Tumors of the Thvmus and Thee
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1 Tumors of the Thvmus Thee Region: 111. Clinic&pathological Skdies on Teratornas Tumors of Germ Cell Type N. P. Bergh, M.D., P. Gatzinsky, M.D., S. Larsson, M.D., P. Lundin, M.D., B. Ridell, M.D. ABSTRACT In a series of 82 patients with tumors of the thymus thymic region there were 11 with teratomas germinal tumors. Four of these patients had benign cystic teratomas, 4 had malignant teratomas, 1 had an embryonal carcinoma, 2 had seminomas. The benign teratomas were removed by simple extirpation without complications. The malignant teratomas were highly invasive, despite extensive operations postoperative radiotherapy, 3 of the 4 patients died within 9 months. One patient with predominantly seminomatous differentiation of the teratoma was alive well more than 3 years after the operation. The patient with an embryonal carcinoma died after 4 months. One of the 2 patients with seminoma remained alive 20 years after radical excision postoperative radiotherapy. The other, who had a huge seminoma, died during operation. The prognosis in patients with seminomas or with predominantly seminomatous structures in teratomas seems to be good after combined radical excision radiotherapy, although nonradical resection followed by radiotherapy may be justified in high-risk patients. Teratoid tumors other tumors of germ cell type are usually primary in the testes or ovaries. Sometimes these masses are found at extragenital sites such as the sacrococcygeal region, pineal body, or mediastinum. In the mediastinum, teratomas are usually located in the thymic region. The aim of the present study was to examine the clinicopathological features of teratoid tumors of the mediastinum in order to evaluate factors influencing the choice of therapy the prognosis. From the Departments of Thoracic Surgery Pathology I, Sahlgren's Hospital, University of Goteborg, Gothenburg, Sweden. Accepted for publication June 21, Address reprint requests to Dr. Larsson, Thoracic Surgical Clinic, Sahlgren's Hospital, Gothenburg, Sweden. Patients Methods There were 4 patients with benig: 'eratoma, 4 with malignant teratoma, 1 wjlh ail,ibryonal carcinoma, 2 with seminoma among 82 patients with benign or malignant tumors in the upper anterior mediastinum. All 11 patients were followed until death or to December 31, All available histological material, together with case records postmortem examination reports, was reviewed. Clinical Findings The 4 benign teratomas occurred in women aged 19 to 41 years. In 2 patients without symptoms the tumor was discovered during radiological surveys. The other 2 patients had obstruction or pains in the thorax, the tumors were found on chest roentgenograms. The 5 malignant teratomas occurred in men ranging from 16 to 53 years of age the embryonal carcinoma in a 19-year-old man. The initial symptoms in 4 of the 5 patients were weight loss, fatigue, cough, dyspnea, thoracic pains. One patient had had a benign teratoma removed abroad 13 years earlier. In 1 patient with a carcinoma of the anus the mediastinal tumor was discovered on chest roentgenogram; this patient had no symptoms from the mediastinal tumor. The 2 patients with mediastinal seminoma were both 35-year-old men. Their initial symptom was thoracic pain. None of these patients had testicular tumors. Extent of the Lesion The benign teratomas ranged from walnut sized to as large as an orange. In 2 cases the mass was adherent to the pericardium in 1 case to the phrenic nerves. The malignant teratomas varied in weight from 400 to 1,400 gm. The pericardium was involved in all patients the lungs in 4. In 1 patient the tumor had grown in continuity into the myocardium. This tumor was biopsied only by The Society of Thoracic Surgeons
2 108 The Annals of Thoracic Surgery Vol 25 No 2 February 1978 No case of spread to the pleura or lymph nodes was found. The embryonal carcinoma was a tumor weighing 850 gm located in the upper anterior mediastinum infiltrating the right lung. One seminoma was radically removed in spite of its weighing 2,100 gm. The other seminoma was of about the same size. Both these tumors had infiltrated the lungs the pericardium. Morphological Findings The benign teratomas were polycystic, the cysts being filled with gelatinous or sebaceous material. Microscopically the cysts were lined with epithelium of different types. In the cyst walls differentiated tissues from three germ layers were found. Thymic tissue was discovered adjacent to the tumor in 2 cases within the tumor in 1. The malignant teratomas had an irregular border contained cysts of varying size as well as nccrotic or fibrotic areas. In all 4 tumors, tissues of different types were found. The tumors were classified according to the principles proposed by Friedman [4]. In 2 cases glular elements cystic structures lined by neoplastic epithelium were seen in a cell-rich stroma (Fig 1). The other 2 malignant teratomas each contained one distinctly malignant component; in 1 case this was classified as an undifferentiated carcinoma, in the other as a seminoma. The embryonal carcinoma showed extensive necrosis bleeding. The vital tumor tissue was composed of large cells exhibiting a pronounced polymorphism several atypical mitotic figures. Some of the tumor cells were arranged in tightly packed cellular areas others in a syncytial fashion (Fig 2), a feature which in some areas gave the tumor the appearance of a choriocarcinoma. Grossly the 2 seminomas were nonencapsulated bosselated, with a soft, whitish gray cut surface traversed by fibrous bs. Microscopically the tumors were composed of isls of large cells with irregular nuclei often prominent nucleoli. These areas were separated by a fibrous stroma with varying collagen content. Collections of lymphocytes were found in the stroma (Fig 3). No other differentiated epithelial or mesenchymal tissues were observed. The mediastinal seminomas had a microscopical appearance similar to that of a testicular seminoma. These 2 tumors had originally been diagnosed as thymomas. Treatment The treatment is summarized in Table 1. All benign teratomas were removed radically. Three patients with malignant teratoma the patient with embryonal carcinoma were subjected to curative resection. One patient with a malignant teratoma had exploration only. Postoperative radiotherapy was given in doses varying Fig 1. Malignatit teratoma with chondroid tissue, cysts lined by a cylindrocellular epithelium, a cell-rich stroma. (H6E.) Fig 2. carcinoma. Polymorphic tumor with areas of syncytial arrangement of tumor cells (S.a.) compact cellular areas (C.a.). (Ha.)
3 109 Bergh et al: Teratomas Germ Cell Tumors from 4,000 to 6,000 rads. One seminoma was radically removed; this patient also received radiotherapy. The other patient with a seminoma was subjected to nonradical surgery. The surgical approach operative procedure are shown in Tables 2 3. No operative or postoperative complications occurred in patients with benign or malignant teratomas. One patient with a huge seminoma died during the operation from uncontrollable bleeding. Fig 3. Seminoma. Tumor lobules composed of cells exhibiting polymorphism, prominent nucleoli, mitotic figures (M). In the stroma there is marked lymphocytic infiltration (arrows). (H6E.) Results All patients with a benign teratoma were alive well after a mean observation time of 93 months (range, 35 to 174 months). Two patients with malignant teratoma the patient with an embryonal carcinoma died of widespread disease 2 to 6 months after the operation. The patient who had a malignant teratoma of the mediastinum anal carcinoma died from spread of his anal lesion 9 months after the thoracic operation. No evidence of spread from the teratoma was found postmortem. One pa- Table l. Treatment Given in 11 Patients with Mediastinal Teratoid Tumors Tera toma Teratoma Carcinoma Seminoma Treatment (N = 4) (N = 5) (N = 2) Resection Radical Nonradical Nonexcisional procedure Postoperative Radiotherapy Table 2. Surgical Approach in 11 Patients with Mediastinal Teratoid Tumors Teratoma Tera toma Carcinoma Seminoma (N = 4) (N = 5) (N = 2) Sternotomy Thoracotomy Left-sided Right-sided Combined approach
4 110 The Annals of Thoracic Surgery Vol 25 No 2 February 1978 Table 3. Operative Procedures in 11 Patients with Mediastinal Teratoid Tumors Teratoma Extent of Teratoma Carcinoma Seminoma Operation (N = 4) (N = 5) (N = 2) Exploratory thoracotomy only Simple extirpation Wedge resection of a lobe Lobectomy Pericardial resection Resection of left innominate vein Resection of phrenic nerve" "Reconstruction with an intercostal nerve graft was done in 1 case. tient with a predominantly seminomatous malignant teratoma was alive well more than 3 years after the operation. One patient who had a seminoma remained alive well after 20 years. The other patient with this type of tumor died during the operation. Comment The mediastinum ranks next to the gonads as the most common site of teratoma. The origin of mediastinal teratomas germ cell tumors is still debated. According to one hypothesis, the tumors arise from primitive cells that descended in the mediastinum with the thymic anlage [8]; this explanation is supported by the fact that teratomas germ cell tumors are usually located in the upper anterior mediastinum near or within the thymus [8]. Another opinion holds that these mediastinal tumors are derived from aberrant embryonal germ cells [3]. In the present series the age sex distributions were fairly similar to those in earlier publications [l, 2, 6, 7, 9, lo]. Thus, most patients were between years of age, there was male dominance among the patients with malignant teratoma. However, the strong female dominance in our small series of benign teratomas is at variance with other studies, in which an equal incidence between the sexes has been reported. The prognosis in patients with malignant teratoma seems to be very poor [6]. In patients who have large malignant tumors, hazardous extensive surgical procedures seem to be of little benefit. Most small medium-sized tumors can be removed without difficulty during surgical exploration. In patients with large tumors a limited surgical procedure for establishing a reliable histological diagnosis should be performed. Reduction of the mass should be considered when the operation can be carried out without any risk to the patient. All patients with malignant teratoma should be given postoperative radiotherapy, chemotherapy, or both. One patient with a surgically removed malignant teratoma was alive well 3 years after operation. Interestingly, a benign teratoma had been removed earlier in this patient. At the second operation there was a malignant teratoma of predominantly seminomatous differentiation. The microscopical finding of seminomatous areas in malignant teratomas seems to support the view that these tumors are closely related to seminomas of the mediastinum. Several cases of mediastinal seminoma have been reported, these tumors have the same morphological features as their counterparts in the testis [5]. One of our 2 patients with seminoma has lived more than 20 years, the single survivor in the group with malignant teratoma had predominantly seminomatous differentiation. The prognosis after radical treatment radiotherapy seems good in patients with this type of tumor, which is consistent with observations reported by other workers [lo]. On the other h, a limited surgical procedure fol-
5 111 Bergh et al: Teratomas Germ Cell Tumors lowed by radiotherapy may be justified in high-risk patients. In patients with large tumors the use of a local bypass shunt reduces the risk of uncontrollable bleeding. When the tumor involves both innominate veins or the superior vena cava, blood may be temporarily shunted past the tumor area by means of a local shunt consisting of a heparincoated tube with a cannula at each end. The distal cannula is secured by pursestring sutures in one of the innominate or jugular veins. The proximal cannula is inserted in the right atrial appendage. The veins are immediately crossclamped on both sides of the tumor to ensure a high flow rate in the tube. A small dose of heparin may be given to prevent clotting. With this technique the central veins can then be resected reconstructed. References 1. Boyd DM, Midell AI: Mediastinal cysts tumors. Surg Clin North Am 48:493, Cox JD: Primary malignant germinal tumors of the mediastinum: a study of 24 cases. Cancer 36:1162, Fried BM: Tumors of the Lungs Mediastinum. Philadelphia, Lea & Febiger, Friedman NB: The comparative morphogenesis of extragenital gonadal teratoid tumours. Cancer 4:265, Levine GD: Primary thymic seminoma-a neoplasm ultrastructurally similar to testicular seminoma distinct from epithelial thymoma. Cancer 31:729, Pachter MR, Lattes R: "Germinal" tumors of the mediastinum: a clinicopathologic study of adult teratomas, teratocarcinomas, choriocarcinomas seminomas. Dis Chest 45:301, Ringertz N, Lidholm SO: Mediastinal tumors cysts. Thorac Surg 31:458, Schlumberger HG: Teratoma of the anterior mediastinum in the group of military age. Arch Pathol41:398, Vidne 8, Levy MJ: Mediastinal tumors. J Thorac Cardiovasc Surg 7:59, Wychulis AR, Payne WS, Clagett OT, et al: Surgical treatment of mediastinal tumors. J Thorac Cardiovasc Surg 62:379, 1971
Region: 11. Clinic6patholo cal Studies
Tumors of the Thvmus and ThVIIliC Region: 11. Clinic6patholo cal Studies on Hodgkin s Disease of Re Thymus N. P. Bergh, M.D., P. Gatzinsky, M.D., S. Larsson, M.D., P. Lundin, M.D., and B. Ridell, M.D.
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