Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD. RESULTS: Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years. CONCLUSIONS: Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

Intraoperative dermoscopic features of onychomatricoma: a review of 10 cases.

BACKGROUND: Amelanotic nail tumours are difficult to diagnose. Dermoscopy is an accessible tool successfully used in diagnosis of amelanotic or melanotic skin tumours. We have previously shown the usefulness of dermoscopy in the preoperative diagnosis of onychomatricoma (OM). In this study, we completed this work by identifying additional intraoperative criteria to better establish the initial diagnosis of this tumour. AIMS: Evaluation of intraoperative dermoscopy in a small series of OM cases in order to define relevant diagnostic criteria. METHODS: In total, 10 patients with OM diagnosed in our centre were enrolled in the study. Six trained dermoscopists individually evaluated each criterion, then the data were compared and a consensus reached after discussion between the observers. For each criterion, we analysed its frequency and its interobserver accordance. We defined three architectural criteria (the 'Sagrada Familia' sign, digitations and the 'mirror sign'), and three vascular criteria (sagittal vessels, dotted vessels and irregular vessels). RESULTS: The Sagrada Familia sign, digitations and mirror sign were found in 100%, 90% and 70% of the cases, respectively, with high interobserver agreement. The vascular criteria were less regularly observed: sagittal, dotted and irregular vessels were respectively found in 80%, 70% and 50% of the OM cases, and were more difficult to assess, as shown by the lower interobserver agreement rates. CONCLUSION: Intraoperative dermoscopy of the nail matrix and bed offers useful information for the diagnosis and management of OM. Larger comparative studies should be performed to evaluate the true benefit of this approach.

Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers.

We addressed uncertainties regarding hereditary leiomyomatosis and renal cell carcinoma (HLRCC) by exploring all French cases, representing the largest series to date. Fumarate hydratase (FH) germline testing was performed with Sanger sequencing and qPCR/MLPA. Enzyme activity was measured when necessary. We carried out whenever possible a pathology review of RCC and S-(2-succino)-cysteine (2SC)/fumarate hydratase immunohistochemistry. We estimated survival using non-parametric Kaplan-Meier. There were 182 cases from 114 families. Thirty-seven RCC were diagnosed in 34 carriers (19%) at a median age of 40. Among the 23 RCC with pathology review, 13 were papillary type 2. There were 4 papillary RCC of unspecified type, 3 unclassified, 2 tubulocystic, and 1 collecting duct (CD) RCC, all 2SC+ and most (8/10) FH-. Of the remaining 14, papillary type 2, papillary unspecified, CD, and clear cell histologies were reported. The vast majority of RCC (82%) were metastatic at diagnosis or rapidly became metastatic. Median survival for metastatic disease was 18 months (95%CI: 11-29). 133 cases (73%) had a history of cutaneous leiomyomas, 3 developed skin leiomyosarcoma. Uterine leiomyomas were frequent in women (77%), but no sarcomas were observed. Only 2 cases had pheochromocytomas/paraganglioma. CONCLUSION: Our findings have direct implications regarding the identification and management of HLRCC patients.

Overview of the use of dermoscopy in academic and non-academic hospital centres in France: a nationwide survey.

BACKGROUND: Dermoscopy is acknowledged to improve the diagnostic accuracy of melanoma by several concordant meta-analyses. However, the use of dermoscopy was not considered as a high level of evidence diagnostic tool by French Health Authorities. However, as shown in Australian, American and in our recent surveys, dermoscopy is used by most of dermatologists in private practice. OBJECTIVES: To analyse the use, beliefs, teaching given and research produced in dermoscopy in dermatology departments of French hospitals. METHODS: A questionnaire about the use, available equipment, teaching activities and published research on dermoscopy was mailed to all chairmen of dermatology departments in French both academic and non-academic hospitals. RESULTS: Seventy-six of 110 mailed questionnaires were returned. The majority of centres claimed to use dermoscopy (97.5%), but it seemed heterogeneous among practitioners according to their age and position. The use of dermoscopy was four times higher in non-academic centres (P = 0.015). Centres located in the south east of France were higher users comparing with others (P = 0.004). Earlier detection of melanoma was the most important advantage reported. Excessive training time was the most important reported disadvantage. Twenty-five percent of centres had dedicated clinics for pigmented lesions. Few centres (14.5%) run formal dermoscopy training programs. Most centres (74.7%) declared a use of dermoscopy for the diagnosis of non-tumoral diseases. CONCLUSIONS: This is the first European study evaluating the use of dermoscopy among hospital. Despite a large use, dermoscopy-dedicated teaching and research time appeared to be insufficient.

Dermoscopy of dermatofibrosarcoma protuberans: a study of 15 cases.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant cutaneous tumour of which diagnosis is often delayed because of the lack of early clinical clues. OBJECTIVES: To describe the main dermoscopic features of DFSP. METHODS: We performed dermoscopic examination in 15 unselected, consecutive cases of biopsy-proven DFSP. Firstly, six dermoscopic features were identified collegially, then all cases were reviewed separately by six experienced dermoscopists. In a given lesion, features recognized only by all dermoscopists were taken into account. RESULTS: The median number of dermoscopic features was four per lesion. The following dermoscopic features were found: delicate pigmented network (87%), vessels (80%), structureless light brown areas (73%), shiny white streaks (67%), pink background coloration (67%) and structureless hypo- or depigmented areas (60%). When detected, vessels were of arborizing type in 11 of 12 cases, and presented as either unfocused only, or both unfocused and focused. CONCLUSIONS: This first study of the dermoscopic spectrum of DFSP identifies six dermoscopic features (often associated in a multicomponent pattern) and a peculiar vascular pattern. Whether dermoscopy can help to identify suspected DFSP remains to be established by further studies.

Second primary melanomas treated with BRAF blockers: study by reflectance confocal microscopy.

BACKGROUND: New primary melanomas arising in patients with stage IV melanoma and receiving BRAF inhibitors have recently been reported. This raises the question of the nature of the earliest cellular events identifiable within pre-existing moles. OBJECTIVES: To use reflectance confocal microscopy (RCM) to investigate changing moles in patients using vemurafenib. METHODS: In the first part of the study 23 lesions were examined by RCM before excision (performed because of digital dermoscopy changes) and histopathological examination. In the second part, 10 randomly chosen lesions in two patients were examined before and after 3 months of vemurafenib treatment. RESULTS: The first step permitted the highlighting of an unusual RCM pattern identified in five lesions characterized by areas of marked atypia in otherwise nondysplastic lesions. In the second step, four initially nondysplastic lesions developed focal or multifocal areas of marked atypia under treatment, which were not always correlated with digital dermoscopy changes, but did correlate with histopathology. All four lesions were finally diagnosed as melanomas. CONCLUSIONS: Although the clinical relevance of such findings remains questionable, RCM allowed us to observe, at the cellular level, the earliest events occurring within vemurafenib-induced changing moles. Moreover, repeated RCM examinations permitted to confirm that microscopic marked atypia that led to the histopathological diagnosis of melanoma appeared under treatment and were not pre-existing.

Dermoscopy use by French private practice dermatologists: a nationwide survey.

BACKGROUND: Dermoscopy is now recognized as an essential tool for discriminating melanoma from other pigmented lesions, as corroborated by several robust meta-analyses. Although it is considered to be widely used in European countries, no published data on this topic are available to date, unlike in Australia and the U.S.A. OBJECTIVES: To describe and quantify the use and learning of dermoscopy among French private practice dermatologists. METHODS: A questionnaire of 19 items regarding demographic characteristics, dermoscopy use and training, and physician's judgment on dermoscopy was mailed to all French private practice dermatologists. Only questionnaires with an answer to the key item, 'Do you use dermoscopy?' were taken into account. RESULTS: Of 3179 mailed questionnaires, 1611 were returned and 1576 were analysable (49·6%). Most respondents declared using dermoscopy (94·6%), using their dermoscope several times a day (82·7%) and/or for the diagnosis of nonpigmented lesions (87·7%). Physicians learned dermoscopy mainly through books (75·8%) and/or conferences (88·6%); 12·8% reported a dedicated university degree. Dermoscopy helps to detect melanoma earlier and to perform fewer biopsies according to 86·6% and 74·6%, respectively. On multivariate analysis, female sex and age under 45 years were significantly associated with higher utilization rate of dermoscopy [odds ratio 1·89, 95% confidence interval (CI) 1·15-3·10; and 2·85, 95% CI 1·14-7·11, respectively]. CONCLUSIONS: This is the first published nationwide survey of dermoscopy practice in Europe. Despite potential classification and/or selection bias, the particularly high penetration rate found in our study suggests that dermoscopy is now widely accepted by French private practice dermatologists for the routine management of both pigmented and nonpigmented lesions.

Reflectance confocal microscopy accurately discriminates between benign and malignant melanocytic lesions exhibiting a 'dermoscopic island'.

BACKGROUND: The 'dermoscopic island' is a term that was recently proposed to design an area of a pigmented lesion with a uniform dermoscopic pattern different from the remainder of the lesion. The positive predictive value of this sign for the diagnosis of melanoma is about 50%. OBJECTIVE: The purpose of our study was to see if reflectance confocal microscopy (RCM) permitted to accurately distinguish between nevi and melanoma in such lesions. METHODS: Five lesions of five consecutive unselected patients, with a dermoscopic island but no feasible clear cut diagnosis on the basis of dermoscopy alone were examined by RCM before excision for histopathological evaluation. RESULTS: Two lesions corresponded to nevi, and three lesions were early melanomas arising on a benign naevus in one case, and on a dysplastic naevus in two cases. In all five cases, RCM permitted to make the correct diagnosis, with a very good correlation with conventional histopathology. CONCLUSION: Reflectance confocal microscopy appears as a promising tool not only to enhance the early diagnosis of melanoma but also to avoid unnecessary excisions of lesions with a dermoscopic island.

Perioperative confocal microscopy of the nail matrix in the management of in situ or minimally invasive subungual melanomas.

BACKGROUND: Although dermoscopy of the nail plate is helpful to discriminate between benign and malignant causes of nail pigmentations, there remain ambiguous cases in which a matricial biopsy is required. When a subungual melanoma is diagnosed histopathologically, a complementary surgical treatment is performed secondarily, the duration of postoperative disability being accordingly prolongated. OBJECTIVES: The purpose of our study was to evaluate the feasibility of an intraoperative diagnosis by reflectance confocal microscopy (RCM). PATIENTS AND METHODS: Our series included nine consecutive patients who underwent a matricial biopsy for an acquired melanonychia (one benign lentigo and eight melanomas). RCM examination was performed in vivo on the nail matrix after reclination of the nail plate, and/or ex vivo on the fresh tissue biopsy. RCM data were compared with histopathology. RESULTS: There was a good correlation between confocal and histopathological features. Seven melanoma cases were unequivocally diagnosed intraoperatively according to the confocal features, whereas the lentigo was correctly classified as a benign lesion according to RCM. The remaining lesion could not be unequivocally classified by RCM and corresponded histopathologically to an early melanoma that required immunostaining to be diagnosed. CONCLUSIONS: Intraoperative RCM examination of the nail matrix is an efficient diagnostic approach of melanonychia striata that permits an extemporaneous diagnosis of malignancy and therefore a one-step surgical treatment of in situ or minimally invasive melanoma, reducing dramatically the duration of postoperative disability.

Dermoscopy of lentigo maligna melanoma: report of 125 cases.

BACKGROUND: Lentigo maligna melanoma (LMM) is the most common subtype of melanoma on the face. Its presentation may be quite subtle, particularly in early stages, and delayed diagnosis is common. Few dermoscopic studies have been performed and the main dermoscopic features of LMM were defined by Stolz and coworkers in 2000. OBJECTIVES: To investigate classical as well as new dermoscopic features in a large series of LMM in a white-skinned population, in order to evaluate their diagnostic value. METHODS: One hundred and twenty-five consecutive histopathology-proven LMMs were analysed retrospectively based on medical records, clinical and dermoscopic photographs by three independent observers for the presence of 19 predefined criteria. RESULTS: At least one of the classical Stolz criteria was present in 87% of cases (hyperpigmented follicular opening, annular-granular pattern, pigmented rhomboidal structures, obliterated hair follicles). Three original criteria were also present at a relatively high frequency: increased density of the vascular network (58%), red rhomboidal structures (40%), target-like patterns (41%). Darkening at dermoscopic examination (when compared with naked-eye examination) was observed in 25% of lesions. Classical dermoscopic features of extrafacial melanoma (atypical pigment network, irregularly distributed globules, dots, streaks and pseudopods) and vertical growth phase-associated dermoscopic criteria (ulceration, blue papular areas and black structureless areas) were rarely seen. A large number of colours, pigmented rhomboidal structures, obliterated hair follicles and red rhomboidal structures were significantly more frequent in invasive LMMs. In contrast, in situ melanomas were more often associated with one or two colours and few distinctive dermoscopic features. CONCLUSIONS: We present herein, in a large series of LMM, confirmation of the diagnostic value of the classical Stolz dermoscopic criteria and describe four additional original criteria, mainly vascular. A correlation between the presence of some dermoscopic features and thicker tumoral invasion has also been demonstrated.

Conservative surgical management of subungual (matrix derived) melanoma: report of seven cases and literature review.

BACKGROUND: Subungual melanoma (SUM) is a rare entity, comprising approximately 0·7-3·5% of all melanoma subtypes. SUM histopathologically belongs to the acral lentiginous pathological subtype of malignant melanoma. Its diagnosis is helped by dermoscopy but pathological examination of doubtful cases is required. Classical management of SUM is based on radical surgery, namely distal phalanx amputation. Conservative treatment with nonamputative wide excision of the nail unit followed by a skin graft has been insufficiently reported in the medical literature even though it is performed in many centres. OBJECTIVES: To report a series of patients with in situ or minimally invasive SUM treated by conservative surgery, to investigate the postoperative evolution and to evaluate the outcome with a review of the literature. METHODS: We performed a retrospective extraction study from our melanoma register of all patients with in situ and minimally invasive SUM treated with conservative surgery in the University Hospital Department of Dermatology, Lyon, France from 2004 to 2009. The patient demographics, disease presentation, delay to diagnosis, histopathology and postoperative evolution were reviewed. RESULTS: Seven cases of SUM treated as such were identified in our melanoma database. All cases had a clinical presentation of melanonychia striata. The mean delay to diagnosis was 2years. Surgical excision of the entire nail unit with a 5-10mm safety margin without bone resection followed by full-thickness skin graft taken from the arm was performed in all cases. No recurrence was observed with a mean follow-up of 45months. Functional results were found satisfactory by all patients and their referring physicians. Sixty-two other cases have been found in the literature and are also discussed. CONCLUSIONS: Conservative surgical management in patients with in situ or minimally invasive SUM is a procedure with good cosmetic and functional outcome and, in our cases as well as in the literature, the prognosis is not changed.

Ungual seborrheic keratosis.

BACKGROUND/OBJECTIVES: Seborrheic keratoses are ubiquitous benign epithelial skin tumours. A number of unusual locations have already been reported. We report herein the case of a seborrheic keratosis of the nail bed with typical histological features. METHODS/RESULTS: A 58-year-old man presented with a 1-year-history of longitudinal leukoxanthonychia of the right hallux. Surgical treatment was performed. The diagnosis of typical seborrheic keratosis of the nail bed was made on histological examination. CONCLUSION: To our knowledge, this is the first report of a typical, histologically documented seborrheic keratosis of the nail bed. Therefore, this condition should be added to the differential diagnosis of acquired longitudinal leukoxanthonychia. However, surgical treatment remains necessary to rule out other causes, including squamous cell carcinoma.