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In medicine (oncology), thymoma is a neoplasm of the thymus. It is a rare disease, best known for its enigmatic association with the neuromuscular disorder myasthenia gravis. There are benign and malignant forms, which present similarly. more...

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Signs and symptoms

  • 33%-50% is detected accidentally on routine X-rays of the chest.
  • 33% presents with complaints due to compression of surrounding structures by the expanding tumor:
    • Vena cava superior syndrome (compression of the upper caval vein)
    • Dysphagia (trouble swallowing)
    • Cough, chest pain
  • A final 33% has autoimmune symptoms; thymomas in these are usually benign. The best known is myasthenia gravis, of which 25-50% is associated with a thymoma. Some others are: pure red cell aplasia and Good's syndrome (thymoma with combined immunodeficiency and hypoimmunoglobulinemia G).
    • Rare associations that have been reported are: acute pericarditis, Addison's disease, agranulocytosis, alopecia areata, ulcerative colitis, Cushing's disease, hemolytic anemia, limbic encephalopathy, myocarditis, nephrotic syndrome, panhypopituitarism, pernicious anemia, polymyositis, rheumatoid arthritis, sarcoidosis, scleroderma, sensorimotor radiculopathy, stiff person syndrome, systemic lupus erythematosus and thyroiditis.

Malignant thymomas can metastasize, generally to pleura, kidney, bone, liver or brain.


When a thymic pass is identified, the diagnosis is achieved with histology (obtaining a tissue sample of the mass). When a thymoma is suspected, a CT/CAT scan is generally performed to estimate the size of the tumor, and can be biopsied with a CT-guided needle. Although there is a risk of pneumomediastinum, mediastinitis and the risk of damaging the heart or large blood vessels.

The tumor is generally located inside the thymus, and can be calcified. Increased vascular enhancement can be indicative of malignancy, as can be pleural deposits.

If the suspicion is real, some blood tests are often performed to gain an appreciation of associated problems or possible spread. These include: full blood count, protein electrophoresis, antibodies to the acetylcholine receptor (indicative of myasthenia), electrolytes, liver enzymes and renal function.

The final diagnosis is made by removing the thymus. Pathological investigation of the specimen will reveal if the tumor was benign or malignant.


Thymomas originate from the epithelial cell population in the thymus. Many subtypes are recognised, some of which have a better- or worse-than-general prognosis.


Men and women are equally affected. The main age for thymomas is 30-40, although cases have been described in every age group.


Surgery is the mainstay of treatment. If the tumor was benign and was removed in its entirety, no further therapy is necessary. Malignant tumors may need additional treatment with radiotherapy, or sometimes with chemotherapy (cyclophosphamide, doxorubicin and cisplatin).


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Giant Cell Tumor of Rib Masquerading as Thymoma: A Diagnostic Pitfall in Needle Core Biopsy of the Mediastinum
From Archives of Pathology & Laboratory Medicine, 4/1/04 by Volmar, Keith E

Giant cell tumor of bone is rarely seen in the rib, where it may present as a mediastinal mass. The diagnosis of giant cell tumor of bone is generally straightforward by fine-needle aspiration or needle core biopsy, but sampling problems may lead to confusion with other neoplasms or inflammatory processes. Here, we report a case of giant cell tumor of rib presenting as a mediastinal mass in a 36-yearold man. Because of inadequate sampling and inaccurate clinical information, the tumor was initially mistaken for thymoma. When the mass failed to respond to conventional chemotherapy, additional tissue was obtained and a giant cell tumor was diagnosed. Consequently, definitive therapy was delayed. The case illustrates an important diagnostic pitfall in the biopsy of mediastinal masses.

(Arch Pathol Lab Med. 2004;128:452-455)

Giant cell tumor of bone is a rare neoplasm usually seen in the long bones or sacrum. The rib is the least frequently affected site; large series at the Mayo Clinic and the Register of Tumors of the Rizzoli Orthopaedic Institute showed only 0.5% to 0.6% of giant cell tumors to be located in the rib.1,2 Giant cell tumor of the thoracic vertebrae presenting as a mediastinal mass has been described previously.3,4 Here, we report a case of giant cell tumor of rib presenting as a mediastinal mass. Because of a combination of inadequate sampling and inaccurate clinical information, the mass was initially misdiagnosed as thymoma and appropriate treatment was delayed. The case illustrates an important diagnostic pitfall in the evaluation of mediastinal masses.


A 36-year-old man presented for evaluation of a mediastinal mass. His clinical course had begun 3 months before, with the onset of flulike symptoms and a nonproductive cough. Over several weeks, he developed shortness of breath, wheezing, and dyspnea that was worse in the supine position and improved in the decubitus position. He noted weight loss of 11.4 kg during the previous year but denied other symptoms, including dysphagia or odynophagia. He was initially diagnosed with allergic bronchitis. During the next 6 weeks his symptoms did not improve, and imaging studies revealed a thoracic mass. A transthoracic biopsy at an outside institution was interpreted as thymoma. The patient was referred to our institution for treatment.

Physical examination revealed a well-developed man in no apparent distress. Vital signs were normal. No lymphadenopathy was evident, and complete physical examination revealed no evidence of a palpable mass. The chest was clear to auscultation; however, there was dullness to percussion over the upper third of the right hemithorax. In addition, collateral blood flow was indicated by dilated veins in the right upper arm and right infraclavicular region. Serum tumor marker studies revealed insignificant levels of beta human chorionic gonadotropin and [alpha]-fetoprotein. No antiacetylcholinesterase antibodies were detected. A computerized tomography scan revealed a homogeneous 11cm mass in the upper right hemithorax, middle and posterior mediastinum. The mass had eroded the posterior right third rib and displaced the mediastinum to the left, with compression of the trachea and extension around the proximal superior vena cava and right brachiocephalic vein. Scattered calcifications were noted in the mass.


Outside pathology was reviewed and consisted of a small core biopsy from what was purported to be an anterior mediastinal mass. The material had small fragments of a cellular neoplasm composed of 3 distinct cell populations: epithelioid cells, spindle cells, and numerous multinucleated giant cells in a background of fibrosis (Figure 1, A and B). The epithelioid cells were polygonal, with moderate eosinophilic cytoplasm and regular round to oval nuclei. Some of the epithelioid cells were reactive with monoclonal antibodies to cytokeratin. The spindle cells had plump oval-shaped nuclei and moderate cytoplasm. Multinucleated giant cells generally had 10 to 20 nuclei, most with morphology similar to that of spindle cell nuclei. None of the cell populations showed significant nuclear pleomorphism or prominent nucleoli. There was no necrosis or significant mitotic activity. Based on these findings, the reported location of anterior mediastinum, and a strong clinical impression of thymoma, a diagnosis of thymoma was rendered. The patient subsequently received 3 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy, but the tumor remained stable and the patient's condition was not improved. The lack of response prompted reevaluation of the tumor, and a computerized tomography-guided fine-needle aspiration of the tumor was performed.

Aspiration smears revealed numerous multinucleated giant cells admixed with plump histiocyte-like mononuclear cells with moderate cytoplasm and some spindle cells (Figure 2). There was mild nuclear pleomorphism, and small nucleoli were seen in some of the histiocytoid cells and spindle cells. Immunohistochemical stains were performed on the cell block, and the histiocyte-like cells were positive for CD99 but negative for cytokeratin. Based on these findings, a diagnosis of giant cell tumor was suggested, and additional tissue was requested. Subsequent excisional biopsies obtained by mediastinoscopy confirmed the diagnosis of giant cell tumor of bone. During the procedure, profuse bleeding from the tumor necessitated a manubriotomy. Opening of the thorax showed extensive compression of the regional vasculature, including the left innominate vein, left subclavian vein, and superior vena cava. In the course of achieving hemostasis, a thymectomy was performed. Routine sections revealed normal thymic tissue with fatty involution and no evidence of tumor.

The resection specimen contained the intrathoracic mass, portions of the second, third, and fourth ribs, and a portion of the right upper lobe of lung. The tumor (11.5 X 10.0 X 6.5 cm) arose from the posterior third rib, with intramedullary permeation, and invaded the posterior chest wall. The tumor showed histology typical of giant cell tumor of bone (Figure 3). Entrapped lung was present, but no pulmonary invasion was seen. The tumor extended to involve multiple rib and soft tissue margins. No lymphovascular invasion or lymph node involvement was evident. Postoperatively, the patient underwent radiation therapy (44 Gy). Follow-up imaging at 6, 10, and 14 months revealed no evidence of recurrent disease.


The most common mediastinal neoplasms diagnosed by fine-needle aspiration are lymphoma, thymoma, and germ cell tumors.5 Diagnosis of mediastinal masses can be problematic, particularly with the limited tissue obtained by core needle biopsy or fine-needle aspiration. Inadvertent sampling of normal structures may further complicate the matter. Yu and coworkers^sup 6^ commented on thymic epithelial cells as a diagnostic pitfall in aspiration of primary mediastinal lymphomas.

In the present case, a giant cell tumor of the rib was initially misdiagnosed as a thymoma. The mass was assumed to be located in the anterior mediastinum, apparently because of inaccurately relayed imaging information. The result was a very strong clinical impression that the tumor was a thymoma. A small-needle core biopsy was obtained, revealing a mixture of epithelioid cells, spindle cells, and multinucleated giant cells in a background of fibrosis. Some of the epithelioid cells were immunoreactive for cytokeratin. The fibrosis and giant cells were assumed to represent an inflammatory or desmoplastic reaction at the edge of the widely invasive tumor. Based on these findings, the tumor was misdiagnosed as thymoma, an error that was not discovered until chemotherapy produced no effect on the tumor. Subsequent biopsies with more substantial tissue confirmed the diagnosis of giant cell tumor. Explanations for the cytokeratin immunoreactivity include locally entrapped mediastinal pleura or pulmonary epithelium. Unfortunately, the scant tissue in the biopsy had been exhausted, precluding immunohistochemical confirmation of this suspicion.

Under most circumstances, distinguishing thymoma from giant cell tumor of bone is quite simple. Biopsy of thymoma typically reveals a dual cell population of a variable proportion of lymphocytes and epithelial cells, which vary from epithelioid to spindle cells, although invasive thymomas and thymic carcinomas may lack significant lymphoid cells.7 Fine-needle aspiration of giant cell tumor of bone yields a cellular smear with a dual cell population. Large osteoclast-like giant cells are seen with 20 to 60 nuclei and may contain fine cytoplasmic granules. A population of mononuclear stromal cells is also present with oval to spindle shapes and uniform nuclei with bland chromatin and small nucleoli. The cytoplasm is moderate and may also contain fine granules.8 However, the existence of giant cells in many bone lesions may lead to confusion with other entities, such as metaphyseal fibrous defect, chondroblastoma, chondromyxoid fibroma, aneurysmal bone cyst, giant cell reparative granuloma, brown tumor of hyperparathyroidism, and giant cell-containing osteosarcoma.1,9,10

Giant cell tumors represent 4% to 5% of total primary bone tumors and approximately 22% of benign bone tumors.1,10 The tumors are generally seen in young adults with a mature skeleton. Most patients are female and in the third and fourth decades of life. Although giant cell tumors have been seen in all parts of the skeleton, they usually occur in the epiphyseal ends of long bones. In descending order, giant cell tumor affects the distal femur, proximal tibia, distal radius, and sacrum. Involvement of the spine above the sacrum is unusual. Radiologically, giant cell tumor in flat bones appears as large lytic defects with expanded contours of bone and a large soft-tissue component. A tumor with giant cell histologic characteristics in a flat bone should prompt consideration of giant cell reparative granuloma, aneurysmal bone cyst, and hyperparathyroidism.1,10

This case of giant cell tumor of the rib presented as a mediastinal mass. Findings from a small-needle biopsy were misinterpreted as thymoma. This error set the patient on a course of chemotherapy, thus delaying appropriate surgical treatment for several months. This case illustrates an important pitfall in the diagnosis of mediastinal masses and re-emphasizes the importance of the "triple test." Correlation of pathologic findings with clinical presentation and imaging studies may prevent confusion with other mediastinal masses that can involve the ribs and vertebra, such as osteosarcoma, chondrosarcoma, Ewing sarcoma, primary lung carcinoma, and the rare giant cell tumor of rib.

We thank John B. Holt, MD, for his photographic assistance.


1. Unni KK. Giant cell tumor (osteoclastoma). In: Unni KK, ed. Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases. 5th ed. Philadelphia, Pa: Lipincott-Raven; 1996:263-284.

2. Briccoli A, Malaguti C, lannetti C, Rocca M, Bertoni F. Giant cell tumor of the rib. Skeletal Radiol. 2003;32:107-110.

3. Agarwal J, Wali JP, Singh NP. Giant-cell tumour of dorsal vertebra presenting as a mediastinal mass. J Assoc Physicians India. 1993;41:48-49.

4. Sakurai H, Mitsuhashi N, Hayakawa K, Niibe H. Giant cell tumor of the thoracic spine simulating mediastinal neoplasm. Am J Neuroradiol. 1999;20: 1723-1726.

5. Shabb NS, Fahl M, Shabb B, Haswani P, Zaatari G. Fine-needle aspiration of the mediastinum: a clinical, radiologic, cytologic, and histologic study of 42 cases. Diagn Cytopathol. 199819;:428-36.

6. Yu GH, Salhany KE, Cokaslan ST, Cajulis RS, De Frias DVS. Thymic epithelial cells as a diagnostic pitfall in the fine-needle aspiration diagnosis of primary mediastinal lymphoma. Diagn Cytopathol. 1997;16:460-465.

7. Ali SZ, Erozan YS. Thymoma: cytopathologic features and differential diagnosis on fine needle aspiration. Acta Cytol. 1998;42:845-854.

8. DeMay RM. Soft tissue tumors. In: DeMay RM, ed. The Art and Science of Cytopathology. Chicago, Ill: ASCP Press; 1996:596.

9. Jain M, Aiyer HM, Singh M, Narula M. Fine-needle aspiration diagnosis of giant cell tumor of bone presenting at unusual sites. Diagn Cytopalhol. 2002;27: 375-378.

10. Dorfman HD, Czerniak B. Giant-cell lesions. In: Dorfman HD, Czerniak B, eds. Bone Tumors. St Louis, Mo: Mosby; 1998:559-606.

Keith E. Volmar, MD; Thomas A. Sporn, MD; Eric M. Toloza, MD, PhD; Salutario Martinez, MD; Leslie G. Dodd, MD; H. Bill Xie, MD, PhD

Accepted for publication December 10, 2003.

From the Departments of Pathology (Drs Volmar, Sporn, Dodd, and Xie), Surgery (Dr Toloza), and Radiology (Dr Martinez), Duke University Medical Center, Durham, NC.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Keith E. Volmar, MD, Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC 27710 (e-mail:

Copyright College of American Pathologists Apr 2004
Provided by ProQuest Information and Learning Company. All rights Reserved

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