Molecular regulation of angiogenesis in the skin.
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Adult↗
Biomedical subjects
M Detmar
Publications and source records attributed to M Detmar.
[Large cell anaplastic Ki-1 positive lymphoma of the skin. 5 personal cases and review of the literature].
Primary cutaneous large cell anaplastic non-Hodgkin lymphomas positive for Ki-1-antigen are rarely described. There are 100 published cases worldwide. Typically large cell anaplastic lymphomas have an inflammatory appearance, which often leads to false diagnosis and unsuccessful treatment with antibiotics. Histological examination reveals a highly malignant non-Hodgkin lymphoma. The tumour is composed of large pleomorphic lymphoid cells composed of T-cells in 80% of the cases and of B-cells in 10%. The immunological phenotype in the remaining 10% remains unclear. Crucial for the diagnosis is the expression of CD30 antigen in > 70% of the tumour cells. This article presents 5 cases of cutaneous Ki-1-positive lymphoma seen in our Berlin department during the last 10 years. In 4 patients the diagnosis was established in clinical stage I of cutaneous lymphoma without further manifestation; 1 patient had lymph node involvement and was in stage II. Total excision of the primary tumour in stage I with adjuvant polychemotherapy in stages II-IV led to complete remission in all cases. Long-term remissions were seen in case 1 (2 years) and in case 5 (1 year), whilst 2 patients showed local relapse, and 1 patient showed generalized lymphogenic and hematogenic metastasis. After repeated surgical removal or irradiation of the tumour and adjuvant polychemotherapy, further complete remission was achieved in 2 patients (up to now lasting 1 and 4 years). another patient has been in partial remission for the last 2 years. Our observations underline the high relapse rate of large cell anaplastic lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Pre-myopathic versus amyopathic dermatomyositis. 2 personal cases and review of the literature].
The so-called amyopathic dermatomyositis is a rare variant of dermatomyositis which has attracted increasing interest during the last years. One finds the classical signs of dermatomyositis such as periorbital edema and erythema, erythematous macular and papular lesions localized at bony prominences (so-called Gottron's papules), generalized pruritus, photosensitivity, and a cutaneous histopathologic picture compatible with skin lesions of dermatomyositis. Crucial for the diagnosis is the exclusion of myositis by clinical examination, EMG and histology. Furthermore, longterm supervision of patients is advisable in order not to miss the appearance of early signs of myositis. The longest reported follow-up of amyopathic dermatomyositis patient is 4 years; however, it cannot be excluded that these cases will eventually culminate in classical dermatomyositis. In this paper we describe two cases and discuss the differential diagnosis and therapy; also, the term "Premyopathic dermatomyositis" is proposed, to indicate that the full picture is to be expected in most cases.
Adult↗
Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells.
Expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is markedly increased in the epidermis of lesional psoriatic skin and in healing skin wounds. In this study, we characterized the effects of several cytokines and growth factors on the expression and secretion of VPF/VEGF mRNA and protein by cultured human epidermal keratinocytes, as well as the effect of VPF/VEGF on the growth of cultured human dermal microvascular endothelial cells. Transforming growth factor-alpha, epidermal growth factor, and phorbol myristate acetate markedly stimulated VPF/VEGF mRNA expression by cultured keratinocytes; as in psoriatic skin, the three most common VPF/VEGF isoforms (encoding proteins of 121, 165, and 189 amino acids) were upregulated to an equal extent. Transforming growth factor (TGF)-alpha, epidermal growth factor, and phorbol myristate acetate also enhanced the secretion of VPF/VEGF by keratinocytes; in contrast, a number of other cytokines including interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor-alpha, interferon-gamma, and transforming growth factor-beta did not induce VPF/VEGF secretion. The VPF/VEGF secreted by keratinocytes was biologically active in that, like recombinant human VPF/VEGF, it potently stimulated dermal endothelial cell proliferation. Scatchard analysis revealed two high-affinity VPF/VEGF binding sites on dermal endothelial cells with dissociation constants of 51 pM and 2.9 pM. These results suggest that the avascular epidermis has the capacity to regulate dermal angiogenesis and microvascular permeability by a paracrine mechanism involving the secretion of VPF/VEGF. Similar mechanisms may be anticipated in a variety of inflammatory and neoplastic skin diseases characterized by microvascular hyperpermeability, edema, and angiogenesis.
Binding Sites↗
Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis, and erythema multiforme.
Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the increased vascular permeability and angiogenesis associated with many malignant tumors. In addition, VPF/VEGF is strongly expressed by epidermal keratinocytes in wound healing and psoriasis, disorders that are also characterized by increased microvascular permeability and angiogenesis. In this study, we investigated the expression of VPF/VEGF in three bullous diseases with subepidermal blister formation that are characterized by hyperpermeable dermal microvessels and pronounced papillary dermal edema. The expression of VPF/VEGF mRNA was strongly up-regulated in the lesional epidermis of bullous pemphigoid (n = 3), erythema multiforme (n = 3), and dermatitis herpetiformis (n = 4) as detected by in situ hybridization. Epidermal labeling was particularly intense over blisters, but strong expression was also noted in areas of the epidermis adjacent to dermal inflammatory infiltrates at a distance from blisters. Moreover, the VPF/VEGF receptors, flt-1 and KDR, were up-regulated in endothelial cells in superficial dermal microvessels. High levels of VPF/VEGF (138-238 pM) were detected in blister fluids obtained from five patients with bullous pemphigoid. Addition of blister fluid to human dermal microvascular endothelial cells exerted a dose-dependent mitogenic effect that was suppressed after depletion of VPF/VEGF by immunoadsorption. These findings strongly suggest that VPF/VEGF plays an important role in the induction of increased microvascular permeability in bullous diseases, leading to papillary edema and fibrin deposition and contributing to the bulla formation characteristic of these disorders.
Adult↗
Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.
VPF/VEGF is a multifunctional cytokine that contributes to angiogenesis by both direct and indirect mechanisms. On the one hand, VPF/VEGF stimulates the ECs lining nearby microvessels to proliferate, to migrate, and to alter their pattern of gene expression. On the other hand, VPF/VEGF renders these same microvascular ECs hyperpermeable so that they spill plasma proteins into the extravascular space, leading to the clotting of extravasated fibrinogen with deposition of a fibrin gel. Extravascular fibrin serves as a provisional matrix that favors and supports the ingrowth of new blood vessels and other mesenchymal cells that generate mature, vascularized stroma. These same principles apply in tumors, in several examples of non-neoplastic pathology, and in physiological processes that involve angiogenesis and new stroma generation. In all of these examples, microvascular hyperpermeability and the introduction of a provisional, plasma-derived matrix precede and accompany the onset of EC division and new blood vessel formation. It would seem, therefore, that tumors have "borrowed" fundamental mechanisms that developed in multicellular organisms for purposes of tissue defense, renewal, and repair. VPF/VEGF, therefore has taught us something new about angiogenesis; namely, that vascular hyperpermeability and consequent plasma protein extravasation are important, perhaps essential, elements in its generation. However, this finding raises a paradox. While VPF/VEGF induces vascular hyperpermeability, other potent angiogenic factors apparently do not, at least in subtoxic concentrations that are more than sufficient to induce angiogenesis. Nonetheless, wherever angiogenesis has been studied, the newly generated vessels have been found to be hyperpermeable. How, therefore, do angiogenic factors other than VPF/VEGF lead to the formation of new and leaky blood vessels? We do not as yet have a complete answer to this question. One possibility is that at least some angiogenic factors mediate their effect by inducing or stimulating the expression of VPF/VEGF. In fact, there is already one clear example of this. TGF-alpha is a potent angiogenic factor but does not itself increase microvascular permeability. However, TGF-alpha strikingly upregulates VPF/VEGF expression in cultured keratinocytes and is thought to be responsible, at least in part, for the overexpression of VPF/VEGF in psoriasis. Moreover, overexpression of TGF-alpha, along with that of the EGF receptor with which it interacts, is characteristic of many malignant tumors, raising the possibility that TGF-alpha acts to stimulate VPF/VEGF expression in other types of epithelial cells and in this manner induces angiogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis.
Psoriatic skin is characterized by microvascular hyperpermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular permeability factor (VPF; vascular endothelial growth factor), a selective endothelial cell mitogen that enhances microvascular permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperpermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.
Base Sequence↗
[Multicentric reticulohistiocytosis and myelodysplastic syndrome].
Multicentric reticulohistiocytosis (MRH) is a rare disorder of skin and joints, and its aetiology is unknown. We describe a male patient who had first developed osteoblastic lesions of the skeleton in 1976 at the age of 59 years. Three years later, he presented with multiple papular and nodular skin lesions, predominantly on the limbs and upper trunk, and 4 years later he developed painful arthropathy. In 1988 skin examination showed multiple brownish-red papulo-nodules, some of which, at mechanically stressed areas, were ulcerated. The patient complained of pronounced arthrotic disorders with reduced joint mobility. Examination of biopsy specimens from active skin lesions demonstrated extensive numbers of macrophages with partial confluence to giant cells with typical ground-glass cytoplasm. Electron microscopy revealed phagocytosis of collagen-like-structures. Examination of bone marrow biopsy specimens revealed diffuse infiltration by histiocytic cells. The diagnosis made was therefore MRH. The patient was treated for several years with different therapeutic regimens, including azathioprin, dapsone, prednisolon, chlorambucil and cyclophosphamide, and complete remission of skin lesions and of bone marrow infiltration was observed. However, a myelodysplastic syndrome with refractory anaemia and ring sideroblasts developed, which is generally understood to be a preleukaemic condition. Myelodysplastic syndromes commonly develop between 3 and 10 years after the start of a therapy with antineoplastic agents.
Antineoplastic Combined Chemotherapy Protocols↗
Phospholipid analogue hexadecylphosphocholine inhibits proliferation and phosphatidylcholine biosynthesis of human epidermal keratinocytes in vitro.
The alkylphospholipid hexadecylphosphocholine (HePC), member of a new class of antineoplastic drugs, has been previously shown to exert cytotoxic effects on neoplastic cell lines in vitro, and a selective antineoplastic activity has been reported after topical application of HePC in vivo, in particular on skin metastases of human mammary carcinomas. Preliminary observations suggest that HePC might also be beneficial in the treatment of non-neoplastic skin diseases characterized by epidermal hyperplasia such as psoriasis. Therefore, we investigated whether HePC might inhibit the proliferation of normal human keratinocytes, and whether its effects might be dependent upon the proliferative status of the treated cells. Moreover, its effects on phosphatidylcholine biosynthesis were studied in keratinocytes. HePC dose-dependently decreased cell numbers, thymidine incorporation, and protein synthesis when applied during the growth phase of keratinocytes grown in serum-free medium, with a minimal inhibitory dose of 10(-7) mol/l for thymidine incorporation, 3 x 10(-7) mol/l for cell numbers, and 10(-6) mol/l for 35S-methionine incorporation. No major differences were observed when keratinocytes were grown under high-Ca++ conditions. In contrast, slowly proliferating confluent keratinocyte cultures showed growth inhibition only after 10(-4) mol/l HePC. Phosphatidylcholine biosynthesis was dose-dependently inhibited by HePC with a half inhibitory concentration of 3 x 10(-6) mol/l, and with translocation of the rate-limiting enzyme. CTP:phosphocholine cytidylyltransferase, to the cytosol, where the enzyme is inactive. These data show a pronounced antiproliferative effect of HePC also on proliferating non-malignant keratinocytes, and are compatible with its possible action on hyperproliferative skin disorders.
Cell Division↗
Vellus hair follicle-derived keratinocyte culture: a new experimental model in human hair research.
Biological and biochemical mechanisms of hair growth are difficult to study in vivo; therefore the development of in vitro models is of great interest. Today, we have of our disposal reliable techniques to cultivate cell populations and entire components of terminal hair follicles; however, in vitro culture models for cells derived from vellus hair follicles have not yet been established. In this study, we present a technique for cultivating vellus hair follicle-derived keratinocytes (VHK) and we present first findings on their characterization. Primary cultures of VHK were obtained as outgrowths of cultured intact vellus hair follicles prepared by microsurgical means after incubation of full-thickness human skin with dispase. (1) VHK cultures reached confluency after 16-20 days and 3-4 subcultures were possible. (2) VHK were characterized as epithelial cells by light and electron microscopy. (3) A multi-layered stratified epithelium with 8-10 cell layers was observed by electron microscopy presenting abundant keratinosomes in individual cells in contrast to outer root sheath keratinocytes. (4) Synthesis studies of two glycoproteins characteristic for undifferentiated (gp 38) and for differentiated (gp 80) keratinocytes revealed higher synthesis levels for gp 80 and lower levels for gp 38 in VHK as compared to normal epidermal keratinocytes in vitro. These findings suggest a distinct morphologic and differentiation pattern of VHK in culture. This experimental model provides a new tool to study mechanisms of hair growth regulation in vellus hair follicles and to compare them to those of terminal hair follicles.
Cell Differentiation↗
Corticosteroids induce proliferation but do not influence TNF- or IL-1 beta-induced ICAM-1 expression of human dermal microvascular endothelial cells in vitro.
The effects of hydrocortisone, dexamethasone, betamethasone 17-valerate and clobetasol propionate at concentrations of 10(-5)-10(-12) M on the proliferation of human dermal microvascular endothelial cells (HDMEC) were studied in vitro. In addition, confluent HDMEC were treated with TNF (1000 U/ml) or IL-1 beta (1000 U/ml) alone or in combination with the corticosteroids (10(-5) M, 10(-6) M) for 24 h, and cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) was assessed by immunocytochemistry. Controls were treated either with growth medium or with the corticosteroids alone. All tested corticosteroids stimulated HDMEC growth after 4 and 6 days of treatment in a dose-dependent manner, as assessed by 3H-thymidine incorporation and the 4-methyl-umbelliferyl heptanoate (MUH) assay. The minimal effective concentration was 10(-9) M for hydrocortisone, 10(-10) M for dexamethasone and betamethasone, and 10(-12) M for clobetasol. In untreated and in corticosteroid-treated cultures, less than 5% of the cells expressed ICAM-1. TNF and IL-1 beta were strong inducers of ICAM-1 expression on 74% and 82% of the cells, respectively. None of the tested corticosteroids significantly influenced cytokine-induced ICAM-1 expression, suggesting that the anti-inflammatory effects of corticosteroids are not related to ICAM-1 modulation on HDMEC.
Adrenal Cortex Hormones↗
Culture of hair matrix and follicular keratinocytes.
In recent years, a variety of in vitro models for the cultivation of hair follicles and their constituents have been developed. Outer root sheath (ORS) keratinocytes (KC) have been mainly studied in explant cultures, planted on bovine eye lens capsules, collagen substrata, 3T3 cell feeder layers, or dermal equivalents, yielding outgrowth of a multilayered stratified epithelium with some biochemical and ultrastructural characteristics of keratinocytic differentiation. More recently, ORS KC cultures have also been initiated from single cell suspensions, and organotypic cultures have been obtained by recombination with dermal cells, inducing a higher degree of epidermal differentiation. Presumptive human hair matrix cells have been isolated from plucked anagen hair follicles and have been successfully propagated on 3T3 cell or normal human fibroblast feeder layers, giving rise to multilayered stratified KC cultures. In contrast, only preliminary data exist concerning the cultivation of bulge cells that have been suggested to represent follicular stem cells. In conclusion we dispose of several in vitro models today to cultivate ORS KC and hair matrix cells that have increased our knowledge on the regulation of the human hair cycle by soluble factors and dermal-epidermal interactions. Further comparative studies on ORS KC, bulge cells and matrix cells have to be carried out to confirm the distinct character of these hair KC subsets.
Animals↗
[Bacillary epithelioid angiomatosis in advanced HIV infection].
A patient with advanced HIV infection developed multiple angiomatous papules and nodules on the upper chest within a few days. At first sight the lesions resembled disseminated Kaposi's sarcoma; the differential diagnosis, however, included eruptive haemangiomas and pyogenic granulomas. Such distinct clinical characteristics as the collarette-like desquamation at the borders of the tumours led to the suspicion of bacillary epithelioid angiomatosis in HIV infection, which was then confirmed by histology and ultrastructural demonstration of bacillary colonies within the lesions. Under systemic antibiotic treatment, marked regression of the lesions was quickly observed within 1 week and complete regression occurred after 4 weeks. It is important to consider bacillary angiomatosis in HIV infection in the differential diagnosis of Kaposi's sarcoma, and it is a separate entity in the form of angioproliferation caused by bacteria.
AIDS-Related Opportunistic Infections↗
Cytokine regulation of proliferation and ICAM-1 expression of human dermal microvascular endothelial cells in vitro.
The effects of recombinant human interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF) on the cell proliferation and the expression of intercellular adhesion molecule-1 (ICAM-1) were assessed in cultured human dermal microvascular endothelial cells (HDMEC). IL-1 alpha and IL-1 beta stimulated the proliferation of HDMEC in a dose-dependent manner, whereas in control experiments using human umbilical vein endothelial cells (HUVEC), IL-1 alpha and IL-1 beta did not stimulate HUVEC growth. Also GM-CSF stimulated the proliferation of HDMEC, whereas IL-6 did not affect endothelial cell growth in vitro. Treatment with IL-1 alpha, IL-1 beta, and TNF markedly increased the expression of ICAM-1 on HDMEC in a time- and dose-dependent manner, in contrast to IL-6 and GM-CSF. By pre-embedding immunoelectron microscopy, membrane-bound expression of ICAM-1 was visualized with pronounced labeling in areas of microvillous cell protrusions. The TNF-induced expression of ICAM-1 on HDMEC was blocked by co-incubation with a neutralizing antibody against TNF, but not with neutralizing antibodies against IL-1 alpha, IL-1 beta, or IL-6. In addition, co-incubation of HDMEC with TNF and the retinoid compound acitretin, dexamethasone, or indomethacin did not abrogate the TNF-induced ICAM-1 expression. These results disclose IL-1 as a major, multifunctional endothelial cell-targeted cytokine and further confirm the concept that pro-inflammatory cytokines exert differential regulatory effects on dermal microvascular endothelial cell proliferation and expression of cell-adhesion molecules.
Adult↗
Growth characteristics and differentiation of basal cell carcinoma in vitro--immunohistochemical, gel electrophoretic, and ultrastructural analysis.
Cell cultures were established from 48 solid basal cell carcinomas (BCC) and from the normal epidermis of the same patients. The growth characteristics and differentiation of BCC cells in vitro were compared with normal keratinocytes (nKC) by using immunohistochemistry, two-dimensional gel electrophoresis including immunoblots, transmission electron microscopy, and soft agar suspension culture. After isolation of the tumor tissue under a stereodissection microscope, explants were cultured on feeder layers of mitomycin-treated 3T3 cells. After 3-5 d, 73% of all explants of BCC could be successfully cultured showing spindle-shaped outgrowing cells. Compared to nKC, cultured BCC cells had a lower growth rate and showed a wider intercellular polymorphism regarding size and shape. Their labeling pattern with a wide panel of monoclonal antibodies showed significant differences from that of nKC. In particular, only weak reactions for various cytokeratins, filaggrin and vimentin depending on the BCC cell type (small, middle, large) were found. Two-dimensional gel electrophoresis revealed expression of keratins 5, 6, 14, 16, and 17 in BCC cells and of K 5, 6, 13, 14, 16, 17, and 19 in nKC. These findings were confirmed by immunoblot. On the ultrastructural level, only a few desmosomes and a lower degree of keratinization markers were detected in BCC cells; finally, when cultured in soft agar BCC cells formed colonies whereas nKC did not. Our findings indicate that cultured BCC cells may preserve in vitro some in vivo characteristics and maintain a growth and differentiation pattern that differs from cultured nKC. The culture model presented here provides further insights into the cytogenetic and histogenetic characteristics of BCC.
Aged↗
Cytokine-stimulated human dermal microvascular endothelial cells produce interleukin 6--inhibition by hydrocortisone, dexamethasone, and calcitriol.
The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor-alpha (TNF), recombinant human interleukin 1-beta (IL-1 beta), and interferon-gamma (IFN-gamma) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1 beta were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-gamma had no effect. IL-1 beta stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24 h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24 h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol, acitretin, and cyclosporin A on TNF- or IL-1 beta-induced IL-6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokine-induced IL-6 production, whereas the inhibition by calcitriol was less pronounced. In contrast, acitretin and cyclosporine A had no influence on cytokine-induced HDMEC IL-6 production. These results disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involved in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production.
Acitretin↗
[Granulocyte colony stimulating factor (G-CSF) in treatment of patients with HIV-associated mucocutaneous Kaposi sarcoma. Successful use in virus and drug-induced leukopenia].
Three patients with HIV-associated Kaposi sarcoma were treated with human recombinant granulocyte colony stimulating factor (G-CSF). They had all developed leucopenia during treatment with recombinant interferon-alpha-2a, in two cases combined with vincristine. In all three patients, there was an obvious rapid stimulation after s.c. injection of 300 or 150 micrograms G-CSF per day; the white blood count reached normal values within only a few days and partial transformation to leucocytosis took place. After discontinuation of G-CSF, leucocyte counts regressed rapidly to pretreatment levels. A dose of 150 micrograms of G-CSF twice to three times per week proved to be sufficient to keep the white blood cell count in the normal range allowing the treatment necessary for Kaposi sarcoma. G-CSF therapy had no serious side effects. One of the patients developed a tumour-like infiltration in his left upper jaw, which histologically simulated Burkitt's lymphoma and which regressed spontaneously after discontinuation of the G-CSF therapy. G-CSF plays an important role in the treatment of patients with HIV-associated Kaposi sarcoma and enables combined treatment with zidovudine, interferon, and cytostatic drugs.
Adult↗
[Linear hyperpigmentation caused by bleomycin].
We report on an uncommon but characteristic cutaneous side-effect of bleomycin. A 52-year-old woman being treated for carcinoma of the cervix developed linear hyperpigmentation in wheals in the lumbosacral region, the lateral thorax and above the elbow. The skin lesions appeared during the fourth cycle of chemotherapy with bleomycin. Histologically, incontinence of melanin, focal parakeratosis and a lymphocytic infiltrate with epidermotropism were prominent. By electron microscopic examination metabolically highly active melanocytes were found, with increased number of melanosomes at all stages of maturation and deposits of extracellular melanin in the underlying dermis. The epidermal keratinocytes were unchanged.
Antineoplastic Agents↗