Figure 1. Chest X-ray with multiple
nodular lesions.
Figure 2. Chest CT-scan with multiple
metastatic lesions.
Figure 3. Abdominal and pelvic CT-scan
with heterogeneous mass.
Cancer
Therapy Vol 3, 153-158, 2005
Ovarian
mixed germ cell tumor presenting as tuberculosis
Fatemeh Ghaemmaghami*, Azam Sadat Moosavi, Malihe Hasanzadeh
Gynecologist Oncologist, Tehran University of Medical
Sciences
__________________________________________________________________________________
*Correspondence: Fatemeh
Ghaemmaghami, Associate Professor, Gynecologist Oncologist, Tehran University
of Medical Sciences. Address: Gynecology Oncology Department, Vali-e-Asr
Hospital, Imam Khomeini Hospital Complex, Keshavarz Blvd., Tehran 14194, Iran.
Phone: #98-21-6939320, Fax: #98-21-6937321, E-mail: valrec2@yahoo.com, ftghaemmagh@yahoo.com
Key words: germ cell tumor, GTN, Tuberculosis, Endodermal sinus tumor,
tumor marker, EMA-EP, MEP
Abbreviations:
Summary
To introduce
a patient with rare ovarian mixed germ cell tumor who presented as miliary
tuberculosis.Patient was a 25 year old Afghani woman who had admitted with
complains of fever, dyspenea, abdominal pain. She had a fixed pelvic mass in
physical examination, abnormal findings in auscultation of the lungs, and chest
X-ray.We suggested miliary tuberculosis at the first time due to socio economic
nature and chest X-ray appearance. We found positive pregnancy test and
echogenic mass with ultrasound in paraclinic work up. We suggested high risk
GTN due to pulmonary manifestation (dyspenea and chest X-ray appearance) at the
second time. So she received EMA-EP regimen.She found acute abdomen cause to
hemorrhage, when she had received EMA part. Mixed germ cell tumor was confirmed
by histological examination after laparatomy and removing tumoral mass. Then
she received MEP regimen four courses and lived being time. In women of
reproductive age who has pulmonary symptoms, GTN and mixed germ cell tumor with
choriocarcinoma element should be considered.
I. Introduction
Mixed germ cell ovarian tumors represent a relatively
small proportion of all ovarian tumors (Disaia and Creasman, 2002).
Since germ cell tumors of the ovary consist fewer than
5% of ovarian cancer and mixed germ cell tumors accounting for approximately
19% of all cases (Hurteau and Williams, 2001). These ovarian tumors accounts
for about 1% of ovarian malignancies.
Mixed germ cell tumors contain at least, two
components of malignant germ cell tumors (Disaia and Creasman, 2002). In a case
series, the most common components of such tumors were reported as;
dysgerminoma (80%), endodermal sinus tumor (70%), immature teratoma (%53),
choriocarcinoma (20%), and embryonal carcinoma (16%). The most common
combination was dysgerminoma and EST (Gershenson et al, 1984).
The most presenting symptom in ovarian germ cell
tumors is abdominal pain with or without pelvic pain that could be seen in %75
of cases (Disaia and Creasman, 2002).
Approximately 10% of patients presents with an acute
abdomen secondary to intracapsular hemorrhage, torsion and/or rupture (Hurteau
and Williams, 2001).
Ovarian germ cell tumors present at a relatively early
stage; stage I (75%); and only few cases present stage IV (5%) (Disaia and
Creasman, 2002).
Mixed germ cell tumors may secret either AFP, HCG,
both or neither depending on components of tumor (Hurteau and Williams, 2001).
There are several case reports about peritoneal tuberculosis
mimicking advanced ovarian cancer (Straughn et al, 2000; Bilgin et al, 2001;
Protopapas et al, 2003). In contrast, ovarian cancer which presented as
tuberculosis may be rare.
II. Case
A 25 year-old, Gravid 3, Parity 3 Afghani woman was
referred to Vali-e-Asr hospital in October 2003 with a history of abdominal
pain, low grade fever during 3 months ago.
In physical examination a fixed mass in lower abdomen
which extends upper the hilus was revealed. In pelvic examination, uterus and
ovary could not be distinguished separately and a fixed pelvic mass could be
palpated. Temperature at admission and during hospitalization was about 38°C, in auscultation of the lungs, abnormal sounds could
be heard.
In urgent chest X-ray showed multiple nodular lesions
suggested metastasis lesions, but pulmonary tuberculosis could not rule out by
radiologist (Figure 1).
In abdominal ultrasound examination a huge mass was
revealed. Abdominal and pelvic CT-scan showed abdominal heterogeneous mass but
it was not possible distinct uterus and ovaries (Figure 2).
Miliary tuberculosis with pulmonary and peritoneal
involvement was suggested due to these signs in Afghani lady at the first time.
We found positive pregnancy test in routine laboratory
examination. We requested sputum samples, blood cultures, tuberculin test for
Acid-Fast bacilli which were negative.
Serum tumor markers measurement were done, b–hCG=815000 mIU/ml,
but results of other tumor markers, CA-125 and AFP took about one week to be
ready. Chest CT-scan showed multiple metastatic lesions (Figure 3).
Figure 1. Chest X-ray with multiple
nodular lesions.
Figure 2. Chest CT-scan with multiple
metastatic lesions.
Figure 3. Abdominal and pelvic CT-scan
with heterogeneous mass.
We suggest choriocarcinoma with pulmonary involvement
and stage III, score 13, due to sever pulmonary symptoms, dyspenea, and
elevated b–hCG. So we considered combined chemotherapy with
EMA-EP. When she had received part of EMA, other tumor markers measurement that
was taken before chemotherapy was ready as follows (CA-125= 54 IU/ml, AFP=2650 ng/ml), so we suggested mixed germ cell tumors with choriocarcinoma
thirdly and we decided to laparatomy so we scatuleated for elective surgery.
But she had acute abdomen, urgent laparatomy was performed.
A large cystic and solid mass weighted 5000gr arising
from right ovary was found, it was firmly adhered to the sigmoid colon. Tumoral
mass was removed intact without rupture.
Mixed germ call tumor with components of Endodermal
sinus tumor and choriocanainoma was reported by histological examination (Figures 4, 5).
We considered BEP regimen chemotherapy in patients with
germ cell tumors. Patient could not receive Bleomycin due to abnormal pulmonary
function test. We considered MEP regimen (Methotrexate, Etoposide, and
Cisplatin).
Patient received four courses of MEP (once every three
weeks) 7 days after surgery. The MEP regimen was given to the patient as
follows:
|
Methotrexate |
40
mg/m2 |
IV
or IM day 1 q 3 weeks |
|
Etoposide |
100
mg/m2 |
IV
daily 1-5 q 3 weeks |
|
Cisplatin |
20
mg/m2 |
IV
daily 1-5 q 3 weeks |
After 2 courses of chemotherapy AFP and CA-125 were both
decreased to normal measurement. After 3 courses of chemotherapy b–hCG was normal (b–hCG<5). Last course of chemotherapy was received by the
patient after negative b–hCG
and now about 9 months after surgery, she is under observation and follow up.
III. Discussion
Different variables make report of this case an
important issue. First, it was a rare case of mixed germ cell tumors which
presented at stage IV. Second, it was presenting as miliary tuberculosis due to
pulmonary symptoms, signs and fever. Third, it was mimicking to GTN stage III
after paraclinic work up due to positive pregnancy test and chest X-ray
appearance.
Cases of mixed choriocarcinoma and Endodermal sinus
tumor are rare and reported just in a few cases reports (Disaia and Creasman,
2002).
Also stage IV of germ cell tumors are just in 5% of
cases (Disaia and Creasman, 2002).
Many points are mimicking this case as miliary
tuberculosis. First, a fever which is prevalent in three categories;
infections, malignancies, and collagen diseases (Zamir et al, 2003).
Second, It is estimated that 8 million new cases of TB
occurred world wide in 1997 that 95 percent of them were occurred in developing
countries; Asia (5 million), Latin American (0.4 million), the Middle East (0.6
million) (Braunwald et al,2001).
It means that in developing countries, tuberculosis
remains endemic and present with non-specific symptoms and signs such as pelvic
and abdominal pain, mass, ascites and hence mimic ovarian cancer (Straughn et
al, 2000; Bilgin et al, 2001; Protopapas et al, 2003).
And the last point is that respiratory symptoms, signs
and radiological patterns of the lungs in choriocarcinoma are similar to
primary pulmonary disease (Hurteau and Williams, 2001).
There are many reports of peritoneal tuberculosis
mimicking as advanced ovarian cancer. In contrast, we could not find any report
that ovarian cancer presented as peritoneal tuberculosis.
This patient may be the first case in this matter.
Such a mimicking is due to Afghani patient who had fever and pulmonary
manifestations.
Figure 4. elements of Endodermal
sinus tumor where are reticular pattern and extra cellular and intra cellular
hyaline droplets were detected.
Figure 5. Elements of choriocarcinoma
where necrosis and hemorrhage and biphasic neoplastic cell was detected.
Mixed germ cell tumors containing Endodermal sinus
tumor elements have elevated serum AFP levels, ranging from >100 to far
higher than 1000ng/ml. The titer of
serum AFP in this case was higher than common range (Aoki et al, 2003). The
presence or absence of choriocarcinoma is considered to influence overall
survival or clinical outcome of the patients with mixed germ cell tumor.
Several cases of mixed germ cell tumor were reported with metastasis foci
composed of pure choriocarcinoma (Peccatori et al, 1995).
EMA-EP regimen as first line chemotherapy in
management of high risk GTN has showed good response (Ghaemmaghami et al,
2004a, b). But Cisplatin containing combination chemotherapy such as Bleomycin,
Etoposide and cisplatin (BEP) chemotherapy recommend in germ cell tumors.
Usually 3 to 4 courses of chemotherapy should be performed .In mixed germ cell
tumors another additional courses, after negative results of tumor markers,
should be considered (Berek and Hacker, 2000). The prognosis of patients with
mixed germ cell tumor can be poor because of the presence of a choriocarcinoma
element and these patients to require more aggressive chemotherapy (Peccatori
et al, 1995).
Methotrexate is the best chemotherapic agent in
management of choriocarcinoma. Since MEP (Methotrexate, Etoposide, Cisplatin)
may be good regimen in mixed germ cell tumor with choriocarcinoma elements
which BEP regimen is not justify due to pulmonary dysfunction.
In conclusion, although the diagnosis of gestational
trophoblastic neoplasia should be considered in any woman of reproductive age
who has pulmonary symptoms, mixed germ cell tumor also should be consider
especially when she has pelvic mass. Combined chemotherapy with MEP regimen may
be good regimen in mixed germ cell tumor with chorionic elements.
Aoki Y, Kase H, Fujita K (2003) Dysgerminoma with a slightly
elevated alpha-fetoprotein level diagnosed as a mixed germ cell tumor after
recurrence. Gynecol Obstet Invest 55, 58-9.
Berek JS, Hacker NF (2000) Non epithelial ovarian and
fallopian tube cancers Chapter 12, in Practical Gynecologic Oncology, third
edition. Lippinkot Williams and Wilkins, 523-551.
Bilgin T, Karabay A, Dolar E
et al (2001) Peritoneal tuberculosis
with pelvic abdominal mass, ascites and elevated CA-125 mimicking advanced
ovarian carcinoma, A series of 10 cases. Int
J Gynecol Cancer 11, 290-299.
Braunwald E,Hauser S,Fauci A
et al: Principals of internal medicin,15 th edition, New York McGraw-hill
2001;1:1024-1025.
Disaia PJ, Creasman WT (2002) Germ cell, stromal and other
ovarian tumors. In: DiSaia PJ, Creasman WT, editors. Clinical Gynecologic
Oncology, 5th ed. St Louis: Mosby Year Book ,351-74
Gershenson DM, Deljunco G,
Copelaned LJ, Ruthledge FN (1984)
Mixed germ cell tumors of the ovary. Obstet
Gynecol 64, 200-206.
Ghaemmaghami F, Behtash N,
Soleimani K, Hanjani P (2004)
Management of patients with metastasic GTN. Gynecol Oncol (in press).
Ghaemmaghami F, Modares M,
Arab M et al (2004) EMA-EP regimen,
as first line of multiple agent chemotherapy in high risk GTN patient (stage
II-IV). Int J Gynecol Cancer 14,
360-365.
Hurteau JA and Williams JS (2001) Ovarian germ cell tumors chapter
20 in ovarian cancers, Book Edited by Steephen C, Rubin. G and Sutton P.
Lippincott Williams & Wilkins.
Peccatori F, Bonzzi C, Chiari
S et al (1995) Surgical management
of malignant ovarian germ cell tumors, 10 years experience of 12 patients. Obstet Gynecol. 86, 367-377.
Protopapas A, Milingos S,
Diakomanolis E et al (2003) Miliary
tuberculosis peritonitis mimicking advanced ovarian cancer. Gynecol Obstet Invest 56, 89-92.
Straughn JM, Robertson MW,
Partridge E (2000) A patient
presenting with a pelvic mass, Elevated CA-125, and fever, a case report. Gynecol Oncology 77, 471-472.
Zamir D, Leibovitz I, Polychuck
I et al (2003) Fever of unknown
origin. Acta Clin Belg 58, 356-9.