Keywords
Pediatrics - rhabdomyosarcoma - secondary somatic-type malignancy - testicular germ
cell tumor
Introduction
Testicular germ cell tumors (GCT) are the most common malignancy in males aged 15–34.[1] The transformation of testicular GCTs into secondary somatic-type malignancies is
rare. We present an unusual case of a mixed nonseminomatous malignant GCT with an
embryonal rhabdomyosarcoma (RMS) component in a 15-year-old male. We highlight our
experience in diagnosing and treating such a tumor at a pediatric institution, utilizing
Children's Oncology Group (COG) protocol.
Methods and Materials
The patient's medical records were accessed and reviewed at Cook Children's Medical
Center in Fort Worth, Texas.
Case Report
Two months following surgical repair of bilateral varicocele, a 15-year-old male with
medical history remarkable for Osgood-Schlatter disease complained of a painless,
hard mass involving his right testicle. A right radical orchiectomy was performed,
and postsurgical resection was achieved with negative margins. Histopathologic examination
of the mass sized 3.3 cm × 2.8 cm × 2.3 cm, showed a mixed malignant GCT with a secondary
somatic-type malignant component. There were large areas of a primitive small cell
malignancy with pleomorphic cells containing variable amount of eosinophilic cytoplasm
[Figure 1]. A few large “strap” cells resembling fetal muscle were seen. Immunostaining of
the tumor confirmed these sarcomatous areas were highlighted with the myogenic markers
desmin and myogenin. The tumor did not express the GCT markers OCT3/4, placental alkaline
phosphatase, or alpha-fetoprotein (AFP). The tumor constituted the following: teratoma
(20%), embryonal RMS (60%), embryonal carcinoma (15%), and yolk sac tumor (<5%). The
tumor was limited to the testis and epididymis, extending to the tunica albuginea
but not the tunica vaginalis. There was no evidence of vascular or lymphatic invasion.
In addition, ipsilateral retroperitoneal lymph node dissection, computed tomography
(CT) scans of the chest, abdomen, pelvis, and bone scan showed no evidence of distant
metastases.
Figure
The mixed GCT component was deemed Stage I because of complete resection and lack
of metastasis; the RMS component was also deemed Stage I due to location in nonbladder/prostate
genitourinary tract and Group I due to complete surgical resection of the mass. Initial
laboratory values showed that AFP and human chorionic gonadotropin (hCG) were not
elevated. We characterized this testicular tumor as low risk.
We then targeted the RMS component with chemotherapy, utilizing COG protocol ARST0331:
4 cycles of vincristine, dactinomycin, and cyclophosphamide followed by 4 cycles of
vincristine and dactinomycin. Following 24 weeks of therapy, the patient's CT scans
of the chest, abdomen, and pelvis were negative, and AFP and hCG laboratory values
remained unremarkable. Approximately 34 months posttherapy, the patient remains in
good health and has shown no evidence of tumor recurrence. Of note, the patient has
sustained recurrence of bilateral varicocele.
Discussion and Conclusion
Childhood extracranial GCTs, arising from primordial germ cells, are broadly classified
into teratomas, malignant GCTs, and mixed malignant GCTs. Malignant GCTs are subdivided
into seminomatous and nonseminomatous GCTs. Seminomatous GCTs are further classified
into seminoma, dysgerminoma, and germinoma; nonseminomatous GCTs are divided into
yolk sac tumor, choriocarcinoma, embryonal carcinoma, and gonadoblastoma.[2]
The development of a secondary somatic-type malignant component from a primary GCT
is a documented phenomenon; however, those arising from testicular masses are rare.[3] Possible secondary somatic-type malignancies include adenocarcinoma, primitive neuroectodermal
tumor, RMS, and leukemia.[4] It is presumed that the RMS arises from the teratoma component of the mixed germ
cell neoplasia. Teratomas in postpubertal males are malignant and often contain highly
atypical areas resembling sarcomas, but these are generally intermixed with other
more mature teratomatous elements. To be accurately classified as a “teratoma with
somatic-type malignancy” requires overgrowth of the sarcoma, or less commonly carcinoma,
to occupy at least a low power (×4) field.[5] The growth may be nodular or infiltrative.[3] In our case, the primitive myogenic sarcoma comprised more than half of the neoplasm.
Primitive malignant sarcomas are seen in rare cases of spermatocytic seminoma, including
a few where the sarcoma is a RMS; however, these tumors generally arise in older adult
men and have a seminoma component, which was not seen in our case.[5] Yolk sac tumors may also occasionally harbor a component of malignant sarcoma. On
occasion, metastatic disease will harbor sarcomatous elements, not seen in the primary
neoplasm.[3]
Currently, there are several reported cases that demonstrate the challenge of treating
patients with testicular tumors with associated rhabdomyosarcomatous components. The
major challenge in treating these tumors is that the chemosensitivities of GCT and
RMS do not overlap; GCT is sensitive to cisplatin while RMS is not.[3] One of the earliest reports of sarcomatous differentiation from a testicular GCT
shows that following eradication of the primary germ cell component by cisplatin therapy,
the sarcomatous component, which was a minor component in the initial specimen, became
the predominant species.[6] Stamatiou et al. also describe a similar case with the treatment of the GCT with
cisplatin therapy. The patient, in this case, died after metastasis-related complications.[7] These two aforementioned cases highlight that although GCT may be the primary tumor,
failure to consider the sarcomatous component in therapy may be deadly to the patient.
Remaining reports highlight various methods of therapy, for example: one targeting
the GCT component, one targeting the rhabdomyosarcomatous component, and one utilizing
surgical resection without chemotherapy.[3],[6],[8] These cases demonstrate the lack of clear treatment guidelines.
Our greatest challenge in prescribing treatment for this tumor was understanding how
to target the disparate components. Current literature suggests that active surveillance
strategies are the recommended treatment for Stage I testicular GCT due to their effectiveness
and minimization of adverse effects from chemotherapy and radiation.[9] Because this patient's primary testicular GCT was Stage I, we chose to follow the
strategy of COG study AGCT0132, which describes that surgery and surveillance are
sufficient in managing patients with low-risk non-seminoma tumors.[1] Furthermore, we targeted the RMS component with chemotherapy as indicated in the
current literature. According to COG protocol ARST0331, in cases of low-risk RMSs,
a 24-week therapy schedule is recommended with 4 cycles of vincristine, dactinomycin,
and cyclophosphamide followed by 4 cycles of vincristine and dactinomycin.[10] We followed this protocol, and the patient finished treatment without any complication.
Regardless, we recognize that such cases remain tremendously challenging, given the
lack of consensus in treating two malignancies whose chemosensitivities do not overlap.
There is little debate over the fact that successful surgical resection aimed toward
securing negative margin remains key inadequate treatment of those with localized
disease.[11] With regard to choice of chemotherapy postoperatively, there is some suggestion
that malignant transformation of GCT responds poorly to cisplatin-based therapy.[4] In fact, Donadio et al., based on the review of 12 patients, suggest that choice
of chemotherapy should be guided by transformed histology unless there is residual
GCT in conjunction with the malignantly transformed element.[4] In another paper, Korfel et al. describe treating a patient with a testicular GCT
and widely metastatic RMS with chemotherapy consisting of epirubicin, ifosfamide,
etoposide, and cisplatin followed by high-dose chemotherapy and stem-cell rescue,
resulting in complete response lasting several years.[12] Based on literature review, in treating a pediatric patient, we suggest that choice
of chemotherapy agents should be influenced by the transformed histological element
as the transformed element may not be responsive to cisplatin-based therapy [Figure 2].
Figure
Our report has limited value given singular patient; however, reporting on large series
of such patients will be challenging given the rarity. We suggest developing a multi-institutional
trial to include both adolescents and adults whose outcomes may be followed closely
to optimize treatment for future patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
