Background

We present the first reported case of transformation of a germ cell tumor (GCT) into a retroperitoneal schwannoma.

Case Presentation

A 48-year-old man who had undergone a left orchiectomy and adjuvant chemotherapy in 2017 for a mixed GCT was referred for consideration of robot-assisted laparoscopic retroperitoneal lymph node dissection (RPLND) for a slowly enlarging para-aortic node. Three years after initial treatment his tumor markers remained normal. Histology from orchiectomy demonstrated a mixed GCT consisting of 70% embryonal carcinoma, with possible elements of seminoma, trophoblastic giant cells and yolk sac tumor.

The para-aortic node had increased from 7 mm to 17 mm in a year. 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) showed low avidity within the enlarged node with a maximum standardized uptake value (mSUV) of 2.1, and no other sites of disease (fig. 1).

Figure 1.Left panel, CT shows enlarged para-aortic node. Right panel, 18F-FDG-PET scan shows low avidity (mSUV 2.1) within same node.

A left template supine robot-assisted laparoscopic RPLND was performed with successful dissection of preaortic, para-aortic and interaortocaval lymph nodes and left gonadal vein. Macroscopic examination of the excised nodes revealed a 17 mm solid spherical nodule (fig. 2) consistent with that seen on PET and computerized tomography (CT). Histological analysis confirmed a schwannoma entirely replacing the node and 33 other normal nodes. Fluorescence in situ hybridization (FISH) analysis of the schwannoma was positive for the presence of isochromosome 12p (fig. 3), strongly supporting a GCT origin rather than an incidental de novo finding. The patient recovered well postoperatively and was discharged back to his oncology team to resume surveillance.

Figure 2.Left panel, 17 mm schwannoma excised with clear margin. Right panel, spindle-shaped cells with nuclear palisading arranged in interlacing bundles characteristic of schwannoma. H&E, reduced from ×100.

Figure 3. Interphase FISH shows presence of two 12p isochromosomes (arrows) identified by 1 red (represents centromeric region of chromosome 12) and 2 green (represents p-arm of chromosome 12) signals.

Discussion

Enlarged retroperitoneal nodes with normal tumor markers in the context of testis cancer present a diagnostic challenge. There may be a role for FDG-PET in the evaluation of equivocal nodal findings seen on CT. ¹ However, this requires further study because a negative node on PET may still harbor small volume viable cancer, and furthermore PET avidity cannot distinguish between viable cancer, teratoma and a reactive node. Minimally invasive RPLND offers a diagnostic and potentially therapeutic option for resolving uncertainty in this situation with relatively little morbidity. ²

In this case the final histology was surprising and did not conform to any of the conventional pathology seen in this context such as seminomatous GCT or nonseminomatous GCT (NSGCT) including yolk sac, embryonal, choriocarcinoma and teratoma. As the schwannoma had entirely replaced the node, it was unclear if this was an incidental tumor or a transformed teratoma. Teratoma can range from benign, well-differentiated (mature) cystic lesions to those that are solid and malignant (immature). Furthermore, teratomas may be monodermal, instead of tridermal, and highly specialized with 1 cell type. ³ Somatic transformation occurs in 3% to 6% of teratomas and is one of the reasons for recommending surgical excision if teratoma is suspected, with the other reason being growing teratoma syndrome. Somatic transformation is characterized by differentiation of pluripotent teratoma cells into somatic tumor cells. The most frequent histological types seen in transformation are rhabdomyosarcoma, adenocarcinoma and primitive neuroectodermal tumors. ³ A range of other histological transformations have been described, but not schwannoma.

When unusual histology is encountered, distinguishing between GCT-associated tumor and nonGCT is not straightforward. Sometimes this distinction is critical to deciding further management. This is where molecular genetic analysis can help. ⁴

Gain of the short arm of chromosome 12, most commonly as an isochromosome 12p ( ⁱ12p), is a highly nonrandom chromosomal marker seen in >80% of GCTs. ⁵ During transition from germ cell neoplasia in situ to invasive tumor, neoplastic cells acquire additional genetic material on the p-arm of chromosome 12, usually in the form of ⁱ12p or the amplification of specific areas of chromosome 12 (12p gain). ⁵

While ⁱ12p is not 100% specific for GCT, the literature indicates it has diagnostic and possible therapeutic relevance for these tumors. ⁴ⁱ12p can be identified on interphase nuclei by FISH, simultaneously using a probe specific for the centromeric region and the short (p) arm of chromosome 12. ⁱ12p can also be detected using quantitative polymerase chain reaction (PCR). ⁱ12p is not seen in de novo schwannomas.

The presence of ⁱ12p in this case effectively confirms the diagnosis of teratoma transformation in the retroperitoneum to schwannoma, which has not previously been described.