Mediastinal germ cell tumor

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: M-GCTs;

Overview

Mediastinal germ cell tumor is a extragonadal tumor derived from germ cell remnants in the mediastinum and a cause of anterior mediastinal mass. Malignant germ cell tumors of the mediastinum are uncommon, representing only 3 to 10% of tumors originating in the mediastinum.

Historical Perspective

• Mediastinal germ cell tumor was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
• In [year], [gene] mutations were first identified in the pathogenesis of mediastinal germ cell tumor.
• In [year], the first [discovery] was developed by [scientist] to treat/diagnose mediastinal germ cell tumor.

Classification

• Mediastinal germ cell tumor may be classified according to histopathological subtype in 2 groups:

• Seminoma
• Non-seminomatous germ cell tumours (NSGCT)

• Embryonal cell carcinoma
• Choriocarcinoma
• Yolk sac tumour
• Teratoma (most common)
• Mixed germ cell tumor

Pathophysiology

• The pathogenesis of mediastinal germ cell tumor is characterized by the abnormal migration of germ cells during embryogenesis.
• Mediastinal germ cell tumor arises from germ cells, which are normally involved in the formation of o the gametes.
• Genetic mutations associated with the development of mediastinal germ cell tumor, include:

• Sex chromosomal abnormalities

• Loss of 1p, 4q, and 6q
• Gain of 1q, 3, and 20q

• On gross pathology, findings of mediastinal germ cell tumor may include:

• Unencapsulated
• Homogenous fleshy mass with indistinct boundaries
• Invasion of adjacent structures

• On microscopic histopathological analysis findings of mediastinal germ cell tumor, include:

• Large tumor cells with clear cytoplasm
• Prominent nucleoli

Causes

• Mediastinal germ cell tumor may be caused by either [cause1], [cause2], or [cause3].
• Mediastinal germ cell tumor is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
• There are no established causes for mediastinal germ cell tumor.

Differentiating mediastinal germ cell tumor from other Diseases

• Mediastinal germ cell tumor must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

• [Differential dx1]
• [Differential dx2]
• [Differential dx3]

Epidemiology and Demographics

• Malignant germ cell tumors of the mediastinum are uncommon
• Malignant germ cell tumors represent only 3 to 10% of tumors originating in the mediastinum

Age

• Patients of all age groups may develop mediastinal germ cell tumor.

• Mediastinal germ cell tumor is more commonly observed among patients aged [age range] years old.
• Mediastinal germ cell tumor is more commonly observed among [elderly patients/young patients/children].

Gender

• Mediastinal germ cell tumor affects men and women equally.

• [Gender 1] are more commonly affected with mediastinal germ cell tumor than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for mediastinal germ cell tumor.

Risk Factors

• Common risk factors in the development of mediastinal germ cell tumor, include:

Natural History, Complications and Prognosis

• The majority of patients with mediastinal germ cell tumor are usually symptomatic at the time of diagnosis
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with mediastinal germ cell tumor may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• The most common complications of mediastinal germ cell tumor is superior vena cava syndrome.
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with mediastinal germ cell tumor is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of mediastinal germ cell tumor is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• Mediastinal germ cell tumors are usually asymptomatic and found incidentally.
• Symptoms of mediastinal germ cell tumor may include the following:

• Chest pain
• Dyspnea
• Cough
• Weight loss
• Superior vena cava syndrome
• Fever
• Nausea

Physical Examination

• Patients with mediastinal germ cell tumor usually are well-appearing.
• Physical examination may be remarkable for:

• Dull percussion
• Tactile fremitus
• Reduced chest expansion
• Crackling or bubbling noises
• Present whispered pectoriloquy

Laboratory Findings

• Laboratory findings consistent with the diagnosis of mediastinal germ cell tumor, include:

• Elevation in serum alpha-fetoprotein (AFP)
• Elevation in beta-human chorionic gonadotropin (beta-hCG)

Imaging Findings

• Chest radiography is the initial imaging modality of choice for mediastinal germ cell tumor.
• On chest radiography, findings of mediastinal germ cell tumor, include:

• Displaced anterior junction line
• Obliterated cardiophrenic angles
• Obtuse angles with the mediastinum
• Obliterated retrosternal clear space
• Effacement/ dense ascending aorta

• On chest radiography, signs of mediastinal germ cell tumor, include:

• Hilum Overlay Sign: hilar vessels through the mass (the mass does not arise from the hilum)

• On CT, findings of mediastinal germ cell tumor, include:

• Anterior mediastinal mass
• Obtuse angles with the mediastinum
• Enhancing septations

Other Diagnostic Studies

• Mediastinal germ cell tumor may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

• Cisplatin-based chemotherapy is the treatment of choice for mediastinal germ cell tumors.
• Common therapies for mediastinal germ cell tumor, include:

• Etoposide
• Ifosfamide
• Cisplatin
• Bleomycin

• Alternative treatment for mediastinal germ cell tumor, include:

• Primary radiotherapy in the absence of metastatic disease

Surgery

• Surgery is the mainstay of therapy for mediastinal germ cell tumor.
• Radical resection in conjunction with chemotherapy/radiation is the most common approach to the treatment of mediastinal germ cell tumor.

Prevention

• There are no primary preventive measures available for mediastinal germ cell tumor.
• Once diagnosed and successfully treated, patients with mediastinal germ cell tumor are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].