Epidemiological changes in cutaneous lymphomas: an analysis of 8593 patients from the French Cutaneous Lymphoma Registry.

BACKGROUND: Primary cutaneous lymphomas (PCLs) are a heterogeneous group of T-cell (CTCL) and B-cell (CBCL) malignancies. Little is known about their epidemiology at initial presentation in Europe and about potential changes over time. OBJECTIVES: The aim of this retrospective study was to analyse the frequency of PCLs in the French Cutaneous Lymphoma Registry (GFELC) and to describe the demography of patients. METHODS: Patients with a centrally validated diagnosis of primary PCL, diagnosed between 2005 and 2019, were included. RESULTS: The calculated incidence was unprecedently high at 1·06 per 100 000 person-years. The number of included patients increased yearly. Most PCL subtypes were more frequent in male patients, diagnosed at a median age of 60 years. The relative frequency of rare CTCL remained stable, the proportion of classical mycosis fungoides (MF) decreased, and the frequency of its variants (e.g. folliculotropic MF) increased. Similar patterns were observed for CBCL; for example, the proportion of marginal-zone CBCL increased over time. CONCLUSIONS: Changes in PCL frequencies may be explained by the emergence of new diagnostic criteria and better description of the entities in the most recent PCL classification. Moreover, we propose that an algorithm should be developed to confirm the diagnosis of PCL by central validation of the cases.

In situ nail unit melanoma: epidemiological and clinic-pathologic features with conservative treatment and long-term follow-up.

BACKGROUND: Nail unit melanoma (NUM) is a rare melanoma variant, usually associated with a poor prognosis because of a delayed diagnosis. Few data are available concerning the management and long-term outcome of in situ NUM. OBJECTIVE: To use a large cohort to provide comprehensive patient data and long-term follow-up information. This will serve to investigate distinctive epidemiological, clinical and histological features of in situ NUM. To report treatment modalities, assess conservative surgery and evaluate its long-term safety. METHODS: Patients with confirmed diagnosis of in situ NUM were retrospectively reviewed. Demographics, clinical presentation, therapeutic data and follow-up were analysed. RESULTS: Sixty-three cases of in situ NUM were identified as follows: 44 were women (70%), with a mean age of 51 years. The mean duration of symptoms prior to consultation was 4.3 years [range 3 months-28 years]. Clinically, with 58 cases, i.e. (92%) longitudinal melanonychia was the most common clinical presentation. The thumb was the most affected digit, being afflicted in 28 cases: 44%. Medical history found a widening and/or recent darkening of the melanonychia in 46 cases (82%). The treatment consisted of, respectively, 56 En bloc excisions of the nail apparatus 89% of the patients we studied, and seven amputations of the distal phalanx. During the follow-up period (mean: 10 years), two patients presented in situ recurrences. CONCLUSION: The recognition of a NUM at an in situ stage allows early treatment and curing of this tumour. At this early stage, a 'functional surgery' is a rational approach with an excellent oncologic safety.

Longitudinal subungual acanthoma: one denomination for various clinical presentations.

BACKGROUND: Benign subungual proliferation of the distal nail matrix and bed such as longitudinal keratosis, seborrhoeic keratosis or onychocytic matricoma should belong to a single spectrum of diseases. OBJECTIVE: This article intends to demonstrate clinically and histologically the different facets of Nail unit longitudinal acanthoma. METHODS: We report three new cases that present as a longitudinal melanonychia with thickening of the nail plate in two of them and as leukoxanthonychia in the third one. We compared them with the two original cases we described in 1999, reminiscent of seborrhoeic keratosis and all the new cases published since then. RESULTS: We therefore consider that all these tumours belong to a single spectrum of diseases, we have called 'nail unit longitudinal acanthoma' which describes a histopathological process. The distinct clinical features of these tumours, melanonychia or leukoxanthonychia may be linked to their variable anatomic locations in different zones of the nail unit.

[Multiple epidermolytic acanthomas of the genitalia]. / Hyperkératose épidermolytique génitale (acanthomes épidermolytiques génitaux multiples).

BACKGROUND: Epidermolytic hyperkeratosis presents a particular histological image common to several clinical pictures, including that of keratinopathic ichthyoses. It may also occur fortuitously in various tumoral and inflammatory lesions. It is the elementary histopathological lesion of epidermolytic acanthoma, which may either be single or multiple, and when it occurs in the genital area, is known as epidermolytic hyperkeratosis of the genitalia or multiple epidermolytic acanthoma of the genitalia. Herein, we report two characteristic cases of epidermolytic hyperkeratosis of the genitalia. PATIENTS AND METHODS: The first patient was a 50-year-old woman consulting for vulvar pain in whom clinical examination revealed the presence of multiple papules on the labia majora and minora. The second patient was a 44-year-old man consulting for verrucous lesions of the scrotum. In both cases, biopsy revealed an histopathological aspect identical with acanthosis, hyperkeratosis, changes in the keratinocytes, in which the cytoplasm contained clear vacuoles, numerous keratohyalin granules and eosinophilic bodies, resulting in a diagnosis of epidermolytic hyperkeratosis of the genitalia. DISCUSSION: Epidermolytic hyperkeratosis of the genitalia is a rare disease, occurring in middle-aged men and women, but chiefly men. The lesions found on the genital organs may be either single, or, more frequently, multiple, and are described as hyperkeratotic papules, which are also reported under the term multiple epidermolytic acanthomas of the genitalia. The aetiology is unknown; certain authors incriminate a traumatic factor; the role of human papillomavirus (HPV) has been suggested but immunohistochemical studies and molecular biology studies generally reveal no viral DNA. Where lesions cause discomfort to the patient, treatment consists of emollients combined with destruction by cryotherapy or CO2 laser. Imiquimod, calcipotriol, tacrolimus and pimecrolimus have all resulted in regression of lesions.

Long-term efficacy and safety of alemtuzumab in advanced primary cutaneous T-cell lymphomas.

BACKGROUND: Alemtuzumab has been proposed as salvage therapy for refractory cutaneous T-cell lymphomas (CTCLs). Long-term follow-up data are scarce. OBJECTIVES: To assess the efficacy and safety of alemtuzumab in the treatment of advanced CTCL. METHODS: A multicentre retrospective analysis was carried out of 39 patients with advanced CTCL treated with alemtuzumab between 2003 and 2013. RESULTS: Thirty-nine patients (median age 62 years, range 20-83) with Sézary syndrome (SS, n = 23) or advanced mycosis fungoides (MF, n = 16) received alemtuzumab 30 mg two to three times per week for a median duration of 12 weeks (range 1-35). Fifteen patients received maintenance therapy for a median duration of 24 weeks (range 6-277). Eleven patients (28%) had transformed disease (MF, n = 10; SS, n = 1). After a median follow-up of 24 months (range 0.3-124), eight patients (21%) were still alive. The overall response rate was 51% in the whole study group (partial response, n = 13; complete response, n = 7); 70% in patients with SS and 25% in patients with MF (P = 0.009). The median time to progression was 3.4 months (range 0.4-42). Six patients (15%; SS, n = 5; MF, n = 1) remained progression free for > 2 years (median 56 months, range 28-117). Five patients experienced cutaneous large T-cell transformation during alemtuzumab treatment and one patient developed primary cutaneous large B-cell lymphoma. Twenty-four patients (62%) had a grade three or higher infectious adverse event and 10 (26%) a haematological toxicity, which led to treatment discontinuation in 17 cases (44%) and death in two (5%). CONCLUSIONS: Alemtuzumab may induce long-term remission in SS but seems ineffective in MF and transformed CTCL.

[Cutaneous revelation of Rosai-Dorfman disease: 7 cases]. / Maladie de Rosai-Dorfman à révélation cutanée: 7 observations.

BACKGROUND: Rosai-Dorfman disease (RDD) is a benign form of non-Langerhans-cell histiocytosis. It is identified by a particular histological profile first observed in febrile lymph nodes. Extranodal sites are frequent. The most common site is the skin, which can reveal the disease despite a difficult and delayed diagnosis. Seven cases of cutaneous revelation of RDD were studied retrospectively in order to delineate the clinical characteristics and facilitate diagnosis and treatment of this extremely rare disease. PATIENTS AND METHODS: Six cases of RDD from 1990 to 2011 were identified in the photographic and histopathological records of the Saint-Louis Hospital and one case came from a Bichat Hospital consultation. The diagnosis was based in all cases on histopathology results. RESULTS: Patients consisted of four men and three women aged between 31 and 69 years. Cutaneous lesions (3 to 20) revealed the disease in all of them and the time from disease onset to diagnosis ranged from six months to five years. The clinical presentation was erythematous or orange popular nodules or plaques, usually on the face. Microscopically, a dense dermal infiltration was observed, in some cases extending into the subcutaneous tissue, with pale histiocytic cells characterised by emperipolesis, plasma cells, lymphocytes, some neutrophils and variable fibrosis. The diagnosis, initially erroneous in 4 cases, was rectified by a second reading of histopathology slides, and immunohistochemical studies showed expression of S-100 protein in histiocytes but not CD1a. Three patients had pure cutaneous RDD. Two neurological sites and one nasal site were also found, with one ENT site and sequelae of previous uveitis in one patient. All extra-cutaneous sites were identified by clinical examination. Different treatments were proposed according to the sites and impact of the disease. In one case, the lesions regressed spontaneously after 18 months. COMMENTS: Few RDD series have been published and they mainly concern Asian patients. The ethnic origin of our patients was varied. The main findings were: 1) common clinical findings (orange or erythematous papules or nodules, mostly on the upper body), which should alert the dermatologist and histopathologist to the possible diagnosis of RRD; 2) the possibility, already mentioned in the literature, of spontaneous regression and a good prognosis; 3) the need for thorough evaluation by thoracic, abdominal and cerebral CT (computed tomography) or more a PET (positron emission tomography) scan to screen for potentially dangerous visceral sites, and also clinical follow up.

[Clinical features of Spitz naevus in children: a retrospective study of 196 cases]. / Caractéristiques du nævus de Spitz chez l'enfant. Étude rétrospective de 196 cas.

AIMS: To better define the characteristics of Spitz naevus (SN) in children, to determine whether it was clinically diagnosed and to examine the differential diagnoses made according to age. In addition, to determine whether atypical spitzoid tumors (AST) have a different presentation from other forms of SN. PATIENTS AND METHODS: A two-centre retrospective survey was made of histopathological reports written over a 4-year period in children aged under 18 years. The inclusion criterion was unequivocal diagnosis of SN or AST. Age, gender, site, size, course, excision methods, presumptive clinical diagnoses and the percentage of correct diagnosis were analyzed for four distinct age groups. RESULTS: One hundred and ninety-six patients were included, 186 with SN and 10 with AST. Mean age at diagnosis of SN was 9 years. Female predominance and predilection for the lower limbs were seen for all age groups. Facial involvement was less frequent and chiefly affected children aged under 11 years. Most SN lesions measured between 4 and 8mm. They were often confused with either pyogenic granuloma or juvenile xanthogranuloma, mainly before the age of 11 years. An accurate diagnosis was made in 29% of cases, chiefly in the 0 to 5 year-old age group. No cases of AST were clinically recognized, but it was diagnosed occasionally on histological grounds for very small tumours and in very young children. CONCLUSION: Clinical diagnosis of SN is not always straightforward and in this study, AST exhibited no special features allowing it to be distinguished from SN. These results underline the need for caution in the event of SN in children, regardless of age or lesion size.

[Post-radiation atypical vascular lesions and angiosarcoma: 11 cases]. / Lésions vasculaires atypiques et angiosarcomes post-radiothérapie : 11 cas.

BACKGROUND: Post-radiation atypical vascular lesions of the skin display clinical and morphological overlap with well-differentiated angiosarcomas, and correct diagnosis may be difficult. PATIENTS AND METHODS: We studied clinical, histological and immuno-histochemical aspects (CD31, CD34, D2-40 and VEGFR-3) of eight post-radiation atypical vascular lesions comparatively with three post-radiation angiosarcomas. RESULTS: All patients were female and received radiation therapy for breast carcinoma. On average, atypical vascular lesions occurred 4.3 years after radiation therapy and presented as small papulonodules or erythematous plaques. The clinical course after simple excision was benign. Histologically, they were relatively circumscribed lesions and showed slit-like vessels dissecting dermal collagen in all cases. On average, angiosarcomas occurred 5 years after radiation therapy and presented as more extensive lesions with a more aggressive clinical course. The lesions showed histological overlap with atypical vascular lesions, but were poorly circumscribed, with deeper invasion, cytological atypia and mitosis. Although the immuno-histochemical profiles were similar, expression of VEGFR-3 was greater in two cases of angiosarcoma. CONCLUSION: Post-radiation atypical vascular lesions are benign lesions that display clinical, histological and immuno-phenotypic overlap with well-differentiated angiosarcoma, and diagnosis requires good clinicopathological correlation. VEGFR-3 may be useful for differential diagnosis, as well as amplification of the MYC gene.