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Constitutional symptoms in patients with germ cell neoplasms
CONSTITUTIONAL SYMPTOMS IN PATIENTS WITH GERM CELL NEOPLASMS* GERALD CLAMON, M.D. KATHY HENRY, P.A. STEFAN LOENING, M.D. From the Departments of Internal Medicine and Urology, University of Iowa, College of Medicine, Iowa City, Iowa
-A patient with a mediastinal germ cell neoplasm evidenced ]ever, weight loss, pruri;ul adenopathy on ingestion of alcohol. Retrospective review revealed that 9 percent of vith advanced germ cell neoplasm evidence constitutional symptoms at presentation.
d symptoms including fever, night weight loss have been associated a's disease in 27 percent of patients and predict poorer response to ~ver was reported as an associated ; percent of 351 patients with a vaLumors. 4 Fever is attributed to maf when there is no evidence of inever appears to be associated with :h or relapse, and control of the to defervescence. ~ Weight loss is a aifestation of malignancy that also with a poor prognosis. 6 Pruritus lymph nodes after alcohol conassociated with Hodgkin's disease. ~1 symptoms in patients with germ ~f the testes or mediastinum have ~monly reported. An index patient t cell tumor who presented with ;, generalized pruritus, and alcolymph node pain was seen at the Iowa Hospital. Records of 104 pa~tage II or III germ cell tumors combination chemotherapy at the ff I o w a Hospital over the past rs, were reviewed for evidence of 1 symptoms. We report here the • index case and the findings in our ients with advanced germ cell tupart by the Iowa Cancer and Leukemia Re-
NOVEMBER 1990
/
Case Report A thirty-two-year-old white man noted generalized pruritus, fever, night sweats, and anorexia beginning in November, 1982. One of his first symptoms was pain in the chest after moderate alcohol consumption. He experienced a 15 lb weight loss over the two months of May and June, 1983. Nightly temperatures ranged from 103°F-104°E At an outside hospital, he was noted to have supraclavicular adenopathy and a mediastinal mass. He was initially staged there with a negative bone marrow, lymphangiogram, abdominal computerized tomography (CT), bone scan, and liver-spleen scan. A supraclavicular node biopsy was performed. Past medical history was unremarkable. Physical examination at the University of Iowa Hospital on July 29, 1983 showed a welldeveloped, well-nourished male with blood pressure 140/72 m m Hg, temperature 37.5°C, pulse 96. The skin showed excoriations over the arms, legs, trunk, and back. Lymph node examination showed two left supraclavicular nodes approximately 1.5 x 2.0 cm, a right anterior cervical node 3.5 x 2.5 cm, no axillary nodes, and small inguinal nodes. The remainder of the physical examination was unremarkable, including testicular examination. A repeat left cervical node biopsy was done on August 3, 1983, and both nodes were compatible with an anaplastic seminoma. Chest xray film revealed a very large mediastinal mass.
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Abdominal CT did not show extension below the diaphragm. Laboratory tests on admission showed ereatinine 1.0 mg/dL, albumin 3.4 g/ dL, aspartate aminotransferase 50 IU/L (nl up to 40), lactic dehydrogenase 300 IU/L (nl up to 225), and alkaline phosphatase 189 IU/L (nl up to 115). Hemoglobin as 9.8 g/dL, white blood cells 15,100/mm 3, and platelets 502,000. Serum beta h u m a n ehorionie gonadotropin and alphafetoprotein were normal. He was started on combination ehemotherapy in August, 1983 with vinblastine, bleomyein, and eis-platinum (VBP). Fever, sweats, and pruritus promptly improved. Subsequently he has had a long complicated course of treatments. After four eyeles of VBP, a biopsy of a residual mediastinal mass was done in November, 1983. This showed a germ eell tumor with anaplastie seminoma and a focus of teratomatous elements. Radiation therapy was given to the residual mass. By February 1984, he had left flank pain, pruritus, reeurrent fevers to 102°F, and abdominal adenopathy on CT scan. He was given six cycles of VP-16, doxorubiein (Adriamyein) and eis-platinum with resolution of all symptoms and normalization of the abdominal CT by early August, 1984. However, by September, 1984, he had new back pain with a positive bone scan at L4, a new lesion on ehest x-ray film, and recurrent pruritus. Due to recurrent disease and no evidence of tumor on bone marrow examination, his bone marrow was harvested for autologous marrow transplantation. He was treated with aggressive doses of BCNU, VP-16, cytosine arabinoside, cyclophosphamide, and 2,500 rad to the lumbar spine. This was followed by rescue with autologous marrow infusion. This marrow transplant was complicated by Staphylococcus epidermidis sepsis and subsequently, a sputum culture positive for Myeobacterium tuberculosis. After completion of the transplant, a further course of radiation therapy to the lumbar spine was given for persistent pain. CT of the spine subsequently suggested possible residual tumor at L4 but a needle biopsy specimen was negative for tumor. The patient is presently asymptomatie and without evidence of disease as of December, 1985. Review of Cases Subsequently, the charts of the 104 patients with advanced Stage II or III germ cell tumors seen at the University of Iowa Hospital from 1966 to 1984 were reviewed. Although a num-
466
UROLOGY
ber of patients had insuffieienl initial evaluations to be sure the constitutional symptoms, 9 pat nite "B" symptoms (fever, night tus, or > 10 % weight loss): 8 ha tory, often with documented ten 38.5°C and negative cultures ar ported a 20 lb weight loss over prior to admission. A patient w: ported a 30 lb weight loss ovel prior to admission. The histolo: tients' tumors were seminoma in bryonal eell cancer with or wit m e n t s in 4, a n d t e r a t o e a r c Treatment was too heterogeneo vent of Velban, bleomyein, and determine prognostie effects oJ symptoms. Comment A patient with a germ eell tuJ not only the systemie symptoms loss, and night sweats assoeiatec of cancer, but also generalized t mor pain seeondary to alcohol, often related to Hodgkin's disea, toms are known to prediet a po~ patients with Hodgkin's disease tion of their significance in a ul and treated population of pati~ cell tumors might be helpful. AI~ percent of patients with advane, mors have evidenced eonstituti in our review. Patients with bl masses or advanced lung diseas, prognosis with standard therap tensive high-dose platinum reg: prove the outeome. 7 If fever symptoms can be demonstrated pendent prognostic value in patl eell tumors, these patients might dates for such aggressive therap Iowa q References 1. Kaplan H8: Hodgkin's Disease, Camb Press, 1972, pp 89-90. 2. Aidenberg AC, Linggood RM, and Le face of Hodgkin's disease, Am J Med 67: 9~ 3. DeVita VT, Canellos GP, and Moxley i bination chemotherapy of advanced Hodg 30:1495 (1972). 4. Petersdorf RG: Fever and cancer, Ho~ 5. Bodel P: Tumors and fever, Ann NY A, 6. DeWys WD, et ah Prognostic effect c chemotherapy in cancer patients, Am J Me 7. Ozols RF, et ah High dose cisplatin Ann Intern Med 100:19 (1984).
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NOVEMBER
1990
/
VOLUME
-A patient with a mediastinal germ cell neoplasm evidenced ]ever, weight loss, pruri;ul adenopathy on ingestion of alcohol. Retrospective review revealed that 9 percent of vith advanced germ cell neoplasm evidence constitutional symptoms at presentation.
d symptoms including fever, night weight loss have been associated a's disease in 27 percent of patients and predict poorer response to ~ver was reported as an associated ; percent of 351 patients with a vaLumors. 4 Fever is attributed to maf when there is no evidence of inever appears to be associated with :h or relapse, and control of the to defervescence. ~ Weight loss is a aifestation of malignancy that also with a poor prognosis. 6 Pruritus lymph nodes after alcohol conassociated with Hodgkin's disease. ~1 symptoms in patients with germ ~f the testes or mediastinum have ~monly reported. An index patient t cell tumor who presented with ;, generalized pruritus, and alcolymph node pain was seen at the Iowa Hospital. Records of 104 pa~tage II or III germ cell tumors combination chemotherapy at the ff I o w a Hospital over the past rs, were reviewed for evidence of 1 symptoms. We report here the • index case and the findings in our ients with advanced germ cell tupart by the Iowa Cancer and Leukemia Re-
NOVEMBER 1990
/
Case Report A thirty-two-year-old white man noted generalized pruritus, fever, night sweats, and anorexia beginning in November, 1982. One of his first symptoms was pain in the chest after moderate alcohol consumption. He experienced a 15 lb weight loss over the two months of May and June, 1983. Nightly temperatures ranged from 103°F-104°E At an outside hospital, he was noted to have supraclavicular adenopathy and a mediastinal mass. He was initially staged there with a negative bone marrow, lymphangiogram, abdominal computerized tomography (CT), bone scan, and liver-spleen scan. A supraclavicular node biopsy was performed. Past medical history was unremarkable. Physical examination at the University of Iowa Hospital on July 29, 1983 showed a welldeveloped, well-nourished male with blood pressure 140/72 m m Hg, temperature 37.5°C, pulse 96. The skin showed excoriations over the arms, legs, trunk, and back. Lymph node examination showed two left supraclavicular nodes approximately 1.5 x 2.0 cm, a right anterior cervical node 3.5 x 2.5 cm, no axillary nodes, and small inguinal nodes. The remainder of the physical examination was unremarkable, including testicular examination. A repeat left cervical node biopsy was done on August 3, 1983, and both nodes were compatible with an anaplastic seminoma. Chest xray film revealed a very large mediastinal mass.
VOLUME XXXVI, NUMBER 5
465
Abdominal CT did not show extension below the diaphragm. Laboratory tests on admission showed ereatinine 1.0 mg/dL, albumin 3.4 g/ dL, aspartate aminotransferase 50 IU/L (nl up to 40), lactic dehydrogenase 300 IU/L (nl up to 225), and alkaline phosphatase 189 IU/L (nl up to 115). Hemoglobin as 9.8 g/dL, white blood cells 15,100/mm 3, and platelets 502,000. Serum beta h u m a n ehorionie gonadotropin and alphafetoprotein were normal. He was started on combination ehemotherapy in August, 1983 with vinblastine, bleomyein, and eis-platinum (VBP). Fever, sweats, and pruritus promptly improved. Subsequently he has had a long complicated course of treatments. After four eyeles of VBP, a biopsy of a residual mediastinal mass was done in November, 1983. This showed a germ eell tumor with anaplastie seminoma and a focus of teratomatous elements. Radiation therapy was given to the residual mass. By February 1984, he had left flank pain, pruritus, reeurrent fevers to 102°F, and abdominal adenopathy on CT scan. He was given six cycles of VP-16, doxorubiein (Adriamyein) and eis-platinum with resolution of all symptoms and normalization of the abdominal CT by early August, 1984. However, by September, 1984, he had new back pain with a positive bone scan at L4, a new lesion on ehest x-ray film, and recurrent pruritus. Due to recurrent disease and no evidence of tumor on bone marrow examination, his bone marrow was harvested for autologous marrow transplantation. He was treated with aggressive doses of BCNU, VP-16, cytosine arabinoside, cyclophosphamide, and 2,500 rad to the lumbar spine. This was followed by rescue with autologous marrow infusion. This marrow transplant was complicated by Staphylococcus epidermidis sepsis and subsequently, a sputum culture positive for Myeobacterium tuberculosis. After completion of the transplant, a further course of radiation therapy to the lumbar spine was given for persistent pain. CT of the spine subsequently suggested possible residual tumor at L4 but a needle biopsy specimen was negative for tumor. The patient is presently asymptomatie and without evidence of disease as of December, 1985. Review of Cases Subsequently, the charts of the 104 patients with advanced Stage II or III germ cell tumors seen at the University of Iowa Hospital from 1966 to 1984 were reviewed. Although a num-
466
UROLOGY
ber of patients had insuffieienl initial evaluations to be sure the constitutional symptoms, 9 pat nite "B" symptoms (fever, night tus, or > 10 % weight loss): 8 ha tory, often with documented ten 38.5°C and negative cultures ar ported a 20 lb weight loss over prior to admission. A patient w: ported a 30 lb weight loss ovel prior to admission. The histolo: tients' tumors were seminoma in bryonal eell cancer with or wit m e n t s in 4, a n d t e r a t o e a r c Treatment was too heterogeneo vent of Velban, bleomyein, and determine prognostie effects oJ symptoms. Comment A patient with a germ eell tuJ not only the systemie symptoms loss, and night sweats assoeiatec of cancer, but also generalized t mor pain seeondary to alcohol, often related to Hodgkin's disea, toms are known to prediet a po~ patients with Hodgkin's disease tion of their significance in a ul and treated population of pati~ cell tumors might be helpful. AI~ percent of patients with advane, mors have evidenced eonstituti in our review. Patients with bl masses or advanced lung diseas, prognosis with standard therap tensive high-dose platinum reg: prove the outeome. 7 If fever symptoms can be demonstrated pendent prognostic value in patl eell tumors, these patients might dates for such aggressive therap Iowa q References 1. Kaplan H8: Hodgkin's Disease, Camb Press, 1972, pp 89-90. 2. Aidenberg AC, Linggood RM, and Le face of Hodgkin's disease, Am J Med 67: 9~ 3. DeVita VT, Canellos GP, and Moxley i bination chemotherapy of advanced Hodg 30:1495 (1972). 4. Petersdorf RG: Fever and cancer, Ho~ 5. Bodel P: Tumors and fever, Ann NY A, 6. DeWys WD, et ah Prognostic effect c chemotherapy in cancer patients, Am J Me 7. Ozols RF, et ah High dose cisplatin Ann Intern Med 100:19 (1984).
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NOVEMBER
1990
/
VOLUME