Cardiovascular pathology in vasculitis.

Vasculitides are diseases that can affect any vessel. When cardiac or aortic involvement is present, the prognosis can worsen significantly. Pathological assessment often plays a key role in reaching a definite diagnosis of cardiac or aortic vasculitis, particularly when the clinical evidence of a systemic inflammatory disease is missing. The following review will focus on the main histopathological findings of cardiac and aortic vasculitides.

CIC-rearranged sarcoma presenting with superior vena cava syndrome: case report.

CIC-rearranged sarcomas are rare mesenchymal neoplasms belonging to the family of undifferentiated small round cell sarcomas. This report details the case of a 45-year-old man presenting with symptoms of mediastinal compression, radiological diagnosis of a mediastinal mass and rapid evolution to full-blown superior vena cava syndrome. The emergency was successfully managed with a pharmacological approach. Formulation of a pathological diagnosis of CIC-rearranged sarcoma was initially supported by fluorescence in situ hybridisation findings and later validated by next-generation sequencing, which showed CIC-DUX4 gene fusion. A chemotherapy regimen was started with immediate benefits for the patient. The spectrum of pathological entities able to cause superior vena cava syndrome is wide, and recognition of rare causes is important to tailor the therapeutic approach to the specific disease. This is, to the best of our knowledge, the first report of CIC-rearranged sarcoma presenting with superior vena cava syndrome.

Malignant Transformation of Giant Cell Tumour of Bone: A Review of Literature and the Experience of a Referral Centre.

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1-9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.

Extremely late-onset pulmonary metastasis from uterine PEComa.

A 79-year-old woman underwent surgical resection of a peripheral, solitary, pulmonary lesion that was diagnosed as malignant PEComa. Her clinical history was positive for uterine leiomyosarcoma, excised 20 years before. Re-evaluation of the primary uterine lesion led to the final diagnosis of lung metastasis from uterine PEComa. While long latency between primary tumour and metastasis is a known and characteristic feature of PEComas, a 20-year interval is unprecedented in the literature.

Acute lymphocytic myocarditis characterized by cardiogenic shock and conduction system abnormalities in patients with Hashimoto's thyroiditis: a case report and review of literature.

Background: Acute myocarditis (AM) is an inflammatory heart disease that may occur as a consequence of autoimmune disorders. Although the correlation between myocarditis and hyperthyroidism has been reported in the literature, the association with hypothyroidism is less frequent. Case summary: We describe a characteristic case of lymphocytic acute myocarditis deteriorated into cardiogenic shock due to Hashimoto's thyroiditis treated with vasopressor and inotropic drugs in combination with corticosteroid. On admission, electrocardiography revealed a sinus tachycardia with 1st degree atrioventricular (AV) block, right bundle branch block (RBBB), and left anterior fascicular block. Laboratory tests demonstrated a severe hypothyroidism and high-titre serum of antibodies against thyroglobulin. She presented a favourable clinical course, restoring haemodynamic stability. A resolution of hypothyroidism and a progressive reduction of the value of antibodies against thyroglobulin occurred. On Day 35, the patient was discharged showing on electrocardiogram the occurrence of left posterior fascicular block, disappearance of 1st degree AV block and partial improvement of RBBB along with the normalization of the left ventricular contractility abnormalities on echocardiography. Discussion: Autoimmune features, mostly Hashimoto's thyroiditis, are associated in lymphocytic acute myocarditis to a worse prognosis and an increased risk of recurrence. More studies are needed to elucidate the underlying mechanism.

AI drives the assessment of lung cancer microenvironment composition.

Purpose: The abundance and distribution of tumor-infiltrating lymphocytes (TILs) as well as that of other components of the tumor microenvironment is of particular importance for predicting response to immunotherapy in lung cancer (LC). We describe here a pilot study employing artificial intelligence (AI) in the assessment of TILs and other cell populations, intending to reduce the inter- or intra-observer variability that commonly characterizes this evaluation. Design: We developed a machine learning-based classifier to detect tumor, immune, and stromal cells on hematoxylin and eosin-stained sections, using the open-source framework QuPath. We evaluated the quantity of the aforementioned three cell populations among 37 LC whole slide images regions of interest, comparing the assessments made by five pathologists, both before and after using graphical predictions made by AI, for a total of 1110 quantitative measurements. Results: Our findings indicate noteworthy variations in score distribution among pathologists and between individual pathologists and AI. The AI-guided pathologist's evaluations resulted in reduction of significant discrepancies across pathologists: three comparisons showed a loss of significance (p > 0.05), whereas other four showed a reduction in significance (p > 0.01). Conclusions: We show that employing a machine learning approach in cell population quantification reduces inter- and intra-observer variability, improving reproducibility and facilitating its use in further validation studies.

PD-L1 testing in metastatic triple negative breast cancer: Results of an Italian survey.

BACKGROUND: Immunotherapy has revolutionized the approach to metastatic triple-negative breast cancers. Atezolizumab was approved for patients with metastatic triple-negative breast cancers whose tumors express PD-L1, determined by SP 142 assay. To assess the availability and practice of SP142 test we administered a survey to all the 15 pathology departments of the Lazio Region during a six-month period. METHODS: The survey comprised 12 questions regarding the availability of SP142 in the pathology departments, the percentage of positive tests, the difficulties of pathologists in cases close to cut-off value and the tested samples. RESULTS: The SP142 assay was available in only eight centers. In case of positive result, most centers (5/8, 62.5%) reported values of PD-L1 expression ranging from > 1 to ⩽ 5%, with values close to the cut-off point (⩾ 1% or < 1%) being the greatest challenge.Most of the centers (6/8, 75%) tested material from both their own and other hospitals. In most centers, the evaluations were performed either on primary tumors or metastasis, in particular lymph nodes (5/8, 62.5%), followed by lung (3/8, 37.5%) and liver (1/8, 12.5%) metastasis. CONCLUSION: Our results raise some important issues concerning the evaluation of PD-L1 in the "real-life" setting, providing strategies for its implementation.

Thoracic Aorta: Anatomy and Pathology.

The aorta is the largest elastic artery in the human body and is classically divided into two anatomical segments, the thoracic and the abdominal aorta, separated by the diaphragm. The thoracic aorta includes the aortic root, the ascending aorta, the arch, and the descending aorta. The aorta's elastic properties depend on its wall structure, composed of three distinct histologic layers: intima, media, and adventitia. The different aortic segments show different embryological and anatomical features, which account for their different physiological properties and impact the occurrence and natural history of congenital and acquired diseases that develop herein. Diseases of the thoracic aorta may present either as a chronic, often asymptomatic disorder or as acute life-threatening conditions, i.e., acute aortic syndromes, and are usually associated with states that increase wall stress and alter the structure of the aortic wall. This review aims to provide an update on the disease of the thoracic aorta, focusing on the morphological substrates and clinicopathological correlations. Information on anatomy and embryology will also be provided.

Recurrent Extreme Bilateral Gigantomastia Caused by Pseudoangiomatous Stromal Hyperplasia (PASH) Syndrome: A Case Report.

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a rare and benign medical condition in which the breast tissue is affected by an abnormal myofibroblastic proliferation, which mimics a low-grade sarcoma angiomatous proliferation. PASH usually presents itself either as a palpable mass or as an incidental diagnosis during breast specimens' histological examination. A few cases have been reported in the literature of a diffuse form of breast PASH syndrome in which the clinical presentation is a bilateral form of gigantomastia without palpable masses. In such cases, the optimal surgical management is still debated due to a significant risk of relapse after breast reduction. Mastectomy seems to be the endpoint of this condition in relapsing cases. Recent studies report a good outcome with a Tamoxifen regimen when surgery cannot be performed, supporting a hormonal component for the etiology of the condition. This study reports on an extremely rare case of bilateral, rapid, and severe PASH in a young patient, presenting as a truly disabling gigantomastia that forced the patient to use a wheelchair due to the excessive breast weights (25 kg the right breast and 21 kg the left). We describe her complicated medical history, her diagnosis, and our course of treatment.

Manual Coronary Thrombectomy in Primary PCI: What a Satisfaction it is Sometimes to Look Into the Catheter.

An 89-year-old woman was referred to our cath lab for a primary percutaneous coronary intervention following electrocardiographic evidence of inferior ST-segment elevation myocardial infarction. A coronary angiography revealed single- vessel disease with complete occlusion of the right coronary artery. After crossing the occlusion with a guidewire, we proceeded with manual thrombectomy using the Eliminate Aspiration Catheter (Terumo Europe). To our knowledge, this is the longest coronary thrombus ever reported to be removed in its entirety.

Adrenocortical carcinoma metastasis. A long story.

INTRODUCTION: Adrenocortical Carcinoma (ACC) is an uncommon adrenal tumor with a predilection for the female population. CASE REPORT: A 55-year-old woman was referred to our attention to undergo laparoscopic cholecystectomy for symptomatic gallstone disease. She underwent a left adrenalectomy for ACC 5 years before; the follow-up was negative for relapse. During the preoperative study an Ultrasound Scanner study demonstrated a liver lesion in S6 - S7, confirmed by a Magnetic Resonance. A PET identified also a lesion on L1 vertebra. The hepatic US-guided biopsy resulted positive for ACC metastasis. After a muldisciplinary evaluation, the patients underwent a local approach to treat both hepatic and vertebral lesions. Laparoscopic cholecystectomy was performed in order to prevent biliary and pancreatic complications. The minimally invasive technique was adopted in order to reduce surgical trauma in oncological patients, even the previous abdominal surgery and percutaneous hepatic treatment. The patient is alive, with no recurrence after 12 months from local treatments. CONCLUSION: This is a very unusual case of double ACC metastases, discovered after the end of standard follow-up and locally treated. The patient is recurrence-free 12 months after these procedures. Minimally invasive approach to treat symptomatic cholecystectomy was used in order to avoid pancreato-biliary complications. This study emphasized the necessity to realize tailored protocols for the follow-up of rare neoplasia, as ACC. KEY WORDS: Adrenocortical carcinoma, Cholecystectomy, Liver metastasis, Thermoablation.

Microenvironmental Factors in Oral Cavity Squamous Cell Carcinoma Undergoing Surgery: Correlation with Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced MRI.

BACKGROUND: In this prospective study, we hypothesized that magnetic resonance imaging (MRI) may represent not only the tumor but also the microenvironment, reflecting the heterogeneity and microstructural complexity of neoplasms. We investigated the correlation between both diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced (DCE)-MRI with the pathological factors in oral cavity squamous cell carcinomas (OSCCs). METHODS: A total of 37 patients with newly diagnosed OSCCs underwent an MR examination on a 3T system. The diffusion coefficient (D), the kurtosis parameter (K), the transfer constants Ktrans and Kep and the volume of extravascular extracellular space ve were quantified. A histogram-based approach was proposed to investigate the associations between the imaging and the pathological factors based on the histology and immunochemistry. RESULTS: Significant differences in the DCE-MRI and DKI parameters were found in relation to the inflammatory infiltrate, tumor grading, keratinization and desmoplastic reaction. Relevant relationships emerged between tumor-infiltrating lymphocytes (TILs) and DKI, with lower D and higher K values being associated with increased TILs. CONCLUSION: Although a further investigation is needed, these findings provide a more comprehensive biological characterization of OSCCs and may contribute to a better understanding of DKI-derived parameters, whose biophysical meaning is still not well-defined.

Prognostic Value of Pre-Treatment [18F]FDG PET/CT Texture Analysis in Undifferentiated Soft-Tissue Sarcoma.

BACKGROUND: Undifferentiated soft-tissue sarcomas (USTS) are one of the most common sarcoma histotypes in adults. The standard of care is surgical excision plus adjuvant radiotherapy, while the use of perioperative chemotherapy is still controversial. The aim of this study was to investigate the value of pre-treatment [18F]FDG PET/CT conventional metrics and textural features in predicting disease-free survival (DFS) and overall survival (OS) in patients with USTS of the limbs and trunk. METHODS: [18F]FDG PET/CT scans of 51 consecutive patients with locally advanced USTS were retrospectively evaluated. Conventional and textural PET parameters were analysed and tested as predictive factors for DFS and OS. RESULTS: During a median follow up of 50.7 months, 23 (45.1%) and 29 (56.9%) patients had death or disease progression, respectively. Univariate analysis revealed a significant association for perioperative treatment, PET volumetric parameters and the textural feature GLCM_correlation with DFS and OS. In multivariate analysis, perioperative treatment and GLCM_correlation were the only independent factors, allowing stratification of the population into three different prognostic classes. CONCLUSION: GLCM_correlation can identify USTS at high risk of relapse and death, thus helping to optimize the perioperative treatment of patients.

On the Additional Information Provided by 3T-MRI ADC in Predicting Tumor Cellularity and Microscopic Behavior.

BACKGROUND: to evaluate whether Apparent Diffusion Coefficient (ADC) values of invasive breast cancer, provided by 3T Diffusion Weighted-Images (DWI), may represent a non-invasive predictor of pathophysiologic tumor aggressiveness. METHODS: 100 Patients with histologically proven invasive breast cancers who underwent a 3T-MRI examination were included in the study. All MRI examinations included dynamic contrast-enhanced and DWI/ADC sequences. ADC value were calculated for each lesion. Tumor grade was determined according to the Nottingham Grading System, and immuno-histochemical analysis was performed to assess molecular receptors, cellularity rate, on both biopsy and surgical specimens, and proliferation rate (Ki-67 index). Spearman's Rho test was used to correlate ADC values with histological (grading, Ki-67 index and cellularity) and MRI features. ADC values were compared among the different grading (G1, G2, G3), Ki-67 (<20% and >20%) and cellularity groups (<50%, 50-70% and >70%), using Mann-Whitney and Kruskal-Wallis tests. ROC curves were performed to demonstrate the accuracy of the ADC values in predicting the grading, Ki-67 index and cellularity groups. RESULTS: ADC values correlated significantly with grading, ER receptor status, Ki-67 index and cellularity rates. ADC values were significantly higher for G1 compared with G2 and for G1 compared with G3 and for Ki-67 < 20% than Ki-67 > 20%. The Kruskal-Wallis test showed that ADC values were significantly different among the three grading groups, the three biopsy cellularity groups and the three surgical cellularity groups. The best ROC curves were obtained for the G3 group (AUC of 0.720), for G2 + G3 (AUC of 0.835), for Ki-67 > 20% (AUC of 0.679) and for surgical cellularity rate > 70% (AUC of 0.805). CONCLUSIONS: 3T-DWI ADC is a direct predictor of cellular aggressiveness and proliferation in invasive breast carcinoma, and can be used as a supporting non-invasive factor to characterize macroscopic lesion behavior especially before surgery.

Clinical Implications of Monogenic Versus Polygenic Hypercholesterolemia: Long-Term Response to Treatment, Coronary Atherosclerosis Burden, and Cardiovascular Events.

Background Familial hypercholesterolemia (FH) may arise from deleterious monogenic variants in FH-causing genes as well as from a polygenic cause. We evaluated the relationships between monogenic FH and polygenic hypercholesterolemia in influencing the long-term response to therapy and the risk of atherosclerosis. Methods and Results A cohort of 370 patients with clinically diagnosed FH were screened for monogenic mutations and a low-density lipoprotein-rising genetic risk score >0.69 to identify polygenic cause. Medical records were reviewed to estimate the response to lipid-lowering therapies and the occurrence of major atherosclerotic cardiovascular events during a median follow-up of 31.0 months. A subgroup of patients (n=119) also underwent coronary computed tomographic angiography for the evaluation of coronary artery calcium score and severity of coronary stenosis as compared with 135 controls. Two hundred nine (56.5%) patients with hypercholesterolemia were classified as monogenic (FH/M+), 89 (24.1%) as polygenic, and 72 (19.5%) genetically undefined (FH/M-). The response to lipid-lowering therapy was poorest in monogenic, whereas it was comparable in patients with polygenic hypercholesterolemia and genetically undetermined. Mean coronary artery calcium score and the prevalence of coronary artery calcium >100 units were significantly higher in FH/M+ as compared with both FH/M- and controls. Finally, after adjustments for confounders, we observed a 5-fold higher risk of incident major atherosclerotic cardiovascular events in FH/M+ (hazard ratio, 4.8; 95% CI, 1.06-21.36; Padj=0.041). Conclusions Monogenic cause of FH is associated with lower response to conventional cholesterol-lowering therapies as well as with increased burden of coronary atherosclerosis and risk of atherosclerotic-related events. Genetic testing for hypercholesterolemia is helpful in providing important prognostic information.

Cocaine Abuse: An Attack to the Cardiovascular System-Insights from Cardiovascular MRI.

Cocaine is the most commonly used illicit drug in the European Union. Its cardiac effects are numerous and diverse, both in acute and chronic abuse, and include myocardial infarction, myocarditis, catecholamine-induced cardiomyopathy, and chronic cardiomyopathy (subclinical, hypertrophic, and dilated phases). Their clinical manifestations are vastly overlapping, and differential diagnosis should be performed using a thorough diagnostic workup featuring clinical history, laboratory tests, electrocardiography, stress test, noninvasive imaging modalities, and coronary angiography. Cardiac MRI has the unique ability of in vivo tissue characterization. This unique feature can play a pivotal role in the differential diagnosis through proper characterization of the myocardial tissue. Especially in acute settings, cardiac MRI makes it possible to distinguish between cocaine-induced myocardial infarction, cocaine-induced myocarditis, and catecholamine-induced cardiomyopathy. Conversely, in chronic cardiomyopathy, cardiac MRI permits evaluation of ventricular function and myocardial tissue, allowing the investigation of the underlying cause. On the one hand, assessing the ventricular function permits differentiation among subclinical, hypertrophic, and dilated phases of chronic cardiomyopathy; on the other hand, cardiac MRI could classify the causes underlying remodeling, including chronic ischemic injury, chronic myocarditis, and cardiac motion impairment. This review analyzes the relationship between pathophysiology, histology, and disease using the existing literature on cardiac MRI cocaine abuse evaluation. © RSNA, 2019.