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RNA tumor virus in human thymomas and thymus hyperplasias.

Human thymomas and thymus hyperplasias were examined for retroviruses. Most of these patients were complicated by systemic immunological diseases such as myasthenia gravis and pure red cell aplasia. The thymus cells were co-cultured with allogenic B cells or peripheral blood lymphocytes (PBL) pretreated with mitomycin C. Retrovirus-like particles were demonstrated in cultured thymus cells in all cases of thymomas and thymus hyperplasias examined by electron microscopy. In most cases, these particles were detected in thymus epithelial cells. Reverse transcriptase activity sedimenting at a density of 1.15-1.17 gm/cm3 in sucrose density gradients was eluted in the culture fluids. Retrovirus-like particles were demonstrated in human T cells infected with these particles. Antibodies to virus-infected T cells were detected in sera of the patients with thymoma and thymus hyperplasia. These results suggest that in thymomas and thymus hyperplasias, retroviruses that can be induced, following a proliferative stimulus, may be involved in the genesis of thymic disorders and in the pathogenesis of systemic immunological diseases.

Adult↗

[Thymus hyperplasia: classification, problems of patho- and morphogenesis, importance in human pathology].

Thymus hyperplasia may be congenital (thymomegaly) and acquired (acquired thymomegaly, "tumour-like" hyperplasia, lymphofollicular hyperplasia). Congenital thymomegaly is represented by variants with hypo- and hyperfunction of an adequately formed thymus and results from the congenital neuro-endocrine disturbances. Thymomegaly with a thymus hypofunction is a marker of the immunodeficiency. Acquired thymomegaly is also represented by two variants with hypo- and hyper-function of the thymus and is in fact a "phenocopy" of the congenital one. "Tumor-like" thymus hyperplasia is a rare form of its pathology with a thymic weight reaching 800 g thus resulting in a syndrome of the mediastinum organs compression. Lymphofollicular thymus hyperplasia can not be always considered to be a thymus pathology but it is characteristic of autoimmune and infectious-allergic diseases with lymphoid follicles localizing in the hyperplastic intralobular perivascular spaces. Thymus parenchyma changes depend on the main disease and play a main role in the development of thymus dysfunction, for example, in the autoimmune diseases. Formation of lymphoid follicles in the dilated perivascular spaces is a non-specific process.

Diagnosis, Differential↗

Glucocorticoid-binding components in human thymus hyperplasia.

Preliminary experiments on thymocyte suspensions derived from human thymus hyperplasia indicated the presence of specific cytoplasmic receptors binding [3H]-dexamethasone with high affinity and specificity. The receptor was rapidly transferred into the nuclei at 28 degrees but not at 2 degrees. With cell-free preparations and ion-exchange cellulose-impregnated paper filters, thymus cytosol bound [3H]dexamethasone with a dissociation constant of 4.3 x 10(-9) M; the concentration of receptor sites was 9.6 x 10(-14) mole/mg cytosol protein. Cytosol contained binding components that sedimented at approximately 7S and 3.6S (low ionic strength) and at 4S (high ionic strength). Competition studies showed high specificity for glucocorticoids since binding of labeled dexamethasone was inhibited in the presence of 10(-6) M beta-methasone, prednisolone acetate, dexamethasone, corticosterone, cortisol, and cortisone. 17beta-Estradiol, testosterone, and dihydrotestosterone at 10(-6) M did not inhibit specific binding of [3H]dexamethasone. Thus, the dexamethasone-binding components of the human thymus hyperplasia had properties similar to those described for steroid hormone receptors present in target tissues.

Cell Nucleus↗

[Thymus hyperplasia following chemotherapy].

Hyperplasia of the thymus, an uncommon development following chemotherapy, raises doubt concerning possible tumor recurrence. We report a case of thymic hyperplasia in a 12-year-old girl who was given chemotherapy for a cervicomediastinal lymphoma. Three months after treatment end, dry cough and an enlargered mediastinum suggested recurrence, but histological examination of tissue biopsy demonstrated benign reactive hyperplasia. Outcome was favorable without recurrence after corticosteroid therapy. According to the literature, thymic hyperplasia is neither tumor nor treatment specific. It generally occurs in children but may be observed in young adults. Hyperplasia of the thymus following chemotherapy would appear to be a good prognosis factor.

Age Factors↗

Thymus hyperplasia, differential diagnosis in the wheezing infant.

Thymus hyperplasia is not a rare condition in infancy, but it is generally considered not to cause any symptoms. We present here a series of 11 children seen at the National Institute of Pediatrics (NIP), Mexico-city, that do have respiratory symptoms secondary to the enlarged gland. Age of onset of the symptoms was median at birth, with age of first visit to the NIP of 6 months. Symptoms were respiratory crisis and various respiratory complaints. Five underwent thoracotomy and resection of the right pulmonary lobe was necessary in one, because of irreversible changes in the lung tissue due to chronic compression. In another patient thymic lobectomy was executed because extrinsic compression of the right upper bronchus resulted in recurrent atelectasia. The five biopsies taken during the intervention showed normal or hyperplastic or involutive thymic tissue without signs of malignancy. The evolution was positive in all the patients. In conclusion thymic hyperplasia must be taken into account in the evaluation of an infant with respiratory symptoms.

Adolescent↗

[Primary and secondary (reactive) thymus hyperplasia in cases of sudden death].

Two post-mortem cases of thymic hyperplasia are studied. The death of patients occurred suddenly, from an acute hypocorticoidism developing in connection with a surgical operation. In the 1st case (a woman of 27) the thymicolymphatic state (TLS) with anomalies of sex organs was observed. A sudden death occurred 2 hours after the operation of colpopoiesis from the pelvic peritoneum. In the 2nd case (a woman of 30) a sudden death occurred at the end of cesarean operation and extraction of two fetuses (the pregnancy was of a normal duration). The patient had hyperprolactinemia and infertility for 8 years and for this reason was treated with parlodel (total dose 780 mg within 4 months). Acute hypocorticoidism in the 1st case was connected with the adrenal hypoplasia characteristic of TLS in which thymic hyperplasia is a manifestation of a congenital immune-endocrine insufficiency. In the 2nd case hypocorticoidism was due to the adrenal atrophy developing apparently as a result of focal sclerosis of the adenohypophysis. Its development may be explained by the disintegration of prolactin-secreting cells resulting from parlodel treatment. Hyperplasia of the thymus in this case is secondary and reflects the degree of adrenal insufficiency.

Adrenal Cortex↗

Myasthenia gravis patients with thymus hyperplasia and myasthenia gravis patients with thymoma display different HLA associations.

Thirty myasthenia gravis (MG) patients (9 with thymoma, 12 with thymus hyperplasia and 9 with thymic atrophy) and 181 Norwegian healthy controls were serologically typed for HLA-A, -B and -DR antigens and genomically typed for HLA-DQA1 and HLA-DQB1 alleles by probing in vitro amplified DNA with sequence-specific oligonucleotides. In patients with thymus hyperplasia the frequency of the DQB1*0201 allele was increased compared to controls (RR = 3.5, p less than 0.05), whereas among the patients with thymoma this allele was not observed (RR = 0.06, p less than 0.01). The frequencies of HLA-B8, -DR3 and -DQA1*0501, which are in strong linkage disequilibrium with DQB1*0201, were increased in patients with hyperplasia and reduced in patients with thymoma. The data suggest that different HLA genes predispose to two different forms of MG.

Alleles↗

Mucosa-associated lymphoid tissue of the thymus hyperplasia vs lymphoma.

In the thymus, the relationship between lymphofollicular hyperplasia and mucosa-associated lymphoid tissue (MALT)-type lymphoma is uncertain. We analyzed 14 cases with a diagnosis of thymic follicular hyperplasia in patients with connective tissue disease (n = 2), myasthenia gravis (n = 11), or both (n = 1). In 11 cases, well-defined reactive lymphoid follicles were surrounded by a continuous layer of medullary epithelial cells. A polyclonal rearrangement of the immunoglobulin heavy chain gene (IgH) was observed. In 3 cases, ill-defined lymphoid follicles with sheets of centrocytic-like B cells disrupting the medullary cytokeratin epithelial network were observed on certain sections. These cells expressed the phenotypic features of memory B cells with CD20, CD79a, and bcl-2 positivity and CD5, CD10, CD23, and bcl-6 negativity, and a monoclonal rearrangement of the IgH gene was detected. Appropriate sampling, cytokeratin staining, and molecular analyses may help to identify early MALT-type lymphoma developing in the setting of thymic lymphofollicular hyperplasia.

Adult↗

Airway compression following thymus hyperplasia in an infant with Pierre Robin sequence and congenital diaphragmatic hernia.

A female infant with respiratory embarrassment due to external compression of the tracheobronchial tree by the thymus is presented. After successful intrauterine drainage of pleural effusions, she was born with a diaphragmatic hernia and Pierre Robin sequence, which required long-term mechanical ventilation and several surgical interventions, including tracheostomy, until she breathed spontaneously. At age 7 months, she was rehospitalized in respiratory failure because of pneumonia. At this time, thymus hyperplasia was first diagnosed, which had caused tracheobronchomalacia and displacement of the tracheobronchial tree. Weaning from the ventilator was unsuccessful for 8 weeks. She underwent thymectomy, following which impairment of breathing resolved immediately. Different manifestations of thymus enlargement and their relation to impaired breathing are discussed.

Female↗

[Thymus hyperplasia in patients with malignant testicular tumors].

Follow-up serial computed tomographic scans of 124 patients treated for testicular cancer with either radiotherapy or retroperitoneal lymphadenectomy alone or in combination with chemotherapy were evaluated. Thymic enlargement occurred three to 20 months after initiation of treatment in 15 of the 124 patients. Thymic enlargement could histopathologically be demonstrated in seven patients as true hyperplasia. One of these seven patients however had evidence of metastatic disease with thymic infiltration by a malignant teratoma. Thus it may be impossible to distinguish benign thymus hyperplasia from tumor-infiltration on the basis of ct information alone and sternotomy may be required. No severe defect of cellular immunity could be found. There is no specific constellation of lymphocytic markers in peripheral blood which could indicate true thymic hyperplasia.

Adult↗

[Heterogeneity and polymorphism of the thymus hyperplasia syndrome in children in the first 3 years of life].

Sixteen years of observation over a large group of children with the syndrome of the enlarged thymus with the use of up-to-date methods of examining the CNS, immune, endocrine, neuroendocrine systems and the autopsy data allowed the heterogeneity and polymorphism of the given syndrome to be revealed. Both transitory and stable enlargement of the thymus may be observed. The syndrome of the stable-enlarged thymus is likely to be formed in the intrauterine period and postnatally as well. It may be associated and not associated with thymus-dependent immunodeficiency. The morphological investigation of the thymus may show an enlargement of the cortical area with enhanced T lymphocyte proliferation in it or formation of lymphoid follicles. In clinical practice, the syndrome of the stable-enlarged thymus should be differentiated with thymic tumor. The working classification of the syndrome and concept of the pathogenesis of the stable-enlarged thymus are offered.

Age Factors↗

Pulmonary embolization-induced thymus hyperplasia in rabbits.

The effects of pulmonary embolization on the thymus glands of rabbits were studied morphologically, morphometrically and immunohistochemically. Pulmonary embolization was induced by an intravenous injection of 0.4 ml of Sephadex bead suspension (particle size; 150 to 300 microns, about 2,000 per ml). Both mean weight and volume of the thymus of rabbits killed at 2 weeks after embolization, were about 1.5 times more than those in control animals treated with physiologic saline. Histological examinations showed enlargement of the cortex and medulla of the thymus, and the embolized Sephadex beads in the branches of pulmonary arteries of the lung. The area ratios of medulla/cortex, in the embolization group and in control, were not significantly different. The cells with immunohistochemically positive staining of anti-nuclear antigen of monoclonal antibody of Ki-67, were found in both portions of the medulla and cortex. These data suggest that pulmonary embolization in the rabbit induces true thymic hyperplasia. An intravenous injection of India ink into the right highest intercostal artery revealed the distribution of bronchial arteries, which send the branches to the right lobe of the thymus. In 2 out of 4 animals killed 2 weeks after pulmonary embolization, the left lobe of the thymus as well as the right were stained with the injected ink. As it is known that pulmonary vascular obstruction caused a marked increase in the bronchial blood flow, these data suggest that the thymus blood supply from the bronchial arteries increases in the conditions of pulmonary embolization, which might contribute to thymus hyperplasia.

Animals↗