The role of detailed medical history for the early diagnosis of familial bradycardia in a patient with associated atrial fibrillation: case report.

Background: Bradycardia represents a frequent reason for medical presentation and has a complex aetiology, including genetic disorders, like LMNA mutation. LMNA mutation is responsible for laminopathies, including LMNA -cardiomyopathy. Cardiac involvement is prevalent and is linked to dilated cardiomyopathy associated with conduction block, which is anticipated by bradyarrhythmia and supraventricular tachyarrhythmia. LMNA mutation carriers have higher risk for sudden cardiac death (SCD), malignant ventricular tachycardia, and extreme bradycardia. Case summary: A 48-year-old female presented for recurrent episodes of dizziness, lightheadedness, headache, and fatigue, occurring at rest. The past medical history was positive for hypertension and one episode of paroxysmal atrial fibrillation. The family medical history was positive; both children and the patient's mother are known with bradycardia. The electrocardiogram showed sinus bradycardia, and the echocardiography revealed a mild concentric hypertrophy of the left ventricle, associated with impaired relaxation diastolic dysfunction. The 24 h Holter monitoring recorded sinus bradycardia, multiple pauses, paroxysmal atrial fibrillation, and multiple episodes of junctional rhythm. The positive family medical history suggested a genetic link. Further, genetic testing was performed, revealing a mutation of the LMNA gene. Discussion: Despite apparently benign at the initial presentation, the correct diagnosis and management required detailed medical history and extensive investigation of both the patient and the first-degree relatives. As the LMNA mutation carriers have a higher risk for SCD and have a mortality risk of 40% at 5 years, we emphasize the role of early diagnosis and periodic monitoring for preventing the worsening of the condition. .

Achenbach Syndrome - Case Report and Discussion on the Interdisciplinary Approach of a Patient.

We present a case of Achenbach syndrome, which is an alarming disease for both patients and physicians, although it is a rare, benign and self-limiting disorder. It is also reported as "paroxysmal finger haematoma", but the majority of cases are misdiagnosed, and unnecessarily investigated and treated.

An unusual shaped mass filling the right cardiac chambers in a woman with a vascular malformation.

We present an interesting case of a patient with uterine leiomyoma and a vascular abnormality of the internal iliac artery and peri­uterine veins presenting a right intracardiac mass with an extremely unusual and misleading shape, requiring surgical removal and pathological examination to confirm the diagnosis.

Primary angiosarcoma of the vulva: report of a case misdiagnosed as a benign tumor.

Primary vulvar angiosarcomas have a propensity for varied macroscopic and histologic appearance that initially may not suggest a vascular malignant neoplasm. Therefore, the rarity of the lesion and it's morphologic diversity may contribute to the high rate of misdiagnosis. We present the case of a 43-year old patient with a primary vulvar lesion, initially misdiagnosed as an angiofibroma. Microscopic examination of the recurrence together with immunohistochemical profile were in favor on a poorly differentiated angiosarcoma. Early diagnoses can improve prognoses in angiosarcomas and, in the case of recurrences, as in the present case, may lead to changes in therapy.

Extensive Left Ventricular Thrombosis with Concomitant Pulmonary Embolism.

A 57-year-old non-obese female patient with a history of heavy smoking, chronic obstructive pulmonary disease and hypertension was admitted to the hospital as an emergency for acute hemoptysis and signs of congestive heart failure. To assess the source of hemoptysis, computed tomography (CT) pulmonary angiography was performed, which confirmed a bilateral pulmonary embolism of the apical branches. The routinely performed transthoracic echocardiography (TTE) revealed an enlarged left ventricle with severely reduced ejection fraction (EF = 25%) due to global hypokinesia and multiple, mobile, echogenic masses. To increase the diagnostic accuracy, real-time three-dimensional (Live 3D) imaging of the masses was added which described multiple left ventricular (LV) thrombi. Successful resolution of intraventricular thrombi was noticed after treatment with oral anticoagulant therapy (acenocumarol), despite the lack of regular INR control.

Endometrial adenocarcinoma with gastrointestinal differentiation - a newly described entity, with morphologic diversity.

Gastrointestinal type of endometrial carcinoma is a newly described entity for which clearly defined diagnostic criteria have only recently been published. Among morphologic criteria, gastrointestinal mucinous adenocarcinoma of endometrium must not show a typical endometrioid component. We present a case with morphologic diversity, with areas showing gastric and intestinal differentiation as well as an endometrioid-like component. However, the endometrioid-like component not only did not show classic squamous metaplasia, but was also MUC6-positive, while the positivity for ER/PR was only focal. The recognition of gastric/gastrointestinal differentiation in endometrial carcinomas is best accomplished using both morphology and immunohistochemistry rather than either alone.

Milia en Plaque of the Earlobe.

Introduction: Milia en plaque is an uncommon benign dermatosis. Case presentation:We present a case of a 43-year-old Caucasian man with a five-month history of asymptomatic symmetric lesions on the earlobes that has been previously treated by self-medication with potent topical steroids, emollients, cosmetic procedures, herbal medication and punch-procedure. Based on clinical examination, a diagnosis of milia on earlobes was established and treated with topical steroids. Discussion and conclusion:Milia en plaque of the earlobes has yet not been reported. Treatment is not different from other localizations.

Primary extrauterine cystic low-grade endometrioid stromal sarcoma mimicking stromal endometriosis. A case report emphasizing the differential diagnosis and its potential local aggressive behavior.

Genital and pelvic endometriosis is a frequently encountered lesion and its importance rely on associated symptoms and its propensity for malignant transformation. In the present paper we comment on the importance of correctly diagnose the malignant transformation of an endometriotic lesion into a cystic low-grade endometrial stromal sarcoma, which is a very rare event. Moreover, we discuss the ability of a low-grade endometrial stromal sarcoma to locally recurr and the differential diagnosis with stromal endometriosis, a lesion that is very rare, almost always microscopic and solid.

Analysis of Clinical-Pathological Data with Impact on Overall Survival in Male Breast Carcinoma: An International Multi-Institutional Study of 217 Cases.

Background: The aim of this study was to evaluate clinical-pathological parameters with impact on overall survival (OS) in male breast carcinoma (MBC). Methodology: We assessed OS at 5 years and at 10 years respectively, as well as OS according to age, tumor size, microscopic type, histological grade, axillary lymph node status, and molecular profile. Results:Two hundred seventeen cases, with a mean age of 62 (range: 18- 85), right breast involvement (52.53%), invasive carcinoma of no special type (86.63%), G2 histological grade (55.4%), T2 (54.41%), N+ (65.89%) and Luminal A molecular subtype (85.29%) were identified. ER, PR and AR were positive in 89.71%, 83.82% and 93.29% of cases, respectively. HER2 was overexpressed in 8.33% of cases and a high Ki67 proliferation index was present in 75% of cases. The 5-year OS was 67.2%, whereas 10-year OS was 48.5%; OS was 92.7% at 5 years and 73.8% at 10 years in axillary lymph node (LN) negative cases, while OS was 59.7% at 5 years and 41.3% at 10 years in axillary LN positive cases (p=0.003). Conclusions: Age at diagnosis ( 60 years), larger tumor size, presence of LN metastases and absence of oncological treatment are negative factors influencing prognosis, with only axillary LN status (p=0.005) and triple negative molecular profile (p=0.05) being statistically significant unfavorable independent prognostic parameters in a multivariate analysis.

Can Morphological and Molecular Parameters of the Primary Breast Tumor Predict the Positivity of Nonsentinel Lymph Nodes After Positive Sentinel Lymph Node Biopsy?

Background: Sentinel lymph node (SLN) biopsy is the gold standard in the evaluation of the axillary status in patients with breast cancer. In cases meeting the Z0011 criteria, no further surgery is needed, while in the remaining cases axillary dissection is required. The aim of the study was to evaluate which morphological and molecular parameters of primary breast tumor or positive SLN can predict the positivity of nonsentinel lymph nodes (NSLN) in order to avoid unnecessary axillary lymphadenectomy. Methods: We conducted a retrospective study on 170 consecutive invasive breast carcinomas, in which SLN biopsy was performed for staging. Results: 42 (24%) cases presented SLN metastases, of which 11 were micrometastases, 6 cases met the Z0011 criteria, requiring no subsequent surgery. 25 patients underwent subsequent ANLD, but only 7 cases (28%) had positive NSLN. In this series, only the tumor diameter 20 mm can predict positive nonsentinel lymph nodes (p= 0.058; CI: 0.05787 to 0.8224). Other parameters such as patient's age (p=0.280; CI:0.7544 to 7.998), histological type (p=0.231; CI: 0.05374 to 9.271), histological grade (p=0.929; CI: 0.2351 to 3.515), molecular profile of the tumor (p=0.362; CI: 0.2416 to 4.663), number of positive SLN (p=0.378; CI: 0.1083 to 1.570), presence of extracapsular extension (p=0.625; CI: 0.5066 to 13.96) and lymph node ratio (p=0.656; CI: 0.5068 to 5.768) cannot predict the presence of metastasis in the NSLN. Conclusion: In cases in which the patient does not meet the Z0011 criteria and/or these criteria are not used, axillary lymph node dissection is the surgical treatment of choice.

The Accuracy of the Preoperative Axillary Ultrasound Examination in Predicting the Status of the Sentinel Lymph Node Involvement in Patients with Infiltrating Breast Carcinoma.

Background: we aimed to determine the accuracy of preoperative axillary ultrasound (US) in predicting the presence of sentinel lymph node (SLN) metastasis in breast cancer patients. Methods and Results: out of 54 cases, visible nodes on US were identified in 35 cases of which, 15 had metastasis. In 19 cases no axillary lymph nodes were visible on US. Of these, only 3 had metastasis. Moreover, our results demonstrated that neither the maximum diameter (p=0.738 Fisher exact test) nor the ratio between the longitudinal and transverse axes (p=0.728 Fisher exact test) can predict the positivity of the SLN. Conclusion: US cannot predict the positivity of the SLN.

Sacral (S1) herpes zoster.

Herpes zoster usually affects the thoracic and lumbar vertebra (T3-L3), while sacral herpes zoster has been very rarely reported. We present a very rare case of herpes zoster involving S1 dermatome in a 35-year-old healthy man who presented aching pain and typical herpes zoster eruption on the lateral aspect of the calcaneus, lateral plantar area and dorsal aspect of digits III and IV.

Novel Therapeutic Options in the Management of Reflex Syncope.

BACKGROUND: Syncope is a symptom associated with a wide range of pathological conditions, ranging from benign to life threatening. The most frequent is the reflex syncope that may be challenging to treat because of the complex and partially unknown pathophysiological mechanism that has to be addressed by the chosen therapy. AREAS OF UNCERTAINTY: Head-up tilt testing is so far the only clinical test able to reproduce reflex syncope, but its diagnostic yield has been recently redefined. A new mechanism such as adenosine-sensitive syncope and idiopathic atrioventricular block have been recently described, and the appropriate therapy is not yet established. There is uncertainty on the efficacy of theophylline and on the use of cardiac pacing in these patients. DATA SOURCES: Clinical trial published data and position paper from the main expert groups on fludrocortisone, midodrine, etilefrine, beta-blockers, and cardiac pacing as useful therapies for patients affected by reflex syncope. THERAPEUTIC ADVANCES: Theophylline proved in observational trials to be efficient in preventing reflex syncope recurrences in patients with documented spontaneous paroxysmal conduction disorders comparable to cardiac pacing in a subgroup of patients. Reboxetine and sibutramine may elicit a significant pressor and tachycardic effect able to delay the onset of symptoms during head-up tilt testing. Droxidopa has short-term effects on improving the symptoms because of orthostatic hypotension. Cardiac pacing is effective in preventing reflex syncope recurrences with best results when the indication for pacemaker implantation was based on the documentation of bradycardia or asystole during the spontaneous event by a cardiac monitor. External compression using elastic bandage or compressive stockings is able to prevent the decrease in blood pressure in patients with orthostatic hypotension. CONCLUSIONS: The optimal management of the complex diagnostic and therapeutic options can be achieved following a standardized and evidence-based approach to the patient with syncope.

MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.

INTRODUCTION: Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM. METHODS AND ANALYSIS: MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed. ETHICS AND DISSEMINATION: MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT02804074; Pre-results.

ER-/PR+ subset of invasive breast carcinoma (IBC): a distinct phenotype with good prognosis.

The expression of the estrogen (ER) and progesterone (PR) receptors in IBC patients represents a well-know prognostic and predictive factor. The existence of ER-/PR+ as a distinct phenotype, however, is controversial as well as is its prognostic significance. The aim of the study was to assess the incidence and prognosis in patients with ER-/PR+ IBC. One hundred and twelve patients with IBC were analyzed regarding ER/PR profile and survival. GraphPad prism 6 for Windows and Kaplan Mayer curve were used to determine overall survival (OS) and disease-free survival (DFS), with p < 0.05 as statistically significant. Of the 112 IBC patients, 75% were ER+/PR-, 16.07% were ER-/PR-, 7.14% were ER+/PR- and only 1.78% were ER-/PR+. OS was 100% in the ER-/PR+ group and 91.6% in the ER+/PR+ group. The lowest OS was found in the ER-/PR- group (72.2%), while OS was 100% in ER-/PR+ group. Regarding DFS, there were no statistically significant differences in the four groups (p = 0.11), although the highest DFS was found in the ER-/PR+ group (100%). ER-/PR+ tumors were associated with younger age (p = 0.72), smaller tumor diameter (p = 0.27), absence of lymph node metastases, and HER2 overexpression. Our results suggest that ER-/PR+ cases represent the rarest phenotype in IBC cases but its association with the best OS and DFS in other ER/PR phenotypes indicates an independent predictive value of PR for treatment considerations.

Encapsulated papillary breast carcinoma in a male patient in association with microdeposits of carcinoma cells in the needle track and sentinel lymph node treated conservatively.

We present an encapsulated papillary breast carcinoma in a male patient, in association with microdeposits of carcinoma cells within the needle track, in the lymphatic spaces of the breast parenchyma and subcapsular sinus of two sentinel lymph nodes in which conservative treatment has been recommended. Both in females and males, papillary tumours and particularly encapsulated papillary breast carcinoma can be associated with microdeposits mechanically displaced, which have to be differentiated from true invasion and metastases and treated conservatively.