The significance of lobular neoplasia on needle core biopsy of the breast

The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological–pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological–pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia.     

Excisional biopsy should be performed if lobular carcinoma in situ is seen on needle core biopsy

CONTEXT: Percutaneous image-guided core biopsy is increasingly becoming the method of choice to evaluate impalpable breast lesions presenting with mammographically detected calcifications or as a mammographically detected mass. Infrequently, a diagnosis of a primary lobular lesion is rendered by needle core biopsy. Although lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) are not themselves detectable by mammography, they can be associated with calcifications. The management of patients with a primary diagnosis of LCIS or ALH on needle core biopsy is uncertain. Recommendations include excisional biopsy, tamoxifen citrate therapy, mammographic surveillance, or a combination of these approaches. OBJECTIVE: The purpose of this study was to report the histologic findings of excisional biopsies performed after ALH or LCIS was found in a needle core biopsy. DESIGN: Hematoxylin-eosin-stained slides of 20 needle core biopsy specimens from patients with a primary diagnosis of LCIS or ALH were retrieved from the consultation and surgical pathology files of New York Presbyterian Hospital-Weill Medical College of Cornell University. Histologic diagnoses were confirmed in all cases. RESULTS: Fourteen cases of primary LCIS and 6 cases of ALH found on needle core biopsy were identified. Subsequent excisional biopsy of the 14 LCIS cases revealed the following: LCIS, ductal carcinoma in situ, invasive carcinoma (1 patient; 7%); LCIS, infiltrating lobular carcinoma (1 patient; 7%); LCIS, ductal carcinoma in situ (1 patient; 7%); LCIS (8 patients; 57%); and ALH with or without atypical ductal hyperplasia (3 patients; 21%). Among the 6 patients with ALH on needle core biopsy, 1 had infiltrating lobular carcinoma and LCIS and 2 had LCIS in subsequent excision; other excisions for ALH were benign. Overall, 3 (21%) of 14 patients with a primary diagnosis of LCIS on needle core biopsy had a more significant lesion (ductal carcinoma in situ or invasive carcinoma) in a subsequent excisional biopsy. CONCLUSIONS: Data obtained in this study and in previously published reports lead us to conclude that excisional biopsy may be indicated and should be considered when LCIS is found on needle core biopsy in order to more fully examine the biopsy site for coexistent, clinically inapparent intraductal or invasive carcinoma that may be present in about 25% of these patients. The small number of ALH cases studied produced inconclusive results. We recommend that excisional biopsy be considered if atypical ductal hyperplasia is present with ALH in a needle core biopsy or if the diagnosis of the biopsy specimen is discordant with the mammographic findings.     

Examination of breast needle core biopsy specimens performed for screen-detected microcalcification

AIMS: To establish the number of histological levels necessary for the evaluation of breast needle core biopsy (NCB) specimens taken from areas of mammographic calcification in patients presenting via the UK National Health Service Breast Screening Programme. METHODS: Retrospective review of a series of breast NCB specimens initially examined routinely at nine levels. The presence of calcification within the histological sections in each of three sets of levels (levels 1-3, 4-6 and 7-9) and the (cumulative) diagnostic B category that would have pertained after each were assessed. RESULTS: Accurate diagnostic classification was possible after examination of three levels in 89% cases. Examination of a further three levels permitted accurate diagnosis in a further eight cases (total 97% cases). In only three cases were nine levels necessary for accurate classification. In only a single case (1%) was it likely that routine examination of six levels could have led to significant misclassification. In a significant group of patients (18%), nine levels were considered to provide additional useful information, although this information did not alter the diagnosis. CONCLUSIONS: NCBs for screen-detected mammographic calcification should be routinely examined at six levels. Further levels may be needed in occasional cases to identify more conclusively the associated pathological abnormality. Further levels may be of particular value when assessing atypical intraductal proliferative epithelial lesions.     

Epithelial displacement during breast needle core biopsy causes diagnostic difficulties in subsequent surgical excision specimens

BACKGROUND: The use of needle core biopsy (NCB) as part of triple assessment for non-operative evaluation and diagnosis of breast lesions is now routine practice. Trauma to breast tissue during NCB may result in displacement of breast epithelium and may lead to diagnostic difficulty in subsequent excision specimens. METHODS: The cases of seven mammographically detected breast lesions in which epithelial displacement due to NCB was identified and caused problems in confirmation of tumour size, assessment of surgical margins, and interpretation of possible invasive carcinoma and lymphovascular invasion are reported here. CONCLUSION: Previous observations that epithelial displacement is more likely to occur when the interval between NCB and surgical excision is short are supported.     

Lobular neoplasia diagnosed on breast Core biopsy: frequency of carcinoma on excision and implications for management

The appropriate follow-up and treatment for patients with a core biopsy diagnosis of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) remains controversial. Several studies have attempted to address this issue, with recommendations ranging from close clinical follow-up or surveillance to mandatory surgical excision in all cases. We report the findings at our institution, where virtually every core needle biopsy diagnosis of lobular neoplasia results in follow-up excision. The goal of the study was to identify potential predictors of upgrade to a more significant lesion. We identified 76 patients over a 15-year period with a core biopsy diagnosis of pure lobular neoplasia and no other high-risk lesions. Subsequent surgical excision identified 10 cases (13%) that were upgraded to carcinoma. Upgrade diagnoses included invasive ductal carcinoma (n = 1), invasive lobular carcinoma (n = 4), ductal carcinoma in situ (n = 3), and pleomorphic lobular carcinoma in situ (n = 2). All 10 upgraded cases had imaging findings suspicious for malignancy including irregular masses, asymmetric densities, or pleomorphic calcifications. Of the 10 upgraded cases, 7 were diagnosed as lobular carcinoma in situ on core biopsy. The data support a role for radiologic-pathologic correlation in the evaluation of suspicious breast lesions and suggest that the extent of lobular neoplasia in core biopsy specimens may be an indicator of the likelihood of upgrade to carcinoma.     

Surgical follow-up results for apocrine adenosis and atypical apocrine adenosis diagnosed on breast core biopsy

Apocrine adenosis (AA) and atypical apocrine adenosis (AAA) are uncommon findings in breast biopsies that may be misinterpreted as carcinoma. The clinical significance and risk implications of AAA diagnosed on core biopsy are not well established. This study aimed to determine the frequency of carcinoma on follow-up excision in patients with a diagnosis of AA or AAA on core biopsy. Forty-one breast core biopsies of AA (n = 29) and AAA (n = 12) were identified during a study period of 12 years. Of the 41 core biopsies with AA or AAA, 10 biopsies showed coexisting/concurrent atypical hyperplasia or carcinoma. In the absence of coexisting/concurrent atypical hyperplasia or carcinoma in core biopsy, none of the follow-up excision specimens after a diagnosis of AA or AAA showed ductal carcinoma in situ or invasive carcinoma. In conclusion, AA or AAA by itself is an uncommon core biopsy diagnosis that may not require surgical excision.     

In situ and invasive lobular neoplasia of the breast

Lobular neoplasia of the breast represents a group of related malignancies with clinical implications ranging from risk lesions [atypical lobular hyperplasia and lobular carcinoma in situ (LCIS)] through to aggressive invasive lesions, notably invasive pleomorphic lobular carcinoma. The diversity in lobular carcinoma is evident at the morphological level, at the molecular marker level and in cytogenetic profiles. Research in these areas is already changing the face of the disease group, for example suggesting that some lobular and ductal carcinomas are closely related and even that one of the lobular group, the tubulo-lobular carcinomas, should, in fact, be regarded as a ductal cancer. More research is required to understand the long-term pathogenic implications of a diagnosis of in situ lobular neoplasia, particularly pleomorphic LCIS , and to understand the genetics behind the well-recognized high risk of bilateral disease. For invasive carcinoma, molecular studies will allow refinement of therapy and the possibility of novel targeted therapies, for example directed against fibroblast growth factor receptor 1.     

Lobular neoplasia in breast core needle biopsy specimens is associated with a low risk of ductal carcinoma in situ or invasive carcinoma on subsequent excision

To address the significance of lobular neoplasia (LN) in breast core needle biopsy specimens, we prospectively obtained LN cases and correlated results of subsequent tissue sampling. LN was diagnosed by core needle biopsy in 467 women; in 101 (21.6%), invasive carcinoma (IC) or ductal carcinoma in situ (DCIS) was diagnosed concurrently. Two patients (0.4%) had previous diagnoses of IC or DCIS, and 17 (3.6%) had a concurrent diagnosis of contralateral IC or DCIS. Of 366 patients without a concurrent diagnosis of IC or DCIS, subsequent tissue diagnoses were available for 156 cases (42.6%). Of 60 cases of LN and atypical ductal hyperplasia on the biopsy, 5 had IC and 10 had DCIS on the excision (total, 25%). Of 4 women with LN and a mucocele-like lesion on the biopsy, none had IC or DCIS on excision. Of 92 with LN alone on the biopsy, 7 had IC (6) or DCIS (1) on excision. Two cases were in sites away from the biopsy site, 3 in subsequent excisions of the biopsy site, and 2 after previous excision of the biopsy site without finding IC or DCIS. Although LN is associated with a high overall rate of IC and DCIS (30%), excision of the biopsy site for women with LN alone on core needle biopsy has a very low rate of IC and DCIS in our center. Women in whom biopsy sites are excised are still at risk for subsequent DCIS and IC.     

Comparative study of histological features between core needle biopsy and surgical excision in phyllodes tumor

We analyzed histopathological features of core needle biopsy (CNB) and surgical excision specimen comparatively in 129 patients with surgically proven phyllodes tumor (PT). Stromal characteristics including cellularity, atypia, mitosis, overgrowth, tissue fragmentation, and the tumor margin were assessed. Benign/borderline/malignant phyllodes tumor (PT) were diagnosed in 90 (69.8%)/30 (23.3%)/9 (7.0%) patients. Among the 90 cases of benign PTs, 67 cases (74.4%) were diagnosed concordantly in CNB. For borderline and malignant PTs, three out of eight (26.6%) and four out of nine (44.4%) cases were diagnosed concordantly in CNBs. All 50 cases of discordant diagnosis were underestimated in matched CNBs, especially in their stromal cellularity and mitosis. The size of tumor is larger in discordant cases of PT (P= 0.013). The concordant rate of diagnosis between CNB and surgical excision was about 60% and accordingly, grading of PT based on the histological findings in CNBs has limitation. The discordance comes from heterogeneous stromal properties of PTs.     

Recommendations for excision following core needle biopsy of the breast: a contemporary evaluation of the literature

Pathologists frequently encounter non‐malignant histological findings in percutaneous core needle biopsies (CNBs). Standards for the management of patients with lesions such as atypical ductal hyperplasia, atypical lobular hyperplasia, and lobular carcinoma in situ, as well as other benign lesions, are not well defined, and recommendations for surgical biopsy or continued clinical and radiological follow‐up are inconsistent. The frequency with which these lesions are ‘upgraded’ to carcinoma in excision specimens is widely variable in the literature. Many CNB studies lack careful radiological–pathological correlation, clear criteria for excision, and clinical follow‐up for patients on whom excision was not performed. This review of the recent literature emphasizes studies with radiological–pathological correlation, with the goal of developing a contemporary, evidence‐based approach to the management of non‐malignant lesions of the breast diagnosed on CNB. The data supporting an emerging consensus on which lesions may not require excision are highlighted. The management of non‐malignant lesions diagnosed on magnetic resonance imaging‐guided CNB is also discussed.     

Surgical excision is warranted following a core biopsy diagnosis of mucocoele-like lesion of the breast

AIMS: Mucocoele-like lesions (MLLs) of the breast are unusual lesions in which mucin-filled ducts or cysts are accompanied by extrusion of mucin into surrounding stroma. A possible diagnosis of MLL may be suggested by the finding of mucin-filled ducts or cysts and/or stromal mucin in a core biopsy sample. Whether such findings should prompt immediate open diagnostic biopsy to exclude malignancy is currently uncertain, although this represents current practice in our institution. In this study we have reviewed 11 cases of possible MLL on core biopsy correlating both pathological and radiological findings in order to determine the risks of associated malignancy and whether excision is the most appropriate management option. METHODS AND RESULTS: Eleven cases of possible MLL presenting via the Breast Screening and Assessment Unit in Leeds since April 1999 were identified by review of pathological records. Histological slides, mammograms and ultrasound images were reviewed. Ten of the 11 had undergone open surgical biopsy for diagnosis. Three of the 10 (30%) proved to derive from malignant lesions. Two were ductal carcinoma in situ (DCIS) and one was an invasive mucinous carcinoma. All three cases had an associated atypical epithelial proliferation which, in a surgical excision, would be classified as atypical ductal hyperplasia (ADH) at least, as well as mucin in the core biopsy sample. The majority of possible MLLs presented radiologically as coarse calcification, but two of four (50%) which had a radiological mass subsequently proved malignant. Seven cases were without atypia on the core and all subsequently proved benign. Three of these, however, were associated with ADH on the excision biopsy. CONCLUSION: Surgical excision is warranted following a core biopsy suggestion of possible MLL when mucin-filled ducts or cysts and stromal mucin have been seen. The risk of malignancy is high when the core biopsy also contains an atypical epithelial proliferation (100% in our series) and also when there is an associated radiological mass lesion. In cases without atypia on the core a significant proportion of cases (43%) are associated with ADH on excision.     

In situ lobular neoplasia of the breast with marked myoepithelial proliferation

Shousha S
(2011) Histopathology  58, 1081–1085
In situ lobular neoplasia of the breast with marked myoepithelial proliferation Aims: To present four new cases of in situ lobular neoplasia associated with marked proliferation of myoepithelial cells. Methods and results: Four recently seen cases showing extensive foci of in situ lobular neoplasia, as confirmed by negative E‐cadherin staining, were stained for myoepithelial cells using CD10, smooth muscle actin and cytokeratin 5/6. Invasive lobular carcinoma was also present in two cases; one case was associated with multiple foci of collagenous spherulosis, and one was associated with a radial scar. Marked myoepithelial proliferation was seen around most of the in situ lobular foci or mingled with lobular cells. Conclusions: Marked proliferation of myoepithelial cells is sometimes encountered in association with extensive in situ lobular neoplasia. It is suggested that this proliferation might have a role in maintaining the in situ status of these lesions or, alternatively, that there is a shared factor responsible for the simultaneous proliferation of certain ‘lobular’ cell types and myoepithelial cells.     

Atypical ductal hyperplasia diagnosis by directional vacuum-assisted stereotactic biopsy of breast microcalcifications. Considerations for surgical excision

In 824 patients who underwent directional vacuum-assisted biopsies (DVABs) of breast microcalcifications, 61 (7.4%) showed atypical ductal hyperplasia (ADH). The 42 who subsequently underwent excision were the subjects of this study. Cases were evaluated for the mammographic characteristics of the lesion, the percentage of lesion removed according to mammography, and histologic findings (including number of large ducts and/or terminal duct-lobular units involved with ADH) in DVAB specimens. Pathologic findings in the surgical specimens in the area of the biopsy site also were recorded. In the DVAB specimens, ADH was confined to an average of 1.5 large ducts or lobular units and was associated with microcalcifications in all of the patients. Surgical specimens showed ADH in 15 cases, no residual lesion in 24 cases, and ductal carcinoma in situ in 3 cases. We found that microcalcifications that contain ADH in less than 3 lobules or ducts and/or that are removed completely by DVAB do not reveal higher-risk lesions on excision; thus, removal is unnecessary. When assessing microcalcifications with ADH, clinicians should consider the percentage of microcalcifications removed by DVAB and the extent of lobular involvement to better assess the need for excision.     

乳腺小叶肿瘤组织学亚型及其分子病理学研究进展

第5版WHO乳腺肿瘤分类(2019), 将小叶瘤变定义为"起源于终末导管小叶单位(terminal ductal lobular units)失黏附上皮细胞的不典型增生, 伴或不伴有终末导管的派杰样播散"。小叶瘤变包括不典型小叶增生(atypical lobular hyperplasia)和小叶原位癌(lobular carcinoma in situ)。根据细胞形态将小叶原位癌细分为经典型小叶原位癌、旺炽型小叶原位癌和多形性小叶原位癌3种组织学亚型。近年来, 随着分子病理学不断发展, 对组织学形态特征的认识不断深入, 加深了对小叶瘤变及其亚型的研究和分析。本文将对小叶肿瘤各组织学亚型的临床病理学特征和分子病理学等方面进行综述。