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Testicular Germ Cell Tumors in Patients with Human
Immunodeficiency Virus Infection
Marcus U. Hentrich, M.D.’
Norbert G. Brack, M.D.’
Peter Schmid, M.D.’
Tobias Schuster, M.D.~
Christoph Clemm, M . D . ~
Reiner C. Hartenstein, M.D.
’
Department of Medicine IV, Division of Hematology-Oncology, Munich Harlaching City Hospital, Academic Teaching Hospital of the University of Munich, Munich, Germany.
Department of Urology Munich Harlaching City
Hospital, Academic Teaching Hospital of the
University of Munich, Munich, Germany.
Oncological Clinic Bad Trissl of the Tumor
Center, Munich, Germany.
Address for reprints: Marcus Hentrich, M.D.,
Department of Medicirie IV, Munich Harlaching
City Hospital, Academic Teaching Hospital of
the University of Munich, Sanatoriumsplatz 2,
81545 Munich, Germany.
Received November 2’1, 1995; revision received
January 29, 1996; accepted January 30, 1996.
0 1996 American Cartcer Society
BACKGROUND. There has been evidence of a higher incidence of testicular germ
cell tumors (GCT) in human immunodeficiency virus (HlV)-seropositive men than
in the non HIV-infected male population. Most authors recommend standard therapy for HIV-positive patients with GCT but the immunosuppressive effects of
Chemotherapy and/or radiotherapy must be considered.
METHODS. The records of all patients in whom testicular cancer was diagnosed
andlor treated at a single institution between January 1986 and July 1995 were
reviewed with regard to HIV seropositivity. Tumor histology, initial staging, treatment, and the patients’ outcomes were analyzed in connection with a review of
the literature.
RESULTS. Six patients with GCT and documented HIV seropositivity at the time of
tumor diagnosis (four homosexuals, one bisexual, and one heterosexual former
intravenous drug abuser) of 192 documented cases of testicular cancer are reported. In addition, 1 patient proved to be HIV seropositive 34 months after completing chemotherapy (vinblastine, ifosfamide, and cisplatin) for Stage IIB (minimal disease) seminoma. Intensified platinum-based chemotherapy was administered to two patients with clinical Stage IIIC (advanced disease) nonseminomal.ous
germ cell tumors (NSGCT).Both patients achieved a transient partial response but
suffered from progressive HIV disease and died 24 and 7 months, respectively,
after orchiectomy. One patient with Stage IIIA (moderate disease) seminoma received four courses of chemotherapy (etoposide, ifosfamide, and cisplatin) and
has remained in complete remission for 40 months. One patient with bilateral
Stage I seminoma underwent adjuvant radiotherapy but was lost to follow-up.
One patient with clinical Stage IIA (minimal disease) NSGCT refused any further
treatment after hemiorchiectomy, but four courses of chemotherapy (cisplatin,
etoposide and bleomycin) had to be given 32 months later because of symptomatic
abdominal disease. A partial remission was obtained and there was no evidence
of active tumor 16 months after the completion of chemotherapy. A retroperitoneal
lymph node dissection was performed in 1 patient with Stage I NSGCT who was
free of disease 111 months after diagnosis. The Centers for Disease Control classification for HIV infection and acquired immune deficiency syndrome (AIDS) did
not change after therapy in two patients, whereas three patients suffered from
progressive HIV disease.
CONCLUSIONS. HIV infection should be considered in patients with testicular cancer who belong to an urban population. Oncologic therapy based on a patient’s
individual situation is recommended. Cancer 1996; 772109-16.
0 1996 American Cancer Society.
KEYWORDS medical oncology, testicular cancer, testicular germ cell tumor, HIV
infection, AIDS, cisplatin, radiotherapy.
N
on-Hodgkin’s lymphoma, Kaposi’s sarcoma, and invasive cervical
cancer are considered AIDS-defining malignancies.’m2
Whether other
2110
CANCER May 15,1996 / Volume 77 / Number 10
malignant diseases occur in higher frequency in HIV-infection is a matter of discussion. The prevalence of human papillomavirus-related anal carcinoma seems to be
greater in HIV infected homosexuals and there is evidence of an increased risk of basal cell carcinoma in HIVpositive hemophiliac^.^,^ Various miscellaneous cancers
have been described in patients with HIV infection, but
epidemiologic studies have failed to demonstrate a statistically significant a s s o ~ i a t i o n . ~ ~ ”
Since the first description of testicular cancer in two
homosexual men with cellular immune deficiency in
1985, several cases of HIV-seropositive patients suffering
testicular cancer have been reported.” Treatment recommendations are conflicting. The Italian Cooperative
Group on AIDS and Tumors (GICAT) reported on 23 patients with testicular germ cell tumors (GCT) associated
with HIV infection, 7 of whom received chemotherapy
that seemed to be well to1erated.l3The authors concluded
that patients with GCT should be offered standard oncologic therapy. However, exact data concerning dose, toxicity, Centers for Disease Control (CDC) classification,
and course of CD4+ cells are missing. Timmermann et
al. found 9 HIV-seropositive patients with GCT out of 272
patients treated for GCT at their in~titution.’~
Because
standard therapy for GCT was well tolerated and in no
case was a patient’s HIV disease classification changed
by antitumor therapy, the authors suggest standard therapy for all HIV-infected patients with GCT. In contrast,
Wilson et al. described two patients with GCT and advanced HIV infection who tolerated chemotherapy
poorly, suggesting the need for a therapeutic procedure
based on a patient’s individual situation.”
We report on six HIV-seropositive patients with testicular GCT treated at a single institution. Another patient
was found to be HIV positive after completion of chemotherapy for GCT.
METHODS
The records of all patients in whom testicular cancer was
diagnosed and/or treated at the Munich Harlaching City
Hospital between 1986 and July 1995 were reviewed with
regard to HIV seropositivity. Tumor histology, initial staging, treatment, and the patients’ outcome were analyzed.
Tumors were classified by stage according to the Lugano
and Indiana classification system. As far as possible the
impact of treatment on the HIV infection was evaluated
comparing CD4-positive cell counts measured before,
during, and after cytostatic chemotherapy or radiotherapy, respectively. HIV disease was classified according to
the revised classification sytem for HIV infection and
AIDS (CDC criteria). I In addition, the available literature
on patients with testicular cancer and HIV infection was
reviewed.
RESULTS
One hundred ninety-two patients with testicular GCT
were diagnosed and/or treated at our institution between
January 1986 and July 1995. Six of these patients (3.1%)
were known to be seropositive for HIV at the time of
tumor diagnosis. One patient proved to be HIV positive
34 months after completing chemotherapy for Stage IIB
testicular seminoma. Patient characteristics are listed in
Table 1. The vast majority of patients were not tested for
HIV antibodies because this procedure is not routinely
performed at our departments. Eighteen patients were
found to be HIV seronegative.
Patient 1
A 35-year-old homosexual businessman, seropositive for
HIV since August 1990 when his CD4 lymphocyte count
was 320/pL (CDC category A2) noticed an enlarged left
testicle in November 1990. Left inguinal orchiectomy was
performed and revealed malignant teratoma. On retroperitoneal lymphadenectomy, 7 of 34 abdominal lymph
nodes were found to be invaded by tumor (Stage IIA,
minimal disease). Alpha-fetoprotein (AFP) and 0-human
chorionic gonadotropin (0-HCG) were within the normal
range. The patient refused adjuvant chemotherapy. In
March 1991, he presented with oral candidiasis (CD4 cell
count of 11O/pL, CDC category B3), pulmonary and hepatic metastases, and bulky abdominal lyrnphadenopathy (advanced disease). Tumor markers AFP and 0-HCG
were elevated at 273 UlmL and 211 IU/L, respectively.
Five courses of intensified chemotherapy were applied
with etoposide, 120 mg/m2,on Days 1-4; cyclophosphamide, 300 mg/m2, on Days 1-4; bleomycin, 12 mg/m2,
given by continuous infusion on Days 1-4; bleomycin,
15 mg bolus injection, on Day 1, and cisplatin, 30 mg/
m2, on Days 1-4 (ECBC).” Apart from severe nausea/
vomiting (World Health Organization toxicity Grade 3)
and peripheral neuropathy (Grade 2), therapy was well
tolerated, and hematologic toxicity was moderate (Grade
1-2). A marker-negative partial response was achieved
but the patient refused surgical removal of residual
masses. During chemotherapy, CD4+ lymphocytes declined from 110 to 20//1L. Regular inhalation of pentamidine as Pneumocystis carinii pneumonia (PCP) prophylaxis was performed starting in March 1991. In September
1991, the patient suffered focal seizures and transient
hemiplegia and cerebral irradiation had to be performed
because of newly diagnosed cerebral metastases. During
irradiation, a cytomegalovirus-retinitis developed that
was consistent with the diagnosis of frank acquired immune deficiency syndrome (AIDS) (CD4, count of 10ipL;
CDC category C3), and could successfully be treated with
ganciclovir. In February 1992, a peripheral pancytopenia
was diagnosed requiring transfusions of platelets and
erythrocytes. The patient refused an examination of the
Testicular Germ Cell Tumors and HlVlHentrich et al.
2111
TABLE 1
Patients Characterislics,Treatment, and Outcome
Patient
No.
lnitital CD(:
category'
Histologylclinical stage
~~~
1
A2
TeraromalllA
2
3
4
.A2
SemiiioniailllA
R3
Al
EinbryonalllllC
Bilateral Serninoma!l
J
A1
G
-
,
Seminoma and Embryoiiallllh
Seminoma and leratomall
SeniinomaiIlH
Last CDC
Category
Primary therapy
Further therapy
Left orchiectoniy KIA
Right orchiectomy PEl i4r)
I.efr orchiertomp
Bilateral orchiectoniy
Paraaortic irradiation
left orchiecioniy
Right orchiectomy R I A
Left orchiectomy
ECRC (5x1: cerebral irradiation
None
I-:CBC Qx), PEl ( I r )
None
(3
A2
c3
PEB (4x1
Sone
VIP 14x1
I32
A2
A3
survival
~~
A2
Died :AIi)S)
Stld 14 - b
Ilird !AII)S)
SEI) lost 10 folio's-up
SFO 527''
SEI) 11 I T
i.os1 to follo\v-up
(bni~ol:1X:BC: rroposide!cispla~in/blrnm~cin/c~tlopl~r~spl~am~d~~:
I'FI: cisplaiin!rloposid~~!iiosia~iiide:PFH: c i s ~ ~ l a r i n ! e f o p n s i ~ l ~ i I ~UP:
l ~ ~ ~vinblajliiir!iiuriaiiiidricisplatin;
~n~ri~i:
KID
o l diswr: FHA. r?\roperiroirralIymphadrireriomy: -. no1 repimed.
"lime IJIluiiior diagnusis.
' \lunrhs froin lieniirirrhiectoniy.
110 widenc?
bone marrow bul chemo- and radiotherapy as well as
treatment with ganciclovir might have contributed to myelosuppression. There was no secondary infection and
granulocyte-coloiiy stimulating factor (G-CSF) was not
used. Acute gastrointestinal bleeding (hemoglobin, 3 g/
dl,) occurred in September 1992. Two months later, the
patient died because of recurrent acute, severe gastrointestinal and cerebral bleeding.
Patient 2
A 46-year-old honiosexual male nurse was admitted in
March 1992 with a 2-year history of swelling of the right
testis. His serum was reactive to HIV antibodies in 1986.
Right orchiectomy and clinical staging led to the diagnosis of clinical Stage IlIA (moderate disease) pure seminoma. p-HCG was slightly elevated at 6.2 I U / L (normal,
< 5 I U / l J . At this time, the CD4+ lymphocyte count was
497/pI. without evidence of symptomatic HIV disease
(CIIC category A2).tie received 4 courses of chemotherapy with etoposide 75 mg/m'; ifosfamide, 1.2 g / m 2 ,and
cisplatin, 20 ing/m.!, on Days 1-4 (PEI)" which was well
tolerated. The patient attained a complete remission and
was free of disease 44 months after diagnosis. During
chemotherapy, his t3D4 + lymphocytes declined from 497
to 297/p1,, but subsequently increased to 441 /PI,. The
patient is doing well and does not receive antiretroviral
treatment. His latest (XI4 t lymphocyte count was 3651
pI. (CDC category A2).
Patient 3
A 45-year-old heterosexual unemployed varnisher was
transferred to our department in June 1993. Three
months before admission, left orchiectomy had been performed because of an enlarged left testicle that had been
noticed by the patient for approximately 2 years. Histo-
logic examination had revealed embryonal carcinoma.
AFP and P-HCC were within the normal range, and lactic
dehydrogenase (LDH) was elevated at 1020 L J / L Abdominal lymphadenopathy and pulmonary metastases were
found o n further examination (Stage IIIB, moderate disease). There was a history of hepatitis 13 and C and he
had been addicted to drugs for many years until 1982.
The patient was known to be positive for HIV since 1990
when he suffered oral candidiasis ( 0 4 lymphocyte
count, 159IpI.: CDC category B3). Since then, he had received azidothymidine, 500 mg per day, and inhaled pentamidine as PCP prophylaxis at %week intervals. Three
months after diagnosis of testicular cancer, the patient
had agreed to be treated with chemotherapy when computed tomography documented progressive disease with
pulmonary and hepatic metastases that were increasing
in size (Stage IIIC, advanced disease). In June 1993, the
patient was given a four-drug chemotherapy ( E C K ) supported by (;-CSF.'" Because of severe side effects (hematologic toxicity WHO Grade 4 , oral mucositis Grade 3 ) ,
the dose of the second course had to be reduced by 25%.
A partial response was obtained with complete disappearance of hepatic metastases. However, toxicity remained considerable (hematologic toxicity WHO Grade
4, oral mucositis Grade 3, diarrhea Grade 3 , and pain
Grade 3). During chemotherapy, his CD4+ lymphocyte
count declined from 108 to 18/pI,. After the second chemotherapy course, the patient developed respiratory failure due to severe pneumonia, which improved with some
delay after broad-spectrum antibiotic therapy (CDC category C3, AIDS). He received another course of chemotherapy with cisplatin, 20 mg/ni'; etoposide, 100 mg/m', and
ifosfamide, 1 g/mLfollowed by G-CSF. Once more, hema..
tologic toxicity was severe (Grade 4) and the patient suffered neutropenic sepsis that subsequently improved by
2112
CANCER May 15,1996 / Volume 77 / Number 10
adequate therapy. However, abdominal lymphadenopathy again increased in size. In view of his poor tolerance of
chemotherapy and tumor progression, further cytostatic
treatment was withdrawn. After recovery, the patient was
discharged, and he died at home a few weeks later.
Patient 4
In May 1993, a 33-year-old homosexual businessman presented with a 5-month history of an enlarged and tender
left testicle. He was known to be HIV seropositive since
1989. His CD4 lymphocytes were lowered to 540/pL at
the time of admission (CDC category All. Left orchiectomy led to the diagnosis of pure seminoma (Stage IA,
minimal disease). AFP and P-HCG were within the normal range and metastases could not be found on further
examination. However, ultrasound revealed a suspect
area within the right testicle. Right orchiectomy was subsequently performed and another Stage IA (pT1) pure
seminoma was documented. Both testes showed intratubular germ cell neoplasia. The patient was treated with
adjuvant infradiaphragmatic paraaortic irradiation and
tolerated therapy without complication. His CD4 lymphocyte count declined from 540 to 3461pL during radiotherapy but there was no evidence of HIV-associated disease (CDC category A2).Unfortunately, the patient was
lost to follow-up after discharge.
Patient 5
A 40-year-old bisexual programmer was admitted in July
1991 with a 3-day complaint of left inguinal pain and
an enlarged left testicle. Six weeks before admission, his
serum was reactive to HIV antibodies. There was a positive history of syphilis, gonorrhea, and hepatitis B. Left
orchiectomy was performed and revealed Stage pT2 seminoma with focal areas of embryonal carcinoma. P-HCG
and AFP were within normal limits. An abdominal computed tomography scan showed some paraaortic lymph
nodes to be questionably enlarged (clinical Stage IIA,
minimal .disease). However, the patient refused a retroperitoneal lymphadenectomy. CD418 ratio (0.54) and the
CD4 lymphocyte count (500/pL) were significantly lowered at the time of diagnosis (CDC categoryA1). In October 1993, he developed oral candidiasis. At this time, the
CD4 count had declined to 380/pL and the CD4/8 ratio
was markedly depressed at 0.2 (CDC category B2). In February 1994, the patient complained of severe abdominal
pain and a subsequent computed tomography scan demonstrated enlarged abdominal lymph nodes (Stage IIB).
Levels of AFP and P-HCG were normal. A tumor biopsy
showed embryonal carcinoma. Between April and July
1994,the patient received 4 courses of chemotherapy with
cisplatin, 20 mg/m’, on Days 1-4; etoposide, 100 mglm’,
on Days 1-4, and bleomycin, 30 mg/m2, on Days 1, 8,
and 15 (PEB). Because of advanced HIV infection (CDC
category B2), doses of cisplatin and etoposide were reduced to 80% of the original PEB protocol.’” Hematologic
toxicity was moderate (WHO Grade 3). A partial remission
could be achieved and secondary surgery was not performed to avoid further immunosuppression. However, a
positron-emission tomography-scan showed no evidence
of vital tumor within the abdominal residual mass. The
patient did not want to have his CD4 and CD8 lymphocyte
values checked but his clinical CDC category B did not
change during chemotherapy. In February 1995, he suffered severe herpes zoster that improved with treatment
with acyclovir. He has remained well without evidence of
progressive HIV disease nor of recurrent testicular cancer
16 months after the completion of chemotherapy.
Patient 6
A 26-year-old homosexual man, who had been known to
be HIV positive since April 1986, presented in August 1986
with a 3-week history of a hard swelling of his right testis.
P-HCG was slightly elevated at 10 mU/L (normal: up to
5 mU1L) and AFP was within the normal range. The CD41
8 ratio was moderately depressed at 0.68. Right orchiectomy revealed a Stage I testicular germ cell tumor of
mixed histology (seminoma and intermediate type malignant teratoma). The level of P-HCG normalized postoperatively and no metastases were found on retroperitoneal
lymph node dissection. There has been no evidence of
recurrent disease on regular follow-up examinations for
more than 9 years. The patient is doing well and does
not suffer HIV-associated diseases. His latest CD4+ lymphocyte count was 350/pL (CDC categoryA2) with a CD4/
8 ratio markedly lowered at 0.3.
Patient 7
A 35-year-old homosexual mechanical engineer was
transferred to our department in October 1987 with a 4month history of abdominal pain and recurrent vomiting.
A retroperitoneal space-occupying lesion of 4 cm x 4.5
cm, which had been revealed on abdominal ultrasound,
was characterized as seminomatous in origin on explorative laparatomy. Levels of AFP and P-HCG were normal.
Left orchiectomy was performed and histologic examination confirmed the diagnosis of a burned-out seminoma.
At this time, the patient was found to be HIV seronegative.
He received four courses of chemotherapy with vinblastine, ifosfamide, and cisplatin (VIP) and attained a durable complete remis~ion.’~
In July 1990, another HIV antibody test was positive. There were no HIV-associated
symptoms, and the CD4+ lymphocyte count was 300/pL
(CDC category A2).In March 1993, the patient showed
no evidence of recurrent GCT or symptomatic HIV disease, but the CD4+ cell count had declined to 1271pL
(CDC categoryA3). Antiretroviral treatment and PCP pro-
Testicular Germ Cell Tumors and HIWHentrich et al.
2113
TABLE 2
Reported Cases of Testicular Germ Cell Tumors (GCT) in HIV Seropositive Patients
No. of
Year
Patients
2
1
Histology (SINSIMx)
Chemotherapyapplied (no. of patients)
2( P W
1 (PVBIPVC)
3 (PEB)
1 (PVBD)
None
None
VB for KS
4 (3PEB 1 PE)
-
1985
1985
1987
1988
1989
1989
1989
1989
1990
1991
1991
1991
1992
1993
1993
1993
1994
1994
1994
1994
2
15
3
23
--
(-111 1)
(- 11 1 -)
(l/-/-)
(5111-)
(11-/-)
(21-1-1
(2121-1
(21-/-)
(1/11-) (bilateral)
(1/-1-)
(4/-1-) (1 bilateral)
(1 1-14) (1 bilateral)
(21-1-) (1 bilateral)
(10151-)
(131101-)
Total
79
(4512115)
1
6
1
2
4
2
1
1
3
1
4
3
3
1
~~~~~~~
None
2
None
1
None
1
-
26
Reference no.
-
12"
23"
24
25
26
27,28,29
30
31
33
34
22
35
15
9
36
37
38
14,39,3:!
40
13
-
1 (Carbo)
7 (3PEB,2PVB lPVB1PEB 1 rn-BACODIPEB)
7 (6 PEB 1 PVB)
~~
Radiotherapy applied
(no. of patients)
1
None
1
6
-
10
22
~~~~~
~~
~
S: seminoma; NS: nonsemincmatous GCT Mx: mixed histology HIV: human immunodeficiency V~IUS; PW cisplatin, vinblastine, bleomycin; PEB cisplatin, etoposide, bleomycin; PVC: cisplatin, vinblastine,
cyclophosphamide; PE: cisplatin, etoposide; PVBD cisplatin, vinblastine, bleomycin, dactinomycin: Carbo: carboplatin; m-BACOD: methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexarnethasone; VB vinblastine, bleomyin; KS: Kaposi sarcoma: -: not reported.
a Clinical and pathologic diagnosis because HlV antibody tests were not available in 1985.
phylaxis were recommended. However, the patient was
unfortunately lost to follow-up.
DISCUSSION
It has been suggested that testicular cancer, which is the
most common malignancy in men aged 20-34 years
with a low age-adjusted incidence rate of 4 per 100,OOO,'o
occurs with a higher frequency in HIV-positive men than
in the healthy male p o p u l a t i ~ n . ' ~ Moyle
~~'~'~
et al., on the
basis of 3 seminomas in 2205 HIV-positive patients, and
Wilson et al., reporting on 5 GCTs in 3015 HIV positive
men, calculated a considerably higher GCT incidence in
HIV-positive individ~als.''~'~
However, this assumption
could not be confirmed by large epidemiologic studies.5,8-11
Seventy-nine cases of patients with testicular GCT
and HIV infection have been documented in the available
literature (Table 2).23-40 Data of 25 patients with testicular
cancer reported by Tessler and Catanese are difficult to
interpret because the authors did not differentiate patients who were found to have AIDS or AIDS-related complex from those who were considered to run a risk of
developing AIDS.21 Furthermore, two cases of extrago-
nadal GCT in HIV-positive patients have been reIt is difficult to establish the prevalance of HIV seropositivity on the basis of an urban testicular cancer population because HIV-infected individuals are mainly concentrated in metropolitan areas, whereas the prevalence
of testicular cancer is the same in rural and urban environments. There are no data on the expected incidence
of HIV-1 in young men in Munich, Germany. However,
since the onset of the HIV epidemic in Germany, the city
of Munich has produced one of the highest rates of HIV
infection. As of June 1995, 55% of all HIV-infected people
and 57% of all AIDS patients registered in Germany lwed
in 6 major
For this reason, one should be careful
about epidemiologic conclusions drawn on the basis of
our Munich experience. In addition, the number of six
HIV-seropositive patients with GCT may be too low because testing for HIV antibodies was only performed in
patients with at-risk behavior or at a patient's special
request, with the vast majority of patients remaining untested. Therefore, all patients with GCT should be routinely tested for HIV-1 prospectively so that the true incidence of the association can be determined.
2114
CANCER May 15, 1996 / Volume 77 I Number 10
Some authors presume that special histologic patterns predominate but more cases of seminomas than
nonseminomas have been reported in the available literature (48 vs. 30; Tables l and 2). However, the number
of cases is still too small for unequivocal conclusions,
especially because seminomas account for approximately
40-55% of all testicular GCT, depending on the series
The available literature described the cases of four
HIV infected patients with bilateral GCT (three patients
with synchronous GCT and one with consecutive bilateral
GCT) and we added another case of Stage I synchronous
bilateral pure ~eminoma.’~“‘”~”~
It is worth noting that
this incidence of 5.9% (5 of 85 HIV-seropositive patients
with GCT) is higher than the bilateral frequency of 1.54.3% reported in the literature.45246
The prognosis of bilateral testicular cancer is generally
Our patient (Patient 4) underwent bilateral hemiorchiectomy and received adjuvant infradiaphragmatic irradiation. During
radiotherapy, a slight increase in the CD4/8 ratio could
be observed despite declining CD4 and CD8 cells. The
CDC category changed from A1 to A2 at the end of radiotherapy. Unfortunately, the patient was lost to follow-up.
Tolerance of radiotherapy in HIV-infected patients
may depend on the CDC category they correspond with
and severe side effects of irradiation should be considered, particularly in patients in advanced stages of HIV
disease.
Patient 1 (CDC category B3) developed cytomegalovirus-retinits (primaryAIDS-definingillness) during radiation therapy for symptomatic cerebral metastases with
a further decline in the CD4 and CD8 lymphocyte counts
as well as the CD4/8 ratio. It cannot be ruled out that
the low level of CD4+ lymphocytes at the beginning of
cerebral irradiation may be responsible for this opportunistic infection. However, the available literature describes several cases of opportunistic infections developing during radiotherapy. Beuzedoc et al., for example,
reported on a HIV-positive patient with Stage IIB seminoma (CDC category B3) who underwent radiotherapy,
resulting in a marked decline in the CD4 counts from
163 to 5/mL3 followed by life-threatening opportunistic
infections.’’ Three cases of PCP after radiotherapy for
Stage I seminoma in HIV-infected men have also been
~ b s e r v e d . “ , ~At~ ~least
~ ‘ one of these patients was in an
advanced stage of HIV disease with a CD4/8 ratio markedly depressed at 0.13.31
By contrast, there are also reports of HIV-seropositive
patients with testicular GCT who underwent radiotherapy
without major complications, although data on the CD4+
lymphocyte count before and after therapy are not available in most of these case^.'^"^^^'
Radiation sensitivity of CD4 lymphocytes has been
described in patients with breast cancer not infected by
HIV and further studies on the influence of radiotherapy
on CD4+ lymphocytes are necessa~y.~’
There is also evidence of a suppressive effect of the combination of local
radiation and chemotherapy on CD4+ lymphocyte
counts in HIV-negative patients with breast and ovarian
~ a n c e r . ~Because
~ ’ ~ ’ declining numbers and percentages
of CD4+ lymphocytes have been established as an important predictor of progression from asymptomatic HIV
infection to AIDS, the course of CD4+ lymphocytes
should be monitored regularly during radi~therapy.~’,~’
In conclusion, radiotherapy should be the treatment
of choice in HIV-infected patients with low stage seminoma unless an AIDS-defining disease is present or CD4+
lymphocyte counts are severely depressed.
Surgical procedures such as orchiectomy and retroperitoneal lymphadenectomy obviously did not alter
CD4+ lymphocyte counts in our patients and similar observations have been made by other a ~ t h o r s . ’ ~ , Nev~’~~~~~’
ertheless, primary chemotherapy with two courses of PEB
in Stage I and three courses of PEB in Stage IIA/B nonseminomatous germ cell tumors (NSGCT) might be an
alternative to retroperitoneal lymphadenectomy.
Our first patient with resected Stage 2A NSGCT and
negative tumor markers refused adjuvant chemotherapy
for fear of deterioration of his immunologic status (CDC
category A2 at the time). Early tumor relapse occurred
(advanced disease) and forced the initiation of chemotherapy when HIV infection had already progressed to
CDC category B3 (oral candidiasis). He achieved a
marker-negative partial response lasting for 6 months, at
which time cerebral metastases became symptomatic.
Three other cases of HIV seropositive males with
Stage IIA NSGCT who were observed after complete retroperitoneal lymph node dissection have been reported in
the available literat~re.’~”‘
Two presented with pulmonary metastases and supraclavicular adenopathy 1 and 9
months later, respectively. At this time, their immunologic status had deteriorated to AIDS and chemotherapy
was poorly t01erated.l~The other patient did not suffer
recurrent testicular cancer and died of AIDS 3 years after
his HIV infection diagn~sis.~’
Thus, to avoid early tumor relapse, adjuvant chemotherapy might be recommended for patients with Stage
IIA NSGCT who do not demonstrate AIDS-indicatingconditions.
In Patient 1, the intensified chemotherapy (ECBC)
led to a decline of CD4+ cell counts from 110 to 201pL.
Patient 3, with advanced embryonal carcinoma and CDC
category B3 indicating severe immunosuppression, tolerated the same protocol (ECBC) poorly. His number of
CD4+ lymphocytes decreased from 108 to 18/pL and
overt AIDS developed during cytostatic treatment. This
corresponds with another report on a patient suffering
both advanced GCT and advanced HIV infe~tion.’~
Testicular Germ Cell Tumors and HlVlHentrich et al.
Lymphocyte depletion during treatment with intensive chemotherapy for cancer in HIV-seronegative patients has been described recently. In addition, thymic
capacity for regeneration of CD4+ lymphocytes appears
to diminish with age.52,53
Interestingly, the results of very
dose-intensive regimens for patients with AIDS-related
lymphomas were also associated with high rates of complicating opportunistic infections leading to death in 2878% of patient^.^^ There is a strong evidence of an increased susceptibility of opportunistic infections in patients with CD4+ cell counts of less than 200lyL and this
phenomenon could be one reason for the poor outcome
of patients with advanced HIV infection treated by intensive chemotherapeutic regimens.55
By contrast, our second patient, who had moderate
disease and was CDC category A l , as well as Patient 5 ,
who had minimal disease and was CDC category B2, tolerated standard chemotherapy well (PEB and PEI, respectively). There are some reports on standard chemotherapy for treatment of GCT in HIV-seropositive men and
PEB does not seem to be associated with more complications in these patient^.'^,^"*^' Vaccher et al., for example,
reported five patients with advanced disease treated with
PEB, which was overall well tolerated without further development of opportunistic infection^.'^ In another series
of seven men receiving PEB or PVB, the patients' HIV
disease classification (CDC category) did not change in
any case.39Because vinblastine is less immunosuppressive and less injurious to platelet production than bleomycin, PVB mighr be substituted for PEB for patients with
Stage II/III NSGCT, minimal or moderate disease, but
vinblastine neurotoxicity must be considered.
In summary, testicular cancer does not appear to be
an AIDS-defining malignancy. Oncologic treatment
should be tailored to the individual HIV-positive patient
with testicular GCT. To avoid therapy-associated complications, CD4+ lymphocyte counts should be monitored
during therapy and PCP prophylaxis must be applied if
the CD4+ lymphocyte count is less than 200lyL. Hematopoetic growth factors (G-CSF) should follow all myelosuppressive therapy and antibiotic prophylaxis might be
given when granulocytes start to decline.
PEBlPVB is recommended in HIV-infected patients
with NSGCT, minimal or moderate disease, and PEI
should be given to patients with advanced seminoma.
Intensive chemotherapy regimens are not indicated for
patients with advanced HIV infection and Stage IIIC testicular cancer (liver andlor brain metastasis).
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