Pleomorphic Lobular Carcinoma Research Articles

Morphological parameters of lobular in situ neoplasia in stereotactic 11‐gauge vacuum‐assisted needle core biopsy do not predict the presence of malignancy on subsequent surgical excision

The management of lobular in situ neoplasia (LN) when diagnosed on core biopsy remains a controversial issue. The present study aimed to investigate the association between morphological parameters of LN on vacuum-assisted needle core biopsy (VANCB) and the presence of malignancy (ductal carcinoma in situ, pleomorphic lobular carcinoma in situ, or invasive carcinoma) at surgical excision (SE). The study included 14 pathology departments in Italy. Available slides from 859 cases of VANCB reporting an original diagnosis of flat epithelial atypia, atypical ductal hyperplasia or LN, all with subsequent surgical excision, were reviewed. Overall, 286 cases of LN, pure or associated with other lesions, were identified, and a malignant outcome was reported at excision for 51 cases (17.8%). Among the 149 cases of pure LN, an increased risk of malignancy emerged in women in mammographic categories R4-R5 as compared with those in categories R2-R3 (OR 2.46; P=0.048). In the series, a statistically significant decreased malignancy risk emerged among cases without determinant microcalcifications (P=0.04). Our results suggest that the diagnosis of pure LN on VANCB warrants follow-up excision, because clinicopathological parameters do not allow the prediction of which cases will present carcinoma at surgical excision.

Proteomics of Genetically Engineered Mouse Mammary Tumors Identifies Fatty Acid Metabolism Members as Potential Predictive Markers for Cisplatin Resistance

In contrast to various signatures that predict the prognosis of breast cancer patients, markers that predict chemotherapy response are still elusive. To detect such predictive biomarkers, we investigated early changes in protein expression using two mouse models for distinct breast cancer subtypes who have a differential knock-out status for the breast cancer 1, early onset (Brca1) gene. The proteome of cisplatin-sensitive BRCA1-deficient mammary tumors was compared with that of cisplatin-resistant mammary tumors resembling pleomorphic invasive lobular carcinoma. The analyses were performed 24 h after administration of the maximum tolerable dose of cisplatin. At this time point, drug-sensitive BRCA1-deficient tumors showed DNA damage, but cells were largely viable. By applying paired statistics and quantitative filtering, we identified highly discriminatory markers for the sensitive and resistant model. Proteins up-regulated in the sensitive model are involved in centrosome organization, chromosome condensation, homology-directed DNA repair, and nucleotide metabolism. Major discriminatory markers that were up-regulated in the resistant model were predominantly involved in fatty acid metabolism, such as fatty-acid synthase. Specific inhibition of fatty-acid synthase sensitized resistant cells to cisplatin. Our data suggest that exploring the functional link between the DNA damage response and cancer metabolism shortly after the initial treatment may be a useful strategy to predict the efficacy of cisplatin.

Atypical epithelioid cell myofibroblastoma of the breast with multinodular growth pattern: A potential pitfall of malignancy

Myofibroblastoma (MFB) of the breast is the prototypical benign spindle cell tumor arising from the mammary stroma. Over the last two decades, several morphological variants of this tumor have been recognized. Epithelioid cell MFB is composed predominantly of neoplastic elements with epithelioid morphology. It represents a potential diagnostic pitfall of malignancy, especially when evaluating small biopsies. We report a unique case of a mammary epithelioid cell MFB composed of large mono- to multi-nucleated cells showing mild to moderate nuclear pleomorphism, predominantly arranged in a multinodular growth pattern. This tumor needs to be distinguished from invasive apocrine, oncocytic, pleomorphic lobular carcinoma, as well as metastases. Immunohistochemistry revealed the fibroblastic/myofibroblatic (positivity for vimentin, desmin, CD34 and focally for α-smooth muscle actin) nature of proliferating cells, and therefore was crucial for a correct diagnosis.

Abstract 1204: Heterogeneity within triple-negative breast cancer (TNBC).

Abstract Background: TNBC refers to those breast cancers which are negative for ER, PR and Her2/neu overexpression, thereby unsuitable for hormone and trastuzumab therapy. Although TNBC overlap with basal-like breast cancers, these terms are not synonymous. We decided, in a single institution cohort, to develop a better understanding of the types of tumors that make up TNBC Materials and Methods: We carried out a clinicopathological study of a cohort of 192 patients diagnosed with TNBC at the University Health Network in 2007. Patient biodata, clinical and histopathological information of proven prognostic importance was retrieved from the records. Tissue microarrays were constructed from duplicate 0.6mm cores of representative tumour tissue and stained with 9 antibodies according to recommended protocols. The TMA slides were interpreted using the Allred method except for the Ki67 staining which was interpreted by the visual estimate method of assessing proportion of nuclei taking up stains. Results were tabulated and summary statistics was done to determine proportions. Results: The age-range is 28 - 99 years. The median and modal age group was 50 -59 years. 70.3% of the patients are aged between 40 and 69 years at the time of diagnosis. The tumour size range was 0.6cm to 16 cm. 41.67% are pT1, 51.04% are pT2 while 6.8% are pT3. Four patients had T4 tumor with skin and nipple involvement. The diagnosis was predominantly invasive ductal carcinoma (IDC) in 84.9% of patients. Metaplastic carcinoma (10.4%), pleomorphic lobular carcinoma (1.5%), and single cases of invasive lobular carcinoma (ILC), tubular, apocrine and poorly differentiated carcinoma were seen. DCIS is a prominent feature in 26.6% of the cases. The number of lymph nodes identified ranged from 0 - 46. 59.90% were in pN0 category, 16.7% in the pN1 category, pN2 - 8.3%, and 15.1% in pN3 category. Extra-nodal metastasis at diagnosis was found in 7.3% of patients. The tumour grade: Grade I - 1.55%, Grade II - 13.47% and Grade III 84.97%. CD44 was positive in 17.71%, p63 - 4.17%, p53 - 51.56%, e-cadherin - 81.77%, Vimentin - 77.60%, Cyclin D1 - 22.40%, BCL-2 - 19.27%, and androgen receptor (AR) - 5.73%. 43.75% of cases show proliferation rates of ≥15%, while 26.04% have proliferation rates of between 5% and ≤14%. Conclusion: While a large proportion of TNBCs show a high proliferation (Ki67, Cyclin D1 and grade III), a substantial number did not show this. This study provides clues to support the current hypothesis that several mechanisms drive the carcinogenesis of TNBC, with a heterogeneous pattern of biomarker expression. Further investigation is needed to better understand the factors driving the development and progression of the different types of TNBC. Citation Format: Adewunmi O. Adeoye, Bruce J. Youngson, Naomi Miller, Susan J. Done. Heterogeneity within triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1204. doi:10.1158/1538-7445.AM2013-1204

Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade?

Pleomorphic lobular carcinoma is regarded as a biologically aggressive variant of invasive lobular carcinoma of the breast. However, there is no consensus on the definition and whether this subtype adds useful information to histological grade. Two-hundred and two grade 2 or grade 3 invasive lobular carcinomas were studied. Tumours were categorised according to the components of histological grade: tubules, pleomorphism and mitoses. Pleomorphic lobular carcinoma was defined as a carcinoma with a lobular growth pattern and marked nuclear pleomorphism (pleomorphism 3). Breast cancer-specific survival was used in analysis of prognosis. Grade 3 pleomorphic lobular carcinomas (tubules 3, pleomorphism 3, mitoses 2 and tubules 3, pleomorphism 3, mitoses 3) had a worse prognosis than grade 2 (tubules 3, pleomorphism 2, mitoses 1) carcinomas. Grade 2 lobular carcinomas with marked nuclear pleomorphism (tubules 3, pleomorphism 3, mitoses 1) had a similar prognosis to grade 2 carcinomas with moderate pleomorphism (tubules 3, pleomorphism 2, mitoses 1). Survival was associated with mitotic score, but not with nuclear pleomorphism on both univariate and multivariate analysis. A non-classical growth pattern was seen more frequently in all subgroups with marked nuclear pleomorphism and was associated with worse survival. Histological grade and nodal status were independent of prognostic factors. This study shows that histological grade (in particular the mitotic component) in invasive lobular carcinomas is of prognostic importance, but pleomorphic type does not provide useful additional prognostic information.

Challenges in the management of pleomorphic lobular carcinoma in situ of the breast

BackgroundPleomorphic Lobular Carcinoma in Situ (PLCIS) is a pathological variant of Lobular Carcinoma in Situ (LCIS) with distinct features. Since first described over a decade ago there are only few papers published about this condition. MethodsMedline and Pubmed based literature overview was done with the aim of describing the different histopathological, radiological and clinical features of this pathological entity to highlight the different clinicopathological presentations and modalities of treatment described. ResultsPLCIS has different biological features when compared to LCIS. It is more likely to be associated with invasive disease and the immuno-histochemical profile shows it is less likely to be ER and PR positive with higher positivity of HER2, Ki-67and p53. It has been suggested that PLCIS should be treated more aggressively than LCIS and surgically excised in similar fashion to DCIS. ConclusionPLCIS is a more aggressive variant of LCIS that needs to be managed differently. Surgical excision with clear margins is advised. Further adjuvant treatments have been described in the literature with little evidence to support their use.

Amyloidosis of the Breast with Multicentric DCIS and Pleomorphic Invasive Lobular Carcinoma in a Patient with Underlying Extranodal Castleman’s Disease

We present an interesting case of focal amyloidosis of the left breast which was intermixed with ductal carcinoma in situ (DCIS). On subsequent staging bilateral breast magnetic resonance imaging (MRI), the patient was found to have an additional suspicious enhancing mass with spiculated borders within the left breast. This mass was biopsy proven to represent pleomorphic invasive lobular carcinoma. A pulmonary nodule within the lingula was also noted on the staging bilateral breast MRI and was biopsy proven to represent extranodal Castleman's disease. Therefore, it is believed that our patient had secondary amyloidosis due to Castleman's disease.

Lobular neoplasia of the breast: review

Lobular neoplasia of the breast refers to lesions characterized by atypical lobular hyperplasia and by lobular carcinoma in situ. Lobular neoplasia is not only a risk factor but a non-mandatory precursor for the development of invasive carcinoma. Pleomorphic lobular carcinoma in situ is a subtype of lobular neoplasm with an aggressive behavior and high nuclear grade that can mimic high-grade ductal carcinoma in situ. Management and monitoring the patients with lobular neoplasm is controversial, especially when diagnosis is made through core biopsy. Molecular and genomic studies have been able to identify genes that can dispel doubts as to its pathogenesis and allow an approach that may lead to safer and more appropriate therapeutic approaches. This review seeks to describe the most up-to-date approaches to lobular neoplasia of the breast.

Abstract P6-06-04: p53 and p16 as Modifiers of HERV-K in Invasive Pleomorphic Lobular Carcinoma and Classic Lobular Carcinoma of Breast

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-06-04.

Breast Surgeon's Survey: No Consensus for Surgical Treatment of Pleomorphic Lobular Carcinoma In Situ

The Breast JournalVolume 19, Issue 1 p. 116-118 Letter to the Editor Breast Surgeon's Survey: No Consensus for Surgical Treatment of Pleomorphic Lobular Carcinoma In Situ Sarah L. Blair MD, Corresponding Author Sarah L. Blair MD University of California, San Diego, CaliforniaAddress correspondence and reprint requests to: Sarah L. Blair, MD, Moores UCSD Cancer Center, 3855 Health Science Dr, La Jolla, CA 92093-0987, USA, or e-mail: [email protected].Search for more papers by this authorDerek K. Emerson MD, Derek K. Emerson MD University of California, San Diego, CaliforniaSearch for more papers by this authorSwati Kulkarni MD, Swati Kulkarni MD The University of Chicago, Chicago, IllinoisSearch for more papers by this authorE. Shelley Hwang MD, MPH, E. Shelley Hwang MD, MPH Duke University Durham, Durham, North CarolinaSearch for more papers by this authorVanessa Malcarne PhD, Vanessa Malcarne PhD San Diego State University, San Diego, CaliforniaSearch for more papers by this authorDavid W. Ollila MD, David W. Ollila MD University of North Carolina, Chapel Hill, North CarolinaSearch for more papers by this author Sarah L. Blair MD, Corresponding Author Sarah L. Blair MD University of California, San Diego, CaliforniaAddress correspondence and reprint requests to: Sarah L. Blair, MD, Moores UCSD Cancer Center, 3855 Health Science Dr, La Jolla, CA 92093-0987, USA, or e-mail: [email protected].Search for more papers by this authorDerek K. Emerson MD, Derek K. Emerson MD University of California, San Diego, CaliforniaSearch for more papers by this authorSwati Kulkarni MD, Swati Kulkarni MD The University of Chicago, Chicago, IllinoisSearch for more papers by this authorE. Shelley Hwang MD, MPH, E. Shelley Hwang MD, MPH Duke University Durham, Durham, North CarolinaSearch for more papers by this authorVanessa Malcarne PhD, Vanessa Malcarne PhD San Diego State University, San Diego, CaliforniaSearch for more papers by this authorDavid W. Ollila MD, David W. Ollila MD University of North Carolina, Chapel Hill, North CarolinaSearch for more papers by this author First published: 10 December 2012 https://doi.org/10.1111/tbj.12062Citations: 23 Accepted for Presentation at the 64th Annual Cancer Symposium March 2–5, 2011, San Antonio TX. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume19, Issue1January/February 2013Pages 116-118 RelatedInformation

Microcalcification Is an Important Factor in the Management of Breast Intraductal Papillomas Diagnosed on Core Biopsy

The follow-up excision (FUE) results were analyzed from 370 cases diagnosed as intraductal papilloma on breast core needle biopsy (CNB) with no history of malignancy or other risk factors. Of these cases, 98.6% were rendered a Breast Imaging Reporting and Data System score of 4 on mammography before the CNB. Fifty-one cases (13.8%) were found to have microcalcifications on microscopic examination of CNB. A total of 7 (1.9%) of 370 cases were upgraded to invasive carcinoma, ductal carcinoma in situ, or pleomorphic lobular carcinoma in situ on FUE. Six of 51 (11.8%) cases with microcalcifications found on imaging and CNB were upgraded to ductal carcinoma in situ or invasive carcinoma, whereas only 1 (0.3%) of 319 cases without microcalcifications was upgraded to pleomorphic lobular carcinoma in situ (P = .003). Results of a multivariate analysis adjusted for age confirmed that microcalcifications was a risk factor for upgrading to cancer, independent of age. Our results indicate that surgical excision is required for intraductal papilloma diagnosed on CNB if microcalcifications are present. However, excision may not be required for those who have no microcalcifications on CNB and no other known risk factors.

Local Regional Recurrence Among Patients With Pleomorphic Lobular Carcinoma In Situ: Is There a Role for Radiation Therapy?

Local Regional Recurrence Among Patients With Pleomorphic Lobular Carcinoma In Situ: Is There a Role for Radiation Therapy?

Infiltrating Lobular Carcinoma of the Breast: A Series of 843 Patients From the National Cancer Institute – Brazil

INTRODUCTION: The infiltrating lobular carcinoma (ILC) is less common than infiltrating ductal carcinoma, comprises approximately 10% of breast cancers. The prognostic implications of its clinicopathologic characteristics remain controversial. OBJECTIVE: Describe the clinical and pathological features of 843 patients with infiltrating lobular carcinoma of the breast in a single institution. METHODS: Retrospective analysis of a large series of cases diagnosed with infiltrating lobular carcinoma (ILC)of the breast at a National Cancer Institute (INCA), between 2000 to 2009. Data were obtained from Cancer Hospital Registry and supplemented by the medical records. Variables collected were related to socio-demographic factors, clinical features, pathology, treatment and follow-up. Descriptive analysis was conducted using central tendency measures for continuous variables and absolute and relative frequencies for categorical variables. This study was approved by INCA’s research and ethics committee. RESULTS AND DISCUSSION: The mean patient’s age at diagnosis was58. 6 years (sd 13. 2). The clinical stage IIIB was the most frequent (24.5%) followed by IIA (23. 3%) and IIB (16. 8%). There were 14. 6% well-differentiated (grade 1) tumors, 57. 3% moderately differentiated (grade 2) tumors, and 28. 1% poorly differentiated (grade 3) tumors. Estrogen receptor positivity was documented in 87. 2% of the cases and progesterone in 71.5%. The mixed lobular carcinoma was presented by 12. 9% and pleomorphic in 13. 6%. The neo adjuvant therapy was performed by 37. 7% of the cases and surgery by 85. 2% (of this, 75. 0% was mastectomy). The sentinel lymph node was performed by 22. 8%, with an average of lymph nodes removed of 2. 3 (sd 1. 4) and metastasis detected in 0.5 (sd 0. 9). The lymphadenectomy was made in 75. 2%, with a mean of lymph nodes removed of 18. 0 (sd 6. 7) and lymph node metastases in 4. 0 (sd 6. 9). The mean follow up time was 64, 27 months (sd 33, 76), with 35, 7% of metastasis and 30, 2% of deaths occurredin the period. Infiltrating lobular carcinoma can have disagreement about prognostic. The different clinicopathologic features of this entity may reflect this disagreement. CONCLUSION: The results of the current study demonstrated the clinicopathologic features of ILC, and the prognosis do not seems to be better than do patients with invasive ductal carcinoma. The pleomorphic lobular carcinoma was associated with more aggressive behavior but the treatment decisions should be based on individual patient and tumor biologic characteristics, and not only on lobular histology.

Is Excisional Biopsy Required After a Breast Core Biopsy Yields Lobular Neoplasia?

The management of lobular neoplasia (LN) on percutaneous core breast biopsies remains controversial. Published upgrade rates after surgical excision vary widely. This study aims to determine the frequency of malignancy following excision in patients with LN found on core biopsy. Our study identified patients from December 2005 through December 2010 with LN as the highest-risk lesion on core biopsy. Patients with flat epithelial atypia on core biopsy were not excluded. Per institutional policy, excision was routinely recommended. An upgrade from the core biopsy of LN was defined as excisional biopsy pathology that revealed ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), or invasive lobular carcinoma (ILC). Between December 2005 and December 2010, 4472 percutaneous breast biopsies were performed, with 71 patients (1.5%) having LN as the highest-risk lesion on core biopsy. Sixty-seven patients (94%) underwent excision. The upgrade rate on excisional biopsy was 16% (11/67 patients), with the type of malignancy on excisional biopsy pathology as follows: DCIS, 36% (4/11); IDC, 18% (2/11); and ILC, 45% (5/11). All patients with pleomorphic lobular carcinoma in situ on core biopsy who proceeded to excision were upgraded to malignancy. After excluding patients with discordant results, patients with pleomorphic lobular carcinoma in situ, and patients with flat epithelial atypia on core biopsy, the upgrade rate of pure LN on excisional biopsy was 9%. LN on core biopsy warrants excisional biopsy given the upgrade rate to malignancy.

Perspectives for Improved and More Accurate Classification of Canine Mammary Gland Neoplasms

We read with particular interest the article by Dr Goldschmidt and colleagues entitled ‘‘Classification and Grading of Canine Mammary Tumors,’’ which was published in Veterinary Pathology. It was a very interesting subject since mammary neoplasms are very important tumors in veterinary medicine because they are the most common neoplasms of intact adult female dogs and have high importance in countries in which dogs are not routinely spayed, such as many European and South American countries. We know that histologic examination of canine mammary gland nodules is the current standard to distinguish benign from malignant epithelial or complex tumors and to classify histologic subtypes, making new data regarding such features such as those provided in Dr Goldschmidt and colleagues’ article very useful. However, there are still some histotypes that are currently recognized in the literature that were not discussed in such article. The morphologic spectrum of mammary neoplasms in canine species is generally quite different from that seen in humans. However, the increase in reports regarding histologic types of mammary tumors occurring in dogs with a striking similarity with their human counterpart has been raising the interest of veterinary pathologists and clinicians about the possibility of facing distinct subtypes with particular and/or aggressive behavior. In our diagnostic services, we have frequently observed certain discrepancies between the last World Health Organization histologic classification for canine mammary neoplasms (CMNs) by Misdorp and colleagues, particularly regarding the so-called rare histotypes, which are not discussed. Classifying conventional CNMs such as papillary and tubular types poses no difficulty, as those morphologic variants are widely recognized in both mammary and other epithelial tumors. However, diagnosing rare histotypes that are not commonly discussed in the veterinary literature many times requires knowledge usually gained by systematically evaluating women’s breast neoplasms, which have a more recent histologic classification that discusses some rare histotypes that can be also observed in dogs. Since histologic evaluation is still the main diagnostic criterion for CMNs and is performed before chemotherapy institution, a new histologic classification is highly desirable, particularly because more than 10 years have passed since its publication and many new data regarding CNMs have been documented in the veterinary literature. Different neoplasms that were not discussed by Misdorp and colleagues’ classification are being more and more published in the veterinary literature, such as micropapillary carcinomas, mammary neoplasms with sebaceous differentiation, lobular carcinomas of the mammary gland, and pleomorphic lobular carcinomas. Important information regarding those tumors were recently published in an useful review. Rare histotypes of CMNs usually have different behavior from the tumors discussed in the Misdorp and colleagues classification, which makes the proposition of a new classification scheme even more important since veterinary pathologists can provide valuable information for practitioners by making a more accurate diagnosis. Given this scenario, a question arises: Isn’t it time to review the canine mammary tumors’ histologic classification? To address this issue, it is necessary to establish guidelines for the diagnosis of canine mammary tumors. Articles such as the one written by Webster and colleagues are good models. These articles represent a consensus statement in veterinary oncology made by veterinary pathologists and oncologists from around the world and constitute an important basis for producing relevant new material regarding canine mammary tumor classification.

Pleomorphic lobular carcinoma in situ: A distinct entity of controversial significance.

177 Background: Pleomorphic lobular carcinoma in situ (PLCIS) is an increasingly diagnosed variant of lobular carcinoma in situ. Histologically, it resembles ductal carcinoma in situ (DCIS), leading to controversy over proper management. Yet, the natural history of PLCIS is unknown. Here we describe our experience with PLCIS. Methods: Review of pathology reports (1995–2012) identified 233 cases of LCIS variants. Patients with synchronous ipsilateral DCIS or invasive cancer (IC) were excluded leaving 25 cases for review. Consensus review by 3 pathologists further excluded 7; leaving 18 cases, 12 of which were classified as PLCIS and 6 as LCIS with pleomorphic features (LCIS-PF). (Table) PLCIS was defined by cellular dyshesion, nuclear pleomorphism with a 2-3 fold size variation, conspicuous nucleoli, mitoses and abundant cytoplasm; lesions not meeting all parameters were classified as LCIS-PF. Loss of e-cadherin was confirmed; clinical data were obtained from medical records. Results: Mean patient age at diagnosis of PLCIS/LCIS-PF was 57 yrs (42-67 yrs). All cases presented with imaging abnormalities. A previous history of breast cancer was present in 7/18 (39%) pts (3/7, ipsilateral; 4/7, contralateral). Following PLCIS/LCIS-PF diagnosis, 6/18 (33%) pts underwent mastectomy and 12/18 had excision alone, with (n=3) or without chemoprevention (n=9). Margin status was negative in 4/12 pts; close in 3/12 pts and positive in 5/12 pts undergoing excision. At a median follow-up of 27 mos (2-148 mos), 2/12 pts treated with excision developed ipsilateral breast cancer (1 DCIS; 1 IC). Both had close margins at initial excision; median time to cancer, 54 mos. Conclusions: Pure PLCIS is an uncommon lesion. Synchronous malignancy or prior history of breast cancer are often present in patients with PLCIS, contributing to the difficulty in determining the actual risk conferred by this lesion and appropriate management. Efforts to systematically characterize LCIS variants and prospective documentation of outcomes are needed to clarify the significance of these lesions. [Table: see text]

Are the imaging features of the pleomorphic variant of invasive lobular carcinoma different from classic ILC of the breast?

The aim of this study was to evaluate whether pleomorphic invasive lobular carcinoma (PILC) is different from classic invasive lobular carcinoma (CILC) in terms of radiologic and clinicopathologic features.We compared the radiologic and clinicopathologic features of 22 surgically confirmed PILCs in 21 patients from 2004 to 2009 and 47 CILCs from 47 consecutive patients. For all cases, we reviewed the imaging findings, medical records and pathological results.PILC had a higher T stage, N stage, nuclear and histologic grade compared to CILC. PILC was more commonly negative for estrogen receptors and positive for HER2 than CILC (all p < 0.05). However, there were no significant differences in age, symptoms, tumor size, extensive intraductal component, lymphovascular invasion, triple negative profile, or multiplicity between the two groups. PILC was not detected on mammography in 1 (4.5%) of 22 cases, whereas CILC was not detected on mammography in 7 (14.9%) of 47 cases and on MRI in 2 (5.0%) of 40 (p = 0.42 and p = 1.000, respectively). MRI identified more frequent multiplicity than mammography for both PILC and CILC (p < 0.001), but was similar to US (p = 0.066). Most lesions showed a spiculated mass or architectural distortion with or without calcifications on mammography and ultrasound. No differences in mass and/or non-mass lesions or kinetics on MRI were observed between the two groups.PILC shows more pathologically aggressive features, but cannot be differentiated from CILC based on imaging findings.

Cytohistological and immunohistochemical features of a mammary invasive pleomorphic lobular carcinoma in a dog

Departamento de Patologia, Faculdade de Medicina de Botucatu Universidade Estadual Paulista (UNESP), Distrito de Rubiao Jr., s/n Botucatu, Sao Paulo 18618-970

Adjuvant capecitabine for invasive lobular/mixed early breast cancer (EBC): USON 01062 exploratory analyses.

547 Background: Randomized phase III USON 01062 trial determining if patients with EBC would benefit from addition of capecitabine to docetaxel after AC (AC-T vs AC-XT). AC-T: docetaxel 100mg/M2 IV; AC-XT: docetaxel 75mg/M2 IV with capecitabine 825mg/M2 PO BID 14/7 days every 21days for 4 cycles. The primary endpoint, improvement in disease-free survival (DFS) at 5 years, was not met (HR=0.84, p=0.12) likely due to lower-than-expected event rate. The secondary endpoint, overall survival (OS), was improved with capecitabine (HR 0.68, p=0.01) (O’Shaughnessy, J. ASCO, 2011). Methods: Molecular analyses demonstrate that pleomorphic lobular (mixed lobular/ductal) carcinomas evolve from the same precursor and/or through the same genetic pathway as classical lobular cancers (Reis-Filho, J., J Path, 2005). We conducted exploratory analyses to evaluate the addition of adjuvant capecitabine in ductal vs lobular or lobular/ductal (mixed) EBC within USON 01062. Histology was classified according to local pathology assessment on patients’ primary cancers. Results: In ductal patients (n=2195), there was no difference in DFS (HR=0.92, p=0.48) and OS (HR=0.75, p=0.07) with AC-T vs AC-XT. In lobular/mixed patients (n=355), adding capecitabine improved DFS (HR=0.55, p=0.055) and OS (HR=0.38, p=0.04). There was no difference in DFS (HR=1.004, p=0.98) in the ER+ ductal patients (n=1258) with the addition of capecitabine. Conclusions: Ductal and lobular cancers have distinct histologic and molecular characteristics; lobular cancers are generally less sensitive to chemotherapy (Cristofanilli, M. JCO, 2005). This exploratory analysis suggests that patients with lobular/mixed EBC may benefit from adjuvant capecitabine. This hypothesis requires evaluation in other adjuvant capecitabine trials. [Table: see text]

Pleomorphic lobular carcinoma: a distinctive clinical and molecular breast cancer type

Pleomorphic lobular carcinoma (PLC) is an aggressive variant of invasive lobular carcinoma. The aim of this study was to redefine PLC in terms of molecular classification. Cases of PLC were selected between 1995 and 2010. Key clinicopathological features were recorded for most of the patients. A panel of immunohistochemical stains including E-cadherin, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin (CK)5/6, CK14, CK17, anti-cytokeratin (CAM) 5.2, CD117, vimentin, epidermal growth factor receptor (EGFR), p53 and gross cystic disease fluid protein-15 (GCDFP-15) were performed. HER2 test by fluorescence in-situ hybridization (FISH) was also performed. The log-rank test was used for statistical analyses. Forty cases fulfilled the criteria for PLC (26 with available tissue). The median age was 61 years and median tumour size was 2.0 cm. There were five of 38 (13.2%) triple-negative cases. The basal type was seen in one of 25 cases (4%), which had a triple-negative phenotype. HER2 was amplified in 14 of 38 cases (35%). Older patients and negative hormonal receptor status correlated significantly with worse clinical outcome (P < 0.03). The 5-year recurrence-free and overall survival was 54.9% and 76.2%, respectively. Pleomorphic lobular carcinoma is a distinctive breast cancer subtype. It has hybrid clinicopathological characteristics of ductal and lobular carcinoma.