GERM CELL TUMOR ASSOCIATED PRIMITIVE NEUROECTODERMALTUMORS
KRISTEN N. GANJOO, RICHARD S. FOSTER, HELEN MICHAEL, JOHN P. DONOHUE ANDLAWRENCE H. EINHORN*
From the Division of Hematology-Oncology, Departments of Medicine, Urology and Pathology, Indiana University Medical Center,Indianapolis, Indiana
Purpose: This retrospective review was done to assess the prognosis and response in patientspresenting with primitive neuroectodermal tumor admixed with germ cell tumor.
Materials and Methods: Of the 40 patients treated at our institution from 1984 to 1999, 15 hadinitial stage I and 25 had initial metastatic disease. Median followup after the diagnosis was 25months (range 4 to 142).
Results: Of the 40 patients 15 presented with clinical stage I disease, including 9 treated withretroperitoneal lymph node dissection and 6 who elected surveillance. Seven of the 9 patients hadnormal lymph nodes and all continuously had no evidence of disease. Two of the 9 patients had lymphnodes involved with teratoma with or without primitive neuroectodermal tumor. Retroperitonealrelapse in 5 of the 6 patients on surveillance was treated with cisplatin based chemotherapy followedby post-chemotherapy retroperitoneal lymph node dissection. Residual primitive neuroectodermaltumor was noted in 4 of the 5 patients and only 3 of 6 are currently without disease at a medianfollowup of 17 months (range 15 to 69). A total of 25 patients presented with metastatic disease, ofwhom 23 underwent cisplatin based chemotherapy. Only 3 patients achieved complete remissionwith chemotherapy alone and 2 of the 3 subsequently relapsed. Of the remaining 20 patients 16underwent post-chemotherapy retroperitoneal lymph node dissection, including 11 with primitiveneuroectodermal tumor in the resected specimen. Two of these 11 patients have continuously had noevidence of disease, while an additional 3 currently have no evidence of disease after further therapy.Teratoma was present in the resected specimen in 5 of 16 patients, of whom 2 have continuously hadno evidence of disease, while an additional 2 currently have no evidence of disease after furthersurgical resection. Therefore, 11 of 25 patients who presented with metastatic disease currently haveno evidence of disease at a median followup of 19 months (range 2 to 111).
Conclusions: Primitive neuroectodermal tumor in the orchiectomy specimen has adverse prognos-tic significance. This condition in the retroperitoneum is potentially curable by retroperitoneal lymphnode dissection but rarely eradicated by chemotherapy. Therefore, we recommend retroperitoneallymph node dissection for all clinical stage I cases with primitive neuroectodermal tumor in theorchiectomy specimen. Patients who present with metastatic primitive neuroectodermal tumorshould be treated aggressively with surgical resection as an integral part of the therapeutic strategy.
KEY WORDS: testis; lymph nodes; metastases; germinoma; neuroectodermal tumors, primitive
Germ cell tumors frequently consist of several cell types,including teratoma. Teratoma may have significant hetero-geneity.1 It may be biologically inert, grow by local extensionor undergo malignant transformation to nongerm cell malig-nancy.2 Teratoma is pluripotent and capable of transformingalong endodermal, ectodermal and mesodermal lines. Prim-itive neuroectodermal tumor develops from the malignanttransformation of teratoma along ectodermal lines, in con-trast to sarcoma, which is mesodermal in origin.3, 4 Primitiveneuroectodermal tumor belongs to a large group of lesionscalled small round blue cell tumors. However, primitive neu-roectodermal tumor arising from germ cell tumor is a distinctentity. It usually does not have the distinct chromosomaltranslocation t(11;22) that is normally present in small roundcell tumors. Some of these neoplasms have an abnormality ofthe isochromosome 12p, as in germ cell tumor, confirming the
germ cell origin of primitive neuroectodermal tumor.5 Prim-itive neuroectodermal tumor most likely arises from terato-matous elements of germ cell tumors.68 These tumors areaggressive and usually do not respond to chemotherapy.However, long-term disease-free status may be achieved bythe complete resection of all tumor.
A total of 1,949 retroperitoneal lymph node dissections wereperformed at our institution between 1984 and 1999. Also, wehave previously reported that 2.4% of all testicular germ celltumors treated at our institution contained primitive neuroec-todermal tumor.8 Therefore, this retrospective study representsa single institution series of a rare disease. The clinical outcomeis reported based on stage at presentation. The results of ther-apy and treatment options are also discussed.
PATIENTS AND METHODS
A total of 40 patients with primitive neuroectodermal tumorarising from testicular germ cell tumor were treated at ourinstitution between 1984 and 1999. All histological slides werereviewed at our facility. All patients had adequate staging withplain chest radiography or chest computerized tomography (CT)
Accepted for publication December 21, 2000.Presented at annual meeting of American Urological Association,
Atlanta, Georgia, May 16, 1999.Supported in part by the Walther Cancer Institute, Indianapolis,
Indiana.*Requests for reprints: Indiana Cancer Pavilion, Indiana Univer-
sity, 535 Barnhill Dr., RT 473, Indianapolis, Indiana 46202.
0022-5347/01/1655-1514/0THE JOURNAL OF UROLOGY Vol. 165, 15141516, May 2001Copyright 2001 by AMERICAN UROLOGICAL ASSOCIATION, INC. Printed in U.S.A.
as well as abdominal and pelvic CT. The majority of patientshad baseline tumor marker studies of b-human chorionic go-nadotropin (b-HCG) and a-fetoprotein (AFP).
Of the 40 patients 15 had clinical stage I disease at diag-nosis. All patients underwent radical orchiectomy followedby retroperitoneal lymph node dissection or surveillance. Iflymph node involvement with any type of germ cell tumorwas documented after pathological examination of the retro-peritoneal lymph node dissection specimen, patients weregiven the option of 2 cycles of adjuvant chemotherapy withetoposide and cisplatin with or without bleomycin. Patientswith negative lymph nodes received no further treatment. Inall cases close followup included a history, physical examina-tion, chest radiography and tumor markers every monthduring year 1, every 2 months during year 2 and once yearlyindefinitely thereafter. Patients who elected surveillance anddid not undergo retroperitoneal lymph node dissection re-ceived more frequent followups with abdominal and pelvicCT every 2 months during year 1 and every 4 months duringyear 2 in addition to a history, physical examination, chestradiography and tumor marker studies. If a patient hadrelapse on surveillance, cisplatin based chemotherapy wasgiven, followed by post-chemotherapy retroperitoneal lymphnode dissection with resection of all residual disease. If apatient had relapse after initial retroperitoneal lymph nodedissection, chemotherapy was administered, followed by sur-gical resection or resection alone.
Of the 40 patients 25 had metastatic disease at presentationwith retroperitoneal disease only, or pulmonary, hepatic or me-diastinal disease. The majority of patients underwent orchiec-tomy and subsequent cisplatin based chemotherapy. Generallyall those with residual tumor underwent post-chemotherapyretroperitoneal lymph node dissection and excision of all resid-ual disease unless disease was surgically unresectable.
The table shows patient characteristics. A total of 15 pa-tients with a median age of 31 years presented with clinicalstage I disease. Pre-orchiectomy tumor marker studies wereavailable in 12 of the 15 cases. Five of 12 patients hadelevated AFP, b-HCG or AFP and b-HCG. All patients un-derwent radical orchiectomy. Of the 15 patients 12 had prim-itive neuroectodermal tumor admixed with other germ celltumor elements in the orchiectomy specimen, while 3 withother germ cell tumor elements but no primitive neuroecto-dermal tumor in the orchiectomy specimen later had relapsewith primitive neuroectodermal tumor.
Nine of the 15 patients who presented with stage I diseaseunderwent post-orchiectomy retroperitoneal lymph node dis-section, including 7 with normal lymph nodes and 6 who werecontinuously without evidence of disease at a median fol-lowup of 26 months (range 4 to 144). One of 7 patients hadrelapse in the pre-sacral area 3 years after retroperitoneal
lymph node dissection and underwent the resection of tera-toma and yolk sac tumor. This patient had relapse again inthe iliac area and underwent chemotherapy and resection ofresidual primitive neuroectodermal tumor. After repeat re-lapse in the abdomen he received radiation therapy withouta response and died of disease.
Two of the 9 patients who underwent retroperitoneallymph node dissection had metastatic tumor, including 1with teratoma only who elected adjuvant chemotherapy andremained without evidence of disease at a followup of 60months. The other patient with teratoma and primitive neu-roectodermal tumor in the lymph nodes required repeat ret-roperitoneal lymph node dissection since he had relapse inthe abdomen 5 months after initial surgery. There was re-lapse again 17 months later in the mesentery and sarcomaresection was done. He currently has no evidence of disease 1month after the last surgical procedure.
Six of the 15 patients who presented with stage I diseaseelected surveillance, including 3 with primitive neuroectoder-mal tumor and teratoma in the orchiectomy specimen, and 3with other germ cell tumor elements. Five of the 6 patients hadrelapse in the retroperitoneum at a median time to relapse of 10months (range 4 to 11). All patients received cisplatin basedchemotherapy and underwent post-chemo