Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis.

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.

Pigmented Deposits in the Skin.

Pigmented deposits can occur in the skin due to many and varied causes. Some of them are systemic conditions accompanied by involvement of internal organs. Others have serious prognostic implications, and early diagnosis can help in the correct and adequate management of the diseases. In addition, some of them are quite innocuous and the correct diagnosis avoids unnecessary treatments. In this article, we review the morphologic features of some of the most common and some of the less usual pigmented deposits in skin other than tattoos.

Osmotic-shock produced by vitrification solutions improves immature human oocytes in vitro maturation.

BACKGROUND: During cytoplasmic oocyte maturation, Ca(2+) currents are vital for regulating a broad range of physiological processes. Recent studies have demonstrated that DMSO and EG cause large transient increases in intracellular Ca(2+) in mouse oocytes. The CP used in vitrifying protocols also increases the intracellular calcium transient. The aim of this study is to evaluate the effects of vitrifying time (before and after IVM) and exposure to the vitrification solutions and ionomycin on oocyte quality and embryonic development. METHODS: 221 GV-oocytes unsuitable for IVF-ICSI cycles were randomly distributed into one of the following three groups. G1 (control group): 41 GV-oocytes IVM until MII; G2: 43 oocytes vitrified at GV stage and IVM until MII stage; and G3: 53 GV-oocytes IVM until MII and then vitrified. In order to clarify the effect of vitrification solutions (VS) on human oocyte IVM through the intracellular Ca(2+) oscillation, the following two groups were also included. G4: 43 GV-oocytes exposed to VS and IVM until MII; and G5: 41 GV-oocytes exposed to ionomycin and IVM until MII. All GV-oocytes that reached MII-stage were parthenogenetically activated to assess oocyte viability. IVM was performed in IVF-medium (24-48 h). Chemical treatment (ionomycin) and osmotic treatment (vitrification solutions) were performed without liquid-N2 immersion. The following rates were evaluated: survival (SR), in-vitro maturation (IVMR), activation (AR), development to 2-cell (DRC), development to morula (DRCM) and development to blastocyst (DRB). Ratios between the different treatment groups were compared using contingency tables analysis (chi-square test). RESULTS: A high survival rate was obtained in G2 (95.5 %) and G4 (96.6 %). In-vitro maturation rate was significantly higher for G4 (86 %) and G2 (83.7 %) compared to G1 (63.4 %), G3 (56.6 %) and G5 (48.8 %). DRCM was significantly higher for G1 and G2 compared to G3 (G1: 15.8 %, G2: 20.7 % and G3: 0 %). DRB was only obtained for the oocytes vitrified before IVM (G2: 3.4 %). AR was also significantly higher for G2 and G4 compared to G5 (G2: 80.5 %, G4: 86.5 % and G5: 55 %). DRCM and DRB were only obtained in G2 and G4. DRCM was significantly higher for oocytes vitrified at GV stage (G2) and for oocytes exposed to the VS in G4 compared to the oocytes exposed to the ionomycin in G5 (G2: 20.7 %; G4: 37.5 % and G5: 0 %). CONCLUSIONS: Vitrifying GV-oocytes improves their IVM. Further investigation could look to increase the oocyte pool and improve fertility preservation options.

Histological Features, p53, c-Kit, and Poliomavirus Status and Impact on Survival in Merkel Cell Carcinoma Patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy from neuroendocrine cells in the skin. Despite being one of the most life-threatening of skin cancers, little is known about the potential signaling mechanism that drives carcinogenesis in MCC. The purpose of this study is to assess the impact of Merkel cell polyomavirus (MCPyV), p53, and c-kit on the histological features and clinical prognosis of MCC treated in our regional hospitals. METHOD: The design was a retrospective study. The specimens were taken between 1993 and 2013 in 2 referral hospitals of Southern Spain. Data were collected retrospectively and analyzed using SPSS software. RESULTS: Thirteen lesions from 13 subjects were included in the study. Positivity for c-kit was associated with the absence of MCPyV viral DNA (P = 0.048) and positivity for p53 (P = 0.002). More rate of mitoses per high-power field was presented significantly in those specimens with: positivity for c-kit (P = 0.046), positivity for p53 (P = 0.05), lesions with infiltrative growth pattern (P = 0.008), and lymphovascular invasion (P = 0.034). We observed an inverse relationship between p53 expression and MCPyV infection (Pearson's coefficient: -0.524; P = 0.046) and between c-kit expression and MCPyV infection (Pearson's coefficient: -0.548; P = 0.05), whereas the relationship was positive between p53 expression and c-kit expression (Pearson's coefficient: 0.884; P < 0.001). CONCLUSION: We conclude that presence of MCPyV DNA has no effect on overall survival. MCCs with p53 and c-kit expressions are associated with the absence of or low MCPyV DNA showing an inverse relationship. A multifactorial molecular pathogenesis where positivity for p53 and c-kit are associated with other mechanisms different than MCPyV (such as pro-mitotic factors) may lead to aggressive clinical behavior.

Molluscum Contagiosum Infection Involving a Benign Epidermoid Cyst in an Immunocompetent Patient.

A 78-year-old man presented with a round- to oval-shaped nodule on his right eyebrow. The lesion first developed 5 years ago as a small solitary white nodule and subsequently enlarged over the past 2 years. His medical history was unremarkable. Clinical examination revealed a 2-cm round to oval dome-shaped yellowish nodule with a dimple on the top center (Figure 1). No similar lesions were found elsewhere. With a clinical suspicion of sebaceous carcinoma, an excision of the lesion was performed under local anesthesia. The histopathologic analysis showed an epidermal cyst containing molluscum bodies along the keratin inside the cyst (Figure 2). With these findings, the diagnosis of molluscum contagiosum (MC) infection into an epidermoid cyst was made. Neither recurrence nor new similar lesions were observed at follow-up.

A minimally invasive methodology based on morphometric parameters for day 2 embryo quality assessment.

The risk of multiple pregnancy to maternal-fetal health can be minimized by reducing the number of embryos transferred. New tools for selecting embryos with the highest implantation potential should be developed. The aim of this study was to evaluate the ability of morphological and morphometric variables to predict implantation by analysing images of embryos. This was a retrospective study of 135 embryo photographs from 112 IVF-ICSI cycles carried out between January and March 2011. The embryos were photographed immediately before transfer using Cronus 3 software. Their images were analysed using the public program ImageJ. Significant effects (P < 0.05), and higher discriminant power to predict implantation were observed for the morphometric embryo variables compared with morphological ones. The features for successfully implanted embryos were as follows: four cells on day 2 of development; all blastomeres with circular shape (roundness factor greater than 0.9), an average zona pellucida thickness of 13 µm and an average of 17695.1 µm² for the embryo area. Embryo size, which is described by its area and the average roundness factor for each cell, provides two objective variables to consider when predicting implantation. This approach should be further investigated for its potential ability to improve embryo scoring.

Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy.

To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non-alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease.

Peritoneal lymphomatosis. A case report.

INTRODUCTION: Involvement of the peritoneum occurs very rarely and is exceptional as an exclusive extranodal presentation of lymphomas. In most cases lymphomas associated with this rare entity are high-grade ones. PL secondary to high-grade nodal lymphoma is more frequent than primary peritoneal lymphoma, and there are only a few cases of the latter described in the literature. DESCRIPTION OF THE CASE: We present the case of a patient with constitutional syndrome and imaging findings suggestive of peritoneal carcinomatosis who was finally diagnosed with a Diffuse Large B-cell Lymphoma (DLBCL) by an ultrasound-guided core needle biopsy (CNB) of peritoneum. The patient received one polychemotherapy cycle; however tumor lysis syndrome occurred with death of the patient in the following days. This case tries to show the existence of a PL without other radiological findings of lymphoma, a fact that is very exceptionally described in the literature. DISCUSSION: The differential diagnosis between PL and others peritoneum diseases such as peritoneal carcinomatosis, malignant primary peritoneal mesotheliomas, tuberculous peritonitis, sarcomatosis, diffuse peritoneal leiomyomatosis or benign splenosis, constitutes a major problem in imaging techniques. An exhaustive analysis of the radiological characteristics as well as a clinical-analytical context allows the differential diagnosis against peritoneal carcinomatosis and the rest of the entities previously referred although the final diagnosis will always be a biopsy. CONCLUSION: PL usually manifests as an aggressive histological subtype of high-grade lymphomas leading to a rapid progression and deterioration of the patient. It is crucial for the radiologist and the clinician to be aware of this rare entity providing the earliest possible diagnosis and optimal treatment to prolong the patient's life.

Lymphoepitelioma-like carcinoma of the skin: report of three cases.

Primary cutaneous lymphoepithelioma-like carcinoma (LELC) is an extremely rare cutaneous neoplasm with histopathological features similar to those seen in the undifferentiated subtype of nasopharyngeal carcinoma. Microscopically, the tumor is well circumscribed and is composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. Its histogenesis remains unknown although an adnexal or epidermic origin has been proposed, and despite its poorly differentiated histology, the LELC prognosis is relatively good. We describe three new cases of this entity that support an epidermic origin.

SARS-CoV-2 Infection in Multiple Sclerosis: Results of the Spanish Neurology Society Registry.

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.

Multiple lentigines confined to a resolving psoriatic plaque.

Development of nevus spilus-like lentigines in zones previously affected by plaques of psoriasis has been described. Most cases have appeared following phototherapy; then it has been suggested that the mechanism involved could be an abnormal reaction to UV light. However, cases of multiple lentigines arising within resolving psoriatic in patients who had not received phototherapy or photochemotherapy have been described as a result of possible post-inflammatory hyperpigmentation. We report the case of patient who developed nevus spilus-like lentigines following therapy with topical calcipotriol on psoriatic plaques. We consider that the mechanism of production of lentigines is an unusual form of postinflammatory hyperpigmentation.

Congenital bilateral absence of the vas deferens (CBAVD): do genetic disorders modify assisted reproductive technologies outcomes? / Ausencia congénita bilateral del conducto deferente: ¿Modifican las alteraciones genéticas los resultados de las tecnicas de reproducción asistida?

OBJECTIVES: To evaluate the impact of common Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations, 5T polymorphism and presence of severe Cystic Fibrosis (CF) on fertility outcomes with Assisted Reproductive Techniques (ART) in patients presenting Congenital Bilateral Absence of Vas Deferens (CBAVD). METHODS: A comparative observational cohort study was performed from 2002 to 2018 with 51 patients with diagnosis of CBAVD. Presence of CFTR mutations and 5T, CF, pregnancy and newborn rates were analyzed. RESULTS: 80.4% percent had some mutation of CFTR gene being ΔF508 the most common (51%). The most frequently described genotype was the 7T/9T (31.4%) with the presence of 5T polymorphism in up to 25.5% of cases. Global newborn rates were 34% in the group using partner spermatozoa. When comparing 5T presence, we observed a decrease in newborn rates when carrying this mutation, without obtaining statistical significance (newborn rate: 5T/non-5T: 7.1/28%, p 0.45). No differences were found when comparing presence of severe CF, common CFTR gene mutations and ICSI-related parameters. CONCLUSION: The analysis of the presence of 5T polymporphism in CBAVD patients may add information when predicting the outcome of assisted reproductive techniques.

OBJETIVOS: Evaluar el impacto de las mutaciones del gen CFTR regulador de la conductancia transmembrana de la fibrosis quística, los polimorfismos 5T y la presencia de fibrosis quística (FQ) grave en los resultados de fertilidad de las técnicas de reproducción asistida en pacientes que presentan ausencia bilateral congénita de conductos deferentes.MÉTODOS: Estudio comparativo observacional de cohortes realizado desde 2002 hasta 2018 con 51 pacientes con el diagnóstico de ausencia bilateral congénita de conductos deferentes. Se analizaron la presencia de mutaciones del gen CFTR y 5T, fibrosis quística y tasas de embarazo y nacimientos. RESULTADOS: 80,4% tenían alguna mutación del CFTR siendo la ΔF508 la más frecuente (51%). El genotipo descrito con mayor frecuencia era 7T/9T (31,4%) con la presencia de polimorfismo 5T en hasta el 25,5% de los casos. Las tasas de nacimientos globales fueron del 34% en el grupo que utilizaba espermatozoides del marido. Cuando se compara la presencia de 5T, observamos una disminución en las tasas de nacimientos en los portadores de esta mutación, sin obtener significación estadística (Tasa de nacimientos 5T/no-5T: 7,1/28%, p=0,45). No se encontraron diferencias en la comparativa entre la presencia de FQ severa, mutaciones comunes del gen CFTR y los parámetros relacionados con la ICSI. CONCLUSIONES: El análisis de la presencia de polimorfismo 5T en los pacientes con ausencia bilateral congénita de conductos deferentes puede añadir información para la predicción de los resultados de las técnicas de reproducción asistida.

[Gastric bronchogenic cysts. An unusual location]. / Quistes broncogénicos gástricos. Una localización inhabitual.

Bronchogenic cysts are rare benign lesions that arise during embryogenesis of the primitive proximal intestine and are located primarily in the lung. They are lined with cuboid or columnar pseudostratified and ciliated epithelium and have elastic fibers, smooth muscle, bronchial glands and cartilage in their walls. Gastric bronchogenic cysts are extremely rare with very few reported cases. Symptoms are usually caused by compression. GIST is the main differential diagnosis and the treatment is surgical resection.

Cutaneous metastasis of breast carcinoma mimicking malignant melanoma in scalp.

Cutaneous metastases of carcinoma of the breast may present a broad spectrum of clinical and histologic appearances. Pigmented metastases of a breast carcinoma have rarely been described in the literature and these metastases are usually located on the chest and abdominal wall close to the mastectomy scar. We report an unusual case of a cutaneous metastasis of carcinoma of the breast simulating malignant melanoma.

Primary giant cell tumor of soft tissue in the finger.

Primary giant cell tumor of soft tissue (GCTST) arising in a finger is a rare event. We report a case of a 54-year-old man with a primary finger giant cell tumor that appeared histologically identical to giant cell tumor of bone. The patient presented with a cystic mass of the finger. The magnetic resonance imaging showed no relation between the nodule and bone, tendons or synovial tissues. The distinction of this entity from other more common primary finger tumors with giant cell morphology is emphasized.

[Dendritic infraclavicular fibromyxolipoma: At the boundary between spindle cell lipoma and solitary fibrous tumour]. / Fibromixolipoma dendrítico infraclavicular: en el límite entre el lipoma de células fusiformes y el tumor fibroso solitario.

Dendritic fibromyxolipoma (DFML) is a rare soft tissue tumor recently described with only 27 cases reported in the literature. None of them have shown recurrence or metastasis after excision. Histologically it is composed of small stellate or spindle cells in a myxoid stroma with abundant collagen bundles mixed with mature adipose tissue. The proliferating cells typically show immunoexpression positive for CD34 and bcl-2. A cytogenetic analysis reveals deletion involving 13q14.3 region. We describe the first reported case to date located in the infraclavicular region. A 69 year old male with a painless mass well circumscribed and 5cm in size of several years of evolution, that after excision (2 years ago) he has not shown signs of recurrence or metastasis. This study reflects the clinicopathological features, differential diagnosis and a review of the literature of the DFML.

Occlusive eccrine hidradenitis presented as a reticulated eruption on the buttocks.

A 13-month-old girl presented a reticulated eruption of 2 months duration located on her buttocks. Histologically, a mononuclear cell inflammatory infiltration was found within and around the eccrine sweat glands, with epithelial cell damage. The lesions were related to several traumatic mechanisms involving the buttocks, such as crawling and repeated trauma with a bathmat carpet.

Peritoneal lymphomatosis. A case report

ABSTRACT Introduction: Involvement of the peritoneum occurs very rarely and is exceptional as an exclusive extranodal presentation of lymphomas. In most cases lymphomas associated with this rare entity are high-grade ones. PL secondary to high-grade nodal lymphoma is more frequent than primary peritoneal lymphoma, and there are only a few cases of the latter described in the literature. Description of the case: We present the case of a patient with constitutional syndrome and imaging findings suggestive of peritoneal carcinomatosis who was finally diagnosed with a Diffuse Large B-cell Lymphoma (DLBCL) by an ultrasound-guided core needle biopsy (CNB) of peritoneum. The patient received one polychemotherapy cycle; however tumor lysis syndrome occurred with death of the patient in the following days. This case tries to show the existence of a PL without other radiological findings of lymphoma, a fact that is very exceptionally described in the literature. Discussion: The differential diagnosis between PL and others peritoneum diseases such as peritoneal carcinomatosis, malignant primary peritoneal mesotheliomas, tuberculous peritonitis, sarcomatosis, diffuse peritoneal leiomyomatosis or benign splenosis, constitutes a major problem in imaging techniques. An exhaustive analysis of the radiological characteristics as well as a clinical-analytical context allows the differential diagnosis against peritoneal carcinomatosis and the rest of the entities previously referred although the final diagnosis will always be a biopsy. Conclusion: PL usually manifests as an aggressive histological subtype of high-grade lymphomas leading to a rapid progression and deterioration of the patient. It is crucial for the radiologist and the clinician to be aware of this rare entity providing the earliest possible diagnosis and optimal treatment to prolong the patient's life.

Bacterial and fungal contamination risks in human oocyte and embryo cryopreservation: open versus closed vitrification systems.

OBJECTIVE: To study the contamination risk in open and closed vitrification devices for oocyte/embryo cryopreservation by evaluating the contaminants present (bacteria and fungi) in the thaw medium and in liquid nitrogen (LN) storage containers. DESIGN: Retrospective study. SETTING: Human reproduction unit. PATIENT(S): None. INTERVENTION(S): Retrospective study of vitrification device safety and LN sterility performed from July to October 2014. MAIN OUTCOME MEASURE(S): From each bank container, both open and closed vitrification devices, devitrification media and LN in the containers and as supplied by the company were evaluated for contaminants. An automated system and the corresponding susceptibility to antibiotics were used for bacteria identification. Fungus detection was performed by evaluating the colony morphology and their microscopic characteristics. RESULT(S): No bacteria or fungi were observed in any of the devitrification media regardless of the type of device used, nor in the LN supplied by the company. No fungi were observed in any of the LN samples tested. Stenotrophomonas maltophilia and Bacillus spp. were found in all oocyte/embryo bank LN containers. There was no relationship between the number of samples or the time that each container had been used and the presence of microbiologic contaminants in the LN. At the container's bottom, Acinetobacter lwoffii, Alcaligenes faecalis ssp. faecalis, and Sphingomonas paucimobilis were found. CONCLUSION(S): Bacteria cross-contamination may not occur in oocyte/embryo banking in either open or closed storage devices. However, microorganisms can survive in LN. The bacteria cross-contamination risk is no greater for open than for closed containers. Storage containers should be cleaned periodically owing to the risk of lost straws or small particles of contaminated material.