Painful nodule on a young woman's cheek.

We present a 30-year-old woman with a solitary circumscribed neuroma (also known as palisaded encapsulated neuroma) diagnosed after surgical excision. We describe the histopathologic correlation and the dermoscopic features we found in this tumor, which have not been previously reported in the literature to our knowledge.

Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

BACKGROUND: Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy. METHODS: Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort. RESULTS: MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil-lymphocyte ratio (NLR) < 5 and epithelioid histology (p < 0.001). CONCLUSIONS: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate potential predictive biomarkers of ICI benefit in MPM.

Enfermedad renal ateroembólica: un análisis de los factores clínicos y terapéuticos que influyen en su evolución / Atheroembolic renal disease: analysis of clinical and therapeutic factors that influence its progression

El embolismo de colesterol es una enfermedad causada por la suelta de cristales de colesterol desde las placas arterioscleróticas ulceradas de la aorta. Esta suelta puede ocurrir de forma espontánea o más frecuentemente tras procedimientos vasculares invasivos o tras tratamientos anticoagulantes o fibrinolíticos. Entre 1989 y 2005, en tres hospitales españoles, se diagnosticaron 45 casos de embolismo renal de colesterol. El diagnóstico fue confirmado mediante biopsia de cualquier órgano afectado o hallazgos típicos en el fondo de ojo. La mayoría de los pacientes eran varones (93,3%), ancianos (el 55,7% era mayor de 70 años), fumadores (91,1%), hipertensos (95,6%) y con varios factores de riesgo cardiovascular. Todos los pacientes presentaron un fracaso renal agudo en el momento del diagnóstico. La creatinina media al inicio fue de 4,3 ± 2,4 mg/dl. El fracaso renal agudo se acompañó frecuentemente de eosinofilia (64,4%) y lesiones cutáneas (57,7%). El 20% de los casos ocurrieron espontáneamente y el 46,7% tras manipulación endovascular (cateterismo/arteriografía); tan sólo un 8,9% ocurrió tras cambios en la anticoagulación. Tras un seguimiento de 12 ± 16,3 meses, el 55,6% (25) de los pacientes requerían diálisis crónica y un 64,4% (29) había fallecido, ocho de ellos tras haber entrado en diálisis crónica. Se observó una recuperación parcial de función renal en 9 pacientes (20%), que presentaban una creatinina media al final del seguimiento de 3 ± 1,7 mg/dl. La comorbilidad cardiovascular y la gravedad clínica del embolismo de colesterol no tuvieron impacto sobre la supervivencia renal o del individuo. La supervivencia renal (Kaplan-Meier) fue mayor en los casos de ateroembolismo espontáneo que en los iatrogénicos. 15 de los 45 pacientes recibieron esteroides. En los tratados se observó una mayor incidencia de fallecimientos (73,3% frente a 60%) y un menor porcentaje de recuperación de función renal (13,3% frente a 23%), aunque sin diferencias estadísticamente significativas. El tiempo medio de evolución a la diálisis fue significativamente más corto entre los tratados con esteroides (p = 0,017). El uso de estatinas no se asoció con una mejoría en el pronóstico renal o vital del individuo. En conclusión, la enfermedad renal ateroembólica constituye un tipo de fracaso renal agudo con unas características clínicas muy determinadas. La supervivencia renal y del paciente es mala, pero existe un porcentaje significativo de recuperaciones espontáneas de la función renal. La supervivencia renal fue significativamente mejor en los casos espontáneos y no observamos efectos beneficiosos del tratamiento esteroideo (AU)

Cholesterol embolism is a disease caused by distal showering of cholesterol crystal released from disintegration of arterial atheromatous plaques. It may occur spontaneously or more often after invasive vascular procedures or thrombolytic/anticoagulant agents. Forty five cases were diagnosed between 1989 and 2005 in three Spanish hospitals. The diagnosis was confirmed by histology or diagnostic ophthalmoscopic findings. The majority were male (93.3%), elder (55.5% were older than 70 years), smoker (91.1%), had hypertension (95.6%), with high prevalence of cardiovascular risk factors. At the time of diagnosis all patients presented acute renal failure. Mean serum creatinine at diagnosis was 4.3± 2.4mg/dl. The acute renal failure was accompanied with eosinophilia (64.4%) and cutanous lesions (57.7%). 20% of cases occur spontaneously and 46.7% after endovascular manipulation (coronary angiography/arteriography) and only 8% after changes in anticoagulant treatment. After a follow-up of 12 ± 16.3 months the 55.6% of patients need chronic dialysis, 64.4% died, 8 of them after the beginning of dialysis. Nine patients recovered renal function, with a mean creatinine of 3 ± 1.7 mg/dl at the end of follow-up. The cardiovascular comorbididy and the clinical severity of the embolism don´t have impact in the renal or patient survival. Renal survival (Kaplan-Mier) were better in spontaneous than in iatrogenic cholesterol embolism. Fifteen of 45 patients were treated with steroids. In treated patients we observed a high incidence of death (73.3% versus 60%) and fewer recovery of renal function (13.3% versus 23%), without statistical significance. The mean time to dialysis was shorter in treatment patients (p= 0.017). Statins treatment was not associated with outcome (renal or individual). In summary, atheroembolic renal disease represents an acute renal failure with special characteristics. Renal and individual outcome is poor, but some patients have spontaneous recovery of renal function. Renal survival was significantly better in spontaneous disease. We don´t observe beneficial effect of steroid treatment (AU)

[Atheroembolic renal disease: analysis of clinical and therapeutic factors that influence its progression]. / Enfermedad renal ateroembólica: un análisis de los factores clínicos y terapéuticos que influyen en su evolución.

Cholesterol embolism is a disease caused by distal showering of cholesterol crystal released from disintegration of arterial atheromatous plaques. It may occur spontaneously or more often after invasive vascular procedures or thrombolytic/anticoagulant agents. Forty five cases were diagnosed between 1989 and 2005 in three Spanish hospitals. The diagnosis was confirmed by histology or diagnostic ophthalmoscopic findings. The majority were male (93.3%), elder (55.5% were older than 70 years), smoker (91.1%), had hypertension (95.6%), with high prevalence of cardiovascular risk factors. At the time of diagnosis all patients presented acute renal failure. Mean serum creatinine at diagnosis was 4.3+/- 2.4 mg/dl. The acute renal failure was accompanied with eosinophilia (64.4%) and cutanous lesions (57.7%). 20% of cases occur spontaneously and 46.7% after endovascular manipulation (coronary angiography/arteriography) and only 8% after changes in anticoagulant treatment. After a follow-up of 12 +/- 16.3 months the 55.6% of patients need chronic dialysis, 64.4% died, 8 of them after the beginning of dialysis. Nine patients recovered renal function, with a mean creatinine of 3 +/- 1.7 mg/dl at the end of follow-up. The cardiovascular comorbididy and the clinical severity of the embolism don t have impact in the renal or patient survival. Renal survival (Kaplan-Mier) were better in spontaneous than in iatrogenic cholesterol embolism. Fifteen of 45 patients were treated with steroids. In treated patients we observed a high incidence of death (73.3% versus 60%) and fewer recovery of renal function (13.3% versus 23%), without statistical significance. The mean time to dialysis was shorter in treatment patients (p= 0.017). Statins treatment was not associated with outcome (renal or individual). In summary, atheroembolic renal disease represents an acute renal failure with special characteristics. Renal and individual outcome is poor, but some patients have spontaneous recovery of renal function. Renal survival was significantly better in spontaneous disease. We don t observe beneficial effect of steroid treatment.

Signet-ring cell dermatofibroma.

Dermatofibroma or cutaneous fibrous histiocytoma is a common benign skin lesion with multiple, distinct histologic variants, including cellular, aneurismal, epithelioid, atypical, lipidized "ankle-type," palisading, and cholesterotic. Although dermatofibromas are considered benign neoplasms, certain variants including cellular and aneurismal ones have shown to have a notable tendency to locally recur after excision. Indeed, although extremely rarely, metastases have been associated with the cellular and aneurysmal/atypical variants. Signet-ring cells are formed by cytoplasmic accumulations of various substances that push the nucleus toward the cellular border. The finding of signet-ring cells in a skin neoplasm always raises the suspicion of metastatic adenocarcinoma, although a number of reports have shown their occurrence in primitive cutaneous neoplasms as well. Signet-ring cell formation, however, has never been described in dermatofibroma. We present, for the first time, a new, distinctive variant of dermatofibroma, so-called signet-ring cell dermatofibroma, in a 16-year-old man with a slowly growing skin tumor on the lateral side of his right leg. Histologic examination demonstrated a striking signet-ring cell appearance of most of the cells in an otherwise fibrohistiocytic looking proliferation. Histochemical and immunohistochemical stainings confirmed the diagnosis of dermatofibroma. The phenomenon described in this case enlarges the histologic spectrum of cutaneous fibrous histiocytoma and may cause substantial differential diagnostic problems.