Combined effect of thymectomy on myasthenia gravis in patients with concomitant auto-immune diseases: a 22-year single-center experience.

Myasthenia gravis (MG) is an autoimmune disease (AD), and patients with MG often have other types of ADs. We analyzed the prognosis of patients with MG complicated by AD after thymectomy. A retrospective analysis was performed for patients with MG complicated by ADs treated surgically in our center over the past 22 years, and their general condition and follow-up data were collected and analyzed. 33 patients were included totally. 28 patients displayed improvement or even complete recovery of MG, and 23 of 36 ADs revealed improvement or even complete recovery. The prognosis of MG is significantly correlated with the duration of postoperative follow-up time (p = 0.028), and in patients with thymoma, the larger the tumor diameter, the better the prognosis of MG (p = 0.026). Thymic hyperplasia patients were predominantly female (p = 0.049) and young (p < 0.001). The most common concomitant AD in this study was a thyroid-associated AD, which was associated with thymic hyperplasia (p < 0.001), Osserman type I MG (p < 0.001), and young age (p < 0.001). Thymectomy had a good therapeutic effect on MG complicated by AD, and there was a close correlation between surgery, thymus, MG, and ADs.

Massive true thymic hyperplasia in a 3-month-old infant: case report and literature review.

BACKGROUND: True thymic hyperplasia (TTH) is characterized as a distinct increase in both size and weight of thymus, which retains normal microscopic and immunohistochemical appearances. Massive true thymic hyperplasia (MTTH) is an extremely rare but significant subtype of TTH in pediatric ages due to its potentially serious consequences. It was reported that the age of cases with MTTH was predominantly between 1 and 15 years, while those before 1 year rarely occurred. By presenting the diagnosis and treatment process of our case as well as reviewing the related literature, we aimed to analyze the clinical characteristics of MTTH for patients younger than 1 year. CASE: A 3-month-old male infant was admitted to our department with a chief complaint of gradually increasing polypnea over 9 days, whose preoperative imaging examination showed a large intrathoracic soft tissue shadow predominantly on the right side. The percutaneous fine-needle biopsy guided by ultrasonography was performed to identify its diagnosis. However, proliferating lymphocytes and Hassall`s corpuscles were seen microscopically in the biopsy tissues, which were immunohistochemically positive for CD3, CD19, CD20, CD99, TdT, PCK and Ki67 ( > 90%). Due to the aggravating symptoms, a second operation with total thymectomy was carried out successfully for this infant, which confirmed the diagnosis of TTH again by both morphological study and immunohistochemical staining from the surgical specimen. CONCLUSIONS: By reviewing the literature, there were only 10 cases with MTTH reported between 1975 and 2020 for children aged < 1 year of life, together with our present one. In MTTH patient`s sex had an obviously male predominance (70%). Nine out of 10 presented initial symptoms or signs related to respiratory system and 6 patients showed respiratory distress. All patients were successfully treated by surgical thymectomy without any postoperative complications. The prognosis of MTTH was very successful.

A rare association between true thymic hyperplasia and thyroid follicular tumor: a case report.

BACKGROUND: True thymic hyperplasia is a rare condition characterized by enlargement of the thymus while its normal structure is retained. True thymic hyperplasia is known to accompany Graves' disease, but no association between true thymic hyperplasia and thyroid follicular tumor has been reported so far. We report a case of true thymic hyperplasia in a patient with a thyroid follicular tumor. CASE PRESENTATION: A 52-year-old Japanese man was referred to our hospital for evaluation of a thyroid mass and a mediastinal mass. His serum thyroglobulin level was high, and hemithyroidectomy was performed to remove the thyroid mass. The resected mass was diagnosed as a follicular tumor of uncertain malignant potential. After resection of the thyroid lesion, the patient's serum thyroglobulin levels were markedly decreased. Seven months later, the patient underwent resection of the mediastinal mass. On pathological examination, the mass was found to consist of lobules, which formed a corticomedullary structure with Hassall's bodies, indicating a normal thymic mass with hyperplastic thymic tissue, less organized cellular cords, and intermingled adipose tissue. Immunostaining for cytokeratin 19 and cytokeratin 7 indicated that the lesion was consistent with thymic tissue. The lesion was diagnosed as true thymic hyperplasia, and the histological findings suggested that secondary atrophy had occurred. No evidence of recurrence was observed at 24 months after surgery. CONCLUSIONS: We present a case of a combination of true thymic hyperplasia and thyroidal follicular tumors that, to our knowledge, has not been reported previously. High serum thyroglobulin levels might play a role in hyperplasia of the thymus. Although true thymic hyperplasia is a rare disorder, it should be included in the differential diagnosis of a mediastinal mass in patients with thyroid disease.

[An enlarged thymus associated with Graves' disease]. / Een vergrote thymus bij ziekte van Graves.

BACKGROUND: Thyrotoxicosis and orbitopathy are the best-known expressions of Graves' disease. There are also rarer and less-known phenomena, such as thymic hyperplasia. Identification of these is important in order to avoid potentially unnecessary invasive interventions. CASE DESCRIPTION: In the case of two young women with lung embolisms, CT pulmonary angiography also revealed an enlarged thymus. This turned out to be caused by as of yet unknown Graves' disease. Since pathological examination of a thymus-biopsy sample was unable to rule out thymoma, thymectomy was performed on the first patient. Pathological examination of the entire thymus revealed hyperplasia. Additional FDG-PET/CT scan of the second patient revealed diffuse hyperactivity in the diffusely enlarged thymus. In this case, we opted for expectant treatment. A follow-up FDG-PET/CT scan 1 year later, revealed a non-abnormal thymus. CONCLUSION: An enlarged thymus caused by thymic hyperplasia is a less well-known manifestation of Graves' disease. In case additional abnormalities develop in patients with Graves' disease, it is important to consider that these might be related to the disease before diagnosing an additional new condition.

Occurrence of thymic pathology in two families. Is familial screening justified?

The familial occurrence of thymic pathology, even though rare, is widely reported in the literature and mainly concerns cases of familial autoimmune myasthenia gravis. Other less frequent cases of familial occurrence of thymoma, thymic carcinoid and thymic hyperplasia have been described. It seems that the familial occurrence is poorly recorded and thus its prevalence is underestimated. We report two families whose members presented different forms of thymic pathology and discuss the necessity of screening programs in family members of patients presenting a thymic lesion.

Modified unilateral video-assisted thoracoscopic extended thymectomy for myasthenia gravis using 5-mm incisions: A case report.

RATIONALE: Myasthenia gravis (MG) is the most common cause of acquired neuromuscular junction disorder. Thymectomy has been established as an effective therapy for MG, as it attenuates the natural course of the disease and may result in complete remission. PATIENT CONCERNS: We report the case of a 22-year-old female with a 6-year history of MG presented with bilateral ptosis, diplopia, and intermittent dysphagia. She denied shortness of breath, dysarthria, and fatigue. DIAGNOSES: She had been diagnosed with MG 6 years previously at the Neurology Department of our hospital. A computed tomography (CT) scan revealed thymic hyperplasia INTERVENTIONS:: She was treated with modified unilateral VATET that minimized incision size. OUTCOMES: Unilateral VATET was performed using two 5-mm incisions to minimize pressure on intercostal soft tissues/nerves and reduce postoperative pain. LESSONS: The lesson learnt from this case report is that this modified VATET method could be a useful approach to the management of non-thymomatous MG. The ability to achieve complete dissection with good cosmetic results may lead to wider acceptance of this technique by patients with MG and their neurologists for earlier thymectomy and improved outcomes. Additional studies are needed to determine the superiority of this approach to established methods.

Different neurologic outcomes of myasthenia gravis with thymic hyperplasia and thymoma after extended thymectomy: A single center experience.

This study aimed to reveal the clinical course and outcomes of myasthenia gravis (MG) in patients with thymic lymphoid hyperplasia and thymoma undergoing extended thymectomy and to identify the clinical prognostic factors of remission for MG. In total, 73 patients undergoing extended thymectomy were divided into two groups: group A with lymphoid hyperplasia (n=39) and group B with thymoma (n=34). According to the MG Foundation of America (MGFA) post-intervention status, the primary endpoint was a composite measure defined as achievement of complete stable remission (CSR), pharmacologic remission (PR), minimal manifestations (MM) or improvement (IM). The secondary endpoint was CSR. The cumulative probabilities of reaching the primary endpoint were 71.8% in group A and 85.3% in group B (p=0.164), respectively. Using Kaplan-Meier survival analysis, the probability of reaching the primary endpoint in group B was remarkably greater than group A (p=0.036). Cox multivariate analysis indicated that pre-operative MGFA class I (HR: 3.019, 95% CI: 1.084-8.410) and MGFA II (2.665, 95% CI: 1.033-6.873) compared to MGFA III and presence of thymoma (HR: 2.229, 95% CI: 1.079-4.606), showed the most consistent association with remission of MG after thymectomy. Finally, thymic lymphoid hyperplasia and severe symptoms may negatively affect prognosis of MG following thymectomy.

Caracterización clínica de los pacientes miasténicos timectomizados / Clinical Characterization of Thymectomized Myasthenic Patients

Introducción: la miastenia gravis es una enfermedad crónica de la unión neuromuscular, de naturaleza autoinmune y es reconocido que la timectomía es una modalidad terapéutica efectiva en esta entidad clínica. Objetivos: realizar una caracterización clínica de los pacientes miasténicos timectomizados. Métodos: se realizó un estudio observacional descriptivo retrospectivo, en el Servicio de Neurología del Hospital Clínico Quirúrgico Hermanos Ameijeiras en el periodo comprendido de enero de 1984 a diciembre de 2014. Resultados: se reclutaron 393 pacientes, la mayoría fueron del sexo femenino y del grupo de edad de 30-39 años, predominó el grado II b (65,3 por ciento) de intensidad de la enfermedad. La hiperplasia tímica (66,9 por ciento) fue la alteración histológica del timo más común. El hipertiroidismo fue la enfermedad autoinmune más frecuente. La crisis miasténica representó la complicación posoperatoria principal y apareció esencialmente en pacientes con timoma. La mortalidad fue de 1,3 por ciento. Conclusiones: fue más común el grado II b de intensidad de la enfermedad, el tipo histológico de hiperplasia tímica y la mortalidad baja(AU)

Introduction: Myasthenia gravis is a chronic disease of the neuromuscular junction, it is autoimmune by nature and it is recognized that thymectomy is an effective therapeutic modality in this clinical entity. Objectives: Clinically characterize the myasthenic thymectomized patients. Methods: A retrospective, descriptive, observational study was conducted in the Neurology Service at Hermanos Ameijeiras Surgical Clinical Hospital from January 1984 to December 2014. Results: 393 patients were recruited; the majority was female and aged 30-39 years. 65.3 percent of them had grade II b of disease intensity. Thymic hyperplasia (66.9 percent was the most common histological alteration of the thymus. Hyperthyroidism was the most frequent autoimmune disease. The myasthenic crisis represented the main postoperative complication and it essentially showed in patients with thymoma. Mortality was 1.3 percent. Conclusions: Grade II b disease intensity was more common, the histological type of thymic hyperplasia and mortality was low(AU)

Caracterización clínica de los pacientes miasténicos timectomizados / Clinical Characterization of Thymectomized Myasthenic Patients

Introducción: la miastenia gravis es una enfermedad crónica de la unión neuromuscular, de naturaleza autoinmune y es reconocido que la timectomía es una modalidad terapéutica efectiva en esta entidad clínica. Objetivos: realizar una caracterización clínica de los pacientes miasténicos timectomizados. Métodos: se realizó un estudio observacional descriptivo retrospectivo, en el Servicio de Neurología del Hospital Clínico Quirúrgico Hermanos Ameijeiras en el periodo comprendido de enero de 1984 a diciembre de 2014. Resultados: se reclutaron 393 pacientes, la mayoría fueron del sexo femenino y del grupo de edad de 30-39 años, predominó el grado II b (65,3 por ciento) de intensidad de la enfermedad. La hiperplasia tímica (66,9 por ciento) fue la alteración histológica del timo más común. El hipertiroidismo fue la enfermedad autoinmune más frecuente. La crisis miasténica representó la complicación posoperatoria principal y apareció esencialmente en pacientes con timoma. La mortalidad fue de 1,3 por ciento. Conclusiones: fue más común el grado II b de intensidad de la enfermedad, el tipo histológico de hiperplasia tímica y la mortalidad baja(AU)

Introduction: Myasthenia gravis is a chronic disease of the neuromuscular junction, it is autoimmune by nature and it is recognized that thymectomy is an effective therapeutic modality in this clinical entity. Objectives: Clinically characterize the myasthenic thymectomized patients. Methods: A retrospective, descriptive, observational study was conducted in the Neurology Service at Hermanos Ameijeiras Surgical Clinical Hospital from January 1984 to December 2014. Results: 393 patients were recruited; the majority was female and aged 30-39 years. 65.3 percent of them had grade II b of disease intensity. Thymic hyperplasia (66.9 percent was the most common histological alteration of the thymus. Hyperthyroidism was the most frequent autoimmune disease. The myasthenic crisis represented the main postoperative complication and it essentially showed in patients with thymoma. Mortality was 1.3 percent. Conclusions: Grade II b disease intensity was more common, the histological type of thymic hyperplasia and mortality was low(AU)

[Characteristics of distribution and quantity of dendritic cells subtypes in hyperplastic thymus in patients with myasthenia gravis].

Objective: To investigate the characteristics of the distribution and amount of different subtypes of dendritic cell (DC) in myasthenia gravis(MG). Methods: We collected the thymic specimens from 32 patients who received thymoctomy because of cardiac surgery from January 2016 to December 2016 and selected 14 of them as normal control. Meantime, 61 MG patients who combined with thymic hyperplasia and received extended thymectomy were collected and selected 8 of them as experiment group.Immunohistochemical methods were used to label the two subtype DCs: plasmacytoid dendritic cell (pDC) and classical/conventional dendritic cell (cDC), to observe the distribution of these two DC subtypes in thymus and also quantify them in different thymus structures by image analysis software.Comparing with normal thymus of the same age, we intended to demonstrate the characteristics of distribution and density of DC subtypes in patients who had MG and hyperplastic thymus. Results: (1) We labeled pDC and cDC by staining with CD123 and CD11c.The two DC subtypes distributed in both cortex and medulla, and the majority gathered in medulla, the density of pDC in thymus cortex was (34±6)/mm(2)(n=14), the density of pDC in thymus medulla was (247±35)/mm(2)(n=14), the density of cDC in thymus cortex was (21±4)/mm(2)(n=14), the density of cDC in thymus medulla was (123±16)/mm(2) (n=14). (2) The density of pDC in thymus cortex and medulla of patients with MG was lower when compared with the normal group (the density of pDC in thymus cortex, [(39±10)/mm(2) vs (29±5)/mm(2)], the density of pDC in thymus medulla, [(279±48)/mm(2) vs (236±49)/mm(2)], but with no significant difference.There was no significant difference between the density of cDC in thymus cortex of patients with MG patients and normal people, however, the amount of cDC increases in medulla and the difference was statistically significant (P<0.05). (3) The density of cDC in thymus medulla (except for germinal center) was higher than normal people (110±18) /mm(2) vs (187±29/mm(2)), though the difference was not statistically significant (P=0.059 9). The density of cDC in the ectopic germinal center (GC) of MG patients increased obviously compared with that in thymus medulla [(203±44) /mm(2) vs (439±69)/mm(2)] and the difference was statistically significant (P<0.05). Conclusions: The density of cDC increases significantly in thymus medulla of MG patients, especially gathering around or in the ectopic GC. It indicates that cDC may play an important role in the formation of ectopic GC in the hyperplasia thymus, thus involves in the disease process.

CD4+ FoxP3+ T regulatory cell subsets in myasthenia gravis patients.

Although myasthenia gravis (MG) is a classic autoantibody-mediated disease, T cells are centrally involved in its pathogenesis. In recent years a number of studies have analyzed the role of CD4+ FoxP3+ regulatory T cells (Treg) in the disease with contradictory results. Here, the generation of Treg was significantly reduced in thymoma as compared to thymic hyperplasia and normal thymus tissue (p=0.0002). In the peripheral blood, Treg subsets classified according to CD49d, HELIOS and CD45RA expression changed after thymectomy and in the long-term course of immunosuppression. Compared to healthy volunteers the frequency of CD45RA+FoxP3low Treg was reduced in MG patients in general (p=0.037) and in particular in patients without immunosuppression (p=0.036). In our study, thymectomy and immunosuppressive treatment were associated with changes in Treg subpopulations. The reduced frequency of CD45RA+FoxP3low Treg we observed in MG patients might play a role in MG pathogenesis.

Effect of thymectomy for thymic atrophy in myasthenia gravis: A retrospective study on 93 patients.

To clarify the efficacy of thymectomy among myasthenia gravis (MG) patients with and without thymoma. We classified MG patients who underwent thymectomy into 3 groups, such as thymic atrophy group, thymic follicular hyperplasia (TFH) group and thymoma group. We compared the data of clinical features and postoperative prognosis at very short-term, short-term, and medium-term. The clinical course of MG patients with atrophic thymus after thymectomy was even better than those of TFH or thymoma, in this retrospective study. However, we found no significant differences in the comparison of mean dose of prednisolone between the 3 groups at each time point.

Prognosis of thymectomy in myasthenia gravis patients with thymus hyperplasia.

PURPOSE: To compare the post-thymectomy prognosis in different conditions of myasthenia gravis (MG) patients with thymus hyperplasia. MATERIALS AND METHODS: Collecting medical record and carrying out the follow-up study of 123 myasthenia gravis patients with thymus hyperplasia who have underwent thymectomy during the period between 2003 and 2013. Dividing into different groups based on gender, age of onset, duration of disease and Myasthenia Gravis Association of America (MGFA) clinical classification to analyze different prognosis in different groups. RESULTS: Complete stable remission (CSR) was achieved in 71 of 123 patients (59.5%). There is no gender-related difference in achieving CSR. Patients with early onset of MG (≤40 years old) or disease duration less than 12 months had significantly higher CSR rates than those with late onset of MG (>40 years old) or disease duration more than 12 months respectively, while no difference was found in remission rate between MGFA clinical classification I and MGFA II. CONCLUSION: Myasthenia gravis patients with thymus hyperplasia who had thymectomy are proved to possess greater chance of achieving CSR. The onset age of disease and duration are the prognostic factors.

Results of surgical treatment for juvenile myasthenia gravis. / Resultados del tratamiento quirúrgico en la miastenia gravis juvenil.

INTRODUCTION: Radical or extended thymectomy is an effective treatment for myasthenia gravis in the adult population. There are few reports to demonstrate the effectiveness of this treatment in patients with juvenile myasthenia gravis. OBJECTIVE: The main objective of this study was to show that extended transsternal thymectomy is a valid option for treating this disease in paediatric patients. RESULTS: Twenty-three patients with juvenile myasthenia gravis underwent this surgical treatment in the period between April 2003 and April 2014; mean age was 12.13 years and the sample was predominantly female. The main indication for surgery, in 22 patients, was the generalised form of the disease (Osserman stage II) together with no response to 6 months of medical treatment. The histological diagnosis was thymic hyperplasia in 22 patients and thymoma in one patient. There were no deaths and no major complications in the postoperative period. After a mean follow-up period of 58.87 months, 22 patients are taking no medication or need less medication to manage myasthenic symptoms. CONCLUSIONS: Extended (radical) transsternal thymectomy is a safe and effective surgical treatment for juvenile myasthenia gravis.

PD-L1, PD-1, CD4, and CD8 expression in neoplastic and nonneoplastic thymus.

The checkpoint protein programmed cell death ligand-1 protein (PD-L1) binds to its receptor (PD-1) activating the PD-L1/PD-1 pathway, an important therapeutic target. There is limited information regarding PD-L1 and PD-1 expression in thymic lesions. Sections from nonneoplastic thymi (n = 20), thymomas World Health Organization types A, AB, B1, B2, and B3 (n = 38) and thymic squamous cell carcinoma (n = 8) were stained for PD-L1 (clone SP142; Spring BioScience), PD-1 (MRQ22; Cell Marque), CD4 (clone SPO32; Cell Marque), and CD8 (JCB117; Ventana). Immunoreactivity for each antibody was classified as focal or diffuse and scored as follows: 0, negative; 1%-5%, 1+; 6%-20%, 2+; and >20%, 3+. The proportions of cases expressing PD-L1, PD-1, CD4, and C8 at score ≥1+ were compared by diagnosis, using χ2 statistics. PD-L1 was expressed in 90% of nonneoplastic thymi, 92% of thymomas, and 50% of carcinomas, with significantly higher scores (P < .01) in B2 and B3 thymomas and carcinomas than in AB and B1 thymomas; PD-L1 was diffuse in most B2 and B3 thymomas and focal in carcinomas. PD-1 was focally expressed, and mostly with scores 1+, in 55% of nonneoplastic thymi, 63% of thymomas, and 37.5% of carcinomas. CD4+ and CD8+ cells were diffusely distributed with scores 3+ in all lesions other than B3 thymomas and carcinomas. The latter showed CD4+ cells mostly at the interface between neoplastic cells and stroma. PD-L1 and PD-1 are not expressed in similar locations and cellular proportions in thymic lesions, raising a question as to whether the PD-L1/PD-1 pathway is an actionable therapeutic target in these lesions.

[The role of plasmapheresis in prevention of complications after thoracoscopic thymectomy in patients with myasthenia combined with thymic hyperplasia]. / Rol' plazmafereza v profilaktike oslozhnenii videotorakoskopicheskoi timektomii u patsientov s miasteniei v sochetanii s giperplaziei vilochkovoi zhelezy.

Surgical indications for thymectomy include thymus tumour of different genesis as well as myasthenia. Minimally invasive methods such as thorascopy and robot-assisted thymectomy have been widely used lately as well as standard surgical methods namely sternotomy and thoracotomy. Regardless the type of access in myasthenia patients specific crisis conditions of respiratory failure can appear in postoperative period that usually requires mechanical ventilation. This study was aimed to estimate the efficacy of pre- and postoperative plasmapheresis in prevention of specific myasthenia-associated complications.

Recovery of pulmonary and skin lesions of sarcoidosis after thymectomy.

OBJECTIVE AND IMPORTANCE: Sarcoidosis is a multisystem inflammatory disorder of unknown etiology. It is characterized by the presence of noncaseating granulomas and an inflammatory process in which T lymphocytes, especially type-1 helper T (Th1) cells, macrophages and different cytokines are involved. Different studies have shown the importance of genetic background in addition to environmental exposure in explaining different clinical phenotypes and disease outcome. In addition, potential auto antigens that might lead to the disease have been identified. CLINICAL PRESENTATION: Here, we present a 53-year-old female patient presenting with subcutaneous nodules and mediastinal hilar lymphadenopathies refractory for corticosteroid treatment. Computed tomography of the thorax revealed a soft-tissue lesion in the thymus location. INTERVENTION: The lesions due to sarcoidosis resolved after thymectomy. CONCLUSION: The remission of skin and pulmonary sarcoidosis only after thymectomy does potentially indicate the critical role that the thymus might play in the pathogenesis of this disease in a certain group of patients.