Skin lesions in neurofibromatosis type 2: diagnostic and prognostic significance of cutaneous (plexiform) schwannomas.

BACKGROUND: Neurofibromatosis type 2 (NF2) is a genetic disease characterized by the appearance of multiple tumours in the nervous system. Cutaneous lesions are common and may provide useful diagnostic and prognostic information, but they have not been widely studied. OBJECTIVES: To characterize cutaneous lesions in a Spanish cohort of patients with NF2 and investigate associations with clinical and genetic severity. METHODS: We studied the clinical and histologic characteristics of cutaneous lesions in 49 patients with NF2 and analysed correlations with phenotype- and genotype-based severity scores. We collected information on the presence/absence of cutaneous lesions, location, age at onset, type of lesion, and histologic features. We also studied level of systemic involvement and genetic mutations involved. RESULTS: Forty-nine patients (31 women [63.3%] and 18 men [36.7%]) were analysed, and 33 (67.3%) had cutaneous lesions presumed to be schwannomas. According to their clinical form, they were distributed as follows: 24 patients (48%) had deep tumours, 21 (42%) had plaque-like lesions, and 3 (6%) had superficial tumours. Histologic examination from 27 lesions analysed out 23 patients showed classic schwannoma or hybrid schwannoma-neurofibroma features in the 8 deep tumours biopsied and plexiform schwannoma features in the 17 plaque-like lesions and the 2 superficial tumours analysed. Early onset (first 2 decades of life) was reported by all patients with plaques and superficial tumours. In our cohort, 100% of the patients with plaque-like lesions and superficial tumours with microscopic features of plexiform schwannoma were in the 2 groups with the most severe clinical phenotypes, and 82.6% of them were in the 3 most severe genotype-based classes. CONCLUSIONS AND RELEVANCE: Cutaneous lesions, specially plexiform schwannomas, are common in NF2, and they usually appear at an early age providing useful diagnostic and prognostic information. These tumours are part of the spectrum of cutaneous manifestations in this disease. Although its diagnostic and prognostic value has been pointed out, there are few studies focussed on their analysis.

Reactive granulomatous dermatitis as a histological pattern including manifestations of interstitial granulomatous dermatitis and palisaded neutrophilic and granulomatous dermatitis: a study of 52 patients.

BACKGROUND: Confusion exists regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic and granulomatous dermatitis (PNGD). OBJECTIVE: To determine whether IGD and PNGD are two different entities, or whether they must be considered as two subtypes of the same reactive pattern, and thus whether the unification of the nomenclature is necessary. METHODS: Observational retrospective multicentre study of patients with IGD and PNGD evaluated between 1999 and 2019 and review of their clinical and histological features. RESULTS: We identified 52 patients (38 women and 14 men). Clinical and histological findings of IGD were observed in 88.4% of cases. The most common cutaneous lesions were plaques/macules (IGD) or annular plaques and papules/nodules (PNGD), located mostly on the limbs and trunk. The rope sign was developed in two patients with IGD that associated autoimmune disorders. Similar associated comorbidities (75%) were found in both entities, mainly autoimmune diseases (53.8%). In IGD, the infiltrate was predominantly lympho-histiocytic. Neutrophilic infiltrates, karyorrhexis and skin lesions with limited clinical course were mainly associated with PNGD biopsies. In biopsies with a limited recurrent course, a predominant lymphocytic inflammatory infiltrate was found. Collagen degeneration was present in 75.9% of cases. The floating sign was observed only in IGD type patients (63%). Overlapping histological findings were found in one fourth of cases, especially between IGD and interstitial granuloma annulare. Interface dermatitis, apparently unrelated to drug intake, was observed in 4 cases of IGD. CONCLUSION: We support the term reactive granulomatous dermatitis to unify both the clinical and histological findings of IGD and PNGD, and the overlapping between IGD and interstitial granuloma annulare. According to this, a spectrum of histological changes will be found depending on the clinical course of the skin lesions.

The First Year of the AEVD Primary Cutaneous Lymphoma Registry. / Registro de linfomas cutáneos primarios de la AEDV: primer año de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas are uncommon. This article describes the Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV) and reports on the results from the first year. PATIENTS AND METHODS: Disease registry for patients with primary cutaneous lymphoma. The participating hospitals prospectively recorded data on diagnosis, treatment, tests, and disease stage for all patients with primary cutaneous lymphoma. A descriptive analysis was performed. RESULTS: In December 2017, the registry contained data on 639 patients (60% male) from 16 university hospitals. The most common diagnoses, in order of frequency, were mycosis fungoides/Sézary syndrome (MF/SS) (348 cases, 55%), primary cutaneous B-cell lymphoma (CBCL) (184 cases, 29%), primary cutaneous CD30+ T-cell lymphoproliferative disorder (CD30+ CLPD) (70 cases, 11%), and other types of T-cell lymphoma (37 cases, 5%). In total, 105 (16.5%) of the cases recorded were incident cases. The most common diagnosis in the MF/SS group was classic MF (77.3%). Half of the patients with MF had stage IA disease when diagnosed, and the majority were either in partial remission (32.5%) or had stable disease (33.1%). The most widely used treatments were topical corticosteroids (90.8%) and phototherapy. The most common form of primary CBCL was marginal zone lymphoma (50%). Almost all of the patients had cutaneous involvement only and nearly half had stage T1a disease. Most (76.1%) were in complete remission. The main treatments were surgery (55.4%) and radiotherapy (41.9%). The most common diagnosis in patients with CD30+ CLPD was lymphomatoid papulosis (68.8%). Most of the patients (31.4%) had stage T3b disease and half were in complete remission. The most common treatments were topical corticosteroids (68.8%) and systemic chemotherapy (32.9%). CONCLUSION: The characteristics of patients with primary cutaneous lymphoma in Spain do not differ from those described in other series in the literature. The registry will facilitate clinical research by the AEDV's lymphoma group.

Core Content for Undergraduate Medical Education in Spain: Recommendations of the Instructors' Group of the Spanish Academy of Dermatology and Venereology (AEDV).

BACKGROUND: Skin problems are among the most frequent reasons for seeking medical attention in primary care. In recent years, as a result of the process of adapting medical curricula to the requirements of the European Higher Education Area, the amount of time students spend learning the concepts of dermatology has been reduced in many universities. MATERIAL AND METHODS: In order to reach a consensus on core content for undergraduate education in dermatology, we sent a survey to the 57 members of the instructors' group of the Spanish Academy of Dermatology and Venereology (AEDV), asking their opinions on what objectives should be set for a dermatology course in Spain. A total of 131 previously selected objectives were listed. We then applied the Delphi method to achieve consensus on which ones the respondents considered important or very important (score≥4 on a Likert scale). RESULTS: Nineteen responses (33%) were received. On the second round of the Delphi process, 68 objectives achieved average scores of at least 4. The respondents emphasized that graduates should understand the structure and functions of the skin and know about bacterial, viral, and fungal skin infections, the most common sexually transmitted diseases (STDs), and the 4 main inflammatory dermatoses. Students should also learn about common complaints, such as itching and bald patches; the management of dermatologic emergencies; purpura and erythema nodosum as signs of internal disease; and the prevention of STDs and skin cancer. During clinical clerkships students should acquire the communication skills they will need to interview patients, write up a patient's medical history, and refer the patient to a specialist. CONCLUSIONS: The AEDV's group of instructors have defined their recommendations on the core content that medical faculties should adopt for the undergraduate subject of dermatology in Spain.

Lupus erythematosus tumidus: a clinical and histological study of 25 cases.

BACKGROUND: Lupus erythematosus tumidus (LET) is a subtype of cutaneous lupus erythematosus (CLE) that has been well characterized in recent years. However, some controversy still remains concerning the histological features of epidermal involvement. OBJECTIVES: The objective of this report is to describe the clinical and microscopic features of LET in patients diagnosed at Hospital Universitari Germans Trias i Pujol, Spain. METHODS: We conducted a retrospective study of 25 patients with a diagnosis of LET. RESULTS: All patients presented with typical LET lesions (smooth, erythematous plaques without macroscopic epidermal changes, such as follicular plugs or scale, that resolved without residual scarring or hypopigmentation). None of the patients fulfilled the criteria for systemic lupus erythematosus during follow-up. Test results for antinuclear antibodies were positive in five patients (20%), with titres below one of 320 in all cases. Twenty-two patients (88%) required antimalarial therapy; response was good in 70% and moderate response in 30%. Minor epidermal alterations were observed in 52% of biopsy specimens, with focal basal vacuolization being the most frequent. CONCLUSIONS: LET is a variant of CLE that has distinctive clinical, histologic and prognostic features. Unlike the patients in the case series previously described in the literature, most of our patients required treatment with antimalarials. Histology revealed mild epidermal alterations in a significant percentage of patients. Thus, in our opinion, the absence of microscopic epidermal alterations is not constant in LET.

Cutaneous lupus erythematosus on the elbows: a peculiar localization.

BACKGROUND: The presence of lesions limited to the elbows as expression of a cutaneous lupus erythematosus (CLE) is very unusual. OBJECTIVES: To describe the clinical and microscopic characteristics of these lesions, as well as their relationship with the different cutaneous lupus erythematosus subsets. METHODS: Seven cases of CLE with lesions on the elbows, collected from 1998 to 2009, were retrospectively analysed. All patients had a previous or concomitant diagnosis of lupus erythematosus based on other typical skin lesions for each subtype of lupus erythematosus, and they all met clinical and microscopic criteria. RESULTS: Six patients were women with a mean age of 33.8 years. Five cases had been previously diagnosed with CLE (three lupus erythematosus [LE] tumidus, one subacute CLE and one acute CLE). In the other two cases, these lesions were the first manifestation of the disease. The lesions consisted of pruriginous, erythematous papules and plaques with a slightly scaly surface, located on both elbows. Microscopically, in addition to the typical features of CLE, other changes were observed, including alterations in the texture and the staining properties of collagen fibres (five cases), an interstitial histiocytic infiltrate (four cases), eosinophils (one case) and a Churg-Strauss granuloma (one case). CONCLUSIONS: These peculiar lesions located on the elbows should be included in the spectrum of cutaneous manifestations of LE. Their histopathology combines changes of both LE and interstitial granulomatous dermatitis.

Population-based incidence of basal cell carcinoma in a Spanish Mediterranean area.

BACKGROUND: Considering the latitude of Spain, the reported age-adjusted incidence rates of basal cell carcinoma (BCC) in this country, similar to those of Northern Europe, are lower than expected. OBJECTIVES: To estimate the actual incidence of BCC in a Mediterranean population from the eastern coast of Spain. METHODS: A registry of BCC cases newly diagnosed between 16 January 2006 and 16 January 2007 was established for the population of residents in the Barcelonès Nord county (369,622 inhabitants). All dermatologists of this area agreed to register their patients. All tumours were registered as 'definite' or 'probable' BCC cases according the existence or not of a proven microscopic diagnosis. If a patient had more than one tumour at different sites, each was counted and registered separately. Sex-specific, age-specific and age-standardized incidence rates were calculated by direct standardization to the World and European Standard Population. RESULTS: Among the 936 cases registered, 81.2% were classified as 'definite' BCC and 18.8% as 'probable' BCC. The overall crude incidence rate was 253.2 per 100,000 person-years, and was 128 per 100,000 person-years and 195.5 per 100,000 person-years after standardizing for the World and European population, respectively. After the age of 65 years, the BCC age-adjusted incidence rates showed a significantly higher increase in men than in women (P = 0.01). CONCLUSIONS: The incidence rates found in our study are higher than those previously reported in Spain. Age-adjusted incidence rates revealed that BCC increases with age in both sexes, this increase being particularly evident in men older than 65 years.

[New autoantibodies in dermatomyositis]. / Nuevos autoanticuerpos en la dermatomiositis.

Dermatomyositis is an idiopathic inflammatory myopathy that affects skeletal muscle and the skin. Idiopathic inflammatory myopathies are characterized by the production of autoantibodies directed against different cell structures. Some of these autoantibodies are specific to idiopathic inflammatory myopathies (myositis-specific antibodies) whereas others are found in a range of overlap syndromes (myositis-associated antibodies). Although they are all associated with certain clinical and physiopathological characteristics of myositis, myositis-specific antibodies are essentially the most useful markers for clinical diagnosis, classification, and prognosis in idiopathic inflammatory myopathies. In recent years, two new myositis-specific antibodies in clinically amyopathic dermatomyositis (CADM), CADM-140 and, in cancer-associated dermatomyositis, anti-p155/p140 have been identified. This is of great importance as no myositis-specific antibodies had previously been detected in these clinical subgroups. The identification of target antigens that are recognized by these antibodies is essential for a better understanding of the pathogenesis of these diseases.

Cutaneous lymphomas showing prominent granulomatous component: clinicopathological features in a series of 16 cases.

BACKGROUND: The presence of a prominent granulomatous tissue reaction in skin biopsies from primary cutaneous or systemic malignant lymphomas with secondary cutaneous involvement is a rare but well-known phenomenon. OBJECTIVE: This paper aims to characterize and study a series of cutaneous lymphomas showing a prominent granulomatous component. PATIENTS AND METHODS: The clinical, histopathological and evolutive features of granulomatous variants of mycosis fungoides (5 patients, 2 of them associating 'granulomatous slack skin' features), Sézary syndrome (1 patient), CD30(+) cutaneous T-cell lymphoma (2 patients), CD4(+) small/medium pleomorphic cutaneous T-cell lymphoma (1 patient), primary cutaneous B-cell lymphoma (3 patients) and peripheral T-cell lymphoma with secondary epithelioid granulomatous cutaneous involvement (4 patients) were reviewed. RESULTS: The observed features were clinically non-distinctive. Only those cases presenting with granulomatous slack skin features were clinically suspected (2 patients). Non-necrotizing granulomata (11 patients) and granuloma annulare-like (4 patients) were the most frequently observed histopathological patterns. In five cases, no diagnostic lymphomatous involvement was initially observed. From our series, no definite conclusions regarding prognosis could be established. CONCLUSION: The diagnosis of cutaneous lymphoma may be difficult when a prominent cutaneous granulomatous inflammatory infiltrate obscures the true neoplastic nature of the condition. However, the presence of concomitant lymphoid atypia may help to suspect the diagnosis. In doubtful cases, the clinical evolution and the demonstration of a monoclonal lymphoid B- or T-cell population may lead to a definite diagnosis.

[Adrenal cortex scintigraphy with and without dexamethasone suppression in the study of primary aldosteronism]. / Gammagrafía suprarrenal cortical con frenación y supresión de la frenación con dexametasona en el estudio del hiperaldosteronismo primario.

AIM OF THE STUDY: To evaluate the diagnostic performance and efficacy of adrenal scintigraphy in primary aldosteronism following the protocol that combines adrenal suppression scintigraphy plus non-suppression study. METHODS AND PROCEDURES: 20 patients referred to our service with the suspicion of primary aldosteronism were studied by combined scintigraphy. Thirteen men and 7 women, mean age of 52 years, aged from 31 to 73 years, were included. Uptake of free iodine by the thyroid was inhibited by oral Lugol 5 % administration. Dexamethasone 4 mg per day was administered from day 7 to the third day of detection, when administration was stopped. Adrenal scintigraphy was performed after intravenous injection of I-131-norcolesterol (37 MBq). Images were taken at 24 and/or 48 hours and on the third day. Afterwards, dexamethasone administration was stopped and late images on 5th and/or 7th days were obtained. The scintigraphic result was confirmed with the final clinical evaluation (FCE) of the patient. RESULTS: 11 patients presented pathological studies, 9 adenomas (8TP + 1FP) and 2 bilateral adrenal hyperplasia (2TP); 7 normal scintigraphies (6TN and 1 non-conclusive FCE) and 2 non-conclusive scintigraphies (1 incidentaloma and 1 non-conclusive FCE). Normal adrenal glands were visualized in all cases on the 5th and/or 7th day scintigraphy. CONCLUSION: The study of adrenal functionalism by the combined protocol of adrenal suppression study plus later non-suppression study made it possible to identify with high precision primary aldosteronism and to confirm the function of normal adrenal glands.

Adverse granulomatous reaction after cosmetic dermal silicone injection.

BACKGROUND: Various alloplastic injectable implants have been developed for soft tissue augmentation without surgery, but different local or systemic adverse reactions have limited their use for cosmetic purposes. OBJECTIVE: To examine the problems associated with silicone injection. METHODS: Case report and literature review. RESULTS: We describe an adverse granulomatous reaction after the injection of liquid silicone for lip augmentation, causing facial disfigurement. Although the initial response to steroids was poor, after 3 years of follow-up the nodules have almost disappeared spontaneously. CONCLUSION: We advise that silicone injection be performed solely by trained physicians using medical-grade silicone or consider other injectable materials.

An immunohistopathologic study in cutaneous necrotizing vasculitis.

In order to investigate the importance of timing in the immunophenotypical characteristics of the inflammatory infiltrate and in the adhesion molecules expression in cutaneous necrotizing vasculitis (CNV) we carried on an immunohistopathologic study. An avidin-biotin-streptavidin peroxidase technique was performed on 21 lesional skin biopsy specimens obtained sequentially at 0 to 24, 72 and 120 hours from seven patients with a CNV presenting as palpable purpura. A panel of monoclonal antibodies specific for inflammatory cells (T lymphocytes, polymorphonuclear leukocytes, macrophages, dendritic cells) and different adhesion molecules (E-selectin, ICAM-1, VCAM-1, LFA-1, VLA-4) was used. Moreover, HECA-450 monoclonal antibody was used to identify cutaneous lymphocyte antigen (CLA) in the inflammatory infiltrate. In all cases, polymorphonuclear leukocytes predominated in the early phase of CNV and their number decreased significantly with time (p = 0.0001). The T lymphocytes were present from the beginning and their number remained stable or increased slightly in time (p = 0.1), thus becoming predominant in the perivascular infiltrate in older lesions. Macrophages were scattered on interstitium since the early phase and they showed a time-dependent increase (p = 0.0003). E-selectin (ELAM-1) expression was detected at the first biopsy and it decreased depending on the age of the evolving vasculitis (p = 0.0033). The expression of CLA decreased also with time in 5 of the 7 cases (p = 0.0001). Our study supports the existence of an unique histopathologic pattern in CNV, in which the inflammatory infiltrate varies with time at the expense of the number of polymorphonuclear cells and macrophages.

Keratotsis punctata of the palmar creases: report of two cases associated with ichthyosis vulgaris.

Two patients with keratosis punctata of the palmar creases are described. The association with ichthyosis vulgaris and other disorders of keratinization is discussed. In both cases, histopathology revealed a close relation between the keratotic plug and the sweat glands. The role of genetic factors and manual activity in the pathogenesis is discussed. Treatment with oral etretinate resulted in a good improvement in the first patient, but prolonged low-dose maintenance therapy was required to prevent recurrence.

p53 immunohistochemical expression in early posttransplant-associated malignant and premalignant cutaneous lesions.

BACKGROUND: Current evidence suggests that p53 accumulation is critical to the development of skin cancer in the general population. It is possible, however, that the molecular steps involved in transplant-associated and non-transplant-associated skin carcinogenesis may differ. OBJECTIVE: Our purpose was to examine p53 expression in premalignant and malignant skin lesions from renal transplant recipients (RTRs) in their first 3 years of immunosuppression, as well as in equivalent lesions from immunocompetent normal individuals. METHODS: p53 expression was examined by routine immunohistochemical methods using the anti-p53 monoclonal antibody DO7. RESULTS: p53 immunoreactivity was more prevalent in dysplastic epidermal keratoses and cutaneous carcinomas from RTRs than in equivalent lesions from nontransplant controls. Statistical analysis revealed significant differences, however, only in premalignant skin lesions (p = 0.03). CONCLUSION: This study demonstrates that accumulation of p53 protein is frequently encountered in both premalignant and malignant skin lesions of RTRs, and that this may occur as an early step in transplant-associated skin carcinogenesis.

Generalized nevus spilus and nevus anemicus in a patient with a primary lymphedema: a new type of phakomatosis pigmentovascularis?

A patient with a generalized nevus spilus associated with a nevus anemicus and primary lymphedema is reported. We believe that this association does not reflect the merely coincidental coexistence of three kinds of anomalies but that it may represent a new type of phakomatosis pigmentovascularis.

Low-grade mucoepidermoid carcinoma on the vermilion border of the lip.

We report a case of primary cutaneous carcinoma with mucoepidermoid features located on the vermilion border of the lower lip, at a distance from both salivary glands and cutaneous adnexal structures. The clinical appearance of the present case, which is similar to that of conventional cutaneous squamous cell carcinoma, as well as the existence of surrounding areas of actinic cheilitis favors the hypothesis of a phenomenon of mucinous metaplastic change in a squamous cell carcinoma. We consider that, independently of their origin, tumors having mucin-secreting and squamous differentiation ought to be named according to the same criteria generally used for other organs, namely, "low grade mucoepidermoid carcinoma" would designate tumors with bland mucin-secreting cells and well-differentiated squamous component, and "high grade mucoepidermoid carcinoma" would indicate their less well differentiated counterpart. We propose to reserve the term "adenosquamous carcinoma" for aggressive tumors with high-grade glandular and squamous elements, marked nuclear atypia, frequent mitoses, and extensive necrosis.