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INTRODUCTION: Approximately 20%-45% of familial melanoma (FM) cases are associated with genetic predisposition. OBJECTIVES: This single-center retrospective study aimed to assess the frequency of pathogenic variants (PV) in the main melanoma-predisposing genes in patients with cutaneous melanoma and investigate the clinical predictors of genetic predisposition. METHODS: Patients included were those diagnosed with cutaneous melanoma at the Dermatology Unit of the University Hospital of Verona, Italy, from 2000 to 2022, presenting at least one of the followings: multiple melanomas (≥ 3); personal/family history of pancreatic cancer (PC) (up to 2nd-degree relatives); ≥ 2 1st-degree relatives with melanoma; ≥ 1 1st-degree relatives with early-onset (<45 years) melanoma and tested for CDKN2A, CDK4, POT1, BAP1, MITF, ATM, and TERT. RESULTS: During the study period, 35 out of 1320 patients (2.7%) underwent genetic testing. Four patients (11.4%) harbored a PV in a melanoma-predisposing gene, three in CDKN2A (8.6%), and one in MITF (2.9%). Variants currently classified as being of unknown clinical significance (VUS) were detected in CDKN2A (N = 1), MITF (N = 1), and ATM (N = 2). Family history of PC and ≥5 melanomas, personal history of ≥50 nevi, and ≥4 melanomas were significantly associated with PV in tested genes (P < 0.05). CONCLUSIONS: The prevalence of PV in predisposing genes in FM was lower than previously reported in Italian registries. Possible reasons include deleterious variants in untested intermediate/low-penetrance genes or yet-to-be-discovered high-penetrance genes and environmental risk factors. A family history of PC, a high number of nevi and melanomas predict a monogenic predisposition to melanoma.
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BACKGROUND: Dermoscopic features differentiating in situ nevus-associated melanoma (NAM) versus in situ de novo melanoma (DNM) are inconclusive. OBJECTIVES: The aim of the study was to investigate the dermoscopic features associated with in situ NAM versus DNM. MATERIALS & METHODS: This was a retrospective observational study. All consecutive in situ melanomas diagnosed in adult patients were retrieved and stratified as NAM vs DNM, and clinical and dermoscopic data were compared between the two. RESULTS: A total of 183 patients with in situ melanoma were collected, of whom 98 (54%) were male with a mean age of 64±14 years. For 129 patients, standardized dermoscopic images were collected (51 for NAM and 78 for de novo MM). The most common dermoscopic features were an atypical pigment network (85%), atypical globules (63%) and regression (42%). No significant differences were found except for regression, which was detected in 54.9% NAM vs 33.3% DNM (p=0.016). Multivariate logistic regression confirmed the association between dermoscopic regression and NAM (OR=2.34, 95% CI: 1.15-4.91). CONCLUSION: Currently, the use of dermoscopy to determine whether a melanoma is associated with a nevus is unreliable, however, the presence of regression adjacent to atypical lesions may raise suspicion of in situ NAM.
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Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Adulto , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Dermoscopía , Nevo Pigmentado/diagnóstico por imagen , Nevo/diagnóstico por imagen , Melanoma/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico por imagenRESUMEN
Background: Enteric-type adenocarcinoma of the lung (lung-ETAC) is a rare form of lung cancer with histologic similarities to colorectal cancer, with aggressive behavior and unfavorable prognosis. Case Presentation: An 81-year-old man presented with discolored skin lesions on the chest and abdomen. After comprehensive evaluation, including skin biopsy and molecular profiling, the patient was diagnosed with having lung-ETAC with a BRAF p.V600E mutation. Treatment with dabrafenib and trametinib initially resulted in positive results, with improvement in skin lesions and overall clinical condition. Nevertheless, approximately 6 months after, the disease had progression with new skin lesions reappearing. Conclusions: We reported a unique case of a patient with BRAF p.V600E-mutant lung-ETAC with metastatic skin lesions achieving complete cutaneous response after targeted treatment with dabrafenib and trametinib, highlighting the potential for targeted therapy in patients with lung-ETAC harboring a BRAF p.V600E mutation.
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Patients with history of malignant melanoma (MM) are at risk of developing subsequent primary MM (SPM). Predictors of SPM may be helpful to identify patients at higher risk. The objective of the study is to investigate the phenotypic traits, indirect actinic exposure features and pathological variables associated with the risk of development of SPM. A ten-year retrospective case-control study was undertaken involving patients following MM excision who underwent regular video-dermoscopic examination at 4-6-month intervals for the first 5 years, followed by annual dermoscopic examination for the following five years. Patients with only one primary cutaneous MM were compared with those who developed at least one SPM. A total of 577 patients were included, 309 (53.6%) men and 268 (46.5%) women (mean age, 55 ± 15 years), comprising 450 patients with single melanoma and 127 with at least one SPM. The median time span to the SPM was 30 (IQR 12-53) months. Compared to the first melanoma, SPM were thinner, mean Breslow 0.56 ± 0.64 mm vs 1.37 ± 1.83 mm (p < 0.001); in situ MM prevalence 12% vs 36% (p < 0.001). 36 % of the patients with SPM developed it in the anatomical site of the previous melanoma. At multivariate analysis, having numerous naevi (i.e. 10-50 nevi) OR = 2.88 (95% CI 1.32-6.28, previous dysplastic naevi excisions OR = 2.51 (95% CI 1.53-4.12), solar lentigo OR = 2.68 (95% CI 1.67-4.31) and actinic keratosis OR = 3.09 (95% CI 1.64-4.31) were associated with an increased risk of SPM. These features may identify persons at increased risk of developing SPM.
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Melanoma , Neoplasias Cutáneas , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/epidemiología , Melanoma/patología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/patología , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Nevoid melanoma (NeM) is a rare variant of melanoma resembling melanocytic nevus. The aim of the study was to systematically review the dermoscopic features of NeM. METHODS: A hospital-based retrospective study was conducted. Dermoscopic features of NeMs diagnosed through excisional biopsy between January 2015 1, and March 1, 2021, were compared to superficial spreading melanomas (SSMs) matched by Breslow's thickness. Then, a literature search was performed. Electronic searches on PubMed database via Medline were conducted to retrieve any manuscript reporting detailed dermoscopic features of histopathologically confirmed NeM. RESULTS: A total of 60 malignant melanomas (MM) comprising 20 NeM and 40 SSM were collected. Twelve out of 20 (60%) NeM showed a nevus-like appearance, including reticular and globular patterns, and in 35% of these cases it was detected because of dermoscopic changes. Then, a total of seven original manuscripts were retrieved from the literature review, comprising 56 cases overall. NeM showed nevus-like pattern in 53% of the cases, multicomponent pattern in 21% and amelanotic in 9%. Enlargement, irregularly distributed dots/globules, irregular pigmentation, and atypical vascular pattern were found in NeM with nevus-like appearance. NeM with multicomponent pattern were characterized by irregular pigmentation, blue-white veil, irregular dots and atypical vascular pattern. Amelanotic NeM is rare and show atypical vascular pattern and milia-like cysts. CONCLUSIONS: Dermoscopy of NeM is challenging as it frequently shows a nevus-like pattern, but clues and detection of dermoscopic changes may help to identify it.
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Quiste Epidérmico , Melanoma Amelanótico , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Dermoscopía , Humanos , Melanoma , Melanoma Amelanótico/patología , Nevo/patología , Nevo Pigmentado/diagnóstico , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Melanoma Cutáneo MalignoRESUMEN
Erosive pustular dermatosis of the leg is an unusual form of sterile pustulosis that typically affects the lower limbs of elderly patients. We report the cases of two women who developed erythematous skin plaques with pustules that coalesced and evolved into erosions and crusted areas. Histology showed epidermal spongiosis with subcorneal pustules and a dermal infiltrate with eosinophils and neutrophils. Lesions were treated with topical clobetasol propionate 0.05% for 10 days followed by topical tacrolimus daily until complete resolution, and then twice weekly for 1 year, without relapse. The response to topical corticosteroids and tacrolimus further support the close relationship with erosive pustular dermatosis of the scalp. Topical therapy with tacrolimus may offer good long-term disease control.
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Inmunosupresores/administración & dosificación , Dermatosis de la Pierna/tratamiento farmacológico , Dermatosis de la Pierna/patología , Tacrolimus/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Pilomatricoma is a relatively common benign cutaneous adnexal tumor and a well-recognized entity, while its pigmented variant is far less common and less reported. Its estimated frequency ranges from 11 to 24%, according to a limited number of published case series. This article describes the case of a 42-year-old man presenting a firm subcutaneous nodule of the periareolar region. Histopathologic examination revealed a cystic lesion composed of matrical and supramatrical cells accompanied by a foreign body granulomatous cell reaction. Interestingly, a hyperpigmented area with numerous hyperplastic melanocytes and few mitoses was detectable. In order to assess the cell lineage of the mitotically active component in the hyperpigmented area, double immunohistochemistry with Ki67/Mart1 and p63/SOX10 was performed. Pigmented pilomatricoma is an underrecognized, underreported variant, and double immunohistochemistry stain is an effective tool in providing the correct interpretation of the proliferative activity in the different cellular populations.
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Erythema nodosum (EN) is a septal panniculitis which may be associated with a wide variety of factors and disorders. In some patients it is recurrent, but few studies have considered recurrent EN. Our aim was to describe the causes of and diseases associated with EN and relapsing EN. Patients diagnosed with EN from 1997 to 2007 were included. EN was defined as post-infective, based on temporal, clinical, laboratory and microbiological criteria. Diagnosis of drug-induced EN was based on a temporal correlation, on the relapse of EN after drug re-introduction and on the absence of relapsing EN with a continuous treatment with the imputed drug. When the above criteria were excluded and EN was not associated with an underlying systemic disease or pregnancy, it was considered idiopathic.124 patients (mean age 39.5 years; median 37 years; range 4-90 years) were visited and re-evaluated after one to ten years (mean ± SD follow up time 5 ± 4 years). In 73 (58.8%) patients an aetiology of the first manifestation of EN was attributed to infections (25.8% of the total number; 32% of those with an attributed aetiology), drugs (mostly sex hormones; 15.3%; 26%), systemic diseases (11.2%; 19.2%) and pregnancy (6.5%; 10.9%). EN relapsed in 33 (26.6%) patients and was mostly attributed to infections and drugs. Factors responsible for the first manifestation of EN frequently differed from those causing relapses in the same patients, with the exception of drug-induced EN. We conclude that drug-induced EN can recur after re-exposure to the same drug, and the recurrence can be predicted.
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Eritema Nudoso/etiología , Adulto , Femenino , Humanos , Modelos Logísticos , Masculino , Recurrencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND/PURPOSE: Videocapillaroscopy (VCP) can be used to explore microcirculatory modifications in skin diseases. Psoriasis presents a specifically altered capillaroscopic pattern with 'bushy' capillaries and a disarranged microangioarchitecture. The aim of the present study is to compare the clinical and capillaroscopic modifications of a psoriatic target lesion during topical therapy. METHODS: Thirty patients with chronic plaque psoriasis were included in the study. Clinical and capillaroscopic modifications in comparable lesions of the elbows were analyzed during different topical therapies (calcipotriol, betamethasone dipropionate and calcipotriol plus betamethasone dipropionate) at baseline, and after 15 and 30 days of therapy. A clinical global score (modified Psoriasis Area Severity Index), the mecapillary density per square mm and the mean diameter of capillary loops were measured. RESULTS: Topical therapy with combined betamethasone dipropionate and calcipotriol induced a higher decrease in erythema, infiltration and desquamation (P<0.001), and a significant reduction of the mean 'bush' diameter (P<0.001) and capillary number/mm(2) (P<0.05) compared with betamethasone and calcipotriol alone. Microvascular restoration to a normal pattern, as detected by VCP, was faster than clinical improvement (P<0.05). CONCLUSION: Videocapillaroscopy is an easily executable and non-invasive technique that detects early microcirculatory changes in psoriasis during topical therapy.
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Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Capilares/efectos de los fármacos , Capilares/patología , Angioscopía Microscópica/métodos , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Administración Tópica , Adulto , Anciano , Betametasona/administración & dosificación , Calcitriol/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Dermoscopía/métodos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Piel/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
Umbilical endometriosis has an estimated incidence of 0.5%-1% of all patients with endometrial ectopia. It is a very rare disease, but should be considered on the differential diagnosis of umbilical lesions. We report on a case of spontaneous umbilical endometriosis in a 38-year-old woman, with a dark brown nodule periodically bleeding, associated with severe abdominal pain. There was no history of endometriosis and she had not been pregnant before. Laparoscopic visualization of pelvic cavity showed bilateral ovarian endometrioma (it was removed while sparing the ovaries). Surgical treatment proved effective. Cutaneous endometriosis could be a sign of internal endometriosis. Presentations may be atypical and pose diagnostic difficulty, mimicking other acute diseases, e.g., skin neoplasm, folliculitis, etc., but it should be suspected in any female presenting with a painful or bleeding mass close to the umbilicus or abdominal surgical scar.
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Cicatriz/patología , Endometriosis/patología , Ombligo , Adulto , Cicatriz/cirugía , Endometriosis/cirugía , Femenino , HumanosRESUMEN
BACKGROUND: Rosacea is a common chronic dermatosis that involves the cutaneous microvasculature of the face. There are no objective measures for assessing the severity of erythematotelangiectatic rosacea. OBJECTIVE: Our purpose was to characterize and provide objective measures of vessel changes in erythematotelangiectatic rosacea by videocapillaroscopy. METHODS: We compared 30 patients with erythematotelangiectatic rosacea with 30 age- and sex-matched patients with facial seborrheic dermatitis and 30 healthy control subjects. Videocapillaroscopy was performed both on the cheeks and on the nailfold region. The analyzed parameters of the face were morphological (background color, vessel irregularities) and quantitative (polygonal net perimeter, telangiectasia, and vessel diameters). RESULTS: Characteristic alterations of skin vessels were observed in facial rosacea, with a pattern distinct from that of facial seborrheic dermatitis. In particular, rosacea showed neoangiogenesis and significantly larger polygons (13.21 +/- 3 vs 7.8 +/- 3 mm; mean +/- standard deviation, P < .001), more prominent telangiectases (267.8 +/- 108 vs 118.2 +/- 35 microm; P < .001) and larger mean vessel diameter (46.71 +/- 9 vs 24 +/- 10 microm; P < .001) compared with seborrheic dermatitis. Seborrheic dermatitis displayed more polygon irregularities and vessel tortuosity. In contrast, no differences were found in the nailfold region. LIMITATIONS: Vessel irregularities and overall erythema may be difficult to quantify. CONCLUSIONS: Videocapillaroscopy may represent a valid adjunctive method in the early diagnosis and measurement of erythematotelangiectatic rosacea.
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Eritema/patología , Angioscopía Microscópica , Microscopía por Video , Rosácea/patología , Telangiectasia/patología , Adulto , Anciano , Estudios de Casos y Controles , Dermatitis Seborreica/patología , Cara/irrigación sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Uñas/irrigación sanguínea , Neovascularización Patológica/patología , Índice de Severidad de la Enfermedad , Piel/irrigación sanguínea , Piel/patologíaRESUMEN
Many genetic alterations, including predisposing or somatic mutations, may contribute toward the development of melanoma. Although CDKN2A and CDK4 are high-penetrance genes for melanoma, MC1R is a low-penetrance gene that has been associated most consistently with the disease. Moreover, BRAF is the most frequently somatically altered oncogene and is a validated therapeutic target in melanoma. This paper reports a case of multiple primary melanoma with germline CDK4 mutation, MC1R variant, and somatic BRAF mutation in nine out of 10 melanomas, indicating that a common pathogenesis, because of a predisposing genetic background, may be shared among distinct subsequent melanomas of probable clonal origin. After 3 months of targeted therapy with BRAF inhibitor, our patient developed resistance with rapid progression of the disease leading to death. This is the first case in which early resistance to BRAF inhibitor has been reported in a patient with CDK4 germline mutation.
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Quinasa 4 Dependiente de la Ciclina/genética , Mutación de Línea Germinal , Melanoma/genética , Neoplasias Primarias Múltiples/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Adulto , Resistencia a Antineoplásicos/genética , Resultado Fatal , Predisposición Genética a la Enfermedad , Humanos , Indoles/uso terapéutico , Masculino , Melanoma/tratamiento farmacológico , Neoplasias Primarias Múltiples/tratamiento farmacológico , Mutación Puntual , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Sulfonamidas/uso terapéutico , VemurafenibRESUMEN
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis of unknown etiology with distinct clinical manifestations, frequently associated with systemic diseases. Four clinical and histological variants have been described: ulcerative, pustular, bullous, and vegetative. We report on a case of superficial granulomatous pyoderma (SGP), a vegetative form of PG, in a 40-year-old woman. Physical examination revealed an erythematous crusted plaque, measuring 2 cm in diameter, located on her left hip, which had appeared 18 months ago. Dermoscopy showed lack of pigment network, large gray-blue ovoid nests, irregular peripheral vessels, and ulceration. Laboratory examinations were normal; smears and cultures for bacteria and fungi were negative. Clinical and dermatoscopical presentation suggested basal cell carcinoma. The lesion was completely removed: histological examination showed pseudoepitheliomatous hyperplasia with intraepidermal micro-abscesses and prominent dermal inflammatory infiltrate with typical three-layered granulomas consisting of palisading suppurative granulomas surrounded by plasma cells and eosinophils (diffuse neutrophilic infiltration with dermal inflammatory infiltrates consisting of epithelioid histiocytes, lymphocytes, and multinucleated giant cells). Based on clinical and histological correlation, the diagnosis of SPG was definitively established.
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Carcinoma Basocelular/diagnóstico , Piodermia Gangrenosa/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Dermoscopía , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , HumanosRESUMEN
Pegylated interferon alpha (PEG-IFN-alpha) is a formulation of recombinant human interferon conjugated with polyethylene-glycol. This preparation has a long half-life (compared with conventional IFN), which allows for once-weekly injection. Elimination half-life of PEG-IFN-alpha 2b is 22-60 hours (average, 35-40 hours). We report the development of a local necrotizing reaction complicating subcutaneous injection of PEG-IFN in a patient with hepatitis C. This case enhances the need of careful training in drug reconstitution and self injection, with as much variation as possible of the injection site.
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Antivirales/efectos adversos , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/efectos adversos , Polietilenglicoles/efectos adversos , Piel/efectos de los fármacos , Antivirales/administración & dosificación , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Necrosis/inducido químicamente , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes , Hombro , Piel/patologíaAsunto(s)
Dermatosis de la Mano/patología , Queratodermia Palmoplantar/patología , Piel/patología , Adenocarcinoma/complicaciones , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Biopsia , Neoplasias del Colon/complicaciones , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Femenino , Dermatosis de la Mano/complicaciones , Humanos , Queratodermia Palmoplantar/complicaciones , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Persona de Mediana EdadRESUMEN
BACKGROUND: Videocapillaroscopy (VCP) can be used to explore microcirculatory modifications in skin diseases. Psoriasis shows specific capillary alterations reflecting typical histopathological changes. OBJECTIVE: To compare capillary morphology, distribution and density in psoriasis and seborrheic dermatitis of the scalp for differential diagnosis. METHODS: VCP was performed on histology-confirmed scalp lesions of 30 patients with chronic plaque psoriasis, 30 age- and sex-matched patients with seborrheic dermatitis and 30 healthy subjects. The morphology, mean density per mm(2) and mean diameter of capillary loops was measured. RESULTS: Scalp psoriasis exhibited homogeneously tortuous and dilated capillaries (bushy pattern), with a 73 +/- 17 mum (mean +/- standard deviation) diameter of capillary bushes. In contrast, scalp seborrheic dermatitis presented a multiform pattern, with mildly tortuous capillary loops and isolated dilated capillaries, but a substantial preservation of local microangioarchitecture. Mean diameter of capillary bush was significantly lower (27 +/- 4 microm; p < 0.001) and similar to that of the scalp of healthy subjects (21 +/- 5 microm). Capillary loop density was similar in patients with psoriasis (23 +/- 5/mm(2)) seborrheic dermatitis (24 +/- 2/mm(2)) and healthy scalp skin (24 +/- 3/mm(2)). CONCLUSION: VCP could be a useful noninvasive approach for differentiating between psoriasis and seborrheic dermatitis, especially when the scalp is the only affected site.
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Dermatitis Seborreica/diagnóstico , Angioscopía Microscópica/métodos , Microscopía por Video , Psoriasis/diagnóstico , Cuero Cabelludo , Piel/irrigación sanguínea , Adulto , Anciano , Capilares/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
A 74-year-old woman was referred to our department in December 1999 for a pyoderma gangrenosum (PG) arising at the edges of chronic leg ulcer. The history was positive for benign monoclonal gammopathy, ischemic hypertensive cardiopathy, polyarthrosis and venous lower leg deficiency. Monoclonal gammopathy of IgA Kappa type was diagnosed 10 years before with a continued benign nature. In 1990 a post traumatic PG of the left leg was diagnosed and a therapy with Cyclosporine A was started with healing of the lesion. In June 1999, 6 months before the hospitalization, a typical venous ulcer of the right leg appeared and was treated with bed-rest, compression bandaging and topical desloughing therapy. In the last month, after a minor surgical debridement of the wound, the lesion developed pustules evolving into a painful, necrotic ulcer with ragged, purple-red, undetermined borders (Fig. 1). A relapse of PG was suspected. Histological examination was consistent with pyoderma gangrenosum and showed massive neutrophilic infiltration, hemorrhage and necrosis of the overlying epidermis. Wound culture was negative. Other laboratory examinations only showed IgA = 8.15 g/L. Investigation of other underlying medical conditions were normal or negative. The venous leg ulcer gradually healed with antiseptic and compression-bandage therapy. After a 4-month course of topical steroid therapy with good results, the PG recurred also involving the proximal area of the leg. Methylprednisolone 50 mg/day was started. Healing began 10 days later and 2 months later the wound healed and epithelialized. Steroid was reduce to 5 mg daily for 4 months. No recurrence was seen when the drug was stopped.