[Main Types of Cysts in Dermatopathology: Part 2]. / Principales tipos de quistes en dermatopatología: Parte 2.

This is the second article in a two-part series published in this journal, in which we examine the histopathological characteristics, as well as the differential diagnosis, of the main entities that present as cystic and pseudocystic structures in cutaneous biopsy. In this second article, we address ciliated cutaneous cysts, branchial cysts, Bartholin's cysts, omphalomesenteric cysts, thymic cysts, thyroglossal duct cysts, synovial cysts, and median raphe cysts, as well as mucocele, ganglion, and auricular and digital myxoid pseudocysts.

Histological interpretation of spitzoid tumours: an extensive machine learning-based concordance analysis for improving decision making.

The histopathological classification of melanocytic tumours with spitzoid features remains a challenging task. We confront the complexities involved in the histological classification of these tumours by proposing machine learning (ML) algorithms that objectively categorise the most relevant features in order of importance. The data set comprises 122 tumours (39 benign, 44 atypical and 39 malignant) from four different countries. BRAF and NRAS mutation status was evaluated in 51. Analysis of variance score was performed to rank 22 clinicopathological variables. The Gaussian naive Bayes algorithm achieved in distinguishing Spitz naevus from malignant spitzoid tumours with an accuracy of 0.95 and kappa score of 0.87, utilising the 12 most important variables. For benign versus non-benign Spitz tumours, the test reached a kappa score of 0.88 using the 13 highest-scored features. Furthermore, for the atypical Spitz tumours (AST) versus Spitz melanoma comparison, the logistic regression algorithm achieved a kappa value of 0.66 and an accuracy rate of 0.85. When the three categories were compared most AST were classified as melanoma, because of the similarities on histological features between the two groups. Our results show promise in supporting the histological classification of these tumours in clinical practice, and provide valuable insight into the use of ML to improve the accuracy and objectivity of this process while minimising interobserver variability. These proposed algorithms represent a potential solution to the lack of a clear threshold for the Spitz/spitzoid tumour classification, and its high accuracy supports its usefulness as a helpful tool to improve diagnostic decision-making.

[Main Types of Cysts in Dermatopathology: Part 1]. / Principales tipos de quistes en dermatopatología: parte 1.

Cystic structures represent one of the most common findings in dermatopathology. These encompass both cystic tumors and pseudocysts resulting from the accumulation of certain substances, such as mucin. In a two-part series (of which this is the first part), we have reviewed the principal types of cysts and pseudocysts that may be observed in cutaneous biopsies, examining their histopathological features and primary differential diagnoses. This first part encompasses infundibular cysts, eruptive dermoid cysts, pigmented follicular cysts, pilonidal cysts, tricholemmal cysts, milium cysts, hybrid cysts, bronchogenic cysts, as well as steatocystoma, hydrocystoma, and comedones.

A Spitzoid Tumor dataset with clinical metadata and Whole Slide Images for Deep Learning models.

Spitzoid tumors (ST) are a group of melanocytic tumors of high diagnostic complexity. Since 1948, when Sophie Spitz first described them, the diagnostic uncertainty remains until now, especially in the intermediate category known as Spitz tumor of unknown malignant potential (STUMP) or atypical Spitz tumor. Studies developing deep learning (DL) models to diagnose melanocytic tumors using whole slide imaging (WSI) are scarce, and few used ST for analysis, excluding STUMP. To address this gap, we introduce SOPHIE: the first ST dataset with WSIs, including labels as benign, malignant, and atypical tumors, along with the clinical information of each patient. Additionally, we explain two DL models implemented as validation examples using this database.

Evaluación preoperatoria de la hemostasia en cirugía mayor electiva / Preoperative evaluation of hemostasis in elective major surgery

Resumen: Introducción: Las pruebas de coagulación carecen de valor para determinar el riesgo de sangrado perioperatorio. Material y métodos: Se realizó un estudio observacional, descriptivo, y transversal en 2,114 pacientes en la consulta de Anestesiología del Hospital Universitario «Dr. Celestino Hernández Robau¼, los resultados se evaluaron mediante estadística descriptiva. Resultados: El tiempo de coagulación y sangrado se realizó en 100% de los casos y el conteo de plaquetas en 93.99%, mientras que el tiempo de protrombina y tiempo de tromboplastina parcial activado se efectuó en 66.27 y 55.62% de los casos respectivamente. De 8.834 exámenes realizados se encontraron 49 alterados en 0.55%. Los pacientes con exámenes alterados fueron 33 en 1.56%, los enfermos en riesgo de sangrado por exámenes de coagulación fueron 30 en 1.42% y los pacientes en riesgo sin antecedentes de sangrados detectados por exámenes de coagulación fueron tres en 0.14%. Se reportó sangrado perioperatorio en 16 pacientes en 0.76%, siete pacientes con interrogatorio positivo y exámenes normales y nueve pacientes con interrogatorio negativo y exámenes normales. Conclusiones: La historia clínica y el examen físico del paciente son las mejores herramientas para predecir el riesgo de sangrado quirúrgico y los exámenes aislados de coagulación no constituyen un buen predictor del sangrado perioperatorio.

Abstract: Introduction: Coagulation tests are no value to determine the risk of perioperative bleeding. Material and methods: An observational descriptive cross-sectional study was carried out in 2,114 patients in the anesthesiology consultation of the University Hospital «Dr. Celestino Hernández Robau¼. Results: The clotting and bleeding time was performed in 100% of cases, the platels count in 93.99%. While the prothrombin time and activated partial tromboplastin time were performed in 66.27 and 55.62% respectively. Of 8,834 tests carried out, 49 were found to be altered for 0.55%. Patients with altered tests were for 1.56%, patients at risk of bleeding from coagulation tests were 30 for 1.42% and patients at risk with no history of bleeding detected by coagulation tests were three for 0.14%. Perioperative bleeding was reported in 16 patients for 0.76%, seven patients with positive questioning and normal tests and nine patients with negative questioning and normal tests. Conclusions: The patient's medical history and physical examination are the best tools to predict the risk of surgical bleeding and isolated coagulation tests do not constitute a good predictor of perioperative bleeding.

Perieccrine Coil Elastosis: An Unusual and Previously Unrecognized Aging-Related Phenomenon.

ABSTRACT: Elastic fibers are present as a thin line around the normal secretory coil of eccrine and apocrine glands, although they are virtually imperceptible with hematoxylin-eosin staining. Skin aging is a consequence of intrinsic and extrinsic factors, and glycation and ultraviolet irradiation are involved in this process favoring elastosis. We report an unusual and prominent perieccrine elastosis on the left temple in the vicinity of a basal cell carcinoma in a 78-year old man with type 2 diabetes, dyslipidemia, and hypertension. Very thick multilamellar and tortuous elastic fibers surrounded the eccrine coils. This increased amount of elastic fibers was confirmed by orcein staining as well as amyloid-P and lysozyme immunostaining. Perieccrine coil elastosis is a very unusual phenomenon that to the best of our knowledge has not been reported. Similar to dermal actinic elastosis, the presence of perieccrine coil elastosis in a skin cancer microenvironment might hypothetically promote tumor growth because of the release of elastin-derived peptides.

Diagnostic Algorithm to Subclassify Atypical Spitzoid Tumors in Low and High Risk According to Their Methylation Status.

Current diagnostic algorithms are insufficient for the optimal clinical and therapeutic management of cutaneous spitzoid tumors, particularly atypical spitzoid tumors (AST). Therefore, it is crucial to identify new markers that allow for reliable and reproducible diagnostic assessment and can also be used as a predictive tool to anticipate the individual malignant potential of each patient, leading to tailored individual therapy. Using Reduced Representation Bisulfite Sequencing (RRBS), we studied genome-wide methylation profiles of a series of Spitz nevi (SN), spitzoid melanoma (SM), and AST. We established a diagnostic algorithm based on the methylation status of seven cg sites located in TETK4P2 (Tektin 4 Pseudogene 2), MYO1D (Myosin ID), and PMF1-BGLAP (PMF1-BGLAP Readthrough), which allows the distinction between SN and SM but is also capable of subclassifying AST according to their similarity to the methylation levels of Spitz nevi or spitzoid melanoma. Thus, our epigenetic algorithm can predict the risk level of AST and predict its potential clinical outcomes.

Manejo anestésico de un paciente con enfermedad de Behçet / Anesthetic management of a patient with Behçet´s Disease Sobre los autores:

RESUMEN Introducción: La enfermedad de Behçet es una enfermedad inflamatoria crónica, recurrente, multisistémica, de etiología desconocida, caracterizada por úlceras orales y genitales recurrentes, inflamación ocular, lesiones cutáneas, artritis, afecciones neurológicas, pulmonares, gastrointestinales y vasculitis sistémica. Objetivo: Describir el manejo anestésico en un paciente portador de enfermedad de Behçet. Presentación del caso: Se reporta el caso de un paciente de 52 años de edad con antecedentes patológicos personales de enfermedad de Behçet que recibe anestesia general para exéresis de adenopatía cervical izquierda metastásica de un carcinoma primario oculto. Conclusiones: El mantenimiento del tratamiento con esteroides, el uso de nadroparina cálcica junto a otras medidas preventivas de la trombosis venosa profunda, el manejo cuidadoso de la vía aérea, la protección ocular y la articular, así como de los puntos de presión y la prevención de la patergia son elementos fundamentales en el manejo de estos pacientes.

ABSTRACT Introduction: Behçet's disease is a chronic, recurrent, multisystemic inflammatory disease of unknown etiology characterized by recurrent oral and genital ulcers, ocular inflammation, skin lesions, arthritis, neurological, pulmonary and gastrointestinal conditions, as well as systemic vasculitis. Objective: To describe the anesthetic management of a patient with Behçet's disease. Case presentation: The case is reported of a 52-year-old male patient with an individual history of Behçet's disease, who receives general anesthesia for removal of left cervical metastatic adenopathy from a hidden primary carcinoma. Conclusions: Keeping the steroid therapy, using calcium nadroparin, together with other measures for preventing deep vein thrombosis; careful airway management, eye and joint protection, as well as attention to pressure points and pathergy prevention are fundamental elements for the management of these patients.

Prognostic Value of IGF2 mRNA-Binding Protein 3 (IGF2BP3) Intratumoral Expression in Melanoma Patients at the Time of Diagnosis: Comparative Analysis of RT-qPCR Versus Immunohistochemistry.

Screening for prognostic biomarkers is crucial for clinical melanoma management. Insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) has emerged as a potential melanoma diagnostic and prognostic biomarker. It is commonly tested by immunohistochemistry (IHC). Our study retrospectively examines IGF2BP3 mRNA and protein expression in primary melanomas, their correlation with clinicopathologic factors, clinical outcome, and selected miRNAs expression, and their efficiency in predicting melanoma progression and survival. RT-qPCR and IHC on IGF2BP3 expression were performed in 61 cryopreserved and 63 formalin-fixed paraffin-embedded primary melanomas, respectively, and correlated to clinicopathologic factors, distant metastasis-free survival (DMFS), and melanoma -specific survival (MSS). The correlation between RT-qPCR and IHC was significant but moderate. IGF2BP3 mRNA showed a stronger association with clinicopathologic factors (Breslow thickness, ulceration, mitosis rate, growth phase, development of metastasis, and melanoma-specific survival) than its protein counterpart. Interestingly, higher IGF2BP3 mRNA expression was detected in primary melanomas that further metastasized to distant sites and was an independent prognostic factor for the risk of unfavorable DMFS and MSS. RT-qPCR outperformed IHC in sensitivity and in predicting worse clinical outcomes. Therefore, RT-qPCR may successfully be implemented for routine IGF2BP3 assessing for the selection of melanoma patients with a higher risk of developing distant metastasis and dying of melanoma.

Fístula traqueoesofágica como complicación de la intubación endotraqueal prolongada / Tracheoesophageal fistula as a complication of prolonged endotracheal intubation

RESUMEN Introducción: La fístula traqueoesofágica consecutiva a intubación endotraqueal prolongada es una lesión grave con elevada morbimortalidad. El alto índice de sospecha, diagnóstico precoz, resolución de las complicaciones y un tratamiento quirúrgico definitivo son los pilares fundamentales en los cuales descansa su manejo correcto. Objetivo: Describir el comportamiento y manejo de la fístula traqueoesofágica en pacientes con intubación endotraqueal prolongada. Presentación del caso: Paciente de 34 años de edad que sufrió trauma craneoencefálico grave con necesidad de intubación endotraqueal prolongada. Su evolución fue favorable, con recuperación neurológica, pero presentaba tos incontrolable después de la deglución, aumento de las secreciones respiratorias y pérdida de 30 Kg de peso no resuelta, lo que motivó se le realizara tomografía computarizada multicorte dual sincronizada con el electrocardiograma, la que permitió de forma rápida y no invasiva, llegar al diagnóstico de la fístula traqueoesofágica. Conclusiones: La intubación endotraqueal prolongada constituye la causa principal de la aparición de la fístula traqueoesofágica. El mecanismo de producción fundamental fue la isquemia provocada por la compresión de las paredes posterior de la tráquea y anterior del esófago entre el manguito insuflado del tubo endotraqueal y la sonda nasogástrica. La tomografía computarizada multicorte dual sincronizada con el electrocardiograma permite realizar el diagnóstico de esta complicación.

ABSTRACT Introduction: Tracheoesophageal fistula following prolonged endotracheal intubation is a serious lesion with high morbidity and mortality. The high index of suspicion, early diagnosis, resolution of complications and definitive surgical treatment are the fundamental pillars on which its correct management rests. Objective: Describe the behavior and management of tracheoesophageal fistula in patients with prolonged endotracheal intubation. Case Presentation: A 34-year-old patient who suffered severe head trauma with the need of prolonged endotracheal intubation. His evolution was favorable, with neurological recovery, but he presented uncontrollable cough after swallowing, increased respiratory secretions and unsolved loss of 30 Kg of weight, which motivated to perform to him a dual multi-cut computed tomography synchronized with the electrocardiogram, which allowed quickly and non-invasively, to reach the diagnosis of tracheoesophageal fistula. Conclusions: Prolonged endotracheal intubation is the main cause of the appearance of tracheoesophageal fistula. The fundamental production mechanism was ischemia caused by compression of the posterior walls of the trachea and anterior walls of the esophagus between the inflated cuff of the endotracheal tube and the nasogastric tube. The dual multi-cut computed tomography synchronized with the electrocardiogram allows the diagnosis of this complication.

The Prognostic Value of miR-125b, miR-200c and miR-205 in Primary Cutaneous Malignant Melanoma Is Independent of BRAF Mutational Status.

BRAF mutations are present in around 50% of cutaneous malignant melanomas and are related to a poor outcome in advanced-stage melanoma patients. miRNAs are epigenetic regulators that modulate different cellular processes in cancer, including melanoma development and progression. However, there are no studies on the potential associations of the genetic alterations of the BRAF gene with miRNA expression in primary cutaneous melanomas. Here, in order to analyze the influence of BRAF mutations in the ability of selected miRNAs to predict clinical outcome and patient survival at the time of diagnosis, we studied the prognostic value of miR-125b, miR-200c and miR-205 expression depending on the BRAF mutational status in fresh, frozen primary tumor specimens. For this purpose, RNA was extracted for studying both BRAF mutations by Sanger sequencing and miRNA expression. Our results indicate that, although there seems to be a slight preference for their predictive ability in the BRAF mutated group, the expression of these three miRNAs serves effectively to predict the clinical outcome of melanoma patients independently of BRAF mutational status at the time of primary tumor diagnosis.

Fluorescent in situ hybridization (FISH): A useful diagnostic tool for childhood conjunctival melanoma.

INTRODUCTION: Conjunctival melanoma is extremely rare in children and has low rates of resolution. Definitive histopathological diagnosis based exclusively on microscopic findings is sometimes difficult. Thus, early diagnosis and adequate treatment are essential to improve clinical outcomes. CLINICAL CASE: We present the first case in which the fluorescent in situ hybridization (FISH) diagnostic technique was applied to a 10-year-old boy initially suspected of having amelanotic nevi in his right eye. Based on the 65% of tumor cells with 11q13 (CCND1) copy number gain and 33% with 6p25 (RREB1) gain as measured by the FISH analysis, and on supporting histopathological findings, the diagnosis of conjunctival melanoma could be made. Following a larger re-excision, adjuvant therapy with Mitomycin C (MMC), cryotherapy and an amniotic membrane graft, the patient has remained disease-free during 9 years of long-term follow-up. CASE DISCUSSION: Every ophthalmologist should remember to consider and not forget the possibility of using FISH analyses during the differential diagnosis of any suspicious conjunctival lesions. Genetic techniques, such as FISH, have led to great advances in the classification of ambiguous lesions. Evidence-based guidelines for diagnosing conjunctival melanoma in the pediatric population are needed to determine the most appropriate strategy for this age group.

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.

Deep Learning for Skin Melanocytic Tumors in Whole-Slide Images: A Systematic Review.

The rise of Artificial Intelligence (AI) has shown promising performance as a support tool in clinical pathology workflows. In addition to the well-known interobserver variability between dermatopathologists, melanomas present a significant challenge in their histological interpretation. This study aims to analyze all previously published studies on whole-slide images of melanocytic tumors that rely on deep learning techniques for automatic image analysis. Embase, Pubmed, Web of Science, and Virtual Health Library were used to search for relevant studies for the systematic review, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Articles from 2015 to July 2022 were included, with an emphasis placed on the used artificial intelligence methods. Twenty-eight studies that fulfilled the inclusion criteria were grouped into four groups based on their clinical objectives, including pathologists versus deep learning models (n = 10), diagnostic prediction (n = 7); prognosis (n = 5), and histological features (n = 6). These were then analyzed to draw conclusions on the general parameters and conditions of AI in pathology, as well as the necessary factors for better performance in real scenarios.

Manejo anestésico de pacientes con trombocitemia esencial / Anesthetic management of a patient with essential trombocythemia

La trombocitemia esencial forma parte del grupo de neoplasias mieloproliferativas. Se caracteriza por síntomas microvasculares y vasomotores, recuento plaquetario superior a 450 x 109/l, proliferación megacariocítica con morfología grande y madura, ausencia de proliferación eritroide y granulocítica, demostración de JAK2V617F u otro marcador clonal y ausencia de evidencia de trombocitosis reactiva. Se reporta el manejo anestésico en una paciente donde las principales consideraciones están relacionadas con la prevención de eventos hemorrágicos y trombóticos. La suspensión de la aspirina, el mantenimiento del tratamiento con hidroxiurea, la preparación con ácido tranexámico, el uso pre y posoperatorio de fraxiparina, hidratación adecuada, uso de medias elásticas en miembros inferiores, deambulación precoz, buena hemostasia quirúrgica y disponibilidad de concentrados de plaquetas son los elementos fundamentales en la conducción anestésica de esta paciente(AU)

Essential thrombocythemia is part of the group of myeloproliferative neoplasms. It is characterized by microvascular and vasomotor symptoms, platelet count over 450x109/L, megakaryocytic proliferation with large and mature morphology, absence of erythroid and granulocytic proliferation, demonstration of JAK2V617F or other clonal marker, and absence of evidence of reactive thrombocytosis. Anesthetic management is reported in a patient, whose case's main considerations are related to the prevention of hemorrhagic and thrombotic events. Aspirin suspension, maintenance of hydroxyurea treatment, preparation with tranexamic acid, pre- and post-operative use of fraxiparin, adequate hydration, use of elastic stockings in lower limbs, early ambulation, good surgical hemostasis, as well as availability of platelet concentrates are the fundamental elements in the anesthetic management of this patient(AU)

An attention-based weakly supervised framework for spitzoid melanocytic lesion diagnosis in whole slide images.

Melanoma is an aggressive neoplasm responsible for the majority of deaths from skin cancer. Specifically, spitzoid melanocytic tumors are one of the most challenging melanocytic lesions due to their ambiguous morphological features. The gold standard for its diagnosis and prognosis is the analysis of skin biopsies. In this process, dermatopathologists visualize skin histology slides under a microscope, in a highly time-consuming and subjective task. In the last years, computer-aided diagnosis (CAD) systems have emerged as a promising tool that could support pathologists in daily clinical practice. Nevertheless, no automatic CAD systems have yet been proposed for the analysis of spitzoid lesions. Regarding common melanoma, no system allows both the selection of the tumor region and the prediction of the benign or malignant form in the diagnosis. Motivated by this, we propose a novel end-to-end weakly supervised deep learning model, based on inductive transfer learning with an improved convolutional neural network (CNN) to refine the embedding features of the latent space. The framework is composed of a source model in charge of finding the tumor patch-level patterns, and a target model focuses on the specific diagnosis of a biopsy. The latter retrains the backbone of the source model through a multiple instance learning workflow to obtain the biopsy-level scoring. To evaluate the performance of the proposed methods, we performed extensive experiments on a private skin database with spitzoid lesions. Test results achieved an accuracy of 0.9231 and 0.80 for the source and the target models, respectively. In addition, the heat map findings are directly in line with the clinicians' medical decision and even highlight, in some cases, patterns of interest that were overlooked by the pathologist.

Trombosis venosa profunda y trombofilia congénita / Deep-vein thrombosis and congenital thrombophilia

Introducción: La trombofilia es un desorden de la hemostasia congénito o adquirido que predispone al desarrollo de trombosis. Las trombofilias congénitas más frecuentes son las deficiencias de antitrombina III, proteína C y proteína S, el factor V Leiden, la mutación del gen de la protrombina (G20210A) y las mutaciones de la enzima metilentetrahidrofolato reductasa (MTHFR). Objetivo: Describir el manejo anestésico en un paciente portador de trombofilia congénita. Presentación del caso: Se reporta un paciente de 19 años de edad con antecedentes de historia familiar y personal de trombosis venosa profunda, tratamiento con doble antiagregación plaquetaria y asociación de tres mutaciones para trombofilia congénita, G20210A, A1298C MTHFR y C677T MTHFR que recibe anestesia espinal para una herniorrafia inguinal. Se mantiene tratamiento con aspirina, se suspende clopidogrel 7 días antes de la cirugía y durante ese tiempo se administra fraxiparina 0.6 Uds. subcutánea diarias hasta 12 h antes de la cirugía, se utiliza medias elásticas, deambulación precoz y reinicio de clopidogrel 24 h después de la cirugía, con evolución satisfactoria. Conclusiones: La tromboprofilaxis en pacientes portadores de trombofilia congénita es mandatoria, por eso resulta determinante la utilización de heparina de bajo peso molecular junto al resto de las medidas de prevención de la trombosis venosa profunda(AU)

Introduction: Thrombophilia is a congenital or acquired hemostasis disorder that predisposes to thrombosis development. The commonest congenital thrombophilias are deficiencies of antithrombin III, protein C and protein S, factor V Leiden, prothrombin gene mutation (G20210A), and methylenetetrahydrofolate reductase (MTHFR) mutations. Objective: To describe the anesthetic management in a patient with congenital thrombophilia. Case presentation: The case is reported of a 19-year-old patient with a family and personal history of deep-vein thrombosis, treatment with double antiplatelet therapy and association of three mutations for congenital thrombophilia (G20210A, A1298C MTHFR and C677T MTHFR), who receives spinal anesthesia for an inguinal herniorrhaphy. Aspirin treatment is maintained. Clopidogrel is suspended seven days before surgery. During this time, fraxiparin is administered subcutaneously in 0.6-mL units daily, up to twelve hours before surgery. Elastic stockings are used, early ambulation is allowed, and clopidogrel is restarted 24 hours after surgery, with satisfactory evolution. Conclusions: Thromboprophylaxis in patients with congenital thrombophilia is mandatory, a reason why the use of low-molecular-weight heparin, together with the rest of the prevention measures against deep-vein thrombosis, is decisive(AU)

Cutaneous Lymphadenoma Is a Distinct Trichoblastoma-like Lymphoepithelial Tumor With Diffuse Androgen Receptor Immunoreactivity, Notch1 Ligand in Reed-Sternberg-like Cells, and Common EGFR Somatic Mutations.

The term "cutaneous lymphadenoma" was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Our goal was to further clarify the phenotypic and genotypic features of cutaneous lymphadenoma in a series of 11 cases. Histologically, a lobular architecture surrounded by a dense fibrous stroma was present in all cases. The lobules were composed of epithelial cells admixtured with small lymphocytes and isolated or clustered large Reed-Sternberg-like (RS-L) cells. The epithelial cells were diffusely positive for the hair follicle stem cell markers CK15, PHLDA1, and for androgen receptor. No immunostaining for markers of sebaceous differentiation was found. Intraepithelial lymphocytes were predominantly CD3+, CD4+, FoxP3+ T cells. RS-L cells showed both strong Jagged-1 and Notch1 cytoplasmic immunostaining. Androgen-regulated NKX3.1 nuclear immunostaining was present in a subset of large intralobular cells in all cases. Double immunostaining showed coexpression of NKX3.1 and CD30 in a subset of RS-L cells. No immunostaining for lymphocytic or epithelial markers was present in RS-L cells. EGFR, PIK3CA, and FGFR3 somatic mutations were found by next-generation sequencing in 56% of the cases. We consider that cutaneous lymphadenoma is a distinct benign lymphoepithelial tumor with androgen receptor and hair follicle bulge stem cell marker expression, RS-L cell-derived Notch1 ligand, and common EGFR gene mutations.