Heike Audring

Porcine ear skin: an in vitro model for human skin

Background/purpose: Porcine ear skin is used in studies of percutaneous penetration as a substitute for human skin. The structure of this tissue, including hair follicles, was studied qualitatively and quantitatively in comparison with human skin.

Granulomatous mycosis fungoides and granulomatous slack skin: a multicenter study of the Cutaneous Lymphoma Histopathology Task Force Group of the European Organization For Research and Treatment of Cancer (EORTC)

BACKGROUNDnGranulomatous cutaneous T-cell lymphomas (CTCLs) are rare and represent a diagnostic challenge. Only limited data on the clinicopathological and prognostic features of granulomatous CTCLs are available. We studied 19 patients with granulomatous CTCLs to further characterize the clinicopathological, therapeutic, and prognostic features.nnnOBSERVATIONSnThe group included 15 patients with granulomatous mycosis fungoides (GMF) and 4 with granulomatous slack skin (GSS) defined according to the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. Patients with GMF and GSS displayed overlapping histologic features and differed only clinically by the development of bulky skin folds in GSS. Histologically, epidermotropism of lymphocytes was not a prominent feature and was absent in 9 of 19 cases (47%). Stable or progressive disease was observed in most patients despite various treatment modalities. Extracutaneous spread occurred in 5 of 19 patients (26%), second lymphoid neoplasms developed in 4 of 19 patients (21%), and 6 of 19 patients (32%) died of their disease. Disease-specific 5-year survival rate in GMF was 66%.nnnCONCLUSIONSnThere are clinical differences between GMF and GSS, but they show overlapping histologic findings and therefore cannot be discriminated by histologic examination alone. Development of hanging skin folds is restricted to the intertriginous body regions. Granulomatous CTCLs show a therapy-resistant, slowly progressive course. The prognosis of GMF appears worse than that of classic nongranulomatous mycosis fungoides.

Impact of sentinel lymph node biopsy in patients with Merkel cell carcinoma: results of a prospective study and review of the literature

PurposeMerkel cell carcinoma (MCC) is the most aggressive of the cutaneous malignancies, showing a propensity to spread to regional lymph nodes (LNs). The aim of this prospective study was to examine the feasibility and clinical impact of sentinel lymph node biopsy (SLNB) in this cutaneous malignancy.MethodsThe study population comprised 23 patients with stage I MCC (median age 70 years, range 50–85 years). Lymphoscintigraphic mapping with 99xa0mTc-nanocolloid was performed in all patients. Sentinel lymph nodes (SLNs) were identified, excised and analysed in serial sections by conventional histopathology and cytokeratin-20 immunohistochemistry.ResultsMetastatic disease was determined in the SLNs of 11 patients (47.8%). Elective lymph node dissection (ELND) was performed in eight of these 11 patients, four of whom had additional positive LNs. During follow-up (median 36.1 months, range 3–79 months), seven of the 23 patients (30%) relapsed: four had a local recurrence and three, in-transit metastases. Recurrence developed in two SLN-negative patients with local LN metastases and in one SLN-positive patient with distant metastases. This patient died, representing the only tumour-related death in our sample. Median survival was 49.1 and 35.5 months for SLN-negative and SLN-positive patients, respectively. This difference was not statistically significant (p=0.3452).ConclusionSLNB allows for exact nodal staging in patients with MCC. Whether additional ELND is of further benefit remains unclear.

Application of optical non‐invasive methods in skin physiology: a comparison of laser scanning microscopy and optical coherent tomography with histological analysis

Background/purpose: Optical, non‐invasive methods, such as fluorescence laser scanning microscopy (LSM) and optical coherent tomography (OCT), have become efficient tools for the characterization of the skin structure in vivo, as well as real‐time investigation of distribution and penetration of topically applied substances.

Morphometry of human terminal and vellus hair follicles

Abstract:u2002 Previous studies suggest that drug delivery systems based on particles can be used to deposit active compounds in hair follicles and to target hair follicle‐associated cell populations. The development of application protocols is complicated by the fact that there is no information available on the size and the position of key target structures in the different hair follicle types and their intra‐ and interindividual variation. Therefore, we performed morphometric measurements on histological sections of human terminal (THF) and vellus hair follicles (VHF) from the scalp and the retroauricular region. With 3864u2003±u2003605u2003μm and 580u2003±u200384u2003μm in THF compared to 646u2003±u2003140u2003μm and 225u2003±u200334u2003μm in VHF, the total length and the length of the infundibulum differed significantly as determined by paired t‐test (Pu2003<u20030.0001). The same level of significance was observed for the position and the length of the bulge region. The thickness of the epithelial lining was lowest in VHF (45u2003±u200314u2003μm at 100u2003μm from skin surface) compared to 65u2003±u200320u2003μm at 150u2003μm in THF, while the thickness of the interfollicular epidermis ranged between 64u2003±u200312u2003μm and 99u2003±u200318u2003μm in VHF‐bearing skin and 72u2003±u200316u2003μm and 136u2003±u200337u2003μm in THF‐bearing skin. In addition, the diameter of the hair follicle opening was determined at 50u2003μm intervals from the skin surface. Our data suggest that hair follicle types in defined body regions represent rather homogenous groups and that particle‐based drug delivery may be a feasible approach, also in larger numbers of individuals. We provide precise information on the size and the position of key target structures in VHF and THF.

Optical investigations to avoid the disturbing influences of furrows and wrinkles quantifying penetration of drugs and cosmetics into the skin by tape stripping

Furrows and wrinkles, as typical structures of human skin, represent a reservoir for topically applied substances. This reservoir can influence penetration experiments of topically applied substances into the stratum corneum by tape stripping. Optical methods such as laser-scanning microscopy, optical coherent tomography, and the microscopical investigation of histological sections obtained by biopsies were used to check a special protocol, which avoids these potential disturbances. The use of a transparent adhesive film with high flexibility and the realization of an intense contact to the stretched skin by pressing the tape with a roll, moved laterally on the tape, are the prerequisites to obtain correct data. The application of this experimental technique and the performance of tape stripping allow the determination of the horny layer profile and the local distribution of topically applied substance, undisturbed by the characteristic structure of the natural skin. These results demonstrate that the presented tape stripping procedure is a valuable tool to determine, quantitatively, the penetration and the bioavailability of drugs and cosmetics inside the human stratum corneum, in relation to the horny layer profile.

The Number of Stratum corneum Cell Layers Correlates with the Pseudo-Absorption of the Corneocytes

The removal of the stratum corneum (SC) using adhesive tapes is a common technique in cutaneous studies. The determination of the varying amounts of the SC removed would be a helpful tool in such investigations. In the present study, the cell layers of porcine SC were counted before and after removal of several tape strips using histological techniques. In addition, the pseudo-absorption of the corneocytes reflecting the amount of these cells was determined using spectroscopy. Different amounts of SC were removed using 20 tape strips. The spectroscopically determined data correlate linearly with the number of removed cell layers. Based on these results, the pseudo-absorption of the corneocytes can be used to calculate the absolute number of cell layers removed with a standard deviation of less than 11%. In this way, the SC can be quantified using the procedure of tape stripping in combination with the spectroscopic determination of the corneocytes.

The porcine snout – an in vitro model for human lips?

Abstract:u2002 The morphology and histology of test sites commonly used to study the penetration of lip products differ significantly from those of the human lip itself. The aim of this study was to investigate whether the porcine snout could serve as an equivalent in vitro model for human lips. The lips of human test subjects and biopsies of porcine snout tissue were compared using histological and microscopic techniques. Using a dermatological laser scanning microscope, the penetration of topically applied fluorescent sodium fluorescein was investigated in vivo on human lips and in vitro on the porcine snout. Biopsies from the in vitro experiments were studied using fluorescence microscopy. Some parts of the porcine snout show a similar morphology and histology as human lips. The stratum corneum (SC) and the epidermis of the porcine snout are thicker than those of human tissue. Both in vivo and in vitro, the topically applied fluorescent dye was detected only on the skin surface and within the uppermost SC layer. These results indicate that porcine snout can be used as an in vitro model for human lips in penetration studies. Both human and porcine tissues exhibit an efficient barrier against the penetration of topically applied substances.

Large primary meningeal melanoma in an adult patient with neurocutaneous melanosis

Neurocutaneous melanosis is often associated with melanoma of the central nervous system. Due to the inconspicuously looking cutaneous melanosis additional examinations are often not performed. We describe a patient with cutaneous melanosis who presented with neurological symptoms due to a large primary meningeal melanoma. The diagnosis of neurocutaneous melanosis was made. This case is an illustration of melanoma development in the central nervous system in a patient with cutaneous melanosis. This phenomenon should be kept in mind when observing patients with such skin lesions, even if they are of minor extent.

Diffuse melanosis cutis in disseminated malignant melanoma

Introduction Diffuse melanosis cutis is a rare complication in patients with metastatic melanoma. About 30 cases of generalized melanosis have been reported in the English literature so far [1]. Patients with melanosis cutis have a bleak prognosis with survival times of only weeks or months after the onset of melanosis [1, 2]. Despite significant efforts to elucidate the pathogenesis of this phenomenon, the exact mechanisms are a matter of debate. We describe 4 additional cases of patients with metastatic melanoma developing generalized melanosis, 3 of whom also had melanuria.