RESUMEN
Secretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM+ plasma cells (PCs) were more abundant in humans than mice and clonally related to a large repertoire of memory IgM+ B cells disseminated throughout the intestine but rare in systemic lymphoid organs. In addition to sharing a gut-specific gene signature with memory IgA+ B cells, memory IgM+ B cells were related to some IgA+ clonotypes and switched to IgA in response to T cell-independent or T cell-dependent signals. These signals induced abundant IgM which, together with SIgM from clonally affiliated PCs, recognized mucus-embedded commensals. Bacteria recognized by human SIgM were dually coated by SIgA and showed increased richness and diversity compared to IgA-only-coated or uncoated bacteria. Thus, SIgM may emerge from pre-existing memory rather than newly activated naive IgM+ B cells and could help SIgA to anchor highly diverse commensal communities to mucus.
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Angiodisplasia/inmunología , Linfocitos B/inmunología , Neoplasias del Colon/inmunología , Pólipos del Colon/inmunología , Inmunoglobulina M/metabolismo , Intestinos/inmunología , Células Plasmáticas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Células Clonales , Femenino , Microbioma Gastrointestinal/inmunología , Humanos , Inmunidad Mucosa , Inmunoglobulina A/metabolismo , Cambio de Clase de Inmunoglobulina , Memoria Inmunológica , Intestinos/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , SimbiosisRESUMEN
AIMS: The current WHO classification of melanocytic tumours excludes neoplasms showing BRAF or NRAS mutations from the Spitz category. This study aimed to review and reclassify atypical melanocytic tumours with spitzoid morphological features diagnosed between 2009 and 2021 in our hospital after expanding the molecular profile, including BRAF and NRAS mutations in all cases. METHODS AND RESULTS: A total of 71 neoplasms showing spitzoid features (Spitz-like) and atypia were included. The risk of progression of tumours was first studied by integrating the morphology, immunohistochemistry (p16, Ki67, HMB45 and PRAME) and fluorescence in-situ hybridisation (FISH) results (melanoma multiprobe and 9p21). In a second step, after expanding the molecular study, including BRAF and NRAS mutational status, the neoplasms were finally classified into four subgroups: atypical Spitz tumour (AST, n = 45); BRAF-mutated naevus/low-grade melanocytoma with spitzoid morphology (BAMS, n = 2); Spitz melanoma (SM, n = 14); and BRAF or NRAS mutated melanoma with spitzoid features (MSF, n = 10). Follow-up of patients revealed uneventful results for AST and BAMS. Only one SM presented lymph node metastasis after 134 months. Conversely, patients with MSF showed an unfavourable outcome: three developed lymph node metastases after a mean time of 22 months, with one patient presenting distant metastasis and dying of the disease 64 months from diagnosis. The progression-free survival showed significant differences between the four groups of spitzoid tumours (P < 0.001) and between both melanoma subtypes (P = 0.012). CONCLUSIONS: The classification and prognostication of atypical neoplasms with spitzoid features requires the integration of histomorphology with the molecular investigation of tumours, which should include BRAF and NRAS mutational status.
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GTP Fosfohidrolasas , Melanoma , Proteínas de la Membrana , Mutación , Nevo de Células Epitelioides y Fusiformes , Proteínas Proto-Oncogénicas B-raf , Neoplasias Cutáneas , Humanos , Biomarcadores de Tumor/genética , GTP Fosfohidrolasas/genética , Melanoma/genética , Melanoma/patología , Melanoma/clasificación , Melanoma/diagnóstico , Proteínas de la Membrana/genética , Nevo de Células Epitelioides y Fusiformes/genética , Nevo de Células Epitelioides y Fusiformes/patología , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/clasificación , Neoplasias Cutáneas/diagnósticoRESUMEN
BACKGROUND: A combined deep-penetrating tumour redefined as WNT-activated deep-penetrating/plexiform melanocytoma (DPM), may pose challenging clinical and histological diagnoses. OBJECTIVES: To review the clinicopathological characteristics of combined DPMs and characterize the molecular profile of atypical and malignant forms. METHODS: The study included 51 patients with combined DPMs diagnosed at the Hospital Clinic of Barcelona and the University of Florence between 2012 and 2020. Clinical data, dermoscopy images (when available) and histological characteristics were reviewed. Immunohistochemistry for ß-catenin, LEF1, HMB45, Ki67, p16 and PRAME (preferentially expressed antigen in melanoma) was performed. Atypical forms underwent next-generation sequencing (NGS) panel analysis, including driver genes implicated in DPMs, TERT-promoter (p) mutations and the investigation of the 9p21 locus via fluorescence in situ hybridization. RESULTS: Among the 51 patients (32 females and 19 males, age range 4-74â years), 68% with available clinical data (15/22) were initially suspected of having melanoma. Except for one patient, complete excision resulted in no recurrences or metastases. One patient who had an incompletely excised combined DPM developed a lymph node melanoma metastasis 10â years later. In the 51 patients, 10 samples (20%) showed atypical histological features; 7 (14%) exhibited a significant loss of p16 expression; and 2 (4%) showed a high-proliferative index (Ki67 over 5%). NGS analysis in 11 patients revealed a double mutation BRAFV600E and exon 3 CTNNB1; no TERTp mutations were detected. CONCLUSIONS: Clinical suspicion of melanoma is common in combined DPMs, but malignant progression is infrequent in tumours lacking high-grade atypia or proliferation. These findings are congruent with the consideration of these lesions as intermediate-grade tumours or melanocytomas.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Succinimidas , Masculino , Femenino , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Melanoma/diagnóstico , Melanoma/genética , Melanoma/metabolismo , Antígeno Ki-67/metabolismo , Hibridación Fluorescente in Situ , Metástasis Linfática , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Mutación , Antígenos de NeoplasiasRESUMEN
Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing. Common mutated genes were BRAF (29%), NRAS (28%), ALK, KIT, and MAP2K1 (5% each). Co-occurring mutations were detected in 29% of the samples, including BRAF with KIT, CTNNB1, EGFR, ALK, HRAS, or MAP2K1. Amplifications and rearrangements were detected in 5% of cases. Only BRAF mutation showed a significant statistical association with sun exposure. For patients with a given genetic profile, the melanoma survival and recurrence-free survival rates were equivalent, but not for stage and LDH values. This expanded knowledge of molecular alterations has helped to more comprehensively characterize our patients and has provided relevant information for deciding the best treatment strategy.
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Melanoma , Mutación , Humanos , Melanoma/genética , Melanoma/patología , Melanoma/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , España , Adulto , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Anciano de 80 o más Años , Estudios de Factibilidad , Proteínas Proto-Oncogénicas B-raf/genética , Biomarcadores de Tumor/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: High-risk mucosal human papillomavirus (HR-HPV) seems to play a role in cutaneous squamous cell carcinoma (cSCC), particularly in nail tumours, where genitodigital transmission has been suggested. The role of HR-HPV in nonungual cSCC of the finger needs to be clarified. AIM: To evaluate the prevalence, clinicopathological characteristics, surrogates and outcomes of HR-HPV in cSCC of the finger. METHODS: This was an observational bicentric study including patients with an excised in situ or invasive cSCC located on the finger. Differences in HR-HPV and non-HR-HPV tumours were evaluated. RESULTS: Forty-five patients (45 tumours) were included. HR-HPV was detected in 33% of cases (22% HPV type 16). The mean age was lower in patients with HR-HPV than in those with non-HR-HPV (62·4 vs. 81·1â years, P = 0·001). HR-HPV tumours were smaller (10â mm vs. 15â mm, P = 0·07) and more frequently intraepidermal (60% vs. 20%, P = 0·004). The absence of elastosis (P = 0·030) and inflammation (P = 0·026) and the presence of basaloid morphology (P = 0·003) were surrogates of HR-HPV detection. Mean p16 positivity was 61% in HR-HPV and 36% in non-HR-HPV tumours (P = 0·061). Recurrence after surgery was more common in HR-HPV tumours (58% vs. 34%), although this was not statistically significant. HR-HPV was detected in 27% of the nonungual tumours. CONCLUSION: HR-HPV-associated cSCC of the finger appears in younger patients, is smaller and is less infiltrative than non-HR-HPV tumours. The presence of a basaloid morphology and the absence of elastosis and inflammation could be used as markers for HR-HPV detection. The high prevalence of HR-HPV in nonungual cSCC suggests its aetiopathogenic role in these tumours.
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Carcinoma de Células Escamosas , Infecciones por Papillomavirus , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/patología , Estudios Retrospectivos , Virus del Papiloma Humano , Inflamación , PapillomaviridaeRESUMEN
BACKGROUND: Blue nevi are benign dermal melanocytic proliferations that are often easy to recognize clinically. Rarely, these lesions can display atypical features, suggesting the presence of a malignant blue nevus or mimicking cutaneous metastases of melanoma. OBJECTIVE: To describe the clinical evolution of blue nevi over time and to assess the need for monitoring these lesions. METHODS: We conducted a retrospective cohort study of 103 patients who were followed between December 1998 and November 2019. An artificial intelligence algorithm was used to identify blue nevi from the databases of two digital epiluminescence devices. Changes in the area of each lesion were calculated with a segmentation neural network. RESULTS: We included 123 blue nevi from 103 patients. Most of the lesions segmented, 99 (91.7%), were considered stable. Of the 9 (8.3%) growing blue nevi identified, 2 (1.85%) showed significant growth. The studied growing blue nevi turned out to be cellular blue nevi, presented with a low tumour mutation burden and GNAQ c.626A>T alteration was identified in both lesions. LIMITATIONS: Some clinical variants of blue nevi might not be included. CONCLUSIONS: Most blue nevi remain stable during their evolution. Rarely, they can show progressive growth, although histopathological or molecular signs of malignancy have not been identified.
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Melanoma , Nevo Azul , Neoplasias Cutáneas , Humanos , Nevo Azul/patología , Estudios Retrospectivos , Inteligencia Artificial , Melanoma/patología , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: SARS-CoV-2 may produce intestinal symptoms that are generally mild, with a small percentage of patients developing more severe symptoms. The involvement of SARS-CoV-2 in the physiopathology of bowel damage is poorly known. Transmission electron microscopy (TEM) is a useful tool that provides an understanding of SARS-CoV-2 invasiveness, replication and dissemination in body cells but information outside the respiratory tract is very limited. We report two cases of severe intestinal complications (intestinal lymphoma and ischaemic colitis) in which the presence of SARS-CoV-2 in intestinal tissue was confirmed by TEM. These are the first two cases reported in the literature of persistence of SARS-CoV-2 demonstrated by TEM in intestinal tissue after COVID 19 recovery and SARS-CoV-2 nasopharyngeal clearance. CASE PRESENTATION: During the first pandemic peak (1st March-30th April 2020) 932 patients were admitted in Hospital Universitari Mútua Terrassa due to COVID-19, 41 (4.4%) required cross-sectional imaging techniques to assess severe abdominal pain and six of them (0.64%) required surgical resection. SARS-CoV-2 in bowel tissue was demonstrated by TEM in two of these patients. The first case presented as an ileocaecal inflammatory mass which turned to be a B-cell lymphoma. Viral particles were found in the cytoplasm of endothelial cells of damaged mucosa. In situ hybridization was negative in tumour cells, thus ruling out an oncogenic role for the virus. SARS-CoV-2 remained in intestinal tissue 6 months after nasopharyngeal clearance, suggesting latent infection. The second patient had a severe ischaemic colitis with perforation and SARS-CoV-2 was also identified in endothelial cells. CONCLUSIONS: Severe intestinal complications associated with COVID-19 are uncommon. SARS-CoV-2 was identified by TEM in two cases, suggesting a causal role in bowel damage.
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COVID-19 , SARS-CoV-2 , Dolor Abdominal , Células Endoteliales , Humanos , Microscopía Electrónica de TransmisiónAsunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Basocelular , Neoplasias Cutáneas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/patología , Masculino , Anciano , FemeninoRESUMEN
With the identification of therapeutic targets for lung adenocarcinoma, it has become mandatory to distinguish it from other entities. Some cases remain classified as non-small cell lung carcinoma, not otherwise specified (NSCLC-NOS) with immunohistochemistry. Electron microscopy (EM) can be useful, allowing the identification of glandular differentiation. The aim of this study was to determine the complementary value of immunohistochemistry and EM.Forty-eight NSCLC-NOS cases were selected (PSMAR-Biobank, Barcelona, Spain). Immunohistochemistry (TTF-1, p40) was performed. Tissue was retrieved from paraffin blocks. Results were compared to the final diagnosis, derived from combination of light microscopy, immunohistochemistry, EM, molecular studies and resection specimen.Immunohistochemistry concurred with final diagnosis in 36 cases (75%, Kappa = 0.517). EM agreed with final diagnosis in 35 (72.9%, Kappa = 0.471). Immunohistochemistry had a sensitivity = 73%, specificity = 100%, positive predictive value (PPV) = 100% and negative predictive value (NPV) = 52.4% for adenocarcinoma. All adenocarcinoma cases not solved by immunohistochemistry (n = 10) were classified by EM, and vice versa. Data from EM were identical to those of immunohistochemistry: sensitivity = 73%, specificity = 100%, PPV = 100% and NPV = 52.4%. Combining both techniques, 47 cases were coincident with final diagnosis (97.9%, Kappa = 0.943).EM can provide valuable information in subtyping NSCLC-NOS, being particularly useful when immunohistochemistry is inconclusive. EM could be considered as a complementary tool for decision-making in NSCLC-NOS.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Inmunohistoquímica/métodos , Neoplasias Pulmonares/diagnóstico , Microscopía Electrónica de Transmisión/métodos , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/patología , Terapia Molecular DirigidaAsunto(s)
Absceso Abdominal/parasitología , Anisakiasis/diagnóstico , Pólipos del Colon/parasitología , Absceso Abdominal/patología , Absceso Abdominal/cirugía , Anisakiasis/complicaciones , Pólipos del Colon/patología , Pólipos del Colon/cirugía , Colonoscopía , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Overexpression of ETS genes is involved in prostate cancer (PrCa), but there is little information on the non-ERG components of this family. We have investigated ETV1, ETV4, and ETV5 overexpression, with or without PTEN loss, and their association with grade group (GG), pathological stage, focality, and PSA recurrence in PrCa. ETS gene expression was analyzed by qPCR in 104 cases. ETV1 and PTEN immunohistochemistry was assessed in TMA sections from 194 additional cases (PSMAR-Biobank, Barcelona, Spain). ETS mRNA overexpression was found in 23.1%, being ETV1 the most frequently overexpressed (18.3%). ETV1 protein overexpression was detected in 30.4% cases (moderate in 19.6%, strong in 10.8%). PTEN protein expression loss was detected in 36.1% cases and was not associated with ETV1. Strong-moderate ETV1 protein overexpression reaches its highest values in GG3-4, whereas its negativity was significantly more common in GG1 tumors (p = 0.034). ETV1-overexpressing tumors were more often unifocal (p = 0.0007) and high stage (p = 0.032). PTEN loss was less common in GG1 (p = 0.012) and showed a trend to be less frequent in pT2 (p = 0.062) tumors. Strong ETV1 immunostaining (histoscore > 177) was associated with shorter time to PSA recurrence in the univariate (p = 0.002) and in the multivariate analysis (p = 0.018). Moreover, when strong ETV1 overexpression was not combined with PTEN loss, its association with PSA recurrence was even stronger (p = 0.0004). In conclusion, non-ERG ETS overexpression, particularly ETV1 overexpression, has a non-negligible role in PrCa. Strong ETV1 protein expression has a negative impact on prostate cancer outcome that seems to be independent of PTEN status.
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Biomarcadores de Tumor/análisis , Proteínas de Unión al ADN/biosíntesis , Neoplasias de la Próstata/patología , Factores de Transcripción/biosíntesis , Anciano , Citoplasma/metabolismo , Proteínas de Unión al ADN/análisis , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/mortalidad , Factores de Transcripción/análisisRESUMEN
The role of DNA MMR genes in prostate cancer (PrCa) is controversial, as genetic alterations leading to microsatellite instability are incompletely defined in these tumors. ERG rearrangements and PTEN loss are concomitant events in PrCa. The aim of this study has been to analyze the immunohistochemical (IHC) expression of MSH2, MSH6, MLH1, PMS2, ERG, and PTEN and their potential association with the grade group (GG) grading system (WHO 2016) and PSA recurrence in a series of 200 PrCa (PSMAR-Biobank, Barcelona, Spain). MSH2, MLH1, PMS2, and PTEN losses were documented in 8%, 5%, 2%, and 36.5%, respectively. ERG expression was found in 48%. MSH6 showed an increase of expression with respect to basal levels in 42.1% of the cases. A statistical association between MSH6 overexpression and GG5 was found (p = 0.0281). ERG-wild-type cases were associated with single MSH2 loss (p = 0.024), and MSH2 and/or MLH1 loss (p = 0.019). The percentage of cases with PTEN loss was 20.5% (8/39) in GG1, 37.6% (53/141) of clustered GG2 to 4, and 60% (12/20) of GG5 (chi-square test, p = 0.01). Thus, PTEN expression loss was statistically more frequent in the upper-grade tumors. PMS2 loss was an infrequent event, but it was statistically associated with shorter time to PSA recurrence (p = 0.011). These results suggest the existence of an alternative non-ERG pathway associated with MSH2 or MLH1 expression loss. MSH6 overexpression could be a marker of aggressiveness in PrCa. The IHC assessment of DNA MMR proteins, ERG and PTEN, could identify different altered PrCa pathways, which could aid patient stratification.
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Biomarcadores de Tumor/análisis , Reparación de la Incompatibilidad de ADN/fisiología , Fosfohidrolasa PTEN/biosíntesis , Neoplasias de la Próstata/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/metabolismo , Regulador Transcripcional ERG/biosíntesisRESUMEN
In non-small cell lung cancer (NSCLC) patients, the recommended minimum requirement for an endoscopy-based mediastinal staging procedure is sampling the largest lymph node (LN) in right and left inferior paratracheal, and subcarinal stations. We aimed to analyze the percentage of cases where the largest LN in each mediastinal station was malignant in a cohort of NSCLC patients with mediastinal metastases diagnosed in the lymphadenectomy specimen. Furthermore, we investigated the sensitivity of a preoperative staging procedure in a hypothetical scenario where only the largest LN of each station would have been sampled.Prospective data of patients with mediastinal nodal metastases diagnosed in the lymphadenectomy specimens were retrospectively analyzed. The long-axis diameter of the maximal cut surface of all LNs was measured on hematoxylin and eosin-stained sections.Seven hundred seventy five patients underwent operation and 49 (6%) with mediastinal nodal disease were included. A total of 713 LNs were resected and 119 were involved. Sixty seven nodal stations revealed malignant LNs: in these, the largest LN was malignant in 39 (58%). In a "per patient" analysis, a preoperative staging procedure that sampled only the largest LN would have attained a sensitivity of 0.67; and if the largest and the second largest were sampled, sensitivity would be 0.87.In patients with NSCLC, nodal size ranking is not reliable enough to predict malignancy. In clinical practice, regardless of the preoperative staging method, systematic thorough sampling of all visible LNs is to be recommended over selective random samplings.
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Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Mediastinoscopía/métodos , Estadificación de Neoplasias , Cirugía Torácica Asistida por Video/métodos , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Masculino , Mediastino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: More than 60% of patients with lung cancer are diagnosed at advanced stages. The introduction of targeted therapies requires molecular diagnosis to guide treatment. The aim of this study was to evaluate the feasibility of performing mutational analysis with brushing specimens obtained by radial-miniprobe endobronchial ultrasound (R-EBUS) plus fluoroscopy-guided bronchoscopy in patients with peripheral pulmonary adenocarcinoma. METHODS: Brushing specimens were deposited on cytological slides and were conserved in Roswell Park Memorial Institute (RPMI) culture medium. DNA was isolated to perform a mutational analysis with real-time quantitative polymerase chain reaction and Sanger sequencing for epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS). RESULTS: Thirty patients with adenocarcinoma were prospectively included. In 100% of the patients, the molecular study was viable with brushing specimens. In 16 (53.3%), KRAS or EGFR mutations were detected: 10 KRAS mutations (33.3%) and 6 EGFR mutations (20%). In a comparison with histological samples, a correlation of 86.6% was detected, and only 2 patients with wild-type results from brushing specimens presented with an EGFR mutation in histological samples. CONCLUSIONS: Brushing specimens conserved in RPMI medium and obtained by R-EBUS plus fluoroscopy-guided bronchoscopy are valid for molecular studies. They allow the detection of EGFR/KRAS mutations in patients with peripheral adenocarcinoma. In addition, invasive techniques are avoided, the risk of complications is reduced, and the obtained samples are optimized.
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Adenocarcinoma del Pulmón/diagnóstico , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Fluoroscopía/métodos , Biopsia Guiada por Imagen/métodos , Neoplasias Pulmonares/diagnóstico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Broncoscopía/métodos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Citodiagnóstico , Análisis Mutacional de ADN , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Estudios Prospectivos , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
TMPRSS2 and SLC45A3 rearrangements may coexist in the same tumor. ERG rearrangements and PTEN loss are concomitant events in prostate cancer (PrCa), and can cooperate in progression. We have reported that mRNA expression of TMPRSS2-ERG and SLC45A3-ERG rearrangements plus PTEN loss define an aggressive tumor subset. The aim of this study has been to validate these results by immunohistochemistry in a large cohort of tumors. ERG, SLC45A3 and PTEN immunostaining and their association with pathological features and PSA progression-free survival were analyzed in 220 PrCa (PSMAR-Biobank, Barcelona, Spain). ERG protein expression was found in 46.8% and SLC45A3 and PTEN loss in 30% and 34% tumors, respectively. Single ERG positive immunostaining was associated with GS = 6 tumors (p = 0.016), double ERG+/PTEN loss with GS = 7 (p = 0.008) and Grade Group 2 (GG) or GG3 cases (p = 0.042), ERG+/SLC45A3 loss/PTEN loss ("triple hit") with GS ≥ 8 (p < 0.0001) and GG4 or GG5 tumors (p = 0.0003). None of GS = 6 nor = GG1 cases showed this combination. In the GS ≥ 8 group, ERG+ (p = 0.002), PTEN loss (p = 0.009) and "triple hit" (p = 0.003) were associated with Gleason pattern 3 component, and single SLC45A3 loss (p = 0.036) with GS ≥ 8 without pattern 3. The number of aberrant events and the triple hit were strongly associated with shorter PSA progression-free survival. In GS = 6 PrCa, single ERG+ was also associated with progression. ERG+ identifies a distinct pathway of PrCa. Additional assessment of PTEN and SLC45A3 adds relevant prognostic information. The triple hit phenotype (ERG+/SLC45A3 loss/PTEN loss) is associated with progression and could be used for patient stratification, treatment and follow-up.
RESUMEN
BACKGROUND: Diffuse dermal angiomatosis (DDA) is a rare, acquired, reactive vascular proliferation, clinically characterized by livedoid erythematous-violaceous plaques, which frequently evolve to ulceration and necrosis. Histopathologically, it is manifested by a diffuse proliferation of endothelial cells within the full thickness of the dermis. DDA has been mainly associated with severe peripheral atherosclerosis. METHODS: We report a 63-year-old woman who presented with multiple erythematous-violaceous plaques with central deep skin ulcers on thighs, lower abdomen, and perianal area, associated with intermittent claudication, low-grade fever, and weight loss. Initially, the clinical picture along with positive cultures for Klebsiella pneumoniae suggested a multifocal ecthyma gangrenosum; nevertheless, a skin biopsy showed a diffuse dermal proliferation of endothelial cells interstitially arranged between collagen bundles. A computed tomography scan revealed severe aortic atheromatosis with complete luminal occlusion of the infrarenal aorta and common iliac arteries. RESULTS: The diagnosis of DDA secondary to severe atherosclerosis was established. The patient underwent a left axillofemoral bypass surgery with a rapidly healing of the ulcers in the next weeks. CONCLUSIONS: DDA should be considered in the differential diagnosis of livedoid ischemic lesions. Recognition of DDA as a cutaneous sign of severe peripheral vascular disease is important for both dermatologists and internists. Recognition of risk factors and their management with an early intervention to correct tissue ischemia can be curative.
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Angiomatosis/diagnóstico , Angiomatosis/etiología , Aterosclerosis/complicaciones , Aterosclerosis/diagnóstico , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/etiología , Aterosclerosis/cirugía , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
La lectura automatizada de citología basada en ThinPrep® es una evidente ayuda para el citotécnico y para el patólogo, al identificar campos de interés para ser evaluados. Algunos autores han demostrado la utilidad de la citología líquida ThinPrep® como sustitución del citospin en citología de orina, pero existe muy escasa información acerca de su utilidad. Objetivo. Evaluar la utilidad de la lectura automática de citología, en citología de orina. Material y métodos. Estudio retrospectivo de 180 extensiones de orina. Procesamiento según protocolo con plataforma ThinPrep®, tinción automatizada con teñidor Leica®, lectura manual de la extensión y diagnóstico. Lectura automatizada de citología utilizando Imager® y posterior revisión por los citotécnicos. Resultados. Los resultados fueron clasificados como positivos, negativos, atipia o polioma. La coincidencia diagnóstica fue del 83,9% (Kappa; IC 95%: 0,713 [0,619-0,807]). Todos los casos positivos fueron detectados por el sistema automático. De los 118 casos interpretados previamente como negativos, 97 (82%) fueron reinterpretados como tales. Ningún caso informado previamente como negativo fue interpretado como positivo. La sensibilidad y el valor predictivo negativo del Imager® para la detección de carcinoma en esta serie son del 100%. La especificidad es del 98%, y el valor predictivo positivo, del 91%. El citotécnico revisó 75 de las 180 laminillas (41,7%), la mayoría por atipias (89,6%) y negativos (32,3%). Conclusiones. El uso del Imager® como pre-cribado podría ayudar en la interpretación de la citología de orina. El porcentaje de casos que no precisan de revisión completa podría aumentar con la experiencia del citotécnico (AU)
ThinPrep® Imager system reading method of liquid-based cytology is currently a very helpful tool for both the cytotechnologist and the pathologist. Some authors have shown the usefulness of liquid-based cytology ThinPrep® as a replacement of the citospin in urine cytology. However, there is very little information about its usefulness. Objective. To evaluate the utility of reading urine cytology using ThinPrep® Imager System. Material and methods. A retrospective study of 180 urine cytology smears was carried out. Processing was done according to ThinPrep® platform protocol, automated staining with stainer Leica® and manual reading of the slide and diagnosis, followed by automated reading of cytology using Imager®. Review by cytotechnologists. Results. The results were classified as positive, negative, atypia or polioma. Diagnostic coincidence was 83.9% (Kappa; 95% IC, 0.713 [0,619-0,807]). All positive cases were detected by the automated system. Of the 118 cases previously interpreted as negative, 97 (82%) were reinterpreted as such. None previously reported as negative were interpreted as positive in the study with Imager®. Sensitivity as well as negative predictive value of the Imager® for the detection of carcinoma in this series are 100%. The specificity is 98% and the positive predictive value is 91%. The cytotechnologist reviewed 75/180 slides (41.7%), mostly with atypia (89.6%) or negative (32,3%). Conclusions. The use of the Imager® as a pre-screening method could help in the interpretation of urine cytology and a useful tool for the cytotechnologist. The percentage of cases that do not require complete revision could increase with the experience of the cytotechnologist (AU)