Utility of the WHO dengue guidelines in pediatric immunological studies.

Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.

[Robot-assisted radical prostatectomy with Retzius-Sparing approach vs. modified Frankfurt: comparison of results at 1 year of follow-up]. / Prostatectomía radical asistida por robot con abordaje Retzius-Sparing vs. Frankfurt modificado: comparación de resultados a 1 año de seguimiento.

Background: Robot-assisted radical prostatectomy has positioned itself as the approach of choice in the treatment of prostate cancer. Objective: To compare the outcomes of robot-assisted radical prostatectomy using the Retzius-Sparing (RS) approach against the modified Frankfurt (MF) technique. Method: To describe the perioperative, functional and oncological outcomes of 13 patients with prostate cancer who underwent RS robotic radical prostatectomy compared to MF, evaluating pathological results, urinary continence, sexual function and oncological control in 1 year of follow-up. Results: The average age was 64 years in RS group vs. 61 years in MF group. The values of total prostate antigen were higher in the RS group (25 ng/dl) vs. MF group (11 ng/dl). The volume of gland in RS group was 40.62 ml vs. 63.33 ml in the RS group. All patients were bilaterally neuropreserved, being statistically significant in favor of MF group (p = 0.016). Positive surgical margins were higher in R-S group (38.4%) vs. MF group (33.3%). Conclusions: With RS the same tendency to urinary continence is observed, with a significant difference in erectile function in favor of MF. This preliminary study shows better impact on erectile function.

Antecedentes: La prostatectomía radical asistida por robot se ha posicionado como el abordaje de elección en el tratamiento del cáncer de próstata. Objetivo: Comparar los resultados de la prostatectomía radical asistida por robot utilizando el abordaje Retzius-Sparing (RS) contra el Frankfurt modificado (FM). Método: Se describen los desenlaces perioperatorios, funcionales y oncológicos de 13 pacientes con cáncer de próstata que fueron llevados a prostatectomía radical robótica con RS, en comparación con FM, y se evalúan los resultados patológicos, continencia urinaria, función sexual y control oncológico a 1 año de seguimiento. Resultados: La media de edad fue de 64 años en el grupo RS y de 61 años en el grupo FM. Los valores de antígeno prostático total fueron mayores en el grupo RS (25 ng/dl) que en el FM (11 ng/dl). El volumen de la glándula fue menor en el grupo RS (40.62 ml) que en el FM (63.33 ml). Todos los pacientes fueron neuropreservados bilateralmente, siendo la diferencia estadísticamente significativa a favor de FM (p = 0.016). Los márgenes quirúrgicos positivos fueron mayores en el grupo RS (38.4%) que en el FM (33.3%). Conclusiones: Con RS se observa la misma tendencia a la continencia urinaria, con diferencia significativa en la función eréctil a favor de FM. Este estudio preliminar muestra mejor impacto en la función eréctil.

Defining the Histopathological Term Atypical Intraepidermal Melanocytic Proliferation: A Retrospective Cross-Sectional Study.

BACKGROUND: Atypical intraepidermal melanocytic proliferation (AIMP) is a general term assigned to melanocytic proliferations of uncertain biological potential when a definitive histopathological diagnosis cannot be achieved. There are few data available describing the possibility of malignancy of AIMP, or ways to further define diagnosis. OBJECTIVE: To determine the rate of diagnostic change of AIMP to melanoma or melanoma in situ (MIS) after conventional excision. In addition, to determine the role of immunohistochemistry (IHC) in defining AIMP biopsies. METHODS: Retrospective cross-sectional, single-center review of biopsies with a diagnosis of AIMP with a follow-up conventional excision from 2012-2016 was performed. In a separate analysis, a search was performed for AIMP biopsied lesions in which IHC was subsequently performed. RESULTS: The rate of diagnostic change of AIMP to MIS was 4.8% (8/167) after excision. Punch biopsy was a risk factor for diagnostic change to MIS (odds ratio 12.94, confidence interval 2.56-65.38, P = 0.008). The rate of diagnostic change of AIMP biopsies after examining with IHC was 21.3% (34/160) to MIS and 4.4% (7/160) to melanoma. CONCLUSION: The possibility of malignancy of AIMP lesions must be taken into consideration when counseling patients and when planning treatment options. IHC is a useful tool and should be used in the evaluation of AIMP specimens.

Non-Melanoma Skin Cancer Tumor's Characteristics and Histologic Subtype as a Predictor for Subclinical Spread and Number of Mohs Stages required to Achieve Tumor-Free Margins.

OBJECTIVE: To describe the behavior of non-melanoma skin cancer (NMSC) based on tumor's characteristics. METHODS: A total of 219 of NMSC were analyzed via a retrospective medical chart review. The data obtained from each record included but was not limited to: number of Mohs micrographic surgery (MMS) stages required for tumor clearance, defect size, repair type and size according to the neoplasm's histopathologic subtype. RESULTS: The mean number of stages required to clear morpheaphorm/infiltrative and micronodular basal cell carcinomas (BCCs) (n= 34) was 2.03, while the nodular and superficial BCCs (n= 125) needed a mean of 1.56 stages (p value= .034). Of the tumors located on a high-risk zone, 59.6% required two or more stages to be cleared while 67.7% of the lesions on a non-high risk zone were cleared with one stage (p value = 0.001). Recurrent tumors required a mean 2.22 MMS stages to be cleared, whereas primary tumors required a mean 1.61 stages (p value= .006). CONCLUSION: Subclinical spread was seen in morpheaform/infiltrative and micronodular BCC histologic subtypes, recurrent tumors, and tumors in high-risk locations. These could help predict aggressive tumor behavior and optimize surgical planning.

Pigmented Lesions of the Nail Unit.

Pigmented lesions of the nail unit are commonly encountered in the clinical setting. Yet, they often present a unique challenge to clinicians because of a broad differential diagnosis or unfamiliarity with clinical and histopathologic features. A wide variety of causes exist ranging from benign lesions such as subungual hemorrhage to malignant lesions such as subungual melanoma. Identifying the underlying cause is key to appropriate management and follow-up in these patients. Although emerging clinical tools such as dermoscopy can be very useful in evaluation of these lesions, histopathologic analysis remains the gold standard. In this review, we discuss and provide a summary of important clinical and histopathological concepts of pigmented lesions of the nail unit with special focus on longitudinal melanonychia, melanotic macule, melanocytic nevus, subungual melanoma, along with discussion of some nonmelanocytic lesions.

Role of Skin Biopsies in the Diagnosis of Hemophagocytic Lymphohistiocytosis.

This is a report of a 15-year-old female who presented with a skin eruption and clinical features consistent with severe sepsis and septic shock. A diagnosis of acquired hemophagocytic lymphohistiocytosis (HLH) was made and confirmed by bone marrow analysis. Skin biopsy showed hemophagocytosis and CD163-positive staining of macrophages. We briefly review the clinical, histologic, and laboratory findings of hemophagocytic lymphohistiocytosis in addition to the potential role of skin biopsies in this condition.

Palisaded Granuloma on the Nose: An Atypical Presentation of Granuloma Annulare.

Granuloma annulare (GA) is a common, asymptomatic dermatosis of unknown etiology. Many variants exist, among them widespread papules, papules in photodistribution, papules marked by tiny crusts ("perforating" GA), patches, plaques, and nodules (subcutaneous GA). The histopathological hallmark is a palisaded histiocytic infiltrate surrounding a central area of degenerated collagen with abundant mucin deposits. We report 2 women who presented with persistent nodules on the nose, which, on histopathological examination, showed a palisaded granuloma. We propose that these cases represent an unusual variant of GA occurring on the nose.

Extraocular Sebaceous Carcinoma-A Clinicopathologic Reassessment.

Sebaceous carcinoma is an aggressive adnexal neoplasm with sebaceous differentiation. Few reports have described the histopathologic characteristics of the sebaceous carcinoma occurring extraocularly. Seventy-two cases of extraocular sebaceous carcinoma were identified from the database of a Dermatopathology Laboratory from January 1, 2007 to May 31, 2013. More cases occurred in men (60%), with a mean age at diagnosis of 65.8 years (range 39-99 years). Neoplasms were histopathologically classified as well-differentiated (22%), moderately differentiated (67%), and poorly differentiated (11%). Sixty-seven percent (67%) of cases demonstrated a squamoid growth pattern and thirty-three percent (33%) demonstrated a basaloid growth pattern. A majority of the neoplasms histopathologically classified as well-differentiated (94%) and moderately differentiated (65%) demonstrated a squamoid growth pattern. Ten percent (10%) of cases exhibited cystic histopathologic changes. The histopathological features reported in this study aid in the understanding of extraocular sebaceous carcinoma and its eventual diagnosis and classification.

Rosacea-Like Leukemia Cutis: A Case Report.

Leukemia cutis describes the infiltration and dissemination of neoplastic leukemic cells into the epidermis, dermis, or subcutis, resulting in clinically identifiable cutaneous lesions. Depending on the type of leukemia, a wide range of clinical and histopathological findings may be encountered. This report describes a patient with a rosacea-like eruption as a unique clinical presentation of T-cell prolymphocytic leukemia.

Clear-Cell Atypical Fibroxanthoma: A Combined Immunohistochemistry Analysis.

Atypical fibroxanthoma is considered to be a low-grade sarcoma, characterized by a proliferation of bizarre spindled cells. A case of a rare variant of this tumor, a clear-cell atypical fibroxanthoma, presenting with rapid growth on a 63-year-old female, is reported. The differential diagnosis of a clear cell proliferation and a review of the immunohistochemistry markers used in the diagnosis of atypical fibroxanthoma are discussed. In particular, the usefulness of markers such as CD10, procollagen 1, CD68, CD163, CD99, and S100A6, and the importance of negative markers such as S100, cytokeratin, and desmin are emphasized. Furthermore, the development of a keratoacanthoma at the site of previous Mohs surgery is recounted.

Superior Efficacy and Safety of a Nonemulsive Variant of the NGcGM3/VSSP Vaccine in Advanced Breast Cancer Patients.

NGcGM3 ganglioside is a tumor-specific antigen expressed in human breast tumors. The NGcGM3/VSSP vaccine, consisting in very small-sized proteoliposomes (VSSP) obtained by the incorporation of NGcGM3 into the outer membrane protein complex of Neisseria meningitidis, has been previously tested in a Phase II trial in patients with metastatic breast cancer (MBC) but emulsified with Montanide ISA 51. An Expanded Access study was carried out in MBC patients aiming to find if a nonemulsive formulation of NGcGM3/VSSP, without Montanide ISA 51, could be more safe and effective. A total of 104 patients were vaccinated with the nonemulsive formulation (900 µg), subcutaneously (SC), or with the emulsive formulation (200 µg), intramuscularly (IM). An intent-to-treat analysis of efficacy was performed with all patients, and 93 patients were split off according to the site of metastases (visceral/nonvisceral). Of note, SC-treated patients exhibited a superior median overall survival (OS) than IM-treated patients (23.6 vs. 8.2 months; log rank P = 0.001). Even though in the subset of patients with nonvisceral metastases SC vaccination duplicated the median OS compared to the alternative option (31.6 vs. 16.5 months), this difference did not reach statistical significance (log rank P = 0.118). Curiously, in patients with visceral metastases, the advantage of the nonemulsive formulation was more apparent (median OS 21.0 vs. 6.2 months; log rank P = 0.005). The vaccine was safe for both formulations.

Design, synthesis and biological evaluation of novel pyrenyl derivatives as anticancer agents.

Polycyclic aromatic hydrocarbons are widespread in nature with a toxicity range from non-toxic to extremely toxic. A series of pyrenyl derivatives has been synthesized following a four-step strategy where the pyrene nucleus is attached with a basic heterocyclic moiety through a carbon linker. Virtual screening of the physicochemical properties and druggability has been carried out. The cytotoxicity of the compounds (1-8) have been evaluated in vitro against a small panel of human cancer cell lines which includes two liver cancer (HepG2 and Hepa 1-6), two colon cancer (HT-29 and Caco-2) and one each for cervical (HeLa) and breast (MCF-7) cancer cell lines. The IC50 data indicate that compound 6 and 8 are the most effective cytotoxic agents in the present set of pyrenyl derivatives, suggesting that having a 4-carbon linker is more effective than a 5-carbon linker and the presence of amide carbonyl groups in the linker severely reduces the efficacy of the compound. The compounds showed selectivity toward cancer cells at lower doses (<5 µM) when compared with the normal hepatocytes. The mechanism of action supports the cell death through apoptosis in a caspase-independent manner without cleavage of poly (ADP-ribose) polymerase (PARP), even though the compounds cause plasma membrane morphological changes. The compounds, whether highly cytotoxic or mildly cytotoxic, localize to the membrane of cells. The compounds with either a piperidine ring (6) or an N-methyl piperazine (8) in the side chain were both capable of circumventing the drug resistance in SKOV3-MDR1-M6/6 ovarian cancer cells overexpressing P-glycoprotein. Qualitative structure-activity relationship has also been studied.

Bismuth nitrate-induced novel nitration of estradiol: an entry to new anticancer agents.

Direct nitration of estradiol was carried out using metal nitrates on solid surfaces under mild condition, and a combination of bismuth nitrate pentahydrate impregnated KSF clay was found to be the best reagent to synthesize 2- and 4-nitroestradiol effectively. Furthermore, various basic side chains were introduced, through O-linker at C-3, to these nitroestradiols. The ability of these derivatives to cause cytotoxicity in Estrogen Receptor (ER)-positive and ER-negative breast cancer cell lines, as well as cancer cell lines of other origins, was examined. Qualitative structure activity relationship (SAR) has also been studied. We found that a basic side chain containing either a piperidine or morpholine ring, when conjugated to 2-nitroestradiol, was particularly effective at causing cytotoxicity in each of the cancer cell lines examined. Surprisingly, this effective cytotoxicity was even seen in ER-negative breast cancer cells.

Clinical and dermoscopic patterns of melanocytic nevi in Hispanic adolescents: a descriptive study.

BACKGROUND: Melanocytic nevi are well-known, important precursors of melanoma among children and adults. The adolescence period is an important period for nevi formation and evolution. This study provides data of a longitudinal study of nevi in a Hispanic adolescent population. MATERIALS AND METHODS: A cross-sectional survey and 1-year prospective follow-up study was performed on Hispanic students from grades 6 and 7 at a school in Caguas, Puerto Rico (n = 90). The survey was completed by the students and one of their parents. The backs of the children were clinically examined for melanocytic nevi using digital photography and dermoscopy. Follow-up was conducted one year later. RESULTS: The study cohort consisted of 53 (59%) boys and 37 (41%) girls, with an average age of 11.9 years (range 11-13 years). At the beginning of the study, 85% (n = 71/90) of the students presented with melanocytic nevi on their backs. After one year, new nevi were identified in 62% (n = 44/71), and there was a mean increase in nevus count of 1.8 (P < 0.001). A trend toward increased nevus count in lighter skin types was observed (P < 0.001). The predominant dermoscopic pattern was reticular (44%). The globular pattern was found most commonly in children with skin-type II (100%), while the reticular pattern was the most common among skin-types III (32%), IV (56%), and V (45%). CONCLUSIONS: This study supports the utility of digital photography and dermoscopy for the evaluation of melanocytic nevi, providing evidence of the interrelationship between nevus count, dermoscopic pattern, and skin phenotype.

Follicular mucinosis presenting as an acneiform eruption: a follow-up study.

It has been proposed by many authors that follicular mucinosis is directly associated with mycosis fungoides (MF). Follicular mucinosis may be classified into 3 main clinical variants: a benign idiopathic form in children and young adults, which includes an acneiform presentation; an idiopathic form in older patients with a benign course; and a third variant that occurs in adults and is associated with MF. Our goal was to study the relationship between the acneiform variant of follicular mucinosis and MF. Eight patients previously diagnosed with the acneiform variant of follicular mucinosis were identified. Biopsy specimens were reviewed to evaluate the histopathologic attributes that characterize the disease and the infiltrate's immunohistochemistry. Also, patient follow-up was assessed to evaluate the clinical course of the disease. Median age of onset of disease was 29.5 years; 95% of lesions were located in the head and neck region. Biopsy specimens showed a moderate to dense perivascular, perifollicular, and interstitial infiltrate of lymphocytes with mucinous deposits within the follicular epithelium. On immunohistochemistry, the infiltrate showed prominent leukocyte common antigen (LCA) positivity and a CD3-positive and CD4-positive infiltrate with rare CD20-positive cells. None of the study patients showed evidence of MF after a mean follow-up of 3 years. The benign course of disease demonstrated in the study patients suggests that the acneiform variant of follicular mucinosis probably represents a subpopulation of the benign idiopathic form of the disease. However, given that histopathologically this variant cannot be distinguished from the lymphoma-associated variant of follicular mucinosis, longitudinal evaluation is still warranted in these patients.

Acquired segmental neuromas.

Neuromas are benign hyperplastic proliferations of normal peripheral nerve components. These can be associated with some genodermatoses, namely Cowden syndrome and multiple endocrine neoplasia (MEN) 2B, especially when numerous lesions are present. Given the potential for malignancy (such as breast cancer, pheochromocytoma, and thyroid cancer) associated with these syndromes, other features indicative of either syndrome should be evaluated in patients presenting with multiple cutaneous neuromas. The evaluation should include a thorough family history and complete physical, dermatologic, and ophthalmologic exams as well as thyroid studies. We report, herein, the case of an 8-year-old female with cutaneous neuromas distributed segmentally with no other associated finding suggestive of an underlying syndrome.

Langerhans cell sarcoma: a case report.

Primary cutaneous neoplasms of histiocytes and dendritic cells are rare. Langerhans cells are a subset of antigen-presenting dendritic cells. Neoplasms of Langerhans cells are classified into cytologically benign Langerhans cell histiocytosis and cytologically malignant Langerhans cell sarcoma. Langerhans cell sarcoma is a rare entity characterized by multiorgan involvement and an aggressive clinical course. To date, only 30 cases of Langerhans cell sarcoma, including the present case, have been reported. We report a new case of Langerhans cell sarcoma that presented with multifocal cutaneous involvement. Diagnosis was done based on histopathological, immunohistochemical evaluation, as well as ultrastructural analysis identifying the presence of Birbeck granules. Our case represents a new case of this extremely rare, overtly aggressive neoplasm of Langerhans cells. Within 2 years of diagnosis, the patient developed metastatic disease and consequently died. Early recognition is important because of the tendency of Langerhans cell sarcoma to recur and metastasize. Therefore, ancillary techniques such as immunohistochemical and ultrastructural studies to confirm the diagnosis are very advantageous.