Renal Disease in Metabolic Syndrome: the Hidden Role of Intrarenal Ischemia.

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project. Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m2; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease. Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) (P = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P < 0.05). These vascular changes were independent of differences in age. Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health.

Short Brown Parallel Lines on the Proximal Nail Fold. Clinical-Dermoscopic-Histologic Correlation of a Melanocytic Nevus of the Eponychium.

Introduction: Although Hutchinson's sign can appear associated with benign conditions, dermoscopic findings of non-melanoma eponychium pigmentation have not yet been described in the literature. We report for the first time to our knowledge the dermoscopic findings of an acral nevus located in the proximal nail fold as well as its clinical-dermoscopic-histologic correlation. Case Report: A twenty-year-old patient presented with a homogeneous longitudinal melanonychia on the left-hand thumb, with benign dermoscopic pattern, and an irregular, 6-mm, dark-brown hyperpigmented macule on the adjacent eponychium (Hutchinson's sign). The eponychium lesion showed on dermoscopy two irregular brown-black pigmented blotches, with superimposed parallel brown lines on a brushy distribution, with a thicker terminal end. The histopathologic examination of the proximal nail fold was performed, revealing scattered nevus cells in the epidermal basal layer and dermal-epidermal junction thecae, without any atypia or mitosis. These features were consistent with nevus of the proximal nail fold. Discussion: Previous descriptions of benign hyponychium's pigmentations, despite the malignant appearance of the overlying melanonychia, were reported to have a similar dermoscopic pattern, known as longitudinal brushy pigmentation. This newly described dermoscopic sign on the eponychium may help distinguish Hutchinson's sign related to subungual melanoma to non-melanoma Hutchinson's sign.

Double CD4/CD8-Positive, Nonpoikilodermic Mycosis Fungoides Expressing CD56 in a Young Man.

ABSTRACT: We report a case of mycosis fungoides (MF) in an 18-year-old man whose neoplastic T cells expressed CD4, CD8, and CD56, with no evidence of TCR-delta or Epstein-Barr virus (EBER) expression. Clinically, neither hypopigmentation nor hyperpigmentation nor poikilodermatous skin lesions were present, and the lesions subsided with oral corticoids and retinoids and environmental solar ultraviolet exposure. Our case represents the oldest patient reported so far with nonpoikilodermatous, CD8/CD56 MF and adds to the phenotypic diversity of MF in the pediatric population. This distinct phenotype does not seem to be linked to a more aggressive course than the classic CD-4 positive one.

The Role of Vascular Lesions in Diabetes Across a Spectrum of Clinical Kidney Disease.

INTRODUCTION: The clinical-histologic correlation in diabetic nephropathy is not completely known. METHODS: We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). RESULTS: Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% <60 ml/min per 1.73 m2). About 170 glomeruli per patient were analyzed, and all samples included vascular tissue. Six subjects (7%) were classified in diabetic nephropathy class I, 61 (68%) in class II-a, 13 (14%) in class II-b, 9 (10%) class III, and 1 (1%) in class IV. Eighty percent to 90% of those with normoalbuminuria or microalbuminuria were classified in class II-a or II-b and <10% in class III; 52% of those with proteinuria were in class II-a, 15% in class II-b, and 19% in class III. Nodular sclerosis (57%) and mesangial expansion (15%) were more frequent in cases with proteinuria than in normoalbuminuria (28% and 8%; P = 0.028 and 0.017). About 20% to 30% of all cases, regardless the level of albuminuria or proteinuria or the histologic class had tubular atrophy, interstitial fibrosis, or inflammation in >10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III. CONCLUSIONS: Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes.

Cd34+ Stromal Cells/Telocytes in Normal and Pathological Skin.

We studied CD34+ stromal cells/telocytes (CD34+SCs/TCs) in pathologic skin, after briefly examining them in normal conditions. We confirm previous studies by other authors in the normal dermis regarding CD34+SC/TC characteristics and distribution around vessels, nerves and cutaneous annexes, highlighting their practical absence in the papillary dermis and presence in the bulge region of perifollicular groups of very small CD34+ stromal cells. In non-tumoral skin pathology, we studied examples of the principal histologic patterns in which CD34+SCs/TCs have (1) a fundamental pathophysiological role, including (a) fibrosing/sclerosing diseases, such as systemic sclerosis, with loss of CD34+SCs/TCs and presence of stromal cells co-expressing CD34 and αSMA, and (b) metabolic degenerative processes, including basophilic degeneration of collagen, with stromal cells/telocytes in close association with degenerative fibrils, and cutaneous myxoid cysts with spindle-shaped, stellate and bulky vacuolated CD34+ stromal cells, and (2) a secondary reactive role, encompassing dermatitis-e.g., interface (erythema multiforme), acantholytic (pemphigus, Hailey-Hailey disease), lichenoid (lichen planus), subepidermal vesicular (bullous pemphigoid), psoriasiform (psoriasis), granulomatous (granuloma annulare)-vasculitis (leukocytoclastic and lymphocytic vasculitis), folliculitis, perifolliculitis and inflammation of the sweat and sebaceous glands (perifolliculitis and rosacea) and infectious dermatitis (verruca vulgaris). In skin tumor and tumor-like conditions, we studied examples of those in which CD34+ stromal cells are (1) the neoplastic component (dermatofibrosarcoma protuberans, sclerotic fibroma and solitary fibrous tumor), (2) a neoplastic component with varying presentation (fibroepithelial polyp and superficial myxofibrosarcoma) and (3) a reactive component in other tumor/tumor-like cell lines, such as those deriving from vessel periendothelial cells (myopericytoma), epithelial cells (trichoepithelioma, nevus sebaceous of Jadassohn and seborrheic keratosis), Merkel cells (Merkel cell carcinoma), melanocytes (dermal melanocytic nevi) and Schwann cells (neurofibroma and granular cell tumor).

Adenocarcinoma villoglandular de cerviz / Villoglandular adenocarcinoma of the uterine cervix

El adenocarcinoma villoglandular de cérvix uterino es una neoplasia poco frecuente, con unas características histológicas y clínicas diferentes de otros tipos de adenocarcinomas de cérvix. No fue introducido en la clasificación de la Organización Mundial de la Salud hasta 1994. El tratamiento de este tipo de tumor debe ser, en la medida de lo posible, conservador si la paciente desea preservar su fertilidad, pues presenta buen pronóstico. Los hallazgos microscópicos son típicos e incluyen: crecimiento exofítico, superficie de aspecto papilar y de leve a moderada atipia nuclear. Presentamos 4 casos clínicos de esta entidad, uno de ellos con progresión y comportamiento agresivo (AU)

Villoglandular adenocarcinoma of the uterine cervix is a rare neoplasm, with histological and clinical features that distinguish it from other types of cervical adenocarcinomas. Until 1994, this entity was not included with the cervical carcinoma classification of the World Health Organization. The prognosis of this tumor is favorable and consequently treatment should be conservative as far as possible if the patient wishes to preserve fertility. Microscopic findings are typical and include exophytic growth, papillary surface and small-to-moderate nuclear atypia. We describe four cases of villoglandular adenocarcinoma, one of which showed aggressive progression (AU)

Facial self-induced paraffinoma in an elderly woman.

A 72-year-old Caucasian woman without remarkable medical history presented with an asymptomatic bilateral periocular swelling, which had been present for 2 months. Physical examination showed symmetric indurated periocular erythematous plaques (Figure 1). Biopsy of a skin lesion revealed aggregates of vacuoles of different sizes (Figure 2) surrounded by a prominent inflammatory infiltrate constituted by macrophages, lymphocytes, neutrophils, and granulomatous foreign body reaction throughout the reticular dermis and hypodermis. These histological findings were consistent with the injection of an oily foreign substance. The patient denied the self-induced nature of the lesions, so she was referred for psychiatric evaluation and admitted having self-injected mineral oil as an impulsive attempt to get attention from her family. She was diagnosed with borderline personality disorder (BPD) and started treatment with oral fluoxetine, showing a rapid decrease of impulsive behavior and anxiety from the second week with a mean dose of 80 mg/d.

The neurotrophic effect of oleic acid includes dendritic differentiation and the expression of the neuronal basic helix-loop-helix transcription factor NeuroD2.

We have shown recently that the presence of albumin in astrocytes triggers the synthesis and release of oleic acid, which behaves as a neurotrophic factor for neurons. Thus, oleic acid promotes axonal growth together with the expression of the axonal growth-associated protein, GAP-43. Here we attempted to elucidate whether the neurotrophic effect of oleic acid includes dendritic differentiation. Our results indicate that oleic acid induces the expression of microtubule associated protein-2 (MAP-2), a marker of dendritic differentiation. In addition, the presence of oleic acid promotes the translocation of MAP-2 from the soma to the dendrites. The time course of MAP-2 expression during brain development coincides with that of stearoyl-CoA desaturase, the limiting enzyme of oleic acid synthesis, indicating that both phenomena coincide during development. The effect of oleic acid on MAP-2 expression is most probably independent of autocrine factors synthesized by neurons because this effect was also observed at low cellular densities. As oleic acid is an activator of protein kinase C, the possible participation of this transduction pathway was studied. Our results indicate that added oleic acid or oleic acid endogenously synthesized by astrocytes exerts its neurotrophic effect through a protein kinase C-dependent mechanism as the effect was inhibited by sphingosine or two myristoylated peptide inhibitors of protein kinase C. The transduction pathway by which oleic acid induces the expression of genes responsible for neuronal differentiation appears to be mediated by the transcription factor NeuroD2, a regulator of terminal neuronal differentiation.

Mielolipoma de suprarrenal: presentación de dos casos / Supradrenal myelolipoma: presentation of two cases

Antecedentes: el mielolipoma es una neoplasia no verdadera de la glándula suprarrenal formada por tejido adiposo maduro con elementos activos de la médula ósea. Puede asociarse con el síndrome de Cushing o con hiperplasia suprarrenal cong,nita o ambos. La mayor parte de los casos estudiados son hallazgos de autopsias. Material y métodos: mujer de 32 años de edad, con antecedente de tres cesáreas, que cursó con hipertensión arterial gestacional. Inició su padecimiento seis meses antes con dolor en el hipocondrio derecho e hipertensión arterial sistémica. Se le realizó un ultrasonido de vías biliares y la tomografía de abdomen, en los que se observó una neoplasia aparentemente dependiente del lóbulo hepático derecho. Se le realizó una laparotomía durante la cual se identificó una lesión en la glándula suprarrenal derecha, y se realizó adrenalectomía. El segundo caso se trata de un hombre de 39 años, con hipertensión arterial sistémica de un año de evolución, el ultrasonido y posteriormente la tomografía abdominal mostraron tumor a expensas de la glándula suprarrenal derecha. Resultados: Desde el punto de vista histológico ambos tumores mostraron tejido adiposo maduro y elementos de la médula ósea, de la serie eritroide, mieloide, megacariocítica, linfocítica, en sus diferentes estadios de diferenciación y maduración, en uno de los casos con focos de hiperplasia corticosuprarrenal. Comentario: los mielolipomas son tumores benignos que pueden cursar asintomáticos y no siempre cursan con hipertensión arterial sistémica. El diagnóstico clínico es difícil y puede confundirse con un feocromocitoma. La determinación del ácido vandilmandélico es de gran ayuda, ya que en los mielolipomas es negativo.

Pseudoquiste suprarrenal / Adrenal pseucyst

El quiste suprarrenal (QS) es un padecimiento raro, con una frecuencia de 0.06 por ciento. La mayor parte son hallazgos incidentales (por imagenología, laparoscopia y como hallazgo de autopsia). Los quistes no neoplásicos incluyen los parasitarios, de retención, embrionarios, endoteliales y los pseudoquistes. Por lo común se presentan entre la quinta y sexta décadas de la vida; en los niños es poco frecuente, aunque hay casos reportados in útero. Nuestro caso es el de una mujer de 45 años de edad que ingresó porque padecía dolor tipo cólico en el hipocondrio derecho, acompañado de náusea y vómito. Se le realizó una ultrasonografía abdominal en la que se observaron litos vesiculares y un tumor retroperitoneal que se corroboró mediante tomografía axial computada. Se le efectuó una colecistectomía y resección de la lesión.