Integrating Biological Advances Into the Clinical Management of Breast Cancer Related Lymphedema

Breast cancer-related lymphedema (BCRL) occurs in a significant number of breast cancer survivors as a consequence of the axillary lymphatics' impairment after therapy (mainly axillary surgery and irradiation). Despite the recent achievements in the clinical management of these patients, BCRL is often diagnosed at its occurrence. In most cases, it remains a progressive and irreversible condition, with dramatic consequences in terms of quality of life and on sanitary costs. There are still no validated pre-surgical strategies to identify individuals that harbor an increased risk of BCRL. However, clinical, therapeutic, and tumor-specific traits are recurrent in these patients. Over the past few years, many studies have unraveled the complexity of the molecular and transcriptional events leading to the lymphatic system ontogenesis. Additionally, molecular insights are coming from the study of the germline alterations involved at variable levels in BCRL models. Regrettably, there is a substantial lack of predictive biomarkers for BCRL, given that our knowledge of its molecular milieu remains extremely puzzled. The purposes of this review were (i) to outline the biology underpinning the ontogenesis of the lymphatic system; (ii) to assess the current state of knowledge of the molecular alterations that can be involved in BCRL pathogenesis and progression; (iii) to discuss the present and short-term future perspectives in biomarker-based patients' risk stratification; and (iv) to provide practical information that can be employed to improve the quality of life of these patients

Retained PTEN Expression Preferentially Identifies Mismatch Repair-Proficient Breast Cancers

Introduction/ Background Loss of phosphatase and tensin homolog (PTEN) expression and alterations in mismatch repair (MMR) genes are regarded as early oncogenic events in breast cancer. It has recently been hypothesized that the polyadenosine tract in PTEN might be a target for mutation in MMR-deficient endometrial tumors. However, the frequency and significance of MMR alterations in breast cancer is debated, and their relationship with PTEN status has not been investigated in the breast. Aims In this study, we sought to explore the relationships between PTEN expression and MMR alterations and to define whether PTEN immunohistochemistry is a predictor of MMR status in breast cancer. Methods 309 cases, including 261 invasive ductal carcinomas, no special type, 32 invasive lobular carcinomas, and 16 invasive ductal carcinomas, mixed types, carefully characterized from clinical and pathological standpoints, were reviewed and used to construct 11 tissue microarrays (TMAs). For each case, a mean of 4.5 tumor tissue cores (range 3 to 6 cores) was sampled, incorporating distinct topographic areas of the tumor, as well as matched non-neoplastic breast tissue, and, when present, associated in situ carcinoma. Taken together, 1381 spots were generated. Each TMA was subjected to immunohistochemical analysis of PTEN and the DNA MMR proteins MLH1, MSH2, MSH6 and PMS2. In order to allow a quick navigation within each TMA, and to minimize human-related biases, each stained slide was digitalized and blindly analyzed by two pathologists using a dedicated software able to segment TMA cores. The pattern of expression was therefore annotated manually on a digital database using a specific add-on module. Results According to clinicopathologic surrogate definition of intrinsic subtypes, PTEN protein loss was more frequent in luminal A-like and triple negative groups compared to luminal B-like carcinomas, as recently observed in other studies. MMR status in Luminal B-like tumors did not differ significantly between PTEN-retained and PTEN-loss groups, regardless HER2 amplification. In particular, retained PTEN expression was a predictor of MMR proficiency in approximately 35% of cases for this group. However, in luminal A-like and triple negative breast cancer groups, retained positive expression of MMR proteins was observed in 100% of cases showing PTEN wild-type immunohistochemical expression. Discussion: The present study is the first to investigate PTEN protein loss in a large set of breast carcinomas based on DNA MMR status by immunohistochemistry. Our findings broaden the understanding of the biology underpinning breast cancer, suggesting that MMR alterations are likely to be independent of PTEN status in the majority of luminal B-like breast cancers and that, in a way akin to endometrial carcinoma, MMR deficiency could play a part in the development of PTEN alterations in luminal A-like and triple negative breast cancers. The integration of traditional pathology with cutting-edge digital tools allowed a rapid quantification of immunohistochemistry and effective data organization in this wide cohort multi-variable study. Conclusion: PTEN immunohistochemistry is a useful adjunct in the clinical evaluation of breast cancer patients, being able to capture all MMR-proficient luminal A-like and triple negative tumors

Histological evaluation of duodenal biopsies from coeliac patients : the need for different grading criteria during follow-up

Background: Coeliac disease is characterised by villous atrophy, which usually normalises after gluten withdrawal. Sometimes the revaluation of duodenal histology is required during follow-up, even if the methodology for comparing duodenal histology before and after introducing a gluten-free diet is not yet established. Our aim was to evaluate a novel criterion to compare duodenal histology in coeliac disease before and after gluten withdrawal. Methods: Duodenal biopsies from coeliac patients were retrospectively reviewed to compare duodenal histology at diagnosis and after at least one year on a gluten-free diet. Two different methods were used: the first was represented by the classical Marsh-Oberhuber score, the second compared the areas covered by each Marsh-Oberhuber grade and expressed as percentages, the final grade being calculated from the analysis of ten power fields per duodenal biopsy. Results: Sixty-nine patients (17 males 52 females, age at diagnosis 36\ub115 years) who underwent duodenal biopsies, were considered. According to the classical Marsh-Oberhuber scale, 32 patients did not present atrophy during follow-up while 37 showed duodenal atrophy, among whom 26 improved the grade of severity and 11 retained the same one. Of these latter, according to the second method, eight patients were considered improved, two showed a worsened duodenal damage and only one remained unchanged; the evaluation changed in 91 % of cases. Conclusions: The proposed semi-quantitative approach (i.e. the second method) for the evaluation of histology at follow-up provides additional information about the progression/regression of the mucosal damage

Rathke's cleft cyst associated with pituitary granulomatosis with polyangiitis : an unusual combination of hypothalamus-pituitary region pathologies

The authors present an unusual case of a patient suffering from visual deficit due to pituitary granulomatosis with polyangiitis (GPA) associated with Rathke's cleft cyst (RCC). The patient was referred to our Neurosurgery Department presenting right eye amaurosis, third cranial nerve palsy, and left temporal hemianopsia. Magnetic resonance imaging documented a sellar or suprasellar lesion with solid and cystic components. The dura mater of the skull base was also strongly enhanced. The patient underwent surgery. Histologic examination revealed RCC associated with pituitary GPA. To our knowledge, this is the first reported case of concomitant pituitary GPA and RCC. Pituitary involvement in GPA is rare, usually diagnosed in hormonal dysfunctions. The patient in case first presented optic chiasm compression, probably due to inflammation of both the pituitary gland and the previously asymptomatic RCC. We focus on the symptoms that led us to diagnose GPA pituitary involvement and on the peculiar and unusual Magnetic resonance imaging of the case presented

Breast Cancer Systemic Treatments and Upper Limb Lymphedema: A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab

Breast cancer related lymphedema (BCRL) is frequent but strategies for an individualized risk assessment are lacking. We aimed to define whether tumor-specific pathological features, coupled with clinical and therapeutic data, could help identify patients at risk. Data from 368 patients with node-positive breast cancers were retrospectively collected, including 75 patients with BCRL (0.4\u207b25.6 years follow-up). BCRL was assessed during the standard follow-up oncology visits using the circumferential measurement. Clinicopathologic and therapeutic factors associated with BCRL were integrated into a Cox proportional hazards regression model. Lymphovascular invasion (LVI) was more common in BCRL patients (n = 33, 44% vs. n = 85, 29%, p = 0.01), akin extra nodal extension (ENE) of the metastasis (n = 57, 76% vs. n = 180, 61%, p = 0.02). Sentinel lymph node excision without axillary dissection and extra-axillary radiotherapy were BCRL-unrelated. A higher number of BCRL-positive patients were treated with taxane-based chemotherapy with or without trastuzumab, compared to BCRL-negative patients (p < 0.01). Treatment with trastuzumab and/or taxanes, adjusted for systemic infections, laterality, therapy, and pathological features (i.e., LVI and ENE), had a significant impact in BCRL-free survival (p < 0.01). This work offers new insights on BCRL risk stratification, where the integration of clinical, therapeutic, and tumor-specific pathological data suggests a possible role of anti-human epidermal growth factor receptor 2 (HER2) therapy in BCRL pathogenesis

Atherosclerotic pattern of coronary myocardial bridging assessed with CT coronary angiography

The aim of our study was to evaluate the atherosclerotic pattern of patients with coronary myocardial bridging (MB) by means of CT Coronary Angiography (CT-CA). 254 consecutive patients (166 male, mean age 58.6 ± 10.3) who underwent 64-slice CT-CA according to current clinical indications were reviewed for the presence of MB and concomitant segmental atherosclerotic pattern. Coronary plaques were assessed in all patients enrolled. 73 patients (29%) presented single (90%) or multiple (10%) MB, frequently (93%) localized in the mid-distal left anterior descending artery. The MB segment was always free of atherosclerosis. Segments proximal to the MB presented: no atherosclerotic disease (n = 37), positive remodeling (n = 23), 50% stenoses (n = 7). Distal segments presented a different atherosclerosis pattern (P < 0.0001): absence of disease (n = 73), no significant lesions (n = 8). No significant differences were found between segments proximal to MB and proximal coronary segments apart from left main trunk. Pattern of atherosclerotic lesions located in segments 6 and 7 significantly differs between patients with MB and patients without MB (P < 0.05). CT-CA is a reliable method to non-invasively demonstrate MB and related atherosclerotic pattern. CT-CA provides new insight regarding atherosclerosis distribution in segments close to MB

Hibernation in Unusual Places: A Pure Typical Hibernoma of the Breast

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