Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships.

BACKGROUND: Gastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors. OBJECTIVES: Evaluate retrospectively the efficacy of a regular and proactive follow-up of NF1 patients to early diagnose abdominal tumors and report their mutations. METHODS: Cohort study performed between 2010 and 2020, with 43 NF1 adult patients followed at our Dermatology department. RESULTS: Eight abdominal tumors were diagnosed in six patients, meaning that 14% of the followed patients developed an abdominal tumor. Five patients (83%) were asymptomatic. Five (83.3%) had a family history of NF1 with abdominal tumors (patients 1,2 and 3,4,5 were relatives). CONCLUSIONS: Although currently gastrointestinal routine screening investigations for asymptomatic patients are not recommended in the guidelines, the family aggregation in our series suggests it should be considered a close follow-up of the relatives of a patient with an NF1-related abdominal tumor. Also, for the first time, two mutations [c.2041C > T (p.Arg681Ter) and c.4537C > T (p.Arg1513*)] have been associated with family aggregation of abdominal tumors in NF1 patients.

Descriptive study of naevus involution in a series of 74 patients with atypical naevus syndrome under SIAscopy digital follow-up.

BACKGROUND: Characterization of nevi involution could help to understand the biological behaviour of melanocytic neoplasms. OBJECTIVE: To describe the frequency and morphology of naevus involution in a series of patients with atypical naevus syndrome under digital follow-up with a SIAscopy program and, in a small sample of fading nevi, to analyse histopathological features and immunohistochemical biomarkers. METHODS: Seventy-four patients registered from April 2007 to July 2014 in the SIAscopy system of the Department of Dermatology of Hospital Arnau de Vilanova of Lleida, Spain, were reviewed. Fourteen naevus cases with fading features were prospectively excised during follow-up. Eleven already excised naevus controls were randomly selected from our archive. RESULTS: We observed that 81% of patients showed, at least, one involutive naevus and 25% of recorded nevi presented this phenomenon; the mean time of involution was 46.7 months. The predominant structural pattern was reticular (>70%), and the most frequently observed regression structures were vascular (33.8%). Histopathological significant higher intensity of inflammatory infiltrate in controls and higher presence of laminar and compact fibrosis and increase of vessels in cases were demonstrated. Regarding immunohistochemical biomarkers, only higher expression of cytoplasmic activated caspase 3 in controls was significant. CONCLUSIONS: Naevus involution is a common phenomenon in patients with dysplastic naevus syndrome. It is usually a slow process, more frequent in naevus with reticular pattern. SIAscopy regression structures are uncommon, with the exception of vascular ones. Histologically, fading involutive pattern is characterized by scarce inflammatory infiltrate and melanophages, delicate fibrosis and increase of vessels.

Examination of cytological smears and cell blocks of pleural fluid: Complementary diagnostic value for malignant effusions / Examen del frotis citológico y bloque celular del líquido pleural: valor diagnóstico complementario en los derrames malignos

Objectives. To evaluate the independent usefulness of pleural fluid smear and cell block (CB) preparations for the diagnosis of malignant effusions. Patients and methods. A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated. Results. The diagnostic yield of a first specimen was 44% regardless of whether a smear or CB cytologic examination was performed. The use of subsequent separated specimens increased the identification of malignancy to 56%. Overall, 11% of samples found to be negative by cytologic smears showed malignant cells on CBs, whereas 15% of negative CBs were reported as positive on smear slides. Pleural fluid specimens with low red and/or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations. Conclusions. If CBs and smears are prepared and examined, the percentage of positive diagnoses will be greater than if only one method is used (AU)

Objetivos. Evaluar la utilidad independiente de frotis y bloques celulares (BC) del líquido pleural para diagnosticar derrames malignos. Pacientes y métodos. Se evaluaron retrospectivamente un total de 632 frotis citológicos y 554 BC de 414 pacientes consecutivos con derrame pleural maligno. Resultados. La sensibilidad diagnóstica de una primera muestra fue del 44%, tanto en frotis como en BC. El análisis de muestras separadas ulteriores aumentó al 56% la identificación de derrames malignos. Globalmente, el 11% de muestras negativas mediante frotis mostraron células malignas en los BC, mientras que el 15% de BC negativos resultaron positivos en el estudio del frotis. Los líquidos pleurales con recuentos bajos de hematíes o leucocitos produjeron con mayor frecuencia BC insuficientes para diagnóstico. Conclusiones. Si se evalúan frotis y BC, el porcentaje de resultados positivos es superior que si se emplean estas técnicas de forma aislada (AU)

Examination of cytological smears and cell blocks of pleural fluid: Complementary diagnostic value for malignant effusions.

OBJECTIVES: To evaluate the independent usefulness of pleural fluid smear and cell block (CB) preparations for the diagnosis of malignant effusions. PATIENTS AND METHODS: A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated. RESULTS: The diagnostic yield of a first specimen was 44% regardless of whether a smear or CB cytologic examination was performed. The use of subsequent separated specimens increased the identification of malignancy to 56%. Overall, 11% of samples found to be negative by cytologic smears showed malignant cells on CBs, whereas 15% of negative CBs were reported as positive on smear slides. Pleural fluid specimens with low red and/or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations. CONCLUSIONS: If CBs and smears are prepared and examined, the percentage of positive diagnoses will be greater than if only one method is used.

Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma.

BACKGROUND: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an important role in cell proliferation. OBJECTIVES: To describe for the first time in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies. METHODS: Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-C overexpression. RESULTS: TT-C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease-free survival (DFS) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1. CONCLUSIONS: TT-C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT-C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-C blockers in targeted therapies.

Mutation profile and clinical outcome of mixed endometrioid-serous endometrial carcinomas are different from that of pure endometrioid or serous carcinomas.

Clinical outcome of 23 patients with mixed endometrioid and serous endometrial carcinomas (mixed EEC-SC) was compared to that of pure endometrioid (EEC) and pure serous (SC) carcinomas. Hotspot mutation frequencies in KRAS, PIK3CA, PTEN, and TP53 and microsatellite instability (MSI) status were determined in mixed EEC-SC, as well as in their EEC and SC microdissected components separately, and alterations were compared to frequencies in pure EEC and SC. Relapse-free (RFS) and overall survival (OS) differed significantly between mixed EEC-SC and pure EEC and SC, revealing that outcome of mixed EEC-SCs was intermediate to that of pure EEC and pure SC. PTEN mutations were absent in pure SC, but occurred in 20 % of pure EEC, and 13 % of mixed EEC-SC. In contrast, TP53 mutations were more frequent in pure SC (17 %) and mixed EEC-SC (22 %) than in pure EEC (2 %). Mutations in mixed EEC-SC were shared by the two microdissected components in 30 %, whereas in 35 %, some mutations were component-specific. Mutation analysis confirms similarities between the EEC and SC components of mixed EEC-SC with pure EEC and pure SC, respectively. However, PTEN and KRAS mutations were more frequent in the SC component of mixed EEC-SC than in pure SC, while TP53 mutations were more frequent in the EEC component of mixed EEC-SC than in pure EEC. Presence of different clonal mutation pattern between EEC and SC components of mixed EEC-SC raises the possibility of divergent tumor heterogeneity or biclonal origin in some cases.

[Cauda equina syndrome caused by paraganglioma of the filum terminale]. / Paraganglioma del filum terminal como causa de síndrome de cauda equina.

Paragangliomas are neuroendocrine tumors that originate from cells migrating from the neural crest. They have a diverse localizations, and are common in the head, neck, mediastinum or retroperitoneum. Their growth in the filum terminale region is very infrequent. We report the case of a patient who suffered an acute cauda equina syndrome. We give a detailed description of the diagnostic process, radiological characteristics, treatment and the macro and microscopic properties of this tumor.

Paraganglioma del filum terminal como causa de síndrome de cauda equina / Cauda equina syndrome caused by paraganglioma of the filum terminale

Los paragangliomas son tumores neuroendocrinos originados a partir de células que migran de la cresta neural. Su localización es diversa, siendo frecuentes encabeza, cuello, mediastino o retroperitoneo. Su crecimiento en la región del filum terminal es muy poco frecuente. Presentamos el caso de una paciente que debuta con un cuadro agudo de cauda equina. Describimos en detalle el proceso diagnóstico, las características radiológicas, el tratamiento y las propiedades macro y microscópicas de este tumor (AU)

Paragangliomas are neuroendocrine tumors that originate from cells migrating from the neural crest. They have a diverse localizations, and are common in the head, neck, mediastinum or retroperitoneum. Their growth in the filum terminale region is very infrequent. We report the case of a patient who suffered an acute cauda equina syndrome. We give a detailed description of the diagnostic process, radiological characteristics, treatment and the macro and microscopic properties of this tumor (AU)