasive carcinoma in small core needle biopsies. In addition, these lesions are often characterized by a spectrum of proliferative changes ranging from usual apocrine change to DCIS.78,86–88 The use of myoepithelial markers is helpful to rule out invasion; however, diagnosing the spectrum of atypical proliferative changes remains a challenge.

Currently, there is no consensus on classification, grading, and clinical significance of apocrine borderline lesions. Some of the current proposed criteria are difficult to apply and they were established without adequate follow-up, lack of patient risk stratification, and different thresholds for the diagnosis of atypia.80,82 Furthermore, there is not enough data available to clearly define biologically significant morphologic criteria for the diagnosis of these atypical lesions. In addition, in comparison with ductal epithelial cells, normal apocrine cells are larger and have prominent nucleoli. Therefore, criteria used to differentiate ADH versus low nuclear grade DCIS are not applicable to apocrine lesions.78,82 Until strict, scientifically validated criteria are established, this area of breast pathology will remain largely subjective. Regardless of these issues, it is our opinion that all atypical/ borderline apocrine proliferations diagnosed on core needle biopsy require follow-up excisional biopsy.

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SUMMARY

Morphologic risk factor refers to lesions that variably increase the risk of future cancer development in both breasts, but are not direct precursors of invasive carcinoma. Among these lesions are ADH, low nuclear grade DCIS, papillary lesions with atypia, radial sclerosing lesions, atypical columnar cell changes, atypical apocrine proliferations, and lobular neoplasia. In contrast, the term borderline lesions of the breast refer to a group of atypical proliferative lesions quantitatively and qualitatively close and difficult to differentiate from some variants of in situ carcinoma. These borderline lesions have been problematic for years, not only for pathologists but also for radiologists and surgeons as there is no consensus on how these patients should be managed. In addition, from the pathologist's point of view, there is a lack of universal consensus about histologic diagnostic criteria, lack of uniformity about diagnostic terminology, and many times lack of adequate clinical history and radiologic findings that precludes appropriate pathologic evaluation and correlation during sign out. All these factors lead to a significant interobserver variability even among experienced pathologists.25,26 Given that the word “carcinoma” has been used to diagnose in situ lesions (ductal carcinoma and LCIS) for many years, and that the clinical implications and our understanding of the significance of these lesions have changed over the years, it may be the time for a terminology change.89,90 It is currently accepted that breast cancer is a diverse group of diseases regarding presentation, morphology, biology, and molecular profile. Molecular studies in low-grade and high-grade tumors have identified alterations possibly associated with different molecular routes in cancer evolution. In addition, coexpression of these alterations between low-grade and high-grade lesions is rare.51,52 Therefore, it is now recognized that low-grade and high-grade tumors are 2 genetically different entities and they do not evolve into each other.

A modest change in the approach to some of these borderline/morphologic risk factor lesions has been seen during the years. The term LN is now largely used and has almost entirely replaced the categories of atypical lobular hyperplasia and LCIS.29 In addition, many experts use the term “papillary lesion” for all nonmalignant papillary lesions diagnosed on core needle biopsy and fine needle aspiration biopsy.58 Similarly, the term “borderline intraductal lesion” may be used to encompass the spectrum of lesions ranging from ADH and low nuclear grade DCIS in core needle biopsy until the lesion is completely excised and entirely evaluated. This approach may save some patients from emotional stress and being unnecessarily labeled as “cancer patients.” However, up to now, suggested terminologies of mammary intraepithelial neoplasia by Dr Rosai and ductal intraepithelial neoplasia by Dr Tavassoli have not been fully embraced by the pathology community. This is despite the fact that the unifying concept of mammary intraepithelial neoplasia may eliminate the use of the term “in situ carcinoma” and may reduce the chances of over treatment.89

The widespread use of mammography has increased the number of nonpalpable abnormalities being biopsied.91,92 Therefore, pathologists are more and more often confronted with a broad variety of borderline proliferative lesions sampled by minimally invasive procedures. In addition to the small size, distortion, and fragmentation of the tissue samples, the possibility of underestimation of some lesions is a real problem. Also the possibility of overdiagnose or misdiagnose some of these lesions is an area of concern as errors will lead to wrong treatment and/ or unnecessary therapies.

In light of these issues, adequate training in breast pathology is essential and should be a critical component of all residency training programs.93 Another important issue of concern is the general assumption that breast pathology is a part of general surgical pathology and does not require special training. This is in contrast to other areas of Pathology such as neuropathology, dermatopathology, hematopathology, cytopathology, and molecular pathology that are recognized by the American Board of Pathology as subspecialties deserving special certification. A few available breast pathology fellowships are currently funded by individual departments and are not officially accepted by the Accreditation Council for Graduate Medical Education. This may result in lack of uniformity in training as some of these programs are not “pure” breast pathology and split breast training with other rotations or electives. Currently, breast pathology training for residents is limited to what is offered during their surgical pathology rotations. Aside from a few major academic institutions, pathology residents are not familiar with the concept of integration of breast pathology into breast care and are not introduced to the multidisciplinary approach to the diagnosis and management of breast disease. Pathology residents find their way into medical centers and medical communities where the majority of patients with breast cancer are treated and they continue the same trend of practice of breast pathology. As long as the discipline of breast pathology remains underrecognized among patients and medical organizations, uniformity and adequate training will be difficult to accomplish.94,95

Currently, there is much to do in the field of diagnostic breast pathology. It is essential to achieve adequate training in breast pathology, uniformity on tissue processing, interpretation, diagnostic terminology, and integration of the pathologist in clinical research and patient's management.89,94,95 Finally, advances in the field of molecular pathology will improve our understanding of the biology and behavior of these so-called borderline breast lesions, in hope of ultimately reaching consensus and improving patient care.

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Keywords:

proliferative breast disease; borderline breast disease; morphologic risk factors; core needle biopsy

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