Diagnosis Of Invasive Lobular Carcinoma Research Articles

Contrast-Enhanced Digital Mammography for the Diagnosis and Determination of Extent of Disease in Invasive Lobular Carcinoma: Our Experience and Literature Review.

Contrast-enhanced imaging, including magnetic resonance imaging and, more recently, contrast-enhanced digital mammography (CEM), is indicated for the precise diagnosis of invasive lobular carcinoma (ILC). The aim of our study was to further validate the use of CEM for evaluation of extent of disease in ILC cases, with digital breast tomosynthesis (DBT) as an adjunct. A retrospective, institutional review board approved study was conducted in a tertiary medical center. All CEM examinations performed on ILC patients between 2017 and 2023 were reread by 2 dedicated breast radiologists. Clinical data and pathology reports were retrieved from electronic medical records. The longest diameter of the enhancing lesion was correlated to pathology findings. In addition, for each case, the readers provided brief commentary on the added value of DBT. Twenty-four CEM examinations were evaluated. The subjects in the study cohort were on average older than expected for ILC patients (74 vs 63 years) and were unable to undergo breast magnetic resonance imaging due to advanced age and comorbidities. Three subjects were treated with neoadjuvant therapy and thus were excluded from the correlation to pathology analysis. Enhancing lesions, ranging from 4-75 mm, strongly correlated to pathology results, with statistical significance. This was demonstrated for mass and nonmass lesions (r = 0.94, P < 0.001 and r = 0.99, P = 0.002, respectively). For most lesions (17/24, 71%), readers remarked that the addition of DBT allowed for improved characterization of lesion margins, mainly detecting architectural distortion. When compared with the pathology findings, ILC was accurately diagnosed and assessed using CEM. The addition of DBT was reported by the interpreting radiologists as a valuable adjunct for margin analysis.

Differences in Histological Subtypes of Invasive Lobular Breast Carcinoma According to Immunohistochemical Molecular Classification.

The aim of this study was to compare the differences between histological and molecular subtypes of invasive lobular carcinoma (ILC) of the breast, in order to be able to predict the behavior and prognosis of the disease, as well as to effectively determine therapy. This study included 263 cases of breast ILC diagnosed over a seven-year period. The diagnosis of invasive lobular carcinoma is based on the characteristic growth pattern and phenotype of cancer cells with the respective subtypes: classic, alveolar, solid, tubulolobular, pleomorphic and mixed lobular type. The examined cases were divided into five groups according to molecular classification based on the expression of ER, PR, HER2 and Ki67 immunohistochemical markers. It was found that the pleomorphic subtype occurred statistically significantly less often as the luminal A subtype compared to others (p = 0.00027), and the HER2-enriched subtype occurred statistically significantly more often in the pT4 stage (p = 0.024). The results of this study significantly singled out the luminal A subtype, and among them classic ILC, as the subtype with the most favorable expression ratio of the investigated predictive/prognostic immunohistochemical markers.

Computational Approach to Identify the Key Genes for Invasive Lobular Carcinoma (ILC) Diagnosis and Therapies

Invasive Lobular Carcinoma (ILC) is a common form of breast cancer that begins in milk-producing glands lobules and spreads to other parts of the breast. According to the American Cancer Society, about 10–15% of breast cancer cases are ILC. ILC risk rises with age. The number of deaths caused by this cancer each year can be decreased through early diagnosis and if accurate therapy is given. However, diagnosis of ILC is difficult due to its development pattern as it grows as single file strands and not as lumps. Treatments of ILC involve chemotherapy, hormonal therapy and radiation therapy. Drugs that are being used for ILC, are commonly used to treat all types of breast cancer and there are no specific drugs that target receptors of ILC are available. Microarray technology’s emergence helps in finding the differentially expressed genes (DEGs) in malignant cells. From the DEGs, highly interacting genes were identified using the online tool, string. Seven key genes were identified based on the interaction and they are FN1, CDKN2A, COL1A1, COL3A1, COL11A1, LEF1 and IL1B. Thus, the drugs targeting these biomarkers were identified by doing molecular docking using the tool Autodock and molecular dynamic (MD) simulation using the tool iMODs. The response of the identified drugs to the ILC cell line was compared with the control drugs by in silico pharmacogenomic analysis and it was found that the identified drugs have a good response to the ILC cell line.

Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features.

Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.

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

RationaleChinese 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 reportThe 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.DiagnosisPathology and immunohistochemistry(IHC), a whole-body bone scan confirmed the first diagnosis of breast cancer with both gastric and bone metastases.InterventionsPalliative treatment with bisphosphonates and CDK4/6i (Palbociclib) in combination with AI (Exemestane) was administered.OutcomesThe patient is currently under regular evaluation and is being followed up.

Abstract PD11-01: An artificial intelligence-based predictor of CDH1 biallelic mutations and invasive lobular carcinoma

Abstract Introduction: Invasive lobular carcinoma (ILC) is the most frequent special histologic subtype of breast cancer (BC). ILC is identifiable by pathologic assessment given its distinctive discohesive growth pattern, largely caused by CDH1 inactivation. Compared to common forms of BC, ILCs display lower responses to chemotherapy and selective estrogen receptor modulators. The low interobserver agreement for the diagnosis of ILC, however, renders the inclusion of histologic subtyping in therapeutic decision-making challenging. Artificial intelligence (AI)-based algorithms hold promise for improving pathologic diagnosis; their performance, however, depends on the ground truth labeling used. Here, we seek to develop an AI-based methodology for detection of ILC using ‘CDH1 biallelic mutations’ (i.e., mutation + loss-of-heterozygosity of the wild-type allele or two pathogenic somatic mutations) as ground truth, reasoning that in BC, &amp;gt;95% of CDH1 bi-allelic inactivation is found in ILCs.Materials and methods: We developed a convolutional neural network system to detect CDH1 biallelic genetic inactivation (AI-CDH1) using whole slide images (WSI) of 1,100 primary BCs with available targeted sequencing data. The model was trained using a 10-fold cross-validation method to detect biallelic mutations. The mean number of positive and negative samples in the training set was 85.2 (SD=2.57) and 562.8 (SD=10.51) per fold, respectively. The evaluation set consisted of a mean of 14.2 (SD=2.04) positive and 93.8 (SD=9.13) negative samples. We evaluated the performance of the AI-CDH1 classifier to predict the lobular phenotype and CDH1 status using original and revised labels, following a histopathologic re-review of the histologic type and CDH1 status curation. The latter was conducted by incorporating information on biallelic CDH1 inactivation beyond CDH1 mutations (homozygous deletions, deleterious structural rearrangements, and loss-of-heterozygosity and gene promoter methylation).Results: The AI-CDH1 classifier predicted biallelic CDH1 mutations with an area under the curve (AUC)=0.944 (95 CI: 0.925-0.963), sensitivity=91.6% and specificity=85.9%, PPV=49.8%, NPV=98.5% and accuracy=86.7%, and the original ‘lobular phenotype’ with an AUC=0.941 (95 CI: 0.922-0.960), sensitivity=89%, specificity=86.7%, PPV=55.6%, NPV=97.7% and accuracy=87.1%. Review of the CDH1 gene status revealed that 7/957 BCs lacking CDH1 biallelic mutations harbored biallelic CDH1 inactivation by promoter methylation, homozygous deletions or structural rearrangements. The AI-CDH1 classifier detected all seven reclassified BCs and predicted the revised CDH1 biallelic inactivation with an AUC=0.948 (95 CI: 0.930-0.966), sensitivity=92%, specificity=86.5%, PPV=52.3%, NPV=98.5% and accuracy=87.2%. Upon histologic re-review, which resulted in reclassification of 36/927 non-lobular BCs as ‘lobular’ and 5/173 ‘lobular’ BCs as ‘non-lobular’, the AI-CDH1 classifier detected the ‘lobular phenotype’ with an AUC=0.953 (95 CI: 0.935-0.971), sensitivity=90.7%, specificity=89.7%, PPV=66.8%, NPV=97.7% and accuracy=89.9%. Using the revised histologic re-classification and CDH1 biallelic inactivation status labels, the AI-CDH1 classifier predicted the lobular phenotype irrespective of CDH1 status (P&amp;gt;0.05).Conclusions: By training a machine learning system to detect ‘CDH1 biallelic mutations’, as ground truth rather than histologic diagnosis of lobular carcinoma, which might be confounded by human subjectivity, we developed an AI-based system that can detect ILCs accurately, providing a new paradigm for the development of AI-based cancer classification systems. Citation Format: Jorge S Reis-Filho, Fresia Pareja, Fatemeh Derakhshan, David N Brown, Jillian Sue, Pier Selenica, Yi Kan Wang, Arnaud Da Cruz Paula, Monami Banerjee, Zahra Ebrahimzadeh, Manuel Isava, Matthew Lee, Ran Godrich, Adam Casson, Ruben Padron, George Shaikovski, Alexander van Eck, Antonio Marra, Higinio Dopeso, Hannah Y Wen, Edi Brogi, Matthew G Hanna, Chris Kanan, Jeremy D Kunz, Felipe C Geyer, Carla Leibowitz, David Klimstra, Leo Grady, Thomas J Fuchs. An artificial intelligence-based predictor of CDH1 biallelic mutations and invasive lobular carcinoma [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD11-01.

114 The Use of Magnetic Resonance Imaging in Patients with A Post-Operative Diagnosis of Invasive Lobular Carcinoma, A Retrospective Analysis

Abstract Aim Magnetic Resonance Imaging (MRI) is recommended pre-operatively for some patients with invasive breast carcinomas, particularly mammographically occult cancers and when tumour size may affect surgical management. Research has shown a higher incidence of both multifocal (32.7%) and bilateral (7%) cancers in invasive lobular carcinoma (ILC), affecting the surgical management of 27% of cases. The study aim was to identify whether MRI is indicated post-operatively when the pre-operative diagnosis is invasive ductal carcinoma (IDC) but post-operative diagnosis is ILC. Method Retrospective analysis of the medical records of patients with dual coding of IDC and ILC over a five-year period (2014-2019) was conducted. Inclusion criteria included a pre-operative diagnosis of IDC but a post-operative diagnosis of ILC. 167 patients were identified. Results Twenty-nine patients (17%) fulfilled the inclusion criteria. Ten (34%) had MRI scans conducted. Six (21%) were performed pre-operatively, three (10%) post-operatively and one (3%) had both a pre-operative and post-operative scan. None of the post-operative MRI scans showed further disease. One pre-operative scan identified a secondary foci, however the patient still underwent breast conserving surgery. The other nineteen patients received annual mammographic follow-up as per multidisciplinary meeting documentation, with no recurrence to date. Conclusions MRI at our unit is carried out as per NICE guidelines pre-operatively. Our results did not identify any further disease in patients with a post-operative diagnosis of ILC, however the sample size was small. There are currently no guidelines on the use of MRI in these patients and further, larger studies are needed to clarify its role.

Diagnosing Invasive Lobular Carcinoma of the Breast

Invasive lobular carcinoma (ILC) represents only 10–15% of all invasive breast cancers. Owing to challenges in screening and detection, diagnosis of ILC is often delayed and susceptible to high false-negative rates. This is a case report of ILC illustrated by mammography, ultrasound, magnetic resonance imaging and ultrasound-guided core-needle biopsy in a postmenopausal female.

New variant of breast-invasive lobular carcinoma with solid and encapsulated papillary carcinoma growth pattern

To date, five cases of invasive lobular carcinoma with solid and encapsulated papillary carcinoma (SPC and EPC) growth pattern were reported. In this article, we describe such a case that might represent a diagnostic pitfall. A 61-year-old woman had a mass on the left breast that was characterized by multiple expansile nodules with a fibrous capsule. Tumor cells were arranged in a solid pattern with inconspicuous delicate fibrovascular cores, some were irregular glandular tubes and papillary, similar to the growth pattern of SPC and EPC. The appearance of the tumor surrounding tissue suggested a special type of lobular carcinoma. The diagnosis of invasive lobular carcinoma was confirmed by immunohistochemistry, which revealed negative E-cadherin, positive cytoplasmic P120, and deleted myoepithelium. Next-generation sequencing revealed CDH1 mutations that further proved the diagnosis of invasive lobular carcinoma. The main differential diagnoses for this tumor are SPC, EPC, neuroendocrine carcinoma, and secretory carcinoma, for which immunohistochemical analysis is an essential diagnostic tool. The growth pattern of invasive lobular carcinoma with EPC and SPC is a variant of the invasive lobular carcinoma newly discovered. The understanding of this variant expands the morphological spectrum of invasive lobular carcinoma and will help prevent misdiagnosis.

AB008. SOH21AS138. Magnetic resonance imaging (MRI) use and its impact on surgical decision making in invasive lobular carcinoma of the breast

Background: Invasive lobular carcinoma (ILC) is more likely to be multifocal, bilateral and mammographically occult than invasive ductal carcinoma. The aim of this study was to assess magnetic resonance imaging (MRI) use and its impact on surgical decision making in a modern cohort of Irish women with a diagnosis of ILC.

MRI Use and its Impact on Surgical Decision Making in Invasive Lobular Carcinoma of the Breast

Background: Invasive lobular carcinoma (ILC) accounts for approximately 10% of all breast cancers. It is more likely to be multifocal, bilateral and mammographically occult than invasive ductal carcinoma. MRI is sometimes warranted to assess the extent of disease but its routine use in ILC is controversial. The aim of this study was to assess MRI use and its impact on surgical decision making in a modern cohort of Irish women with a diagnosis of ILC.

Population Trends in Lobular Carcinoma of the Breast: The Ontario Experience.

Invasive lobular carcinoma (ILC) is less common that invasive ductal carcinoma (IDC), and more challenging to diagnose by examination and screening mammography. This study evaluated current trends in ILC incidence, and described the 5-, 10-, and 15-year survival probabilities for women diagnosed with ILC in Ontario, Canada. This retrospective cohort analysis included all women aged 18years and older diagnosed with breast cancer between 1991 and 2015. Health administrative data from the Institute of Clinical Evaluative Sciences and the Ontario Cancer Registry were used to identify breast cancer cases. Age-adjusted incidence was plotted by year. Crude proportions were plotted by year of diagnosis for stage and hormone receptor status. Kaplan-Meier curves were generated to determine the 5-, 10-, and 15-year survival probabilities for ILC and IDC. From 1991 to 2015, there were 194,065 cases of breast cancer in Ontario, 14.7% of which were ILC. The age-adjusted incidence of breast cancer increased 1.04-fold, while ILC rates increased 1.53-fold. All bilateral breast cancers were of lobular origin. The proportion of stage 1 ILC decreased, while the proportion of stage 2-4 ILC increased. The 5-, 10-, and 15-year overall survival probabilities for women diagnosed with ILC were 82.7%, 65.3%, and 50.2%, respectively. This study contains the largest population dataset of ILC evaluated to date. While total breast cancer incidence rates in Ontario are largely unchanged, ILC incidence rates are steadily increasing and there is a trend towards diagnosis of ILC at a later stage. These trends highlight the ongoing diagnostic and treatment challenge ILC presents for patients and clinicians.

Non-Palpable Invasive Lobular Carcinoma Initially Diagnosed by Inguinal Lymph Node Biopsy

Metastasis from breast cancer to the inguinal lymph nodes or the vulva is a rare event with very few cases reported in literature. A 38-year-old lady presented complaining of progressive abdominal enlargement. Physical examination was unremarkable apart from abdominal enlargement and enlarged right inguinal lymph node. Radiology showed marked ascites, omental thickening, bilateral small ovarian masses, suspicious right inguinal lymph node (LN) as well as breast fibrocystic disease. Cytological examination of the ascitic fluid revealed malignant cells. Core needle biopsy from the inguinal LN suggested metastatic breast carcinoma. Breast MRI showed heterogeneous fibro-glandular tissue and moderate parenchymal enhancement. Random core needle biopsies from the breast led to the diagnosis of invasive lobular carcinoma. The patient received 8 cycles of docetaxel/carboplatin protocol, with partial response. Next, she was maintained on hormonal treatment (Anastrazole) till the ascites re- accumulated. Vulvar nodules appeared whose biopsy revealed infiltration by the same tumoral tissue. She received 6 cycles of Endoxan and Pharmarubicin till regression was achieved, and then she was subjected to Exemestane. Thorough clinical assessment including of all lymph node basins and gynecological assessment are crucial in all breast cancer patients, particularly those with invasive lobular subtypes.&#x0D; Keywords: Breast neoplasms, Lobular, Vulva, Vulvar metastasis, Neoplasm metastasis

Abstract P5-02-09: The prevalence of invasive lobular carcinomas with unconventional immunohistochemical phenotypes

Abstract Background The prognosis of invasive lobular carcinoma (ILC) is controversial. Some studies report equivalent or better outcomes than invasive ductal carcinoma, likely due to ILC’s favorable prognostic phenotype. Classic ILC (CL) is typically of low histologic grade, estrogen receptor (ER) positive and human epidermal growth factor receptor-2 (HER2) negative. However, worse long term outcomes have been observed because ILC tends to be multicentric, bilateral, and to show higher rates of late metastases in uncommon sites. Additionally, subtypes of ILC, including solid (SOL) and pleomorphic (PL), have been reported to display more aggressive behavior. Yet current treatment paradigms are distinguished by hormone receptor profile and stage, not by tumor morphology. This study aimed to evaluate the clinicopathologic and immunohistochemical (IHC) characteristics of ILC, particularly those with unusual patterns. Methods From 2009-2018, consecutive in-house biopsy and resection specimens with the diagnosis of ILC were identified by a retrospective review of our institutional database. Demographic, morphologic, and IHC data were obtained from pathology reports. Cases with equivocal HER2 IHC results are sent for fluorescence in situ hybridization analysis at our Center. CL ILC was defined by small cells with low nuclear grade and discohesive growth arranged in single file or cords. PL ILC is composed of larger, more atypical cells, which still exhibit discohesion typical of lobular phenotype. SOL ILC consists of tumors growing in large sheets with minimal intervening stroma. Results Over the nine year study period, a total of 3,028 ILCs from 2,322 patients were identified. Most (74%, 2229/3028) cases were classified as CL while 22% (665/3028) were PL and 4% (134/3028) SOL (Table 1). The median patient age was 60 years (range 32-95). The median tumor size was larger for PL (2.3 cm) and SOL (2.4 cm) subtypes than CL (1.1 cm). IHC results were available for 896 specimens. The majority of all ILCs showed an expected phenotype: ER positive and HER2 negative (99% CL, 84% PL, 97% SOL). A smaller subset of ER positive ILC were also HER2 positive (1% CL, 8% PL, 3% SOL). No CL or SOL ILC were ER negative; in contrast 8% (21/270) of PL ILC were ER negative. Twelve (5%) PL ER negative cases were also HER2 negative. Overall, 15% of ILC were HER2 positive, with the PL variant showing the highest incidence (11%, 30/270). Lymph node (LN) metastases were seen in 22% (66/291) of CL cases, 55% (53/96) PL and 29% (17/58) SOL. Metastases in 10 or more LN (N3) was seen only in PL and SOL cases (13% and 5%, respectively). Conclusions In this study, up to 8% of ILC cases were found to be ER negative, a finding unique to the PL variant. No CL or SOL ILC was ER negative. HER2 positivity, not typically expected in ILC, was seen in 15% of cases, most commonly in the PL type. ILC that was both negative for ER and HER2 was observed in 5% of cases, and only within the PL subgroup. PL ILC showed higher median tumor size at presentation than CL and nodal metastases were also more common in PL than in CL or SOL ILC (55% vs 22% and 29%, respectively). Our findings are in keeping with prior observations that compared to CL ILC. PL ILC exhibits features associated with unfavorable clinicopathologic features, such as higher tumor and nodal stage at presentation. Additionally, this is the first study to systematically examine the prevalence of unconventional IHC phenotypes of ILC (ER negativity and/or HER2 positivity) in a large series from one institution. Table 1. Summary of Clinicopathologic FeaturesClassicPleomorphicSolidILC types (n=3028)2229665134Median age, (range)60 yrs (32-94)61 yrs (31-95)66 yrs (44-93)Median size, cm 1.12.32.4Immunophenotype (n=896)ER+/HER2-99% (551/559)84% (228/270)97% (65/67)ER+/HER2+1% (8/559)8% (21/270)3% (2/67)ER-/HER2+0% (0/559)3% (9/270)0% (0/67)ER-/HER2-0% (0/559)5% (12/270)0% (0/67)Lymph node status (n=445)N077% (225/291)45% (43/96)71% (41/58)N120% (59/291)31% (30/96)19% (11/58)N22% (7/291)11% (11/96)5% (3/58)N30% (0/291)13% (12/96)5% (3/58) Citation Format: Matthew G Hanna, Anne Grabenstetter, Dara S Ross, Lee K Tan. The prevalence of invasive lobular carcinomas with unconventional immunohistochemical phenotypes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-02-09.

Metaplastic Carcinoma and Invasive Lobular Carcinoma of Breast: Rare Collision Tumor of Breast With Review of Recent Literature

Collision tumors are type of tumors where two histologically distinct type of tumors occur at the same anatomic location. Breast collision tumors comprising carcinoma and lymphoma or invasive ductal carcinoma with invasive lobular carcinoma are relatively common. However, a collision tumor between metaplastic breast carcinoma (MBC) and invasive lobular carcinoma (ILC) is extremely rare. Here, we report a case of collision tumor in breast comprising MBC and ILC. A 60-year-old female patient presented in outdoor department with palpable painless firm mass in left breast. FNAC diagnosis of class V smears was made. Wide local excision was done and specimen sent for frozen section analysis. On frozen section, diagnosis of malignant neoplasm was made and suspicion of malignant phyllodes and MBC was raised. All margins were reported free as free of the tumor. Further sectioning revealed another tumor, 0.1 cm away from main tumor. Sections from this tumor showed a malignant neoplasm arranged in cords with tumor cells having eccentric nuclei and moderate amount of cytoplasm. Immunohistochemical (IHC) analysis showed spindle cell tumor with profile favoring MBC while IHC analysis of second tumor was consistent with the diagnosis of ILC. Final diagnosis of collision tumor was made. © 2019 Tehran University of Medical Sciences. All rights reserved. Acta Med Iran 2019;57(4):271-275.

Unilateral indurated plaque in the axilla: a case of metastatic breast carcinoma

Breast cancer is the most commonly diagnosed cancer among American women and is also the most common internal malignancy to metastasize to the skin. Rarely, cutaneous metastases represent the first indication of breast carcinoma, putting dermatologists in an instrumental position to make the diagnosis of breast carcinoma. We report the case of a 71-year-old woman with a 10-year history of a slowly-enlarging, indurated plaque in the right axilla. Review of symptoms was significant only for occasional numbness and tingling that extended from the right axilla to the right hand. Biopsy revealed cells infiltrating in a single-file between the collagen bundles in the dermis and subcutis and immunohistochemical staining consistent with a diagnosis of invasive lobular carcinoma. Subsequent work up revealed a primary breast lesion and extensive bony metastases.

Contralateral breast cancer: incidence according to ductal or lobular phenotype of the primary

To identify differences in the incidence of contralateral breast cancer between patients with a primary tumour diagnosis of invasive ductal carcinoma (IDC) and those with a diagnosis of invasive lobular carcinoma (ILC). Data from two large cancer registries (registry A & B) the Northern and Yorkshire Cancer Registry Information Service (NYCRIS) and the West Midlands Cancer Intelligence Unit (WMCIU) from 1998-2003 for all cases of invasive breast cancer of either pure ductal or pure lobular reported histology were obtained. The invasive status of the contralateral tumour diagnosis and tumour morphology was collected. Chi-square tests were undertaken to examine the differences in contralateral rates for both registries and univariate analysis to ascertain which predictors affected contralateral breast cancer risk for registry A the WMCIU cases. A total of 38,132 patients were studied, 32,735 patients with IDC and 5397 (14.2%) patients with ILC over the 6-year period. There was no significant difference between the occurrence and time to occurrence of contralateral breast cancer according to original cancer histology, 901 (2.8%) patients with IDC versus 166 (3.1%) patients with ILC (p=0.169). The analysis of registry A cases showed no association between original histology (ductal versus lobular), age at diagnosis, tumour grade, use of radiotherapy for the primary cancer or use of systemic therapy (chemotherapy and/or endocrine therapy), and development of a contralateral breast cancer. There is no apparent increase in risk of developing a contralateral breast cancer according to the primary cancer histology either IDC or ILC. Standard mammographic follow-up does not need to take account of original tumour pathology. Increased intervention or post-treatment surveillance for the contralateral breast is not indicated in the context of ILC. The role of MRI should be restricted to those patients with ILC who are planning breast-conservation surgery, but not for assessing the contralateral breast.

Abstract P4-04-03: A microgenomic approach using LCM procured breast cancer cells to identify clinically relevant gene signatures that underlie favorable response of ILC to aromatase inhibitors

Abstract Based on CGH analyses, invasive lobular carcinoma (ILC) is closely related to low grade invasive ductal carcinoma (IDC), and is genetically unrelated to intermediate and high grade invasive carcinomas (Pathol Res Pract 2005; 201:713). Results from the BIG 1-98 trial, showed that patients with ILC and luminal B (intermediate/high grade) IDC treated with Letrozole, an aromatase inhibitor (AI), had a significant improvement in overall survival, whereas patients with luminal A (low grade) IDC did not (Cancer Res 2012; 72(24 Suppl):Abstract nr S1-1). Despite genetic evidence suggesting a close relationship between ILC and low grade IDC, and disparity between ILC and intermediate and high grade IDC, a clinically relevant gene set underlying a tumor's biologic responsiveness to AIs likely exists. We are deciphering a gene subset that would differ in expression between low grade IDC and ILC, and would be shared by ILC and luminal B IDC. Identification of such a gene set should lead to a more robust marker for identifying AI responsive tumors rather than relying solely on histomorphology and/or immunohistochemistry for the pathologic diagnosis of ILC, since the distinction between ILC and IDC is not always straight forward in pathology practice. Using 247 de-identified human breast carcinoma biopsies collected under standardized, stringent conditions, total RNA was extracted from carcinoma cells procured by laser capture microdissection to perform microarray analyses of approximately 22,000 genes to identify expression signatures associated with breast cancer characteristics. Of the 247 samples, 169 samples were used for the analysis and included 16 ILCs, 13 low grade IDCs, 55 intermediate grade IDCs and 85 high grade IDCs. Preliminary analyses identified 1267 genes that were differentially expressed (p&amp;lt;0.01) between cell samples from patients with IDC compared to those with ILC. Gene expression levels in breast cancer cells from patients with low grade IDC compared to those with ILC yielded 200 genes that were statistically differentially expressed (p&amp;lt;0.01). When comparing high grade IDC to ILC, 149 of these genes were not differentially expressed indicating that this gene set may serve as a panel of candidate genes for identifying cancers responsive to AIs. Pathway analysis software (Ingenuity®) identified that these genes were associated with key molecular and cellular functions, e.g., cell-to-cell signaling, cell morphology, cell death and survival, cellular assembly and organization and carbohydrate metabolism. qPCR analyses are used to validate and refine the gene subset distinguishing ILC from low grade IDC. Our approach is revealing subtle molecular features that discriminate these lesions based on clinical behavior. Supported in part by a grant from the Phi Beta Psi Charity Trust. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-04-03.

Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma

Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma

Relevance of systems biological approach in the differential diagnosis of invasive lobular carcinoma & invasive ductal carcinoma.

Breast cancer is a malignant neoplasm originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. ILCs and IDCs vary from each other with respect to various histological, biological and clinical features. Remarkably, ductal tumors tending to form glandular structures, whereas lobular tumors are less cohesive and tends to invade in single file. The high degree of similarity in the prognoses of IDC and ILC makes it beneficial to develop a differential diagnostic protocol to classify the two conditions. The main goal of the study is to construct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences, in order to explore the potential significant gene regulatory networks that can differentiate IDC and ILC and thereby understand the complex interactions that are influenced by the genetic networks. Out of the 54676 genes present on the GPL570 platform- 29 genes exhibited 4 fold up regulation in case of IDC and 22 in the case of ILC. The ductal and lobular tumors displayed a striking difference in the expression of genes associated with cell adhesion, protein folding, and protein phosphorylation and invasion. Construction of separate gene regulation networks for IDC and ILC on the basis of gene expression altercation can be utilized in understanding the distinction in the possible mechanism that underlies the pathological differences between the two, which can be exploited in identifying diagnostic or therapeutic targets.AbbreviationsILC - Invasive lobular c carcinoma, IDC - invasive ductal carcinoma, ER - Estrogen Receptor.