Thymic rebound after adjuvant chemotherapy in breast cancer: a case report

Abstract

Chemotherapy, especially for malignant tumors, can affect the thymus, leading to its atrophy and a decreased production of naïve T lymphocytes. However, regenerative process can occur in children and rarely in adults manifesting as thymic hyperplasia. A 49-year-old female patient was diagnosed with stage I breast cancer. She was treated with surgery, adjuvant chemotherapy followed by radiotherapy and hormonotherapy. Follow-up computed tomography scan showed a mediastinal retro-sternal mass, raising concern for tumor recurrence. However, no other signs of relapse were evident. A thymic rebound was suspected, with the lesion presenting as a triangular-shaped mediastinal mass suggestive of thymic morphology and consisting of mixed fat and soft tissue density with smooth borders. Close monitoring was then decided. A follow-up CT scan of the chest showed regression of the mediastinal mass. The diagnosis of thymic rebound after chemotherapy was then retained. The patient is currently in remission, seven years from her original diagnosis of breast cancer. Thymic hyperplasia after chemotherapy can rarely occur in adults. Clinicians should be aware of this unusual presentation to prevent needless investigation and therapy.

PLAIN LANGUAGE SUMMARY

This article describes a rare situation where thymus gland grows larger after chemotherapy for breast cancer in an adult woman. Normally, the thymus shrinks after puberty and is inactive in adults. Sometimes, after chemotherapy, the thymus can grow back, and this phenomenon is called thymic rebound. This growth can look like cancer recurrence on scans, but it is actually harmless and usually goes away on its own. Recognizing this condition is important to avoid unnecessary tests and treatments. This article is about a case who experienced thymus regrowth and was carefully monitored without needing further treatment.

ARTICLE HIGHLIGHTS

• Thymic rebound is a rare but recognized condition, presenting as thymic enlargement after chemotherapy, typically observed in pediatric oncology but infrequently reported in adult patients.

• Thymic rebound after chemotherapy reflects thymic regrowth with preserved normal architecture, likely driven by immunological mechanisms.

• This condition may mimic tumor recurrence on imaging, leading to potential misdiagnosis and unnecessary invasive procedures if not properly identified.

• Imaging features include a triangular-shaped anterior mediastinal mass with mixed fat and soft tissue density, well-defined margins, and no invasion of adjacent structures.

• Clinical management involves close radiological and clinical follow-up, with most cases resolving spontaneously without therapeutic intervention.

• Awareness of this entity among clinicians and radiologists is crucial to prevent overtreatment.

Introduction

The thymus is a gland with immunological function showing great variation in both size and shape. After initial rapid growth in childhood, there is an involution of the gland beginning after puberty, to be an inactive organ in adulthood. In children and young adults, excessive regrowth of the thymus may be observed in some situations and it’s called rebound thymic hyperplasia [1]. This condition is a well-documented entity in pediatric oncology after chemotherapy for cancers most commonly associated with lymphomas [2,3]. However, it is rarely observed in adults due to the physiological involutional process of the thymus and may be confused with tumoral recurrence leading to unnecessary investigations. Here in, we report a case of thymic enlargement related to thymic rebound after chemotherapy for breast cancer in adult female patient.

Observation

A 49-year-old Caucasian female patient was diagnosed with breast cancer in August 2018. Routine mammography showed a 15 mm lesion located on the upper-outer and lower-outer quadrants of the right breast. Tissue sampling with core-needle biopsy revealed invasive ductal carcinoma grade 2. Imaging, including thoraco-abdomino-pelvic and cerebral computed tomography scan along with bone scintigraphy, was conducted to evaluate metastatic spread and revealed no evidence of metastases. Conservative breast surgery in the form of a lumpectomy was performed, and the postoperative course was uneventful. Histology examination confirmed a 13 mm invasive ductal carcinoma grade 2 and immunohistochemical study showed positive hormonal receptor ER (90%, 3+), PR (90%,3+), Her-2 (−) and Ki67: 60%. The tumor was classified as pT1, N0, M0. The patient began adjuvant chemotherapy consisting of Doxorubicin (Adriamycin), Cyclophosphamide, and Paclitaxel, followed by radiotherapy, which was completed in 2019. Subsequently, she was initiated on oral hormone therapy. During follow-up, CT scan performed in January 2020 revealed the appearance of retro-sternal soft-tissue density mass measuring 45 * 20 mm (Figure 1) not described on the baseline CT scan. Physical careful examination was normal with no palpable lymph node. The patient meanwhile was in excellent condition, tumor markers were within normal limits and no other signs of relapse were evident. A thymic rebound was suspected, with the lesion presenting as a triangular-shaped mediastinal mass suggestive of thymic morphology and consisting of mixed fat and soft tissue density with smooth borders. Close monitoring was decided. A follow-up CT scan of the chest done six months later showed regression of the mediastinal mass previously described with no evidence of any thymic mass. Considering the clinical state and imaging results, thymic rebound after chemotherapy was the most likely diagnosis, and follow-up observation was done without therapy. The patient is currently in remission seven years from the original diagnosis of breast cancer.

Figure 1.

Non-enhanced (a) and contrast-enhanced (b) computed tomography scan in the mediastinal window showing a triangular-shaped anterior mediastinal mass consistent with thymic rebound.

Discussion

Thymic hyperplasia post chemotherapy is rare but a well-known phenomenon reflecting thymic regrowth after atrophy of the gland with normal microscopic architecture. It’s mainly described in children and young adults classically with lymphoma after chemotherapy, but also in patients with other malignancy such as nephroblastoma, leukemia, osteosarcoma, Ewing’s sarcoma ovarian and testicular cancer [1]. However, it’s much rarer when occurring in adult patient as thymic renewal capacity is limited and reported as case reports or small series in the literature mainly following the treatment of breast cancer [4–6] but also ovarian cancer [7], lung cancer [5] and testicular cancer [8]. In contrast to the pediatric context, the thymic rebound in adults is exceptionally described after treatment of lymphoma.

The physiopathology of thymic rebound is imperfectly known. Some histological studies have shown an increased activity of medullary epithelial cells and regeneration of thymic lymphocytes [9]. These findings support the role of immunological mechanisms as adult thymus appears to be pivotal for restoration of T lymphoid immunity after chemotherapy induced immunodepression [10]. Other authors have suggested that thymic hyperplasia is caused by chemotherapy-induced gonadal atrophy, which results in increased luteinizing hormone secretion [11]. In a study investigating associated factors of thymic regeneration, only age was found to be an independent predictor for thymic regrowth after chemotherapy (odds ratios = 4.710, 95% confidence intervals: 1.727–12.845, P = 0.002) [12].

The real incidence of thymic hyperplasia is not well-known in adult population. In a combined experience of two centers, 8 cases of thymic hyperplasia were reported between 2004 and 2015 in female patients with breast cancer (N = 7) and lymphoma (N = 1). The median time for diagnosis of thymic hyperplasia was 7 months following completion of chemotherapy (range: 1–11 months) and all eight patients remain in complete remission from their primary cancers as our patient [4].

Thymic rebound is most often asymptomatic and incidentally detected in CT scan monitoring during follow-up as tissue filling in the anterior superior mediastinum. Most rebound thymic hyperplasia has obvious features on imaging, which are helpful for the differential diagnosis. It appears as being a mediastinal mass of a triangular shape maintaining the normal thymic morphology, with a fine mixture of fat and lymphoid tissue, well-defined margins and slight enhancement [3]. There is no invasion of vessels or adjacent tissues, and no pericardial effusion or pleural effusion.

Thymic rebound is a reactive phenomenon that can resolve spontaneously in most cases within few months rarely years and simply requires clinical and radiological monitoring. However, due to its rarity in adult population, thymic rebound may be confused with recurrent or residual malignancy and can be frequently challenging for both radiologists and physicians. Consequently, misdiagnosis may lead to overtreatment or further unnecessary procedures such as needle aspiration [13], surgical biopsy [14,15] or thymectomy [6,7] as reported while investigating mediastinal mass after chemotherapy in the literature. This can result in avoidable medical issues which may cause additional morbidity and mortality especially that the mediastinum area is fully of great vessels. In some cases, it can be difficult to make the distinction between a mediastinal mass due to thymic enlargement or malignancy on clinical and CT scan criteria alone. According to a recent study aimed at identifying the parameters that differentiate between Hodgkin lymphoma relapse and thymic rebound, disease recurrence should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass likely corresponds to rebound thymic hyperplasia [16]. When significant doubt exists, further assessment may be necessary to not compromise the patient’s prognosis. In our case the approach used was performing follow-up CT scan in combination with careful clinical assessment and laboratory tests, reinforced by close follow-up of the patients.

In conclusion, we report a case of new soft-tissue masses emerging at the anterior mediastinum related to thymic rebound after the completion of chemotherapy in patient with breast cancer. Thymic hyperplasia is a well-documented phenomena but a rare condition when occurring in adults’ patients and thus not very well recognized. Therefore, diagnosis may be challenging especially that thymic rebound may be confused with malignancy and must be the subject of a multidisciplinary consultation that identifies its characteristics. However, physicians and radiologists should be aware of this condition to avoid unnecessary invasive investigations and unneeded concerns as thymic rebound requires only close monitoring.

Authors’ contributions

Myriam Ayari and Sarah Ben Azouz were involved in the literature search, conception, data acquisition and in writing the manuscript. Amira Chehaider assisted in the preparation and writing of the manuscript. Sarra Ben Rejeb and Taieb Jomni contributed to the critical review of the manuscript. All authors reviewed the manuscript.

Ethical conduct of research

The authors state that they have obtained verbal and written informed consent from the patient for the inclusion of their medical and treatment history within this case report. This case report has been reported in accordance with the CARE guidelines. A completed CARE checklist has been submitted as a supplementary file

Financial and competing interests’ disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.