Practice Essentials
Testicular choriocarcinoma is one of the histologic types of nonseminomatous germ cell tumors (NSGCTs), which along with testicular seminoma constitute the two major histologic groups of testicular cancers. Choriocarcinoma is not uncommonly a component of NSGCTs. [1] Pure choriocarcinoma of the testis is one of the least common but most aggressive forms of NSGCTs. [2]
Like other germ cell tumors (GCTs), choriocarcinoma typically affects younger men. Unlike other such cancers, choriocarcinoma metastasizes hematogenously, and bleeding from metastatic sites is characteristic. At presentation, the testicular primary tumor is often small or even "burned out." Laboratory studies in patients with pure choriocarcinomas typically show marked elevation in beta–human chorionic gonadotropin levels.
In most reports, the tumor responds poorly to radiation and chemotherapy and carries a high mortality rate. Surgery is usually limited to radical orchiectomy for tissue diagnosis. [3] Chemotherapy for disseminated disease is principally with cisplatin-based regimens, particularly combination chemotherapy with bleomycin, etoposide, and cisplatin. [4]
For patient education information, see Testicular Cancer and Testicular Self-Exam.
Pathophysiology and Etiology
Choriocarcinoma recapitulates placental tissue development. For unknown reasons, it metastasizes early via hematogenous routes to the lung, liver, and brain, among others. [3, 5]
Patients with a history of cryptorchidism are at a greatly increased risk of testis cancer (by a factor of 10-40 times). Abdominal undescended testis is associated with a greater risk than the inguinal form. An abdominal testis cancer is more likely to be seminoma, while cancer in a testis that was surgically brought to the scrotum via orchiopexy is more likely to be an NSGCT. Orchiopexy allows for earlier detection by physical examination but does not alter the risk of GCT. Ten percent of patients with a GCT have a history of cryptorchidism. In a series of 125 patients with a history or clinical evidence of cryptorchidism and testis tumor, 3 (2%) were pure choriocarcinoma, which is similar to the overall incidence of choriocarcinoma among GCTs. [6]
Genetic changes in the form of amplifications and deletions are observed predominantly in the 12p11.2-p12.1 chromosomal region. Gain of 12p sequences is associated with invasive growth of seminomas and nonseminomas. In contrast, spermatocytic seminoma shows a gain of chromosome 9, and most infantile yolk sac tumors and teratomas show no chromosomal changes. [7]
Other risks include the following:
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Maternal estrogen exposure
Epidemiology
United States
Testicular GCTs are rare, representing only 1%-2% of all malignancies in males and occurring in 1 of 250 men by age 65 years. However, these tumors represent the most common malignancy in males aged 15-35 years. The incidence rates are 3.7 cases and 0.9 cases per 100,000 per year in White males and Black males, respectively. Subtypes and frequencies of GCTs include the following:
-
Seminoma (40%)
-
Embryonal tumor (25%)
-
Teratocarcinoma (25%)
-
Teratoma (5%),
-
Choriocarcinoma (pure; 1%)
International
The incidence of testis cancer increased worldwide from the early 1960s to the mid 1980s. The malignancy is more common in Whites than in nonwhites. The highest rates are in Denmark (8.4 cases per 100,000 per y) and Switzerland (6.2-8.8 cases per 100,000 per y), and the frequency varies across Europe. In a histologic review of 1010 orchiectomies from 1999 to 2011 from a single Mexican oncology institution, 0.6% were pure choriocarcinomas and 0.9% were mixed germ cell tumors with a predominant choriocarcinoma component. [8]
Age
In a literature review of 10,000 cases of germinal testicular cell tumors, Ramon y Cajal et al found 54 (0.5%) cases of pure choriocarcinoma. Most patients were aged 20-30 years; the oldest patient with a pure choriocarcinoma was 63 years old. [9] The patient died of aspiration shortly after initiation of chemotherapy, so a determination of treatment efficacy in this age group was impossible. In a 2008 review of GCTs in 50 men older than 60 years, only one was found to have a component of choriocarcinoma. [10]
Prognosis
In most reports, choriocarcinoma carries a dismal prognosis due to its early hematogenous spread. Long-term survival in patients with pure choriocarcinoma is rare. [11, 12, 13] A review by Batata et al in 1982 reported a 5-year survival rate of 0% (0 of 20 patients) [14] A 1979 literature review by Vugrin et al found five cases of pure choriocarcinoma with brain metastases; all patients died, and median survival was 1 month despite treatment with multi-agent chemotherapy. [15]
A review of survival after a diagnosis of testicular germ cell cancers in Germany and the United States from 2002-2006 found that 5-year relative survival was lowest with choriocarcinomas: 80.1% in Germany and 79.6% in the US; this compared with survival rates of 93.3% and 91.0% with nonseminomas generally. [16]
A 2014 review by Alvarado-Cabrero et al found that of six patients with pure testicular choriocarcinoma, all died of their disease after a median of 9.5 months; of eight patients with predominant choriocarcinoma, five died of the disease after a median of 27 months, one was alive with disease, and two were alive with no evidence of disease at 60 and 72 months of follow-up, respectively; the latter two patients were the only ones with nonretroperitoneal nodal or pulmonary metastases (M1a disease) on presentation. [8]
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Testicular choriocarcinoma has multinucleated syncytiotrophoblastic cells that drape over smaller cytotrophoblastic cells, which together appear to form a border along a blood-filled villouslike space (upper right). Used with permission from Ernstoff MS, Heaney JA, and Peschel RE, eds. Testicular and Penile Cancer. Malden, Mass: Blackwell Science, Inc; 1998:20.
Tables
S |
LDH |
HCG (mIU/mL) |
AFP (ng/mL) |
||
Sx |
Not assessed |
Not assessed |
Not assessed |
||
S0 |
Normal |
and |
Normal |
and |
Normal |
S1 |
< 1.5 x N |
and |
< 5000 |
and |
< 1000 |
S2 |
1.5-10 x N |
or |
5000-50,000 |
or |
1000-10,000 |
S3 |
> 10 x N |
or |
> 50,000 |
or |
> 10,000 |
*N=upper limit of reference range for the LDH assay
|
|||||
Stage grouping |
T |
N |
M |
S |
Stage 0 |
pTis |
N0 |
M0 |
S0 |
Stage I |
pT1-T4 |
N0 |
M0 |
Sx |
Stage IA |
pT1 |
N0 |
M0 |
S0 |
Stage IB |
pT2-4 |
N0 |
M0 |
S0 |
Stage IS |
Any pT/TX |
N0 |
M0 |
S1-S3 |
Stage II |
Any pT/TX |
N1-3 |
M0 |
Sx |
Stage IIA |
Any pT/TX |
N1 |
M0 |
S0-S1 |
Stage IIB |
Any pT/TX |
N2 |
M0 |
S0-S1 |
Stage IIC |
Any pT/TX |
N3 |
M0 |
S0-S1 |
Stage III |
Any pT/TX |
Any N |
M1 |
Sx |
Stage IIIA |
Any pT/TX |
Any N |
M1a |
S0-S1 |
Stage IIIB |
Any pT/TX |
N1-3 |
M0 |
S2 |
| Any pT/TX | Any N | M1a | S2 | |
Stage IIIC |
Any pT/TX |
N1-3 |
M0 |
S3 |
| Any pT/TX | Any N | M1a | S3 | |
Any pT/TX |
Any N |
M1b |
Any S |
