Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy.

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences.

Aggressive Angiomyxoma of the Vulva: Which Is the Best Management Strategy? Description of a Case Report and Review of Literature of the Last Ten Years.

BACKGROUND: Aggressive angiomyxoma is a rare mesenchymal tumour of the genital tract with a high incidence in women of reproductive age. The aim of our work is to understand which is the best management strategy for this condition, starting from the description of a rare case report up to the performance of a narrative review of the literature. METHODS: We report a case of a 46-year-old woman who came to our attention because of the growth of a 10-centimetre pedunculated, non-soft, non-tender mass of the left labium majus. She underwent surgical excision, and the histologic diagnosis was aggressive angiomyxoma. Due to a lack of tumour-free margins, radicalization surgery was carried out after three months. A review of the literature of the last ten years was performed following the PRISMA statement on MEDLINE (PubMed). We obtained data from twenty-five studies describing thirty-three cases. RESULTS: Aggressive angiomyxoma is characterized by a high recurrence rate of between 36 and 72% after surgery. There is no universal consensus about hormonal therapy, and most studies (85%) describe surgical excision followed by only clinical and radiological follow-up. CONCLUSION: Wide surgical excision is the gold-standard treatment for aggressive angiomyxoma, succeeded by either clinical or radiological (ultrasound or MRI) follow-up.

Identification of novel targets for the diagnosis and treatment of liver fibrosis.

Liver fibrosis is characterized by the excessive deposition of extracellular matrix (ECM) in the hepatic parenchyma and represents an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. Hepatic stellate cells (HSCs) are the major cell type responsible for liver fibrosis. Following liver injury, HSCs become activated and transdifferentiate into myofibroblasts (MFBs) that lead to intrahepatic ECM accumulation. In the present study, we performed a meta­analysis of datasets which included whole-genome transcriptional data on HSCs in the quiescent and activated state from two different rodent species and identified commonly regulated genes. Several of the genes identified, including ECM components, metalloproteinases and growth factors, were found to be well­known markers for HSC activation. However, other significant genes also appeared to play important roles in hepatic fibrosis. The elucidation of the molecular events underlying HSC activation may be key to the identification of potential novel pharmacological targets for the prevention and treatment of liver fibrosis.

Wilms' tumor 1 (WT1) protein expression in human developing tissues.

Several genes playing crucial roles in human development often reproduce a key role also during the onset and progression of malignant tumors. WT1, a transcription factor expressed with a dynamic pattern during human development, has either oncogenic or suppressor tumor properties. A detailed analysis of the immunohistochemical profile of WT1 protein in human developmental tissues could be exploitable as the rational for better understanding its role in cancerogenesis and planning innovative WT1-based therapeutic approaches. This review focuses on the dynamic immunohistochemical expression and distribution of WT1 protein during human ontogenesis, providing illustrations and discussion on the most relevant findings. The possibility that WT1 nuclear/cytoplasmic expression in some tumors mirrors its normal developmental regulation will be emphasized.

A fatal stab wound causing selective injury to the left anterior descending coronary artery, myocardial infarction and delayed cardiac tamponade.

We describe an unusual case of delayed cardiac tamponade that led to death 9 days after a penetrating stab wound. The injury consisted of a longitudinal tear in the LAD coronary artery, with an occlusive thrombus and the rupture of the coronary wall into a pseudo-aneurysmatic peri-coronary hematoma. As imaging evidence of pericardial effusion and ischemic electrocardiographic changes were lacking, the diagnosis was only made during post-mortem examination.

Incidental Epstein-Barr virus associated atypical lymphoid proliferation arising in a left atrial myxoma: a case of long survival without any postsurgical treatment and review of the literature.

We report a case of left atrial cardiac myxoma harbouring an incidental atypical B-cell lymphoid proliferation. Histology disclosed classic myxoma cells embedded in a mucopolysaccharide-rich matrix and a micronodular atypical lymphoid proliferation under the surface of the mass. Myxoma cells were immunoreactive for calretinin, while lymphoid cells expressed B lineage markers (CD 20+, CD79a), without evidence of clonality. Moreover, they were LMP1 positive; EBNA2 negative; KSHV/HHV8 negative; and, by in situ hybridization, EBER/Epstein-Barr virus (EBV) positive and Kappa and Lambda negative. According to the 2008 WHO schemes, the present case shares close similarities either with diffuse large B-cell lymphomas growing in the context of long-standing chronic inflammation or with primary effusion lymphomas, solid variant, both associated with EBV infection. This is the sixth case of incidental atypical lymphoid proliferation discovered in a cardiac myxoma reported so far. The optimal treatment of such lesions remains undefined, but their clinical course is indolent. After an accurate staging workup, without any postsurgical treatment, the patient we observed has been well with no recurrence of the disease at 6 years of follow-up.

Multiple coronary artery-left ventricular fistulas causing sudden death in a young woman.

Multiple coronary artery fistulae arising from right and left coronary arteries were found at autopsy in a 22-year-old woman, dying suddenly while playing football. This is the fifth pathologic description of this finding with biventricular involvement. We found microscopic evidence of postischemic scars and foci of myocardial calcifications in the left ventricular wall.