Anastomotic hemangioma (AH) is a rare benign vascular tumor primarily occurring in the genitourinary tract; however, only two cases have been reported in the thigh. In this report, a 42-year-old female patient presented to the hospital for examination due to "a subcutaneous mass on the lateral aspect of the left thigh discovered 9 months ago, which has been gradually enlarging." Subsequently, the lump was removed via local surgery. Histological examination reveals: At low magnification, the tumor was situated within the superficial subcutaneous fascia layer, presenting a loose lobular structure. Most of its margins were well - defined, while a small portion displayed expansile infiltrative changes. There were well - differentiated vascular lumens arranged in a communicating or anastomosing pattern, along with pseudopapillary structures. At high magnification, tumor cells were oval or short spindle - shaped, with vacuoles in the cytoplasm that contain red blood cells or homogeneously red - stained glassy globules. Moderate atypia was present, and mitotic activity was frequent, with hot spots averaging approximately 4/mm2. PCR-GNAQ mutation detection result: detected a missense mutation at codon 209 in exon 5 (c.627A>T, p. Q209H). Follow-up revealed tumor recurrence 10 months after surgery. Given the rarity of AH occurring on skin surfaces, coupled with the high proliferative activity observed in this case and its recurrence following excision, we report the diagnostic and therapeutic process along with the clinical and pathological features of this AH case. This aims to enhance the understanding of this disease among clinicians and pathologists.
Nonoperative management for rectal cancer is increasingly used, offering organ preservation for patients with a clinical complete response after neoadjuvant therapy. However, patients undergoing nonoperative management face a heightened risk of local regrowth and undergo intensive surveillance. Despite growing interest in nonoperative management, the patient experience and factors contributing to suboptimal surveillance are not well characterized. To explore patient perceptions, priorities, barriers, and facilitators related to care while undergoing nonoperative management after total neoadjuvant therapy for rectal cancer. Qualitative descriptive study using semistructured Zoom interviews that explored the patient experience with nonoperative management. Inductive thematic analysis was performed on interview transcripts. Single academic institution. Purposively sampled adults diagnosed with stage I to III rectal adenocarcinoma who completed total neoadjuvant therapy, achieved a clinical complete or near complete response, and elected nonoperative management were included. Patient perceptions and priorities in rectal cancer care for those on nonoperative management, as well as the barriers and facilitators to achieving recommended surveillance. Fifteen patients (8 women, 13 White individuals, median age 66 years [range, 56-81 years]) who were a median of 5 years from their decision to pursue nonoperative management participated in this study. Local regrowth occurred in 5 patients, 4 experienced distant metastases, and 1 had a permanent stoma. Treatment team recommendations strongly influenced treatment choice. Facilitators of surveillance included trusting, communicative provider relationships, positive patient outlook, and social support. Frequent appointments and uncertainty surrounding recurrence contributed to anxiety, which interfered with engagement in surveillance. This study is limited by selection bias and focus on a single-institution experience. Patients undergoing nonoperative management generally reported positive experiences supported by provider relationships and social networks. However, emotional burden and social and logistical demands posed significant barriers to surveillance. These findings can inform shared decision-making and highlight the need for system-level interventions to support patients throughout nonoperative management. See Video Abstract. ANTECEDENTES:El tratamiento no quirúrgico del cáncer rectal se utiliza cada vez más, ya que permite preservar el órgano en pacientes con una respuesta clínica completa tras la terapia neoadyuvante. Sin embargo, los pacientes sometidos a tratamiento no quirúrgico se enfrentan a un mayor riesgo de recidiva local y son objeto de una vigilancia intensiva. A pesar del creciente interés por el tratamiento no quirúrgico, la experiencia de los pacientes y los factores que contribuyen a una vigilancia subóptima no están bien caracterizados.OBJETIVO:Explorar las percepciones, prioridades, barreras y facilitadores de la atención de los pacientes mientras se someten a un tratamiento no quirúrgico después de una terapia neoadyuvante total para el cáncer rectal.DISEÑo:Estudio descriptivo cualitativo mediante entrevistas semiestructuradas por Zoom que exploraron la experiencia de los pacientes con el tratamiento no quirúrgico. Se realizó un análisis temático inductivo de las transcripciones de las entrevistas.ENTORNO:Una sola institución académica.PACIENTES:Adultos seleccionados deliberadamente diagnosticados con adenocarcinoma rectal en estadio I-III que completaron la terapia neoadyuvante total, lograron una respuesta clínica completa o casi completa y optaron por el tratamiento no quirúrgico.PRINCIPALES MEDIDAS DE RESULTADO:Percepciones y prioridades de los pacientes en la atención del cáncer rectal para aquellos en tratamiento no quirúrgico, así como las barreras y los facilitadores para lograr la vigilancia recomendada.RESULTADOS:Participaron quince pacientes (8 mujeres, 13 blancos, edad media de 66 años [rango: 56-81 años]), con una mediana de 5 años desde su decisión de seguir un tratamiento no quirúrgico. Se produjo un recidiva local en 5 pacientes, 4 experimentaron metástasis a distancia y 1 tuvo un estoma permanente. Las recomendaciones del equipo de tratamiento influyeron considerablemente en la elección del tratamiento. Los facilitadores de la vigilancia incluyeron la confianza, las relaciones comunicativas con los proveedores, la actitud positiva de los pacientes y el apoyo social. Las citas frecuentes y la incertidumbre en torno a la recurrencia contribuyeron a la ansiedad, lo que interfirió en la participación en la vigilancia.LIMITACIONES:Este estudio tiene limitaciones debido al sesgo de selección y al hecho de centrarse en la experiencia de una sola institución.CONCLUSIONES:Los pacientes sometidos a un tratamiento no quirúrgico informaron en general de experiencias positivas respaldadas por la relación con el proveedor y las redes sociales. Sin embargo, la carga emocional y las exigencias sociales y logísticas supusieron importantes obstáculos para la vigilancia. Estos resultados pueden servir de base para la toma de decisiones compartida y ponen de relieve la necesidad de intervenciones a nivel del sistema para apoyar a los pacientes a lo largo del tratamiento no quirúrgico. (AI-generated translations ).
Patients older than 70 years account for 44% of all rectal cancer cases. Although surgery is the criterion standard treatment, elderly patients can also be offered other treatments, such as total neoadjuvant therapy with watch and wait. This study aimed to investigate whether postoperative 90-day mortality is higher in elderly patients than in younger patients. This nationwide retrospective study included all consecutive resections of rectal cancer performed between 2005 and 2016 using data from the RALAR study. Patients were divided into 2 groups based on age: nonelderly (younger than 70 years) and elderly (70 years or older). Data were obtained from 19 Italian referral centers for colorectal surgery. A total of 3573 patients underwent rectal surgery: 2071 (57.9%) nonelderly and 1502 (42%) elderly. The primary end point was 90-day postoperative mortality. Secondary end points included intensive care unit stay, hospitalization, surgical and general postoperative complications, overall survival, disease-specific survival, and recurrence rate. Ninety-day postoperative mortality was comparable between groups (0.41% nonelderly vs 1.05% elderly, p = 0.087). Elderly patients were monitored more frequently in intensive care units and developed more postoperative general complications, whereas no differences were found between the groups in terms of postoperative surgical complications. Hospitalization was longer in elderly patients (median [interquartile range]: 12.3 [9.7] vs 11.1 [14.6] days). Five-year overall survival was higher in the nonelderly group (77.3%) than in the elderly group (45.8%; adjusted OR 1.70; 95% CI, 0.57-5.65), whereas the disease-specific survival was similar between groups. There are limitations inherent in this retrospective study, including the long accrual period and the unknown proportion of patients who did not undergo surgery. Although elderly patients experience a higher rate of postoperative general complications without an increase in postoperative mortality, rectal surgery yields similar surgical and oncological outcomes compared with younger patients. This study suggests that age alone should not exclude a patient from surgery. See Video Abstract . ANTECEDENTES:Los pacientes mayores de 70 años representan el 44 % de todos los casos de cáncer rectal. Aunque la cirugía es el tratamiento de referencia, a los pacientes de edad avanzada también se les pueden ofrecer otros tratamientos, como la terapia neoadyuvante total con vigilancia y espera.OBJETIVO:El objetivo de este estudio fue investigar si la mortalidad postoperatoria a los 90 días es mayor en los pacientes de edad avanzada en comparación con los pacientes más jóvenes.DISEÑO:Este estudio retrospectivo a nivel nacional incluyó todas las resecciones consecutivas de cáncer rectal entre 2005 y 2016 utilizando datos del estudio RALAR. Los pacientes se dividieron en dos grupos según su edad: no ancianos <70 años y ancianos.ENTORNO:Los datos se obtuvieron de 19 centros de referencia italianos para cirugía colorrectal.PACIENTES:Un total de 3573 pacientes se sometieron a cirugía rectal: no ancianos (2071, 57,9 %) y ancianos (1502, 42 %).PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la mortalidad postoperatoria a los 90 días. Los criterios de valoración secundarios incluyeron la estancia en la unidad de cuidados intensivos, la hospitalización, las complicaciones quirúrgicas y generales postoperatorias, la supervivencia global, la supervivencia específica de la enfermedad y la tasa de recurrencia.RESULTADOS:La mortalidad postoperatoria a los 90 días fue comparable entre los grupos (0,41 % en los no ancianos frente al 1,05 % en los ancianos, p = 0,087). Los pacientes de edad avanzada fueron monitorizados con mayor frecuencia en la unidad de cuidados intensivos y desarrollaron más complicaciones generales posoperatorias, mientras que no se encontraron diferencias entre los grupos en cuanto a complicaciones quirúrgicas posoperatorias. La hospitalización fue más prolongada en los pacientes de edad avanzada (mediana [IQR]: 12,3 [9,7] frente a 11,1 [14,6] días). La supervivencia global a cinco años fue mayor en los no ancianos (77,3 %) en comparación con los ancianos (45,8 %, OR ajustado 1,70, IC del 95 %: 0,57, 5,65), mientras que la supervivencia específica de la enfermedad fue similar entre los grupos.LIMITACIONES:Este estudio retrospectivo presenta limitaciones inherentes, como el largo periodo de acumulación y la proporción desconocida de pacientes que no se sometieron a cirugía.CONCLUSIONES:Aunque los pacientes de edad avanzada experimentan una mayor tasa de complicaciones generales postoperatorias sin un aumento de la mortalidad postoperatoria, la cirugía rectal produce resultados quirúrgicos y oncológicos similares a los de los pacientes más jóvenes. Este estudio sugiere que la edad por sí sola no debería ser motivo para excluir a alguien de la cirugía. ( AI-generated translation ).
Synchronous colon cancer is defined as 2 or more primary colon cancers diagnosed simultaneously or within 6 months. It comprises 3% to 5% of all colon cancer diagnoses. Although increased risk of postoperative morbidity has generally been reported, the impact on long-term outcomes remains unclear. This study evaluated the impact of synchronous colon cancer on disease-free and overall survival compared with solitary tumors in the total population (primary objective) and in stratified subgroups (secondary objective) by sidedness and by stage of the most advanced tumor. This was a retrospective, observational, cross-sectional, collaborative, multicenter, population-based study. The dominant tumor of synchronous cancers was determined by pathological stage and clinical features. Bilateral tumors were defined as synchronous left- and right-sided tumors. Multicenter collaborative research involving 50 Dutch hospitals. Patients with a curatively intended oncological resection for stage I to III colon cancer, between January 1, 2014, and December 31, 2015, were included. Follow-up details were provided by local collaborators from October 2021 until June 2024. Disease-free and overall survival. A total of 7982 patients with stage I to III colon cancer were included, of whom 269 patients (3.4%; 95% CI, 3.0-3.8) had synchronous colon tumors. Of those, 155 patients (58%) had a right-dominant tumor and 190 (71%) had unilateral tumors. The median follow-up was 60.1 months (interquartile range 36.2-68.8). No differences between solitary and synchronous colon cancer were found in 5-year disease-free survival (70.0% ± 0.01 vs 65.7% ± 0.03, p = 0.10) or overall survival (75.5% ± 0.01 vs 72.4% ± 0.03, p = 0.59), nor after stratification for stage. No differences in disease-free or overall survival between unilateral and bilateral synchronous colon cancer, nor between right-dominant versus left-dominant synchronous colon cancer, were observed. A limitation of this study was its retrospective nature. This study demonstrated no significant differences in 5-year disease-free or overall survival between solitary and synchronous colon cancer, nor between subgroups of synchronous colon cancer depending on tumor location. See Video Abstract . ANTECEDENTES:El cáncer de colon sincrónico se define como dos o más cánceres de colon primarios diagnosticados simultáneamente o en un plazo de seis meses. Comprende entre el 3 % y el 5 % de todos los diagnósticos de cáncer de colon. Aunque en general se ha informado de un mayor riesgo de morbilidad posoperatoria, el impacto en los resultados a largo plazo sigue sin estar claro.OBJETIVO:Este estudio evaluó principalmente el impacto del cáncer de colon sincrónico en la supervivencia libre de enfermedad y la supervivencia global en comparación con los tumores solitarios en la población total y, en segundo lugar, en subgrupos estratificados por lateralidad y por estadio del tumor más avanzado.DISEÑO:Se trata de un estudio retrospectivo, observacional, transversal, colaborativo, multicéntrico y basado en la población. El tumor dominante de los cánceres sincrónicos se determinó por el estadio patológico y las características clínicas. Los tumores bilaterales se definieron como tumores sincrónicos del lado izquierdo y derecho.ENTORNO:Investigación colaborativa multicéntrica en la que participaron 50 hospitales neerlandeses.PACIENTES:Se incluyeron pacientes con una resección oncológica con intención curativa para el cáncer de colon en estadio I-III, entre el 1 de enero de 2014 y el 31 de diciembre de 2015. Los detalles del seguimiento fueron proporcionados por colaboradores locales desde octubre de 2021 hasta junio de 2024.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia libre de enfermedad y supervivencia global.RESULTADOS:Se incluyó a un total de 7982 pacientes con cáncer de colon en estadio I-III, de los cuales 269 (3,4 %, IC del 95 %: 3,0-3,8) tenían tumores de colon sincrónicos. De ellos, 155 pacientes (58 %) tenían un tumor dominante en el lado derecho y 190 (71 %) tenían tumores unilaterales. La mediana del seguimiento fue de 60,1 meses (IQR 36,2-68,8). No se encontraron diferencias entre el cáncer de colon solitario y el sincrónico en cuanto a la supervivencia libre de enfermedad a 5 años (70,0 % ± 0,01 frente a 65,7 % ± 0,03, p = 0,10) y la supervivencia global (75,5 % ± 0,01 frente a 72,4 % ± 0,03, p = 0,59), ni tras la estratificación por estadio. No se observaron diferencias en la supervivencia libre de enfermedad o global entre el cáncer de colon unilateral y el sincrónico bilateral, ni entre el cáncer de colon sincrónico dominante en el lado derecho y el dominante en el lado izquierdo.LIMITACIONES:Una limitación de este estudio fue su naturaleza retrospectiva.CONCLUSIONES:Este estudio no demostró diferencias significativas en la supervivencia libre de enfermedad y global a 5 años entre el cáncer de colon solitario y el sincrónico, ni entre los subgrupos de cáncer de colon sincrónico en función de la localización del tumor. (AI-generated translation ).
Granular cell astrocytoma (GCA) is a rare, morphologically distinct variant of IDH-wildtype glioblastoma that can appear deceptively low-grade yet behave aggressively. Its molecular features remain poorly defined, and no methylation-based classification has previously been reported. Two GCAs diagnosed in our clinical neuropathology department were described with the integration of clinical, intraoperative, histopathological, and molecular data, including DNA methylation profiling, a targeted next-generation sequencing panel, and, in one case, whole genome sequencing (WGS). The patients were aged 63 and 54 years old, respectively, both presenting with supratentorial tumors showing granular cell morphology. Case 1 showed a densely cellular tumor composed entirely of bland-appearing granular cells without a conventional astrocytic component. Case 2 showed low-grade granular cell areas transitioning into high-grade astrocytic regions with mitoses, microvascular proliferation, and necrosis. Despite these morphological differences, both cases matched the methylation class "Glioblastoma, IDH-wildtype, mesenchymal subtype" and shared molecular features typical of glioblastoma, including chromosome +7/-10 and CDKN2A/B deletion. Both patients harbored oncogenic NF1 variants. WGS in Case 2 also revealed homozygous MTAP loss and chromoanasynthesis on chromosome 9. Case 1 received Stupp protocol chemoradiotherapy, recurred after 3 months of treatment, and died 11 months after diagnosis. Case 2 has progressed with a new posterior fossa lesion while on adjuvant temozolomide. These cases demonstrate that GCAs span a morphological spectrum yet molecularly correspond to the mesenchymal subtype of IDH-wildtype glioblastoma. Integrated molecular testing is therefore essential for accurate diagnosis and for guiding clinical management, including consideration for potential clinical trial enrollment.
Solid papillary carcinoma (SPC) is a rare type of breast cancer that accounts for approximately 1% of all breast cancers. Although SPC is considered an indolent tumor, metastasis occurs in a few cases. The biological behavior and genomic characteristics of invasive SPC (ISPC) need to be further explored. A 44-year-old woman presented with a mass in her right breast in 2016 and ultrasound-guided mammotome (MMT) vacuum-assisted biopsy (VAB) pathology indicated an invasive lobular carcinoma (ILC). The patient subsequently underwent right partial mastectomy and axillary lymph node dissection, followed by radiotherapy and hormonal therapy. Eight years later, in 2024, ultrasonography revealed a 1.3 cm*1.0 cm mixed echogenic mass in her right breast, and biopsy pathology showed solid tumor nests with mucus secretion and thin fibrovascular cores. The pathological diagnosis was SPC with positive expression of the neuroendocrine marker synaptophysin (syn). The patient underwent right subcutaneous mastectomy with prosthesis implantation, followed by hormonal therapy. Four months later, multiple masses were found in her liver by ultrasonography and contrast-enhanced magnetic resonance imaging (MRI), which were eventually confirmed as metastatic SPC by pathology. A comprehensive next-generation sequencing (NGS) panel test was performed, and more genetic changes were identified including CCND1, FGF19, GATA3, KMT2C, MEN1, TP53, BRCA2, PI3KC3, and ERCC2::KLC3 fusion. The patient was treated with hormonal therapy combined with CDK4/6 inhibitors and so far no new lesions have appeared. We report a case of ISPC with liver metastasis in a patient with a history of ILC. Some meaningful genetic variations were identified by NGS. Further studies are needed to elucidate the molecular characteristics of SPC and explore the best therapeutic strategies.
Colorectal cancer (CRC) is diagnosed during approximately 1 in 13,000 pregnancies and is associated with worse outcomes, including a higher incidence of metastatic disease at diagnosis and reduced maternal survival compared to non-pregnant patients. In this study, we investigated two key contributors to this phenomenon: (1) the increased cancer aggressiveness driven by elevated prolactin (PRL) levels during pregnancy and (2) the limited treatment options available to pregnant CRC patients. For the first time, we demonstrate that pregnancy-level PRL directly enhances JAK2/STAT3 and JAG1/NOTCH1 signaling in CRC cells, promoting epithelial-mesenchymal transition (EMT) and cancer stem-like protein expression. We developed and fitted a computational model of the JAK2/STAT3 signaling pathway to our in vitro data, identifying specific nodes within the cascade that are most sensitive to PRL fluctuations during pregnancy. Clinically, we highlight data from CRC cases at Vanderbilt University Medical Center, which underscore the more advanced stage at diagnosis in pregnant patients and the limited treatment options available due to concerns about fetal safety. Additionally, we show that PRL exposure sensitizes CRC cells to TRAIL-induced apoptosis, supporting the potential of TRAIL-based therapies, particularly in liposomal form, as a pregnancy-compatible treatment approach. This study provides the first mechanistic link between pregnancy-level prolactin and increased CRC aggressiveness through JAK2/STAT3 and JAG1/NOTCH1 signaling. It also suggests a novel therapeutic direction by demonstrating that PRL sensitizes CRC cells to TRAIL-induced apoptosis. Together, our findings highlight the need for new therapeutic strategies for safe and effective treatment of CRC in pregnant patients. El cáncer colorrectal (CRC) se diagnostica durante aproximadamente 1 de cada 13.000 embarazos y se asocia con peores pronósticos, incluyendo una mayor incidencia de metastásis en el momento del diagnóstico y una menor supervivencia en comparación con pacientes no embarazadas. En este estudio investigamos dos factores clave que contribuyen a este fenómeno: (1) el aumento de la agresividad de las células cancerígenas causado por los niveles elevados de prolactina (PRL) durante el embarazo, y (2) las limitaciones de las opciones terapéuticas disponibles para pacientes embarazadas con CRC. Por primera vez demostramos que los niveles de PRL durante el embarazo aumentan la señalización JAK2/STAT3 y JAG1/NOTCH1 en células de CRC, incrementando la transición epitelio-mesénquima (EMT) y la expresión de proteínas asociadas a un fenotipo de células madre cancerosas. Desarrollamos y ajustamos un modelo in silico de la vía de señalización JAK2/STAT3 basado en nuestros datos in vitro, identificando nodos específicos dentro de la cascada que son especialmente sensibles a las fluctuaciones de PRL durante el embarazo. Clínicamente, destacamos datos de casos de CRC del Vanderbilt University Medical Center, que muestran un estadío más avanzado en el diagnóstico en pacientes embarazadas y las opciones terapéuticas restringidas debido a preocupaciones sobre la seguridad fetal. Además, mostramos que la exposición a PRL sensibiliza a las células de CRC a la apoptosis inducida por TRAIL, lo que respalda el potencial de terapias basadas en TRAIL, particularmente en liposomas, como un enfoque terapéutico compatible con el embarazo. Este estudio proporciona el primer vínculo mecanístico entre los niveles de prolactina durante el embarazo y el aumento de la agresividad del CRC a través de la señalización JAK2/STAT3 y JAG1/NOTCH1. También sugerimos una nueva dirección terapéutica al demostrar que la PRL sensibiliza las células de CRC a la apoptosis inducida por TRAIL. En conjunto, el estudio subraya la necesidad de nuevas estrategias terapéuticas para el tratamiento seguro y eficaz del CRC en pacientes embarazadas.
Testicular germ cell tumors (TGCTs), though typically responsive to therapy, may rarely develop somatic-type malignancy (STM), a transformation associated with poor prognosis and chemoresistance. This study presents two cases of postpubertal-type teratoma with intestinal-type adenocarcinoma as STM, offering insights into their clinical, histopathological, immunophenotypic, and molecular profiles. The first patient, a 63-year-old male, presented with pulmonary and retroperitoneal metastases and underwent orchiectomy, revealing an intratesticular intestinal-type adenocarcinoma. Molecular testing confirmed 12p overrepresentation and pathogenic mutations in CTNNB1, STK11, and MDM2. The second patient, initially diagnosed at age 35 with a mixed TGCT, developed STM as a late recurrence 16 years post-orchiectomy, manifesting as a retroperitoneal mass with vertebral invasion. Histology again confirmed intestinal-type adenocarcinoma, and molecular testing revealed amplification of ERBB2, KRAS, along with mutations in TP53 and PIK3CA. Both cases were managed with capecitabine-oxaliplatin plus bevacizumab, followed by maintenance therapy, achieving disease stabilization for at least 9 months. These cases illustrate the diagnostic and therapeutic complexities of STM, particularly with adenocarcinoma morphology that may mimic primary gastrointestinal neoplasms. Accurate diagnosis required exclusion of alternate primary sites and demonstration of chromosome 12 aberrations using FISH and next-generation sequencing. Our findings emphasize the importance of long-term follow-up in TGCT patients, particularly those with teratomatous elements, and highlight the value of cytogenetic and molecular profiling in confirming STM and identifying potential therapeutic targets. Given the rarity of STM, especially in metastatic or recurrent settings, there is an urgent need for standardized diagnostic protocols and evidence-based treatment strategies. These cases support the use of tumor-specific chemotherapy regimens guided by the histological and molecular characteristics of STM.
Cutaneous adnexal carcinomas (CACs) comprise a diverse group of malignant tumors that show morphological differentiation toward one of the four main adnexal structures in normal skin: hair follicles, sebaceous glands, sweat-apocrine glands, and sweat-eccrine glands. These tumors can arise sporadically or may be associated with rare genetic syndromes. A total of 276 CACs cases underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of genomic alterations (GA). Sequencing data were used to determine microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), genomic ancestry, and COSMIC mutational signatures. PD-L1 expression was evaluated by immunohistochemistry (TPS; Dako 22C3). Statistical analyses were performed using Fisher's exact test, with false discovery rate correction via the Benjamini-Hochberg method. Sequencing was performed on primary cutaneous tumors in 131 cases (47.4%) and on local recurrence or metastatic site biopsies in 145 cases (52.5%). Across all groups, there was a male predominance (64-81%) and similar mean ages (59-63 years), with apocrine (APO) tumors occurring in older patients than eccrine (ECC) tumors (72 vs. 62 years; p = 0.001). Histologically, 173 tumors (62.7%) were sweat gland-derived (SWT), 55 (19.9%) sebaceous gland-derived (SEB), 14 (5.1%) hair follicle-derived (HRF), and 34 (12.3%) unclassified (UNK). Among SWT tumors, 150 (86.7%) were eccrine and 23 (13.3%) apocrine. SWT tumors included digital papillary adenocarcinomas (DPA, 6.9%), mucinous carcinomas (MC, 6.3%), porocarcinomas (POR, 11.0%), spiradenocarcinomas (SPR, 8.1%), syringoadenocarcinomas (SRNG, 5.8%), and 77 (44.5%) unclassified cases. The number of GA per tumor was highest in SEB compared with SWT tumors (7.9 vs. 4.9; p = 0.005) and lowest in DPA (2.1 vs. 5.0 in non-DPA; p = 0.03). No differences in ancestry distribution were observed. Compared with SWT tumors, SEB tumors exhibited higher frequencies of RB1 (38.2% vs. 8.1%; p < 0.0001) and TP53 alterations (76.4% vs. 43.4%; p = 0.0002), suggesting potential neuroendocrine differentiation. MC tumors showed significantly higher PTCH1 alterations than non-MC tumors (36.4% vs. 1.8%; p = 0.044). MSI-high status was most frequent in SEB tumors compared with all other groups (15.7% vs. 1.2%; p = 0.005), and gLOH > 16% was also more common in SEB than SWT tumors (19.6% vs. 7.2%; p = 0.081). The MMR signature occurred more frequently in SEB than SWT tumors (32.0% vs. 2.1%; p = 0.005). Mean TMB was elevated across most CACs types, ranging from 10.4 mutations/Mb in HRF to 38.8 mutations/Mb in MC, with the exceptions of APO (2.7 mut/Mb; p = 0.001) and DPA (1.4 mut/Mb; p = 0.003). PD-L1 expression was generally low and did not differ significantly between SWT and SEB tumors (37.0% vs. 33.3%; NS). Given the limited data on CAC treatment, this study provides a catalog of commonly observed GA. SEB tumors exhibited the highest frequency of genomic alterations. Prospective clinical trials are needed to determine the prognostic and predictive value of CAC-specific biomarkers for immune checkpoint inhibitor (ICI) response, which is essential for integrating novel therapies into the evolving treatment landscape.
Hungary ranks among the countries with both the highest incidence and mortality of head and neck cancers worldwide. The COVID-19 pandemic, caused by the SARS-CoV-2 virus placed a significant burden on the healthcare system. Our study aims to investigate its impact on Hungarian head and neck cancer patients by analyzing changes in stage at presentation, patient delay and overall survival due to the viral pandemic. A retrospective cohort study was performed analyzing patients' medical records from a tertiary head and neck surgical center in Hungary. The inclusion criteria required the tumor to be a squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Based on the timing of restrictive measures due to the pandemic, patients were divided into two groups: Group A: "pre-COVID-19" (3 September 2012 - 11 March 2020) and Group B: "post-COVID-19 onset" (12 March 2020 - 5 December 2022) The latter group was further subdivided into Group C: "during-COVID-19" (12 March 2020 - 13 June 2021) and Group D: "post-COVID-19" (14 June 2021 - 5 December 2022). 620 patients met the inclusion criteria. Group A had 427 patients, Group B had 193, Group C had 69, and Group D had 124. Compared to Group A (54.1%), there was a higher proportion of N+ status patients in Group B (69.6%), Group C (63.8%), and Group D (73.0%), with a significant difference throughout. Changes in T status and patient delay time was not present. Analyzing symptoms, there was a significant increase in delay time for patients with hemoptysis (from 2.1 to 16.3 weeks). No significant difference in overall survival was observed between the study groups. There are limited publications available on this topic in Europe, particularly in Hungary, especially studies that compare the periods before, during, and after the COVID-19 pandemic. Head and neck cancer patients were found to have more advanced clinical nodal disease after the COVID-19 onset, despite no changes in patient delay time and overall survival. Our findings highlight the importance of further studies on how viral infections and pandemics affect oncology care pathways to improve preparedness for future public health crises.
Gastric carcinomas (GC) are heterogeneous malignancies characterised by distinct histological and molecular subtypes. The microsatellite instability (MSI) molecular subtype, resulting from deficient DNA mismatch repair (dMMR), accounts for approximately 22% of global GC cases. Empirical evidence indicates differences in clinicopathological features, demographics, and treatment response in MSI GC compared to microsatellite stable (MSS) GC. MSI status has emerged as a potential biomarker for advanced GC, and this study aimed to determine the MSI prevalence of histopathologically confirmed GC cases at our centre. This was a retrospective cross-sectional analysis of GC cases from 2018 to 2022, which were retrieved from the laboratory information system. DNA from these cases was isolated and assessed for MSI using a pentaplex PCR panel and confirmatory IHC on MSI-H was performed. Samples with no allelic size variation in the 5 microsatellite markers were classified as microsatellite stable (MSS), variation in 1 marker as microsatellite instability low (MSI-L), and variation in 2 or more microsatellite markers as MSI-H. The study consisted of 64 cases with a MSI prevalence of 21.9% (n = 14) displaying a male predominance (n = 10; 71.4%) and a mean age of 62.7 years. Among these 14 MSI cases, 42.9% (n = 6) were classified as MSI-H with a mean age of 59.3 years. Half (n = 3) of these cases presented with upper gastrointestinal bleeding, with a majority of them diagnosed with moderately differentiated adenocarcinomas (66.7%). Microsatellite instability low was seen in 57.1% (n = 8) of the cases with a mean age of 65.3 years, and of these, patients presented with vomiting, epigastric pain and dysphagia with equal frequency at 25% (n = 2 respectively). The frequency of MSI cases in this study is congruent with global trends, highlighting the importance of microsatellite status in GC for understanding clinicopathological differences between MSI and MSS patients. These findings support the potential of MSI status as a biomarker.
Pelvic exenteration is the treatment of choice for selected patients with locally advanced primary and recurrent rectal cancer. Involvement of major pelvic neurovascular structures and bone was historically considered a contraindication due to unacceptably high rates of morbidity and low R0 resection rates. To compare the outcomes of these "high-complexity" exenterative resections to those of "conventional" pelvic exenteration. International multicenter retrospective cohort study. Sixteen specialized exenteration centers. Those who underwent total pelvic exenteration for locally advanced primary and recurrent rectal cancer between 2018 and 2023 at participating centers. Perioperative resource utilization, morbidity, mortality, and R0 resection rates were reported. Seven hundred sixty-three patients underwent total pelvic exenteration, of whom 478 (63%) and 285 (37%) required conventional and high-complexity procedures, respectively. High-complexity pelvic exenteration was associated with longer operating time (600 vs 480 minutes, p < 0.001 for locally advanced primary rectal cancer, 623 vs 480 minutes, p < 0.001 for locally recurrent rectal cancer), intensive care stay (2 vs 1 day, p < 0.001 and 3 vs 1 day, p < 0.001), hospital stay (19 vs 15 days, p = 0.008 and 23 vs 15 days, p < 0.001), and higher blood loss (2000 vs 1236 mL, p < 0.001 and 3000 vs 1600 mL, p < 0.001). Morbidity and mortality outcomes and R0 resection rates were similar between the groups. Generalizability of findings outside of expert units. High-complexity pelvic exenteration for the treatment of rectal cancer is associated with similar morbidity, mortality, and R0 resection rates, but it has a significantly higher operative time, blood loss, and hospital resource utilization compared to conventional pelvic exenteration. In high-volume, specialized centers, these techniques are considered the standard of care for appropriately selected patients with tumors that involve major pelvic bone or neurovascular structures. See Video Abstract . ANTECEDENTES:La exenteración pélvica es el tratamiento de elección para determinados pacientes con cáncer rectal primario y recurrente localmente avanzado. La afectación de las principales estructuras neurovasculares y óseas pélvicas se consideraba históricamente una contraindicación debido a las tasas inaceptablemente altas de morbilidad y a las bajas tasas de resección R0.OBJETIVO:Comparar los resultados de estas resecciones exenteración «de alta complejidad» con los de la exenteración pélvica «convencional».DISEÑO:Estudio de cohorte retrospectivo multicéntrico internacional.ENTORNOS:Dieciséis centros especializados en exenteración.PACIENTES:Aquellos que se sometieron a una exenteración pélvica total por cáncer rectal primario y recurrente localmente avanzado entre 2018 y 2023 en los centros participantes.PRINCIPALES MEDIDAS DE RESULTADOS:Se informaron la utilización de recursos perioperatorios, la morbilidad, la mortalidad y las tasas de resección R0.RESULTADOS:763 pacientes se sometieron a una exenteración pélvica total, de los cuales 478 (63 %) y 285 pacientes (37 %) requirieron procedimientos convencionales y de alta complejidad, respectivamente. La exenteración pélvica de alta complejidad se asoció con un tiempo quirúrgico más prolongado (600 frente a 480 minutos, p < 0,001 para el cáncer rectal primario localmente avanzado, 623 frente a 480 minutos, p < 0,001 para el cáncer rectal localmente recurrente), estancia en cuidados intensivos (2 frente a 1 día, p < 0,001 y 3 frente a 1 día, p < 0,001), estancia hospitalaria (19 frente a 15 días, p = 0,008 y 23 frente a 15 días, p < 0,001) y mayor pérdida de sangre (2000 frente a 1236 ml, p < 0,001 y 3000 frente a 1600 ml, p < 0,001). Los resultados de morbilidad y mortalidad, así como las tasas de resección R0, fueron similares entre los grupos.LIMITACIONES:Generalización de los resultados fuera de las unidades especializadasCONCLUSIONES:La exenteración pélvica de alta complejidad para el tratamiento del cáncer de recto se asocia con tasas similares de morbilidad, mortalidad y resección R0, pero con un tiempo quirúrgico, una pérdida de sangre y una utilización de recursos hospitalarios significativamente mayores en comparación con la exenteración pélvica convencional. En centros especializados con un gran volumen de casos, estas técnicas se consideran el tratamiento estándar para pacientes adecuadamente seleccionados con tumores que afectan a los huesos pélvicos principales o a las estructuras neurovasculares. ( AI-generated translation ).
Ki-67 proliferation indices (PIs) define the grading of GastroEnteroPancreatic NeuroEndocrine Neoplasms (GEPNENs) and are crucial for therapeutic decisions. The precise Ki-67 assessment relies on manual counting, which is time-consuming, hardly accessible during routine pathological signout and thus usually replaced by the easier eye-estimation/balling method prone to interobserver variability and differences originating from the hot-spot size, localisation and tumor heterogeneity. These discrepancies can significantly affect the final PI resulting in misgrading of GEPNENs with potential adverse patient outcomes. In the era of digital pathology more and more applications are available to overcome this problem. In our retrospective study of 60 surgically resected GEPNEN cases, we tested the equivalence of traditional clinical (C) grading, manual counting with a MarkerCounter (MC) application and automatic grading with tumor recognition PatternQuant application with subsequent NuclearQuant (NQ) PI-assessment within 3DHistechs digital pathology platform. We found almost perfect agreement between the various grading methods (Spearman rank-order correlations: C vs. MC: ρ = 0.912, C vs. NQ: ρ = 0.883, MC vs NQ: ρ = 0.953) without clinically significant misgradings. Also the numerical values of the PIs derived with the various methods showed close correlations (Linear regression: C vs. MC: r = 0.952, C vs. NQ: r = 0.925, MC vs NQ: r = 0.978). The automated PI-assessment involved a mean 5-fold more tumor cells, better approximating the global/total Ki-67 PI, which was earlier shown to deliver more robust prognostic power and decreased interobserver variability. Furthermore, G3 tumors differed from G2 and G1 tumors in their cytomorphological parameterers: high grade tumors had significantly larger and more polymorphic, less regular tumor cell nuclei, which parameters could be also utilized for grading and/or prognostication purposes. Our study applied a simple, quick, easy-to-use, Machine Learning-based method that could be incorporated into routine digital pathology signout alleviating pathologists' workload and increasing precision and recall rate.
Duchenne muscular dystrophy (DMD) is a progressive, severe muscle-wasting disease caused by mutations in DMD, encoding dystrophin, that leads to loss of muscle function with cardiac/respiratory failure and premature death. Since dystrophic muscles are sensed by infiltrating inflammatory cells, and gut microbial communities can cause immune dysregulation and metabolic syndrome, we sought to investigate whether intestinal bacteria support the muscle immune response in the mdx dystrophic murine model. We highlighted a strong correlation between DMD disease features and the relative abundance of Prevotella. Furthermore, the absence of gut microbes through the generation of mdx germ-free animal model, as well as modulation of the microbial community structure by antibiotic treatment, influenced muscle immunity and fibrosis. Intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function. This work identifies a potential role for the gut microbiota in the pathogenesis of DMD.
Leiomyomas of the gastrointestinal tract (GI) are benign smooth muscle neoplasms with limited genetic characterization. Molecular investigations may improve diagnostic classification and enhance understanding of their biological behavior. RNA sequencing using multiple fusion-detection algorithms was performed on an ileal leiomyoma. Key findings were validated by RT-PCR and Sanger sequencing. A MYH11::GLI3 fusion was identified. Additional chimeric transcripts were detected but interpreted as secondary events based on limited read support. The biological relevance of MYH11::GLI3 relates to smooth muscle specific MYH11 expression and GLI3-mediated Hedgehog signaling. This study reports, for the first time, the identification of a MYH11::GLI3 chimera in gastrointestinal leiomyoma, thereby expanding the molecular spectrum of these tumors. Deregulation of GLI3 may represent an alternative mechanism of Hedgehog pathway perturbation in this neoplasm. The frequency and clinical significance of GLI3-rearranged gastrointestinal smooth muscle tumors remain to be determined.
Only a few reports have exclusively assessed urinary function after laparoscopic rectal surgery, despite long-term investigations. To investigate urinary function after laparoscopic low rectal cancer surgery using 3 types of questionnaires collected during a prospective clinical phase II trial (ULTIMATE trial) involving 47 Japanese hospitals. Prospective. Japanese tertiary hospitals. A total of 300 patients undergoing laparoscopic low rectal cancer surgery. Residual urine was measured twice daily on postoperative days 5 to 7. The International Prostate System Score, Overactive Bladder Symptom Score, and International Consultation on Incontinence Questionnaire-Short Form scoring were used to evaluate urinary disorders. Short-term voiding dysfunction was diagnosed in 78 patients and was associated with surgery duration, which was the only factor that affect voiding function in multivariate analysis. The differences in International Prostate System Score before and after surgery were significantly larger in patients who underwent abdominoperineal resection; in these patients, the urinary function did not recover over time. The mean International Prostate System Score in patients older than 75 years was significantly worse postoperatively than before surgery, and the difference was significantly larger in the older group than in the younger group. In the multivariate analysis, the type of surgery, abdominoperineal resection, and age older than 75 years were significant factors affecting the International Prostate System Score after surgery. There were no significant differences in the Overactive Bladder Symptom Score or International Consultation on Incontinence Questionnaire-Short Form score after surgery, even with respect to the clinical and operative variables. The trial was limited only to early-stage rectal cancer and recruited patients from 47 hospitals with a range of surgical techniques. Our findings indicated urinary function deterioration in those who underwent abdominoperineal resection and those with advanced age after laparoscopic surgery for early low rectal cancer. See Video Abstract . UMIN000011750. ANTECEDENTES:A pesar de las investigaciones a largo plazo, pocos estudios han evaluado exclusivamente la función urinaria tras la cirugía rectal laparoscópica.OBJETIVO:Investigar la función urinaria tras la cirugía laparoscópica de cáncer de recto bajo mediante tres tipos de cuestionarios recopilados durante un ensayo clínico prospectivo de fase II (ensayo ULTIMATE) en el que participaron 47 hospitales japoneses.DISEÑO:Prospectivo.ÁMBITO:Hospitales terciarios japoneses.PACIENTES:Un total de 300 pacientes sometidos a cirugía laparoscópica de cáncer de recto bajo.PRINCIPALES MEDIDAS DE RESULTADO:Se midió el volumen de orina residual dos veces al día entre los días 5 y 7 del postoperatorio. Para evaluar los trastornos urinarios, se utilizaron la Escala Internacional del Sistema Prostático, la Escala de Síntomas de Vejiga Hiperactiva y la versión corta del Cuestionario Internacional de Consulta sobre Incontinencia.RESULTADOS:Se diagnosticó disfunción miccional a corto plazo en 78 pacientes, la cual se asoció con la duración de la cirugía, siendo este el único factor que afectó la función miccional en el análisis multivariante. Las diferencias en la puntuación del Sistema Internacional de la Próstata (SIP) antes y después de la cirugía fueron significativamente mayores en los pacientes sometidos a resección abdominoperineal; en estos pacientes, la función urinaria no se recuperó con el tiempo. La puntuación media del SIP de los pacientes mayores de 75 años fue significativamente peor después de la cirugía que antes de la misma, y las diferencias fueron significativamente mayores en el grupo de mayor edad que en el grupo más joven. En el análisis multivariante, el tipo de cirugía, la resección abdominoperineal y la edad superior a 75 años fueron factores significativos que afectaron la puntuación del SIP después de la cirugía. No se observaron diferencias significativas en la puntuación de los síntomas de vejiga hiperactiva ni en la puntuación del Cuestionario Internacional de Consulta sobre Incontinencia (versión corta) después de la cirugía, incluso considerando las variables clínicas y quirúrgicas.LIMITACIONES:El estudio se limitó a pacientes con cáncer de recto en estadio temprano y reclutó pacientes de 47 hospitales con diversas técnicas quirúrgicas.CONCLUSIONES:Nuestros hallazgos indicaron un deterioro de la función urinaria en quienes se sometieron a resección abdominoperineal y en aquellos de edad avanzada tras una cirugía laparoscópica por cáncer de recto bajo en estadio temprano. (AI-generated translation )REGISTRO DEL ENSAYO CLÍNICO:UMIN000011750.
Rapid on-site evaluation (ROSE) during bronchoscopy provides the opportunity to assess the adequacy of the sampling site, thus enabling diagnosis. The rapid evaluation of smears is typically performed by cytopathologists, but this is not always feasible. At our institution, a university-trained clinical biochemist performs the evaluation of ROSE smears. Our aim was to compare ROSE evaluations conducted by a laboratory specialist and a cytopathologist. We assessed the adequacy of lymph node samples from 78 patients using ROSE: 37 samples were obtained via EBUS-TBNA and 41 via TBNA. All smears were examined by the laboratory specialist, and simultaneously prepared parallel smears from the same needle passes were sent to the Department of Pathology for evaluation. Of the 78 samples, both the laboratory specialist and the pathologist team deemed 63 samples adequate and 8 samples inadequate. In 7 cases, there was a disagreement between the pathologist team and laboratory specialist. This resulted in a 92.3% agreement. The Cohen's kappa value was 0.71, indicating strong and Gwet's AC1 value was 0.90 corresponding to almost perfect agreement. The diagnostic performance was also excellent. Our conclusion is that ROSE performed by a laboratory specialist is a suitable alternative to on-site evaluation by a pathologist. It may help to overcome the resource shortage of interventional pulmonologists and cytopathologists.
MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology and cardiovascular disease. miR-106b-5p, a member of the miR-106b-25 cluster, has been widely studied for its oncogenic activity in various malignancies. However, its role as a direct molecular driver of anthracycline-induced cardiotoxicity has only recently been uncovered. This finding highlights new therapeutic possibilities at the intersection of oncology and cardiovascular medicine. This review outlines the dual role of miR-106b-5p as a key modulator in both tumor progression and chemotherapy-induced cardiac dysfunction. miR-106b-5p is upregulated in numerous cancers-including breast, prostate, lung, gastric, colorectal, hepatocellular, and esophageal-and promotes tumorigenesis via suppression of tumor suppressors such as PTEN, BTG3, p21, and SMAD7, leading to activation of oncogenic pathways like PI3K/AKT and TGF-β. Importantly, we present the first evidence that miR-106b-5p is significantly upregulated in the myocardium in response to doxorubicin treatment, where it drives left ventricular dysfunction by targeting PR55α, a key regulator of PP2A activity. This pathway results in cytoplasmic HDAC4 accumulation, aberrant activation of the YY1 transcription factor, and upregulation of sST2, a biomarker linked to adverse cardiac remodeling and poor prognosis. In response, we developed AM106, a novel locked nucleic acid antagomir that silences miR-106 b-5p. Preclinical studies demonstrate that AM106 restores PR55α/PP2A activity, reduces sST2 expression, and prevents structural and functional cardiac damage without compromising anti-tumor efficacy. In parallel, artificial intelligence (AI) tools could be leveraged in the future-based on established AI applications in miRNA cancer research-to accelerate the identification of miR-106b-5p-related biomarkers and guide personalized therapy selection. Our findings position miR-106b-5p as a previously unrecognized molecular bridge between cancer and doxorubicin-induced cardiotoxicity. The development of the AM106 antagomir represents a promising approach with potential clinical applicability in cardio-oncology, offering dual benefits: tumor control and cardioprotection. Coupling this innovation with AI-driven analysis of patient data may enable precision risk stratification, early intervention, and improved outcomes. miR-106b-5p thus emerges as a central therapeutic target and biomarker candidate for transforming the clinical management of cancer patients at risk for heart failure.
Anal squamous-cell cancer incidence has risen 2.2% each year during the past decade. Current screening methods include anal cytology and high-resolution anoscopy but are burdened with sampling errors and patient discomfort. To analyze the T-cell microenvironment of normal, premalignant (including low- and high-grade squamous intraepithelial lesions), and cancerous tissues. Institutional review board-approved prospective study of patients with anal dysplasia and cancer. Normal, dysplastic, and/or cancerous tissues were obtained from patients. Tissue was digested to obtain a single-cell suspension. Flow cytometry analysis was performed on matched patient samples to evaluate T-cell biomarkers. A single tertiary-care academic center. Patients older than 18 years and scheduled to undergo high-resolution anoscopy, examination under anesthesia, or abdominoperineal resection were included. Descriptive statistics were used to understand differences in the tumor microenvironment of normal, premalignant, and malignant tissue. Twenty patients underwent immunophenotyping. Normal tissue was characterized by the presence of a few infiltrating lymphocytes. Anal cancers contained 30% to 50% regulatory T cells, whereas these cells were infrequent in dysplasia. In anal cancer, conventional CD4 + T cells expressed high levels of inducible co-stimulator and programmed cell death protein-, reflective of tumor antigen recognition. In premalignant lesions, CD4 + conventional T cells also expressed inducible co-stimulator and programmed cell death protein-1 but lacked coexpression of chronic activation and proliferation markers. CD8 + T cells with a CD103 + CD39 + phenotype, indicative of chronic stimulation and tissue residency, were increased in anal cancer. This study was limited by its small sample size. Results may not be generalizable to a larger population. The data demonstrate that T-cell infiltrates differ between normal, premalignant, and malignant lesions, with tissue from anal squamous-cell cancers containing activated, chronically stimulated T cells. Future clinical diagnostic technology would yield a T-cell pathological footprint that differentiates between premalignant and malignant lesions, in addition to the development of a less invasive serum T-cell biomarker test. See Video Abstract . ANTECEDENTES:La incidencia del cáncer de células escamosas anales ha aumentado un 2,2 % cada año durante la última década. Las pruebas de detección actuales incluyen citología anal y anoscopia de alta resolución, pero presentan errores de muestreo y molestias para el paciente.OBJETIVO:Analizar el microambiente de las células T en casos normales, premalignos, incluidas las lesiones intraepiteliales escamosas de bajo y alto grado, y cancerosos.DISEÑO:Estudio prospectivo aprobado por el Comité de Ética en Investigación (IRB) de pacientes con displasia anal y cáncer. Se obtienen tejidos normales, displásicos y/o cancerosos de los pacientes. El tejido se digiere para obtener una suspensión de células individuales. Se realiza un análisis de citometría de flujo en muestras de pacientes emparejadas para evaluar los biomarcadores de las células T.ENTORNO:Un único centro académico de atención terciaria.PACIENTES:Mayores de 18 años y programados para someterse a una anoscopia de alta resolución, un examen bajo anestesia o una resección abdominoperineal.PRINCIPALES MEDIDAS DE RESULTADOS:Se utilizan estadísticas descriptivas para comprender las diferencias en el microambiente tumoral del tejido normal, premaligno y maligno.RESULTADOS:Veinte pacientes se sometieron a inmunofenotipado. El tejido normal se caracterizó por la presencia de pocos linfocitos infiltrantes. Los cánceres anales contenían entre un 30 % y un 50 % de células T reguladoras, que eran poco frecuentes en la displasia. En el cáncer anal, las células T CD4+ convencionales expresaban niveles elevados de ICOS y PD-1, lo que reflejaba el reconocimiento del antígeno tumoral. En las lesiones premalignas, las células T CD4+ convencionales también expresaban ICOS y PD-1, pero carecían de la coexpresión de marcadores de activación crónica y proliferación. Las células T CD8+ con un fenotipo CD103 + CD39 + , indicativo de estimulación crónica y residencia en el tejido, aumentaban en el cáncer anal.LIMITACIONES:Este estudio está limitado por el pequeño tamaño de la muestra. Es posible que los resultados no sean generalizables a una población más amplia.CONCLUSIONES:Los datos demuestran que los infiltrados de células T difieren entre las lesiones normales, premalignas y malignas, y que el tejido del cáncer de células escamosas anal contiene células T activadas y estimuladas crónicamente. La futura tecnología de diagnóstico clínico proporcionaría una huella patológica de las células T para diferenciar entre lesiones premalignas y malignas, además de la creación de una prueba de biomarcadores de células T en suero menos invasiva. (AI-generated translation ).