Introduction
Extragonadal germ cell tumors are most frequently found in the anterior mediastinum, accounting for 50 to 70 percent of all cases. Rarely do posterior mediastinum germ cell tumors occur. There are biochemical and histologic similarities between primary mediastinal germ cell tumors and gonadal germ cell tumors, including the presence of isochromosome 12p. Klinefelter syndrome and a number of hematologic malignancies have been linked to mediastinal germ cell tumors. Teratomas, other non-seminomatous tumors, and seminomas are the three primary kinds comparable to gonadal germ cell tumors. Regarding prognosis and therapy, each of these contains significant differences.
Most mediastinal germ cell tumors are discovered by chance during imaging studies. 20 to 40 percent of patients are asymptomatic at diagnosis. Initial symptoms are typically linked to mediastinal cavity expansion and protrusion into nearby structures. Chest pain, coughing, dyspnea, fever, night sweats, and weight loss are typical clinical signs. The tumor's size and histological subtype both affect how it presents itself. Depending on the histological subtype, the recommended course of treatment is either surgical resection or cisplatin-based chemotherapy followed by surgical resection.
What Is the Etiology of Mediastinal Germ Cell Tumors?
The gonads, most frequently the testicles in men and the ovaries in women, are where germ cell tumors develop. Rarely, the non-gonadal origin can come from midline organs like the mediastinum, retroperitoneum, pineal, or suprasellar regions. Several theories exist, but the exact cause of germ cell malignancy found outside the gonads is still unknown.
The migration of primordial germ cells from the proximal epiblast to the dorsally situated urogenital ridge is necessary for testicular creation throughout embryonic development. According to the main theory, there is a halt in their descent, which ultimately causes a tumor to grow in the anterior mediastinum. The other theory is that altered germ cells migrate backward in the gonads. This hypothesis is supported by common genetic cell origin data, but it does not account for all of the reported biological discrepancies.
What Is the Epidemiology of Mediastinal Germ Cell Tumors?
Only 15 percent of all tumors in the mediastinum are germ cell tumors, making them a rare entity. Although they make up the majority of germ cell tumors outside the gonads, they only make up 1 to 3 percent of all germ cell malignancies. With a mean age of 31 years, mediastinal germ cell tumors are more common in men (97 percent) and younger patients. Klinefelter syndrome has been linked to mediastinal germ cell tumors, particularly for non-seminomatous types.
What Is the Pathophysiology of Mediastinal Germ Cell Tumors?
There are similarities between mediastinal and gonadal germ cell tumors, such as the gain of isochromosome 12p. In addition, there are certain changes in a number of components, such as greater rates of TP53 mutations, specific forms of yolk sac tumors, and elevations in alpha-fetoprotein.
What Is the Histopathology of Mediastinal Germ Cell Tumors?
The majority of cases of mediastinal germ cells are teratomas, which account for about 44 percent of all cases. Of all mediastinal germ cell tumors, non-seminomatous germ cell tumors make up about 70 percent of the total. Approximately 30 percent of cases are seminomas.
What Are the Symptoms of Mediastinal Germ Cell Tumors?
Imaging scans may unintentionally reveal mediastinal germ cell tumors, which could be asymptomatic. Larger mediastinal germ cell tumors, on the other hand, manifest symptoms when they enclose or block neighboring structures. In a few cases, the tumor is infected. Proteolytic or digestive enzymes can occasionally be present in a tumor's internal composition. These tumors have the potential to rupture spontaneously, causing inflammation in the nearby structures. The most harmful side effects are rupture or erosion into the pericardial or pleural region.
If there is erosion, bronchial obstruction may manifest as hemoptysis or post-obstructive pneumonia. In contrast to seminomas and teratomas, non-seminomatous mediastinal germ cell tumors have a higher propensity for symptoms and a higher likelihood of lymph node metastasis. They can cause superior vena cava syndrome and be accompanied by weight loss, fever, cough, dyspnea, and chest pain.
What Is the Treatment for Mediastinal Germ Cell Tumors?
Similar treatment recommendations apply to gonadal germ cell tumors and mediastinal germ cell tumors. The disease is uncommon, hence big prospective randomised controlled studies have not been possible. Non-seminomatous mediastinal germ cell tumors are regarded as "poor risk" tumors by the International Germ Cell Cancer Collaborative Group.
Based on tumor markers and signs of metastasis at presentation, teratomas, and seminomatous mediastinal germ cell tumors are categorized as good or intermediate risk. Chemotherapy does not affect benign mature teratomas; as a result, surgery is advised when they are symptomatic. A median sternotomy or posterolateral thoracotomy is required for surgical resection. Since these tumors typically do not have an extra-mediastinal invasion, incomplete resection to avoid vital structure involvement does not require additional chemotherapy and radiation therapy.
Depending on whether the patient has seminomatous mediastinal germ cell tumors, the recommended course of treatment is 3 or 4 cycles of the chemotherapeutic drugs bleomycin, etoposide, and cisplatin. First-line treatment for tumors with low prognosis typically includes chemotherapy, followed by surgical removal of any remaining tumor. Bleomycin, etoposide, and cisplatin were administered four cycles as the initial chemotherapy treatment.
This caused pulmonary problems, which were observed to be hazardous in patients with mediastinal germ cell tumors who could require significant thoracic surgery after chemotherapy. Ifosfamide was used in place of bleomycin to remedy this. Surgery is essential in cases of post-chemotherapy residual disease because unresectable germ cell tissue can result in the rare but well-documented developing teratoma condition. Repeated surgical resection improves long-term survival and is advised in good surgical candidates. Radiation therapy is a viable alternative for individuals with remaining tissue close to essential organs.
Relapse might happen after therapy is over. Only 11 percent of patients with mediastinal germ cell tumors were long-term disease-free, according to a retrospective analysis of 79 cases. Most of these patients should therefore receive a second round of chemotherapy, even though there are no established standards for the best second-line chemotherapy treatment. Studies indicate that cure rates for salvage therapy patients range from 5 to 10 percent, regardless of the chemotherapy regimen utilized.
What Are the Complications of Mediastinal Germ Cell Tumors?
Mediastinal gem cell tumors might spread to nearby structures as the disease progresses. Adjacent structures such as the bone, lungs, liver, and thoracic lymph nodes are frequent sites of metastasis. Chemotherapy-related problems can occur while receiving treatment. Additionally, it is possible for post-surgical issues like the onset of pyothorax, phrenic nerve damage, and excessive blood loss to arise when treating mediastinal germ cell tumors.
Conclusion
Gem cell tumors of the mediastinum are highly carcinogenic. The primary care physician should start tumor marker screening when an anterior mediastinal mass is found. If the tumor affects pulmonary structures or causes breathing issues, a referral to a pulmonologist is necessary.
