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Purpose Classical type of lobular neoplasia (LN) spans a spectrum of disease, including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), classical lobular neoplasia (LN), and the three-tiered classification of lobular intraepithelial neoplasia (LIN-1, -2, -3). This study addressed inter-observer variability of classical lobular neoplasias (LN) (B3 lesions) in preoperative breast biopsies among breast and gynecopathologists Methods A retrospective, observational, cross-sectional study was conducted. 40 preoperative digital images of breast core/vacuum biopsies were analyzed by eight experienced breast- and gynecopathologists. Evaluation criteria were ALH, LCIS, LN classic, LIN-1, LIN-2, LIN-3, focal B3 (one focus), extensive B3 (> one focus). Kappa-index and Chi-square tests were used for statistics. Digital scanned slides were provided to each participant. Agreement between the categories was defined as at least six of eight (cut-off 75%) concordant diagnoses. Results The highest agreement between eight pathologists was reached using the category lobular neoplasia (LN, classical), 26/40 (65%) cases were diagnosed as such. Agreements in other categories was low or poor: 12/40 (30%) (ALH), 9/40 (22%) (LCIS), 8/40 (20%) (LIN-1), 8/40 (20%) (focal B3), 3/40 (7.5%) (LIN-2), and 2/40 (5%) (extensive B3). Chi-square-test (classical LN versus the other nomenclatures) was significant (p = 0.001137). Conclusion Our data suggest that among Swiss breast pathologists, the most reproducible diagnosis for B3 lobular lesions is the category of classical LN. These data further support lack of consistent data in retrospective studies using different terminologies. Validation of reproducible nomenclature is warranted in further studies. This information is useful especially in view of retro- and prospective data analysis with different diagnostic categories.

Resume Objectif Les neoplasies lobulaires intraepitheliales (NLI) diagnostiquees par biopsie mammaire radioguidee peuvent etre associees a un cancer non diagnostique lors de la biopsie. Dans ce cas, on parle de sous-diagnostic. La prise en charge de ces lesions est par consequent souvent chirurgicale et de nombreuses chirurgies s’averent finalement inutiles. L’objectif de notre travail etait de definir des criteres permettant d’eviter une chirurgie inutile. Materiels et methodes Il s’agit d’une etude monocentrique, retrospective issue d’une base de donnees collectees de maniere prospective. Quatorze mille biopsies ont ete analysees, parmi lesquelles 456 NLI ont ete diagnostiquees. Les taux de sous-diagnostic ont ete analyses en fonction de nombreux criteres. La duree moyenne de suivi etait de 45 mois. Resultats Pour les hyperplasies lobulaires atypiques (HLA), nous avons obtenu 7,6 % de sous-diagnostic et en combinant plusieurs criteres, nous obtenions un risque tres faible de cancer (2 %). Pour les CLIS, ce taux etait de 23 % et aucun sous-groupe a faible risque n’a pu etre identifie. Conclusion Les HLA se traduisant par des microcalcifications ≤ 20 mm, sans autre lesion atypique associee, histologiquement focales et dont l’exerese radiologique est representative peuvent beneficier d’une surveillance clinico-radiologique. Pour les autres lesions de NLI, une chirurgie reste indiquee.

The terms ductal and lobular intraepithelial neoplasia (DIN and LIN) were introduced by Tavossoli 15 years ago, who proposed they should replace, respectively, ductal and lobular carcinoma in situ (DCIS and LCIS). This proposal has been slowly gaining ground. We argue that DCIS and LCIS should now be definitively abandoned. Bringing together ‘in situ’ and other entities into the simpler and more logical DIN/LIN framework–as has been done with intraepithelial neoplasias of cervix, vagina, vulva, prostate, and pancreas–would eliminate the artificial and illogical distinctions between ‘not cancers’ (e.g. flat epithelial atypia, atypical ductal hyperplasia–now classified as low grade DIN) and ‘cancers’ (e.g. DCIS–now considered medium–high grade DIN). Elimination of the term ‘carcinoma’ from entities that cannot metastasize will reduce confusion among health professionals and patients, and contribute to reducing the risk of overtreatment, as well as reducing adverse psychological reactions in patients.

Autologous lipoaspirate grafting (ALAG) has become a widely used treatment in breast reconstruction after mastectomy (MST) or breast-conserving treatment (BCT), although there is an ongoing debate about its oncological safety. The aim of this systematic review was to identify, evaluate, and synthesize all clinical evidence examining the oncological risks associated with the procedure.An extensive electronic search was performed in PubMed, Embase, and the Cochrane Library using the keywords "breast" and "autologous lipoaspirate grafting" and synonyms.The search yielded a total of 269 unique hits. Twenty clinical trials investigated ALAG in breast reconstruction after cancer. Although nine of them provided oncological follow-up data, only one retrospective cohort and four case series were suitable for analysis. The former reported no significant differences in the locoregional recurrence (LRR) incidence rates between the intervention and control groups for patients with MST as well as BCT. A large multicenter case series reported LRR incidence rates of 1.35 and 2.19 for MST and BCT patients, respectively. The remaining two series were far smaller trials with shorter follow-up and reported no recurrences. No randomized, controlled trials were identified. Most of the available studies consisted of cohorts and case series with short follow-up and no control subjects.Although the first reports on cancer recurrence after ALAG are inconclusive, they show promising results. Whether lipoaspirate grafting promotes LRR in breast cancer patients is still unclear. To be able to answer this question, larger prospective trials with longer follow-up are needed.

Stacher E, Boldt V, Leibl S, Halbwedl I, Popper H H, Ullmann R, Tavassoli F A & Moinfar F (2011) Histopathology59, 549–555 Chromosomal aberrations as detected by array comparative genomic hybridization in early low-grade intraepithelial neoplasias of the breast Aims: Low-grade flat ductal intraepithelial neoplasia (DIN1a, flat epithelial atypia) is one of the earliest morphologically recognizable neoplastic lesions of the breast. Frequently, it occurs concomitantly with lobular intraepithelial neoplasia (LIN). We aimed to elucidate chromosomal aberrations in these early neoplastic breast lesions with the use of array comparative genomic hybridization analysis. Methods and results: Laser capture microdissection of 12 archival formalin-fixed, paraffin-embedded specimens harbouring foci of both DIN1a and LIN was performed. All analysed cases of DIN1a and LIN showed chromosomal gains and losses. The aberration encountered most often was loss of 16q, noted in seven DIN1a (70% of those successfully examined) and 10 LIN (91%) cases. The next most common alteration was a gain on 1q, noted in four DIN1a (40%) and seven LIN (64%) cases. Conclusions: The results show concurrent chromosomal aberrations of 1q gains and 16q losses in several cases with coexisting LIN and DIN1a. These aberrations are known to be common in low-grade invasive (ductal and lobular) carcinomas as well as in more advanced (conventional) types of low-grade ductal intraepithelial neoplasia (DIN) (low-grade ductal carcinoma in situ). Our results raise the possibility of similar molecular-genetic pathways in coexisting LIN and low-grade flat DIN.

In this article we will describe our proposed changes to the breast cancer tumor node metastasis (TNM) classification which, while retaining TNM structure to ensure backwards compatibility, will render it more useful and better able to accommodate future developments. We propose changing T to specify exact tumor size (a tumor of pathological diameter 1.7 cm would be pT1.7); changing N to specify the number of metastatic lymph nodes over the total number removed (e.g., pN5/21); adding suffixes to M to indicate metastatic site; removing in situ neoplasms from the classification, since they are not carcinomas and are incapable of metastasizing; and removing the terms ‘infiltrating’ and ‘invasive’ since they are redundant. Finally, we would include hormone receptor, HER2, and other biological indicators of prognosis, as they are verified, in a placeholder system appended to the TNM. These proposals shift the emphasis from the quantity of tumor present to the quality of the cancer.

Az elmúlt évtizedekben az emlőpatológia mind klasszikus, mind modern, molekuláris patológiai értelemben óriási fejlődésen ment keresztül. Ismereteink gyarapodását az előbbi vonatkozásában a széles körű szűrővizsgálatok bevezetése, az utóbbi vonatkozásában a patológiában zajló molekuláris technikai „forradalom” segítette elő. Ez az állandóan gyarapodó tudás a fogalmaink, a régóta használt osztályozások és legfőképpen a szemléletünk változását eredményezte. A ductalis és lobularis in situ carcinomák, vagy a ma egyre inkább terjedő szóhasználattal intraepithelialis neoplasiák összefoglaló ismertetésével a patológiában jelenleg érvényes nézeteket és álláspontokat szeretném közreadni.

Reduction mammoplasty is a frequently performed procedure for the treatment of macromastia and for the achievement of symmetry in breast cancer patients following lumpectomy. Slides from 516 consecutive bilateral reduction mammoplasties performed for macromastia over 15 years were reviewed. Among these, 92 (18%) low-risk ductal intraepithelial neoplasia/intraductal hyperplasia, 28 (5%) ductal intraepithelial neoplasia 1 (1 low-grade ductal carcinoma in situ, 11 atypical intraductal hyperplasia, and 16 flat type), 17 (3%) lobular intraepithelial neoplasia, and 1 (0.2%) tubular carcinoma were identified. The patients were categorized into 3 age groups

Breast lesions classified as of uncertain malignant potential (B3) on biopsy form a diverse group of abnormalities, which pose a diagnostic and management challenge. In this paper, we discuss the imaging and pathology features as well as the management of the most controversial B3 lesions, consisting of papillary lesions, complex sclerosing lesions/radial scars, lobular intraepithelial neoplasia, and atypical epithelial proliferation of ductal type. As there is an association with malignancy at the time of diagnosis, as well as an increase in the risk of subsequent development of cancer, a multidisciplinary discussion is almost always required to tailor treatment.

The term lobular neoplasia (LN) includes lobular carcinoma in situ (LCIS) and atypical lobular neoplasia (ALH). It is generally considered to be a risk lesion and a non-obligatory precursor for the subsequent development of an invasive carcinoma in the ipsilateral or contralateral breast. LN has also been termed lobular intraepithelial neoplasia (LIN). A grading system (LIN 1-LIN 3) has been suggested as a tool for a more precise estimation of the individual risk. When LN is the most significant finding in a core biopsy, the probability of a higher grade lesion is about 17% in the follow-up surgical biopsy, justifying follow-up surgery in the majority of cases. A higher risk of progression is attributed to LIN 3 (pleomorphic LN, extensive LN, and signet ring cell LN) compared to LIN 1 or LIN 2. These special forms of LN may have an unusual presentation clinically or histologically. Using immunohistology, LN are characterized by the loss of E-cadherin, low proliferative activity and by positive hormone receptor status. The molecular characteristics of LN are similar to those of invasive lobular carcinomas, indicating the nature of LN as a precursor lesion.

Ductal intraepithelial neoplasia (DIN) is descriptive of in situ breast lesions from usual ductal hyperplasia (UDH) to advanced ductal carcinoma in situ (DCIS). A total of 2628 cases of DIN diagnosed at the Armed Forces Institute of Pathology were separated based on their grade. These were assessed for the presence of invasive carcinoma (ductal or lobular) and lobular intraepithelial neoplasia (LIN) grades 1-3. The frequency of invasive cancer (ductal and lobular) appearing with DIN increased with increasing DIN grade from 2% in low-risk DIN (UDH) to 37% in DIN 2-3 (DCIS grades 2-3). The frequency of these invasive carcinomas, which were either lobular or displayed lobular features, however, decreased with increasing grade of DIN with a peak of 28% in DIN 1-flat type, (flat epithelial atypia) to a low of 2% in DIN 3. Likewise, the frequency of LIN appearing with DIN decreased as the grade of DIN increased, with a peak of 26% in DIN 1-flat type to a low of 9% in DIN 3. Lower-grade LIN 1 comprised 14% of the LIN in low-risk DIN cases, but only 4% of the LIN seen in DIN 3 cases. Conversely, higher-grade LIN 3 comprised only 6% of the LIN seen in low-risk DIN cases, while accounting for 15% of the LIN in DIN 3 cases. The frequency of invasive carcinoma in DIN 1 ranged from 4% in quantitatively limited DIN 1 less than or equal to 2 mm (atypical ductal hyperplasia) to 27% among the more abundant DIN 1 greater than 2 mm (DCIS grade 1). The frequency of LIN associated with DIN 1 less than or equal to 2 mm was 13.4%, and the frequency of LIN associated with DIN 1 greater than 2 mm was 16.6% when there was no DIN 1-flat type present. However, the frequency of the LIN seen in combination with DIN 1-flat type was reduced by 50% as the quantity of DIN exceeded 2 mm. Based on this retrospective analysis of DIN, we noted that: (1) invasive carcinoma is most frequently associated with the higher grades of DIN; (2) the grade of LIN parallels the grade of coexisting DIN; (3) a relationship exists between DIN 1-flat type and the occurrence of LIN and (4) this relationship in association with DIN less than or equal to 2 mm is not maintained in DIN greater than 2 mm.

After publication of our article [1], it has come to our attention that Professor Cesare Formisano was incorrectly excluded from the list of authors in the initial version of this manuscript. We publish this correction to update the author list to include Professor Formisano as an author. The correct author list is as follows

copyrighted material, used by arrangement with john wiley & sons limited. for personal use only, must not be reproduced or shared with third parties. anyone wishing to reproduce this content in whole or in part, in print or in electronic format, should contact digitalrightsuk@wiley.com browse the abc series at www.wiley.com ### Overview Two main types of non-invasive (in situ) cancer can be recognised from the histological pattern of disease and cell type (Table 1). Ductal carcinoma in situ is the most common form of non-invasive carcinoma, making up 3–4% of symptomatic and 20–25% of screen-detected cancers. It has increased in frequency because of the widespread use of screening mammography (Figure 1). The increase is across all age groups, with a 12% annual increase in the 30–39-year age group and an 18.1% annual increase in women over the age of 50. Ductal carcinoma in situ is characterised by distortion, distention and complete involvement by a similar and neoplastic population of cells of adjacent ducts and lobular units (Figure 2). By contrast, lobular carcinoma in situ, now known as lobular intraepithelial neoplasia (LIN), which incorporates what was previously known as lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH), is rare (

To evaluate the underestimation rate and clinical relevance of lobular neoplasia in vacuum-assisted breast biopsy (VABB).A total of 161 cases of LN were retrieved from 6,435 VABB. The histological diagnosis was ALH (atypical lobular hyperplasia) in 80 patients, LCIS (lobular carcinoma in situ) in 69 patients and PLCIS (pleomorphic lobular carcinoma in situ) in 12 patients. Seventy-six patients were operated on within 2 years after VABB and 85 were clinically and radiologically monitored. The mean follow-up was 5.2 years, and the prevalence of malignancy was evaluated in the group of 85 patients.The clinico-pathological characteristics significantly favouring surgery were larger lesions, occurrence of a residual lesion following VABB and histological LCIS and PLCIS subtypes. The VABB underestimation rate as compared to surgery was 7.1% for ALH, 12% for LCIS and 50% for PLCIS. Overall, 11 of the 148 patients included in this survival analysis developed an ipsilateral tumour.Although obtained retrospectively in a relatively small series of patients, our data suggest that only patients with a diagnosis of PLCIS in VABB should be treated with surgery, whereas patients with ALH and LCIS could be monitored by clinical and radiological examinations.• The treatment of ALH and LCIS in VABB is still debated • Some authors favour radical treatment and others a more conservative approach • Only patients with PLCIS in VABB should be treated by surgery.

Background Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer. Case presentation A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. Conclusions The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating follow-up. According to our experience, when patients are older than 40 years and have a familial history of breast cancer, we prefer to carry out lumpectomy with follow up to avoid the risk of underestimation in situ foci within the lump.

International audience; AIM: Determination of the prevalence, of the radiological and clinical characteristics, and outcome of atypical hyperplasia (AH) of the breast within a population subjected to routine screening (double-view mammography with double reading, performed every two years between 50 and 75 years of age). PATIENTS AND METHODS: The clinical and radiological records and histological findings of percutaneous and surgical biopsy specimens of sixty-eight patients presenting with AH were reviewed together with patient follow-up data after percutaneous and surgical biopsy. RESULTS: AH incidence in the population was 0.19‰ with the following distribution of lesions: atypical epithelial hyperplasia (AEH, 53%), columnar cell metaplasia with atypia (CCMA, 32%), and lobular intraepithelial neoplasia (LIN, 8%). The mean patient age was 58 years and 24% of patients were receiving hormone replacement therapy. The main radiological finding was the presence of microcalcifications for AEH and CCMA lesions in particular, and the mammograms were valid (correlation between American College of Radiology score and risk of lesion, only 3% of lesions were recognized on the second reading). A total of 13.7% of AH cases were underestimated and a real risk of AH progression was observed, regardless of whether or not surgical biopsy had been performed. CONCLUSION: The clinical and radiological characteristics of AH observed in a population subjected to routine breast cancer screening are identical to those for patients with the same lesions referred to specialist centers. Surgical biopsy remains the recommended option due to the risk of underestimation of lesions by percutaneous biopsy and the risk of progression justifies the need for continued close monitoring.

Objective Lobular intra-epithelial neoplasia (LIN) is a rare breast disease that has been regarded alternately as a risk factor for invasive breast cancer in both breasts or a true breast cancer precursor. The controversy is largely dependent on the estimation of the IBC (Invasive Breast Cancer) risk after LIN; however a systematic review of the published data has not been previously performed. We aimed to review the IBC after LIN and the characteristics of those cancers. Methods A PubMed search was performed to identify the published articles in English addressing the breast cancer risk after LIN. Results There was a wide range in the figures estimating the risk of the breast cancer among the 22 studies that form the basis of this review. The cumulative average risk of invasive breast cancer (IBC) was 8.7% (range 0–33). It was 4.7% (range 0–25) for the ipsilateral and 4.2% (range 0–16) for the contralateral breast. 52% of the breast cancers occurred more than 10 years after the initial LIN. A lobular histotype was present in 30% (range 0–67%) of all IBC. Conclusions LIN should be considered both as a risk factor (low and similar level of IBC risk for both breasts, long delay between LIN and IBC) and a precursor for IBC (over-representation of lobular histotype).

Due to a transcription error, the author names in the article entitled “Underestimation rate of lobular intraepithelial neoplasia in vacuum-assisted breast biopsy”, were incorrectly published. We would like to clarify that the author list should read as follows: Meroni S, Bozzini AC, Pruneri G,Moscovici OC,Maisonneuve P, Menna S, Penco S, Meneghetti L, Renne G, Cassano E. We apologise for this error in the author list; the error was multifactorial.