Isolation of an "Early" Transit Amplifying Keratinocyte Population in Human Epidermis: A Role for the Low Affinity Neurotrophin Receptor CD271.

In the interfollicular epidermis (IFE), stem cells (KSC) generate transit amplifying (TA) cells that, after symmetric divisions, produce differentiating daughters. Here, we isolated and characterized the highly proliferative interfollicular epidermal basal cell population "early" TA (ETA) cells, based on their capacity to adhere to type IV collagen. Proliferation and colony-forming efficiency in ETA cells are lower than in KSC but higher than in "late" TA (LTA). Stemness, proliferation, and differentiation markers confirmed that ETA cells display a unique phenotype. Skin reconstructs derived from ETA cells present different features (epidermal thickness, Ki67, and Survivin expression), as compared to skin equivalents generated from either KSC or LTA cells. The low-affinity neurotrophin receptor CD271, which regulates the KSC to TA cell transition in the human epidermis through an on/off switch control mechanism, is predominantly expressed in ETA cells. Skin equivalents generated from siRNA CD271 ETA cells display a more proliferative and less differentiated phenotype, as compared to mock-derived reconstructs. Consistently, CD271 overexpression in LTA cells generates a more proliferative skin equivalent than mock LTA cells. Finally, the CD271 level declines with cellular senescence, while it induces a delay in p16INK4 expression. We conclude that ETA cells represent the first KSC progenitor with exclusive features. CD271 identifies and modulates ETA cells, thus participating in the early differentiation and regenerative capacity of the human epidermis.

Gynecomastia: an uncommon, destabilizing condition of the male adolescent. our therapeutic choice.

Gynecomastia is the benign enlargement of breast's the glandular tissue in male population. Gynecomastia can involve fatty and/or glandular tissue. At the basis of pediatric gynecomastia there is a multifactorial imbalance in the ratio of estrogen to androgens tissue levels. In more than 95% of the cases gynecomastia development is idiopathic. Secondary causes of gynecomastia in adolescents are relatively rare (less than 5%) and may arise from uncommon pathological conditions. Gynecomastia is self-limited and regresses in 1-3 years in 84%, 47% and 20% of adolescents with mild, moderate and severe gynecomastia. The correct first line of therapy is observation and reassurance in the treatment of mild cases. In order to manage adolescent gynecomastia is advised to adopt a tailored therapy. Despite gynecomastia is a common condition only few adolescents need cosmetic or antalgic treatment. Medical therapy should be considered in patient with emotional distress or psychological limitation on normal activities. Finally, if gynecomastia does not go in remission after two years surgical procedures should be performed. The aim of this article is to be an updated discussion of pubertal gynecomastia in every way and report our surgical experience with a retrospective study. In conclusion surgical treatment of this condition is a quiet rare procedure but, in according to global literature we demonstrated that it is a safe surgery with low rate of complications.

Townes-Brocks syndrome with craniosynostosis in two siblings.

This report describes a novel truncating c.709C > T p.(Gln237*) SALL1 variant in two siblings exhibiting sagittal craniosynostosis as a unique feature of Townes-Brocks syndrome (TBS, OMIM #107480). TBS is a rare autosomal dominant syndrome with variable phenotypes, including anorectal, renal, limb, and ear abnormalities, which results from heterozygous variants in the SALL1 gene, predominantly located in the 802 bp "hot spot region" within exon 2. Recent studies have suggested that aberrations in primary cilia and sonic hedgehog signalling contribute to the TBS phenotypes. The presence of the novel c.709C > T p.(Gln237*) SALL1 variant was confirmed in both the siblings and their father, whereas no mutations currently associated with craniosynostosis were detected. We hypothesise that the truncating c.709C > T p.(Gln237*) SALL1 variant, which occurs outside the "hot spot region" and inside the glutamine-rich domain coding region, could interfere with ciliary signalling and mechanotransduction, contributing to premature fusion of calvarial sutures. This report broadens the genetic and phenotypic spectrum of TBS and provides the first clinical evidence of craniosynostosis as a novel feature of the syndrome.

Once-daily intrapleural urokinase treatment of complicated parapneumonic effusion in pediatric patients.

In this paper, we describe our experience in the treatment of childhood empyema using urokinase. Patients' ages ranged from 2 to 12 years. Urokinase (dosage: 3,100 IU/kg/day) was diluted in normal saline to produce 1000 IU/ml (maximum dosage 100,000 IU in 100 ml of normal saline). After 2 hours, the clamped catheters were released and connected to water-seal suction at a negative pressure of 10 cm H2O. Pleural irrigations were continued once a day until thoracostomy tube output decreased to less than 10 ml/day (urokinase treatment mean duration: 11.5 days). The complete resolution of the chest effusion was assessed on chest ultrasound scan and radiographs. None of the patients experienced any side effects due to urokinase. It would now seem reasonable to advocate small chest tube thoracostomy and intrapleural urokinase as first-line treatment of pleural empyema in children, with surgery indicated as a secondary intervention.

An unusual case of familial adenomatous polyposis with very early symptom occurrence.

We report the clinical case of a patient who showed an "accelerated" form of polyposis, with development of major lesions within the first decade of life. The patient belongs to a familial adenomatous polyposis family-already described in 2001-featured by profuse polyposis at an early age of onset and desmoid tumors in the majority of affected individuals (of both sexes). The family was characterized by an uncommon mutation of the APC gene (c.4391_4700del310insCACCTACTGCTGAAA, previously defined as c.4394ins15del310) consisting in a large deletion of 310 bp at codon 1,464 with duplication of the breakpoint leading to a stop codon at position 1,575. The proband was affected by desmoids tumors at the age of 3 years. In the same year (2004) numerous polyps in the large bowel and a hepatoblastoma developed. After several months new desmoids appeared in the surgical scar. In 2010, at age 9, the patient was operated of total colectomy and endorectal pull-through of the small intestine owing to profuse colorectal adenomatosis. New desmoids developed in 2011 and 2012, and required chemotherapy. Further analysis of the APC gene in the proband revealed several polymorphisms. One of these (c.398A>G) had not been previously reported, nor was present in two other affected members of the family. The clinical case, and the practical implications for therapy, are discussed according to the most recent theories of colorectal cancer development. Long-term treatment with Cox-2 inhibitors might represent a good option for this patient.

A case of frozen pelvis: primary actinomycosis of urinary bladder in a young boy.

We report a case of urinary bladder actinomycosis in childhood. In children abdominal actinomycosis is rare and unlikely involves the urinary tract, so it is often misdiagnosed. An 7-year-old boy was referred to a secondary level hospital because of abdominal pain and dysuria. Physical examination revealed a left hypochondrial mass. Hypothesizing a pelvic rhabdomyosarcoma, a biopsy with mini-laparotomy access was performed. The first histopathological analysis did not show any malignant cells, and a 14-day antibiotic course was ineffective. Reoperation and biopsy was needed, and the histopathological examination made the diagnosis possible.

Bilateral xanthogranulomatous funiculitis and orchiepididymitis in a 13-year-old adolescent boy.

Xanthogranulomatous orchitis is an extremely rare inflammatory nonneoplastic lesion of the testis. We report a case of a 13-year-old adolescent boy who presented a painless left hemiscrotal swelling. The subsequent ultrasonography and magnetic resonance imaging revealed the presence of abnormal expanding tissue located in both testes and spermatic cord, reaching the internal inguinal ring. Testicular tumor markers were normal. The frozen section examination of the surgical specimen showed only inflammatory tissue and not neoplastic tissue. No orchiectomy was performed. Definitive histopathologic diagnosis was xanthogranulomatous inflammation. To our knowledge, this is the youngest case of xanthogranulomatous orchiepididymitis and funiculitis found in medical literature.