A novel perspective on dissemination: somatic metastasis of germ cell tumors from the central nervous system

Abstract

Purpose: Primary germ cell tumors (GCTs) of the central nervous system are rare malignancies, with somatic metastasis being even less common. This study aims to propose a novel classification framework for dissemination patterns in CNS GCTs.

Methods: A group of 4 patients with somatic metastasis were identified among 284 germ cell tumors. The characteristics of patients were identified through clinical history, imaging, and histopathology. Hematoxylin-eosin (H&E) and Immunohistochemistry (IHC) confirmed the pathological features, while radiology was used to determine the temporal and spatial characteristics of metastasis. Univariate analysis was conducted to assess the factors contributing to abdominal spread. Fisher's exact test was used for categorical data analysis. The dissemination process was systematically analyzed.

Results: This disease is extremely rare, and the progression of metastatic germ cell tumors is often complex. All four patients underwent surgery, radiotherapy, and chemotherapy. In one case, the tumor spread to the anterior superior mediastinum via hematogenous metastasis; in two cases, it spread to the abdominal cavity through a ventriculoperitoneal shunt; and in one case, intraspinal spread occurred via cerebrospinal fluid. Over a follow-up period of 9 to 67 months, only one patient died from the disease. H&E and IHC staining confirmed pathological features. Analyzing dissemination introduced concepts like dynamics, components, mediums, ranges, portals, and patterns, creating a framework for understanding disease spread.

Conclusion: Our findings offer valuable insights for guiding treatment strategies and improving patient outcomes. CNS GCTs can be managed effectively with accurate diagnosis and appropriate treatment. The introduction of new concepts and classifications of dissemination can inform and guide treatment strategies.

Keywords: Dissemination; Germ cell tumor; Somatic metastasis; Treatment.

Fig. 1

Imaging changes in the nervous system of tumors in time dimension. A An endodermal sinus tumor in the suprasellar region showed significant, uniform enhancement with MRI enhancement and a large tumor size (red arrow). Low signal (yellow arrow) of the cerebrospinal fluid shunt device and discontinuous skull can be seen in the right temporal area. Subsequent images are also shown in the corresponding area. B After stereotactic biopsy, MRI enhancement shows a clear, uniform enhancement (red arrow). C After 6 cycles of chemotherapy, the tumor volume was significantly reduced (red arrows). D The residual lesions after chemotherapy were surgically resected, and the postoperative reexamination MRI showed the enhanced shadow in the operative area of the enhanced image, which was considered as postoperative change. E and F were treated with chemotherapy and radiotherapy after resection. No tumor signal was found on the enhanced MRI images after radiotherapy. E brain; F the spinal cord

Fig. 2

Distribution patterns outside the primary site of the tumor in spatial dimension. A Dissemination of the tumor in the spinal canal. (Left) Sagittal MRI image enhancement shows a distinct, homogeneous, and large tumor (contrast-enhancing lesion, red arrow) in the horizontal spinal canal of T3, and a linear enhanced spread (red arrow) in other parts of the spinal canal. (middle) MRI axial image enhancement shows a distinct, uniform, large tumor in the upper spinal canal (contrast-enhancing lesion, red arrow), and anterior, etc. the spinal cord with low signal is compressed to thin (yellow arrow); (Right) Coronal MRI image enhancement shows a distinct, uniform, large tumor mass in the upper vertebra (contrast-enhancing lesion, red arrow), with smaller diffuse foci scattered elsewhere (red arrow). B Dissemination of tumor in the thorax. (left) PET sagittal image showing a high metabolic tumor signal (red arrow) in the anterior upper mediastinum. (Center) PET axial image showing a high metabolic tumor signal (red arrow) in the anterior upper mediastinum. (Right) PET coronal image showing a high metabolic tumor signal (red arrow) in the anterior upper mediastinum. C Intraperitoneal tumor Dissemination. (Left) Sagittal PET image showing abnormally high metabolic tumor signals (red arrows) in abdominal cavity and pelvic cavity; (Middle) PET axial image showing an abnormally high metabolic tumor signal (red arrow) in the left abdominal cavity; (Right) PET coronal image showing multiple high-metabolic tumor signals (red arrows) in the abdominal cavity and pelvic cavity

Fig. 3

Histologically different pathological types of tumors. A H&E of an immature teratoma with well-differentiated squamous epithelium (red arrows). B H&E of an immature teratoma with an area of bone differentiation within the tumor (red arrow), surrounded by fibrous components. A and B were derived from the primary site tumor of case 4. C H&E of endodermal sinus tumor with disorganized distribution of tumor cells, deep staining of nuclei, and heterotypic mitotic image (red arrow). A large number of foam cells are visible (yellow arrows). C comes from the primary site of Case2. D HE of germinoma shows a large number of dense, hyperchromic tumor cells with a heterotypic mitotic image (red arrow). Scattered lymphocytes (yellow arrows) are seen. D abdominal metastases from Case3

Fig. 4

Immunohistochemistry of tumor biomarkers. A Diffuse strong positive AFP; B negative AFP; C negative CD30; D Scattered positive CD117; E negative CK5/6; F partial positive CK; G negative HCG; H Ki60(focal 20% positive); I negative Oct3/4; J negative PLAP; K partial positive S100; L positive SALL4. A and L are yolk sac tumor of Case1; B–K are germinoma of Case3