Teratoma

Acquired thymic cysts are multilocular and show florid xanthomatous and myofibroblastic inflammation. They usually occur in association with mediastinal neoplasms, systemic autoimmune diseases, or trauma. We describe 2 cases (in a 12-year-old girl and an 11-year-old boy) of acquired thymic cysts occurring in association with cystic teratomas, an association that to our knowledge has not been described previously in the literature.

Cysts of the thymus can be either congenital or acquired. Congenital cysts are usually unilocular and thin walled. They are thought to develop from remnants of the thymic duct and are often located in the lateral neck. Acquired thymic cysts are multilocular and have thick walls resulting from chronic, often xanthomatous inflammation. They are associated with a variety of mediastinal and systemic diseases.1-11 Suster and Rosai1 postulated that multilocular cysts and their associated inflammatory reaction were induced by inflammation within the thymus or by the inflammatory component of adjacent mediastinal disease. We report 2 cases of acquired multilocular thymic cysts with characteristic intrinsic inflammation in association with noninflamed mature mediastinal teratomas.

REPORT OF CASES

Case 1

Clinical History and Radiological Examination.-A 12-year-old girl presented with a 2-week history of chest pain and difficulty in breathing. A computed tomographic scan of the thorax, performed at an outside facility, showed an anterior mediastinal mass, with the radiological differential diagnoses being teratoma and lymphoma. The lesion was resected without complication.

Gross Pathology.-The specimen was a 7.5 × 5.5 × 3.5-cm mass of soft brown-tan tissue. The external surface was smooth except for a focal rough area with a disrupted cyst. Sectioning of the specimen revealed multiple cysts varying in size from 0.2 to 3.5 cm in diameter. The cysts were filled with hemorrhagic material and had partially smooth and partially ulcerated inner surfaces. The cystic areas were interspersed with areas of firm, graytan tissue with scattered pale yellow foci.

Microscopic Pathology.-Histologie sections showed 2 distinct lesions. The first was a benign, largely cystic teratoma composed of disorganized but otherwise unremarkable cutaneous, bronchial, and pancreatic tissue. The other lesion was composed of benign thymic tissue containing multiple cysts lined by hyperplastic, stratified nonkeratinizing squamous epithelium, with associated dense lymphoid infiltrate. The lining was disrupted at multiple foci by hemorrhage and acute and chronic inflammation, including many foamy macrophages (Figure 1). The xanthomatous response appeared to derive from disrupted epithelium. An exuberant fibroblastic proliferation encompassed the inflamed cysts and was composed of plump, haphazardly arranged fibroblasts and myofibroblasts laying down abundant collagen (Figure 2). These cells were negative for ALK protein (Dako Corporation, Carpinteria, Calif) by immunohistochemical staining.

Case 2

Clinical History and Radiological Examination.-An 11-year-old boy presented with a 1-month history of chest pain, fatigue, and flushing with physical activity. A computed tomographic scan of the thorax showed a predominantly left-sided anterior mediastinal mass containing multiple areas of low density that were interpreted as cystic or necrotic foci. The radiological differential diagnoses included germ cell tumor, lymphoma, and thymoma. The lesion was resected without complication.

Gross Pathology.-The specimens included a 9.0 × 6.0 × 3.0-cm, apparently encapsulated, pink-brown mass, and a separate 6.0 × 2.0 × 1.0-cm fragment of thymus. Sectioning of the mass revealed a mixed solid and cystic appearance with the cysts ranging from 1.0 to 3.0 cm in diameter. The cyst contents were hemorrhagic, and the cyst walls were irregular with polypoid bluegray projections into the lumens. The intervening solid areas were edematous, yellow-gray, and focally hemorrhagic. The separate fragment of thymus was uniformly pink-tan except for a small yellow-gray focus.

Microscopic Pathology.-The sections from the mass showed 2 lesions. The first was a mature teratoma composed of mature skin; various epithelia, including keratinizing squamous, respiratory, gastric, small intestinal, and colonie; pancreatic tissue; and mesenchymal tissues, including cartilage, smooth muscle, and fat. The second lesion was composed of benign thymic tissue with multiple cysts lined by focally disrupted stratified nonkeratinizing squamous epithelium. An intense fibroblastic and myofibroblastic proliferation with acute and chronic inflammation, including many foamy macrophages, surrounded the cysts.

COMMENT

Multilocular thymic cysts may occur de novo2 or may be associated with a variety of systemic and localized mediastinal disorders. The latter include human immunodeficiency virus infection, seminoma, yolk sac tumor, Hodgkin lymphoma, non-Hodgkin lymphoma, thymoma, Langerhans cell histiocytosis, Sjogren syndrome, myasthenia gravis, systemic lupus erythematosus, and prior thoracic surgery or irradiation.3-11 An association with benign mediastinal teratomas has not been described previously. In 1991, Suster and Rosai1 reviewed the clinical and pathologic features of 18 cases of multilocular thymic cyst. Four of the 18 patients had an "incidental" thymoma or thymic carcinoma. They concluded that cystic transformation of the ductal epithelium, which produced the multiple cysts, was a secondary reactive process induced by an "idiopathic" inflammatory process within the thymus. They also postulated that multilocular thymic cysts associated with tumors were induced in some manner by an inflammatory component within the tumor rather than by the mass effect of the tumor. The authors expressed the hope "to have convinced the reader about the possible existence of an unifying theme, both in terms of the pathogenesis of the thymic lesion and its link with other cystic processes in the region."1

One component of Suster and Rosai's argument was that multilocular thymic cysts are not associated with thymic tumors that lack an intrinsic inflammatory component, such as teratocarcinoma. The 2 tumors described in the present report were benign cystic teratomas and, as expected in such tumors, did not harbor an intrinsic inflammatory component. Yet, the surrounding thymus displayed the typical pronounced acute and chronic inflammatory response and old hemorrhage characteristic of multilocular thymic cysts. Perhaps the thymomas and thymic carcinomas present in 22% of the cases described by Suster and Rosai1 were not incidental, but were the inciting agents, sharing a common mechanism for the induction of cyst formation and inflammation with the teratomas described in our cases. A mechanism other than inflammation within the primary tumor must be at play in these instances. While inflammation within the thymus may well be the mechanism for cyst induction, the underlying cause for and the intensity and character of the inflammation and hemorrhage associated with multilocular cysts remain unexplained. The "confusion that has surrounded [this issue] over the years"1 remains and is not resolved by the term idiopathic.

The magnitude of the reactive fibroblastic process in one of the patients described in the present report was sufficient to suggest the diagnosis of inflammatory myofibroblastic tumor (inflammatory pseudotumor) and bears resemblance to the cellular phase of sclerosing mediastinitis. However, ALK-1, which is often expressed in inflammatory myofibroblastic tumors, was not identified by immunohistochemistry. Because an exuberant fibroblastic response is often a feature of multilocular thymic cysts, the as yet undefined factors that result in the pronounced inflammation likely also explain the associated robust myofibroblastic reaction. The literature contains no evidence to suggest that this reactive change progresses in the manner of sclerosing mediastinitis.

References

1. Suster S, Rosai J. Multilocular thymic cyst: an acquired reactive process: study of 18 cases. Am I Surg Pathol. 1991;15:388-398.

2. Choi YW, McAdams HP, Jeon SC, et al. Idiopathic multilocular thymic cyst: CT features with clinical and histopathologic correlation. Am J Roentgenol. 2001; 177:881-885.

3. Kontny HU, Sleasman JW, Kingma DW, et al. Multilocular thymic cysts in children with human immunodeficiency virus infection: clinical and pathologic aspects. I Pediatr. 1997;131:264-270.

4. Lewis CR, Manoharan A. Benign thymic cysts in Hodgkin's disease: report of a case and review of published cases. Thorax. 1987;42:633-634.

5. Borgna-Pignatti C, Andreis IB, Rugolotto S, Baiter R, Bontempini L. Thymic cyst appearing after treatment of mediastinal non-Hodgkin lymphoma. Med Pediatr Oncol. 1994;22:70-72.

6. Liang SB, Ohtsuki Y, Sonobe H, et al. Multilocular thymic cysts associated with thymoma: a case report. Pathol Res Pract. 1996;192:1283-1287.

7. Moran CA, Suster S. Mediastinal yolk sac tumors associated with prominent multilocular cystic changes of thymic epithelium: a clinicopathologic and immunohistochemical study of five cases. Mod Pathol. 1997;10:800-803.

8. Jaramillo D, Perez-Atayde A, Griscom NT. Apparent association between thymic cysts and prior thoracotomy. Radiology. 1989;172:207-209.

9. Kondo K, Miyoshi T, Sakiyama S, Shimosato Y, Monden Y. Multilocular thymic cyst associated with Sjogren's syndrome. Ann Thorac Surg Oct. 2001;72: 1367-1369.

10. Shapiro J, Gallant A, Wechsler RJ, Steiner RM. Thymic cyst secondary to cervical irradiation: a complication of treated laryngeal cancer. Comput Med Imaging Graph. 1991;15:319-322.

11. Wakely P Jr, Suster S. Langerhans' cell histiocytosis of the thymus associated with multilocular thymic cyst. Hum Pathol. 2000;31:1532-1535.

Dinesh Rakheja, MD; Arthur C. Weinberg, MD

Accepted for publication September 11, 2003.

From the Departments of Pathology (Dr Rakheja) and Pediatrics (Dr Weinberg), The University of Texas Southwestern Medical Center, Dallas; and Children's Medical Center, Dallas, Tex (Dr Weinberg).

Reprints: Dinesh Rakheja, MD, Department of Pathology, Mail Code 9073, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235 (e-mail: dinesh.rakheja@utsouthwestern. edu).

Copyright College of American Pathologists Feb 2004
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