Epstein-Barr virus in tumor-infiltrating B cells of myasthenia gravis thymoma: an innocent bystander or an autoimmunity mediator?

The thymus plays a key role in myasthenia gravis (MG), a B cell-mediated autoimmune disorder affecting neuromuscular junction. Most MG patients have thymic abnormalities, including hyperplasia and thymoma, a neoplasm of thymic epithelial cells. Epstein-Barr virus (EBV) is associated with autoimmune diseases and tumors. Recently, we showed EBV persistence and reactivation in hyperplastic MG thymuses, suggesting that EBV might contribute to intra-thymic B cell dysregulation in MG patients. Here, we investigated EBV involvement in thymoma-associated MG, by searching for EBV markers in MG (n=26) and non-MG (n=14) thymomas. EBV DNA and EBV-encoded small nuclear RNA (EBER) 1 transcript were detected in 14/26 (53.8%) and 22/26 (84.6%) MG thymomas, and only in 3 of 14 (21.4%) non-MG thymomas. Latent EBNA2 and late gp350/220 lytic transcripts were undetectable in all, but one, thymomas, and early lytic BZLF1 transcript was absent in all samples, suggesting that early infection events and EBV reactivation were very rare in thymomas. EBER1 and 2-positive cells were detected in MG, but not in non-MG, thymomas, as well as cells expressing EBV latency proteins (EBNA1, LMP1, LMP2A), that were mainly of B cell phenotype, indicating EBV association with MG rather than with thymoma. Toll-like receptor (TLR) 3 transcriptional levels were higher in MG than non-MG thymomas and positively correlated with EBER1 levels, suggesting a role for EBERs in TLR3 activation. Our findings show that EBV is commonly present in thymoma-infiltrating B cells of myasthenic patients, indicating a contribution of EBV to B cell-mediated autoreactivity in MG associated with thymic tumor.

Blunt rectal trauma Case report and literature review.

Blunt colorectal traumas are rare clinical entities with a challenging diagnostic and operative management. We describe the case of a 40-year-old man, victim of an accidental fall from a height of four meters who was subsequently diagnosed to have a blunt rectal trauma. A first CT scan showed fracture of the skull and an extensive subcutaneous haematoma of the lower back associated with a fracture of the left transverse processes of lumbar vertebrae. No other visceral abdominal lesions were recognized and patient was admitted to our department for observational studies. After 48 hours from admission the patient presented a subcutaneous emphysema suspicious for hollow viscus injuries. A digital rectal examination detected a laceration both of the posterior rectal wall and the superior anal margin. The patient was successfully managed with spur colostomy, transanal evacuation of the retroperitoneal haematoma and primary repair of both the sphincteric muscle and the rectal wall. As soon as the patient achieved full recovery we performed a reversal colostomy. Diagnosis and management of rectal blunt trauma is still a matter of debate and no definitive recommendation treatments are available. The surgical treatment should be tailored on patient medical conditions and clinicians should maintain a high index of suspicious because a delay in diagnosis can result in higher morbidity and mortality rate. KEY WORDS: Colorectal blunt injury, Colostomy, Laparoscopy, Trauma.

Cutaneous metastasis from lung cancer. Case report.

UNLABELLED: Lung cancer is the most common neoplasm diagnosed worldwide. Metastatic presentation of the disease is frequent. Apart from the usual sites of metastatic disease (bone, adrenals, liver, brain), a particular site for metastases is represented by skin. The case we report is about a 66 year-old man with cutaneous metastasis from lung cancer. A 66 year-old man, with a previous history of abdominal aortic aneurism, chronic obstructive pulmonary disease, cardiopathy, diabetes mellitus, was admitted to our institution for left lower lobe lung cancer. After accurate preoperative staging, patient underwent a thoracotomic left lower lobectomy. Histological examination revealed a squamocellular carcinoma: G2-3, pT2bN0. Patient underwent oncological evaluation for the scheduled follow up. After 6 months patient went back to our observation for the appearance of a skin nodule, firm, dischromic, painful and ulcerated, localized in right iliac fossa. Biopsies demonstrated the nodule to be squamocellular carcinoma. Patient underwent a CT scan of the abdomen and thorax, which revealed the absence of infiltration of the deep fascial and muscular planes by the neoplasm. Patient underwent surgical removal of the lesion. Final histological examination confirmed the lesion to be metastasis of squamocellular lung cancer. Metastases from lung cancer occur in about 2,5-7,5% of cases. Median survival for these patients is 2,9 months. The most common type of neoplasm, according to Japanese Authors, is adenocarcinoma followed by squamocellular carcinoma. Some studies demonstrated the adequacy of surgery followed by chemotherapy, in case of single lesion. In case of multiple cutaneous metastases, many Authors suggest only chemotherapy, although the ideal scheme hasn't been discovered yet. Cutaneous metastases from lung cancer are rare; however the appearance of skin lesions, in patients with a positive oncological history, requires much attention. Accurate evaluation of the patient is paramount in choosing the adequate therapeutic algorithm. KEY WORDS: Chemotherapy, Lung Cancer, Skin Metastases.

Video-assisted thoracoscopic extended thymectomy and extended transsternal thymectomy (T-3b) in non-thymomatous myasthenia gravis patients: remission after 6 years of follow-up.

The aims of this study were to assess the efficacy of video-assisted thoracoscopic extended thymectomy (VATET) as a treatment for myasthenia gravis (MG) and to identify prognostic factors for thymectomy success. Clinical efficacy and variables influencing outcome were assessed by life-table and Cox proportional hazards regression analysis. Complete stable remission (CSR), as defined by the MGFA Medical Task Force, was the end point for efficacy. VATET was performed in 159 MG patients and T-3b in 47 MG patients. At 6 years of follow-up, CSR, assessed by life-table analysis, was 50.6% in non-thymomatous VATET patients and 48.7% in non-thymomatous T-3b surgery. By univariate analysis, the presence of thymic hyperplasia (P=0.0002) and treatment only with anticholinesterases (P<0.0001) were positively associated with the probability of CSR. By multivariate analysis, the chance of complete remission was significantly increased by the use of anticholinesterases (odds ratio [OR] 2.45; 95% confidence interval [CI] 1.44-4.17; P=0.001) and the presence of thymic hyperplasia (OR 1.96; 95% CI 1.05-3.68; P=0.036). VATET seems to be effective in inducing CSR in MG with an efficiency similar to that of the T-3b transsternal (TS) approach; it is easy to perform in experienced hands and is associated with low morbidity and negligible esthetic sequelae.