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Aims Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. Methods and results All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. Conclusions Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy.

The precise B cell of origin and molecular pathogenesis of nodal marginal zone lymphoma (NMZL) remain poorly defined. To date, due to the rarity of NMZL, the vast majority of already-published studies have been conducted on a limited number of samples and the technical approach to analyze the immunoglobulin genes was of amplifying rearranged variable region genes with the classical direct sequencing of the PCR products followed by cloning. Here, we studied the B cell Ig heavy-chain repertoires by next-generation sequencing (NGS) in 30 NMZL cases. Most of the cases were mutated (20/28; 71.5%) with homologies to the respective germ line genes ranging from 85 to 97, 83%, whereas 8/28 (28.5%) were unmutated. In addition, our results show that NMZL cases have a biased usage of specific immunoglobulin heavy-chain variable (IGHV) region genes. Moreover, we documented intraclonal diversity in all (100%) of the mutated cases and ongoing somatic hypermutations (SHM) have been confirmed by hundreds of reads. We analyzed the mutational pattern to detect and quantify antigen selection pressure and we found a positive selection in 4 cases, whereas in the remaining cases there was an unspecific stimulation. Finally, the disease-specific survival and the progression-free survival were significantly different between cases with mutated and unmutated IGHV genes, pointing out mutational status as a possible new biomarker in NMZL. Electronic supplementary material The online version of this article (10.1007/s00428-019-02712-8) contains supplementary material, which is available to authorized users.

Alveolar soft part sarcomas (ASPSs) are rare malignant tumors representing ∼1% of all soft tissue sarcomas. Most ASPS occurring in the central nervous system are metastases. In contrast, primary intracranial ASPSs are extremely rare and only 8 cases have been previously reported in English literature. Here, we report a case of primary alveolar soft part sarcoma in a 16-year-old female patient with no evidence of primary extracranial tumors. Histologically this case fulfilled the criteria of ASPS, and a molecular confirmation has been archived. To date, only 9 primary intracranial ASPS cases, including ours, have been reported in the literature. This report highlights the clinical and pathological characteristics, differential diagnosis, and molecular analysis of primary ASPS of the central nervous system.

Patient: Male, 63-year-old Final Diagnosis: Erdheim-Chester disease Symptoms: Splenic rupture Medication: — Clinical Procedure: Splenectomy Specialty: Anatomy • Hematology • Pathology Objective: Rare disease Background: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by foamy histiocytes, Touton-like giant cells, and fibrosis, typically affecting the diaphyseal and metaphyseal region of the long bones but that can involve any organ or tissue. ECD is usually associated with the BRAF V600E mutation or with other molecular mutations inserted in the MAPK cascade. Case Report: We present the case of a 63-year-old man with a previous history of myocardial infarction who underwent an emergency splenectomy for splenic rupture after an accidental fall. Histological examination of the spleen showed a diffuse xanthogranulomatous proliferation (CD68+, CD163+, S100–, CD1a–) with rare Touton-like giant cells in the red pulp. Based on the histologic findings, a diagnosis of ECD was made. However, skeletal involvement and BRAF V600E mutation were not detected. Conclusions: Cases of non-Langerhans cell histiocytosis that are histologically consistent with ECD in unusual sites have been increasingly described. There is also anecdotal evidence for cases being associated with mutations besides BRAF V600E or with no genetic alteration and no skeletal involvement. Likewise, the spectrum of clinical and molecular features of ECD can be broader than previously considered. Furthermore, there is evidence that various phases of the disease can show different clinical presentations with distinct prognostic impact, according to the mutational spectrum. Recognizing ECD at an early stage allows more effective patient management, and pathologists and clinicians should be aware of the unusual clinical presentations of this rare condition.

Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38 years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis.

Dysembryoplastic neuroepithelial tumors (DNT) is a benign (World Health Organisation, WHO, grade I) glioneuronal tumor and it represent one of the most frequent neoplasm in patient affected by seizures. The epileptic neuronal activity can be determined by abnormal synchronization, excessive glutamate excitation and\or inadequate GABA inhibition. Increasing evidence suggests that the astrocytes might be involved in this process even if neurons play a relevant role. In particular astrocytes promote the clearance of glutamate, a potent excitatory neurotransmitter of the central nervous system. Indeed, elevated concentrations of extracellular glutamate may determine iper-excitability and seizures as well as other neurological disorders. So, astrocytes, converting glutamate into glutamine via the enzyme glutamine synthetase (GS), could play a protective anti-seizures role. In the present study, we analyzed the immunohistochemical expression of GS in 20 DNTs specimens documenting a constant immunoistochemical expression of GS in astrocytes of the lesional tissue and of the cerebral cortex.

Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38 years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRAS

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a benign lesion composed of histiocytes and mesothelial cells, usually found during cardiac surgery. To date, no more than 50 cases are reported in literature, and pathogenesis is still unclear even if different theories have been proposed. Here we report a case of MICE encountered during aortic valve replacement with typical histological features and extensive immunohistochemical investigation. To date, little information is available about the pathogenesis of MICE. We review the current literature focusing on the role of adhesion molecules such as CD31.

Objective This study presents a review of our experience with minimally invasive mitral valve surgery (MIMVS) in patients with a previous cardiac procedure performed through a sternotomy over a 10-year period. Methods From November 2003 to August 2013, 173 patients (age 61.3 ± 12.4 years) underwent reoperative MIMVS through a right minithoracotomy. Previous operations were coronary artery bypass grafting (n = 49; 28.6%), a mitral valve procedure (n = 120; 70.1%), an aortic valve procedure (n = 32; 18.7%), and other operations (n = 14; 8.1%). The mean euroSCORE was 11.2 ± 3.8. The time to redo surgery was 6.9 ± 4.2 years. Results Procedures were performed with central aortic cannulation in 55 patients (31.7%) and peripheral cannulation in 118 (68.3%). A transthoracic clamp was used in 58 patients (33.5%), an endoaortic balloon in 72 (41.6%), hypothermic ventricular fibrillation in 23 (13.2%), and beating heart in 20 (11.5%). Mean cardiopulmonary bypass and crossclamp times were 160 ± 58 minutes and 82 ± 49 minutes, respectively. Mitral repair was performed in 53 patients (30.6%). Forty-three patients (24.7%) had an additional cardiac procedure. Conversion to sternotomy was necessary in 2 patients (1.1%) and reoperation for bleeding in 11 patients (6.3%). Thirty-day mortality was 4.1% (n = 7). Major morbidities included stroke (n = 11; 6%) and new-onset dialysis requirement (n = 4; 2.3%). The mean blood transfusion requirement was 1.4 ± 1.1 units. Mean follow-up was 3.3 ± 2.6 years. Survival at 1, 5, and 10 years was 93.1% ± 1.9%, 87.5% ± 2.7%, and 79.7% ± 3.8%, respectively. Conclusions Reoperative mitral valve surgery can be safely performed through a right minithoracotomy with good early and late outcomes. The avoidance of extensive surgical dissection, optimal valve exposure, and low blood transfusion are the main advantages of this technique.

OBJECTIVES: Triple valve surgery (TVS) is still a challenge for surgeons because of prolonged cardiopulmonary bypass (CPB) and myocardial ischaemic times. The reported operative mortality rate for TVS ranges between 2.5 and 25%; long-term survival is also diminished, with reported survival rates at 5 and 10 years of 75–82 and 61–75%, respectively. The objective of our study is to define early and late clinical outcomes, reporting the initial experience in the treatment of triple valve disease through a minimally invasive approach. METHODS: A retrospective, observational, cohort study was undertaken of prospectively collected data on 106 patients who underwent TVS at our institution between October 2001 and June 2013. A total of 101 procedures were done through the standard median sternotomy; however, in 5 patients, the surgical procedure was carried out through a right minithoracotomy. Univariate analysis was performed to identify predictors of early and late survival. RESULTS: The in-hospital mortality rate was 5.6% (6 of 107 patients). Predictors of early mortality were: previous cardiac surgery [odds ratio (OR) 4, 95% confidence interval (CI) 1.08–5.2, P= 0.04], preoperative left ventricular ejection fraction (LVEF) (OR 0.9, 95% CI 0.8–1.1, P= 0.003), prolonged CPB time (OR 1.02, 95% CI 1.01–1.04, P= 0.01) and postoperative pulmonary complications (OR 8, 95% CI 5.8–41, P= 0.0001). Five- and 10-year survival rates were 85 ± 3 and 65 ± 9%, respectively. In univariate analysis, diabetes [hazard ratio (HR) 2.5, 95% CI 1–6.2, P= 0.045], preoperative dialysis (HR 3, 95% CI 2–4.7, P= 0.001), unstable angina (HR 4.8, 95% CI 1–18, P= 0.03), preoperative LVEF (HR 0.9, 95% CI 0.8–1.1, P= 0.02), concomitant coronary artery bypass grafting (CABG) (HR 2.5, 95% CI 1.5–5.7, P= 0.006), prolonged CPB time (HR 1.02, 95% CI 1.01–1.13, P= 0.006), postoperative pacemaker (PMK) implantation (HR 6.2, 95% CI 1.3–18, P= 0.01) and postoperative pulmonary complications (HR 3.3, 95% CI 2.1–7.3, P= 0.002) were found to be significant predictors of late mortality following TVS. The freedom rates from valve-related complications and reoperation at 10 years were 95 ± 2 and 97 ± 2%, respectively. The 10-year freedom rates from thromboembolism and anticoagulation-related haemorrhage were 88 ± 5 and 88 ± 4%, respectively. CONCLUSIONS: TVS offers encouraging short-term and long-term patient survival; these good results after TVS in patients with advanced valvular heart disease justify aggressive surgical therapy in these patients. TVS with a minimally invasive approach is feasible and could be another treatment option.

OBJECTIVES: The aim of the present study was to monitor performance and learning effects for thoracic aortic surgery. In addition, we evaluated the volume–outcome relationship of patients undergoing surgery of the thoracic aorta, comparing the results of two highervolume surgeons (HVSs) with six lower volume surgeons. METHODS: A total of 867 thoracic aortic procedures (elective cases n= 753 and Type A acute dissection n= 114) were performed from 2003 to 2013 by eight surgeons (range 28–238 procedures) at our institution. Departmental and individual performance was monitored using control charts, with a predetermined acceptable failure rate of 10%. Perioperative death or one or more of four adverse events constituted failure. Moreover, results of two higher-volume operators (n= 460; 53%) were compared with those of six lower-volume operators (n= 407; 47%). RESULTS: The incidence rate of in-hospital mortality for elective cases was 2% and for Type A dissection repair 9.6%. Institutional control charts revealed that the surgical process was under control for all the study periods apart from small periods of worse than expected performance which were congruent with new surgeons joining the programme. The predominant surgical failure was reoperation for bleeding. There were differences between surgeons with regard to the learning curves and performance. No significant differences were observed between high- and low-volume surgeons in terms of mortality and morbidity for elective cases. However, high-volume surgeons presented a trend suggesting a higher mortality rate in Type A aortic dissection repair (17.1 vs 6.3%; P= 0.09). CONCLUSIONS: Thoracic aortic surgery can be performed with similar results by high- and low-volume surgeon. Control charts can facilitate learning effects and performance monitoring. Implementation of continuous departmental and individual performance monitoring is practicable.

OBJECTIVES: Mitral valve (MV) surgery for ischaemic mitral regurgitation (IMR) in patients with depressed left ventricular ejection fraction (LVEF) is associated with poor outcomes. The optimal surgical strategy for IMR in these patients remains controversial. The objective of this study was to compare the early mortality and mid-term survival of MV repair versus MV replacement in patients with IMR and depressed LVEF undergoing coronary artery bypass grafting (CABG). METHODS: A retrospective, observational, cohort study was undertaken of prospectively collected data on 126 consecutive CABG patients with IMR and LVEF

Background We aimed to study the results of minimally invasive mitral valve repair performed by 5 young surgeons who were trained in mitral valve repair directly through a minimally invasive approach, and a senior surgeon who introduced the technique at our institution and was responsible for the training program. Methods This was a retrospective, observational cohort study of prospectively collected data from 595 consecutive patients who underwent minimally invasive mitral repair performed by 5 trainees (n = 240, 40.3%) and by our lead consultant (n = 355, 59.7%) between 2007 and 2013. Treatment selection bias was controlled by constructing a propensity score from core patient characteristics and it was included along with the comparison variable in the multivariable analyses of outcome. Results Patients operated on by trainees were more likely to be female ( p = 0.04), older ( p = 0.001), and with history of atrial fibrillation ( p = 0.001). Trainees required a significant longer cardiopulmonary bypass (137 ± 56 vs 123 ± 52 minutes; p = 0.003) and aortic clamp time (97 ± 41 vs 83 ± 40 minutes; p = 0.001). I-hospital mortalities were 1.3% in the trainees group and 0.8% in the senior surgeon group ( p = 0.6). The incidence of stroke (1.7% vs 2.5%; p = 0.5), conversion to sternotomy (2.6% vs 3.5%; p = 0.5), and conversion to mitral valve replacement (12.5% vs 10.9%; p = 0.6) were similar between groups. No differences were found regarding other complications. Five-year survival (88.9% vs 89.5%; p = 0.4) and freedom from reoperation (94.5% vs 95.1; p = 0.6) were similar between groups. Conclusions Minimally invasive mitral valve repair is a safe and reproducible surgical technique that can be taught successfully to cardiac trainees.

Figure 1: 3D Angio-computed tomography (CT) scan reconstruction showing type B dissection in the presence of an aberrant right subclavian artery coexisting with a common bicarotid trunk. The common carotid trunk arose as the first branch, followed by the left subclavian artery and the aberrant right subclavian artery. Figure 2: Postoperative 3D angio-CT scan reconstruction. The patient underwent a hybrid procedure consisting of aortic arch replacement with a trifurcated Dacron prosthesis plus frozen elephant trunk. The right aberrant subclavian artery was ligated and its origin covered with the stent graft.