Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study.

BACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97-2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0-2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.

Pain identifies squamous cell carcinoma in organ transplant recipients: the SCOPE-ITSCC PAIN study.

Organ transplant recipients (OTR) are at high risk for cutaneous squamous cell carcinomas (SCC). We aimed to define clinically meaningful patient-reported warning signals predicting the presence of invasive SCC.Patient-reported signs and symptoms of 812 consecutively biopsied skin lesions from 410 OTR were determined by questionnaire and physical examination and related to the subsequent biopsy-proven diagnoses. Receiver-operating characteristic (ROC) curve analyses were used as a measure of distinction between the predictive values of patient-reported warning signals and the occurrence of SCC. Pain was an independent predictive patient-reported warning signal for a biopsy-proven invasive SCC. The odds ratio from the fully adjusted model predicting SCC was 4.4(95% confidence interval: 2.4­8.2). Higher scores on the visual analog scale (VAS) for pain were associated witha greater likelihood for the presence of SCC compared to none or mild pain. The for scores on the VAS from 1to 3, 4 to 6 and 7 to 10 were 4.9 (2.2­10.5), 2.3 (0.96­5.5)and 16.5 (3.6­75.8), respectively. Pain is the most powerful patient-reported warning signal for invasive cutaneous SCC in OTR. Empowerment of patients by education could accelerate diagnosis and treatment of cutaneous SCC.

Skin rash as useful marker of erlotinib efficacy in NSCLC and its impact on clinical practice.

Erlotinib is an epidermal growth factor receptor tyrosine kinase inhibitor used in treatment of advanced NSCLC. Patients harboring EGFR or KRAS mutations represent minority of all patients in caucasian population and there is no available predictor for a predominant group of patients harboring the wild-type EGFR and wild-type KRAS genes. Skin rash is the most frequent manifestation of cutaneous toxicity of erlotinib. Rash is associated with a good therapeutic response. We aimed at the evaluation of rash as a predictor of therapeutic effect of erlotinib in patients harboring the wild-type EGFR and KRAS wild-type genes and to assess its possible usage in a clinical practice.Totally 184 patients with advanced stage NSCLC (IIIB, IV) harboring the wild-type EGFR and wild-type KRAS genes were analysed. Comparison of ORR, PFS and OS according to the occurrence of rash was performed. In order to assess the impact of rash in clinical practice it was conducted landmark analysis of the group of patients whose rash was observed during first month of treatment (n=124). Patients in whom progression was observed during the first month of treatment were excluded from the landmark analysis. The comparison of ORR was performed using Fisher's exact test, visualization of survival was performed using Kaplan-Meier survival curves and the differences in survival were tested using the log-rank test. Median PFS in patients who were observed with rash during the treatment was 3.0 vs. 1.2 months in patients with no rash (p<0.001), median of OS in patients who were observed with rash during the treatment was 13.9 vs. 5.8 months in patients with no rash (p<0.001). ORR in patients who were observed with rash during the treatment was 17.4% vs. 3.3% in patients with no rash (p=0.001). Median of PFS after 1 month of treatment in patients who were observed with rash during the first month was 2.9 vs. 1.1 months in patients with no rash (p=0.027). Median of OS after 1 month of treatment in patients who were observed with rash during the first month was 13.8 vs. 9.9 months in patients with no rash (p=0.082). Rash is strongly associated with better survival and ORR in patients harboring wild-type EGFR and wild-type KRAS genes. Occurrence of rash during the first month of treatment is a useful predictor of better effect of erlotinib after one month of treatment. Patients who were not observed with rash during the first month of treatment are in high risk of progression. Optimization of the treatment of these patients can contribute restaging after two months of treatment, assessment of plasma levels of erlotinib and eventually attempt to dose escalation.

Extraordinary response to erlotinib therapy in a patient with lung adenocarcinoma exhibiting KRAS mutation and EGFR amplification.

Case reports on the co-incidence of Kirsten rat sarcoma (KRAS) mutation and epidermal growth factor receptor (EGFR) amplification in patients with NSCLC are very rare. This combination is usually considered a negative prognostic factor, despite EGFR amplification alone having positive predictive value. The whole course of treatment of a patient with both EGFR amplification and KRAS mutation present is decribed. The patient in question was a smoker for whom both first- and second-line chemotherapy had been unsuccessful. In stage IV disease biological therapy was administered and proved highly beneficial. Today, 38 months since commencing the treatment, the patient still has no signs of progression and the therapy is still in progress.

Linfoma no Hodgkin oral relacionado al sida (LNHORS): Actualización y presentación de un caso clínico / Aids related oral no Hodgkin lymphoma (ARONHL): up today and report of a case

Introducción: Los linfomas No- Hodgkin presentan características propias cuando se asocian a la infección por el Virus de la Inmunodeficiencia Humana. La cavidad bucal es una de las localizaciones a tener en cuenta en pacientes con Sida (LNHORS) Si bien se registran casos en los primeros estadios de la infección, el diagnóstico previo diferencial estomatológico y su seguimiento no se realizan en nuestro medio con la frecuencia que esta enfermedad requiere. En los pacientes VIH positivos, las características generales están relacionadas con la edad de los pacientes, el estado de base inmunológico de la infección, la adherencia a los tratamientos, una historia de más de 35 años de drogadicción intravenosa y el tipo de linfoma. El presente trabajo tiene dos objetivos: 1) Presentar una actualización del tema ya que en los últimos años se han investigado los diferentes tipos y subtipos histológicos, su estratificación y tratamientos en forma intensa y 2) presentar un caso clínico de Linfoma no Hodgkin con localización en la cavidad bucal de evolución no frecuente. Desarrollo: Una paciente de 34 años de edad con una masa tumoral en el hueso maxilar mucosa gingival y paladar duro y blando. La lesión estaba ulcerada en la primera consulta y hacía protrusión a través de la cavidad bucal. Resultados: se realizaron estudios sistémicos, biopsias de las lesiones orales, estudio histológico y marcación inmunohistoquímica,, búsqueda por diagnóstico por imágenes de otras manifestaciones y localizaciones de linfomas. Fueron establecidos tratamientos, seguimiento y evolución. Conclusiones: Un diagnóstico eficiente y temprano de los pacientes con LNHORS por un equipo de salud, puede incrementar las sobrevidas, en un marco, donde pueda ser posible la reconstitución de la función inmunológica y puedan ser aplicados los nuevos regímenes de infusión contínua con quimioterápicos (AU)

Introduction: Non-Hodgkin Lymphoma presents their own characteristics when it is associated with the human immunodeficiency virus syndrome (HIV). Oral cavity is one localization in Aids patients (LNHOES) and its manifestations are registered on the first state of HIV infection. But oral differential diagnoses is not so frequent as this disease needs, in our environment. On HIV patients general characteristics are related to the age of patients, immunological status, treatment compliance, intravenous drug addictions for more of 35 years and lymphoma type. The present work has two objectives: 1) To present this subject in order to actualize epidemiological news, histological types and subtypes classification, illness stratification and advances on therapy., because it has been, in recent years, intensive researches about it. 2) To report a clinic HIV+ case with NHL, with an infrequent evolution. A female patient of 34 years old, with a tumor mass on maxilla bone, gingival mucosa and hart and soft palate. Lesion was ulcerated at the first consultation and hat protrude trough the mouth. Results considered different systemic studies, biopsies of the oral lesions, histological study and immuno histochemical marcation, and searching of other lymphoma´s manifestations and locations by scan´s studies. Treatments, follow up and evolution were assessed Conclusions: An efficient and early diagnostic of ARONHL by a health team work, can increase longer survival for this patients, in an scene, where it can be possible the reconstitution of immunological function and where it could be applied Continous Infusion Chemotherapy new regimens (AU)