Annotation protocol and crowdsourcing multiple instance learning classification of skin histological images: The CR-AI4SkIN dataset.

Digital Pathology (DP) has experienced a significant growth in recent years and has become an essential tool for diagnosing and prognosis of tumors. The availability of Whole Slide Images (WSIs) and the implementation of Deep Learning (DL) algorithms have paved the way for the appearance of Artificial Intelligence (AI) systems that support the diagnosis process. These systems require extensive and varied data for their training to be successful. However, creating labeled datasets in histopathology is laborious and time-consuming. We have developed a crowdsourcing-multiple instance labeling/learning protocol that is applied to the creation and use of the CR-AI4SkIN dataset.2 CR-AI4SkIN contains 271 WSIs of 7 Cutaneous Spindle Cell (CSC) neoplasms with expert and non-expert labels at region and WSI levels. It is the first dataset of these types of neoplasms made available. The regions selected by the experts are used to learn an automatic extractor of Regions of Interest (ROIs) from WSIs. To produce the embedding of each WSI, the representations of patches within the ROIs are obtained using a contrastive learning method, and then combined. Finally, they are fed to a Gaussian process-based crowdsourcing classifier, which utilizes the noisy non-expert WSI labels. We validate our crowdsourcing-multiple instance learning method in the CR-AI4SkIN dataset, addressing a binary classification problem (malign vs. benign). The proposed method obtains an F1 score of 0.7911 on the test set, outperforming three widely used aggregation methods for crowdsourcing tasks. Furthermore, our crowdsourcing method also outperforms the supervised model with expert labels on the test set (F1-score = 0.6035). The promising results support the proposed crowdsourcing multiple instance learning annotation protocol. It also validates the automatic extraction of interest regions and the use of contrastive embedding and Gaussian process classification to perform crowdsourcing classification tasks.

Clinical and pathological features of Merkel cell carcinoma: A 4-year follow-up observational retrospective study in Spain.

BACKGROUND: Merkel cell carcinoma (MCC) is a malignant skin cancer with a 5-year survival rate of approximately 50%. Knowledge of MCC has increased in recent years mostly due to improved diagnosis techniques. In Spain there is lack of information regarding the incidence and tumour characteristics, and the treatment approaches are not standardised. The objective of this study was to provide information of the clinical and epidemiological characteristics of MCC patients in Spain. METHODS: Retrospective, observational study involving 192 patients from 25 Spanish hospitals. Evaluated variables included overall survival and incidence rate of Merkel cell polyomavirus, in patients diagnosed from 2012 to 2016. RESULTS: The Spanish incidence rate was estimated 0.32/100,000 inhabitants/year, with variations according to geographical regions, being slightly higher in areas with greater sunlight exposure. In total, 61.5% of tumours showed expansive growth (progressive growth of the tumour), 78.6% showed localisation in UV-exposed skin. 97.4% of patients were diagnosed by excisional biopsy. Surgery was the first line treatment in 96.6% of patients, radiotherapy in 24.6%, and chemotherapy in 6.3%. These treatments were not mutually exclusive. Median overall survival was 38.3 months (78.4% at 12 months and 60% at 24 months). MCPyV was present in 33.8% of patients. CONCLUSION: The incidence of MCC in Spain is one of the highest in Europe, with a slight predominance in men. The sample has shown that a biopsy is available for diagnosis in most cases. Moreover, the treatment is surgical when the tumour is localized and is associated with lymphadenectomy, and/or it is radiotherapy if widespread.

Blind color deconvolution, normalization, and classification of histological images using general super Gaussian priors and Bayesian inference.

BACKGROUND AND OBJECTIVE: Color variations in digital histopathology severely impact the performance of computer-aided diagnosis systems. They are due to differences in the staining process and acquisition system, among other reasons. Blind color deconvolution techniques separate multi-stained images into single stained bands which, once normalized, can be used to eliminate these negative color variations and improve the performance of machine learning tasks. METHODS: In this work, we decompose the observed RGB image in its hematoxylin and eosin components. We apply Bayesian modeling and inference based on the use of Super Gaussian sparse priors for each stain together with prior closeness to a given reference color-vector matrix. The hematoxylin and eosin components are then used for image normalization and classification of histological images. The proposed framework is tested on stain separation, image normalization, and cancer classification problems. The results are measured using the peak signal to noise ratio, normalized median intensity and the area under ROC curve on five different databases. RESULTS: The obtained results show the superiority of our approach to current state-of-the-art blind color deconvolution techniques. In particular, the fidelity to the tissue improves 1,27 dB in mean PSNR. The normalized median intensity shows a good normalization quality of the proposed approach on the tested datasets. Finally, in cancer classification experiments the area under the ROC curve improves from 0.9491 to 0.9656 and from 0.9279 to 0.9541 on Camelyon-16 and Camelyon-17, respectively, when the original and processed images are used. Furthermore, these figures of merits are better than those obtained by the methods compared with. CONCLUSIONS: The proposed framework for blind color deconvolution, normalization and classification of images guarantees fidelity to the tissue structure and can be used both for normalization and classification. In addition, color deconvolution enables the use of the optical density space for classification, which improves the classification performance.

Role of artificial intelligence in multidisciplinary imaging diagnosis of gastrointestinal diseases.

The use of artificial intelligence-based tools is regarded as a promising approach to increase clinical efficiency in diagnostic imaging, improve the interpretability of results, and support decision-making for the detection and prevention of diseases. Radiology, endoscopy and pathology images are suitable for deep-learning analysis, potentially changing the way care is delivered in gastroenterology. The aim of this review is to examine the key aspects of different neural network architectures used for the evaluation of gastrointestinal conditions, by discussing how different models behave in critical tasks, such as lesion detection or characterization (i.e. the distinction between benign and malignant lesions of the esophagus, the stomach and the colon). To this end, we provide an overview on recent achievements and future prospects in deep learning methods applied to the analysis of radiology, endoscopy and histologic whole-slide images of the gastrointestinal tract.

Histological Changes Related to Symptomatic Improvement of Spontaneous Keloids Treated with a Low-Dosage Regimen of UVA-1 Phototherapy.

Keloids are a difficult-to-treat disease characterized by an imbalance in mechanisms of tissue reparation. We present the case of a middle-aged woman with spontaneous keloids which histologically and clinically improved after UVA-1 phototherapy treatment. There are few reported cases of keloids treated with high doses of UVA-1 phototherapy. We used a low-dosage regimen with a good response in only one cycle, which could diminish the risk of skin cancer development.

Quiste broncogénico gástrico: una localización singular / Gastric bronchogenic cyst: a singular presentation

Los quistes broncogénicos son formaciones quísticas originadas por una anomalía de desarrollo del eje traqueobronquial durante la embriogénesis a partir de la pared ventral del intestino anterior. Se define al quiste broncogénico como una yema pulmonar ectópica cuya localización más frecuente es en la carina, intraparenquimatoso y en el mediastino; presenta otras localizaciones atípicas y menos comunes, como las regiones cervical, supraclavicular, esofágica, retroperitoneal y cutánea. Se presenta el caso de una mujer joven que consultó al servicio de urgencias con síntomas de dolor abdominal, a quien se le practicaron múltiples pruebas y se le diagnosticó un quiste broncogénico gástrico.

Bronchogenic cysts are cystic formations originated by a tracheobronchial axis developmental anomaly during embryogenesis from the ventral wall of the anterior intestine. A bronchogenic cyst is defined as an ectopic pulmonary bud with most frequent location in the carina, intraparenchymal and mediastinal, presenting atypical and less common locations such as the cervical, supraclavicular, esophageal, retroperitoneal, and cutaneous regions. We present the case of a young woman, who consults the emergency department with abdominal pain, who is subjected to multiple tests being diagnosed as gastric bronchogenic cyst

Familial frontal fibrosing alopecia: A cross-sectional study of 20 cases from nine families.

BACKGROUND/OBJECTIVES: Frontal fibrosing alopecia (FFA) is a scarring alopecia whose prevalence is increasing. The pathogenesis of this disease is not well known. Genetic, environmental, hormonal and autoimmunity related factors have been considered; however, only a few cases of familial frontal fibrosing alopecia have been reported. MATERIAL AND METHODS: A cross-sectional study was performed at University Hospital in Granada (Spain). Twenty patients with frontal fibrosing alopecia belonging to nine different families were included, and clinical and dermoscopic features were analysed. RESULTS: Overall, 90% of the patients studied were women (mean age 61.4 years). About 50% of the patients had grade II frontal fibrosing alopecia at the time of diagnosis, whilst 35% had grades III or V. Mean recession was 2.83 cm in the frontal area and 1.99 cm in the temporo-parietal area. Daughters presented a shorter recession area and earlier debut of the disease than mothers. Androgenetic alopecia was found in only two patients (10%). The dermoscopic signs most commonly found were perifollicular erythema (85%), hyperkeratosis (85%), and absence of vellus hair in the hairline (78.9%). CONCLUSION: This study adds to the growing evidence that there is a genetic component to frontal fibrosing alopecia. The clinical pattern of frontal fibrosing alopecia was not different from that found in non-familial cases, but the debut of the disease in daughters of mothers with frontal fibrosing alopecia may be earlier.

Pseudoangiosarcomatous squamous cell carcinoma of the skin: A need for a more rigorous nomenclature for histopathological variants of squamous cell carcinoma.

Over the years, squamous cell carcinomas (SCC) that mimicked vascular lesions have been encompassed within different classifications and the underlying etiopathogenic mechanisms have been interpreted in different ways by different authors. Here, we present a case of SCC with pseudovascular areas in the right leg of a 96-year-old woman with chronic venous insufficiency. Histopathological examination closely resembled an angiosarcoma, but the immunohistochemical negativity for endothelial markers and the strong positivity for the pancytokeratin marker AE1/AE3 revealed the epithelial nature of the neoplasm. After a comprehensive review of all similar previously published cases, we believe that it is necessary to separate SCC with pseudoluminal structures composed of glandular-like areas (pseudoglandular or adenoid SCC) from those mimicking vascular lumina (pseudovascular and pseudoangiosarcomatous SCC). We would like to emphasize that acantholytic SCC, a definitive variant of SCC, can be further classified into the common or ordinary subtype of acantholytic SCC, that shows solid nests containing numerous acantholytic atypical keratinocytes without any mimickers for specific structures, and pseudoglandular, pseudovascular and pseudoangiosarcomatous subtypes when glandular or vascular structures are mimicked, respectively.

Comparative Study of Shrinkage in Human Skin, Artificial Human Skin, and Mouse Skin.

INTRODUCTION: The shrinkage of surgical specimens (SS) is known in human skin (HS) but has not been studied in an artificial skin (AS) or mouse skin (MS). OBJECTIVES: To quantify the degree of shrinkage of SS and establish its timing in HS and an in vitro and animal model to explore the possible causes of this phenomenon. METHODOLOGY: We collected 100 SS of HS, 50 SS of AS synthesized with fibrin-agarose biomaterials and 21 SS of MS. The width and length of specimens were measured before the surgical excision (pre-SE), at 5 minutes postsurgery (ex vivo), and after 24 hours of fixation in formalin (postfixation). Histological staining was performed to analyze the differences between HS, AS, and MS that may explain the differences in shrinkage. RESULTS: Between pre-SE and postfixation, the width and length shrank by 16.1% and 17.1% in HS, 14.5% and 8.5% in AS, and 26.5% and 23.1% in MS (P < 0.01), respectively. Shrinkage largely occurred between pre-SE and ex vivo. Cells and interstitial fibers were scant in AS and abundant in MS. CONCLUSIONS: Almost all of the shrinkage occurred during the first 5 minutes postsurgery. According to the AS model findings, 53.6% of SS shrinkage would be explained by the action of dermal fibers and other cellular components of the dermis.

Atypical Kaposi's sarcoma in young inmunocompetent patient.

Kaposi´s sarcoma is a rare tumor associated with human herpes virus 8 (HHV-8) infection. Four main clinical subtypes have been described. This study reports on a form of KS in an HIV negative and immunocompetent middle-aged man. The only remarkable factor is that he has sex with other men. This form of Kaposi´s sarcoma is rare. It occurs more in younger patients than in the classic form, is limited to the skin, and is associated with a good prognosis. The means of transmission of the virus is through saliva in oroanal or orogenital sexual practices. Mechanisms of tumor development are still not well known. Given the possible increased number of this variant, it would be interesting to extend this study.

Proliferative nodule in melanocytic nevi mimicking deep penetrating nevus.

Proliferative nodules can occasionally arise on congenital and acquired melanocytic nevi. At first sight their clinical and pathologic features cause alert to both dermatologist and dermatopathologist. However, proliferative nodules are typically benign, regression is common and there is minimum risk of malignization. We present a new case of proliferative nodule in melanocytic nevi with features of deep penetrating nevus.

Proliferative nodule in melanocytic nevi mimicking deep penetrating nevus

Abstract: Proliferative nodules can occasionally arise on congenital and acquired melanocytic nevi. At first sight their clinical and pathologic features cause alert to both dermatologist and dermatopathologist. However, proliferative nodules are typically benign, regression is common and there is minimum risk of malignization. We present a new case of proliferative nodule in melanocytic nevi with features of deep penetrating nevus.

Smoothelin and WT-1 expression in glomus tumors and glomuvenous malformations.

BACKGROUND: Smoothelin is a specific marker for smooth muscle cells with contractile capacity which has not been widely studied in glomus lesions. In the same way, the expression for Wilms tumor 1 (WT1) has only been studied occasionally in the endothelial cells of glomovenous malformations and in the glomus cells of glomus tumours. OBJECTIVE: We studied the significance of immunohistochemical expression of smoothelin and WT1 in 25 glomus lesions. METHODS: We assessed 9 cases of solid glomus tumors (SGT), 8 cases of glomus tumors with vascular ectasia (VEGT), 2 cases of glomangiomyomas (GMM) and 6 cases of glomuvenous malformation (GM). Immunohistochemistry was performed, evaluating the expression of WT1, smoothelin, smooth muscle actin (SMA), smooth muscle myosin (SMM), h-caldesmon and desmin. RESULTS: Glomic cells showed cytoplasmic positivity for smoothelin, and WT1 expression was present in all studied cases. SGT showed WT1 positivity in all endothelia. However, in regarding VEGT and GMM, WT1 endothelial expression was positive in some areas, but not in others. GM did not show endothelial cell positivity for WT1. CONCLUSIONS: Smoothelin expression in glomic cells indicates that they are contractile smooth muscle cells, and thus its role in routine diagnosis should be considered. The absence of WT1 expression in the endothelium of the vascular structures of the GM is a differential characteristic between SGT, VEGT and GMM.

Ghrelin and adipose-derived mesenchymal stromal cells improve nerve regeneration in a rat model of epsilon-caprolactone conduit reconstruction.

OBJECTIVE: Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of adipose-derived mesenchymal cells (ASCs) and ghrelin (GHR), a neuropeptide with neuroprotective, trophic, and developmental regulatory actions, on peripheral nerve regeneration in a model of severe nerve injury repaired with nerve conduits. MATERIAL AND METHODS: The right sciatic nerves of 24 male Wistar rats were 10-mm transected unilaterally and repaired with Dl-lactic-ε-caprolactone conduits. Rats were then treated locally with saline, ASCs, or GHR. At 12 weeks post-surgery, we assessed limb function by measuring ankle stance angle and percentage muscle mass reduction and evaluated the histopathology, immunohistochemistry, ultrastructure, and morphometry of myelinated fibers. MAIN RESULTS: Rats receiving GHR or ASCs showed no significant increased functional recovery in ankle stance angle (p=0.372) but a higher nerve area (p=0.015), myelin area (p=0.046) and number of myelinated fibers (p=0.012) in the middle and distal segments of operated sciatic nerves in comparison to saline-treated control animals. CONCLUSION: These results suggest that utilization of ghrelin or ASCs may improve nerve regeneration using Dl-lactic-ε-caprolactone conduits.

Hobnail Hemangioma With an Unusual Clinical Presentation.

Hobnail hemangioma, also known as targetoid hemosiderotic hemangioma, is an uncommon vascular proliferation that clinically presents as a small solitary red to purple papule or macule, located on the limbs or trunk. Multiple lesions and atypical locations have been described. Histopathologically, it exhibits a biphasic pattern, with dilated vessels in the superficial dermis and angulated vessels in the deeper dermis, with endothelial cells that show a hobnail appearance. There is controversy about the histogenetic origin of hobnail hemangioma, although recent studies support that it is a lymphatic malformation. The investigators report the case of a 41-year-old man with an irregular lesion, red to purple in color, with a maximum diameter of 4 cm, on the scalp. The location and in particular the clinical appearance are uncommon. Immunohistochemical analysis showed negativity for WT1 and focal positivity for D2-40. Clinical-pathologic correlation acquires particular importance in the case of lesions with atypical clinical presentation.

Atypical Kaposi's sarcoma in young inmunocompetent patient

Abstract: Kaposi´s sarcoma is a rare tumor associated with human herpes virus 8 (HHV-8) infection. Four main clinical subtypes have been described. This study reports on a form of KS in an HIV negative and immunocompetent middle-aged man. The only remarkable factor is that he has sex with other men. This form of Kaposi´s sarcoma is rare. It occurs more in younger patients than in the classic form, is limited to the skin, and is associated with a good prognosis. The means of transmission of the virus is through saliva in oroanal or orogenital sexual practices. Mechanisms of tumor development are still not well known. Given the possible increased number of this variant, it would be interesting to extend this study.