Thymic rebound hyperplasia post-chemotherapy mistaken as disease progression in a patient with lymphoma involving mediastinum: a case report and reflection.

BACKGROUND: Chemotherapy can cause thymic atrophy and reduce T-cell output in cancer patients. However, the thymus in young adult patients has regenerative potential after chemotherapy, manifesting as thymic hyperplasia which can be easily mistaken as residual disease or recurrence in patients suffering lymphoma. CASE PRESENTATION: This study reports a case of lymphoma in a young female adult who was initially diagnosed with an anterior mediastinal mass, and was found to have soft tissue occupying the anterior mediastinum repeatedly after chemotherapy, suggesting a lymphoma residue or disease progression. From discussions by a multi-disciplinary team (MDT), the anterior mediastinal mass of the patient was considered unknown and might be thymus tissue or tumor tissue, and it was eventually identified as thymus tissue via histopathology. CONCLUSIONS: The anterior mediastinal mass appearing after chemotherapy in patients with lymphoma can be considered as enlarged thymus, and such phenomenon is frequent in young adult patients who undergo chemotherapy or autologous hematopoietic stem cell transplantation. Additionally, detection of thymic output cells in peripheral blood might be a feasible approach to differentiate thymic hyperplasia from lymphoma.

Thymic hyperplasia following double immune checkpoint inhibitor therapy in two patients with stage IV melanoma.

Hyperplasia of the thymus is commonly seen in myasthenia gravis and other autoimmune disorders. Thymic size also varies with age, corticosteroid use, infections, and inflammatory disease. Although thymic hyperplasia has been described following chemotherapy, there is no known association of true thymic hyperplasia with immune checkpoint inhibitor therapy. We present two cases of suspected true thymic hyperplasia in patients with stage IV melanoma who were treated with the combination of nivolumab and ipilimumab, which was complicated by immune-related toxicity requiring corticosteroid therapy, and then subsequently also by secondary hypoadrenalism requiring replacement hydrocortisone. In one patient, histological and flurocytometric analyses of an incisional biopsy of the thymus revealed findings consistent with true thymic hyperplasia. In the other case, the stable fluorodeoxyglucose positron emission tomography/Computed tomography (FDG-PET/CT) findings were consistent also with true thymic hyperplasia. These are the first described cases of true thymic hyperplasia following combination immune checkpoint inhibitor therapy for metastatic melanoma. We hypothesize that the true thymic hyperplasia in these cases results from initial lymphocyte depletion caused by intense corticosteroid therapy followed by rebound thymic hyperplasia during the period of relative hypocortisolism, which may have been aggravated by the onset of secondary hypoadrenalism.

Late Relapse of Ovarian Germ Cell Tumour.

BACKGROUND: Malignant ovarian germ cell tumours typically require multimodal therapy including surgery and systemic platinum-based chemotherapy. Most patients are cured, with survival rates exceeding 95%. CASE: This report describes an unusual case of ovarian germ cell tumour (GCT) recurring 15 years after surgery and manifesting as metastatic disease to the liver, lung, and retroperitoneal lymph nodes. CONCLUSION: Thymic hyperplasia was a confounding finding in this case, and it should be considered in the differential diagnosis of a mediastinal mass in heavily treated patients with GCT.

Reactive thymic hyperplasia following chemotherapy for children with lymphoma: computed tomography may be able to provide valuable information to avoid over-treatment.

OBJECTIVES: To analyse the clinical and computed tomography (CT) findings related to reactive thymic hyperplasia in order to improve the recognition of this phenomenon and avert over-treatment. METHODS: Fifty-two children with pathologically proven lymphoma developed reactive thymic hyperplasia following chemotherapy, which was confirmed with long-term review and follow-up. The clinical and CT findings of these 52 children were retrospectively analysed. RESULTS: The median follow-up period for the whole study group was 32.9 months. Fifty-one children survived free of disease; 23 of these had been with tumour invasion and the remaining 29 without. The median period from complete remission (CR) of the mediastinal lesions to the date of recurrent mediastinal masses was 8.6 months, which was not statistically significantly different from that of 9.5 months from commencement of treatment to the date of newly developed mediastinal masses (P = 0.495). The median maximal diameters of the recurrent and newly developed mediastinal masses were not significantly different (P = 0.091). All of the 52 cases presented with a single mediastinal mass; 42 masses (42/52, 81%) of those showed trapezoidal or triangular shapes and were well-circumscribed; 10 masses (10/52, 19%) manifested diffuse shapes and were ill-circumscribed. Forty-two masses (42/52, 81%) showed homogeneous density. All of the masses revealed mild enhancement after contrast administration. Forty-two masses (42/52, 81%) slightly displaced and 10 masses (10/52, 19%) partly surrounded adjacent vessels. After long-term follow-up, 42 masses (42/52, 81%) shrank naturally, and 10 (10/52, 19%) remained unchanged. CONCLUSIONS: Reactive thymic hyperplasia can, and often does, occur in children receiving regular chemotherapy for lymphoma, regardless of whether the tumour initially invades the mediastinum. Knowing the characteristic CT findings of this benign entity is helpful in differentiating it from residual or recurrent lymphoma and averting unnecessary treatment.

[Filling of the thymic space after chemotherapy for ovarian cancer]. / Comblement de la loge thymique après chimiothérapie pour cancer de l'ovaire.

INTRODUCTION: Enlargement of the thymus following remission of a cancer treated by chemotherapy poses a problem of differential diagnosis between benign thymic hyperplasia and relapse of a mediastinal tumour. CASE REPORT: We report the case of a thymic tumour developing 6 months after chemotherapy for ovarian cancer in a woman of 31 years. Because of the risk of a mediastinal recurrence, the patient was submitted to thymectomy by mediastinotomy. Histopathological examination revealed benign thymic hyperplasia in reaction to the chemotherapy. The postoperative course was uneventful. CONCLUSION: Benign thymic hyperplasia may develop after chemotherapy. It is an inflammatory reaction that subsides after a few months. A multidisciplinary discussion to consider the possibility of benign hyperplasia may save the patient unnecessary surgery.

Rebound thymic enlargement on CT in adults.

The objective of this study is to report the development of thymic enlargement in adults, mainly associated with chemotherapy for malignancy. The typical CT features of this phenomenon are described. The clinical data and CT studies of 13 adult patients with newly appearing thymic enlargement on CT were reviewed. These patients were followed-up mainly for malignancy. Further follow-up CTs were studied when available. Medical records were reviewed as to the primary disease, its medical treatment and the time of initial appearance of the enlarged thymus in relation to treatment. The study group included 13 adult patients, 12 with malignant disease and one with a slowly resolving pneumonia. The enlarged thymus appeared as a triangular, arrowhead-shaped structure, with a bilobed configuration and convex borders. Density measurements were consistent with homogeneous soft tissue. Location was in the anterior mediastinum, in the normal site of the thymus. In nine patients, follow-up studies were available. The observation period ranged from 5 months to 8 years from the initial appearance of the enlarged thymus. In five of the nine patients, the thymic enlargement resolved after 1-4.5 years. In four of the nine patients, the thymus remained enlarged during a follow-up ranging from 5 months to 2.5 years. Thymic enlargement, while a rare phenomenon in adults, may occur, mainly after chemotherapy. This phenomenon should be included in the differential diagnosis of a soft tissue mass appearing in the anterior mediastinum on follow-up CT in adult patients particularly following treatment for malignancy.

Thymic hyperplasia in a child treated with growth hormone.

OBJECTIVE: To report a case of thymic hyperplasia diagnosed three months after initiation of recombinant human growth hormone (GH) for the treatment of GH deficiency. DESIGN: Retrospective chart review was conducted to evaluate the temporal relationship between treatment with GH and thymic enlargement in a 7-year-old girl who had a history of embryonal rhabdomyosarcoma of the nasopharynx diagnosed at the age of 3 years. RESULTS: The diagnosis of GH deficiency was made based on clinical and auxological criteria, an insufficient response to clonidine-arginine stimulation testing (peak GH level of 4.8 microg/L) and low insulin-like growth factor 1 (IGF-1) level (30 ng/mL, -2.7 SD). The patient was started on GH at a dose of 0.3mg/kg/week. At the initiation of treatment with GH, the baseline growth velocity was 0.8 cm/year (-6.0 SD) and height was 112.5 cm (-1.7 SD). After three months of treatment with GH, her height increased by 4.2 cm (from -1.7 to -1.2 SD), and the IGF-1 level from -2.7 SD to -1.1 SD. A chest CT performed at that time for recurrence surveillance showed 89% increase in thymic volume relative to previous scan before treatment with growth hormone. A thoracoscopic biopsy of the thymus was performed and revealed hyperplasia with normal thymic architecture without evidence of malignancy. CONCLUSIONS: The timing of the development of thymic hyperplasia, along with data from in vitro and in vivo animal studies showing that GH and IGF-1 can directly stimulate growth of the thymus, suggests that GH contributed to the development of thymic hyperplasia in this patient.

Positive gallium-67 and thallium-201 scans in thymic rebound after chemotherapy for lymphoma.

It is a diagnostic problem to distinguish thymic rebound or rebound thymic hyperplasia from thymic malignancy, but it is frequently made more difficult because most patients have had previous malignancies. Recently we evaluated a six-year-old girl with thymic rebound after chemotherapy for lymphoma, by both gallium-67 and thallium-201 scans. On gallium-67 scan, intensive uptake was seen in the anterior mediastinum. CT revealed a triangular-shaped, homogeneous mass in the anterior mediastinum. On early scan of thallium-201 study, slight accumulation was seen in the anterior mediastinum and was enhanced in delayed scans. Considering the clinical state and imaging results, thymic rebound after chemotherapy was the most likely diagnosis, and follow-up observation was done without therapy. During the course, there were no signs of relapse. Some reports have described both positive and negative thallium-201 accumulation in thymic rebound. Although more experience with similar cases is necessary, it is likely that thallium-201 also tends to accumulate in thymic rebound as well as gallium-67.

[Clinical analysis of reactive thymic hyperplasia following chemotherapy for childhood malignant lymphoma].

BACKGROUND & OBJECTIVE: Reactive thymic hyperplasia following chemotherapy for malignant tumors is likely to be misdiagnosed as tumor residue or relapse, therefore, leads to unnecessary treatment. This study was to analyze the clinical features of reactive thymic hyperplasia following chemotherapy for childhood malignant lymphoma. METHODS: Clinical data of 13 children with reactive thymic hyperplasia following chemotherapy for malignant lymphoma, treated from Mar. 1999 to Mar. 2004, were retrospectively analyzed. Of the 13 cases, 5 were Hodgkin's disease (HD), and 8 were non-Hodgkin's lymphoma (NHL). All patients received computed tomography (CT) to evaluate the therapeutic effect. When a new thymic mass emerged, positive electron tomography/computed tomography (PET/CT) was performed to identify its quality. RESULTS: At diagnosis, 10 patients had mediastinal involvement. Reactive thymic hyperplasia occurred following the completion of chemotherapy in 9 cases, or during the maintenance of chemotherapy in 4 cases. CT showed that the longest diameters of the new mediastinal masses were 2.2-6.0 cm (mean 3.7 cm). The interval from last chemotherapy cycle to the occurrence of thymic hyperplasia was 2-12 months (mean 4 months). PET/CT was performed to 5 cases, and showed no vital tumors in the mediastinum. Three cases were misdiagnosed as tumor residue or relapse, and received second-line therapy. All patients were followed-up for 1-6 years (median 4 years), and none suffered tumor relapse. CONCLUSIONS: Reactive thymic hyperplasia may occur following intensive chemotherapy for childhood malignant lymphoma. It should not be misdiagnosed as malignant tumors and overtreated.

Thymic hyperplasia after adjuvant chemotherapy in breast cancer.

We report 2 patients with breast cancer who were treated with surgery and adjuvant chemotherapy for stage IIa and stage I breast cancers. Follow-up CT scans showed an anterior mediastinal mass, raising concern for tumor recurrence. Thymectomy performed on the first patient, and close follow-up with radiographic studies on the second patient, revealed benign thymic enlargement. Thymic hyperplasia can occur after cytotoxic chemotherapy and may be due to rebound enlargement after initial atrophy caused by chemotherapy. Thymic hyperplasia after chemotherapy has been reported mostly in young age groups and is described in the literature to be associated with various types of cancers, including lymphomas, leukemias, testicular cancer, and sarcomas, and in the stem cell transplant setting. This is the first case series describing 2 patients with early stage breast cancer who, following adjuvant standard dose chemotherapy, developed thymic hyperplasia. Awareness of this unusual side effect in patients treated with chemotherapy may prevent unnecessary investigation and surgical intervention.

Co-administration of dopamine D1 and D2 agonists additively decreases daily food intake, body weight and hypothalamic neuropeptide Y level in rats.

This study investigated whether co-administration of dopamine D1 and D2 agonists might additively inhibit the feeding effect and whether this effect was mediated by the action on hypothalamic neuropeptide Y (NPY). The D1 agonist SKF 38393 (SKF) and D2 agonists apomorphine (APO) or quinpirole (QNP) were administered, alone or in combination, to examine this possibility. In single administration, decreases of daily food intake were observed only in rats treated twice a day with a higher dose of SKF, APO or QNP. However, combined administration of D1 and D2 agonists, with each agent at a dose that alone did not induce anorexia in one daily treatment, exerted a significant effect. These results reveal that co-activation of D1 and D2 receptors can additively reduce daily food intake and body weight. The same treatment also decreased the level of hypothalamic NPY 24 h post-treatment. These results suggest an additive effect during combined activation of D1 and D2 receptor subtypes to decrease food intake and body weight that are mediated by the action of hypothalamic NPY. Similar to the effects seen in healthy rats, combined D1/D2 administration was also effective in the reduction of food intake in diabetic rats, revealing the efficiency of D1/D2 agonist in the improvement of hyperphasia in diabetic animals.

Increased metabolic activity in the thymus gland studied with 18F-FDG PET: age dependency and frequency after chemotherapy.

UNLABELLED: This study was designed to evaluate the age dependency of 18F-FDG uptake in the thymus and the frequency of PET confirmation of thymus hyperplasia after chemotherapy in cancer patients. METHODS: Whole-body FDG PET recordings of 168 patients were retrospectively examined for a retrosternal lesion in the anterior mediastinum that was attributable to the thymus. The patients were assigned to the following four groups: children with malignant lesions before the first therapy (group Ia; n = 15; mean age +/- SD, 11.9 +/- 3.7 y), children with malignant disease after chemotherapy (group Ib; n = 12; mean age, 10.3 +/- 5.0 y), adults with histologically confirmed malignant lymphoma before the first therapy (group IIa; n = 37; mean age, 43.9 +/- 16.7 y), and adult lymphoma patients 3 wk to 4 mo after chemotherapy (group IIb; n = 104; mean age, 40.9 +/- 14.6 y). RESULTS: Increased FDG accumulation in the thymus was seen in 11 patients (73%) of group Ia and 9 patients (75%) of group Ib. Thymus hyperplasia was found in 5 patients (5%) of group IIb. The eldest of these 5 patients was 25 y old. No increased FDG accumulation in the thymus was observed in any of the group IIa patients. In cases of visible FDG uptake in the thymus, standardized uptake values did not exceed 4. CONCLUSION: FDG accumulation in the thymus is a common finding in children and can occasionally be observed in young adults after chemotherapy. Knowledge of the characteristics of a typical retrosternal lesion in conjunction with the clinical history allows avoidance of diagnostic uncertainty and unnecessary procedures.

Thymic hyperplasia after high-dose chemotherapy and autologous stem cell transplantation: incidence and significance in patients with breast cancer.

OBJECTIVE: The purpose of this study was to determine the incidence and clinical significance of thymic hyperplasia after high-dose chemotherapy and autologous stem cell transplantation for treatment of metastatic or high-risk primary (with at least four positive lymph nodes) breast cancer. MATERIALS AND METHODS: We retrospectively reviewed clinical records and CT scans of 102 breast cancer patients treated with high-dose chemotherapy and autologous stem cell transplantation. Patients were 26-63 years old (mean, 46 years). The length and width of the thymus gland were measured on serial CT scans obtained before and after treatment. Moderate thymic hyperplasia was recorded if a focal or diffuse increase was seen in the oblong, triangular soft-tissue opacity conforming to the configuration of the normal gland within the anterior mediastinum after therapy. Minimal hyperplasia was recorded when a minimal increase was seen in soft-tissue attenuation conforming to the configuration of the normal bilobed thymus gland within the anterior mediastinum, but no discrete mass was visible. RESULTS: CT showed no thymic hyperplasia in 91 (89%) of the 102 patients. CT showed thymic hyperplasia in the other 11 patients (11%). Three patients (3%) had moderate hyperplasia, and eight patients (8%) had minimal hyperplasia. When comparing patients with and without hyperplasia, we found no difference in mean age or survival. CONCLUSION: Thymic hyperplasia is rare after high-dose chemotherapy and autologous stem cell transplantation in adult patients with metastatic or high-risk primary breast cancer. In this population, thymic hyperplasia does not appear to correlate with survival.

[Thymus hyperplasia following chemotherapy]. / Hyperplasie thymique post-chimiothérapie.

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.

[Diffuse thymus hyperplasia following chemotherapy for nodular sclerosing Hodgkin lymphoma]. / Diffuse Thymushyperplasie nach Chemotherapie eines nodulär-sklerosierenden Hodgkin-Lymphoms.

A persistent or new mass in the anterior mediastinum after chemotherapy for mediastinal lymphoma poses a major differential diagnostic problem. Misinterpretation as a persistent or recurrent tumor may lead to additional unnecessary and potentially harmful therapy. Benign mediastinal tumors, albeit very rare, need confirmation by biopsy since they cannot be distinguished by radiological methods from persistence or relapse of lymphoma. We present a case report of a patient with diffuse thymic hyperplasia following successful chemotherapy for nodular sclerosing Hodgkin's disease, with a review of the literature.

Thymic hyperplasia in adults following chemotherapy for malignancy.

BACKGROUND: The accuracy of the assessment of patients with malignant disease and of their response to chemotherapy has been significantly improved with the routine availability of computerized tomography (CT) scanning. CT abnormalities, however, may be non-specific, especially after chemotherapy. Rebound enlargement of the thymus gland after chemotherapy induced atrophy is one cause of an abnormal thoracic CT scan on re-staging. AIMS: This phenomenon has previously been reported mainly in relation to the treatment of lymphoma and germ cell cancers. This paper highlights the occurrence of thymic hyperplasia after chemotherapy in these and other tumour types. METHODS: We discuss five cases including three patients with malignancies other than lymphoma in whom thymus enlargement occurred during or after intensive chemotherapy. RESULTS: Clear identification of the nature of CT abnormalities after chemotherapy, particularly in the mediastinum, is required prior to embarking on further anti-cancer treatments.