Regional lymph node metastases in a patient with adenosquamous breast cancer with syringomatous component

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Regional lymph node metastases in a patient with adenosquamous breast cancer with syringomatous component

IntroductionLow-grade adenosquamous breast cancer (ASBC) is a rare histological subtype of metaplastic breast cancer. Even tough it is a triple negative cancer, it is characterised by a good prognosis, low probability of distant metastases and higher risk of local relapses.Clinical CaseThis is a clinical case of a 65-year-old woman with a retroareolar nodule on the left breast. After histological examination a diagnosis of low-grade adenosquamous breast cancer was established. Further examination of lymph nodes showed regional metastasis of ASBC.DiscussionDue to its specific growth patterns the diagnosis could easily be mistaken, mostly on core biopsy samples. Vast differential diagnosis is required. The definitive diagnosis could be given on histological examination of surgical sample. Therefore, the recommended treatment is surgical removal of the lesion until more follow-up data is available in literature.

Latest changes in the molecular classification of breast cancer and triple negative breast cancer

Breast cancer (BC) is a heterogeneous disease including multiple histological subtypes with different biological behavior and clinical outcome for the patient. Due to its heterogeneity, BC is classified into different groups, providing possibilities for target therapies and improving the outcome – histological, TNM classification, molecular classification. The molecular classification, proposed at the beginning by Perou et al in 2000, divides BC into 5 subtypes - Luminal A, Luminal B, HER 2 enriched, claudin-low and basal like.More attention should be paid to the further classification of basal like BC. This is also a heterogeneous disease including triple negative breast cancers (TNBC). They show no expression of ER, PrR or HER2 and are considered difficult to treat. Despite the bad prognosis, some of these patients demonstrate great benefit from the traditional neoadjuvant chemotherapy. Lehman et al. identified 6 molecular subtypes of TNBC, using gene expression profiling – basal like 1 (BL1), basal like 2 (BL2), mesenchymal (M), mesenchymal stem-like (MSL), immunomodulatory (IM) and luminal androgen receptor (LAR).However, after histopathological quantification and laser-capture microdissection they refined their classification and in 2016 the new molecular classification of TNBC excluding the IM and MSL types was published. The working group has concluded that the characteristics of the tumors in these two groups were due to tumor-infiltrating lymphocytes and tumor-associated stromal cells and not to the tumor cells. The refinement of the classification of TNBC provides a better distribution of the patients into the different groups and better response to the applied therapy

Exceptional and Durable Responses to TDM-1 After Trastuzumab Failure for Breast Cancer Skin Metastases: Potential Implications of an Immunological Sanctuary

Breast Cancer (BC) skin metastases represent a challenging clinical scenario. Although they usually arise when other distant metastases are already present, they may also represent a form of locoregional recurrence (LRR). Systemic therapy in this setting may have a role both in case a radical locoregional approach is unfeasible in order to achieve disease control, and as adjuvant strategy after radical removal of cutaneous lesions, in order to prevent or delay subsequent disease spread. Systemic therapy for HER2+ metastatic BC (MBC) currently relies on anti-HER2 targeted agents. In this context TDM1 is an option in trastuzumab-resistant patients.Here we present 2 cases of isolated skin metastases in patients with HER2+ BC progressing during or early after trastuzumab-based therapy, showing impressive responses to TDM1. We hypothesize that the unique properties of skin immune microenvironment may explain the failure of trastuzumab, which exerts its action also through immunological mechanisms, and the subsequent outlier responses to TDM1, that relies on a partially different mechanism of action

Exceptional and Durable Responses to TDM-1 After Trastuzumab Failure for Breast Cancer Skin Metastases: Potential Implications of an Immunological Sanctuary

Breast Cancer (BC) skin metastases represent a challenging clinical scenario. Although they usually arise when other distant metastases are already present, they may also represent a form of locoregional recurrence (LRR). Systemic therapy in this setting may have a role both in case a radical locoregional approach is unfeasible in order to achieve disease control, and as adjuvant strategy after radical removal of cutaneous lesions, in order to prevent or delay subsequent disease spread. Systemic therapy for HER2+ metastatic BC (MBC) currently relies on anti-HER2 targeted agents. In this context TDM1 is an option in trastuzumab-resistant patients.Here we present 2 cases of isolated skin metastases in patients with HER2+ BC progressing during or early after trastuzumab-based therapy, showing impressive responses to TDM1. We hypothesize that the unique properties of skin immune microenvironment may explain the failure of trastuzumab, which exerts its action also through immunological mechanisms, and the subsequent outlier responses to TDM1, that relies on a partially different mechanism of action

Integration of tumour infiltrating lymphocytes, programmed cell-death ligand-1, CD8 and FOXP3 in prognostic models for triple-negative breast cancer: Analysis of 244 stage I-III patients treated with standard therapy.

Tumour infiltrating lymphocytes (TILs) are an established prognostic biomarker for triple-negative breast cancer (TNBC). We evaluated the role of programmed cell-death ligand-1 (PD-L1), CD8 and FOXP3 expression in refining a prognostic model for non-metastatic TNBC beyond classic factors and TILs.Primary tumour samples from 244 early patients with TNBC, all treated with surgery and chemotherapy, were collected. Stromal TILs were evaluated on haematoxylin-eosin slides according to guidelines. PD-L1, CD8 and FOXP3 were assessed by immunohistochemistry and evaluated by digital pathology.TILs, PD-L1, CD8 and FOXP3 were positively correlated with each other (P 0.001). TILs were confirmed as an independent prognostic factor. When PD-L1, CD8 and FOXP3 were added to multivariable models including classic factors (age, stage, histologic grade) and TILs, PD-L1 provided the largest amount of additional prognostic information: likelihood ratio χBeyond clinicopathological factors and TILs, other immune biomarkers may add prognostic information for early TNBC. The increased PD-L1 expression on residual disease after neoadjuvant chemotherapy strengthens the rationale of testing immune checkpoint inhibitors in the post-neoadjuvant setting

ERBB2mRNA expression and response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-positive breast cancer

Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the levels of human epidermal growth factor receptor 2 gene (ERBB2) mRNA.We analyzed ERBB2 expression using a clinically applicable assay in formalin-fixed para n-embedded (FFPE) tumors (primary or metastatic) from a retrospective series of 77 patients with advanced HER2+ BC treated with T-DM1. The association of ERBB2 levels and response was further validated in 161 baseline tumors from the West German Study (WGS) Group ADAPT phase II trial exploring neoadjuvant T-DM1 and 9 in vitro BC cell lines. Finally

Molecular Biomarkers in Triple-Negative Breast Cancer // Молекулярни биомаркери при тройно негативни карциноми на гърдата

Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen and progesterone receptors and HER2 expression. TNBC is characterized by the worst clinical behaviour with the highest risk of local and distant metastasis and relapses. We aim to evaluate the prognostic role of TILs, CD8 and FOXP3 and their correlations with the clinical and pathological characteristics and disease-free survival (DFS). All analyses were performed with digital software. Our study included 244 patients with TNBC. The clinical and morphological characteristics of the examined cohort include: older patients (>50 years, 56%), patients with II clinical stage disease (49.2%), with ductal invasive breast cancer of non-special type (NST BC) (90,5%), high-grade tumours (87.7%) and tumours with high proliferative index (84.5%). The cut-offs for the examined parameters are TILs -30%, CD8 – 474, FOXP3 – 57. Our results show that high TILs, CD8 and FOXP3 correlate with younger age (<50 years) (р=0.001, р=0.003 and р=0.023), with high grade tumors (p=0.001, p=0.007 and р=0.002), with some histological subtypes (ductal infiltrating NST BC, medullar BC and metaplastic BC) (р=0.008, р=0.002 and р=0.001) and high proliferative index (р=0.046, р=0.027 and р=0.003). TILs were strongly correlated with CD8 and moderately correlated with FOXP3. Also, CD8 strongly correlates with FOXP3. Patients with high CD8 and FOXP3 have better DFS (р=0,001 and р=0,004).Тройно негативният карцином на гърдата (ТНКГ), характеризиращ се с липса на експресия на рецептори за естроген, прогестерон и HER2, е с най-агресивно поведение, най-висок риск от метастази и рецидив. Целта на проучването е да се изследва прогностичната ролята на тумор инфилтриращите лимфоцити (TILs) и експресията на CD8 и FOXP3 от стромалните клетки във връзка с клинико-морфологичните характеристики на изследваните пациенти и преживяемостта без заболяване (DFS). Всички анализи са осъществени с дигитален софтуер. В проучването са включени 244 пациента с ТНКГ. Клинико-морфологичните характеристики на изследваните пациенти включват: пациенти над 50 години (56,60%), диагностицирани във II клиничен стадий (49,2%), с дуктален инвазивен КГ (90,5%), с карциноми с ниска степен на диференциация (87,7%) и висок пролиферативен индекс (84,5%). В проучване cut-off стойностите на изследваните показатели са следните: TILs 30%, CD8 - 474 и FOXP3 – 57. Резултатите ни показват, че високите стойности на TILs CD8 и FOXP3 корелират с по-млада възраст (<50 години) (р=0.001, р=0.003 и р=0.023), с ниската степен на диференциация (p=0,001, p=0,007 и р=0.002), с някои хистологични варианти (дуктален, медуларен и метапластичен) (р=0.008, р=0.002 и р=0.001) и с високия пролиферативен индекс (р=0.046, р=0.027 и р=0.003). TILs демонстрират силна позитивна корелация с CD8 и умерена такава с FOXP3. Установена е корелация и между CD8 и FOXP3

Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms of the Pancreas

Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare neoplasms, composed of at least two components. The neuroendocrine part is always present. Histology is the most important tool for the diagnosis, but in the case of MiNEN, it is also important for the use of immunohistochemistry, which should include neuroendocrine but also ductal and acinar markers. Each component should be specifically described in the final pathology report, including the percentage on the entire tumor mass. The prognosis of MiNEN is very heterogeneous and depends on the different tumor components

New insights in gastrointestinal "pediatric" neoplasms in adult patients: pancreatoblastoma, hepatoblastoma and embryonal sarcoma of the liver. A practical approach by GIPPI-GIPAD Groups

: Pediatric solid neoplasms are rare and very different from those observed in adults. The majority of them are referred to as embryonal because they arise as a result of alterations in the processes of organogenesis or normal growth and are characterized by proliferation of primitive cells, reproducing the corresponding tissue at various stages of embryonic development. This review will focus on embryonal gastrointestinal pediatric neoplasms in adult patients, including pancreatoblastoma, hepatoblastoma, and embryonal sarcoma of the liver. Although they are classically considered pediatric neoplasms, they may (rarely) occur in adult patients. Hepatoblastoma represents the most frequent liver neoplasm in the pediatric population, followed by hepatocellular carcinoma and embryonal sarcoma of the liver; while pancreatoblastoma is the most common malignant pancreatic tumor in childhood. Both in children and adults, the mainstay of treatment is complete surgical resection, either up front or following neoadjuvant chemotherapy. Unresectable and/or metastatic neoplasms may be amenable to complete delayed surgery after neoadjuvant chemotherapy. However, these neoplasms display a more aggressive behavior and overall poorer prognosis in adults than in children, probably because they are diagnosed in later stages of diseases