[Nagashima-type palmoplantar keratoderma: A little-known palmoplantar keratoderma in Europe]. / Kératodermie palmo-plantaire de Nagashima : une kératodermie palmo-plantaire méconnue en Europe.

BACKGROUND: Herein we present a case of palmoplantar keratoderma (PPK) in a young adopted girl of Chinese origin living in France. OBSERVATION: The patient, aged six years, had presented transgressive PPK since birth, as well as erythema progressing in congestive inflammatory episodes, palmoplantar hyperhidrosis and progressive characteristics (moderate hyperkeratosis in areas of rubbing other than the palms and soles, namely the elbows and knees). Histopathological examination of a skin biopsy revealed a thick epidermis with lengthening and thickening of crests. The epithelium displayed a thick granular layer. Electron microscopy showed hyperorthokeratosis with hypergranulosis and loss of lamellar structure of the keratinosomes, as well as cleavage between corneocytes. Molecular studies showed the presence of two composite heterozygous mutations of the SERPINB7 gene, enabling a diagnosis of Nagashima-type PPK (NPPK) to be made. DISCUSSION: NPPK is an autosomal recessive disease caused by a mutation in the SERPINB7, a member of the superfamily of serine protease inhibitors. It was described by Nagashima in 1977 with molecular characterisation by Kubo following in 2013. It is the most widespread form of PPK in Asia (with a prevalence of 1.2/10,000 in Japan and 3.1/10,000 in China). It is distinguished from the other PPKs in terms of transgressive soft hyperkeratosis, inflammatory episodes and hyperhidrosis, as well as by its non-progressive nature. In the present case, while the clinical presentation was characteristic, diagnosis was only made thanks to sequencing of a panel of over 50 genes responsible for PPK. The disease is effectively little-known in Europe. This study highlights the increasing importance of diagnostic investigation methods involving the use of gene panels.

[Cutaneous and systemic T-cell lymphoma treated with haploidentical bone marrow transplantation]. / Lymphome T cutané et systémique traité avec succès par greffe haplo-identique.

BACKGROUND: Herein, we report a case of systemic cutaneous T-cell lymphoma refractory to standard therapy, the course of which resulted in haplo-identical bone marrow grafting. PATIENTS AND METHODS: A 53-year-old woman consulted for facial erythema with infiltration, keratotic lesions on the trunk, and adenopathies measuring around 1cm on the axilla and inguinal folds. A diagnosis was made of Sézary syndrome (SS), a leukaemic form of epidermotropic cutaneous T-cell lymphoma. After three years of treatment with methotrexate, the patient developed transformed SS with visceral involvement. Given the high risk of relapse and the absence of an HLA-compatible donor, haploidentical bone marrow grafting was performed. The patient was still in complete remission two and a half years later. The disease course was nevertheless marked by the emergence one year after grafting of a Blaschko-distributed lichenoid eruption having histological features consistent with chronic graft-versus-host disease (GVHD); treatment with topical betamethasone proved efficacious. DISCUSSION: To our knowledge, this is the first reported case of haploidentical grafting for systemic and transformed cutaneous T-cell lymphoma. This approach could henceforth represent a therapeutic option for patients requiring an allograft in the absence of compatible donors. The Blaschko-distributed lichenoid lesions attributed to chronic GVHD could be the result of reduced immune tolerance to abnormal embryological clones leading to a T-lymphocyte-mediated inflammatory reaction.

[Immunohistochemistry using clone VE1 is an economic, specific and sensitive method for detecting the presence of BRAFV600E mutations in melanoma]. / L'immunohistochimie (clone VE1) est une méthode économique, spécifique et sensible pour détecter la présence d'une mutation BRAFV600E dans le mélanome.

BACKGROUND: Determination of BRAF mutation status is mandatory in the management of patients with inoperable stage IIIC or stage IV melanoma. Currently, molecular biology (MB) has been validated for detecting the presence of BRAF mutations. OBJECTIVE: To compare the sensitivity, specificity and cost of immunohistochemistry (IHC) (clone VE1) versus BM methods (qPCR and Sanger sequencing). PATIENTS AND METHODS: All the samples for which BRAF mutation status was requested between March 2013 and February 2015 at the cellular and molecular analysis laboratory of the Angers Hospital were included retrospectively and consecutively. The IHC (clone VE1) and BM analyses were performed with the same formalin-fixed paraffin embedded tumour samples. The cost of these two methods was determined on the basis of the cost for the French Health Insurance. RESULTS: Two hundred and seven samples were subjected to a determination of BRAF mutational status in IHC and BM. Only one sample was discordant between these two methods (positive in IHC, negative in BM). The sensitivity and specificity of the IHC was 100% and 99.25% respectively. The ratio of the cost of IHC/BM testing was 1:2.1. CONCLUSION: IHC (clone VE1) is a specific, sensitive and economic method for determining BRAFV600E mutation status. Nevertheless, this method must be validated in order to be integrated into a decisional algorithm, alongside BM methods, to determine whether targeted BRAF-inhibitor therapy is indicated.

High-frequency (20-50 MHz) ultrasonography of pseudoxanthoma elasticum skin lesions.

BACKGROUND: In most patients pseudoxanthoma elasticum (PXE) manifests with yellowish cutaneous papules and dermal elastorrhexis on skin biopsy. In a small number of cases there are no skin manifestations on clinical examination, and establishing a diagnosis of PXE in such patients is challenging. High-frequency ultrasonography (HFUS) may be of use in predicting skin areas that would yield a biopsy specimen positive for elastorrhexis. OBJECTIVES: To describe characteristics of clinically visible PXE skin using HFUS, and to evaluate its relevance for diagnosis. METHODS: HFUS was performed in a cohort of patients with PXE and in controls at a referral centre. HFUS images of PXE skin were compared with those of other conditions. Five operators blind-scored multiple HFUS images of photoprotected or photoexposed skin from patients with PXE and controls. The diagnostic indices (sensitivity, specificity, likelihood ratios, interobserver agreement) were calculated. RESULTS: The HFUS changes considered as diagnostic for PXE were primarily oval homogeneous hypoechogenic areas in the mid-dermis. The size of these areas closely matched the extent of the histological changes. The sensitivity and specificity of the diagnostic items and interobserver agreement were high, particularly in photoprotected skin. Dermal hypoechogenicity in PXE could be related to high hydration of connective tissue due to the presence of glycosaminoglycans despite elastic fibre mineralization. CONCLUSIONS: HFUS provides suggestive images of PXE skin lesions. HFUS should now be studied to determine whether it is a potentially valuable technique for the noninvasive identification of elastorrhexis in patients with PXE in whom skin involvement is clinically minimal or absent.

[Atypical eruptive collagenoma: two cases]. / Collagénomes éruptifs atypiques: deux cas.

BACKGROUND: Eruptive collagenoma is a rare cutaneous lesion seen in young adults. It consists of asymptomatic, flesh-coloured papules that are usually localised on the trunk and the root of the upper limbs. Herein we report two cases on account of the atypical topography of the lesions and the advanced age of the patients. CASE REPORTS: Case n 1: a 69-year-old man consulted for firm, whitish papules on the wrists, elbows, popliteal fossae and groin without associated signs, and which first appeared several years earlier. The standard laboratory assessment and ocular fundus test were normal. Case no 2: a 69-year-old woman had very firm, flesh-coloured papules on the trunk and the root of the limbs, which appeared after the age of 40. The results of ocular fundus, cardiovascular investigation and laboratory examinations were normal. The histology of papules was similar in both cases and revealed a nodular zone in the reticular dermis, comprising disorganized collagen bundles and excessive quantities of elastic fibres, without elastorrhexis. This histology was consistent with collagenoma. DISCUSSION: We report two singular cases that were atypical in terms of patient age and localisation in the flexion folds. Histological analysis of a papule enables a diagnosis of collagenoma to be made. Such analysis usually reveals a hamartoma in which the amount of collagen is increased, with variable quantities of elastic tissue, though often decreased. The principal differential diagnoses are elastoma and pseudoxanthoma elasticum.

Nemaline bodies as unique pathological feature in the course of treated dermatomyositis.

Dermatomyositis was diagnosed on clinical and muscle histological criteria in a 42-year-old woman. Despite treatment, the patient complained of deterioration of her muscle condition. Since her symptoms were discordant with the rest of the data, muscle biopsy was performed and disclosed rod-bearing non-atrophic fibers as the unique and predominant pathological feature. Their significance is examined in this paper.

An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease affecting tissues rich in elastic fibers such as the skin, retina, and cardiovascular system. Mutations in the ABCC6 gene are known to be causative in most patients. Generalized arterial calcification of infancy (GACI) is characterized by extensive hydroxyapatite deposits in the internal elastic laminae in large and medium-sized arteries, leading to arterial stenoses and early and severe myocardial ischemia. GACI has been found to be primarily caused by mutations in the ENPP1 gene. We report two brothers born to unrelated parents. The elder developed uncomplicated PXE in adolescence and harbored mutations in the ABCC6 gene. The younger child died of a condition strikingly reminiscent of GACI at 15 months of age. This case of GACI was independent of mutations in the ENPP1 gene but was probably related to ABCC6 mutations. We demonstrate that matrix Gla protein and fetuin-A, involved in PXE, are also expressed in this case of GACI. These proteins could act as local and systemic inhibitors to limit the extension of mineralization. This report emphasizes concurrently that ABCC6 may be a relevant candidate gene in some cases of GACI with no mutations in the ENPP1 gene, and that GACI may be an atypical and severe end of the vascular phenotype spectrum of PXE.

[Endoscopic removal of a mandibular ameloblastic fibro-odontoma]. / Chirurgie endoscopique d'un fibro-odontome améloblastique mandibulaire.

INTRODUCTION: Ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs predominantly in children and young adults. This article reports a case of ameloblastic fibro-odontoma affecting a young boy who was treated by endoscopy. CASE REPORT: An 11-month-old child was admitted for a right mandibular rapidly growing mass. Computed tomography confirmed the presence of a large radiopaque mass on the right mandible containing compartmented tooth-germs. A biopsy exeresis was performed to completely remove the tumor with an endonasal endoscope. The histological diagnosis was an ameloblastic fibro-odontoma. DISCUSSION: We performed the enucleation with a nasal endoscope to make sure that the entire lesion had been removed. Bone resection was minimal which should decrease the risk of growth disorders. The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor usually asymptomatic and slow growing. Histopathology proves the diagnosis. The treatment is curettage, preserving the adjacent teeth.

[Bortezomib-induced acute neutrophilic dermatosis]. / Dermatose neutrophilique aiguë induite par le bortezomib.

INTRODUCTION: Bortezomid is a potent proteasome inhibitor used in patients with relapsing or refractory multiple myeloma and provides a 35% response with a median duration of response of 12 months. Numerous adverse effects are known, mainly comprising haematological and neurological complications. A wide variety of cutaneous complications have also been described in 10 to 20% of patients. CASE REPORT: We report a case of bortezomib-induced Sweet syndrome. The diagnostic criteria required for drug-induced Sweet syndrome were present. DISCUSSION: The importance of this description is that this induced Sweet syndrome may not necessarily require cessation of bortezomid since administration of corticosteroids prevents its recurrence.

[Two cases of papular elastorrhexis]. / Elastorrhexie papuleuse : deux cas.

BACKGROUND: Papular elastorrhexis is a rare dermatosis characterized by asymptomatic papules on the trunk and the upper extremities. Histological examination shows loss and fragmentation of elastic fibres as well as thickening of collagen bundles. PATIENTS AND METHODS: Case 1: a 46-year-old man was examined with asymptomatic papular lesions for 20 years. Firm and clearly delineated papules ranging from few millimetres to 2cm in diameter became wrinkled at their surface. They were located on the back and symmetrically on the upper limbs. The oldest of them were 15cm wide. Histological examination showed thickened collagen bundles with almost complete loss of dermal elastic fibres, fragmentation of elastic fibres around the lesion and mucin deposits. Standard laboratory tests and bone X-rays were normal. Case 2: a 34-year-old man consulted for clearly delineated asymptomatic papules on the back present for four years. Histological examination was similar to the previous patient and the laboratory tests were normal. He developed Hodgkin's lymphoma. DISCUSSION: We report these two cases because of their particularities as well as the rarity of papular elastorrhexix. The first exhibited large lesions and mucin deposits while the second was associated with Hodgkin's disease. Differential diagnosis of papular elastorrhexis includes Buschke-Ollendorff syndrome, eruptive collagenoma and elastic tissue disorders: macular anetoderma, mid-dermal elastolysis, nevus anelasticus, acne scars and pseudoxanthoma elasticum. The aetiology is unknown. There are no extracutaneous signs.

[Cutaneous angiosarcoma of the leg without lymphoedema]. / Angiosarcome cutané de jambe sans lymphoedème associé.

BACKGROUND: Cutaneous angiosarcoma is a rare aggressive vascular neoplasm with a poor prognosis, seen chiefly in elderly subjects and usually on the scalp or face. The present case is original because of its localization on the leg without any chronic lymphoedema and because of the long survival period. The treatment modalities are discussed. CASE REPORT: An 87-year-old woman presented with a rapidly growing large deep-purple ulcerated tumour on the anterior aspect of the leg. In addition, two nodules with a similar aspect appeared on the outer surface of the foot. Histological examination showed vascular channels lined with atypical cells consistent with a diagnosis of angiosarcoma. Computed tomography revealed no metastases. Amputation was performed at the thigh and there was no recurrence 30 months later. DISCUSSION: The leg is a rare site of cutaneous angiosarcoma. Treatment usually consists of surgical excision with wide margins followed by radiotherapy, but in some cases amputation is unavoidable.

[Basal cell carcinoma of the first toenail]. / Carcinome basocellulaire de l'appareil unguéal de l'hallux.

BACKGROUND: Basal cell carcinoma is a very common form of skin cancer but its occurrence on the toenail unit is very rare. We report such a case of basal cell carcinoma localized on the proximal nail fold of the right hallux. CASE REPORT: A 67-year-old woman had a 7-year history of a non-healing ulcer on the proximal nail fold of the right hallux after antibiotics and treatment of her onychomycosis. Bowen's disease and squamous cell carcinoma were suspected. Histopathologic examination of a biopsy specimen revealed infiltrative basal cell carcinoma. The lesion was surgically excised with a 0.5 cm margin and the defect was repaired by full-thickness skin graft with good functional and cosmetic results. DISCUSSION: Basal cell carcinoma is the most common skin cancer but its localization on fingers, toes and nail units is very rare. Only six cases of basal cell carcinoma on the toe nail unit have been reported to date in the literature. Clinical aspects often mimic benign processes, resulting in misdiagnosis. Treatment requires simple excision or Mohs micrographic surgery. Our case emphasizes the value of biopsy for all nail unit lesions of atypical appearance, course or therapeutic response.

[Pemphigus vulgaris and intraepithelial neoplasia localized to the vagina]. / Pemphigus vulgaire et néoplasie intra-épithéliale de localisation vaginale.

BACKGROUND: Involvement of the vaginal mucosa in pemphigus vulgaris is a rare occurrence. Here we report an original case that resulted in discovery of intra-epithelial neoplasia at the same site. PATIENTS AND METHODS: A 63 year-old woman was followed for 18 years for pemphigus vulgaris treated with prednisone, initially in combination with azathioprine. An erosive lesion was discovered in the pouch of Douglas during routine gynecological examination and demonstrated the histological features of pemphigus, despite remission of the disease at other sites. In spite of resumption of azathioprine and prednisone, the vaginal lesion continued to spread. A further biopsy revealed intra-epithelial vaginal neoplasia together with images of suprabasal cleavage and acantholysis. Surgical removal was carried out. DISCUSSION: Intra-epithelial carcinoma associated with pemphigus vulgaris has been described in rare cases in the cervix but never in the vagina.

[Necrotic livedo after injection of buprenorphine (Subutex)]. / Livédo nécrotique après injections de buprénorphine (Subutex): rôle de l'amidon de maïs contenu dans l'excipient.

INTRODUCTION: Use of buprenorphine (Subutex) is widely used as substitution treatment in opiate addiction although its side-effects are little known. We report a case of localised necrotic livedo subsequent to injection of Subutex. OBSERVATION: A 34 year-old male drug addict on Subutex substitution treatment presented a necrotic livedo and an ulcer with clearly demarcated edges on the skin of the inner elbow. Histological analysis revealed PAS-positive particles in a hypodermic inflammatory lymphohistiocytic infiltrate that were reflective and formed a Maltese cross under polarised light and were identified as maize starch. DISCUSSION: This clinical case describes necrotic livedo lesions induced by injection of Subutex. The underlying mechanisms are associated with maize starch, an excipient used in Subutex. Unauthorised subcutaneous injection of buprenorphine (Subutex) is common among drug addicts but there is little description of the associated complications. In our patient, the presence in cutaneous biopsy samples of maize starch, an excipient of buprenorphine, provides evidence of intravenous administration of this drug.

[Malignant nodular hidradenoma and multiple nodular hidradenomas in a hypogonadic patient]. / Hidradénome nodulaire malin et hidradénomes nodulaires multiples chez un malade hypogonadique.

BACKGROUND: We report a case of multiple benign nodular hidradenomas associated with malignant nodular hidradenoma in a hypogonadic patient. CASE-REPORT: A 49 year-old man presented 11 benign nodular hidradenomas in the pectoral region. A malignant nodular hidradenoma had recently appeared in this region some distance from the pre-existing benign modular hidradenomas. This patient had peripheral hypogonadism associated with congenital bilateral cryptorchidia responsible for gynecomastia due to "relative hyperestrogenism". Large numbers of estrogen receptors were demonstrated in each of the benign nodular hidradenomas. The malignant nodular hidradenoma mass was unavailable and screening for these receptors was not possible. DISCUSSION: Cases of multiple nodular hidradenoma are extremely rare: we have seen only two. To the best of our knowledge, there have been no reports to date of combined malignant nodular hidradenoma and multiple benign nodular hidradenoma. However, there is histological evidence of transition forms. The coexistence of endocrine anomalies associated with this type of tumour has never been reported. However, the presence of estrogen receptors has occasionally been demonstrated in benign nodular hidradenomas. Our patient's endocrine disease may have played a role in the presentation of multiple hidradenomas, but this cannot be demonstrated.