# First Case of Neuroblastoma‐Like Somatic‐Type Malignancy Arising in the Teratomatous Component of a Mixed Non‐Seminomatous Testicular Germ Cell Tumor in an Adult

**Authors:** Karl Ziade, Jana Kotaich, Serge Assaf, Valerie Aftimos, Adib Ziade

PMC · DOI: 10.1002/ccr3.72216 · 2026-03-06

## TL;DR

This paper reports the first case of a rare testicular tumor with neuroblastoma-like features arising in a teratoma, highlighting the challenges in diagnosis and treatment.

## Contribution

The paper presents the first documented case of neuroblastoma-like somatic-type malignancy in a testicular teratoma.

## Key findings

- The patient, a 25-year-old male, had a mixed non-seminomatous germ cell tumor with teratomatous and embryonal carcinoma components.
- Histopathology and immunohistochemistry confirmed neuroblastoma differentiation within the teratoma.
- The patient achieved complete remission after orchiectomy and chemotherapy.

## Abstract

Somatic malignant transformation (SMT) in germ cell tumors (GCTs) is a rare but clinically significant event. Among non‐seminomatous germ cell tumors (NSGCTs), teratomas can undergo malignant transformation, with neuroblastoma‐like differentiation being exceptionally rare. No standardized treatment protocols exist, and management is typically extrapolated from conventional approaches for GCTs and neuroblastoma. We report the first documented case of neuroblastoma arising within a testicular teratoma in a 25‐year‐old male presenting with a painless right testicular mass. Serum tumor markers showed elevated beta‐hCG, while AFP and LDH were normal. Imaging revealed no metastases. Radical orchiectomy was performed, and histopathology confirmed a mixed NSGCT with teratomatous and minor embryonal carcinoma components, with immunohistochemistry confirming neuroblastoma differentiation. The tumor was staged as pT1 (AJCC 8th edition). The patient completed four cycles of chemotherapy and remains in complete remission. Neuroblastoma arising within a testicular teratoma is an exceptionally rare occurrence, posing diagnostic and therapeutic challenges. Early diagnosis, histopathological evaluation, and multidisciplinary management are crucial for optimal outcomes. Further research is needed to refine treatment strategies for such rare malignancies.

This case highlights the first documented occurrence of neuroblastoma arising within a testicular teratoma, expanding the spectrum of SMT in GCTs. Given the rarity and chemoresistance of such malignancies, early recognition, comprehensive histopathological assessment, and multidisciplinary management are essential for optimizing patient outcomes. This case underscores the need for further research to establish standardized treatment protocols for SMT in GCTs.

## Linked entities

- **Diseases:** neuroblastoma (MONDO:0005072), testicular germ cell tumor (MONDO:0003758), teratoma (MONDO:0002601), embryonal carcinoma (MONDO:0003581)

## Full-text entities

- **Genes:** PLAA (phospholipase A2 activating protein) [NCBI Gene 9373] {aka DOA1, NDMSBA, PLA2P, PLAP}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, GPC1 (glypican 1) [NCBI Gene 2817] {aka glypican}, PHOX2B (paired like homeobox 2B) [NCBI Gene 8929] {aka CCHS, NBLST2, NBPhox, PMX2B}, ENO2 (enolase 2) [NCBI Gene 2026] {aka HEL-S-279, NSE}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, MYCN (MYCN proto-oncogene, bHLH transcription factor) [NCBI Gene 4613] {aka FGLDS1, MODED, MPAPA, MYCNsORF, MYCNsPEP, N-myc}, DES (desmin) [NCBI Gene 1674] {aka CDCD3, CSM1, CSM2, LGMD1D, LGMD1E, LGMD2R}, CGA (glycoprotein hormones, alpha polypeptide) [NCBI Gene 1081] {aka CG-ALPHA, FSHA, GPA1, GPHA1, GPHa, HCG}, SYP (synaptophysin) [NCBI Gene 6855] {aka MRX96, MRXSYP, XLID96}, TNFRSF8 (TNF receptor superfamily member 8) [NCBI Gene 943] {aka CD30, D1S166E, Ki-1}, AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}
- **Diseases:** yolk sac tumors (MESH:D018240), sarcoma (MESH:D012509), GCNIS (MESH:D009373), Neuroblastoma (MESH:D009447), varicoceles (MESH:D014646), squamous cell carcinoma (MESH:D002294), SMT (MESH:C563738), testicular teratoma (MESH:C562472), tumorigenesis (MESH:D063646), testicular neoplasms (MESH:D013736), papillary thyroid carcinoma (MESH:D000077273), carcinomas (MESH:D009369), adenocarcinoma (MESH:D000230), GCT (MESH:C537296), Testicular GCTs (MESH:C563236), epithelial malignancies (MESH:D002277), testicular (MESH:D013733), inguinal hernia (MESH:D006552), pain (MESH:D010146), hydrocele (MESH:D006848), ovarian neuroblastoma (MESH:D010049), terato-oligospermia (MESH:D009845), carcinoid tumors (MESH:D002276), embryonal carcinoma (MESH:D018236), chills (MESH:D023341), mature teratomas (MESH:D013724), NSGCT (MESH:C537844), neuroectodermal tumors (MESH:D017599), metastases (MESH:D009362)
- **Chemicals:** HVA (MESH:D006719), MIBG (MESH:D019797), H&amp;E (MESH:D006371), Caldesmone (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965839/full.md

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Source: https://tomesphere.com/paper/PMC12965839