25-Hydroxyvitamin D and Cardiorespiratory Fitness in Prepubertal Overweight and Obese Children.

Childhood obesity has become a major global health problem. Vitamin D deficiency and poor cardiorespiratory fitness are highly prevalent in children with overweight or obesity, but little is known about their relationships. In this study, we aimed to analyze the relationship between serum 25-hydroxyvitamin D (25(OH)D) and cardiorespiratory fitness parameters in prepubertal obese and overweight children. A cross-sectional design with a sample of 57 prepubertal children, aged 9-11 years, with overweight or obesity was used. The fasting concentration of 25(OH)D was analyzed with a chemiluminescent microparticle immunoassay. Fat and lean body masses were determined by using DXA. Maximal oxygen uptake (VO2max) was measured with the maximal treadmill test. A total of 68.4% of the sample had sufficient levels of 25(OH)D. As expected, their cardiorespiratory fitness was poor compared with that of normal-weight children, but 60% of the group exceeded the median obesity-specific reference values. No differences were found between the sexes for relative VO2max or 25(OH)D levels. Moreover, no correlations were found between 25(OH)D and body composition or cardiorespiratory parameters for sex or vitamin D groups. Vitamin D status seems not to be directly related to body composition or cardiorespiratory fitness in prepubertal overweight or obese children.

Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway.

In solid tumors, cancer stem cells (CSCs) or tumor-initiating cells (TICs) are often found in hypoxic niches. Nevertheless, the influence of hypoxia on TICs is poorly understood. Using previously established, TIC-enrichedpatient-derived colorectal cancer (CRC) cultures, we show that hypoxia increases the self-renewal capacity of TICs while inducing proliferation arrest in their more differentiated counterpart cultures. Gene expression data revealed macroautophagy/autophagy as one of the major pathways induced by hypoxia in TICs. Interestingly, hypoxia-induced autophagy was found to induce phosphorylation of EZR (ezrin) at Thr567 residue, which could be reversed by knocking down ATG5, BNIP3, BNIP3L, or BECN1. Furthermore, we identified PRKCA/PKCα as a potential kinase involved in hypoxia-induced autophagy-mediated TIC self-renewal. Genetic targeting of autophagy or pharmacological inhibition of PRKC/PKC and EZR resulted in decreased tumor-initiating potential of TICs. In addition, we observed significantly reduced in vivo tumor initiation and growth after a stable knockdown of ATG5. Analysis of human CRC samples showed that p-EZR is often present in TICs located in the hypoxic and autophagic regions of the tumor. Altogether, our results establish the hypoxia-autophagy-PKC-EZR signaling axis as a novel regulatory mechanism of TIC self-renewal and CRC progression. Autophagy inhibition might thus represent a promising therapeutic strategy for cancer patients. ABBREVIATIONS: ATG: autophagy related; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CQ: chloroquine; CSC: cancer stem cells; CRC: colorectal cancer; HIF1A/HIF-1α: hypoxia inducible factor 1 subunit alpha; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PRKC/PKC: protein kinase C; SQSTM1/p62: sequestosome 1; TICs: tumor-initiating cells.

Apocrine hidrocystoma of the foreskin. A case report and review of the literature.

Apocrine hidrocystoma (AH) is an uncommon benign cystic tumor that is rarely located in the genitalia. We present the case of a 52-year-old uncircumcised man who presented an AH on his foreskin. The lesion was non-proliferative. Including the present report, only 10 cases of penile AH have been published to date. Most patients are adult (mean age 39.2 years, range 25-56 years) and only one case in one child and another case in one adolescent have been reported. The lesion involves more commonly the foreskin followed by the shaft. The average maximum diameter was 1.6 cm (range 0.3-3 cm). The majority (70%) of tumors are unilocular. The main differential diagnosis of AH includes eccrine hidrocystoma, epidermal inclusion cyst and male median raphe cyst. Complete excision of the lesion is curative.

Viability of Pathologic Cartilage Fragments as a Source for Autologous Chondrocyte Cultures.

OBJECTIVE: To study if a culture of chondrocytes can be obtained from pathologic hyaline cartilage (PHC) fragments. DESIGN: Twenty-five men and 9 women with osteochondritis dissecans (OCD) in 11 cases, arthrosis in 13 patients, and trauma in the remaining 10 cases were included. The PHC fragments and a small sample of the next healthy cartilage were extracted by arthroscopy. According to the appearance, the PHC samples were divided into fixed (3 cases), flapped (6 patients), or loose bodies (25 cases), depending on the attachment degree of the cartilage to the subchondral bone. Approximately half of each pathologic sample and the whole healthy one were digested to isolate the cells trying to establish the cell culture. RESULTS: We were able to establish a cell culture in 7 out of 34 (20.6%) PHC samples (positive samples), whereas in the remaining 27 (79.4%) no cell growth was observed (negative samples). Most of the negative samples were loose bodies (P = 0.005) taken from patients with OCD or arthrosis (P = 0.001) with an evolution time of more than 1 year (P < 0.001). The best binary logistic regression model (P < 0.001) showed that the only factor affecting the establishment of cell culture was the evolution time (P = 0.044). CONCLUSION: It is possible to culture chondrocytes from osteochondral fragments if they are traumatic, within a year of injury and not from fragments due to arthrosis or OCD.

Incidental Melanocytic Nevi in Hemorrhoidectomy Specimens.

BACKGROUND: Benign melanocytic nevi (MN) of the anal canal are exceptional and require adequate differential diagnosis. There are no data on incidence of these lesions. Only a single case report of hemorrhoid with an MN has been reported. The necessity of routine pathologic evaluation of hemorrhoidectomy specimens has been questioned. MATERIAL AND METHODS: The authors undertook a retrospective histologic study of the hemorrhoidal tissue obtained in a series of 1918 consecutive hemorrhoidectomies performed between January 2004 and November 2012. RESULTS: Incidental hemorrhoidal MN were detected in 4 (0.21%) patients. The ratio observed was 1 nevus in 480 specimens. Lesions were intradermal or purely junctional in nature. There were no mitoses or architectural disorder. An intradermal nevus showed localized pagetoid melanocytes. The mean age of the patients was 56.5 years (range 47-73 years). The mean size of nevi was 5.86 mm (range 1.89-13.86 mm). All cases were present in external hemorrhoids. CONCLUSIONS: Although uncommonly, incidental MN can be observed in hemorrhoidal tissue. They may show features of flexural nevi and pagetoid melanocytes. Routine histopathological study of hemorrhoidectomy specimens would help to detect benign or malignant melanocytic tumors of the anal canal as these neoplasms can be easily missed clinically. Furthermore, this practice would allow early diagnosis of significant associated processes.

Lichen sclerosus and granuloma annulare of the foreskin: a significant association.

Lichen sclerosus (LS) is considered to be a disease resulting of local immune dysregulation. A delayed-type hypersensitivity reaction and cell-mediated immune response are hypothesized to be the pathogenesis of granuloma annulare (GA). The case is presented of an uncircumcised 45-year-old man who developed lesions of LS and GA in his foreskin. Both processes were treated with circumcision. GA is rarely located in the foreskin. As far as we are aware, only one previous case presented this location. We describe herein for the first time LS associated with GA in the foreskin. Both processes have a common autoimmune pattern suggesting a link between them. Although we cannot exclude that comorbidity may be a coincidence, we think this combination of lesions is not just coincidental but significantly associated through immunopathological mechanisms.

Low-grade serous primary peritoneal carcinoma incidentally found in a hernia sac.

Very rarely, a primary peritoneal serous carcinoma can be observed in a hernia sac. We herein describe a low-grade serous primary peritoneal carcinoma incidentally found in a postmenopausal woman following examination of the femoral hernia repair sac. Our case is significant for its unusual presentation. The lesion initially appeared as a 0.3-cm tumor that disseminated in the peritoneum, persisted, and progressed for 75 months. The absence of ovarian disease indicated a primary peritoneal origin. Tumor cells were immunohistochemically positive for PAX8, claudin-4, and VE1, excluding the possibility of being of mesothelial origin. Recognition that a low-grade serous primary peritoneal carcinoma can be incidentally found in a hernia sac should simplify future diagnoses. Immunohistochemistry is helpful in making the correct diagnosis.

Well-differentiated papillary mesothelioma manifesting in a hernia sac.

Well-differentiated papillary mesothelioma (WDPM) is a tumor of uncertain malignant potential that usually occurs as a multifocal lesion of the female peritoneum, and is incidentally found at the time of surgery. We present here a multifocal case that had arisen from the lining of a hernia sac. To our knowledge, only four cases of this event have been previously described. A review of the five cases reported, including our case, revealed that the mean age of the patients was 56.6±8.35 years. There was predominance in men (4:1). In four cases, the lesion was incidental. Most tumors were found in inguinal hernias. Four cases presented with gross abnormalities in the hernia sac. All the five patients were alive with no evidence of WDPM after a mean follow-up of 38.6 months. Extensive sampling of this rare lesion helps to rule out an epithelial malignant mesothelioma and prevents overtreatment.

Subcutaneous infiltrative nodule at the injection site of low-molecular weight heparin simulating malignancy.

Low-molecular weight heparins (LMWHs) are the standard agents used for the prevention and treatment of thromboembolic disorders. Despite their widespread use, reports on adverse effects from LMWHs are uncommon. The present report describes a 23-year-old woman with a 3.8-cm solitary, fibrofatty, poorly demarcated nodule involving the subcutaneous tissue of the infraumbilical abdominal wall that appeared 4 years after iterative local administration of LMWH. Microscopically, the nodule showed atypical cells, with bizarre nuclei in the septa of cellular fibrous tissue dissecting the adipose lobules, in the absence of any other malignant changes. To the best of our knowledge, this kind of LMWH-related lesion has not been previously reported. The lesion may result from the combination of an idiosyncratic reaction to the LMWH with local trauma being a probable promoting factor. Alternatively, this reactive proliferation may be entirely due to the trauma represented by repeated injections. This rare process could easily be confused with liposarcoma. As the clinical history of injections is often not provided in the requisition form, pathologists should be aware of this adverse effect from LMWH to avoid misdiagnosis and excessive treatment.

Cardiac papillary fibroelastoma: retrospective clinicopathologic study of 17 tumors with resection at a single institution and literature review.

Cardiac papillary fibroelastomas (PFEs), which are mainly found in the valves, are rare benign tumors that can cause embolism. Single-center surgical experience in the treatment of this tumor is uncommon. All patients surgically treated for this neoplasm at our institution from January 1995 to October 2012 (15 patients with 17 lesions) were queried for clinical and pathologic characteristics, and the literature was reviewed. The mean age of detection was 55.8±11.48 years. Twenty percent of the patients were male. The tumor was an incidental finding in 60%. Symptoms directly related to PFEs occurred in 40% of patients. The most common clinical presentation in symptomatic cases was embolism (40%), mostly transient ischemic attack or stroke. Cardiac valves were predominantly involved (76.5%); the most commonly valve affected was the aortic valve (29.4%), followed by the mitral valve (17.6%). Concurrent valvular disease was observed in 41.7% of patients. The mean size of tumors was 11.4±7.9mm (range 2-25mm). In 86.7% of the patients, the tumor was solitary. The mitral valve was the most common origin of tumor systemic embolism. Fronds core could be the end stage of hypermature elastic fibers, which grows in apposition to young fibers. Simple surgical excision or valvular reconstruction was accomplished in most patients (58.3%). PFE is usually small, appears singly, and can cause potentially serious complications. Symptomatic and left side tumors should undergo surgical excision with valve-spare surgery when possible. Surgical removal of PFE is safe, efficacious, and definitive.

Mucin-secreting clear cell renal cell carcinoma. A rare variant of conventional renal cell carcinoma.

We report herein one case of conventional renal cell carcinoma (RCC) producing extensive extracellular mucinous secretion in a 71-year-old man. To the best of our knowledge, the presence of mucinous secretion in this tumor has not been documented. Mucin production, despite its low frequency, can be considered an additional feature of conventional RCC. Therefore, clear cell RCC should be added to the list of parenchymal renal tumors that can show significant mucin secretion; and it should be included in the inventory of morphologic variations of this tumor, which may cause diagnostic difficulties. It is of primary importance to distinguish mucin-secreting clear cell RCC from the metastasis of a mucin-secreting tumor to conventional RCC. Presence of mucin in a clear cell carcinoma does not exclude a renal origin.

Simultaneous papillary fibroelastomas of the pulmonary and aortic valves.

Cardiac papillary fibroelastomas (PFEs) are uncommon valve tumors. Multiple PFEs at the same or different locations in the heart account for less than 10% of patients with PFE. We herein describe a case of an asymptomatic PFE of both pulmonary and aortic valves which was incidentally diagnosed by echocardiography in a 60-year-old woman. Both PFEs were removed surgically without valve replacement. To our knowledge, this combination of lesions has not been previously reported. Even though PFEs are classified as benign cardiac tumors, they can present serious complications, such as embolic episodes, mechanical obstruction or valvular dysfunction. Valve-sparing shave excision of the lesions can be readily accomplished in most instances with good long-term results. All surgically removed valvular lesions should be histopathologically examined to confirm the echocardiographic diagnosis.

Bilateral xanthogranulomatous orchitis in a tetraplegic patient.

Xanthogranulomatous orchitis (XGO) is a rare chronic inflammatory process characterized by destruction of tissue that is replaced by an outstanding cellular infiltrate of lipid-laden macrophages. To date, 20 cases of this process have been reported previously. We present herein the case of a 55-year-old man who had sustained complete tetraplegia at C-6 level and neuropathic bladder for 21 years. After repeated episodes of urinary tract infection, the patient developed a bilateral XGO and a right xanthogranulomatous epididymitis (XGE) that were treated with bilateral orchiepididymectomy. To our knowledge, a bilateral XGO has not yet been reported. Repeated episodes of high-pressure urinary reflux along the vas deferens during dyssynergic voiding possibly led to retrograde extension from the urinary tract by common urinary pathogens and development of bilateral XGO and right XGE. Since tissue destruction is a feature of this process, curative treatment required antibiotic therapy followed by bilateral excision of testes and epididymes.

Hypodermal decidualized endometrioma with aberrant cytokeratin expression. A lesion mimicking malignancy.

Decidualized endometrioma is a pseudoneoplastic lesion that may appear as a solitary nodule in the hypodermis, simulate a malignant epithelioid tumor, and can represent a diagnostic challenge. A 36-year-old woman delivered a full-term baby by cesarean. At the immediate puerperium, she complained of a subcutaneous nodule measuring 2.5 cm, underneath a previous caesarean scar from the former full-term delivery 3 years earlier. Histologic features included a nodular growth pattern of large monomorphic epithelioid cells showing diffuse positivity for cytokeratin (AE1/AE3, 18), human placental lactogen, and CD10 and focal positivity for inhibin alpha. The main differential diagnoses include trophoblastic neoplasia and deciduoid mesothelioma. Good clinicopathological correlation is essential for the correct diagnosis. Immunohistochemical stains can be misleading. An important clue is the combination of large decidualized cells and lumens lined by flat or low cuboidal cells that are atrophic endometrial glands. This lesion has a benign behavior.

Mucin-producing renal oncocytoma. An undescribed variant of oncocytoma.

We report here one case of renal oncocytoma producing focal extracellular mucinous secretion in a 47-year-old woman. To the best of our knowledge, the presence of mucinous secretion in this tumor has not yet been reported. Mucin production, despite its low frequency, can be considered an additional feature of renal oncocytoma. Therefore, oncocytoma should be added to the list of parenchymal renal tumors that can show significant mucin secretion, and it should be included in the inventory of morphologic variations of oncocytoma which may cause diagnostic difficulties.

Nodular spindle cell proliferation in the wall of a varicose vein mimicking Kaposi's sarcoma.

Exuberant reparative reactions resembling sarcoma have been reported in the genitourinary tract, thyroid, breast, lymph node, oral cavity and skin, but not in a varicose vein. Presented herein is the case of a 55-year-old man who showed an incidental nodular lesion in the wall of a varicose vein on the left leg. The nodule consisted of fascicles of spindled cells with ovoid or elongated nuclei and delicate chromatin that showed diffuse reactivity for CD31, alpha-smooth muscle actin and D2-40. This histopathological appearance, when coupled with extravasated erythrocytes and interstitial hemosiderin deposits, resembled Kaposi's sarcoma or spindle cell angiosarcoma. Key features helpful for recognizing that the proliferation we describe is a form of tissue repair include an association with obvious hemorrhage; lack of well-formed curved fascicles of spindled cells; lack of intracytoplasmic hyaline globules; lack of intracellular vacuolization; cytological blandness; low mitotic count; absence of inmmunoreactivity for human herpesvirus-8 (HHV-8) latent nuclear antigen-1; and absence of HHV-8 in polymerase chain reaction (PCR) analysis.