|Year : 2019 | Volume
| Issue : 5 | Page : 193-196
Rapid progression of thymoma in a 3-year-old-girl
Hui-Ling Peng1, Wan-Ling Ho2, Chia-Yu Chang3, Chun-Hung Ko4
1 Department of Diagnostic Radiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan
2 Department of Pediatrics, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan
3 Department of Pediatric Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan
4 Department of General Surgery, Lohas Clinic, Taipei City, Taiwan
|Date of Submission||22-May-2019|
|Date of Decision||19-Jun-2019|
|Date of Acceptance||30-Jul-2019|
|Date of Web Publication||25-Oct-2019|
Dr. Chun-Hung Ko
Department of General Surgery, Lohas Clinic, No. 12, Shida Road, Da'an District, Taipei City 106
Source of Support: None, Conflict of Interest: None
Thymoma is an uncommon neoplasm that derived from thymic epithelial cells. Clinically, it is slow-growing and most patients are over 40 years old. Thymoma corresponds to 30% of anterior mediastinal tumors in adults but <1% in pediatric patients. However, thymoma in pediatric group is considered to be highly aggressive. We report a case of invasive thymoma in a 3-year-old girl, presented as respiratory distress with massive pleural effusion. She developed a superior vena cava syndrome soon after admission. A subsequent computed tomography demonstrated a large mediastinal mass with compression of great vessels. Due to the rare occurrence of thymoma at such a young age, an accurate diagnosis was made only after an open biopsy had been performed. The patient underwent a near-complete resection of the mass as well as adjuvant chemotherapy. She has remained well at the 6-year follow-up.
Keywords: Invasive thymoma, pediatric thymoma, thymoma
|How to cite this article:|
Peng HL, Ho WL, Chang CY, Ko CH. Rapid progression of thymoma in a 3-year-old-girl. Formos J Surg 2019;52:193-6
| Introduction|| |
Thymoma is a neoplasm of thymic epithelial cells. Nearly, all thymomas occur in patients over the age of 20 and about 70% of thymomas occur in adults aged over 40. It is an extremely rare neoplasm in children and adolescent. Most thymomas are encapsulated, but approximately 20% are associated with local invasion of the adjacent mediastinal structures and chest wall. These tumors are generally highly aggressive in the pediatric group, and often present with fulminant clinical courses and high mortality rates. In this article, we present an invasive thymoma in a very young girl only 3 years old. The diagnosis and treatment are challenging since the rarity and the lack of experience of this occurrence in pediatric population. Despite the presence of unfavorable clinical and histopathological features (Masaoka Stage III, WHO type B2) of thymoma in our case, she was well 6 years after surgical intervention and adjuvant chemotherapy.
| Case Report|| |
A 3-year-old girl, known case of asthma, developed mild cough and low-grade fever for 1 week. She presented to the emergency room because of a 2-day history of progressive respiratory difficulty. On physical examination, she was tachypneic with markedly decreased breath sounds in both lung fields. There were no wheezes or crackles. Neurological examination was normal. A chest X-ray showed bilateral massive pleural effusion [Figure 1]. She was then admitted for antibiotic treatment under the impression of lung infection with bilateral pleural effusion. Shortly after admission, she was intubated due to progressive dyspnea with CO2 retention. Edema of the face, neck, and upper extremities compatible with superior vena cava (SVC) syndrome were developed next day. A subsequent computed tomography (CT) showed a large, somewhat heterogeneous and lobulated, anterior mediastinal mass arising from the thymus gland. The mass was encasing and compressing the SVC, and abutting the pericardium with loss of the fat planes. There was gross pleural and pericardial effusion and parts of the lungs collapsed [Figure 2]. Laboratory evaluations including workup for germ cell tumors, that is, α-fetoprotein and β-human chorionic gonadotropin were within the normal limit. The bone marrow aspirate and biopsy were unremarkable. A mini-thoracotomy for wedge biopsy was done under general anesthesia and pathology demonstrated a thymoma. Due to progression of the respiratory distress and SVC syndrome, a midline sternotomy for tumor resection was subsequently performed. At surgical exploration, she was found to have an extensive anterior mediastinal mass invading the pleura and pericardium [Figure 3]. The SVC and brachiocephalic vein were markedly compressed by this overlying mass. There was no gross invasion of the great vessels, bronchus, or phrenic nerve. The tumor was dissected from the nearby tissues and removed as much as possible. Only a very thin layer of tumor residue, which was tightly adherent to the surface of SVC and left brachiocephalic vein, could not be cleared due to the high risk of vascular injury. She, therefore, underwent a near-complete resection of the mass (9 cm × 6.5 cm × 3 cm, 75.4 g). The involved pericardium and pleura were also removed [Figure 4]. The pathologic examination of the resected specimen confirmed a WHO type B2 thymoma with positive surgical margin. Thereafter, she was treated with six courses of adjuvant chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide. She was discharged on the 28th postoperative day after completion of the first course of chemotherapy. The remaining courses of chemotherapy had been given at the outpatient department. The patient had followed with chest CT scans every 3 months for 2 years which did not reveal any residual tumor or tumor recurrence. Clinical examination and chest X-ray were also unremarkable at the 6-year follow-up.
|Figure 1: Supine chest X-ray demonstrated bilateral massive pleural effusion. The trachea was not displaced. It is hard to comment the mediastinal size as its width could be exaggerated in supine position|
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|Figure 2: Contrast-enhanced computed tomography of the chest, with axial (a) and coronal (b) reconstructions, showed a large, somewhat lobulated and heterogeneous anterior mediastinal mass (M). The mass presented an intimate relationship with the surrounding tissues. Marked compression of the superior vena cava (S) and mild compression of the airway (T) were noted. Parts of the lungs collapsed (L). There was gross pleural (P) and pericardial (C) effusion|
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|Figure 3: After midline sternotomy, a large mass lesion (white arrow) occupying the anterior mediastinum with extension into the surrounding tissues was found|
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|Figure 4: Resected specimen showed extension of the mass throughout the capsule (white arrow). Adherent pericardium (white star) and pleura (white triangle) were also removed|
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| Discussion|| |
Thymoma is a tumor arising from epithelial cells of the thymus. It is rare even in adults and accounts for <1% of all mediastinal neoplasms in children., Thymoma is usually divided into “ noninvasive” and “invasive” types. Noninvasive thymoma manifests as a completely encapsulated tumor, whereas invasive thymoma demonstrates extension of growth outside the tumor capsule, occasionally showing pleural implants, and rarely, hematogenous and lymphatic metastasis. Pathologically, only approximately 20% of thymomas are invasive. However, it is impossible to differentiate between these two types solely on the basis of histologic features as an invasive thymoma may lack histologic features of malignancy.
In children, thymomas are generally aggressive and associated with an unfavorable prognosis., Rapid evolution of clinical symptoms is one of the most striking features of invasive thymoma in the pediatric population. These patients may present with respiratory symptoms that rapidly progress within hours or a few days to SVC obstruction shown in our case. Clinical presentations, which relate to the degree of local invasiveness by these tumors, may vary widely; from asymptomatic to symptoms associated with mass effects such as cough, chest pain, dysphagia, dyspnea, and SVC syndrome. Some children with thymomas have paraneoplastic syndrome manifested as myasthenia gravis, hypogammaglobulinemia, red cell aplasia, and connective tissue diseases.,,
With regard to thymoma staging, the one proposed by Masaoka et al. is the most widely used. This staging system is divided into four categories and is based on the degree of encapsulation and presence of invasion or metastases: Stage I – macroscopically encapsulated and microscopically no capsular invasion; Stage II – macroscopic invasion into surrounding fatty tissue of mediastinal pleura or microscopic invasion into capsule; Stage III – macroscopic invasion into neighboring organs (great vessels, pericardium, or lung); Stage IVa – pleural or pericardial dissemination; and Stage IVb – lymphogenous or hematogenous metastasis., In our patient, the tumor had grossly invaded the adjacent pleura and pericardium and was therefore classified as Stage III. This clinical staging system is found to correlate with 5-year survival rates. The WHO proposed another classification scheme in 1999 that is based on the morphology of epithelial cells as well as the lymphocyte-to-epithelial cell ratio: type A (medullary); Type AB (mixed); Type B1 (lymphocyte rich, predominantly cortical), B2 (cortical), and B3 (epithelial, well-differentiated thymic carcinoma); and Type C (thymic carcinoma). This histological classification scheme correlates with invasiveness and prognosis of thymic epithelial tumors: Types A and AB are usually clinically benign and encapsulated (Stage I), Type B has a greater likelihood of invasiveness (especially Type B3), and Type C is almost always invasive.
Imaging is an essential part of the workup for thymic tumors. In conjunction with patient's history and physical examination, imaging study is often the only investigation needed prior to treatment. Contrast-enhanced CT is the imaging modality of choice in the evaluation and staging of thymoma. CT allows for the characterization of tumors as well as an assessment of possible invasion into surrounding structures and the presence of pleural and extrapleural seeding. Contrasted studies are preferred to assess vascular invasion and cystic components., On CT scans, thymomas usually appear as homogeneous, oval, rounded, or lobulated soft-tissue masses. Larger lesions may have hypodense areas of old hemorrhage, necrosis, or cysts. Occasionally, salt-grain calcifications are seen. Low-risk thymomas commonly have smooth contours, septation, complete or near-complete capsules, and homogeneous enhancement. High-risk thymomas and thymic carcinomas usually have lobulated contours, mediastinal fat and great vessel invasion., CT features associated with more frequent recurrences and metastases include lobulated or irregular contours, oval shape, mediastinal fat or great vessel invasion, and pleural seeding.
The main differential diagnosis of thymoma in pediatric patients includes thymic hyperplasia, T-cell lymphoblastic lymphoma, and thymic carcinoma. Diffuse symmetric enlargement of the gland is the key imaging feature of thymic hyperplasia, whereas thymoma tends to manifest as a focal mass. CT findings of T-cell lymphoblastic lymphoma are regular contour, presence of pericardial effusion and associated cervical and abdominal lymphadenopathy, and splenomegaly. Irregular contour, necrotic or cystic components, heterogeneous enhancement, lymphadenopathy, and great vessel invasion suggest thymic carcinomas. However, distinguishing thymoma from other thymic masses may be difficult based on imaging features alone. A pretreatment biopsy is usually mandatory except those resectable lesions which are unequivocally thymomas on imaging.
Surgical resection is the mainstay of treatment for thymoma. According to the literature for adult patients with thymoma, the most significant prognostic factor is tumor stage, WHO histologic type, and status of respectability. Radiotherapy should be supplemented in the tumors which are incompletely resected. Chemotherapy is reserved for treatment of metastatic disease or recurrent disease., In children, standard chemotherapy protocol have not been clearly defined due to its rarity; however, most authors have favored regimens similar to those used for adult patients. Different drug combinations have been administrated, generally based on cisplatin, doxorubicin, prednisolone, and cyclophosphamide., Despite the fact that thymomas are sensitive to both chemotherapy and radiation, there is a paucity of literature regarding adjuvant chemotherapy alone for invasive or incompletely resected thymoma. Previous studies revealed that adjuvant chemotherapy appeared to be ancillary to radiotherapy and was rarely administered without radiotherapy. However, information on the indications for each approach was not available in these literatures.
Debate has ensued over the adjuvant therapy in our patient who had an incompletely resected, invasive (Type B2), and Stage III thymoma. In treating the case like ours, usually postoperative radiotherapy or chemoradiotherapy rather than chemotherapy alone would be recommended. However, radiation therapy to the chest is not benign. It should be avoided, if possible, in children due to its morbidity., Hamaji et al. performed a study to investigate survival and treatments in patients with incompletely resected thymoma. Their results suggest that adjuvant chemotherapy should be favored over adjuvant radiotherapy as the former tends to improve progression-free survival. Moreover, in most cases of incomplete resection, the locations of recurrence or progression are often outside the mediastinum. This suggests that adjuvant chemotherapy could be effective in managing potential microscopic metastatic disease at the time of debulking surgery., After considering the possible benefits of chemotherapy and the potential sequelae of mediastinal irradiation,,, we prescribed chemotherapy as the adjuvant treatment for our patient. The initial outcome appears to be satisfactory. However, due to rarity of thymoma in pediatric patients, the development of an effective standard treatment protocol still requires further study and multi-institutional cooperation.
In conclusion, owing to paucity of cases, knowledge and experience with thymoma in pediatric patients are limited. Our case represents the diagnostic and treatment challenges for this age group. CT is the modality of choice for evaluation of thymomas. Our patient who had an invasive thymoma appeared to have achieved satisfactory survival after a near-complete resection and adjuvant chemotherapy. Nevertheless, more data and additional experience are still needed to establish the optimal treatment strategy for this rare occurrence in children.
Declaration of patient consent
The authors certify that they have obtained all appropriate guardians' consent forms. In the form the guardians have given their consent for the images and other clinical information to be reported in the journal. The guardians understand that the names and initials will not be published and due efforts will be made to conceal their children's identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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