|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 22, No 5 (March 1), 2004: pp. 955-957 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.05.134
Difficult Diagnostic and Therapeutic CasesCASE 2. Thymoma and Tumor Lysis Syndrome in an AdolescentFrom the Departments of Pediatric Hematology/Oncology, Pathology, and Pediatric Surgery, The Children's Hospital of Denver; University of Colorado School of Medicine; and University of Colorado Cancer Center, Denver, CO A 16-year-old previously healthy white male presented with left rib and shoulder pain associated with decreased energy and exercise tolerance, and occasional "blue lips" in cold weather for 2 months. He had no cough, shortness of breath, weight loss, or fever. He denied orthopnea, but slept with two pillows for the last 2 years. Physical examination was remarkable for chest asymmetry, with the left hemithorax appearing more expanded anteriorly, and markedly decreased left-sided aeration. He had no tachypnea or increased work of breathing, and his oxygen saturation in room air was normal. There was no hepatosplenomegaly or lymphadenopathy. Laboratory evaluation disclosed a normal complete blood count, normal creatinine of 0.9 mg/dL, normal serum electrolytes, normal liver enzymes, a high normal lactate dehydrogenase (LDH) of 228 U/L (normal range, 130 to 230), and uric acid of 8.0 mg/dL (normal range, 4 to 8.4). Serum beta-human chorionic gonadotropin and alpha-fetoprotein were normal. Chest radiograph showed nearly complete opacification of the left hemithorax with a large mass and slight mediastinal shift to the right (Fig 1A). On computed tomography scan, the mass was heterogeneous without calcifications, but with multiple pleural metastases (Fig 1B). Echocardiography showed an ejection fraction of 45% and compression of the left pulmonary artery and vein with good dynamic flow. A bone scan was normal, and an octreotide scan subsequently showed uptake within the tumor. He was admitted and underwent a left thoractomy with multiple biopsies and chest tube placement. Grossly, the tumor was partially encapsulated with extensive invasion of surrounding tissue and with multiple pleural implants. He received no steroids intraoperatively. A frozen section of the tumor was interpreted as lymphoblastic lymphoma. On the first postoperative day, he developed emesis and increased chest tube output. That evening, he developed hypotension with blood pressures of approximately 100/40 with oliguria. He received a normal saline bolus, but remained completely oliguric for 12 hours. Serum chemistries showed marked change from baseline: potassium of 5.1 mmol/L, bicarbonate of 17 mmol/L, blood urea nitrogen 67 mg/dL, creatinine of 3.3 mg/dL, ionized calcium of 0.9 mmol/L (normal range, 1.2 to 1.4), LDH 331 U/L, phosphorus of 14 mg/dL, and uric acid of 33.8 mg/dL. Urinalysis had more than 100 RBCs and 10 to 25 WBCs per high power field, and uric acid crystals. A renal ultrasound showed significant focal increased density. He was given calcium, amphojel, allopurinol, and furosemide, and hemodialysis was initiated. CSF and bone marrow aspirate with biopsy were normal. Intrathecal cytarabine was administered. After 3 days of hemodialysis, his phosphorus decreased to 8.9 mg/dL, creatinine was 5.2 mg/dL (after a peak of 6.3), blood urea nitrogen was 59 mg/dL, calcium was 4.2 mEq/L, potassium was 4.1 mmol/L, LDH was 270 U/L, and uric acid was 8.9 mg/dL.
The final pathologic diagnosis was widely invasive thymoma, mixed lymphoepithelial subtype (WHO B2). The tumor capsule was only focally intact with extensive invasion. There were no Hassall's corpuscles or residual thymus. There were sheets of cells and well-demarcated lobules, which were subdivided by fibrous trabeculae of variable thickness (Fig 2A). Within the background of lymphocytes, were lighter, larger malignant polygonal epithelial cells with vesicular chromatin and small nuclei (Fig 2B). The tumor cells were obscured by a dense lymphocytic infiltrate, which extended throughout all areas of the tumor. There were perivascular lakes, but no significant tumor necrosis. The lymphocytes were mainly thymic T-cells with CD3 positivity (Fig 2C). The tumor cells were strongly positive for cytokeratin (Fig 2D).
After dialysis was discontinued (day 4), chemotherapy was started with cyclophosphamide (600 mg/m2) and doxorubicin (50 mg/m2) over 48 hours and 5 days of prednisone. Cisplatin was postponed because of the recent severe renal impairment. He responded well and did not have worsening of tumor lysis. A computed tomography scan of his chest showed a decreased mass. After the third course of chemotherapy with the addition of cisplatin (80 mg/m2), he underwent resection of the thymoma via a median sternotomy. A left upper lobectomy, partial pleurectomy, and partial pericardectomy were carried out. There were separate tumor masses in the left paraspinal region at approximately T6 and T7, and other separate tumor masses along the left lateral chest wall the surface of the diaphragm. Pathologic evaluation of the resected tumor showed approximately 30% residual viability in most areas. Because there were positive resection margins, postoperative radiation therapy was initiated with 44.97 Gy in 25 fractions to the area of mediastinal disease, 18.3 Gy to the left hemithorax, and a boost of 20 Gy to the posterior lateral pleural cavity. One month after treatment had been completed, he had additional resection and radiotherapy for recurrent pleural disease outside the radiation field. At 13 months after completion of therapy, and 22 months from diagnosis, he underwent resection and is receiving chemotherapy for pleural and peritoneal recurrence. Thymomas are rare in pediatric patients, with a median age at presentation of approximately 55 years [1]. Tumor lysis syndrome in a patient with a thymoma is extremely rare, with one case reported in the literature. A 33-year-old male with advanced invasive thymoma with lymphocyte predominance and peripheral blood T-cell lymphocytosis developed tumor lysis syndrome after receiving chemotherapy with cisplatin, doxorubicin, and methylprednisolone [2]. Our patient developed tumor lysis syndrome following diagnostic surgery before administration of chemotherapy or steroids. His tumor was heavily infiltrated with lymphocytes. Thus, the tumor lysis syndrome likely resulted from lysis of lymphocytes as a result of endogenous stress steroid release following thoracotomy. This case highlights the importance of serial evaluations of electrolytes, creatinine, and urine output in any patient with an anterior mediastinal mass, even if the diagnosis is not likely to be lymphoma. Disease recurred in the pleura outside of the radiation field, illustrating the importance of radiation to the entire hemithorax including the pleura, especially in patients with pleural disease. This has been observed previously in patients with and without overt pleural disease. At initial diagnosis, 11 patients with invasive thymoma received radiation therapy and all had a complete remission; however, three recurred locally outside of the radiation field [3]. In another report, 70 patients with thymomas underwent surgery and mediastinal radiation therapy. Of 22 patients with pleural disease, nine developed pleural recurrences [4]. For patients with pleural disease, radiation therapy to the complete hemithorax may be necessary to improve the prognosis. In conclusion, thymomas should be considered in patients with mediastinal masses, especially those with chronic symptoms or evidence of chest deformity. Though extremely uncommon, tumor lysis syndrome may occur, especially in patients with lymphocyte-rich tumors. One must always be cautious of a potential misdiagnosis of lymphoma when this occurs. In addition to chemotherapy, for example, with anthracyclines, cyclophosphamide, vincristine, and cisplatin [5–8], radiation therapy to the complete hemithorax encompassing all pleura should be considered in patients with pleural disease. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES 1. Ogawa K, Toita T, Uno T, et al: Treatment and prognosis of thymic carcinoma. Cancer 94:3115–3119, 2002[CrossRef][Medline] 2. Yokoi K, Miyazawa N, Kano Y, et al: Tumor lysis syndrome in invasive thymoma with peripheral blood T-cell lymphocytosis. Am J Clin Oncol 20:86–89, 1997[CrossRef][Medline] 3. Uematsu M, Kondo M: A proposal for treatment of invasive thymoma. Cancer 58:1978–1984, 1986 4. Haniuda M, Moriomoto M, Nishimura H, et al: Adjuvant radiotherapy after complete resection of thymoma. Ann Thorac Surg 54:311–315, 1992[Abstract] 5. Rea F, Sartori F, Loy M, et al: Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg 106:543–549, 1993[Abstract] 6. Hejna M, Haberl I, Raderer M: Nonsurgical management of malignant thymoma. Cancer 85:1871–1884, 1999[Medline] 7. Macchiarini P, Chella A, Ducci F, et al: Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 68:706–713, 1991[CrossRef][Medline]
8. Berruti A, Borasio P, Roncari A, et al: Neoadjuvant chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in invasive thymomas: Results in six patients. Ann Oncol 4:429–431, 1993
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
