Síndrome de Klinefelter diagnosticado en un adulto a raíz del estudio de infección respiratoria recurrente y masa mediastínica: caso clínico / Thymoma in a patient with klinefelter syndrome: case report

Klinefelter syndrome (47, XXY in most cases) is a frequently underdiagnosed chromosomal anomaly associated with multiple comorbidities in adult life. Patients with Klinefelter syndrome have a higher risk of cancer. Specifically, these patients have a higher risk for mediastinal germ cell tumors. It is estimated that 8% of male patients with mediastinal tumors have Klinefelter. We report a 42-years-old male who suffered recurrent respiratory infections. During the study, a mediastinal mass was found, whose pathological study disclosed a type B thymoma. The patient had a history of infertility, high stature, gynecomastia, obesity with gynecoid distribution of body fat and testicular atrophy. A karyotype was requested (47, XXY), confirming the diagnosis of Klinefelter syndrome.

Carcinoma tímico en un adulto / Thymic carcinoma in an adult

Se presenta el caso clínico de un paciente de 50 años de edad, quien acudió a la consulta de Oncología del Hospital General Docente Dr Juan Bruno Zayas Alfonso de Santiago de Cuba, por presentar un tumor tímico de 4 meses de evolución. Se le realizó timectomía y linfadenectomía mediastinal, así como una biopsia que indicó la presencia de carcinoma tímico de tipo linfoepitelioma (II) de alto grado de malignidad, estadio IVA; por tal razón se decidió efectuar tratamiento con quimioterapia y radioterapia. Debido a la persistencia del tumor se planificó la segunda línea de quimioterapia, pero el paciente falleció.

The case report of a 50 year-old patient is presented who visited the Oncology department of Dr Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, due to a 4 months thymic tumor. A thymectomy and mediastinal lymphadenectomy were carried out , as well as a biopsy which indicated the presence of thymic carcinoma, type II lymphoepithelioma of high degree of malignancy, stage IV A; for such a reason it was decided to carry out a treatment with chemotherapy and radiotherapy. Due to the tumor persistence the second chemotherapy line was planned, but the patient died.

Chemotherapy and prognosis in advanced thymic carcinoma patients

OBJECTIVE: The role of chemotherapy in treating advanced thymic carcinoma is unclear. The purpose of the current study was to investigate the efficacy of chemotherapy and the prognostic factors for patients with advanced thymic carcinoma. METHODS: A retrospective review of the medical records of 86 patients treated with chemotherapy for advanced thymic carcinoma was conducted between 2000 and 2012 at our institution. The clinical characteristics, chemotherapy regimens and prognostic factors were analyzed. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazard model was used for multivariate analysis. RESULTS: Of the 86 patients, 56 were male and 30 were female. The median survival time was 24.5 months. For the first-line chemotherapy treatment, the objective response rate was 47.7% and the disease control rate was 80.2%. The median progression-free survival for all patients was 6.5 months for first-line chemotherapy. No significant differences in progression-free survival were observed among the different chemotherapy regimens. Multivariate analyses revealed that the prognostic factors for overall survival included performance status (p=0.043), histology grade (p=0.048), and liver metastasis (p=0.047). CONCLUSION: Our results suggest that there is no difference in efficacy between multiagent and doublet regimens. The prognosis of patients with advanced thymic carcinoma can be predicted based on histological grade, liver metastasis and performance status.

Síntomas de miastenia grave en un paciente con antecedente de timectomía por timoma invasor / Symptoms of myasthenia gravis in a patient with a history of thymectomy for invasive thymoma

Introducción. La miastenia grave es una enfermedad autoinmunitaria mediada por anticuerpos. Entre 10 y 15 % de quienes la padecen tienen timoma y su presencia se asocia con una mayor gravedad de los síntomas, crisis miasténicas y fracaso del tratamiento de primera línea. La timectomía se recomienda en pacientes jóvenes con miastenia grave generalizada y en todos los pacientes con timoma. Caso clínico. Se presenta el caso de una mujer de 43 años que, en el 2005, presentó una primera crisis miasténica asociada con un timoma invasor que se trató con timectomía y radioterapia. Durante los siguientes tres años, presentó síntomas graves y dos crisis más, que obligaron a suministrarle respiración mecánica asistida e inmunoglobulina. Al cabo del tratamiento, no se evidenciaron signos de recurrencia en las tomografías de tórax con contraste. Entre el 2009 y el 2012, la gravedad de los síntomas fue menor. En el 2013, estos se exacerbaron y una resonancia magnética de tórax con contraste reveló una lesión en el mediastino anterior, ya observada en el 2011, sugestiva de tejido residual o fibrosis. Se inició el tratamiento usual con inmunoglobulina y se hizo una tomografía por emisión de positrones cuyos resultados no fueron concluyentes, por lo que se llevó a cabo una nueva resección y se constató que no había recurrencia del tumor. Conclusiones. Los pacientes con miastenia grave y aquellos con timoma asociado, deben someterse a la timectomía como parte del tratamiento. Sin embargo, la exacerbación de los síntomas o su reaparición después del procedimiento no necesariamente implica una nueva alteración en el timo.

Introduction: Myasthenia gravis is an antibody-mediated autoimmune disease. Approximately 10-15% of patients present with a thymoma, the presence of which is associated with greater severity of symptoms, myasthenic crisis, and irresponsiveness to front-line therapy. A thymectomy is recommended in young patients with generalized myasthenia gravis and in all patients presenting with thymoma. Clinical case: The patient was a 43-year-old woman, who first showed symptoms of myasthenic crisis in 2005 and presented with invasive thymoma managed with thymectomy and radiotherapy. In the subsequent three years, the patient presented with severe symptoms and two myasthenic crises that required mechanical ventilation and immunoglobulin treatment. Contrast chest computed tomography examinations showed no recurrence. Between 2009 and 2012, the patient experienced decreased symptom severity. In 2013, the patient presented with an exacerbation of symptoms; a contrast chest magnetic resonance scan showed a lesion in the anterior mediastinum, previously observed in 2011, suggestive of residual tissue as opposed to fibrosis. Regular management was started with immunoglobulins; a positron emission tomography scan was inconclusive, requiring a new resection, which showed no evidence of tumor recurrence. Conclusions: Patients with myasthenia gravis and those with myasthenia-related thymoma both share thymectomy as an element of treatment. However, following the procedure, exacerbation or reappearance of symptoms does not necessarily represent new alterations in the thymus.

Masa intraauricular derecha en paciente chagásico con marcapasos definitivo / A mass inside the lright atrium in a patient with chagas disease and a pacemaker

Se presenta un paciente de 60 años, chagásico crónico y usuario de marcapasos definitivo con masa en aurícula derecha asociada a Síndrome de Vena Cava Superior y baja de peso.

A 69 year old man, with Chagas Disease and an implanted pacemaker develop a superior vena cava syndrome and weight loss.

Thymoma: First large Indian experience.

BACKGROUND: Thymoma is the most common tumor of the anterior mediastinum. Surgery is mainstay of treatment, with adjuvant radiation recommended for invasive thymoma. Because of rarity, prospective randomized trials may not be feasible even in multicentric settings hence the best possible evidence can be large series. Till date Thymoma has not been studied in Indian settings. MATERIALS AND METHODS: All patients presenting to Thoracic disease management group at our Centre during 2006‑2011 were screened. Sixty two patients’ with histo‑pathological confirmation of thymoma medical records could be retrieved and are presented in this study. Mosaoka staging and WHO classification was used. The clinical, therapeutic factors and follow up parameters were recorded and survival was calculated. Effects of prognostic factors were compared. RESULTS: Sixty two patients were identified (36M, 26F; age 22‑84, median 51.5 years) and majorities (57%) of thymoma were stage I‑II. WHO pathological subtype B was most common 30 (49%). Mean tumor size was smaller in patients with myasthenia (5.3cm) than the entire group (7.6cm). Neoadjuvant therapy was offered to five unresectable stages III or IV a patient’s with 40% resectability rates. Median overall survival was 60 months (Inter quartile‑range 3‑44 months) with overall survival rate (OS) at three year being 90%. Resectable tumors had better outcomes (94%) than non resectable (81%) at three years. Mosaoka Stage was the only significant (P = 0.03) prognostic factor on multivariate analysis. CONCLUSION: This is first thymoma series from India with large number of patients where staging is an important prognostic factor and surgery is the mainstay of therapy. In Indian context aggressive multimodality treatment should be offered to advanced stage patients and which yields good survival rates and comparable.

Síndrome de Good y aplasia pura de la serie roja, reporte de un caso y revisión de la literatura: Report of one case / Association of Good syndrome with pure red cell aplasia

Background: The association between Good's syndrome (hypogammaglobulinemia and thymoma) with pure red aplasia is very uncommon. We report a 70-year-old male, who had a thymoma excised nine years before. Afterwards, he suffered frequent respiratory infections, which were attributed to a humoral immunodeficiency. Nine years later, he developed a pure red cell aplasia. He received prednisone and cyclosporine, resulting in a progressive rise of hemoglobin level, after one month of treatment. The patient died shortly thereafter due to infection, complicating a domestic accident.

Resection and reconstruction of mediastinal great vessels in invasive thymoma.

Objective : To evaluate the safety, feasibility, and outcome following radical excision of thymoma with resection and reconstruction of invaded mediastinal vessels. Study Design : A retrospective study. Patients and Methods : Six patients with thymoma invading the superior vena cava (SVC) and/or the brachiocephalic veins (BCVs) were reviewed in this study. All the patients underwent radical excision of the tumor along with invaded mediastinal vessels followed by vessel reconstruction or repair. The clinical presentation, operative details, postoperative course, and follow-up were reviewed and analyzed. Results : Three patients presented with features suggestive of SVC syndrome. Contrast-enhanced computed tomography of the chest was the primary imaging modality, which detected a tumor with invasion of major mediastinal veins. WHO type B2 was the commonest histologic type, which was seen in 4 cases. Intraoperatively, SVC invasion, SVC and BCV invasion, and BCV invasions alone were seen in 1, 2, and 3 cases, respectively. The vessels were reconstructed with a prosthetic graft in 3 patients, and autologous pericardial tube graft was used in 1 patient. Two patients had primary repair of the wall of the involved vessel. Postoperative course was complicated by ventilator support requirement in 2, graft thrombosis in 2, acute renal failure in 1 and pneumonia in 1 patient. All patients are alive at the end of follow-up period ranging between 18 and 24 months. Conclusion: Thymoma excision with the reconstruction of SVC or BCV is safe and feasible in experienced hands.

Incidental invasive thymoma during coronary artery bypass surgery

We encountered 2 incidental cases of invasive thymomas at Jordan University Hospital, Amman, Jordan; during routine coronary artery bypass graft surgery between 2005 and 2008 with an incidence of 0.6%. Both patients presented with angina pain. None of the 2 patients had pressure symptoms cough, shortness of breath or superior vena cava syndrome or Myasthenia Gravis symptoms. Total thymectomy with dissection of perithymic fat was performed on both cases. No radiotherapy was given. No recurrence of the tumor was seen in 2 years follow up. These cases are presented to emphasize the occurrence of this tumor

La citometría de flujo en el estudio de tumores mediastinales ricos en elementos linfoides / Flow cytometry for the study of mediastinal tumors with abundant lymphoid elements

El mediastino anterior es un sitio frecuente de localización de tumores ricos en elementos linfoides. La identificación correcta de cada entidad es de importancia en el tratamiento de los pacientes. En ocasiones puede plantearse el diagnóstico diferencial entre timoma y linfoma linfoblástico con fenotipo de precursor T (LLB-T). La Citometría de Flujo (CF) es una técnica complementaria útil para estos tumores de la cual se obtiene información cualitativa y cuantitativa. Revisamos 38 tumores mediastinales que tenían estudio de CF. Además comparamos los resultados de CF de timomas y tejido tímico normal con 42 casos de LLB-T de otras localizaciones anatómicas. De los 38 tumores mediastinales 6 eran lesiones benignas, 9 linfomas difusos de células grandes con fenotipo B (LDCG-B), 10 linfomas de Hodgkin (LH), 11 timomas y 2 LLB-T. En 24 casos la CF aportó información positiva, definiendo el inmunofenotipo de las células linfoides neoplásicas, o los linfocitos característicos que acompañan a los timomas. La CF en los 10 casos de LH y en 4 lesiones benignas permitió descartar otros tipos de linfoma (LDCG-B, LLB-T, etc.). Las marcaciones para CD3, CD4 y CD8 fueron las más útiles para el diagnóstico diferencial entre timomas y LLB-T. En conclusión, la CF es una técnica complementaria de utilidad que aporta información en lesiones mediastinales de manera rápida, requiriendo cantidades pequeñas de material, tanto para el diagnóstico inicial como para el monitoreo de estas enfermedades.

The anterior mediastinum is a common site of tumors with abundant lymphoid elements. Flow cytometry is a useful complementary technique to analyze this type of tumors, which provides qualitative and quantitative information. A differential diagnosis can be sometimes made between thymoma and precursor T-lymphoblastic lymphoma (T-LBL). Correct identification is of utmost importance for patient treatment. A total of 38 mediastinal tumors were analyzed, and samples were separated for flow cytometry. Flow cytometry data from thymomas and normal thymic tissue were compared with 42 cases of T-LBL from other anatomical locations. Among 38 mediastinal tumors, we found 6 benign lesions, 9 diffuse large B-cell lymphomas (DLBCL), 10 Hodgkin lymphomas (HL), 11 thymomas and 2 T-LL. Flow cytometry provided positive information in 24 cases, and defined lymphoid neoplastic cells immunophenotype or the typical lymphocytes accompanying thymomas. Flow cytometry helped differentiate 10 cases of HL and 4 benign lesions from other lymphomas (DLBCL, T-LBL, etc.). CD3, CD4 and CD8 expressions were most useful for the differential diagnosis of thymomas and T-LL. To conclude, flow cytometry is a valid complementary technique, which promptly provides information on mediastinal lesions, requiring small quantities of tissue for both early diagnosis and follow up of these diseases.

Histopatholgical spectrum of thymic neoplasms: twelve-year experience at a referral hospital in north India.

This study was undertaken to determine the histopathological spectrum and clinical profile of thymic neoplasms at a tertiary referral care centre. A total of 96 thymectomy specimens were received during the study period (1992-2004), which consisted of 54 neoplasms and 42 benign lesions. Among the neoplasms there were 48 thymic epithelial tumors, 3 thymolipomas and 3 thymic carcinoids. The former comprised of 36 male (75%) and 12 female patients (25%) ranging in age from 2-70 years (mean 37 years). Among paraneoplastic syndromes in thymic epithelial tumours, 27 out of 48 (56.25%) cases were associated with myasthenia gravis and one case was associated with pure red cell aplasia. The most frequent histological subtype was cortical thymoma (43.24%) followed by predominantly cortical (24.32%) and well-differentiated thymic carcinoma (18.92%). On staging, all cases of mixed and predominantly cortical subtype were stage 1 whereas one medullary and 2 cortical thymomas and 4 well differentiated thymic carcinoma (WDTC) showed pleural and pericardial invasion (stage III). This study has revealed that half of thymic epithelial tumours presented as myasthenia gravis. The cortical thymoma was the most frequently encountered histologic subtype and most commonly associated with myasthenia gravis.

Thymoma: a pathological study of 50 cases.

BACKGROUND: A combination of epithelial cells and lymphocytes results in a varied histomorphology of thymomas and consequent varied classification systems. AIM: To correlate the Marino and Muller-Hermelink (MMH) classification with the invasive behaviour of thymomas. SETTING AND DESIGN: Retrospective analysis. MATERIALS AND METHOD: Thymomas encountered in the past 21 years were re-classified with the MMH classification and correlated with Masaoka's staging and clinical presentation. RESULTS: The thymomas formed 91% of the primary thymic epithelial tumours. Predominantly cortical thymomas (n=21) and cortical thymomas (n=22) were the common subtypes and 60% and 77% of these, respectively, were in stages II or III. Cystic change, necrosis or haemorrhage played no role in predicting invasive behaviour. Cortical epithelium correlated well with the presence of para-thymic syndromes, especially myasthenia gravis. CONCLUSION: MMH classification is easy to apply. Cortical thymomas in stage I should be followed up for possible recurrence.

Thymoma with Pseudosarcomatous Stroma

Thymoma with psuedosarcomatous stroma is a recently described, rare variant of thymomas that are characterized by having a biphasic histologic pattern which consists of both an epithelial and a spindle cell stromal component. So far only 11 cases having similar histologic findings have been reported world wide. At this time we report a case of this rare variant of thymoma which occurred in a 53-year-old Korean man. This previously healthy patient presented with coughing and an anterior mediastinal mass was then detected radiographically. Mediastinal exploration revealed a 9 x 8 x 8 cm-sized well- encapsulated, ovoid, cystic mass. Histological examination showed a biphasic neoplasm composed of anastomosing nests of epithelial cells and somewhat cellular stromal spindle cells that had advanced degenerative changes. Immunohistochemical staining using the antibodies for cytokeratins, EMA, e-cadherin, and p75NGFR showed a strong expression of these markers in the epithelial component but no expression in the spindle stromal cells. The epithelial tumor cells showed no reactivity to CD5 and L26 and a high proportion of the infiltrated lymphocytes were the cortical type that expressed CD99 and terminal deoxynucleotidyl transferase. Ultrastructural examinations revealed tonofilaments in the spindle cells. Follow up has been done for 5 years after the surgical excision and the patient has been free of disease during that period. Similar to previous reports, this patient had a benign clinical course that was unassociated with myasthenia gravis which appears to be a characteristic of this histologic variant of thymoma. However, our case also showed advanced degenerative features and we could demonstrate ultrastructural evidence of epithelial differentiation in the stromal spindle cells that were not mentioned in the previously reported cases. Based on the results of our studies, we suggest this entity is a distinct type of organotypic thymoma that shows cortical differentiation and abundant cellular stroma.

Invasive medullary thymoma associated with myasthenia gravis: an unusual case

Thymomas are tumors characterized by a remarkable morphological heterogeneity and variable clinical behavior. This tumor has unique clinical associations, most notably with hematological abnormalities and myasthenia gravis. According with the Müller-Hermelink criteria, there are significant differences between the histological types of thymomas and the association with myasthenia gravis. Among the different histological types, medullary thymoma is the least frequent variant associated with this autoimmune disease. In this report we describe a case of medullary thymoma presenting in a 71-year- old woman with a myasthenic syndrome

A study of myasthenia gravis in patients with and without thymoma.

This study was undertaken to compare the clinical, neurophysiological, radiological and prognostic features of myasthenia gravis with and without thymoma. 37 patients with myasthenia gravis (27 males, 10 females), with age range of 4.5 to 72 (mean 39) years, were managed at a tertiary care centre in India. Four patients were below 15 years of age and 6 above 55 years. Most of the patients were in stage II (34). There were 2 patients in stage III and 1 in stage I. 27 patients underwent thymectomy. Thymoma was detected in 10 cases. The decrement in patients with thymoma ranged between 11 and 62% (mean 27.9%) and nonthymoma group 10-75% (mean 28%). CT scan of thorax revealed mediastinal mass in 5 out of 10 cases of thymoma and 2 out of 27 patients without thymoma. Outcome of myasthenia gravis with thymoma was worse than without thymoma at 1 year followup. Severity of illness, extent of decrement, lack of facilitation, duration of illness and age of the patients were not related to the outcome. It is concluded the clinical and neurophysiological changes in myasthenia gravis with and without thymoma do not differ. However, patients with thymoma have a worse outcome.

Timoma invasivo: vias locais de disseminaçäo: avaliaçäo por tomografia computadorizada / Invasive thymoma: local pathways of dissemination: computed tomography assessment

Três pacientes com diagnóstico comprovado de timoma invasivo foram estudados por tomografia computadorizada, para determinar as diferentes vias de disseminaçäo local, de acordo com a sua história natural. O envolvimento pleural mediastinal, o envolvimento das estruturas cardiovasculares mediastinais e os implantes pleurais extramediastinais foram os achados mais freqüentes, seguidos pelos implantes pleurais, no ângulo cardiofrênico, nos ângulos costofrênicos, no hiato aórtico e envolvimento retroperitoneal, näo se observando, neste estudo, o envolvimento pulmonar e os implantes pericárdicos e diafragmáticos. Concluímos que a tomografia computadorizada é excelente método de imagem para predizer o caráter invasivo dos timomas, permitindo observar com detalhe as interfaces entre as diferentes estruturas e uma visibilizaçäo clara das superfícies dos grandes vasos do mediastino, das pleuras e da junçäo toracoabdominal