Breast Radiologists' Perceptions on the Detection and Management of Invasive Lobular Carcinoma: Most Agree Imaging Beyond Mammography Is Warranted.

OBJECTIVE: To determine breast radiologists' confidence in detecting invasive lobular carcinoma (ILC) on mammography and the perceived need for additional imaging in screening and preoperative settings. METHODS: A 16-item anonymized survey was developed, and IRB exemption obtained, by the Society of Breast Imaging (SBI) Patient Care and Delivery Committee and the Lobular Breast Cancer Alliance. The survey was emailed to 2946 radiologist SBI members on February 15, 2023. The survey recorded demographics, perceived modality-specific sensitivity for ILC to the nearest decile, and opinions on diagnosing ILC in screening and staging imaging. Five-point Likert scales were used (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree). RESULTS: Response rate was 12.4% (366/2946). Perceived median (interquartile range) modality-specific sensitivities for ILC were MRI 90% (80-90), contrast-enhanced mammography 80% (70-90), molecular breast imaging 80% (60-90), digital breast tomosynthesis 70% (60-80), US 60% (50-80), and 2D mammography 50% (30-60). Only 25% (85/340) respondents were confident in detecting ILC on screening mammography in dense breasts, while 67% (229/343) were confident if breasts were nondense. Most agreed that supplemental screening is needed to detect ILC in women with dense breasts (272/344, 79%) or a personal history of ILC (248/341, 73%), with 34% (118/334) indicating that supplemental screening would also benefit women with nondense breasts. Most agreed that additional imaging is needed to evaluate extent of disease in women with newly diagnosed ILC, regardless of breast density (dense 320/329, 97%; nondense 263/329, 80%). CONCLUSION: Most breast radiologists felt that additional imaging beyond mammography is needed to more confidently screen for and stage ILC.

Invasive lobular carcinoma metastasis to pancreas mimicking pancreatic signet ring cell carcinoma: A case report and systematic review of the literature.

Metastasis to the gastrointestinal tract is a rare instance in the natural history of breast cancer, usually in association with lobular histology and widespread dissemination of disease. We report the case of a 74-year-old woman with a history of invasive lobular carcinoma presenting with a pancreatic metastasis mimicking a primary pancreatic adenocarcinoma; we also present a systematic review of the relevant literature. The presentation of pancreatic metastasis in the setting of breast cancer is unspecific, and histology is of paramount importance for a correct diagnosis; surgical metastasectomy could be of some benefit in the correct clinical setting.

Axillary lymph node status and invasive lobular breast cancer : Analysis of the Clinical Tumor Register of the AGO Austria.

BACKGROUND: Invasive lobular carcinoma (ILC) represents the second most common type of invasive breast cancer (BC). Although ILC generally have good prognostic properties (positive estrogen receptor, ER, low tumor grade), they are generally diagnosed at a more advanced stage. The data on the axillary lymph node status in ILC compared to invasive ductal carcinoma (IDC) are considered controversial. Therefore, the aim of this study was to compare the pathological node stage (pN) between ILC and IDC in an Austria-wide register. METHODS: Data of the Clinical Tumor Register (Klinisches TumorRegister, KTR) of the Austrian Association for Gynecological Oncology (AGO) were retrospectively analyzed. Patients with primary early BC, invasive lobular or ductal, diagnosed between January 2014 and December 2018, and primary surgery were included. A total of 2127 tumors were evaluated and compared in 2 groups, ILC n = 303, IDC n = 1824. RESULTS: A total of 2095 patients were analyzed in the study. In the multivariate analysis, pN2 and pN3 were observed significantly more frequently in ILC compared with IDC (odds ratio, OR 1.93; 95% confidence interval, CI 1.19-3.14; p = 0.008 and OR 3.22; 95% CI: 1.47-7.03; p = 0.003; respectively). Other factors associated with ILC were tumor grades 2 and 3, positive ER, and pathological tumor stage (pT) 2 and pT3. In contrast, concomitant ductal carcinoma in situ, overexpression of the human epidermal growth factor receptor 2 (HER2), and a moderate and high proliferation rate (Ki67) were found less frequently in ILC. CONCLUSION: The data show an increased risk of extensive axillary lymph node metastasis (pN2/3) in ILC.

First diagnosed invasive lobular carcinoma of the breast combined with gastric metastasis and bone metastasis: a case report and review of the literature.

RATIONALE: Chinese women topped the list of new breast cancers, the first diagnosed gastric metastasis and bone metastasis is extremely infrequent. The clinical and pathological diagnosis of metastatic breast cancer is difficult. To our knowledge, this is the first reported case of the first diagnosis of breast cancer with both gastric metastasis and bone metastasis. CASE REPORT: The female patient was found to have abdominal distension for 15 days with nausea and vomiting. The patient underwent a gastroscopy at an outside hospital 4 days ago, showing: duodenal bulb changes, gastric retention and chronic non-atrophic gastritis. Gastroscopic biopsy showed chronic inflammation and edema of the duodenal mucosa with glandular hyperplasia. Conservative treatment was given with no relief of symptoms. She was seen in our hepatobiliary and pancreatic surgery department. After admission, palliative surgery was performed, and the swelling and surrounding involved tissues were taken for examination during surgery. The rapid pathological return could not exclude tumor lesions, and the postoperative pathology confirmed the diagnosis of invasive lobular carcinoma of the breast with gastric metastases, and the systemic examination revealed combined bone metastases. DIAGNOSIS: Pathology and immunohistochemistry(IHC), a whole-body bone scan confirmed the first diagnosis of breast cancer with both gastric and bone metastases. INTERVENTIONS: Palliative treatment with bisphosphonates and CDK4/6i (Palbociclib) in combination with AI (Exemestane) was administered. OUTCOMES: The patient is currently under regular evaluation and is being followed up.

Uncommon invasive lobular carcinoma with papillary architecture-clinicopathologic and molecular characterization with review of the literature.

Breast cancer is the most common malignancy in woman, and its associated mortality is still rising worldwide. Among all the different subtypes of breast cancer, invasive lobular carcinoma (ILC) is the second most frequent. Several histological variants of ILC currently exist such as solid, alveolar, pleomorphic, tubulo-lobular, and mixed types. Recently, a new variant of ILC with a papillary growth pattern has been described. Here, we make a review of the literature and report the sixth case of a woman suffering from this very uncommon variant. Of note, she had a concomitant axillary lymph node metastasis, a manifestation not yet described so far. Molecular analysis showed CDH1 and PIK3CA mutations, along with similar quantitative chromosomal alterations in both primary and metastasis. Because ILC and papillary carcinoma are managed differently, our aim here is to raise awareness among the pathologists to avoid misdiagnosis of this unusual variant and subsequent inappropriate treatment.

Molecularly Confirmed Female Donor-Transmitted Lobular Breast Cancer to Male following Renal Transplantation.

INTRODUCTION: Lobular breast cancer represents 10%-15% of breast cancers in women but is virtually nonexistent in men, related to the typical absence of the anatomic breast lobule structure in male breast tissue. We describe donor-transmitted metastatic lobular carcinoma to a male after kidney transplantation. Determining whether a post-transplant cancer is transplant associated, donor transmitted, or donor derived is significant for treatment, prognosis, and possibly management of other organ recipients. CASE REPORT: A 74-year-old Caucasian male presented to the emergency department with lower abdominal pain and macro-hematuria. Past medical history included two renal transplantations. Computed tomography identified a 4-5-cm space-occupying lesion in the native left kidney. A left native nephrectomy was performed. Histology pathologic examination demonstrated lobular (as opposed to ductal) breast carcinoma. Fluorescent in situ hybridization probes to identify X- and Y-chromosomes showed tumor cells with an XX genotype, whereas the surrounding host cells were of XY genotype. These findings confirmed the female-sex origin (donor) of the tumor within the XY native male (current patient) tissues. DISCUSSION/CONCLUSION: Due to discordance between the donor and recipient sex, fluorescent in situ hybridization as a molecular technique correctly identified the origin of an individual's cancer in the post-transplant setting. The metastatic breast cancer behaved more indolently than usually seen. Expanded criteria donors (ECD) are those who cannot donate under standard criteria for organ transplantation; expanded criteria widen the potential organ donor pool at the expense of increased risk for post-transplant complications (e.g., graft failure, the transmission of malignancy). The case provides a potential area of future research into considering allowing ECDs with a distant history of cancer with very low transmission risk when the biochemical environment of the recipient would, in the unlikely event of transmission, induce the tumor to pursue an indolent clinical course.

[From an enterovesical fistula to mammary carcinoma]. / Von einer enterovesikalen Fistel zum Mammakarzinom.

We report a case of a 83-year-old woman with the initial diagnosis of an occult invasive lobular breast carcinoma due to gastrointestinal metastasis with an entervesical fistula.

Lobular Neoplasia.

Lobular neoplasia (LN) is a term that describes atypical epithelial lesions originating in the terminal duct-lobular unit (TDLU) of the breast, including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS). LN is both a risk factor and nonobligate precursor to invasive breast cancer. A diagnosis of LCIS is associated with a 7-to-10-fold increased risk of breast cancer compared with the general population. When classic LN is diagnosed on a core needle biopsy (CNB), the patient may proceed with either increased screening or excisional biopsy of the lesion. Physicians should counsel patients diagnosed with LN on the risk of developing invasive carcinoma and inform them of the current screening and chemoprevention recommendations to reduce risk.

Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer.

BACKGROUND: There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC). METHODS: The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values. RESULTS: Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P < .001). Estrogen receptor-positive ILCs were of lower grade (grade 1 and 2: 90% in ILC vs 72% in IDC) but larger in size (T3 and 4: 14.3% in ILC vs 3.4% in IDC) (corrected P < .001), and since 1990, the mean ILC size detected at diagnosis increased yearly. Patients with estrogen receptor (ER)-positive ILC underwent statistically significantly more mastectomies compared with ER-positive IDC (57% vs 46%). Using Kaplan-Meier analysis, patients with ER-positive ILC had statistically significantly worse disease-free survival and overall survival than ER-positive IDC although 6 times more IDCs were classified as high risk by OncotypeDx Breast Recurrence Score assay. CONCLUSIONS: This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.

The Effect of PACS in Breast Tumor Diagnosis Based on Numerical Analysis.

The incidence and mortality rates are increasing year by year, and the incidence of the disease is gradually becoming younger. The purpose of this study was to investigate the clinical diagnostic value of PACS in breast tumor patients. Methods. 20 patients with breast tumor diagnosed by PACS were selected for the study, and the diagnosis was confirmed by pathological puncture or surgery. Results. The detection rates of breast tumor by MRI and CT were 94.44% and 96.67%, the sensitivities were 18.82% breast tumor and 96.67%, and the specificities were 53.84% and 54.54%, with no statistically significant difference (P > 0.05). There was no statistically significant difference in the detection rate of invasive lobular carcinoma (LDC) and PACS (P > 0.05). Conclusion. PACS has a greater detection rate for breast tumor and offers some diagnostic usefulness in diagnosing malignant breast tumor. The detection rate of breast tumors can be increased by selecting the most appropriate diagnostic tool for the patient's current circumstances.

The morphologic spectrum of lobular carcinoma in situ (LCIS) observations on clinical significance, management implications and diagnostic pitfalls of classic, florid and pleomorphic LCIS.

Lobular carcinoma in situ (LCIS) is a non-invasive proliferation of atypical dyscohesive epithelial cells characterized by loss or functional alteration of E-cadherin-mediated cell adhesion. The morphologic spectrum of LCIS encompasses classic (C-LCIS), florid (F-LCIS) and pleomorphic LCIS (P-LCIS), as recently defined by the World Health Organization (WHO) Expert Consensus Group. Atypical lobular hyperplasia (ALH) is also part of this spectrum.This article highlights the morphologic and immunohistochemical features of the three forms of LCIS and summarizes their management implications and prognosis, with emphasis on F-LCIS and P-LCIS.

Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials. RESULTS: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC. CONCLUSION: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST.

Avoiding "False Positive" and "False Negative" Immunohistochemical Results in Breast Pathology.

Immunohistochemistry (IHC) plays an important role in the evaluation of breast pathology specimens to provide both diagnostic and prognostic/therapeutic information. Although most IHCs used in breast pathology can be easily interpreted, pitfalls do exist, especially in some uncommon scenarios. This review intends to focus on the challenging areas such as the interpretation of myoepithelial cell markers in differentiating benign proliferation and in situ carcinoma from invasive carcinoma, lobular cell markers in differentiating lobular from ductal carcinoma, cytokeratin and other markers in diagnosing metaplastic carcinoma, and breast tissue origin markers in diagnosing breast primary carcinoma. The challenges in interpreting prognostic and predictive markers will be also discussed.

Breast biomarkers profile of invasive lobular carcinoma in a cohort of arab women shows no significant differences from carcinoma of no special type.

Objectives: Invasive lobular carcinoma (ILC) of the breast is known for its common presentation at an older age, and the frequent expression of favourable profile of estrogen and progesterone receptors (ER & PR) positivity, and human epidermal growth factor receptor 2 (HER2) negativity combined with low proliferation rate as measured by Ki67. This study aimed to test these clinicopathological features of ILC in an Arabic cohort. Methods: All breast biopsies diagnosed as IDC or ILC were retrospectively reviewed over 2 years period (2017-2018) in an academic centre. Variables were compared using Fisher's exact test for statistical significance. Results: A total of 134 cases were recruited, 12.7% were ILC. The median age was 52 years for both types. Clustering of ILC cases was noticed in luminal A subtype (47.1%), but there was no statistically significant difference in subtyping between the 2 histologic groups. Ki67 was significantly lower in ILC than IDC category. Conclusions: Our study showed that ILC in our cohort lacks the advantage of older age and the common high expression of ER positivity in comparison to IDC. There is, however, significant difference of the value of Ki67 proliferation marker. The prognosis of lobular morphology is questionable in our cohort.

The 70-gene signature test as a prognostic and predictive biomarker in patients with invasive lobular breast cancer.

PURPOSE: Genomic expression assays provide prognostic information and guide adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive breast cancer. Few studies have evaluated the utility of such assays for invasive lobular carcinoma (ILC). The objective of this study is to evaluate the 70-gene signature test (ST) as a prognostic and predictive tool for ILC using a national cancer database. METHODS: We identified patients diagnosed with stage I-III ER-positive ILC from 2004 to 2016 using the National Cancer Database. All patients underwent 70-gene ST testing. We used the Kaplan-Meier method and Cox proportional hazard analyses to determine overall survival based on genomic risk classification. We also determined the benefit of adjuvant chemotherapy for patients with high-genomic risk ILC based on 70-gene ST testing. RESULTS: We identified 2610 patients with ILC who underwent 70-gene ST testing; 280 (11%) were classified as high genomic risk. Five-year overall survival rates were significantly worse for patients classified as high risk (83%) as compared with those classified as low risk (94%, p < 0.05). In Cox models, high genomic risk was independently associated with a significantly increased hazard of death. In our Cox models of patients who were high genomic risk, adjuvant chemotherapy was not significantly associated with improved overall survival. CONCLUSION: In this large database study, we found that the genomic risk category determined by the 70-gene ST was significantly associated with survival outcomes for patients with ILC. However, the 70-gene ST failed to predict the benefit of adjuvant chemotherapy for patients with high genomic risk.

Expression of N-Terminal-Deficient E-Cadherin Protein in Invasive Lobular Carcinoma of the Breast.

Invasive lobular carcinoma (ILC) of the breast is characterized by the discohesive growth of tumor cells, which is mainly associated with the complete loss of E-cadherin (E-cad) expression. However, some aberrant expression patterns of E-cad protein that are inconsistent with their morphologies have been reported in ILC. We report herein ILC cases expressing a new type of abnormal E-cad protein that lacks the N-terminal domain, but conserves the C-terminal domain on the cell membrane. Immunohistochemical staining of 299 ILC cases using specific antibodies against the N-terminal or C-terminal region of E-cad revealed that 227 (76%) cases showed loss of the membranous expression of both terminuses (N-/C-) and 72 (24%) cases showed expression of only the C-terminus (N-/C+). In all cases, the expression of p120-catenin and ß-catenin coincided with the expression of the C-terminus of E-cad. Clinicopathologic analysis revealed that N-/C+ expression in ILC cells was significantly associated with the histologic subtype (especially mixed-type ILC with another histologic type) and immunohistochemical molecular subtype (especially the triple-negative subtype), but not with prognostic factors (pT or pN). In addition, 12 of 15 cases (80%) with aberrant cytoplasmic localization of the N-terminal of E-cad showed diffuse membranous expression of the C-terminal domain. Additional immunohistochemistry using an antibody recognizing the extracellular juxtamembrane region showed that 28 (39%) of the N-/C+ cases had lost membranous expression, suggesting diversity in the deletion pattern of the N-terminal region. Our findings provide a novel mechanism for the loss of E-cad function because of N-terminal-deficient E-cad protein in ILC.