Human decellularized dermal matrix seeded with adipose-derived stem cells enhances wound healing in a murine model: Experimental study.

OBJECTIVE: Full-thickness cutaneous wounds treated with split-thickness skin grafts often result in unaesthetic and hypertrophic scars. Dermal substitutes are currently used together with skin grafts in a single treatment to reconstruct the dermal layer of the skin, resulting in improved quality of scars. Adipose-derived stem cells (ASCs) have been described to enhance wound healing through structural and humoral mechanisms. In this study, we investigate the compatibility of xenogen-free isolated human ASCs seeded on human acellular dermal matrix (Glyaderm®) in a murine immunodeficient wound model. METHODS: Adipose tissue was obtained from abdominal liposuction, and stromal cells were isolated mechanically and cultured xenogen-free in autologous plasma-supplemented medium. Glyaderm® discs were seeded with EGFP-transduced ASCs, and implanted on 8 mm full-thickness dorsal wounds in an immunodeficient murine model, in comparison to standard Glyaderm® discs. Re-epithelialization rate, granulation thickness and vascularity were assessed by histology on days 3, 7 and 12. Statistical analysis was conducted using the Wilcoxon signed-rank test. EGFP-staining allowed for tracking of the ASCs in vivo. Hypoxic culture of the ASCs was performed to evaluate cytokine production. RESULTS: ASCs were characterized with flowcytometric analysis and differentiation assay. EGFP-tranduction resulted in 95% positive cells after sorting. Re-epithelialization in the ASC-seeded Glyaderm® side was significantly increased, resulting in complete wound healing in 12 days. Granulation thickness and vascularization were significantly increased during early wound healing. EGFP-ASCs could be retrieved by immunohistochemistry in the granulation tissue in early wound healing, and lining vascular structures in later stages. CONCLUSION: Glyaderm® is an effective carrier to deliver ASCs in full-thickness wounds. ASC-seeded Glyaderm® significantly enhances wound healing compared to standard Glyaderm®. The results of this study encourage clinical trials for treatment of full-thickness skin defects. Furthermore, xenogen-free isolation and autologous plasma-augmented culture expansion of ASCs, combined with the existing clinical experience with Glyaderm®, aid in simplifying the necessary procedures in a GMP-laboratory setting.

Laser-assisted photodynamic therapy for superficial basal cell carcinoma and Bowen's disease: a randomized intrapatient comparison between a continuous and a fractional ablative CO2 laser mode.

BACKGROUND: Laser-assisted photodynamic therapy is being explored as a method to enhance efficacy of photodynamic therapy (PDT). OBJECTIVE: To compare a continuous (CL) and a fractional (FL) ablative CO2 laser-assisted methyl aminolevulinate (MAL) PDT in the management of superficial basal cell carcinoma (sBCC) and Bowen's disease (BD). METHODS: Thirty treatment areas in fifteen patients with inoperable, histologically verified sBCC or BD received CL or FL after intrapatient randomization. Laser treatment was followed by MAL application and illumination occurred 3 h later. This treatment was repeated after 2 weeks. An equivalence analysis was performed on the primary endpoint efficacy, while secondary endpoints pain, side-effects and aesthetics were evaluated using paired samples tests. Patients were also asked for their preferred treatment. RESULTS: An excellent efficacy of 92.9% (sBCC, 100%; BD, 80%) was found in both CL + PDT and FL + PDT after 12 months. Equivalence could not be established. Little pain was perceived in most patients during PDT illumination. PDT treatment in FL + PDT was less painful, significantly during the second treatment (P = 0.026). Side-effects were mild to moderate with erythema being the most frequent immediate side-effect, followed by oedema, crusting and burning sensation. Pigmentary changes occurred in 21% (CL + PDT) to 29% (FL + PDT), and aesthetics were good to excellent in all patients. CL + PDT and FL + PDT did not significantly differ in side-effects (P = 0.219-1.000) or aesthetics (P = 0.157-1.000). CONCLUSIONS: Results in this pilot study support the promising role of laser-assisted PDT. Both treatment arms demonstrated the same efficacy as well as comparable side-effects and aesthetics. PDT illumination was significantly less painful in the FL + PDT group, suggesting a preference for FL + PDT. The authors recommend further investigation with a larger sample size, a subgroup analysis between sBCC and BD and comparison of different treatment protocols before one technique could be preferred to another.

Differentiation of a single melanocytic lesion of the esophagus: primary malignant melanoma of the esophagus or esophageal metastatic melanoma.

A single melanocytic lesion of the esophagus should be differentiated from a primary malignant melanoma of the esophagus (PMME) or an esophageal metastatic melanoma (MME). This paper reviews the current knowledge about these entities and how to differentiate between them. Melanocytosis as a precursor of PMME is discussed as well.

A Rare Presternal Soft Tissue Tumor: Ectopic Hamartomatous Thymoma (Branchial Anlage Mixed Tumor).

Ectopic hamartomatous thymoma is a rare benign tumor in adults, mostly located in the lower neck region. It was first reported in 1982 by Smith and McClure. Histopathologically these tumors are typically well marginated and composed of a mixture of spindle cells, mature adipose tissue, and epithelial cells, including both glandular and squamous elements. The histogenesis of this tumor is controversial. Recently, an origin from a remnant of the cervical sinus of His was proposed. Ectopic hamartomatous thymoma needs to be differentiated from malignant lesions such as synovial sarcomas or malignant peripheral nerve sheath tumors. These tumors can have similar clinical features and radiologic images. Recognition of this tumor is important because it follows a benign clinical course and conservative surgical excision is the treatment of choice. To our knowledge, 61 cases have previously been reported. We present the case of a 45-year-old women with an uncomplicated presternal located ectopic hamartomatous thymoma. The morphological and immunohistochemical findings are discussed and a review of literature is made.

Another case of "European hantavirus pulmonary syndrome" with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages.

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Multiple abdominal cysts in a patient with Gorlin-Goltz syndrome: a case report.

A rare case of symptomatic mesenteric cysts in a patient with Gorlin-Goltz syndrome, associated with various neoplasms, is presented. The patient, known with Gorlin-Goltz syndrome, consulted with increasingly severe abdominal pain and large abdominal cysts. At surgery, the cysts were excised and the postoperative course was uneventful. In conclusion, this case reminds clinicians to always maintain a wide differential diagnosis when dealing with patients known with Gorlin-Goltz syndrome.

Ectopic pancreatic tissue at the umbilicus in childhood: a case report and review of the literature.

Ectopic pancreatic tissue at the umbilicus is very rare. To our best knowledge, only fourteen cases of ectopic pancreatic tissue at the umbilicus are reported. In this paper we present the case of a two-year-old boy with an abrasion at the umbilicus. He had a poorly healing scar that started bleeding after recurrent injuries. Abdominal ultrasound revealed an unclear cystic structure with no communication to intra-abdominal structures. Surgical resection was performed without complications. Histology diagnosed an ectopic pancreatic tissue with reactive epidermal changes. We present a review of the literature and the clinical manifestations and treatment of the previously reported fourteen cases.

Solitary fibrous tumour of the nasal cavity: a case report and literature review.

A solitary fibrous tumour (SFT) is a rare tumour that originates from the mesenchyme and arises mainly in the pleura. In this report, we present a rare case of a 77-year-old man with a SFT in the left nasal cavity. On CT and MRI, a large mass is seen in the left nasal cavity, extending to the choana. The mass was radically resected via functional endoscopic sinus surgery (FESS). Histological examination showed a fibroblastic mesenchymal tumour with a prominent hemangiopericytic vascular branching pattern that stained diffusely positive for the immunohistochemical markers CD34, Bcl-2, and CD99, which was compatible with the histopathological diagnosis of a SFT. Imaging and histological features are discussed, along with the reports in literature, clinical management, and follow-up of this pathology.

An unusual tumour causing neonatal respiratory distress.

PROBLEM: We present the case of a term neonate referred shortly after birth because of breathing and feeding difficulties. METHODOLOGY: Fiber-endoscopic examination of the nasal cavity showed a pendulating mass in the nasopharynx. RESULTS: A complete surgical resection was performed and the baby recovered completely. Microscopic examination of the mass showed an overlying non-keratinized squamous cell lining with an atypical cell population in some fragments. Histological features were compatible with a high-grade epithelial tumour like a midline carcinoma, but a final diagnosis of a salivary gland anlage tumour was established. CONCLUSION: Flexible fiber endoscopy is the method of choice for examining the nasal passages and oropharynx in neonates with respiratory distress. Congenital salivary gland anlage tumour is a rare cause of neonatal nasal obstruction; it is benign and complete excision results in a cure. Histologically, it may mimic a malignant tumour owing to the high mitotic index.

Complete metabolic remission of an irresectable mediastinal solitary fibrous tumour with concurrent chemoradiation.

Solitary fibrous tumour is a rare mesenchymal tumour of uncertain origin that occurs most frequently in the pleura, although it has also been described in extraserosal sites. The biological behaviour of the tumour is unpredictable. The case history is described of a patient diagnosed with a large symptomatic irresectable mediastinal solitary fibrous tumour who achieved a clinical, radiological and metabolic response after concurrent chemotherapy and radiotherapy.

Intraspinal dermoid and epidermoid tumors: report of 18 cases and reappraisal of the literature.

Intraspinal dermoid and epidermoid tumors are two histopathological subtypes of cutaneous inclusion tumors of the spine. This classification is based on obsolete embryological knowledge. In fact, according to current embryology, both tumor types consist of ectodermal derivatives. Therefore, we hypothesized that dermoid and epidermoid tumors do not differ in clinical practice. To explore this hypothesis, we studied the clinical, radiological and intraoperative findings of 18 patients, and related these findings to the histopathological characteristics of the tumor. No differences were found between dermoid and epidermoid tumors regarding clinical presentation, radiological examination and outcome, while intraoperative diagnosis by the surgeon correlated with the histopathological diagnosis in only 8 of 18 cases. Therefore, the histopathological difference between intraspinal dermoid and epidermoid tumors is not important in clinical practice and should be avoided. A new nomenclature is proposed in which both tumor types are referred to as 'spinal cutaneous inclusion tumors'.

Synchronous bilateral epithelial-myoepithelial carcinoma of the parotid gland: case report and review of the literature.

Synchronous bilateral malignancy in the parotid glands is extremely rare. The English literature reveals nine case reports. The most common synchronous bilateral malignancies are acinic cell carcinoma. Epithelial-myoepithelial carcinoma is an uncommon neoplasm comprising 1% of all salivary gland tumours. In this case report, we describe, to our best of knowledge, the first case of a patient with a synchronous bilateral epithelial-myoepithelial carcinoma of the parotid gland. The clinical histopathological and immunohistochemical peculiarities are elucidated. Imaging studies like ultrasonography are mandatory for both parotid glands and upper necks in the clinical presence of a unilateral parotid gland tumour.

Linitis plastica of the rectum secondary to bladder carcinoma: a report of two cases and its MR features.

Rectal linitis plastica (RLP) is a circumferentially infiltrating intramural anaplastic carcinoma that results in a rigid constricted rectum with thickened walls. A long delay between the onset of symptoms and the diagnosis often occurs because RLP can mimic a lot of diseases and endoscopy and biopsies are often negative, owing to the fact that the mucosa is frequently unaffected in RLP. RLP secondary to bladder cancer is rarely described in the English literature. We present the first report of the MR features of secondary rectal linitis plastica from a bladder carcinoma. Two patients presented with changed bowel habits. All diagnostic tests were inconclusive. In both patients, pelvic T(2) weighted MR images revealed a double-layered thickening of the rectal wall with an inner isointense circumferential thickening of the submucosa and outer hypointense circumferential thickening of the muscular rectal wall. Based on MRI, further investigations were performed and secondary RLP was diagnosed. It is important to establish the diagnosis of RLP early because of its bad prognosis. The value of MRI in supporting the diagnosis of RLP should not be underestimated. As endoscopy plus biopsy can often be negative, we suggest that, if pelvic MRI shows a concentric double layered thickening of the rectal wall over a long segment, then the diagnosis of RLP should be considered. This should prompt further investigations either to confirm or rule out the diagnosis of RLP by performing endoscopy with deep rectal wall biopsies.

Histopathological characteristics of metastasizing squamous cell carcinoma of the skin and lips.

AIMS: The reported incidence of metastasis from squamous cell carcinoma (SCC) of the skin and lip varies between 0.5% and 16%. Clinical and histopathological criteria have been proposed to identify tumours that may have an increased risk of metastasis. The aim of this study was to define such high-risk tumours, especially since the incidence of SCC of the skin is increasing. METHODS AND RESULTS: Histopathological features of metastasized skin and lip tumours and a matched group of non-metastasizing tumours were reassessed. Characteristics studied were: tumour width, excision margins, histological subtype, Clark level, Breslow depth, tumour differentiation, inflammation, perineural and angio-invasive growth, ulceration and desmoplasia. Data were statistically analysed separately for skin and labial lesions. Desmoplasia, Clark level, Breslow depth, maximum diameter, angio-invasion, grading, perineural invasion, plasma cells and eosinophilic inflammatory response proved to be statistically significantly related to metastasis of skin tumours. Breslow depth, plasma cells and grading appeared to be statistically significantly related to metastasis of SCC of the lips. CONCLUSIONS: A typical metastatic SCC showed: a tumour width of at least 15 mm, a vertical tumour thickness (=Breslow) of at least 2 mm, less differentiation, presence of desmoplasia and an inflammatory response with eosinophils and plasma cells.

Infiltrating aggressive epitheliosis of the temporal bone: a newly described disease entity.

Two patients with a highly destructive histologic nondysplastic squamous epithelial lesion of the temporal bone are described. Both tumors were characterized by the production of copious amounts of keratin material which progressively extended in the temporal bone, surrounding bony structures, soft tissue and intracranially, with concomitant functional disorders. Only small amounts of epithelial cells were found. CT scanning revealed extensive and progressive destruction of the temporal bone, skull base in both patients, clivus and arch of atlas in one patient, besides intracranial and intracerebellar abscess formation. Despite extensive surgical therapy, the disorder was unmanageable. Histology showed a normal squamous epithelial basal cell layer with remarkable acanthosis and extensive hyperkeratosis. Material obtained at autopsy demonstrated intracerebellar extension of keratin material in one patient and in the hemicerebellectomy specimen of the other patient. To our knowledge, this disease entity has not been reported before.