RESUMEN
Early detection and treatment are critical for improving the outcome of patients with cancer1. Understanding the largely uncharted biology of carcinogenesis requires deciphering molecular processes in premalignant lesions, and revealing the determinants of the intralesional immune reaction during cancer development. The adaptive immune response within tumours has previously been shown to be strongest at the earliest stage of carcinoma2,3. Here we show that immune activation and immune escape occur before tumour invasion, and reveal the relevant immune biomarkers of the pre-invasive stages of carcinogenesis in the lung. We used gene-expression profiling and multispectral imaging to analyse a dataset of 9 morphological stages of the development of lung squamous cell carcinoma, which includes 122 well-annotated biopsies from 77 patients. We identified evolutionary trajectories of cancer and immune pathways that comprise (1) a linear increase in proliferation and DNA repair from normal to cancerous tissue; (2) a transitory increase of metabolism and early immune sensing, through the activation of resident immune cells, in low-grade pre-invasive lesions; (3) the activation of immune responses and immune escape through immune checkpoints and suppressive interleukins from high-grade pre-invasive lesions; and, ultimately, (4) the activation of the epithelial-mesenchymal transition in the invasive stage of cancer. We propose that carcinogenesis in the lung involves a dynamic co-evolution of pre-invasive bronchial cells and the immune response. These findings highlight the need to develop immune biomarkers for early detection as well as immunotherapy-based chemopreventive approaches for individuals who are at high risk of developing lung cancer.
Asunto(s)
Carcinogénesis/inmunología , Carcinogénesis/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Escape del Tumor/inmunología , Adulto , Anciano , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Detección Precoz del Cáncer , Transición Epitelial-Mesenquimal , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Escape del Tumor/efectos de los fármacos , Escape del Tumor/genética , Microambiente TumoralRESUMEN
Alimentary tract duplications are rare congenital malformations that occur most commonly in the jejunoileal part of the gastrointestinal tract. Management of this pathologic condition is usually drawn up. We report a case of descending colonic communicating duplication in which clinical presentation and anatomopathologic results were unexpected. A slightly echogenic abdominal mass reaching 72 x 36 mm in the left flank was diagnosed in a female fetus during the third trimester ultrasound examination. At birth, volume of the mass rapidly evolved, and despite no intestinal obstruction was observed by compression of the adjacent gastrointestinal tract, abdomen was distended. Abdominal plain film showed a large air collection, and the barium enema demonstrated a slight leak of contrast in the aerated mass, suggesting a communication with the sigmoid colon. No other abnormalities were seen. The patient underwent surgery in emergency. The mass was then totally excised through an antimesenteric resection of the tubular tract joining cystic mass and sigmoid colon. A lateral suture of the colon was subsequently performed. The wall of the duplication is usually composed of a smooth muscle layer covered by an epithelium, mostly of intestinal type. Herein, we describe a descending colonic duplication completely lined with nonkeratinizing squamous epithelium. Therefore, the association of a colonic mucosa (of endodermic origin) and a squamous epithelium (derived from the ectoderm) in our case is an interesting finding and is not explained by the various theories. Furthermore, the clinical characteristics, diagnosis, and treatment of intestinal duplications are discussed with regard to literature.
Asunto(s)
Colon Sigmoide/anomalías , Colon Sigmoide/cirugía , Sulfato de Bario , Colon Sigmoide/diagnóstico por imagen , Colon Sigmoide/patología , Medios de Contraste , Diagnóstico Diferencial , Enema , Femenino , Humanos , Recién Nacido , RadiografíaRESUMEN
Epstein-Barr virus (EBV)-associated lymphoid proliferations that are similar to post-transplantation lymphoproliferative disorders may occasionally occur in the setting of human immunodeficiency virus (HIV) infection. Herein, we describe such a lesion involving the adenoids in a HIV-seropositive adolescent who acquired immunity against EBV during childhood. On microscopic examination, the marginal zone of B follicles and the interfollicular area were enlarged due to the accumulation of small or intermediate-sized lymphocytes, immunoblasts, epithelioid histiocytes, and plasma cells. A few atypical immunoblasts resembling Reed-Sternberg cells were also present. Most of the cells seen in these expanded regions belonged to the B-cell lineage and displayed a phenotype consistent with that of postgerminal center B cells. No clonal rearrangement of the genes coding for the heavy chain of the immunoglobulin could be demonstrated by polymerase chain reaction analysis. In-situ hybridization studies revealed the presence of EBV early RNA in a significant number of these cells, which suggests the participation of this virus in the pathogenesis of such a B-cell proliferation. The clinical course was benign; no progression or recurrence could be seen more than 24 months after the diagnosis. This atypical lymphoproliferative disorder is probably related to polyclonal reactivation of a latent EBV infection due to a local or systemic immune imbalance induced by HIV replication. Recognition of this reactive condition is important to prevent overtreatment.
Asunto(s)
Tonsila Faríngea/patología , Linfocitos B/patología , Infecciones por Virus de Epstein-Barr/patología , Centro Germinal/patología , Infecciones por VIH/patología , Trastornos Linfoproliferativos/virología , Tonsila Faríngea/inmunología , Adolescente , Antígenos CD , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Femenino , Centro Germinal/inmunología , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Humanos , Hiperplasia , Hibridación in Situ , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/patología , Reacción en Cadena de la Polimerasa , Células de Reed-Sternberg/patologíaRESUMEN
In most hospitals, making a microscopic examination to tonsil and adenoid specimens from pediatric patients who present recurrent infections has become a standard practice. However, studies have shown that systematic examination of tonsils and adenoids was not needed for individual aged 21 or less. In this context, we describe the third report of an unsuspected tonsillar sarcoidosis revealed by histologic examination. A 5-year-old white girl was referred to our department because of frequent nasal and pharyngeal infections. Both tonsillectomy and adenoïdectomy were performed. Histologic evaluation revealed noncaseous epithelioid granulomas morphologically compatible with a diagnosis of sarcoidosis. Our observation illustrates the benefit of histological analysis in every tonsillectomy and adenoïdectomy specimen.
Asunto(s)
Tonsila Palatina/patología , Tonsila Palatina/cirugía , Sarcoidosis/diagnóstico , Tonsilitis/cirugía , Adenoidectomía , Preescolar , Diagnóstico Diferencial , Femenino , Granuloma , Humanos , Recurrencia , Tonsilectomía , Resultado del TratamientoRESUMEN
Although pilomatrixomas are well known among dermatologists and dermatopathologists, head and neck surgeons confronted with these lesions in the infra-auricular region do not consider this benign neoplasm in the differential diagnosis. Aggressive pilomatrixoma is a benign tumor of the hair matrix cells affecting mainly children. Histologically, the border between aggressive pilomatrixoma and pilomatrix carcinoma is still not clear. We report the case of a 15-year-old Turkish boy suffering from an aggressive pilomatrixoma of the infra-auricular region and review the literature about this unclear entity.