Hormonal receptors in cutaneous vascular malformations: 51 cases.

Vascular malformations (VMs) are rare congenital anomalies that develop during embryogenesis in different types of vessels. Several triggering factors of cutaneous VMs include trauma, infections, or hormonal changes. We investigated the expression of hormonal receptors (androgen, estrogen, progesterone) in tissue samples of well-characterized VMs. A secondary objective was to identify self-reported triggering factors for these VMs, including hormonal changes, in the cohort of patients. We included patients with VM samples obtained in the tertiary center for vascular anomalies of the University Hospital Center of Tours, France, from January 1, 2007, to August 1, 2018. Immunohistochemistry was used to detect the expression of hormonal receptors (estrogen, progesterone, androgens). We obtained 51 samples from 51 patients: 13 cystic lymphatic malformations (CLMs), 16 venous malformations (VeMs), 11 arteriovenous malformations (AVMs), 4 combined VMs, 4 PIK3CA-related overgrowth spectrum, 1 Parkes-Weber syndrome, 1 Gorham syndrome, and 1 multiple lymphangioendotheliomatosis with thrombopenia. In total, 38 (74.5%) samples were positive for androgen receptor: 11 (84.6%) CLMs, 12 (75.0%) VeMs, 8 (72.2%) AVMs, and 7/11 (63.5%) other samples. All samples were negative for estrogen and progesterone receptors. Triggering factors were self-reported in 7 cases and were most frequently hormonal changes (n = 6, 18.2%). Hormonal triggers were frequent in AVMs (n = 4). Among patients with identified hormonal triggers, VM samples were positive for androgen receptor in 3 and negative in 3. Three-quarters of our VM samples expressed androgen receptor, and most CLM, VeM, and AVM samples were positive. Hormonal triggers were identified in 6/33 patients, mostly with AVMs.

Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell polyomavirus (MCPyV) is the main aetiological agent of Merkel cell carcinoma (MCC). Serum antibodies against the major MCPyV capsid protein (VP1) are detected in the general population, whereas antibodies against MCPyV oncoproteins (T antigens) have been reported specifically in patients with MCC. OBJECTIVES: The primary aim was to assess whether detection of serum antibodies against MCPyV proteins at baseline was associated with disease outcome in patients with MCC. The secondary aim was to establish whether evolution of these antibodies during follow-up was associated with the course of the disease. METHODS: Serum T-antigen and VP1 antibodies were assessed by enzyme-linked immunosorbent assay using recombinant proteins in a cohort of 143 patients with MCC, including 84 patients with serum samples available at baseline. RESULTS: Low titres of VP1 antibodies at baseline (< 10 000) were significantly and independently associated with increased risk of recurrence [hazard ratio (HR) 2·71, 95% confidence interval (CI) 1·13-6·53, P = 0·026] and death (HR 3·74, 95% CI 1·53-9·18, P = 0·004), whereas T-antigen antibodies were not found to be associated with outcome. VP1 antibodies did not differ between patients in remission and those with recurrence or progression during follow-up. However, T-antigen antibodies were more frequently detected in patients with recurrence or progression at 12 months (P = 0·020) and 24 months (P = 0·016) after diagnosis. CONCLUSIONS: VP1 antibodies constitute a prognostic marker at baseline, whereas T-antigen antibodies constitute a marker of disease recurrence or progression if detected > 12 months after diagnosis.

[Frequency of lymphoscintigraphic anomalies in the contralateral limb and progression of unilateral primary lymphedema in children]. / Fréquence des anomalies lymphoscintigraphiques infracliniques controlatérales et évolution des lymphœdèmes primaires unilatéraux de l'enfant.

BACKGROUND: Primary lymphoedema (LE) is the consequence of lymphatic insufficiency, usually associated with hypoplasia of the lymph vessels and/or nodes. Lymphoscintigraphy allows early diagnosis. OBJECTIVES: To assess the frequency of contralateral LE by lymphoscintigraphy in children with unilateral primary LE of one limb; to assess facets of clinical bilateralization of LE. METHODS: This retrospective single-centre study included children with unilateral LE followed up at the Tours university hospital centre between 2004 and 2014. Parents were contacted by phone to obtain follow-up data. RESULTS: Of the 13 children included, 6 (46%) displayed bilateral lymphatic anomalies on lymphoscintigraphy. Within a median follow-up period of 6 years, clinical bilateralization was observed in one girl after progression of her LE for 7 years; in her case, bilateral lymphatic insufficiency was detected at the initial lymphoscintigraphy. CONCLUSION: While contralateral subclinical lymphatic insufficiency is frequent in children with unilateral primary LE of the limbs, clinical bilateralization appears only rarely.

Serial lymphoscintigraphic findings in a patient with Gorham's disease with lymphedema.

Gorham's disease is a rare disorder characterized by vascular, "lymphangio- matous" and/or "hemangiomatous" lesions in bone and surrounding soft tissues. Associated lymphedema has not been reported and clinical evolution is unpredictable. Plain radiographs, CT, MRI, and occasionally bone scintigraphy, are used to detect the bone and soft tissues changes. Biopsy is a major component of the diagnostic process. We report the findings of serial lymphoscintigraphy in a young boy with a polyostotic Gorham's disease associated with lymphangioma of the thigh and lower limb lymphedema. In this patient, lymphoscintigraphy was useful for diagnosis and follow-up of primary lymphedema. It provided valuable information concerning the occurrence, location, and progression of lymphatic lesions in both bone and soft tissues.

Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients.

BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.

[Thigh root reconstruction with a pedicled DIEP flap]. / Reconstruction d'une perte de substance de racine de cuisse sur membre lymphœdèmateux par un lambeau DIEP pédiculé

Root thigh extensive loss of substance requires surgical coverage. The presence of chronic lymphedema (LC) makes random with the postoperative healing time longer. We report an original case of reconstruction of extensive loss of substance from the root of the thigh using a pedicled deep inferior epigastric flap perforator (DIEP) flap. A 22-year-old woman with angiosarcoma occurring in hemi-body lymphedema. The defect generated by the oncologic resection was 16×24cm. She was reconstructed by a pedicled DIEP flap. Skin wound healing was obtained within 30 days. Donor site healing was obtained within 15 days. The pedicled DIEP flap seems to be effective for root thigh reconstruction.

Contributions of SPECT/CT imaging to the lymphoscintigraphic investigations of the lower limb lymphedema.

Lymphoscintigraphy is a safe and reliable technique for investigating lymphedema. However, interpretation of delayed planar conventional imaging may be questionable due to the superimposition of soft tissues. Therefore, the aim of this retrospective study was to evaluate the contribution of single photon emission computed tomography/computed tomography (SPECT/CT) to lymphoscintigraphic investigation in a selected population with abnormal interstitial activity. Forty one patients with lower limb lymphedema either primary (n=17) or secondary (n=5), or associated with chronic venous insufficiency (n=19) underwent lymphoscintigraphy according to a standard protocol. SPECT/CT imaging that started immediately after planar imaging covered the part of the lower limbs with the most significant interstitial activity. The CT images were also analyzed separately to identify the typical honeycomb pattern of lymphedema. SPECT/CT identified additional abnormalities in vessels and soft tissues in 19 patients (46%). The additional information, primarily related to dermal collateralization of flow, dermal backflow, lymphangioma, and lymphorrhea, aided in understanding the physiopathology of edema and may have influenced management in 35 patients (85%). The honeycomb appearance of the soft tissues was noted on CT in most patients (90%). This study suggests that SPECT/CT is a promising addition to planar imaging in lymphoscintigraphic investigations of lymphedema.

Visceral and mucosal involvement in neonatal haemangiomatosis.

BACKGROUND: Two types of neonatal haemangiomatosis (NH) are distinguished: diffuse which is associated with a high rate of mortality linked to mucosal/visceral involvement, and benign. OBJECTIVES: First, this study aimed to examine the frequency of mucosal and visceral (especially hepatic) involvement in NH, according to skin extension, and second, it aimed to examine clinical, pathological (with glucose transporter 1 (GLUT-1) immunostaining), and imaging features of NH, including follow-up data. METHODS: This was a descriptive retrospective study carried out in the University Hospital Center of Tours, France. RESULTS: The study included 19 patients with cutaneous NH (number of skin haemangiomas ranging from 5 to >100). Mucosal involvement was observed in 32% of all cases (100% and 19% in diffuse and other cutaneous cases respectively) and hepatic involvement in 42% (67% and 38% respectively). The number of hepatic haemangiomas ranged from 1 to >10. Half of the hepatic haemangiomas cases exhibited increased hepatic arterial blood flow. CONCLUSIONS: Mucosal and hepatic involvement was frequent in cases with a high number of cutaneous haemangiomas (>100), but only frequency of mucosal involvement was statistically significant (P = 0.021).

[Original treatment of constitutional painful callosities by surgical excision, collagen/elastin matrix (MatriDerm(®)) and split thickness skin graft secured by negative wound therapy]. / Traitement original des callosités plantaires douloureuses constitutionnelles par exérèse, matrice de collagène et d'élastine (MatriDerm(®)) et greffe de peau mince en un temps, associée à une thérapie par pression négative.

Constitutional painful callosities is an unusual pathology, integrated in the frame of "palmoplantar keratodermia" (PPK). Lesions are located at areas of support of the sole. These lesions are painful and disable the normal walking. Treatments are suspensive and painkillers. We report our experience of a single surgical treatment: surgical excision, split thickness skin graft applied on a dermal substitute and secured by negative wound therapy. A 28-year-old patient, affected by this disease, has a desire of pregnancy but her treatment is highly teratogen. A year post-op, wounds were healed. The walk was possible with a relief of the pain, without any ulcerations. The surgical treatment by excision and graft or flaps was previously reported for PPK. The use of dermal substitute was never described for this indication. Dermal substitute compensate the thickness of the soft tissue defect and give an accurate quality of elasticity in this localisation .The negative wound therapy enhances the quality and shortens the length of graft taking, and the adhesion of the dermal substitute on his bed.

[Efficacy and risks of topical 5-fluorouracil in Darier's disease]. / Traitement de la maladie de Darier par 5-fluorouracile topique: quelle efficacité, quels risques?

BACKGROUND: Darier's disease, an autosomal dominant disorder, is often resistant to therapy. There have been few encouraging reports in recent years of treatment using topical 5-fluorouracil (5FU) in this indication. We describe three cases of Darier's disease treated with Efudix: though it initially proved very effective, after several months this treatment became inefficacious. PATIENTS AND METHODS: Case 1: a 16-year-old girl with Darier's disease refractory to conventional treatments. Treatment with topical 5FU was initiated. After 3 weeks, her cutaneous lesions had practically disappeared, leaving only pigmented scars. At 6 months, worsening of the disease was controlled by increasing 5FU. At 11 months, the disease worsened and 5FU, which proved inefficient, was stopped. Case 2: a 59-year-old woman presenting treatment-resistant Darier's disease was given 5FU. After 1 week, improvement began and was evident at 4 months. However, after 13 months of treatment, the disease progressed, and increased 5FU proved completely ineffective. Case 3: a 29-year-old woman was hospitalized for inflammatory Darier's disease. Topical 5FU was applied to the left half of the body and a short course of oral corticosteroids was prescribed. After 10 days of treatment, there was a clear improvement. After 6 weeks, the patient showed episodes of healthy skin. However after 3 months, the patient stopped taking her treatment due to inefficacy. DISCUSSION: While topical 5FU seems to be effective initially in treating Darier's disease, this efficacy subsides over time. Although no adverse effects were noted in our patients, use of 5FU can result in serious adverse reactions. Because of the loss of efficacy of this treatment following initial success, coupled with its poorly evaluated safety, caution must be exercised when prescribing it, particularly in patients with dihydropyriminidine dehydrogenase (DPD) deficiency or for use on damaged skin.

Successful treatment of ulcerated haemangioma with propranolol.

BACKGROUND: Ulceration is a frequent complication of proliferating haemangioma. METHODS: Four patients with ulcerated hemangioma aged 2, 4, 5 months and 5 weeks were treated with 2 mg/kg KG propranolol. RESULTS: Efficacy and safety of propranolol were excellent in all four cases. CONCLUSIONS: Propranolol may be the first-choice therapy for ulcerated haemangioma.