Potential complications of the growing teratoma syndrome in

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ORIGINALES BREVES
Potential complications of the growing teratoma
syndrome in patients with advanced germ-cell
tumors: description of three cases
Jorge Aparicio, Regina Gironés, José Alejandro Pérez-Fidalgo, Verónica Calderero,
Roberto Díaz and Joaquín Montalar
In order to illustrate potential complications of the growing teratoma syndrome
(GTS), three out of 180 pa- tients with
germ-cell tumors from a single institution were identified. Despite surgical
resection of recurrent mature teratoma,
one patient developed a renal failure due
to structure compression, one patient
presented malignant transformation to
squamous cell lung cancer, and a third patient had an unresectable mediastinal
mass. Although the treatment of choice
for GTS is complete surgical resection, it
is not always possible and then recurrence is common.
Aparicio J, Gironés R, Pérez-Fidalgo JA, Calderero V, Díaz R,
Montalar J. Potential complications of the growing teratoma syndrome in patients with advanced germ-cell tumors:
description of three cases. Rev Oncol 2002;4(4):210-2.
Key words: germ cell tumors, growing teratoma
syndrome, complications.
Complicaciones potenciales del síndrome de
crecimiento del teratoma en pacientes con
tumores germinales avanzados: descripción de
tres casos
Para ilustrar las complicaciones potenciales del síndrome de crecimiento del teratoma (SCT) hemos identificado tres casos entre 180 pacientes con tumo-res
germinales tratados en un solo centro. A
pesar de la resección de lesiones con teratoma maduro recidivante, un paciente
desarrolló una insuficiencia renal por
compresión de estructuras, otro presentó
Correspondence: Dr. J. Aparicio.
Servicio de Oncología Médica.
Hospital Universitario La Fe.
Avda. Campanar, 21.
46009 Valencia.
E-mail: japairiciou@seom.org.
Received 19 November 2001; Revised 14 February 2002;
Accepted
210
una transformación a carcinoma epidermoide de pulmón y un tercero padeció una
masa mediastínica irresecable. Aunque el
tratamiento electivo del SCT es la resección quirúrgica completa, ésta no siempre
es posible y entonces la recidiva es frecuente.
Palabras clave: tumores germinales, síndrome de
crecimiento del teratoma, complicaciones.
INTRODUCTION
The growing teratoma syndrome (GTS) is characterized by enlargement of residual mass lesions
(composed of mature teratoma, in absence of viable malignant tumor, and with normal serum tumor markers) during or after chemotherapy for
metastatic non-seminomatous germ cell tumor
(NSGCT). It is an uncommon finding. The treatment of choice is surgical resection because these
Rev Oncol 2002;4(4):210-2
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APARICIO J, GIRONÉS R, PÉREZ-FIDALGO JA, ET AL. POTENTIAL COMPLICATIONS OF THE GROWING TERATOMA SYNDROME
IN PATIENTS WITH ADVANCED GERM-CELL TUMORS: DESCRIPTION OF THREE CASES
lesions do not respond to chemotherapy. If a complete excision is not possible, several complications may occur due to compression of neurovascular
or
visceral
structures
(mainly
retroperitoneal
and
mediastinal),
malignant
transformation, or even may be responsible for
the development of late relapses and distant me1,2
tastases .
Between 1975 and 2000, 180 patients with testicular and extragonadal germ cell tumors have been treated in our department; we have identified
three cases with unresectable or recurrent lesions that exemplify the evolutionary spectrum of
the GTS.
dose carboplatin, etoposide and cyclophosphamide
with autologous stem cell rescue in May 1996). A
second partial response was achieved (negative
markers, unresectable residual mass). In January
1997, a new marker increase was detected (AFP
7368 ng/ml, BHCG 3475 UI/l), and he received
oral chemotherapy with low-dose continuous etoposide; in spite of a good marker decline curve, the
patient was admitted to hospital 3 months later
with an episode of oliguria and back pain. The abdominal mass had notably grown (fig. 1), thus producing a right hydronephrosis, absence of renal arterial perfusion (detected by radionuclide scans) and
an acute renal failure (serum creatinine, 9 mg/dl).
He did not respond to fluids, dopamine and hemodialysis, and died a few days later.
CASE REPORTS
Case 1
Case 2
A 25 year-old man was diagnosed in October
1993 of a right testicular, mixed histology
NSGCT (embryonal carcinoma, mature teratoma,
and choriocarcinoma), staged IV-C-L3 according
3
to Royal Marsden´s classification . Retrospectively revised, he fulfilled intermediate IGCCCG
4
prognosis criteria (alpha-fetoprotein, AFP 4,800
ng/ml; beta-human chorionic gonadotropin, BHCG
32,600 UI/l). An inguinal orchiectomy was performed, and he received 8 courses of alternating
5
chemotherapy BOMP/EPI , thus attaining a partial
response (negative markers, persistence of a
cystic retroperitoneal mass, and absence of distant metastases). The residual mass encompassed
the great vessels and the right ureter, and was
therefore deemed unresectable.
By July 1995 the patient presented a retroperitoneal and supraclavicular node relapse with raised
serum markers (AFP 331 ng/ml), and received salvage chemotherapy with several sequential schemes (ACE/PEV, VeIP, paclitaxel and, finally, high-
A 22 year-old male was diagnosed in November
1984 of a testicular teratocarcinoma, Royal
Marsden stage IV-B-L3 with intermediate IGCCCG
criteria. He received a left orchiectomy and systemic chemotherapy with 4 cycles of PVB (cisplatin, vinblastine and bleo-mycin); a partial response was achieved (persistence of lung nodules with
negative serum markers). A right thoracotomy
was
performed
with
resection
of
2 nodules. Their histologic analysis revealed mature teratoma. A few contralateral micronodules
were left and carefully watched. Five years later, one of them grew and was resected, the
diagnosis being again mature teratoma.
In November 1994 he suffered a late retroperitoneal
relapse with increased serum markers (AFP 197
ng/ml) and received salvage chemotherapy with 4
courses of BOMP/EPI and a retroperitoneal resection again revealing mature teratoma without
malignant elements.
Fig. 1. CT scan of the abdomen. Large cystic masses involving the great vessels.
Fig. 2. CT scan of the thorax. Parahillar lung nodule with
malignant transformation.
Rev Oncol 2002;4(4):210-2
211
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APARICIO J, GIRONÉS R, PÉREZ-FIDALGO JA, ET AL. POTENTIAL COMPLICATIONS OF THE GROWING TERATOMA SYNDROME
IN PATIENTS WITH ADVANCED GERM-CELL TUMORS: DESCRIPTION OF THREE CASES
Today, the patient lives without sequelae, but his
mediastinal lesions are slowly growing (fig. 3);
there are no signs of neurovascular injure, and a
wait-and-watch policy has been decided.
DISCUSSION
Fig. 3. CT scan of the thorax. Slowly-growing, mediastinal
cystic mass.
By June 1998 a progressive growth of a preexisting parahillar lung nodule was noted (fig. 2), in
the absence of symptoms and with a discrete elevation of AFP (53 ng/ml). A fiberoptic bronchoscopy and transbronchial biopsy was diagnostic of
squamous cell lung cancer, that was deemed unresectable. He received chemotherapy (carboplatin
plus paclitaxel) and thoracic irradiation (55 Gy),
but 6 months later developed brain metastases
and died shortly thereafter (about 15 years after
the initial diagnosis).
Case 3
A 20 year-old man presented an extragonadal retroperitoneal, mixed histology (immature teratoma plus embryonal carcinoma) NSGCT in June
1985. Distant (hepatic, pulmonary, supraclavicular and mediastinal lymph node) metastases were
present, with (today´s) IGCCCG poor prognostic
criteria. AFP was 5,000 ng/ml and BHCG was 446
mU/ml.
He
received
6
courses
of alternating BEP/PVB chemotherapy, and attained a complete biological response (negative serum markers) with residual lesions in retroperitoneum and posterior mediastinum. Both of them
were surgically resected in a combined intervention in December 1985. The histologic exam revealed mature teratoma, with fibrous and necrosis
elements.
Since then, the patient has persisted disease-free
and with negative markers. However, in subsequent CT scans, several small cystic lesions were
visible next to the great vessels at the mediastinum. In April 1994, one of these lesions grew
producing irradiated back pain, and was again resected. The surgical procedure was incomplete
because of vascular involvement. The histology
was mature teratoma once more.
212
Testicular cancer has become the model of a curable neoplasm. After the recognition of the ability of cisplatin-containing combination chemotherapy to successfully treat advanced disease,
more than 90 percent of patients with newly
diagnosed germ-cell tumors are likely to be cured
of their disease. Surgical resection of residual disease is necessary in patients with NSGCT who
have normal serum tumor markers after chemotherapy. About 45 percent of these masses display
necrotic debris or fibrosis on pathological examination, 40 percent have evidence of mature teratoma, and 15 percent show viable malignant cells.
Only in the last case further therapy is required,
and two additional chemotherapy courses are re6
commended to maximize the cure rate .
Enlargement of tumor masses in the context of
declining or normal tumor markers values (during
of shortly after chemotherapy) generally represents a unique entity, the so-called GTS, and also
requires surgical resection. Since the original
description of this syndrome, multiple case reports have been published but only a few clinical
series with an adequate methodology of study ha1,2,7-10
ve been reported
. Some conclusions may be
drawn
from
these
studies:
a) the GTS is uncommon, occurring in 2 to 8 percent of metastatic NSGCT (i.e., seminomas are
excluded), including testicular, ovarian and extragonadal primaries; b) involved sites are only
locations
previously
affected by the disease, mainly retroperitoneum
and chest, but have also been described at mediastinum, cervical lymph nodes, forearm, and
pineal gland; c) the appearance of cysts in the
growing masses, detected at computed tomography scan, is characteristic; d) the presence of
mature teratoma in any or both the primary tumor and its postchemotherapy residual masses is
associated with an increased risk of GTS;
e) tumor masses do not respond to either chemotherapy or radiotherapy, and only partial respon11
ses to interferon have been described ; f) surgical resection is the treatment of choice. It
confirms the absence of malignant histology, prevents local complications, and avoids malignant
transformation or dissemination; however, complete resection is not always possible, and g) recurrences are frequent, usually in the form of
mature teratoma, but also may content malignant
Rev Oncol 2002;4(4):210-2
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APARICIO J, GIRONÉS R, PÉREZ-FIDALGO JA, ET AL. POTENTIAL COMPLICATIONS OF THE GROWING TERATOMA SYNDROME
IN PATIENTS WITH ADVANCED GERM-CELL TUMORS: DESCRIPTION OF THEREE CASES
germ-cell (producing mainly serum AFP) and non
germ-cell elements.
The cases presented here (and their images) are
representative of these potential complications of
the GTS. Despite its low incidence, it should be
stressed the importance of a complete (repetitive
if necessary) resection of residual masses and a
prolonged follow-up of these patients. Case 2 is
unique because the transformation of mature teratoma into squamous cell carcinoma is exceptional; however, a casual aggregation of two independent malignancies can not be definitively ruled
out.
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