Sergio Almenar

Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers.

Aims:  To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers.

Dermatofibrosarcoma protuberans: clinical, pathological, and genetic (COL1A1‐PDGFB ) study with therapeutic implications

Aims: To analyse the presence of collagen type I alpha 1–platelet‐derived growth factor beta (COL1A1–PDGFB) transcripts in 20 cases of dermatofibrosarcoma protuberans (DFSP) and to assess the relationship between COL1A1 breakpoints and clinical and histopathological variables.

Problems in Defining Melanoma Regression and Prognostic Implication

Between 10 % and 35 % of all melanomas show histological regression. That is, there is an area within the melanoma where the tumor retreats or disappears to be progressively replaced by fibrosis with presence of melanophages and variable degrees of inflammation, and neovascularization. Such regression is generally considered an indicator of poor prognosis in melanoma, although a number of studies contradict this affirmation. In this review, we summarize the leading articles about the influence of regression on melanoma prognosis. The results of these studies are very inconsistent, and so the prognostic significance of regression is somewhat controversial. We believe that some of these differences can be explained by differing criteria for regression and so we propose clear histological criteria to define early and sustained regression.

CKS1B amplification is a frequent event in cutaneous squamous cell carcinoma with aggressive clinical behaviour

Genetic mechanisms giving rise to the development of cutaneous squamous cell carcinoma (cSCC) are poorly understood and development of genomic high resolution techniques has led to a better knowledge of the genetic basis of several human cancers. In this study, 16 cSCC were analyzed using array comparative genomic hybridization (arrayCGH). The most common aberrations found were gains of 3q11q13, 1q21.3q25, 13q34, and 19p13, and losses of 1p36p31, 3p24p21, 10p15q22, and 13q11q21. We detected gains (3/16) and amplification (1/16) of the 1q21.1q21.3 region. A potential candidate gene in this region, CKS1B (1q21.2), was selected for validation in an independent cohort and correlations with clinicopathological features were carried out. CKS1B gene and protein status were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in a series of 53 cSCC, 22 actinic keratoses (AK), and 10 normal skin samples. cSCC presented a higher frequency of chromosome 1 polysomy than AK (70% vs. 46%, P = 0.047). Association between CKS1B protein overexpression and both polysomy and amplification was demonstrated in cSCC (P < 0.001). Regarding amplifications, 11 cSCC patients (21%) presented CKS1B gene amplification. Interestingly, 8/11 (73%) patients who showed a CKS1B amplification had presented metastatic spread (mcSCC). Differences between the presence of CKS1B amplification and the presence or absence of mcSCC were observed (mcSCC [8/14] vs. cSCC [3/39]) (P < 0.001). Several drugs targeting CKS1B have been reported and may be useful for treating patients with cSCC and CKS1B amplifications.

Congenital fibrosarcoma simulating congenital hemangioma.

purpura, abdominal pain, and vessel wall granulocytes on biopsy specimens (2).However, the diagnostic criteria of HSP were recently modified by the EULAR ⁄PReS (European League against Rheumatism and Paediatric Rheumatology European Society) (3). They highlighted the need to include ‘‘predominant IgAdeposition’’ in any biopsy specimen (skin or kidney), because IgA deposition has been regarded as highly characteristic of HSP. They also suggested the deletion of the age criterion (because HSP also occurs in adults), and the addition of arthritis and renal involvement to the group of criteria (because these are common presentations of HSP) (3). Using the new EULAR ⁄PReS criteria for HSP, Aalberse et al (4) recently reported that HSP (characterized by a leukocytoclastic vasculitis with IgA deposits) could be diagnosed in only 160 of the 179 patients with nonthrombocytopenic purpura if skin biopsy is used as a diagnostic tool for HSP. Therefore, they speculated that a number of patients classified as HSP might present in fact with hypersensitivity vasculitis (characterized by a leucocytoclastic vasculitis without IgA deposits), and concluded that the correct diagnosis using skin biopsy might be important at the initial stage of the disease, becauseHSPnephritis can lead to chronic renal failure at long-term even after apparent complete recovery, while hypersensitivity vasculitis has complete recovery (4–6). However, Davin et al (7) reported that the cutaneous punch biopsy should be performed at the edge of fresh lesions to maximize the chance of finding IgA deposits and to avoid the disappearance of IgA deposits by proteolytic effects in the center of necrotic lesions and by phagocytosis with time. Thus, these situations should be considered if skin biopsy in a patient withHSP shows no IgA deposition as in the Chan et al (1) patient. In conclusion, IgA deposition in biopsy specimens emerged as one of the important diagnostic cirteria for differentiating HSP from hypersensitivity vasculitis. Therefore, skin biopsy should be considered in patients presenting with nonthrombocytopenic purpura not only for correct diagnosis but also for prognostic evaluation.

Pleomorphic hyalinizing angiectatic tumor: a report of 3 new cases, 1 with sarcomatous myxofibrosarcoma component and another with unreported soft tissue palpebral location.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is an uncommon soft tissue tumor usually located in extremities or trunk. We report 3 new cases with histopathologic diagnosis of PHAT, one with recurrence and sarcomatous myxofibrosarcoma component and another with unreported soft tissue palpebral location. Clinical data, histopathology, immunohistochemistry, fluorescence in situ hybridization, and follow-up data are described. The histopathology showed a tumor with angiectatic blood vessel proliferation and perivascular hyaline material associated with focal pleomorphic cells. The recurrent tumor revealed a histopathologic pattern corresponding to a myxofibrosarcoma. Vimentin and CD99 were positive in tumor cells and CD34 was strongly positive in the tumor cells from the recurrence. Ki-67 was poor positive but with increased positivity in the recurrence. The positivity of p53 and chromosome 22 polysomy were detected in the recurrence. At present, the 3 patients are free of disease and no metastases have been detected. Indeed, the possibility that PHAT may represent a histopathologic pattern and not a true neoplastic entity with specific genetic alterations cannot be excluded at present, and further studies are required.

Pápulas linfangiomatosas benignas secundarias al tratamiento de cáncer de mama

Resumen —Los linfangiomas son tumores poco frecuentes que normalmente aparecen en el nacimiento y estan formados por vasos linfaticos dilatados que pueden llegar hasta el tejido celular subcutaneo. Se han descrito casos de linfangiomas adquiridos secundarios a numerosas etiologias. Las papulas linfangiomatosas benignas secundarias a radioterapia constituyen una entidad, con unas particularidades especificas, dentro de las lesiones linfangiomatosas adquiridas. Se presenta el caso de una mujer que habia sido tratada con radioterapia y linfadenectomia axilar por un carcinoma lobulillar infiltrante en la mama izquierda y que 6 anos despues presento multiples papulas en la misma mama. La biopsia practicada mostro una proliferacion de vasos linfaticos ligeramente dilatados en la dermis superior. Estas papulas linfangiomatosas de la piel parecen ser el resultado del dano producido tanto por la radioterapia como por la linfadenectomia practicadas para el tratamiento del cancer de mama.

Uncommon vascular tumor of the ovary. Primary ovarian epithelioid hemangioendothelioma or vascular sarcomatous transformation in ovarian germ cell tumor

Epithelioid hemangioendothelioma (EHE) is an unusual vascular tumor, which usually occurs in the soft tissue, liver, breast, lung and bone. We submit a case of EHE, a tumor never before reported in the ovary. A 20-year-old woman was admitted with a medical history of unilateral ovarian tumor. The right ovary was totally removed and histologically, the tumor was composed of epithelioid cells with eosinophilic cytoplasm and prominent intracytoplasmic vacuoles associated with myxohyaline matrix. No morphologic evidence of germ cell tumor was observed. Immunohistochemically, the tumor cells were positive for CD31 and CD34. However, all germ cell tumor markers were negative. The final diagnosis was EHE of the ovarian gland and sarcomatous transformation in ovarian germ cell tumor was excluded after extensive histopathological and immunohistochemical study. EHE is an uncommon vascular tumor, which is rarely seen in female genital tract and this is the first report of EHE in ovarian gland. Final diagnosis depends on histopathological and immunohistochemical features.

Linfadenectomía selectiva (ganglio centinela) en el melanoma. Experiencia con 55 casos

Resumen Introduccion El ganglio centinela (NC) es la primera estacion de drenaje linfatico de una lesion primitiva y, por tanto, con la maxima probabilidad de albergar una metastasis. El objetivo de este trabajo es ahorrar la morbilidad y coste de linfadenectomias innecesarias en pacientes con melanoma clinicamente no diseminado (75-89%) y mejorar la estadificacion por localizacion del NC fuera del area de drenaje habitual. Pacientes y metodos Se han estudiado 55 pacientes con diagnostico de melanoma de riesgo intermedio (Breslow 0,75-4 mm). Para localizar las areas de drenaje linfatico, a todos los pacientes se les realizo una linfogammagrafia mediante la inyeccion intradermica subcicatrizal de sulfuro coloidal-99mTc antes de la intervencion. Veinte minutos antes de esta se inyecto igualmente 1 cm3 de azul de isosulfan (Lymphazurin®). La busqueda intraoperatoria del NC se realizo en 9 pacientes con el colorante exclusivamente y en 46 con la tecnica combinada del colorante y una sonda detectora de rayos gamma (Navigator®). Resultados El NC se localizo en 53 pacientes (96%), estaba infiltrado en siete de ellos (13%) y era el unico ganglio afectado en cinco (71,5%). Conclusiones La linfadenectomia selectiva en el melanoma es una tecnica de escasa morbilidad, que puede evitar linfadenectomias completas innecesarias en pacientes con melanoma de riesgo intermedio.