Mireia Sàbat

Clinical spectrum and histological analysis of 32 cases of specific cutaneous sarcoidosis

Background:  Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology in which skin involvement is frequent.

Multicentric Reticulohistiocytosis-Mimicking Dermatomyositis

Multicentric reticulohistiocytosis is a rare disorder of unknown etiology, characterized by skin and mucosal papulonodular eruptions and destructive polyarthritis. Histopathological study of these lesions shows a nodular infiltrate composed of histiocytes and multinucleated giant cells, with an eosinophilic, granular, ‘ground-glass’ cytoplasm. We report a case of multicentric reticulohistiocytosis with skin lesions mimicking dermatomyositis and we also review previously reported cases describing such a clinical situation. Our case further emphasizes that multicentric reticulohistiocytosis can mimic clinical features of dermatomyositis. A macular or patch-like erythema in a photodistributed fashion, in addition to other clinical manifestations, can be mistaken for dermatomyositis. However, skin biopsies from these areas may early differentiate both conditions with different treatment options and morbidity.

Cutaneous granulomatous vasculitis in metastatic Crohn's disease.

To the Editor Crohn’s disease is a chronic inflammatory disorder of uncertain aetiology, characterized by non-caseating granulomas that can involve the gastrointestinal tract from the oral mucosa to the perianal tissue. Metastatic Crohn’s disease is a rare extraintestinal manifestation of this condition. It is defined by non-caseating granulomatous inflammation remote to the gastrointestinal tract. The skin is the most frequent location of metastatic Crohn’s disease, although it has been described affecting other organs such as the lung.1 The presence of vasculitis in this entity is exceptional. A 29-year-old woman was affected by Crohn’s disease with jejune, ileon, right colon and perianal lesions. She was being treated with oral mesalazine 2 g/day, remaining asymptomatic of her intestinal disease. She was referred for a necrotic plaque located on the right leg that appeared 45 days prior. Physical examination showed a well-defined plaque of 4 cm, with erythematousviolaceous margin (fig. 1). No adenopathies were found and the rest of general examination was normal. This lesion appeared one and a half months prior. A cutaneous biopsy was performed. The histopathological study showed epithelioid granulomas with occasional multinucleated giant cells in the subcutaneous tissue. A granulomatous infiltrate around the blood vessels with vasculitis was observed in deep and mid-dermis (fig. 2). These findings supported the diagnosis of metastatic Crohn’s disease. PAS-diastase, Gomori, Giemsa and Ziehl-Neelsen tinctions did not detect the presence of microorganisms. The patient was treated with prednisone 30 mg/day with healing of the lesions in 6 weeks. Cutaneous manifestations of Crohn’s disease are relatively common. Usually, it postdates or coincides with gastrointestinal involvement. Only rarely has it preceded the onset of gastrointestinal symptoms.2 Metastatic Crohn’s disease is a rare condition because of the appearance of granulomatous lesions that are non-contiguous to the gastrointestinal tract and are separated by normal skin. It is more frequently observed when the colon is affected and its evolution is not related to the intestinal disease activity as in our patient.3 In addition, the treatment of the intestinal disease does not always improve the cutaneous lesions.4 The aetiology of metastatic Crohn’s disease is unknown, although it has been suggested as an immunological mechanism resulting from the deposition of immune complexes in the skin or to a type IV hypersensitivity reaction.5,6 Clinically, metastatic Crohn’s disease is initially characterized by the appearance of erythema and oedema progressing to abscess formation, ulcers, fistula and scarring. The histology shows the same changes of the intestinal lesions, with noncaseating granulomas and multinucleated giant cells. It is important to emphasize in our case the finding of granulomatous vasculitis reported as an occasional feature in Crohn’s disease, whether intestinal or metastatic.7 Some authors have considered the role of vasculitis and the perivascular location of the granulomas, but there is no consensus about these vascular changes being an initial element in the pathogenesis of the disease, or otherwise being secondary to the perivascular location of the infiltrate.7,8 The presence of this vasculitis could probably explain the clinical manifestation as an ulcerated and necrotic plaque that made us consider the diagnosis of pyoderma gangrenosum associated with our patient’s inflammatory gastrointestinal disease.

Initial Evaluation, Diagnosis, Staging, Treatment, and Follow-up of Patients with Primary Cutaneous Malignant Melanoma. Consensus Statement of the Network of Catalan and Balearic Melanoma Centers

The consensus statement on the management of primary cutaneous melanoma that we present here was based on selection, discussion, review, and comparison of recent literature (including national and international guidelines). The protocols for the diagnosis, treatment, and follow-up used in the hospital centers throughout Catalonia and the Balearic Isles belonging to the Network of Catalan and Balearic Melanoma Centers were also considered. The main objective of this statement was to present the overall management of melanoma patients typically used in our region at the present time. As such, the statement was not designed to be an obligatory protocol for health professionals caring for this group of patients, and neither can it nor should it be used for this purpose. Professionals reading the statement should not therefore consider it binding on their practice, and in no case can this text be used to guarantee or seek responsibility for a given medical opinion. The group of dermatologists who have signed this statement was created 3 years ago with the aim of making our authorities aware of the importance of this complex tumor, which, in comparison with other types of cancer, we believe does not receive sufficient attention in Spain. In addition, the regular meetings of the group have produced interesting proposals for collaboration in various epidemiological, clinical, and basic applied research projects on the subject of malignant melanoma in our society.

Linear lupus erythematosus following the lines of Blaschko

1 Jones R. Congenital pilonidal sinus of the nose. Aust N Z J Surg 1992; 62: 497. 2 Paulose KO, al Kalifa S, Raj SS, Saeed T. Pilonidal sinus of the nose. J Laryngol Otol 1989; 103: 1210–1213. 3 Schache DJ, Stebbing A, Rees M. Congenital pilonidal sinus of the nose. Aust N Z J Surg 1989; 59: 511–512. 4 Paller AS, Pensler JM, Tomita T. Nasal midline masses in infants and children. Dermoids, encephaloceles, and gliomas. Arch Dermatol 1991; 127: 362–366.

Melanoma Incidence Increases in the Elderly of Catalonia But Not in the Younger Population: Effect of Prevention or Consequence of Immigration?

The remodeling of Ca2+ signaling is a common finding in cancer pathophysiology serving the purpose of facilitating proliferation, migration, or survival of cancer cells subjected to stressful conditions. One particular facet of these adaptive changes is the alteration of Ca2+ fluxes through the plasma membrane, as described in several studies. In this review, we summarize the current knowledge about the expression of different Ca2+ channels in the plasma membrane of melanoma cells and its impact on oncogenic Ca2+ signaling. In the last few years, new molecular components of Ca2+ influx pathways have been identified in melanoma cells. In addition, new links between Ca2+ homeostasis and specific cell processes important in melanoma tumor progression have been unveiled. Thus, not only do Ca2+ channels appear to have a potential as prognostic markers, but their pharmacological blockade or gene silencing is hinted as interesting therapeutic approaches.All cases of MM diagnosed in 23 hospitals in Catalonia, from 2000 to 2007 were recorded and melanoma incidence calculated and adjusted for the European standard population via the direct method. The age standardised rate/100,000 inhabitants varied from 6.74 in 2000 to 8.64 in 2007 for all melanomas and from 4.79 to 5.80 for invasive MMs; the Breslow thickness was stable during the period. The increase in invasive melanoma incidence in the elderly was remarkable, the crude rate/100,000 inhabitants increasing from 11.04 (2000) to 15.49 (2007) in the 60-64 year population, while remaining more stable in the 30-34 year range, from 3.97 in 2000 to 4.55 in 2007, and with a tendency to decrease from 5.1 in 2000 to 2.5 in 2007 for the age range of 25-29 years. These lower age ranges are much more affected by immigration. Despite the large immigrant population (nearly one million immigrants arrived in Catalonia during the study period from countries with a low melanoma incidence), melanoma incidence in our region has risen considerably and this trend is likely to persist in the near future.

Carcinoma epidermoide sobre lupus vulgar

Resumen —La tuberculosis cutanea es una infeccion poco frecuente en Espana. Su forma clinica de presentacion mas comun es el lupus vulgar. Es conocido que pueden desarrollarse carcinomas epidermoides sobre ulceras y lesiones cutaneas inflamatorias de larga evolucion, entre ellas el lupus vulgar, sobre todo si han sido tratados previamente con radioterapia. Se presentan 2 casos de carcinoma epidermoide desarrollado sobre lesiones de lupus vulgar de mas de 40 anos de evolucion, localizadas en la region pectoral en el primer caso y en la cara en el segundo. Ninguno de ellos habia recibido ningun tratamiento antes del diagnostico del carcinoma epidermoide. La prueba de la tuberculina fue fuertemente positiva en ambos casos, pero solo en uno de ellos pudo aislarse Mycobacterium tuberculosis en el cultivo de las lesiones cutaneas. Cabe destacar que en nuestros casos la radioterapia no ha intervenido como factor inductor en el desarrollo de la neoplasia.

Granuloma anular macular. Estudio de cinco casos

Resumen —Introduccion. El granuloma anular es una dermatosis de gran variabilidad clinica. Una variante de reciente descripcion es la denominada macular. Se describen 5 casos de esta entidad y se efectua una revision bibliografica. Pacientes y metodo . Se incluyeron en el estudio 5 pacientes que desarrollaron lesiones cutaneas compatibles con un granuloma anular de la variedad macular. En todos ellos se realizo una biopsia «en sacabocados» y se revisaron las caracteristicas epidemiologicas, clinicas y anatomopatologicas. Resultados . Se trataba de 4 mujeres y un varon, con edades comprendidas entre los 58 y 66 anos. Todos ellos presentaban lesiones de meses de evolucion localizadas en los muslos, excepto en un caso, que presentaba las lesiones en los antebrazos. Se trataba de maculas redondeadas eritematoviolaceas o parduscas de 5 a 15 cm de diametro y sin cambios epidermicos. Tres pacientes tenian una unica lesion y los otros dos, varias de distribucion bilateral y simetrica. En el estudio histologico se observo en todos los casos un infiltrado linfohistiocitario intersticial con necrobiosis difusa y depositos de mucina. Conclusion . El granuloma anular macular se caracteriza, en la clinica, por la aparicion de lesiones maculares eritematosas de crecimiento centrifugo. En la microscopia, el infiltrado linfohistiocitario y la necrobiosis se disponen de una forma difusa, siguiendo un patron intersticial. El diagnostico de esta variante de granuloma anular es dificil si no existe un alto indice de sospecha por parte del clinico y del patologo.

Localized Xanthomas Associated with Primary Lymphedema

Abstract:  Cutaneous xanthomas arising in chronic lymphedema are rare. We present a case of verruciform xanthoma involving the left foot and toes of a 10‐year‐old boy who had developed a primary lymphedema (lymphedema praecox) in the left lower extremity. Laboratory studies demonstrated a normal lipid profile.

Cutaneous granulomatous panniculitis and sarcoidal granulomatous papular eruption in a patient with metastatic melanoma treated with a BRAF inhibitor

Dear Editor, Metastatic malignant melanoma is associated with poor outcomes. The fact that up to 80% of cases of primary melanoma harbor mutations in the BRAF gene has led to the development and recent approval of novel BRAF inhibitor drugs that, in comparison with dacarbazine, significantly improve progression-free survival. Because of limited experience with these drugs, a number of unusual side-effects have not yet been described. A 41-year-old Caucasian woman was included in a clinical trial of dabrafenib therapy (150 mg twice daily) because she had a stage IV melanoma, harboring a BRAF mutation, that failed to respond to radiotherapy and ipilimumab (CTLA-4 inhibitor). Eight months after inclusion, she presented with high fever, arthralgia, joint swelling and tender, painful, erythematous subcutaneous nodules located mainly in the upper and lower limbs (Fig. 1a). A punch biopsy revealed a lobular pattern of panniculitis with a predominantly lymphohistiocytic infiltrate forming non-necrotizing granulomas, a scarcity of neutrophils and no evidence of vasculitis (Fig. 1b). The lesions resolved completely in response to a tapered regime of corticosteroids. Five months later, the patient presented with multiple 1–1.5mm non-painful erythematous and violaceous papules and nodules, scattered bilaterally and symmetrically over the antecubital skinfolds and dorsal aspect of the hands (Fig. 1c). The patient had no systemic symptoms. Anatomopathological findings for a second punch biopsy revealed a full-thickness dermal infiltrate of numerous epithelioid histiocytes and giant multinucleated cells forming non-necrotizing granulomas. A surrounding crown of lymphocytes was present in all the granulomas, prominent in approximately half and less noticeable otherwise (Fig. 1d). No Melan-A-positive cells were found in relation to the inflammatory infiltrate in either of the biopsies, indicating an absence of cancer cells. The rash responded well to treatment with a topical steroid ointment. The main causes of non-necrotizing granulomas, namely, sarcoidosis and infections, were excluded and both the 8and 13-month reactions were attributed to treatment with dabrafenib. After 18 months, pulmonary progression of malignant melanoma was detected and dabrafenib therapy was suspended. The remaining granulomatous papules resolved completely within 2 weeks of dabrafenib suspension. Although the pathogenic mechanisms of granuloma formation have not yet been unraveled, our case reflects a previously unreported association between two infrequent granulomatous toxicities in the same patient, mild in nature and requiring no treatment discontinuation. Isolated noncaseating granulomas as reported by us were found in one of two cases of panniculitis described by Zimmer et al. for patients receiving BRAF inhibitor therapy. As for the diagnosis of granulomatous dermatitis, only two cases have been described to date, referring to three patients treated with BRAF inhibitors. In these cases, the rash consisted of multiple asymptomatic erythematous non-scaly and violaceous papules scattered bilaterally over the upper and lower (a)