COVID-19 in patients with thymic epithelial tumors with or without Good's syndrome: a single-center retrospective study.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good's syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS. METHODS: Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations. RESULTS: Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher's exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS. CONCLUSIONS: Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols.

Five Times Reactivation of COVID-19 in a Patient with Thymoma.

BACKGROUND: The possibility of recurrence in COVID-19 is very rare and hence mostly underdiagnosed. In the face of pandemic, this can lead to circulation of the virus like a hidden iceberg. Better understanding about this topic can improve our knowledge of the COVID-19 pathogenesis and ways to control the transmission. CASE PRESENTATION: A 41 year old male with no known comorbidities was admitted five times during a period of 7 months each time after being detected RTPCR positive for SARS-CoV-2 and more symptomatic than previously. He had no contact with other COVID-19 patients and was asymptomatic in between admissions. Despite this, he did not develop antibodies against SARSCoV-2. Later on, he was diagnosed with thymoma on biopsy of the anterior mediastinal mass. Patient's condition deteriorated on last hospitalization and he died, despite the treatment. Here we present an interesting report on multiple times recurrent COVID-19 infection, probably a case of reactivation and different plausible explanations on the role of thymoma.;Conclusion: Acknowledging the potential of SARS-CoV-2 to cause recurrence is very important during the pandemic as a part of the long term transmission mitigation. The case report shows that previous infection does not guarantee complete immunity from COVID-19, especially in immuno-compromised patients. Hence, despite the status of prior infection, vulnerable individuals who recovered from COVID-19 should be under surveillance.

The Duke myasthenia gravis clinic registry: I. Description and demographics.

INTRODUCTION: The Duke Myasthenia Gravis (MG) Clinic Registry is a disease-specific database containing physician-derived data from patients seen in the Duke MG Clinic since 1980. METHODS: Data from 1060 MG patients initially seen between 1980 and 2008 were reviewed. RESULTS: Fifty-four percent were male. Symptoms began after age 50 in 66% of males and 42% of females. Peak onset age in males was in their 60's; females had no predominant onset age. Onset age for both sexes increased from 1980 to 2008. Thymoma was present in 8.5%. Weakness was limited to ocular muscles for at least 2 y in 22% and became generalized later in 8.3% of these. Acetylcholine receptor antibodies were present in 78% overall, 82% with generalized MG and 52% with ocular MG (OMG). The distribution of MG disease class was similar in males and females, except that a greater proportion of women experienced myasthenic crisis and men were more likely to have OMG. DISCUSSION: Data in the Registry permit comprehensive and longitudinal analysis of a validated MG population. Analysis of Registry data shows that the frequency of AChR antibody negative MG, ocular MG, and thymoma are similar to other reports, but the onset age and proportion of males have progressively increased compared to studies published more than 20 y ago. These observations demonstrate the value of collecting comprehensive clinical information and comparing historic and contemporary populations. Other potential uses of Registry data include comparison of outcome measures in different disease subgroups and the response to specific treatments.

Clinical characteristics and outcomes of thymoma-associated myasthenia gravis.

BACKGROUND AND PURPOSE: Prognosis of myasthenia gravis (MG) in patients with thymoma is not well established. Moreover, it is not clear whether thymoma recurrence or unresectable lesions entail a worse prognosis of MG. METHODS: This multicenter study was based on data from a Spanish neurologist-driven MG registry. All patients were aged >18 years at onset and had anti-acetylcholine receptor antibodies. We compared the clinical data of thymomatous and nonthymomatous patients. Prognosis of patients with recurrent or nonresectable thymomas was assessed. RESULTS: We included 964 patients from 15 hospitals; 148 (15.4%) had thymoma-associated MG. Median follow-up time was 4.6 years. At onset, thymoma-associated MG patients were younger (52.0 vs. 60.4 years, p < 0.001), had more generalized symptoms (odds ratio [OR]: 3.02, 95% confidence interval [CI]: 1.95-4.68, p < 0.001) and more severe clinical forms according to the Myasthenia Gravis Foundation of America (MGFA) scale (OR: 1.6, 95% CI: 1.15-2.21, p = 0.005). Disease severity based on MGFA postintervention status (MGFA-PIS) was higher in thymomatous patients at 1 year, 5 years, and the end of follow-up. Treatment refractoriness and mortality were also higher (OR: 2.28, 95% CI: 1.43-3.63, p = 0.001; hazard ratio: 2.46, 95% CI: 1.47-4.14, p = 0.001). Myasthenic symptoms worsened in 13 of 27 patients with recurrences, but differences in long-term severity were not significant. Fifteen thymomatous patients had nonresectable thymomas with worse MGFA-PIS and higher mortality at the end of follow-up. CONCLUSIONS: Thymoma-associated MG patients had more severe myasthenic symptoms and worse prognosis. Thymoma recurrence was frequently associated with transient worsening of MG, but long-term prognosis did not differ from nonrecurrent thymoma. Patients with nonresectable thymoma tended to present severe forms of MG.

Extra-appendicular neuroendocrine tumors: A report from the TREP project (2000-2020).

BACKGROUND: Extra-appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking. PATIENTS AND METHODS: Patients with a diagnosis of extra-appendicular NET registered on the Tumori Rari in Età Pediatrica - Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients' presentation, tumor features, treatment, and outcome were reviewed. RESULTS: Twenty-seven patients with extra-appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3-year event-free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5-95% vs 33% 95% CI 5-68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3-year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow-up, and one is alive with disease; five died, and five were lost to follow-up. CONCLUSIONS: Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease.

Thymomatous myasthenia gravis: 10-year experience of a single center.

OBJECTIVES: To summarize the clinical features of thymomatous myasthenia gravis (T-MG), examine the association between MG and thymoma, and identify the related factors or predictors for long-term prognosis of T-MG. METHODS: A retrospective, observational study was conducted on 100 patients with T-MG and 96 patients with non-T-MG (NT-MG) between January 1, 2009 and December 31, 2019. The baseline characteristics were recorded for each patient. Logistic regression was used to measure the association between all clinical variables and T-MG prognosis. RESULTS: Between the T-MG and NT-MG groups, age at onset (45.66 ± 11.53 years vs 39.06 ± 14.39 years); age >40 years (72.0% vs. 40.6%); AChR-Ab positive rate (100.0% vs. 83.3%); Myasthenia Gravis Foundation of America (MGFA) classification at the worst condition (≥grade III, 61.0% vs. 33.0%); thyroid dysfunction (7.0% vs. 20.8%); and outcome (complete stable remission + pharmacologic remission + improvement, 74.0% vs. 93.7%) were statistically significant (P < .05). Presence of thymoma (OR = 0.196, 95%CI = 0.076-0.511, P = .001) was a risk factor for MG. Male sex, post-operative complications, higher grade of MGFA classification, and thymoma Masaoka-Koga pathological stage were risk predictors for long-term prognosis of T-MG (P < .1). Use of preoperative anticholinesterase drugs (OR = 5.504, 95%CI = 1.424-21.284, P = .013) was identified as an independent predictor for T-MG. CONCLUSION: T-MG is clinically different from NT-MG, and thymoma is considered a risk factor for MG. Preoperative anticholinesterase drug use is a protective factor for long-term prognosis of T-MG. A comprehensive understanding of the characteristics of T-MG will likely help improve its prognosis.

Survival of malignant mesothelioma and other rare thoracic cancers in Germany and the United States: A population-based study.

Evidence on survival of malignant mesothelioma (MM) and other rare thoracic cancers is limited due to the rarity of these cancer sites. Here, we provide a comprehensive overview of MM incidence and survival after MM and other rare thoracic cancers in Germany and the United States (US). Incidence was estimated from a German National Cancer Database and from the Surveillance, Epidemiology and End Results (SEER) 18 database for 2000-2014. Patients diagnosed in 1997-2013 with malignant epithelial tumors of the trachea (Etra), epithelial tumors of the thymus (Ethy) and MM were extracted from a German cancer survival database and from the SEER 13 database. Period analysis was employed to compute 5-year relative survival (RS). During 2000-2014, an annual average of 0.9 and 0.6 MM cases per 100,000 person-years was diagnosed in Germany and the US. Rates decreased in Germany and in the US. Patients with Ethy had highest 5-year RS with US patients surviving longer (69.1% compared to 63.7%, p = 0.02). Survival after Etra was comparable in both countries (Germany 33.6%, US 34.4%, p = 0.07). Survival in MM patients was poor overall (Germany 11.8%, US 12.1%, p < 0.01). Survival improvements were only observed in MM patients in Germany (10.8% [2002-2007] vs. 13.0% [2008-2013], p < 0.01). The lack of progress in survival for Etra and Ethy patients underlines the need of novel preventive, therapeutic and diagnostic approaches. MM incidence significantly decreased in Germany and in the US. Further monitoring of MM incidence is warranted given that a peak in incidence is expected in 2020-2030 in Western countries.

Relationship of possible biomarkers with malignancy of thymic tumors: a meta-analysis.

BACKGROUND: Role of biomarkers for promotion of tumor proliferation (BPTPs) and for promotion of apoptosis (BPAs) in thymic malignant tumors is still unclear. The purpose of this study was to evaluate the relationship between BPTPs and/or BPAs and malignancy of thymic malignant tumors. METHODS: Studies on thymic malignant tumors and biomarkers were searched in PubMed, ISI Web of Knowledge, and Embase databases, and all statistical analyses were conducted using Review Manager. RESULTS: Twelve articles related to biomarkers and thymic malignant tumors were selected and analyzed. A relationship between BPAs and Masaoka stage was demonstrated for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 138 stage I/II patients and 74 stage III/IV patients, and BPAs were significantly correlated with high Masaoka staging (P = 0.03). We further found a relationship between BPAs and degree of malignancy for four markers, namely Bax, p73, Casp-9 and Bcl-2, included 176 thymoma patients and 36 thymic carcinoma patients, and BPAs were significantly correlated with thymic carcinoma (P = 0.010). In addition, a relationship between BPTP and Masaoka staging was demonstrated for seven markers, namely Podoplanin, Glut-1, Muc-1, Egfr, Igf1r, c-Jun, and n-Ras, included 373 patients with stage I/II and 212 patients with stage III/IV, and BPTPs were significantly correlated with high Masaoka staging (P < 0.001). We also found a relationship between BPTPs and degree of malignancy for ten markers, namely Mesothelin, c-Kit (CD117), Egfr, Lat-1, Muc-1,Ema, Glut-1, Igf1r, c-Jun, and n-Ras, included 748 thymoma patients and 280 thymic carcinoma patients, and BPTPs were significantly correlated with thymic carcinoma (P < 0.001). CONCLUSION: These findings show that high levels of BPTPs or BPAs are more closely related to thymic carcinoma and Masaoka stage III/IV, suggesting that BPTPs and BPAs may play an important role in the occurrence and development of thymic malignant tumors.

Refractory myasthenia gravis: Characteristics of a portuguese cohort.

INTRODUCTION: Some myasthenia gravis (MG) patients are refractory to conventional treatments. METHODS: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. RESULTS: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). DISCUSSION: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019.

Comparative Incidences and Biological Outcomes for Thymoma in Various Rat Strains in National Toxicology Program Studies.

Thymomas from 277 Fischer 344/N (F344/N), 10 Sprague Dawley (HSD:Sprague Dawley SD) (SD), 129 Wistar Han [Crl:WI(Han)] (WH), and 4 Wistar Outbred (WO) rats were reviewed from long-term studies in the National Toxicology Program (NTP) database. The incidence of thymomas in F344/N rats was slightly higher in males than in females, while the incidences in SD and WH rats were higher in females than in males. Only male WO rats were used in NTP studies. Of the 277 thymomas in F344/N rats, 235 (84.8%) were benign and 42 (15.2%) malignant, 14 of which exhibited metastasis. Of the 10 thymomas in SD rats, 5 (50%) were benign and 5 (50%) were malignant, one of which exhibited metastasis. Of the 129 thymomas in WH rats, 126 (98%) were benign and 3 (2%) were malignant, 1 with metastasis. Of the 4 thymomas in WO rats, 3 (75%) were benign and 1 (25%) was malignant, with no metastases. Malignant thymomas in F344/N and WH rats showed a propensity to be the cause of death and to result in early mortality, whereas the benign thymomas were associated less often with decreased survival. No occurrences of this neoplasm were reported to be related to exposure to any test articles.

Histotyping of Indian thymomas: A clinicopathologic study from north India.

Background & objectives: Thymomas are rare, but most common anterior mediastinal lesions. The histomorphologic spectrum of thymic epithelial tumours (TETs) in Indian population has not been explored in depth. This study was aimed to assess the histomorphology of TETs in the Indian patients and correlate clinical parameters with pathological features. Methods: It was a retrospective study conducted in a tertiary referral hospital in north India. All morphologically confirmed cases of TETs since 2009 were included. Clinical details and histology slides were reviewed using the Modified Masaoka-Koga staging system and WHO 2015 classification. Clinicopathological correlation and survival analysis were done. A comparative review from other published Indian studies was performed. Results: A total of 219 cases of TETs (138 resections and 81 biopsies) were identified. The most common histomorphologic type was B2, and the most frequent stage was I. Types A/AB were common in older age (P<0.01). Clinically, higher stage tumours were found mostly in men (P<0.01), and these were Type B thymomas (P<0.01). Myasthenia gravis was more common in women (P<0.02) and in lower stages (P<0.05). Survival analysis revealed significant association between recurrence and tumour stage. Although thymic carcinoma was diagnosed on biopsy, no resectable case was identified. Interpretation & conclusions: Our findings showed that the thymomas in Indian patients were most commonly Stage I tumours of B2 and AB histotypes. Resected thymic carcinomas were conspicuously absent in our study. More studies need to be done to establish the frequency and biology of TETs from India.

Clinical and epidemiological features of myasthenia gravis in Chilean population.

OBJECTIVE: To provide an estimated prevalence and describe the clinical features of myasthenia gravis (MG) in Chile. METHOD: We carried out (i) a prevalence study of MG using the capture-recapture method and the hospital register of pyridostigmine prescription in South-East Santiago (ii) a nationwide survey of MG patients. RESULTS: Prevalence in adults in South-East Santiago was estimated to be 8.36/100 000 inhabitants (CI: 95%, 7.98-8.80). From the nationwide survey, 405 questionnaires were analysed, there was a female/male ratio of 2.2:1. The mean age of onset of symptoms was 38.7 years (range 1-89). The onset was ocular in 46.4%, oculobulbar in 11.6%, bulbar in 8.9%, limbs in 11.6% and generalized in 21.4%. Of the 13.3% of patients who had had a diagnosis of thymoma, only four of these patients were >60 years old at onset. Thymomas were commoner in patients living in mining counties. Patients ≥60 years old at onset of MG formed 19.5% of the sample, female/male ratio 0.97:1. Associated autoimmune diseases were reported in 14% of patients and in family members of 31.8% of patients. A total of 78 patients had to change work due to MG and 68 needed help in carrying out daily activities. CONCLUSIONS: This study reduces the gap in information about MG in South America. The prevalence of MG in Chile is within the range described worldwide. We did not see an increase in male frequency in the older age of onset group and thymoma was more frequent in the fifth and sixth decades.

Prognosis of Good syndrome: mortality and morbidity of thymoma associated immunodeficiency in perspective.

Good syndrome (GS) or thymoma-associated immunodeficiency, is a rare condition that has only been studied in retrospective case series. General consensus was that GS has a worse prognosis than other humoral immunodeficiencies. In this study, physicians of GS patients completed two questionnaires with a two year interval with data on 47 patients, 499 patient years in total. Results on epidemiology, disease characteristics, and outcome are presented. Mean age at diagnosis was 60years and median follow-up from onset of symptoms was 9years. There was a high frequency of respiratory tract infections due to encapsulated bacteria. Median survival was 14years. Survival was reduced compared to age-matched population controls (5-year survival: 82% versus 95%, p=0.008). In this cohort survival was not associated with gender (HR 0.9, 95% CI 0.3-3.0), autoimmune diseases (HR 2.9, 95% CI 0.8-10.1) or immunosuppressive use (HR 0.3, 95% CI: 0.1-1.2).

Do acetylcholine receptor and striated muscle antibodies predict the presence of thymoma in patients with myasthenia gravis?

INTRODUCTION: Acetylcholine receptor (AChR) and striated muscle antibodies (StrAbs) are found frequently in myasthenia gravis (MG) patients with thymoma. In this study we aimed to determine the positive predictive value (PPV) and negative predictive value (NPV) of these antibodies for thymoma in patients with MG. METHODS: Antibody findings, thymic histology, and onset age were reviewed for 1141 patients with MG. PPV and NPV of these antibodies for thymoma were determined. RESULTS: The PPV of AChR binding antibodies plus StrAbs was highest (50.0%) with onset before the age of 40 years. The PPV of all antibodies was low (<9%) after age 40. Higher StrAb levels did not increase the PPV. The NPV of AChR binding antibodies was high (99.7%) for all ages. CONCLUSIONS: Patients without AChR binding antibody are not likely to have a thymoma. StrAbs and AChR binding antibodies are not diagnostic for thymoma, but in early-onset MG their presence should raise the clinical suspicion for thymoma.

Myasthenia and risk of cancer: a population-based case-control study.

BACKGROUND AND PURPOSE: To evaluate the association between having non-thymoma myasthenia and the risk of extra-thymic cancer in a population-based setting. METHODS: A nationwide case-control study was conducted in Denmark based on medical registries. The study included all cases with a first time diagnosis of cancer during 2000-2009. Each case was matched by birth year and gender with eight population controls using risk set sampling. Subjects with myasthenia were identified through a validated register-based algorithm. Conditional logistic regression was used to compute crude and adjusted odds ratios (ORs), with 95% confidence intervals (CIs), for cancer associated with a prior diagnosis of myasthenia. RESULTS: In all, 233 437 cases and 1 867 009 controls were identified. A total of 80 cases and 518 controls had a prior diagnosis of myasthenia. Myasthenia was not associated with an increased risk of overall cancer (OR 1.1; 95% CI 0.9-1.4). Adjusted ORs for major cancer sites were also close to unity, whereas an elevated risk of lymphomas was observed (OR 2.0; 95% CI 0.8-5.5). Early-onset myasthenia was associated with a slightly increased OR for overall cancer (1.5; 95% CI 1.0-2.3); however, this estimate was based on small numbers. CONCLUSIONS: Non-thymoma myasthenia was not associated with an increased risk of overall cancer. Larger studies are necessary to evaluate the association between myasthenia and risk of lymphoma and the potential effect modification by age of myasthenia onset in relation to cancer risk.

8 years' experience with robotic thymectomy for thymomas.

BACKGROUND: The accuracy of a three-dimensional robotic-assisted videothoracoscopic approach may favor a radical resection of thymomas. The aim of this study was to demonstrate the feasibility of the robotic approach by reporting 8 years experience in a single referral center of surgical treatment of thymomas. METHODS: We retrospectively analyzed all consecutive patients who underwent a thymectomy from April 2004 to April 2012. We analyzed the procedure time, morbidity, mortality, conversions, hospitalization, freedom from recurrence, time to progression, and overall survival. RESULTS: From 2004 until 2012, a total of 138 robotic procedures for mediastinal tumors were performed in our center, of which 37 patients with a mean age of 57.3 years underwent a thymectomy for a thymoma. Histological analysis revealed four type A thymomas (10.8 %), seven type AB thymomas (18.9 %), seven type B1 thymomas (18.9 %), fourteen type B2 thymomas (37.8 %), four type B3 thymomas (10.8 %), and one thymus carcinoma (2.7 %). The Masaoka­Koga stages were as follows: stage I in twenty patients (54 %), stage IIA in five patients (13.5 %), stage IIB in eight patients (21.6 %), stage III in three patients (8.1 %), and stage IVa in one patient (2.7 %). The mean overall procedure time was 149 min (range 88­353). No surgical mortality was reported, and there were no peri-operative complications. No conversions were needed for surgical complications. In three cases, a conversion to sternotomy was preferred by the surgeon because tumor invasion in greater vessels was suspected. Two patients (5.4 %) suffered from a myasthenic crisis postoperatively and required prolonged mechanical ventilation. One patient (2.7 %) underwent a procedure for a thoracic herniation 6 months following thymectomy. The median hospitalization was 3 days. The follow-up analysis showed an overall survival of 100 % and tumor recurrence in one patient (2.7 %). CONCLUSIONS: Robotic thymectomies are safe in patients with early-stage thymomas. Robotic surgery may also be feasible for some selected advanced thymomas.

Incidence of second malignancies in patients with thymic carcinoma and thymic neuroendocrine tumor.

OBJECTIVES: Thymic carcinoma and thymic neuroendocrine tumor (NET) are rare and are more likely to develop second malignancies. The purpose of this study was to explore the incidence and lifetime risk of second malignancies in thymic carcinoma and thymic NET. METHODS: The standardized incidence ratio (SIR) and the age-adjusted cancer incidence of the thymic carcinoma and thymic NET patients with second malignancies were retrospectively calculated by using the Surveillance, Epidemiology, and End Results (SEER) database. Prognosis results were also determined by Kaplan-Meier analysis and Cox regression. RESULTS: 1130 patients with thymic carcinoma (73 patients had second malignancies) and 263 patients with thymic NET (19 patients had second malignancies) from 2000 to 2018 are included. Patients with thymic carcinoma (SIR: 1.36, 95% CI 1.08-1.69) and with thymic NET (SIR: 1.73, 95% CI 1.13-2.54) demonstrate an increased overall risk of developing second malignancies in various organ systems. The age-adjusted cancer incidence of second malignancies in patients with thymic carcinoma is 3058.48 per 100,000 persons (4178.46 per 100,000 persons in patients with thymic NET). Age at diagnosis is a significant risk factor for the development of second malignancies. CONCLUSION: The incidence of second malignancies in patients with thymic carcinoma and thymic NET is significantly higher than the patients in the normal population. The occurrence of second malignancies is not related to the use of different treatments. It is important to extend the follow-up period and add other screening methods.

The consequences of not having eosinophils.

Several lines of evidence suggest that deficiency of eosinophils is not associated with any characteristic abnormality. Patients lacking eosinophils, in the setting of immunodeficiency or as a consequence of IgG-mediated eosinophil precursor destruction, do not display any distinguishing abnormalities related to eosinophil reduction. The observation that eosinophil-deficient mice do not display any distinctive syndrome or failure of their health is evidence that, under ordinary laboratory conditions, the eosinophil does not play a critical role in the well-being of mammals. Observations that monoclonal antibodies to interleukin-5 (IL-5) are well tolerated appear unsurprising in light of these findings. For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor α-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated. Thus, data to the present suggest that reduction of eosinophils appears to have no characteristic ill effects on normal health, and monoclonal antibodies that deplete eosinophils have the potential to be widely employed in the treatment of eosinophil-associated diseases.