Gundula Schaumburg-Lever

Human Melanoma Progression in Skin Reconstructs : Biological Significance of bFGF

Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.

Patterns of local horizontal spread of melanomas: consequences for surgery and histopathologic investigation.

Understanding local spreading patterns of melanomas is a precondition for the localized surgical treatment and histopathologic investigation. We used hematoxylin and eosin-stained paraffin sections for a two-phase, cellular and microscopic study of patterns of lateral spread in superficial spreading melanomas (SSMs), nodular melanomas (NMs), lentigo maligna melanomas (LMMs), and acral lentiginous melanomas (ALMs). Complete histologic examination of vertical excisional margins was carried out with paraffin sections 5 mm beyond the clinical tumor border of 1395 SSMs, 376 NMs, 179 LMMs, 46 ALMs, and 37 acrally located SSMs or NMs. Further sections of embedded material were analyzed when tumor-positive margins were found. In case of continuous tumor spread, reoperations were continued until the tissue was free of tumor cells. In case of noncontinuity, a final excision was made to a minimum safety margin of 10 to 20 mm. Concentrically consecutive, 5-microm thick hematoxylin and eosin-stained sections were taken from the outside of a 10-mm safety margin inward to the clinical borders of 34 SSMs, five NMs, 10 LMMs, and five ALMs. Noncontinuous subclinical spread was found in all SSMs and NMs in the form of few isolated cell nests at the epidermis-dermis junction. Ninety-two percent of these were located within 6 mm of the central tumor. All LMMs and ALMs showed a clearly demonstrable, uninterrupted spread into the periphery at the epidermis-dermis junction, too, usually in groups of outgrowths. The probability of finding these outgrowths 5 mm beyond the clinical tumor border was 54% in LMM and ALM. Complete histologic examination of vertical excisional margins (micrographic surgery) is therefore the therapy of choice only for LMM and ALM and is inefficient for SSM and NM.

Epidermolysis bullosa acquisita: Efficacy of high-dose intravenous immunoglobulins

A 16-year-old boy had a 6-year history of a generalized bullous eruption that was resistant to multiple therapies. Findings of immunofluorescent split-skin studies and electron microscopy were consistent with a diagnosis of epidermolysis bullosa acquisita. Treatment with cyclosporine and prednisolone decreased new blister formation. Additional therapy with high-dose intravenous immunoglobulins was successful in controlling the patients disease.

Malignant chondroid syringoma: immunohistopathology.

Malignant chondroid syringoma, also called malignant mixed tumor of the skin, is a rare variant of a malignant tumor derived from sweat gland cells. Histologically the tumor is composed of an epithelial and a mesenchymal component. The epithelial structures show glandular differentiation and carcinomatous features. They are embedded in a mucinous stroma with spindle mesenchymal cells and areas of chondroid differentiation. The epithelial cells express cytokeratins. The luminal epithelial cells show binding to the lectin Ulex europaeus; intraluminal cells are carcinoembryonic antigen positive. The stromal cells are cytokeratin negative and sporadically positive for vimentin. Chondroid areas are S-100 protein and vimentin positive. No labeling for actin is seen.

Granulomatous mycosis fungoides : Report of a case with some histopathologic features of granulomatous slack skin

We describe a case of granulomatous mycosis fungoides, tumor stage, mimicking sarcoidosis in an 82-year-old man with a 2-year history of skin disease. The final diagnosis was established after one of seven biopsy specimens showed a nongranulomatous histologic picture of patch-stage mycosis fungoides. Monoclonality was proven for the lymphocytic population by T-cell-receptor rearrangement studies. The unusually extensive granulomatous inflammation with huge giant cells surrounded by CD1a-positive cells in the other six biopsy specimens was suggestive of the histopathology of granulomatous slack skin, another rare granulomatous cutaneous T-cell lymphoma. Because both a clinical and histologic overlap between granulomatous mycosis fungoides and granulomatous slack skin have been reported in the literature, we conclude that they may belong to the spectrum of a single disease.

Klinik und Histologie des malignen Melanoms

Das maligne Melanom ist ein invasiver maligner Tumor, der von den Melanozyten ausgeht. Mehr als 90% der Tumoren entwickeln sich primar an der Haut, da die Melanozyten uberwiegend in der Basalzellreihe der Epidermis lokalisiert sind. Daruber hinaus verbleiben Pigmentzellen in der Dermis und den Schleimhauten, den Leptomeningen, der Uvea und Retina des Auges und der Kochlea sowie dem vestibularen Labyrinth des inneren Ohres. Entsprechend konnen an diesen Lokalisationen auch maligne Melanome entstehen. Neben den Dermatologen haben sich daher mit dem malignen Melanom ebenfalls internistische Onkologen und Chirurgen, aber auch Ophthalmologen und HNO-Arzte eingehend befast.

Primary cutaneous large-cell anaplastic (Ki-1) lymphoma in a child

During a 2-week period, a 9-year-old girl developed a tender, dark red, centrally ulcerated 3 cm tumor on her left thigh, associated with inguinal lymphadenopathy. Histologic and immunohistopathologic evaluation disclosed a Ki-1+ large-cell anaplastic lymphoma. The patient received multiagent chemotherapy followed by autologous bone marrow transplantation and is in her second remission.