Undifferentiated pleiomorphic sarcoma simultaneously occuring with thymoma

Introduction

Thymoma is a tumor of anterior mediastinum, however, thymomas may develop at various other sites like neck, trachea, thyroid, lung, and heart (1). It is the most common neoplasm of thymus, more common in men and in eighth decade of life (2). Thymoma is an uncommon neoplasm which arises from thymic epithelium. Thymomas are associated with paraneoplastic syndromes such as myasthenia gravis, hypogammaglobulinemia (3), pure red cell aplasia (4), and many kinds of immune mediated systemic disorders; however, few cases of extrathymic malignancies have been reported. Reported incidence of extrathymic malignancies is 2.6-27% (5-8). We report here a case of mediastinal thymoma with coexisting neuroendocrine tumor.

Case report

A 65-year-old male, presented with easy fatigability and a lump in the left side of his axilla for four months. On general examination mild pallor was noticed. Local examination of left axilla showed a lump of 8 cm × 8 cm, firm in consistency, fixed to underlying structures, and overlying skin was normal. Investigations showed Hemoglobin is 7 g/dL and Erythrocyte sedimentation rate 25 mm in first hour. X-ray chest posteroanterior view revealed a mediastinal mass. CECT obtained at the level of arch of aorta and main pulmonary artery showed a well-defined enhancing mass of soft tissue attenuation in the left anterior mediastinum abutting arch of aorta, main and left pulmonary artery with maintained fat planes.

Adjacent mediastinal fat plane was partially obliterated. CT guided FNAC was done which showed moderately cellular smears consisting of a dual population of epithelial cells and mature appearing lymphocytes. The epithelial cells comprised of oval to elongated nuclei with dispersed chromatin and inconspicuous nucleoli.

Mitosis was not seen. Histopathology of mass revealed loose aggregates of lymphocytes admixed with neoplastic epithelial cells. A diagnosis of thymoma was rendered. Excisional biopsy of axillary mass was done which was composed of cells having pleomorphic, hyperchromatic spindle-shaped nuclei with clumped chromatin. Mitotic rate was high. Occasional multinucleated cell was also seen. Immunohistochemical analysis showed positivity for vimentin and focal positivity for CD 68 along with negative smooth muscle actin, desman, epithelial membrane antigen, CD 45, CD 3 and CD 30. On the basis of the above findings a diagnosis of thymoma with co-existent undifferentiated pleomorphic sarcoma was made. Postoperatively patient was discharged on 6^th post-operative day. Follow up in our patient with invasive thymoma (surgical resection), treatment is based on induction chemotherapy and post-surgical radiation. 5-year survival for invasive thymoma is between 12-54% regardless of any myasthenia gravis symptoms.

Discussion

The coexisting thymomas with other malignancies is relatively rare, and the most common site for these extrathymic malignancies is colorectal (6,8) followed by lung, thyroid, prostate, female reproductive organs, breasts, kidney and skin melanoma. Only few cases of co-existent thymoma with coexisting undifferentiated pleomorphic sarcoma not otherwise specified (9,10) are reported in the literature. The pathogenesis of these associations is still unclear. In most of the cases associated tumors were diagnosed either before or at the same time of thymoma as in our case, which suggests that these patients may be genetically predisposed to develop tumors (11). Several different theories about the pathological basis have been proposed. According to Friedman (12), the onset of thymoma indicates defect within the thymus epithelium which is responsible for immune defect and increased incidence of neoplasia. Another theory suggests the potential ability of thymoma epithelial cells to stimulate T cells which predisposes to the onset of tumors (13,14). Undifferentiated pleomorphic sarcoma is the most common soft tissue sarcoma in adults, usually arising in extremities with a peak in seventh decade although cases in children have been reported (15,16). It can also develop at the site of previous radiation therapy (17). Enzinger and Weiss classified it histologically into storiform-pleomorphic, myxoid, giant cell, and inflammatory types (18). Storiform pleomorphic is the most common histologic type which consists of highly pleomorphic tumor cells arranged in storiform pattern. Immunohistochemistry is required for confirmation of diagnosis. Vimentin positivity and smooth muscle actin, desmin, epithelial membrane antigen, CD 45, CD 30, and CD 3 negativity as in our case made the final diagnosis. Local recurrence and metastasis to distant sites especially lungs and regional lymph nodes are common (19). Treatment is surgical resection and with or without adjuvant radiation and/or chemotherapy.

Acknowledgements

Disclosure: The authors declare no conflict of interest.

References

1. Myers PO, Kritikos N, Bongiovanni M, et al. Primary intrapulmonary thymoma: a systematic review. Eur J Surg Oncol 2007;33:1137-41. [PubMed]
2. Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer 2003;105:546-51. [PubMed]
3. Jacob S, Irani SR, Rajabally YA, et al. Hypothermia in VGKC antibody-associated limbic encephalitis. J Neurol Neurosurg Psychiatry 2008;79:202-4. [PubMed]
4. Rosenow EC 3rd, Hurley BT. Disorders of the thymus. A review. Arch Intern Med 1984;144:763-70. [PubMed]
5. Wilkins KB, Sheikh E, Green R, et al. Clinical and pathologic predictors of survival in patients with thymoma. Ann Surg 1999;230:562-72; discussion 572-4. [PubMed]
6. Masaoka A, Yamakawa Y, Niwa H, et al. Thymectomy and malignancy. Eur J Cardiothorac Surg 1994;8:251-3. [PubMed]
7. Hata M, Negishi N, Niino S, et al. A case of multiple colon cancer appeared after thymectomy for thymoma with myasthenia gravis. Nihon Geka Gakkai Zasshi 1993;94:1061-3. [PubMed]
8. Pan CC, Chen PC, Wang LS, et al. Thymoma is associated with an increased risk of second malignancy. Cancer 2001;92:2406-11. [PubMed]
9. Murphey MD. World Health Organization classification of bone and soft tissue tumors: modifications and implications for radiologists. Semin Musculoskelet Radiol 2007;11:201-14. [PubMed]
10. Nakagiri T, Okumura M, Inoue M, et al. Thymoma-associated graft-versus-host disease-like erythroderma. J Thorac Oncol 2007;2:1130-2. [PubMed]
11. Moran CA, Travis WD, Rosado-de-Christenson M, et al. Thymomas presenting as pleural tumors. Report of eight cases. Am J Surg Pathol 1992;16:138-44. [PubMed]
12. Honma K, Shimada K. Metastasizing ectopic thymoma arising in the right thoracic cavity and mimicking diffuse pleural mesothelioma--an autopsy study of a case with review of literature. Wien Klin Wochenschr 1986;98:14-20. [PubMed]
13. Payne CB Jr, Morningstar WA, Chester EH. Thymoma of the pleura masquerading as diffuse mesothelioma. Am Rev Respir Dis 1966;94:441-6. [PubMed]
14. Suster S, Rosai J. Histology of the normal thymus. Am J Surg Pathol 1990;14:284-303. [PubMed]
15. Maggi G, Casadio C, Cavallo A, et al. Thymoma: results of 241 operated cases. Ann Thorac Surg 1991;51:152-6. [PubMed]
16. Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg 2003;76:878-84; discussion 884-5. [PubMed]
17. Regnard JF, Magdeleinat P, Dromer C, et al. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg 1996;112:376-84. [PubMed]
18. Okumura M, Shiono H, Inoue M, et al. Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to world health organization histologic classification system. J Surg Oncol 2007;95:40-4. [PubMed]
19. Lucchi M, Davini F, Ricciardi R, et al. Management of pleural recurrence after curative resection of thymoma. J Thorac Cardiovasc Surg 2009;137:1185-9. [PubMed]