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Gastro-Intestinal Stromal Tumours (GISTs) are a kind of neoplasm whose diagnosis in common clinical practice just started in the current century, implying difficulties for proper registration. Staff from the Cancer Registry of Murcia, in southeastern Spain, were commissioned by the EU Joint Action on Rare Cancers into a pilot study addressing GIST registration that also yielded a population-based depiction of GISTs in the region, including survival figures. We examined reports from 2001 to 2015 from hospitals as well as cases already present in the registry. The variables collected were sex, date of diagnosis, age, vital status, primary location, presence of metastases, and risk level according to Joensuu’s Classification. In total, 171 cases were found, 54.4% occurred in males, and the mean age value was 65.0 years. The most affected organ was the stomach, with 52.6% of cases. Risk level was determined as “High” for 45.0%, with an increment of lower levels in recent years. Incidence for the year 2015 doubled that of 2001. Overall, the 5-year net survival estimation was 77.0%. The rising incidence magnitude is consistent with trends in other European countries. Survival evolution lacked statistical significance. A more interventional approach in clinical management could explain the increase in the proportion of “Low Risk GISTs” and the first occurrence of “Very Low Risk” in recent years.

The anatomical location of cutaneous melanoma is a relevant independent prognostic factor in melanoma. The aim of the study is to know the prognosis of lower limb cutaneous melanoma related to their location within the limb, regardless of the histological type, and if there are any other influencing variables. A real-world data observational study was developed. The lesions were divided depending on the location of the melanoma (thigh, leg and foot). Bivariate and multivariate analysis were performed, and melanoma-specific survival and disease-free survival rates were calculated. When these analysis were done, the results showed that, in melanomas of the lower limb, location on the foot presented a lower melanoma-specific survival rate compared to more proximal locations, and only the anatomical location presents statistical significance to discriminate cases with a higher mortality risk and a lower disease-free survival rate among distal melanomas (mainly on the foot). In conclusion, this study confirms that a more distal location of lower limb cutaneous melanoma is a relevant prognostic factor.Trial registration number NCT04625491 retrospectively registered.

Our main objective was to compare liver transplant (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors aged >70 years and up to 80 years. All DCD-LTs performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD-LT immediately after each DCD-LT. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut-off point at 70 years. Survival results for LT with DCD and super rapid recovery were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the cost of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor.

Recently, the quantification of mitoses in cutaneous melanoma has been discharged from the main prognostic variables of the TNM classification. To investigate the prognostic value of the presence of mitoses in primary cutaneous melanoma and to establish the number of mitoses per mm2 that may have prognostic significance. A retrospective observational study was performed on 141 patients treated for cutaneous melanoma, who were assessed by the same pathologist, and who had a minimum follow-up of 2 years. Clinical, epidemiological, histopathological and follow-up variables were gathered and compared with the number of mitoses to distinguish the significance of differences by means of univariate, multivariate, and survival analyses. The cut-off level related to a better sensitivity and specificity was 1.50 mitoses per mm2. The presence of two or more mitoses/mm2 showed a better relationship with prognostic variables and both the overall and disease-free survival than the presence of 1 or more mitoses/mm2. This happens especially in melanomas thicker than 0.8 mm and it could affect the staging in cases with Breslow between 1 and 2 mm. A mitotic rate of two or more mitoses per mm2 in cutaneous melanoma should be considered as a more accurate prognostic factor than one or more mitoses per mm2, particularly in tumors equal or greater than 0.8 mm in thickness.

Background Donation after circulatory death (DCD) is related to a warm ischemia time and more complications compared with traditional donors (donation after brain death [DBD]). Methods This study included biopsy samples retrospectively collected from November 2014 to December 2018 to compare histologic and biological markers of DCD and DBD liver grafts. The analysis includes marker of early apoptosis (p21), senescence (telomerase reverse transcriptase [TERT]), cell damage (caspase-3 active), endothelial damage (vascular endothelial growth factor), stem cell (CD90), hypoxia (HIF1A), inflammatory activation (COX-2), and cross-organ allograft rejection (CD44). A propensity score matching (PSM) was used to match patients receiving DCD livers to those receiving DBD livers. We analyzed the immunohistochemical initial liver damage–related warm ischemia time. Results Positive staining expression of liver damage biomarkers (COX-2, CD44, TERT, HIF1A, and CD90) was found, but no significant differences were found between DCD and DBD and with ischemic cholangiopathy. After PSM, there was a significant relationship between CD90 and male donors (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.07-0.91), TERT with donor sodium (OR, 1.11; 95% CI, 1.02-1.2), HIF1A with steatosis (OR, 0.33; 95% CI, 0.13-0.83), and CD44 with donor vasoactive drugs (OR, 0.36; 95% CI, 0.13-1) and glutamic oxaloacetic transaminase 1 week increase (OR, 1.01; 95% CI, 1-1.03). Conclusions DCD immunohistochemical initial liver damage was found to behave similarly to DBD. The increase in complications and cholangiopathy associated with warm ischemia could be related to a different later phenomenon.

Liver transplantation is the only curative treatment option in patients diagnosed with end-stage liver disease. The low availability of organs demands an accurate selection procedure based on histological analysis, in order to evaluate the allograft. This assessment, traditionally carried out by a pathologist, is not exempt from subjectivity. In this sense, new tools based on machine learning and artificial vision are continuously being developed for the analysis of medical images of different typologies. Accordingly, in this work, we develop a computer vision-based application for the fast and automatic objective quantification of macrovesicular steatosis in histopathological liver section slides stained with Sudan stain. For this purpose, digital microscopy images were used to obtain thousands of feature vectors based on the RGB and CIE L*a*b* pixel values. These vectors, under a supervised process, were labelled as fat vacuole or non-fat vacuole, and a set of classifiers based on different algorithms were trained, accordingly. The results obtained showed an overall high accuracy for all classifiers (&gt, 0.99) with a sensitivity between 0.844 and 1, together with a specificity &gt, 0.99. In relation to their speed when classifying images, KNN and Naïve Bayes were substantially faster than other classification algorithms. Sudan stain is a convenient technique for evaluating ME in pre-transplant liver biopsies, providing reliable contrast and facilitating fast and accurate quantification through the machine learning algorithms tested.

Background The application of immune-based therapies has revolutionized cancer treatment. Yet how the immune system responds to phenotypically heterogeneous populations within tumors is poorly understood. In melanoma, one of the major determinants of phenotypic identity is the lineage survival oncogene MITF that integrates diverse microenvironmental cues to coordinate melanoma survival, senescence bypass, differentiation, proliferation, invasion, metabolism and DNA damage repair. Whether MITF also controls the immune response is unknown. Methods By using several mouse melanoma models, we examine the potential role of MITF to modulate the anti-melanoma immune response. ChIP-seq data analysis, ChIP-qPCR, CRISPR-Cas9 genome editing, and luciferase reporter assays were utilized to identify ADAM10 as a direct MITF target gene. Western blotting, confocal microscopy, flow cytometry, and natural killer (NK) cytotoxicity assays were used to determine the underlying mechanisms by which MITF-driven phenotypic plasticity modulates melanoma NK cell-mediated killing. Results Here we show that MITF regulates expression of ADAM10, a key sheddase that cleaves the MICA/B family of ligands for NK cells. By controlling melanoma recognition by NK-cells MITF thereby controls the melanoma response to the innate immune system. Consequently, while melanoma MITFLow cells can be effectively suppressed by NK-mediated killing, MITF-expressing cells escape NK cell surveillance. Conclusion Our results reveal how modulation of MITF activity can impact the anti-melanoma immune response with implications for the application of anti-melanoma immunotherapies.

Small cell carcinoma of ovary-hypercalcemic type is an undifferentiated carcinoma. We describe two cases in women aged 32 and 29. Both presented with large masses and complete surgical extirpation was impossible. Histologically, the images were similar, with diffuse cell proliferation, accompanied by the presence of follicle-like spaces. In both cases it was necessary to make a differential diagnosis with entities such as adult or juvenile granulosa cell tumour, small cell carcinoma of pulmonary type, dysgerminoma and even peripheral neuroectodermal tumour. The absence of SMARCA4/BRG1 immunostaining proved very useful in the diagnosis of hypercalcemic small cell ovarian carcinoma.

Resumen Introduccion y objetivo La tecnica de la biopsia selectiva del ganglio centinela (BSGC) es la mejor herramienta para la estadificacion ganglionar en el melanoma, permitiendo la realizacion de una linfadenectomia selectiva, es decir, reservada solo a aquellos pacientes que muestran el GC positivo para metastasis. Nuestro objetivo fue evaluar el coste economico de la tecnica de la BSGC, ya que se ha convertido en el procedimiento recomendado como estandar en la atencion al paciente con melanoma, y es necesaria para la inclusion de los pacientes en los ensayos clinicos. Existe ademas escasa bibliografia en nuestro medio sobre su relevancia economica. Metodo De forma prospectiva se recogieron 100 pacientes a los que se realizo la tecnica entre los anos 2007-2010 con un procesamiento histologico transhiliar bivalvo multisecciones. Realizamos un calculo aproximado del precio de la tecnica utilizando las tarifas de precios oficiales de la Region de Murcia. Resultados El porcentaje de positividad de nuestra serie fue del 20%, con un numero medio de ganglios de 1,96 y un 44% de melanomas delgados. El precio total de la tecnica es de 9.486,57-10.471,29 euros, siendo una parte muy importante de la misma atribuible al procesamiento histopatologico (5.769,36 euros). Discusion La tecnica de la BSGC tiene un precio muy considerable, aunque en consonancia con otras referencias americanas previamente descritas. La optimizacion de la tecnica vendra dada en funcion de la seleccion cada vez mas adecuada de los pacientes que deben someterse a ella, y a la estandarizacion de un modelo histopatologico sensible en la deteccion, pero a la vez sencillo en el procesamiento.

Introduction and objective Sentinel lymph node biopsy (SLNB) is the most useful tool for node staging in melanoma. SLNB facilitates selective dissection of lymph nodes, that is, the performance of lymphadenectomy only in patients with sentinel nodes positive for metastasis. Our aim was to assess the cost of SLNB, given that this procedure has become the standard of care for patients with melanoma and must be performed whenever patients are to be enrolled in clinical trials. Furthermore, the literature on the economic impact of SLNB in Spain is scarce. Method From 2007 to 2010, we prospectively collected data for 100 patients undergoing SLNB followed by transhilar bivalving and multiple-level sectioning of the node for histology. Our estimation of the cost of the technique was based on official pricing and fee schedules for the Spanish region of Murcia. Results The rate of node-positive cases in our series was 20%, and the mean number of nodes biopsied was 1.96; 44% of the patients in the series had thin melanomas. The total cost was estimated at between €9486.57 and €10 471.29. Histopathology accounted for a considerable portion of the cost (€5769.36). Discussion The cost of SLNB is high, consistent with amounts described for a US setting. Optimal use of SLNB will come with the increasingly appropriate selection of patients who should undergo the procedure and the standardization of a protocol for histopathologic evaluation that is both sensitive and easy to perform.

Resumen Introduccion La mayoria de los estudios pronosticos en el carcinoma diferenciado incluyen un alto numero de carcinomas papilares y pocos foliculares, por lo que no todas sus conclusiones son aplicables a este ultimo. Objetivo Analizar los factores pronosticos, tanto clinicos, histologicos como terapeuticos, del carcinoma folicular de tiroides. Pacientes y metodos Criterios de seleccion: pacientes con el diagnostico histologico de carcinoma folicular, sin enfermedad diseminada al diagnostico, con cirugia potencialmente curativa, y con un seguimiento minimo de 5 anos. Variables de estudio: se considero recidiva del tumor: a) lesiones tumorales con citologia sospechosa de malignidad; y/o b) el aumento de los niveles de tiroglobulina mayor de 2 ng/ml en pacientes con tiroidectomia total. Para valorar los factores pronosticos se analizan variables clinicas, terapeuticas e histologicas. Estadistica: curvas de supervivencia aplicando el test de Breslow. Modelo de regresion de Cox. Resultados Se han presentado 25 recidivas (38%) en los 66 pacientes estudiados. La mayoria eran recidivas analiticas (n = 20) que fueron tratadas con I-131. En los casos restantes (n = 5) se realizo exeresis de la lesion localizada y posteriormente se aplico I131. Actualmente, dos casos (3%) presentan metastasis a distancia, y otros dos (3%) han sido exitus por evolucion de la enfermedad. El tiempo medio libre de enfermedad fue de 154 ± 14 meses, siendo las tasas de pacientes libres de enfermedad a los 5, 10, 15 y 20 anos del 71, 58, 58 y 58% respectivamente. Los factores que influyen en la recidiva son: 1) la edad (p = 0,0035); 2) el sexo (p = 0,0114); 3) la clinica local (p = 0,0026); 4) la infiltracion de estructuras vecinas (p = 0,0000); 5) el tipo de carcinoma (p = 0,0000); 6) el tamano (p = 0,0162); 7) la invasion vascular (p = 0,0085); y 8) las adenopatias (p = 0,046). En el estudio multivariante persisten la clinica local (p = 0,018) y la infiltracion de estructuras (p = 0,045). Conclusiones En el carcinoma folicular los principales factores predictivos son la presencia de clinica local al diagnostico y la infiltracion de estructuras vecinas.

Introduction Most prognostic studies in differentiated carcinoma have included a high number of papillary carcinomas and few follicular carcinomas, and not all of their conclusions therefore apply to the latter. Objective To analyze the prognostic factors of follicular thyroid carcinoma. Patients and methods Selection criteria: Patients with histological diagnosis of follicular carcinoma who had undergone potentially curative surgery, had no disseminated disease at diagnosis, and had been followed up for at least 5 years. Study variables: Tumor recurrence was defined as: (1) tumor lesions with cytological analysis suggesting malignancy and/or (2) patients with total thyroidectomy with thyroglobulin levels >2 ng/mL. Clinical, therapeutic, and histological parameters were analyzed to assess prognostic factors. Results Recurrence was found in 25 (38%) of the 66 study patients during a follow-up period of 99 ± 38 months. Most patients with recurrence (n = 20) had increased Tg levels without anatomical location, and were initially treated with radioactive I131. In the remaining five cases, surgical excision of the lesion was performed, and three patients required surgery during the follow-up period. Two patients died due to the disease (3%), and two other patients (3%) currently have distant metastases. Mean disease-free interval was 154 ± 14 months, and rates of disease-free patients at 5, 10, 15, and 20 years were 71, 58, 58, and 58% respectively. Clinical factors influencing recurrence included (1) age ( p = 0.0035), (2) sex ( p = 0.0114), and (3) cervical pain ( p = 0.0026). Histological/surgical factors associated with recurrence included (1) infiltration into neighboring structures ( p = 0.0000), (2) type of carcinoma ( p = 0.0000), (3) size ( p = 0.0162), (4) vascular invasion ( p = 0.0085), and (5) adenopathies ( p = 0.046). In the multivariate study, cervical pain ( p = 0.018) and extrathyroid invasion ( p = 0.045) continued to be significant factors. Conclusions In follicular carcinoma, rates of disease-free patients are 71% at 5 years and 58% at 10 years, and the main predictive factors are presence of local clinical symptoms and infiltration into neighboring structures.

This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical–pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained.

Morbid obese patients have a high rate of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NASH is related to the progression and poor evolution of chronic hepatopathy in NAFLD, so that its detection makes it possible to identify the subjects who are most at risk in order to prioritize treatment. The ELF test (Enhanced Liver Fibrosis test; Siemens Diagnostics, NY, USA) has been assessed for its capacity to detect fibrosis in patients with NAFLD, but its capacity for diagnosing NASH has not been checked. Our objective is to determine the utility of the ELF test for detecting NASH in morbid obese patients with suspected NAFLD. ELF values were determined in a cohort of obese patients who underwent bariatric surgery with suspected NAFLD. Liver biopsy was used as the reference standard. The values of ELF were significantly higher in patients with NASH (p = 0.002) and in those who presented with metabolic syndrome (p = 0.047). An ELF cut-off point of 8.72 allows the detection of patients with NASH with a sensitivity of 71.4% and a specificity of 74.1% (AUC = 0.742, p = 0.002). The ELF test is efficient for the identification of obese patients with NAFLD and early signs of steatohepatitis and fibrosis.

Small cell carcinoma of ovary-hypercalcemic type is an undifferentiated carcinoma. We describe two cases in women aged 32 and 29. Both presented with large masses and complete surgical extirpation was impossible. Histologically, the images were similar, with diffuse cell proliferation, accompanied by the presence of follicle-like spaces. In both cases it was necessary to make a differential diagnosis with entities such as adult or juvenile granulosa cell tumour, small cell carcinoma of pulmonary type, dysgerminoma and even peripheral neuroectodermal tumour. The absence of SMARCA4/BRG1 immunostaining proved very useful in the diagnosis of hypercalcemic small cell ovarian carcinoma.

Resumen Objetivo Presentar un metodo de analisis grafico de costes ocasionados por los falsos positivos (FP) y falsos negativos (FN) de una prueba diagnostica. Material y metodos Construimos una funcion de costes ligada a la sensibilidad (S) y a la especificidad (E) de la prueba diagnostica. A partir de esta funcion obtenemos lineas de isocoste, cuya pendiente es la relacion coste FP/coste FN. Representamos cada prueba diagnostica en el espacio ROC como el punto (1-E, S). Resultados Las lineas de isocoste permiten visualizar si el gasto asociado a FP y FN de una nueva prueba diagnostica es menor o igual que el de la antigua. Conclusiones El analisis grafico de la funcion de costes de una prueba diagnostica ayuda a decidir su introduccion o su rechazo.

Introduction Keratoacanthoma is a fast-growing crateriform skin tumor. Approximately 25% of such tumors undergo malignant transformation and develop areas of squamous cell carcinoma (SCC). The presence of laminin-322 has been associated with progression to invasive forms of SCC. The aim of this study was to determine whether or not immunohistochemical staining for laminin-322 would be of value in distinguishing between keratoacanthomas, keratoacanthomas with areas of squamous cell carcinoma, and SCCs. Material and methods Seventy-four lesions were selected from the pathology archives of our hospital and divided into 4 groups: 20 keratoacanthomas without SCC, 20 keratoacanthomas with areas of squamous cell carcinoma, 20 invasive SCCs (8 with crateriform morphology) unrelated to keratoacanthoma, and 14 problem lesions (keratoacanthomas with areas suggestive of SCC). All 74 lesions were stained for laminin-322. Results Laminin-322 staining was strongly positive both in areas of SCC in keratoacanthomas with malignant transformation and in invasive SCCs (mostly at the invasive front of the SCC). However, in benign keratoacanthomas, it was only weakly positive and furthermore it was confined to isolated cells or small groups of cells. The 14 problem lesions were reexamined after laminin-322 staining and 8 were diagnosed as keratoacanthomas with incipient SCC and 6 as keratoacanthomas without SCC. Conclusions Laminin-322 staining is different in keratoacanthomas and SCCs and would thus be a useful test for differentiating keratoacanthomas from both invasive SCCs and keratoacanthomas with areas of squamous cell carcinoma. It would also be of value in diagnosing keratoacanthomas with areas suggestive of SCC or with incipient SCC.

Resumen Introduccion El queratoacantoma (QA) es un tumor cutaneo crateriforme, de crecimiento rapido; aproximadamente el 25% de los QA presentan transformacion maligna (QAm), observandose areas de carcinoma epidermoide (CE). La laminina-332 se ha relacionado con progresion a fases invasoras en diversos CE. El objetivo de este estudio es evaluar si la tincion con laminina-332 es util para distinguir QA, QAm y CE. Material y metodos Seleccionamos 74 casos del archivo de Anatomia Patologica. Se analizaron 4 grupos: 20 QA sin CE, 20 QAm con areas evidentes de CE, 20 CE invasores sin relacion con QA (8 con morfologia crateriforme) y 14 casos «problema» (QA con «dudosas» areas de CE). Posteriormente se realizo tincion inmunohistoquimica para laminina-332 a todas estas lesiones. Resultados En las areas de CE asociado a QAm y en los CE invasores, la tincion con laminina fue positiva de forma intensa, habitualmente en el frente invasor del CE, a diferencia de los QA, en que la tincion fue positiva solo de forma debil y focal, en celulas aisladas o en pequenos «grupos» celulares. Los casos «problema» se reexaminaron tras valorar la tincion con laminina-332 (8 se diagnosticaron de QA con CE incipiente, 6 de QA sin CE). Conclusiones La tincion con laminina-332 es diferente en los QA respecto a los CE, por lo que ayudaria a diferenciar los QA de los CE invasores y de las areas de CE en QAm, asi como en el diagnostico de QA con «dudosas» areas de CE y QA con CE incipientes.

Background and objectives Positive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or alfa subtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC. Material and methods Paraffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR). Results In the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages. Conclusions According to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease.

Introduction Solar elastosis, or basophilic degeneration of collagen, may be a histologic sign of chronic sun damage. Material and methods We reviewed 222 cases of squamous cell carcinoma (SCC) to identify the presence of solar elastosis and its possible invasion of the upper, middle, or deep reticular dermis. We also analyzed clinical variables such as SCC location, location in exposed areas of the skin, age, sex, and immunosuppression. Patients included had undergone surgical excision of an SCC. Results Severe solar elastosis was found in most cases (182 patients, 82%): 87 extended to the middle reticular dermis and 95 had reached the deep reticular dermis. Only 6 (2.7%) patients had no solar elastosis. In some cases elastosis was so severe that it had affected the subcutaneous cellular tissue or venous or arteriolar walls. Deeper solar elastosis was significantly associated with older age and female sex. Conclusions Solar elastosis was found in most patients with SCC and seems to indicate chronic severe solar damage. Exposure to ultraviolet radiation would be the main cause of SCC, although other factors might also be implicated, particularly in patients who did not have severe solar elastosis. Systemic or localized immunosuppression was associated with nearly all the SCC cases studied, consistent with the marked immunosuppressant effects of sun exposure, the aging process, or both.

Malignant nodular hidradenoma or hidradenocarcinoma is a rare, malignant tumour of sweat glands that usually arises de novo, although a few cases originating in a nodular hidradenoma have been reported. They are very aggressive neoplasms that recur locally and frequently metastasize to the lymph nodes. The treatment of choice is surgical excision with wide margins, followed by chemotherapy and/or radiotherapy when metastases have occurred. Recently, sentinel lymph node sampling and treatment with Trastuzumab have been proposed for cases with overexpression of Her-2/neu. A case of hidradenocarcinoma arising in a nodular hidradenoma of the breast skin of a 55 year old woman is presented. The tumour was surgically removed with a wide excision and the patient treated with postoperative radiotherapy. She is alive and well without evidence of metastatic disease one year later.

Resumen Introduccion Se han publicado pocos casos de carcinoma espinocelular (CE) de celulas claras, aunque creemos que es frecuente observar celulas claras en los CE. Material y metodos Hemos estudiado 249 CE. Analizamos distintas variables clinicas e histologicas. Hemos usado diversas tecnicas de inmunohistoquimica (metodo de inmunoperoxidasa) para valorar si existia diferenciacion anexial. Resultados Observamos 96 CE con mas de un 25 % de celulas claras. Existe mas cantidad de celulas claras en los CE desarrollados o «no incipientes» y en los derivados de enfermedad de Bowen (EB). Describimos dos patrones histologicos: a) celulas claras alrededor de las perlas corneas del CE, que se asocia a la existencia de queratosis actinica como lesion previa y a signos indirectos de virus del papiloma humano (VPH) en infundibulos pilosos, y b) celulas claras que simulan diferenciacion anexial, relacionado con EB como lesion previa. Tambien hemos encontrado 19 carcinomas con verdadera diferenciacion anexial. Conclusiones Es frecuente observar celulas claras en los CE, aunque solo algunos presentan una gran cantidad. El desarrollo de celulas claras en los CE seria progresivo y solo apareceria en los CE mas desarrollados. Cuando se observan celulas claras en los CE, se tiende a pensar que existe diferenciacion anexial, sin embargo, en la mayoria de casos se trataria solo de EB de celulas claras que infiltra estructuras anexiales normales. En un pequeno porcentaje de casos (7,6 % en nuestro estudio) si existe verdadera diferenciacion anexial. Por otra parte, el patron histologico descrito como celulas claras alrededor de perlas corneas practicamente nos descartaria dicha diferenciacion.

Resumen Los Diagnosticos Criticos en Anatomia Patologica han sido recientemente introducidos y son equiparables a los establecidos a nivel clinico, de forma que, situaciones clinicas concretas pueden precisar de un diagnostico rapido (ya sea por parte del patologo o del citopatologo) y del contacto urgente con el clinico con el fin de facilitar una intervencion clinica urgente o instaurar un tratamiento determinado, de los que el paciente se beneficiaria. Basandonos en la experiencia diaria, presentamos diferentes situaciones clinico- patologicas en las que el diagnostico es critico.

Lymph node involvement is a very important prognostic factor for cutaneous melanoma. In this paper we try to validate a nomogram that was created at the Memorial Sloan–Kettering Cancer Center, New York, to predict the probability of metastases in the sentinel nodes of patients with cutaneous melanoma. Values of the following variables were collected in 218 patients with cutaneous melanoma and sentinel lymph node: age, thickness, level of Clark, location of the lesion, and ulceration or not, and the nomogram was applied to assess the probability of sentinel node involvement in each patient. The discrimination of the nomogram was assessed by calculating the area under the receiver operating characteristics (ROC) curve, and to assess the accuracy of the nomogram actual probabilities were plotted against the nomogram-calculated predicted probability. The overall predictive accuracy of the nomogram was 0.869 (95% confidence interval 0.813–0.925). Mean predicted probability of sentinel node metastasis was highly correlated to the observed risk (r = 0.953; P

Introduction Epidermodysplasia verruciformis (EV) is associated with greater susceptibility to infection by certain oncogenic subtypes of human papillomavirus (HPV). Among other histologic findings, large, clear, oval or rounded cells (EV cells) are observed in the granular layer in EV, and some authors consider these cells to be markers of immunosuppression. Material and Methods We analyzed 229 squamous cell carcinomas (SCC) to determine whether EV cells were present and to assess whether their presence was associated either with localized or cutaneous immunosuppression (tumors with signs of severe chronic actinic damage or severe stasis dermatitis) or with systemic immunosuppression (immunocompromised or elderly patients). Results We observed EV cells in 33 SCC. No statistically significant relationship was observed between the presence of EV cells and immunosuppression. We performed polymerase chain reaction in 8 lesions, but the results were not informative as the DNA was denatured. Conclusions We found no relationship between the presence of EV cells and localized or systemic immunosuppression, possibly because the sample was inadequate (almost all SCC studied were associated with signs of immunosuppression, irrespective of the presence or absence of EV cells). Further studies will be required to compare lesions associated with immunosuppression with those in which immunosuppression is absent. The presence of EV cells may be the result of cytopathic effects of certain HPV subtypes, such as HPV 5 or 8, but this will need to be demonstrated using techniques such as polymerase chain reaction.

The involvement of the human leukocyte antigen (HLA) in liver graft acceptance is controversial, but the frequency of acute rejection (AR) remains high in spite of the use of the modern immunosuppressive agents. The present study was aimed at determining whether an association exists between liver recipient HLA-C polymorphism and AR development that could influence graft acceptance. Four hundred and forty-six liver recipients and 473 controls were studied within the framework of a collaborative study carried out by the Spanish Transplant Immunotolerance Group (RED-GIT). HLA-A and -B were typed by the standard microlymphocytotoxicity technique, and HLA-C by polymerase chain reaction–sequence-specific oligonucleotide probes (PCR-SSOP). A statistically significant decrease in the HLA-Cw*07 allele frequency was found in liver recipients suffering AR episodes compared to those without AR (NAR). Studies regarding the possible influence of the Asn 80 and Lys 80 epitopes showed that the Asn 80 epitope also could be associated with AR. However, further analysis considering Asn 80 alleles others than HLA-Cw*07, confirmed that the apparent protective effect of the Asn 80 epitope was actually from the HLA-Cw*07 allele. In conclusion, the HLA-Cw*07 allele carried by the liver recipient is negatively associated with AR development, and could be considered a predictive factor for liver graft acceptance.

During the course of cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, and this plasticity is enabled by underlying shifts in epigenetic regulation. Our results identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. The modulation of SET9 expression in breast cancer cells revealed a connection with E2F1 and the silencing of SET9 was sufficient to complete an epigenetic program that favored epithelial-mesenchymal transition and the generation of cancer stem cells, indicating that SET9 plays a role in modulating breast cancer metastasis. SET9 expression levels were significantly higher in samples from patients with pathological complete remission than in samples from patients with disease recurrence, which indicates that SET9 acts as a tumor suppressor in breast cancer and that its expression may serve as a prognostic marker for malignancy.

Resumen Introduccion La localizacion anatomica del melanoma cutaneo se ha considerado como un factor pronostico independiente. En este trabajo se trata de comprobar si la localizacion del tumor primario influye en la deteccion del ganglio centinela en el melanoma cutaneo. Pacientes y metodo Se ha estudiado a 212 pacientes con melanoma cutaneo primario (96 en los miembros, 89 en el tronco y 27 en la cabeza o el cuello) en los que se realizo la biopsia del ganglio centinela. Se estudio la adecuada localizacion gammagrafica y quirurgica y se compararon las variables epidemiologicas e histopatologicas, el numero de drenajes por lesion y de ganglios centinela por drenaje y la positividad del estudio de los ganglios. Para los drenajes procedentes de los tumores de la cabeza y el cuello se estudio el drenaje hacia territorio de la glandula salival como variable relacionada con la localizacion del ganglio centinela. Resultados La localizacion fue peor para los tumors de cabeza y cuello (88,8%), tanto gammagrafica (p Conclusiones Los melanomas cutaneos localizados en la cabeza y el cuello presentaron mas fallos en la identificacion del ganglio centinela. La localizacion del ganglio centinela adyacente a una glandula salival es un factor que influye en su adecuada deteccion. Los melanomas cutaneos del tronco presentan un mayor numero de drenajes por lesion que los localizados en las extremidades o en la cabeza y el cuello.

Background Sentinel lymph node biopsy is an appropriate method to assess lymphatic involvement in cutaneous melanoma. We collated clinical and histo-pathological parameters of primary tumours to assess their predictive value of sentinel lymph node involvement.

Epithelioid-cell blue nevus is an unusual cytologic variant of blue nevus that has been recently described mostly in patients with Carney complex, although the lesion may also appear in patients with no evidence of Carney complex. This variant of blue nevus is composed of melanin laden large polygonal epithelioid melanocytes situated within the dermis. The neoplastic cells show no maturation with progressive descent and, in contrast with the usual stromal changes in blue nevi, epithelioid-cell blue nevus exhibits no dermal fibrosis. This report describes a congenital giant melanocytic nevus with pigmented epithelioid cells located on the back of a 2-year-old male. The lesion was present at birth and the patient had no evidence of Carney complex. Histopathologically, the lesion consisted of a large and entirely intradermal melanocytic nevus composed of heavily pigmented epithelioid melanocytes involving the full-thickness of dermis, but extending also to the subcutaneous fat and underlying soft tissues. Immunohistochemically, epithelioid neoplastic melanocytes expressed immunoreactivity for S-100 protein, HMB-45, Melan-A, NK1C3, and microphthalmia transcription factor (MiTF) antibodies. MIB-1 cellular proliferation marker was expressed in the nuclei of only a few scattered epithelioid melanocytes. This report demonstrates that epithelioid-cell blue nevus is a distinctive histopathologic variant of blue nevus that may also appear as a giant congenital melanocytic nevus.

A 54-year-old patient was seen for a tumor on the upper lip present for 4 months and clinically compatible with a basal cell carcinoma (Figure 1A). This was surgically removed. Histopathology revealed a clearly defined tumor proliferation composed of lobed formations of cells with clear cytoplasm presenting the typical peripheral palisading of trichilemmoma (Figure 1B). The periphery contained an area of desmoplasia, with small epithelial cells forming chords and nests, immersed in hyalinized collagen (Figures 1B y 1C). The cell membranes were CD34-positive (Figure 1D) and the lesion was diagnosed as trichilemmoma with desmoplastic areas.

A thyroid nodule with elevated plasma levels of calcitonin is usually suggestive of a medullary thyroid carcinoma (MTC); however, thyroid and extrathyroid conditions have been reported with elevated plasma calcitonin levels in the absence of MTC. We report the case of a patient with a thyroid nodule and an elevated basal plasma calcitonin level of 315 pg/ml (normal value

Resumen La diverticulosis apendicular es una entidad poco frecuente que se puede presentar como diverticulos falsos (los mas frecuentes), verdaderos y seudodiverticulos. Su diagnostico suele ser casual (radiologico, quirurgico o histologico) y, cuando se produce clinica, generalmente se trata de un cuadro secundario a la complicacion de los diverticulos, sobre todo, inflamacion y perforacion. El tratamiento de la diverticulosis complicada es la apendicectomia, y en los casos de diagnostico incidental puede estar discutido. Presentamos dos casos de diverticulitis apendicular en el seno de una diverticulosis verdadera.

The formation of an epidural hematoma from an eosinophilic granuloma of the skull is an exceptional occurrence. A 9-year-old boy presented with severe headache, somnolence and vomiting following a minor head injury. Cranial computerized tomography scan showed a seemingly depressed skull fracture together with an epidural hematoma in evolution. A neoplasm and an epidural hematoma were removed at operation. Histopathological study of the excised mass confirmed the diagnosis of eosinophilic granuloma.

Background: ProExC is a new marker for identification of precursor lesions of cervical carcinoma. Its utility in noncervical squamous cell carcinoma in situ (SCCIS) such as Bowen's disease (BD) and actinic keratosis (AK) where human papillomavirus (HPV) plays a role has not been elucidated. Our aim was to ascertain the immunohistochemical features and clinical utility of ProExC in SCCIS of the skin. Methods: HPV presence was tested in SCCIS (38 BD and 7 AK) using GP5+/6+ and Short PCR fragment (SPF) primers and subsequently genotyped. Histopathologic sections were stained for ProExC and Ki67. A set of non-neoplastic skin proliferative lesions were included for immunohistochemical evaluation [14 psoriasis (PS) and 6 psoriasiform dermatitis (PSD)]. Results: HPV was detected in 18.9% BD. ProExC and Ki67 in the whole epidermis thickness was observed in 86.5 and 37.1% BD, respectively (p < 0.0001). ProExC and Ki67 were restricted to the lower third of the epidermis in PS and PSD. Conclusions: ProExC expression is not associated with HPV in SCCIS of the skin. Proliferating cells are better delineated in SCCIS by ProExC which may be useful to assess the extent of these lesions. Different immunohistochemical profiles seen in neoplasic and non-neoplastic skin lesions suggest diverse alteration of cell-cycle kinetics. Sanchez-Hernandez M, Conesa-Zamora P, Garcia-Solano J, Corbalan-Velez R, Martinez-Barba E, Perez-Guillermo M. Expression profiles of ProEx C and Ki67 in squamous cell carcinoma in situ of the skin and their relationship with human papillomavirus genotypes.

The anatomical location of cutaneous melanoma has been suggested to be an independent prognostic factor. The aim of the present study was to determine whether the location of the primary tumor influences sentinel node detection in cutaneous melanoma.Two hundred twelve patients with primary cutaneous melanoma (96 of the limbs, 89 of the trunk and 27 of the head or neck) who underwent sentinel lymph node biopsy were studied. Adequate lymphoscintigraphic and surgical localization was evaluated and epidemiological and histopathological variables, the number of lymph nodes draining the site of the primary lesion, sentinel nodes per drainage basin, and tumor-positive nodes were compared.Localization was less successful for tumors of the head and neck (88.8%), both with lymphoscintigraphy (P.001) and surgery (P.0005), especially for lymph nodes adjacent to salivary glands (P.0005). Melanomas of the trunk showed a greater number of nodes per lesion and wider variability in drainage pathways (P.0005), although there were no differences in the number of sentinel nodes per drainage basin (P=.455).Sentinel node detection with less successful in cutaneous melanomas located in the head and neck. Location of the sentinel node adjacent to a salivary gland is a factor that influences its detection. Cutaneous melanomas of the trunk showed a higher number of draining nodes per lesion than those located in the limbs or head and neck.

Report a new case of renal angiosarcoma treated by surgery and adjuvant chemotherapy with bad results.72-year-old male undergoing right nephrectomy for renal tumor. Pathology reports renal angiosarcoma.Three months after surgery patient refers lumbar pain and hemoptysis and CT scan reveals the existence of multiple bone and lung metastasis; a regimen of systemic chemotherapy with Doxorrubicine+ Ifosfamide was started without response; he died two months later.Primary renal angiosarcoma is very rare, with less than 10 cases in the literature before 1998, and it is always associated with bad prognosis. Diagnosis is based on immunohistochemical studies (antibodies against CD31, CD34 and factor VIII related antigen) to define the endothelial differentiation of the tumor. There is no experience to define the best therapeutic strategy against this entity.

Background. Sestamibi scintigraphy has become the fundamental technique for preoperative location of hyperfunctioning glands responsible for hyperparathyroidism, especially in the case of adenomas. However, little is known about the mechanisms of tracer uptake and retention by these glands, mechanisms that have been related to an increased gland metabolism. Our goal was to determine whether there is a relationship between the positive result of gammagraphy with sestamibi, for diagnosing the location of parathyroid adenomas, and the cell proliferation index. Patients and Methods. Six glands corresponding to sestamibi false negatives and 12 true positives were studied in patients with single-adenoma primary hyperparathyroidism. The following data were recorded in all the patients: age, gender, clinical and analytical data, gland weight, and parathyroid hormone (PTH)/gland weight ratio. An immunohistochemical study of the glands was also done with the use of Ki67, with determination of the mean proliferation index of each group for comparison purposes. Results. On comparing the 2 groups, we found no differences between the clinical or analytical parameters. Differences were found only for proliferation index—(5.7% in true positive glands versus 0.3% in false negative glands (P

of multiple eccrine hidrocystomas was made and a biopsy was performed for confirmation. The biopsy revealed a smooth muscle hamartoma compressing the eccrine glands, thereby causing cystic ectasia of both the secretory coils and the eccrine ducts. Immunostaining with anti-actin antibodies and Massontrichrome stain was positive in muscle fibers (Figure 2). Treatment was initiated with antiperspirant drugs (aluminum chlorohydrate, 20%) and produced a slight improvement; the patient’s symptoms have since remained stable with no new lesions or growth of the existing lesions. Although the pathogenesis of eccrine hidrocystoma is not well understood, some authors consider that the lesion is due to retained sweat resulting from obstruction of the eccrine duct. 5-7 This is therefore true cystic ectasia of the dermal part of the eccrine duct. In our case, histology revealed a smooth muscle hamartoma that was compressing the excretory ducts of the eccrine sweat glands, thereby causing cystic dilation of the ducts and giving rise to lesions clinically suggestive of multiple eccrine hidrocystomas. This case supports the hypothesis that hidrocystoma is not a true tumor but the result of the obstruction of the excretory part of the sweat gland; it would also explain why the lesions were unilateral in our patient—unlike previously published cases. Treatment of solitary or Smith-type forms will essentially consist of surgical removal of the lesions. In multiple or Robinson-type forms, however, surgical treatment is not appropriate; several other therapeutic options have therefore been tried, with varying results. Patients should firstly be advised to avoid situations that trigger worsening of the lesions, such as exercise and very hot environments. Oral atropine has also been used, but the systemic side effects outweigh the benefits. However, topical To the Editor: Eccrine hidrocystomas are rare cystic ductal lesions of the eccrine sweat gland. They were described by Robinson 1 in 1983 as multiple lesions that appeared on the face of women who worked in hot and humid environments. In 1973, Smith and Chernosky 2 described another group of patients in whom the lesion presented singly or in small numbers. Since then, these forms of presentation have become known as the classic or Robinson type and the solitary or Smith type, respectively. They present clinically as transparent or slightly blueish vesicular papular lesions measuring between 2 and 4 mm, on the face and torso. The lesions typically improve in winter and worsen in summer when they are exacerbated by sweatproducing stimuli, such as exercise and a warm humid environment; they may also be exacerbated by hormonal abnormalities such as hyperthyroidism. 3 Smooth muscle hamartoma is a benign process characterized by a proliferation of bundles of smooth muscle in the dermis. Almost all cases are congenital but acquired cases, such ours, also exist. These acquired forms are extremely rare and very few cases have been reported in the literature; to date, we have found only 1 published case of lesions on the face. 4

Resumen Presentamos un caso de tumor de celulas granulares. Su interes radica en su caracter multicentrico y sincronico en el estomago, el area periampular y el pancreas. Se comentan las caracteristicas clinicas y anatomopatologicas de estos tumores.