High-grade Invasive Ductal Carcinoma Research Articles

Rare breast cancers with seemingly benign features on conventional imaging: Radio-pathological correlation and review of literature

Oval or rounded breast masses with circumscribed margins, absence of microcalcifications, and architectural distortions are usually benign. However, 10-20% of breast cancers may have circumscribed margins, which may be misdiagnosed as benign breast mass or lead to delayed diagnosis in advanced stages of cancer. Most frequently, circumscribed breast cancers are high-grade invasive ductal carcinoma of triple-negative molecular subtype. However, there are many other rare histological subtypes of cancers in the breast with circumscribed margins or less aggressive features on imaging and mimic benign breast lesions. A radiologist needs to be familiar with the imaging features of various atypical malignant breast tumors to avoid delay in diagnosis. These rare malignant breast tumors are mucinous carcinoma, papillary carcinoma, lymphoma, leukemia, myeloma, metastasis from extramammary primaries, adenoid cystic carcinoma, signet-ring carcinoma, malignant phyllodes tumor, mesenchymal sarcoma, Ewing’s sarcoma, and medullary carcinoma. This pictorial review illustrates the clinical, multimodality imaging features of rare malignant breast tumors with less aggressive features on conventional breast imaging with pathological correlation.

Novel computational biology modeling system can accurately forecast response to neoadjuvant therapy in early breast cancer

BackgroundGeneralizable population-based studies are unable to account for individual tumor heterogeneity that contributes to variability in a patient’s response to physician-chosen therapy. Although molecular characterization of tumors has advanced precision medicine, in early-stage and locally advanced breast cancer patients, predicting a patient’s response to neoadjuvant therapy (NAT) remains a gap in current clinical practice. Here, we perform a study in an independent cohort of early-stage and locally advanced breast cancer patients to forecast tumor response to NAT and assess the stability of a previously validated biophysical simulation platform.MethodsA single-blinded study was performed using a retrospective database from a single institution (9/2014–12/2020). Patients included: ≥ 18 years with breast cancer who completed NAT, with pre-treatment dynamic contrast enhanced magnetic resonance imaging. Demographics, chemotherapy, baseline (pre-treatment) MRI and pathologic data were input into the TumorScope Predict (TS) biophysical simulation platform to generate predictions. Primary outcomes included predictions of pathological complete response (pCR) versus residual disease (RD) and final volume for each tumor. For validation, post-NAT predicted pCR and tumor volumes were compared to actual pathological assessment and MRI-assessed volumes. Predicted pCR was pre-defined as residual tumor volume ≤ 0.01 cm3 (≥ 99.9% reduction).ResultsThe cohort consisted of eighty patients; 36 Caucasian and 40 African American. Most tumors were high-grade (54.4% grade 3) invasive ductal carcinomas (90.0%). Receptor subtypes included hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+, 30%), HR+/HER2− (35%), HR−/HER2+ (12.5%) and triple negative breast cancer (TNBC, 22.5%). Simulated tumor volume was significantly correlated with post-treatment radiographic MRI calculated volumes (r = 0.53, p = 1.3 × 10–7, mean absolute error of 6.57%). TS prediction of pCR compared favorably to pathological assessment (pCR: TS n = 28; Path n = 27; RD: TS n = 52; Path n = 53), for an overall accuracy of 91.2% (95% CI: 82.8% – 96.4%; Clopper–Pearson interval). Five-year risk of recurrence demonstrated similar prognostic performance between TS predictions (Hazard ratio (HR): − 1.99; 95% CI [− 3.96, − 0.02]; p = 0.043) and clinically assessed pCR (HR: − 1.76; 95% CI [− 3.75, 0.23]; p = 0.054).ConclusionWe demonstrated TS ability to simulate and model tumor in vivo conditions in silico and forecast volume response to NAT across breast tumor subtypes.

Investigating the expression of cytokeratin 5/6 in benign and malignant breast lesions

Introduction: Breast cancer (BC) is the most common cancer in women, which is the second most common malignancy in terms of mortality and prevalence after lung cancer. BC is a group of very diverse diseases that can be detected at a molecular, histopathological and clinical level. Objectives: The aim of the present study was to evaluate the expression of CK5/6 and its relationship to some of the factors affecting prognosis, such as tumor grade, lymph node involvement. Patients and Methods: In this cross-sectional study with descriptive and analytical aspects, 40 malignant and 20 benign tumors were collected in 2020 from the archives of the pathology department of two educational hospitals in the city of Ahvaz. The demographic and clinical characteristics of each specimen, including age, patient, lymphovascular and perineural invasion, lymph node involvement, tumor grade and tumor type were extracted from the patients’ record. Then the expression of CK5/6 intensity staining was examined by immunohistochemistry. Results: All benign breast lesions had positive expression for CK5/6 and staining intensity between six and nine. In the malignant group, 33 samples showed negative expression of CK5/6 and only seven samples (17.5%) showed positive expression with a low-staining index. A positive expression with a low-staining index. All seven positive specimens were invasive ductal carcinoma (IDC) lesions with staining index 2, 4, and 6. Additionally, none of the ductal carcinoma in situ (DCIS) specimens which immunostained were positive for CK5/6. In the present study, all IDCs with weak expression of CK5/6 were grade III. No statistically significant relationship was observed between perineural and lymphovascular invasion and lymph node involvement with the intensity of CK5/6 expression. Conclusion: Our study showed that cytokeratin immunohistochemical intensity is able to distinguish benign lesions from malignant IDC and DCIS lesions and accordingly in determining of tumor grade after weak staining in high-grade IDC, which may be due to squamous metaplasia in these tumors; however, more extensive research with a larger sample size are required to assess its effect in lymphovascular and perineural invasion and also lymph node involvement.

Assessment of the immunoexpression profile of breast ductal carcinoma with Cyclin D1, Her-2/Neu and p53 at Yangon General Hospital, Myanmar

One hundred cases of histologically proven invasive ductal carcinomas were histologically graded based on modified Bloom and Richardson Grading. Out of these 17 cases each of low grade, intermediate grade, and high grade invasive ductal carcinomas were selected for Immunostaining using the monoclonal antibodies Cyclin D1,pP53 and Her2/neu. It was found that for all three monoclonal antibodies the lowest histological grade of Invasive Ductal Carcinoma of the Breast showed the lowest positivity with Cyclin D1 ( 11.76%) and p53 ( 17.64%) and Her2/neu ( 47.05%). The intermediate grade tumour showed ( 70.58% ) positivity with Cyclin D1 and 58.58 % in p53 and Her2/neu. The high grade invasive ductal carcinoma of the breast showed the highest positivity of Cyclin D1 (76.47%) , p53 (88.24% ) ,Her2/neu ( 94.12% ); These suggest that Cyclin D1 , P53 and Her2/neuimmunoexpression positivity increases with rising histological grades of invasive ductal carcinoma of breast.

Clinical and X-ray characteristics for expressions of different receptors in patients with breast cancer.

Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer. A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed. Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67≥20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively). Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.

Four Lessons in Transcranial Lesions

Background Lesions involving the skull are rare and often discovered incidentally by imaging studies. Skull lesions are most commonly benign but may also be malignant. Typically, lesions of the skull are evaluated by computed tomography and/or magnetic resonance imaging. Imaging features can also suggest whether an identified lesion is benign or malignant. Definitive diagnosis of transcranial lesions ultimately requires biopsy and surgical resection. Cases Atypical meningioma: A 57-year-old woman with a history of hypertension and arthritis presented with a left frontal scalp mass. Imaging revealed a large left frontal transcranial heterogeneous mass with intracranial and extracranial extension. Malignant ossifying fibromyxoid tumor: A 26-year-old woman with history of hypothyroidism, polycystic ovarian syndrome, and sciatica presented with a left parietal scalp mass. Imaging demonstrated a large left homogenous parietal transcranial mass with intracranial and extracranial extension. Breast carcinoma metastasis: A 64-year-old woman with history of ER/PR/Her2-neu–negative, high-grade invasive ductal carcinoma status post mastectomy, lymph node dissection, and chemotherapy with early termination due to adverse effects presented with a left parietal scalp mass. Imaging demonstrated a large left parietal transcranial mass. Glioblastoma: A 52-year-old man with a history of glioblastoma status post resection x2, chemoradiation, and craniectomy, who was found to have a second recurrence. Imaging demonstrated tumor surrounding the resection cavity in the left parietal/temporal region with extension through the craniotomy defect into the scalp soft tissue.

A Correlation of Pathological Characteristics and Immuno Histo Chemistry (IHC) Based Biomarker Expression in Triple Negative Breast Carcinomas

Background and aim: Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2). In India, several reports have suggested that TNBC incidence is higher and up to 31%. Histological features of triple-negative breast cancer are reported to be common with those of basallike subtype, comprising of high-grade invasive ductal carcinoma, no special type, invasive ductal carcinoma with a large central acellular zone, typical medullary carcinoma, and metaplastic carcinomas. In the present study, we aimed to correlate the pathological characteristics and evaluate IHC based expression of basal type biomarkers in triple negative breast carcinomas. Our study showed heterogeneity in histology, most of the TNBC cases in our study were IDC, NOS and there were a slightly higher percentage of atypical medullary cases as compared to other studies. Most of the cases were high grade based on modified NBR grading and majority of them turned out to be basal like on IHC. Distinctly found in our cases which had metastatic axillary lymph node was, basal immune phenotype unlike the case in other studies which demonstrated a higher proportion of lymph node negativity. As expected a high proportion of triple negative tumors showed a consistent basal cytokeratin expression (CK5/6-66%, CK14-72%, CK17-68%). EGFR and p53 positivity did not show statistical significance between basal and non-basal groups. Proliferation marker Ki67 was statistically significant in basal like groups. Gene expression profiling is the gold standard for TNBC molecular subtype classification, however, IHC is an accepted 'surrogate marker' for identifying and classifying the 'basal like group'. Our findings suggest that pathologic characteristics cannot be used to accurately classify triple-negative breast cancer into basal and non-basal groups. Relevance to patients: DNA microarray based molecular profiling may not be accessible always in clinical settings, this study has emphasized that identification of basal like subtype of breast cancers can be done by doing easily available surrogate Immunohistochemical biomarkers on TNBC, and thus help to provide the patient with relevant target based therapeutic benefit.

Lactating Adenoma Co-Existing with High Grade Invasive Ductal Carcinoma; Collision Tumour or Mere Co-Incidence

Background: Lactating adenoma are benign lesions that can presents as a solitary or multiple freely movable breast mass during pregnancy or puerperium. The lesion is actually a localized focus of hyperplasia in the lactating breast, which may also develop in ectopic locations such as the axilla, chest wall, or vulva. Breast cancer developing during pregnancy or puerperium is known as pregnancy associated breast cancer. We report a case of lactating adenoma co-existing with high grade invasive ductal carcinoma in young patient in puerperium with a positive family history of breast cancer. We present a 19-year-old female with a palpable mass on her right upper outer quadrant of her right breast measuring 5x4x2cm with ipsilateral supraclavicular lymph node enlargement. Cytomorphology of the lesion showed tumour cells arranged in nests and solid sheets with abundant fibromyxoid stroma. Also seen are abnormal mitosis and areas of lymphovascular invasion. Proliferating glands are seen lined by cuboidal cells with cytoplasmic vacuolations. Immunohistochemical stain show tumour cells were triple negative (negative for progesterone receptor (PR), estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) and strongly positive for EMA in both tumours. Conclusion: This study indicated that lactating adenoma can co-exist with high grade invasive ductal carcinoma in a young patient in puerperium. The fact that this patient has a positive family history of breast cancer in first degree relative may explain the presentation at a very young age. It may be very difficult to ascertain whether this is a collision tumour or a mere co-incidence of lactating adenoma with breast cancer in this patient.

Breast cancer metastasis to urinary bladder related hematuria and concomitant venous thromboembolism—case report of a challenging clinical scenario

: Breast cancer metastasis to the urinary bladder is uncommon and its true incidence may be underreported, requiring a high level of clinical suspicion to diagnose them. Venous thromboembolism (VTE) is a known complication in breast cancer and guidelines recommend treatment with the use of anticoagulation therapy unless contraindicated by active bleed or high bleeding risk. We present a rare case of 42-year-old female patient presenting with concurrent VTE and visible hematuria due to breast cancer metastasis to the urinary bladder. The patient initially underwent radical mastectomy and axillary lymph node dissection for high grade invasive ductal breast carcinoma (pT3N3cM0). Despite adjuvant radiotherapy, chemotherapy and hormonal therapy, the patient subsequently developed interval liver and bladder metastasis. She presented with right lower limb VTE 6 years after the initial mastectomy. The patient developed painless visible hematuria after starting anticoagulation therapy. Hence treatment of VTE was contraindicated and was managed instead with insertion of an inferior vena cava (IVC) filter. In the literature, breast cancer metastasis to the urinary bladder is rare, with 65 published to date. Our case report is unique as there was concomitant symptomatic VTE, thereby posing a clinical challenge of not being able to use anticoagulation therapy. We postulate that as the cancer specific and overall survival rates for breast cancer patients continues to improve, the incidence of patients presenting with metastasis to the urinary bladder may increase. Urinary bladder metastasis in breast cancer populations have variable presentations, requiring a high level of clinical suspicion. Prompt collaboration with urologists and pathologists is recommended in this group of patients who complaints of hematuria. Prognosis is usually poor and the optimal management is currently unknown.

PAX8 Expression in Breast Cancer.

PAX8 expression is frequently detected in renal, thyroidal, and Müllerian carcinomas, and PAX8 immunohistochemistry is often used to confirm the origin of these tumors. Tumors metastatic to the breast may masquerade as primary breast lesions. PAX8 is strongly expressed in tumors of Müllerian origin and largely negative in breast primaries, but an immunohistochemical expression of PAX8 in breast cancer has not been systematically evaluated in a large series. We analyzed 266 cases of invasive carcinoma of the breast on tissue microarrays and whole tissue sections with a PAX8 monoclonal antibody. Both the extent (focal or diffuse) and intensity (weak, moderate, or strong) of nuclear staining were assessed in the tumor cells. In total, 16 cases (6.02%) were positive for PAX8 (12 with weak and 4 with moderate staining). Expression was diffuse in 7 cases and focal in 9 cases. All 16 PAX8-positive tumors were histologic grade III invasive ductal carcinomas, 13 of these were triple-negative, 2 were HER2-positive, only and 1 was progesterone receptor-positive only. Strong PAX8 nuclear expression was not seen in any of the cases. PAX8 was negative in breast tumors with neuroendocrine features. Our study demonstrated a low rate of PAX8 expression in breast cancer. When present, PAX8 expression was only seen in high-grade invasive ductal carcinomas, mostly triple-negative. The presence of PAX8 immunoreactivity alone cannot exclude mammary origin, especially when only weak to moderate staining is observed, so the correlation with available clinical and pathologic data helps to ensure an accurate diagnosis.

Impact of radiomics on the breast ultrasound radiologist’s clinical practice: From lumpologist to data wrangler

ObjectiveThe study aims to assess the impact of radiomics in the clinical practice of breast ultrasound, to determine which lesions are undetermined by the software, and to discuss the future of the radiologist’s role. MethodsConsecutive analyses of 207 ultrasound masses from January 2018 to April 2019 referred for percutaneous breast biopsy. Breast masses were classified using dedicated ultrasound software (AI). The AI software automatically classified the masses on a scale of 0–100, where 100 is the most suspicious. We adopt the histology results as the gold standard. The cut-off point of malignancy by radiomics was determined, with ±10 % of margin error according to the Youden’s index. We considered these lesions as undetermined masses. The performance of the AI software and the radiologist classification was compared using the area under roc curves (AUROC). We also discuss the impact of radiologist validation of AI results, especially in undetermined lesions. ResultsOf the 207 evaluated masses, 143 were benign, and 64 were malignant. The Youden’s index was 0.516, including undetermined masses with a varied range of 10 % (0.464−0.567). Twenty-one (14.58 %) benign and twelve (19.05 %) malignant masses were in this range. The best accuracy performance to classify masses was the combination of the reader and AI (0.829). The most common undetermined masses in AI were fibroadenoma, followed by phyllodes tumor, steatonecrosis as benign. Whereas, low-grade, and high-grade invasive ductal carcinoma represents the malignant lesions. ConclusionsArtificial Intelligence has a reliable performance in ultrasound breast masses classification. Radiologist validation is critical to determine the final BI-RADS assessment, especially in undetermined masses to obtain the best classification performance

Pleomorphic Ductal Carcinoma of Breast: Two Cases and Review Literature

Abstract- We report two cases of pleomorphic breast carcinoma, a rare variant of high-grade invasive ductal breast carcinoma of no special type, which is a combination of pleomorphic and bizarre giant cells in an adenocarcinoma background. For gaining better insights, available literature is also reviewed. © 2019 Tehran University of Medical Sciences. All rights reserved.

The molecular mechanisms underlying reduced E-cadherin expression in invasive ductal carcinoma of the breast: high throughput analysis of large cohorts

E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the underlying mechanisms and molecular implications of E-cadherin loss in invasive ductal carcinoma. This study used large, well-characterized cohorts of early-stage breast cancer-evaluated E-cadherin expression via various platforms including immunohistochemistry, microarray analysis using Illumina HT-12 v3, copy number analysis using Affymetrix SNP 6.0 arrays, and next-generation sequencing for differential gene expression. Our results showed 27% of high-grade invasive ductal carcinoma showed reduced/loss of E-cadherin membranous expression. CDH1 copy number loss was in 21% of invasive ductal carcinoma, which also showed low CDH1 mRNA expression (p = 0.003). CDH1 copy number was associated with copy number loss of TP53, ATM, BRCA1, and BRCA2 (p < 0.001). Seventy-nine percent of invasive ductal carcinoma with reduced CDH1 mRNA expression showed elevated expression of E-cadherin transcription suppressors TWIST2, ZEB2, NFKB1, LLGL2, CTNNB1 (p < 0.01). Reduced/loss E-cadherin expression was associated with differential expression of 2143 genes including those regulating Wnt (FZD2, GNG5, HLTF, WNT2, and CER1) and PIK3-AKT (FGFR2, GNF5, GNGT1, IFNA17, and IGF1) signaling pathways. Interestingly, key genes differentially expressed between invasive lobular carcinoma and invasive ductal tumors did not show association with E-cadherin loss in invasive ductal carcinoma. We conclude that E-cadherin loss in invasive ductal carcinoma is likely a consequence of genomic instability occurring during carcinogenesis. Potential novel regulators controlling E-cadherin expression in invasive ductal carcinoma warrant further investigation.

Expression of PTEN, Androgen Receptor, HER2/neu, Cytokeratin 5/6, Estrogen Receptor-Beta, HMGA2, and PLAG1 in Salivary Duct Carcinoma.

Salivary duct carcinoma (SDC) is an aggressive neoplasm that resembles high-grade invasive ductal carcinoma of the breast. It can develop de novo or from the malignant transformation of pleomorphic adenoma (PA). We performed immunohistochemical stains for phosphatase and tensin homologue [PTEN androgen receptor (AR)], HER2/neu, cytokeratin 5/6, estrogen receptor-beta, high-mobility group AT-hook 2 (HMGA2), and pleomorphic adenoma gene 1 (PLAG1) on tissue microarray samples of 75 SDCs and 31 adenocarcinomas, not otherwise specified (NOS). Our data showed the following in SDC samples: loss of PTEN was found in 17 of 60 (28.3%); AR was expressed in 43 of 62 (69.4%); HER2/neu was overexpressed in 25 of 58 (43.1%); cytokeratin 5/6 was expressed in 14 of 54 (25.9%); estrogen receptor-beta was expressed in 37 of 56 (66.1%); HMGA2 was expressed in 29 of 63 (46.0%); and PLAG1 was expressed in 0 of 62 (0%). In addition, there was no statistically significant difference in the age at onset between patients with HMGA2-positive SDCs (range 32-85years; mean: 64.3years; median: 64.5years) and those with HMGA2-negative SDCs (range 41-79years; mean: 62.5years; median: 64.5years). There was also no statistically significant difference in overall survival between patients with HMGA2-positive and HMGA2-negative SDCs (follow-up period range 3-201months; mean: 49.8months; median: 30months). Among 10 patients with a definite PA component (SDC ex-PA), 6 were positive and 4 were negative for HMGA2. Our data were consistent with previous findings that AR and estrogen receptor-beta are expressed in most SDCs, whereas HER2/neu overexpression and loss of PTEN are expressed in a subset of SDCs. In our cohort of patients, HMGA2 was expressed in approximately half of SDCs. HMGA2 and PTEN are promising therapeutic targets for salivary gland tumors.

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

BackgroundMonoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis.MethodsWe employed various in-vitro and in-vivo techniques and clinical samples.ResultsWe studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen.ConclusionsSuppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

Contemporary classification of breast cancer

Studies of breast cancers using gene expression profiling have identified several major subtypes. The best characterised are luminal A, luminal B, HER2-enriched and basal-like, which differ in their gene expression patterns, clinical features, response to treatment and outcome. One of the most novel findings has been the characterisation of basal-like breast cancers, which are often high-grade invasive ductal carcinomas with solid architecture, high mitotic rate, stromal lymphocytic infiltrate, pushing border, geographic necrosis and/or a central fibrotic focus. They are typically ER-, PR-, and HER2-negative and have a poor prognosis. Interestingly, some tumours with a favourable prognosis also cluster in the basal-like group (adenoid cystic and secretory carcinomas). Approximately 70–80% of basal-like tumours are clinically triple negative and vice versa.

Pleomorphic lobular carcinoma: is it more similar to a classic lobular cancer or to a high-grade ductal cancer?

BackgroundPleomorphic invasive lobular carcinoma (P-ILC) is an uncommon variety of invasive lobular carcinoma with aggressive clinical features. Little is described in the literature regarding this topic.Materials and methodsWe reviewed our experiences from 2010 to 2015 and compared 40 patients with P-ILC, 126 patients with classic-ILC (C-ILC) and 574 cases of high-grade invasive ductal carcinoma (HG-IDC). We studied the histologic and immunohistochemical features, clinical presentation and surgical treatment.ResultsP-ILC is diagnosed at the same age and tumor diameter as those of the other two histologic types. It is associated more frequently with multiple lymph node metastases and high proliferative index, and HER2/neu is amplified in 10% of cases. In spite of sharing some histologic characteristics with C-ILC (same growth pattern, loss of E-cadherin expression, same genetic pathway), its clinical and pathologic features define an autonomous entity. Its surgical treatment is similar to those of C-ILC and HG-IDC.ConclusionThis is the first review comparing these three pathologic entities. Our findings may be useful in understanding this variety of invasive lobular carcinoma, and further studies are certainly needed in this field.

Invasive ductal carcinoma ex pleomorphic adenoma of the lacrimal gland - a long term follow-up case

We experienced a case of malignant orbital tumor in a 72-year-old Japanese man. He noticed protrusion of his left eye, and received resection of the left orbital tumor. The tumor contained several different components such as high-grade invasive ductal carcinoma, low-grade/minimally invasive adenocarcinoma and pleomorphic adenoma. Pathological diagnosis of high-grade invasive ductal carcinoma ex pleomorphic adenoma of the left lacrimal gland was made. He had undergone surgical removal of the left lacrimal gland tumor at the other hospital 19years before, and the surgical specimen revealed that most part of the tumor was pleomorphic adenoma but low-grade/minimally invasive adenocarcinoma was included as a minor component (low-grade/minimally invasive adenocarcinoma ex pleomorphic adenoma). Thus, we could observe the natural course of low-grade/minimally invasive adenocarcinoma ex pleomorphic adenoma which transformed into high-grade invasive ductal carcinoma ex pleomorphic adenoma. Lacrimal gland ductal carcinoma is an extremely rare tumor, and only 25 cases have been reported before in English literature. Moreover, our case is the 5th case of lacrimal gland ductal carcinoma ex pleomorphic adenoma.

Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI

We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis. A CEST-FISP MRI protocol was used to image a flank SKOV3 tumor model. Bloch fitting modified to include the direct estimation of pH was developed to generate parametric maps of tumor pHe in the SKOV3 tumor model, a patient with high-grade invasive ductal carcinoma, and a patient with metastatic ovarian cancer. The acidoCEST MRI results of the patient with metastatic ovarian cancer were compared with DCE MRI and histopathology. The pHe maps of a flank model showed pHe measurements between 6.4 and 7.4, which matched with the expected tumor pHe range from past acidoCEST MRI studies in flank tumors. In the patient with metastatic ovarian cancer, the average pHe value of three adjacent tumors was 6.58, and the most reliable pHe measurements were obtained from the right posterior tumor, which favorably compared with DCE MRI and histopathological results. The average pHe of the kidney showed an average pHe of 6.73 units. The patient with high-grade invasive ductal carcinoma failed to accumulate sufficient agent to generate pHe measurements. Optimized acidoCEST MRI generated pHe measurements in a flank tumor model and could be translated to the clinic to assess a patient with metastatic ovarian cancer.

P53 alteration in morphologically normal/benign breast tissue in patients with triple-negative high-grade breast carcinomas: breast p53 signature?

p53 alterations have been identified in approximately 23% of breast carcinomas, particularly in hormone receptor-negative high-grade carcinomas. It is considered to be an early event in breast carcinogenesis. Nevertheless, the putative precursor lesion of high-grade breast carcinoma remains elusive. Breast excision specimens from 93 triple-negative high-grade invasive ductal carcinomas, 48 estrogen receptor (ER)-positive/progesterone receptor-positive/Her2-negative non-high-grade invasive ductal carcinomas, and 50 mammoplasty breasts were selected. At least 2 tissue blocks with tumor and adjacent benign tissue were sectioned and subjected to immunohistochemistry staining for p53. TP53 gene sequencing was performed on select tumors. Further immunohistochemistry staining for ER and Ki-67 was performed on consecutive sections of tissue with p53-positive normal/benign cells. Of the 93 high-grade carcinomas, 51 (55%) were positive for p53 alteration, whereas only 3 (6.25%) of the 48 non-high-grade carcinomas were p53 altered. Focal p53 positivity in adjacent normal/benign breast tissue was identified in 19 cases, and 18 of them also had p53 alteration in their carcinomas. Only 1 case had focal p53 staining in normal/benign tissue, but the tumor was negative for p53 alteration. No p53 staining positivity was identified in the mammoplasty specimens. The p53-stained normal/benign cells were ER negative and did not show an increase in the Ki-67 labeling index. These findings indicate that the p53 staining positivity in normal/benign breast tissue is not a random event. It could be considered as the "p53 signature" in breast and serve as an indicator for future potential risk of p53-positive high-grade breast carcinoma.