The diagnosis of a mediastinal germ cell tumor should be considered in all young males with a mediastinal mass. In addition to physical examination and routine laboratory studies, initial evaluation should include CT of the chest and abdomen, and determination of serum levels of HCG and alpha-fetoprotein.

Because this is a rare tumor, not many family physicians or oncologists are familiar with this disease. DSRCT in young patients can be mistaken for other abdominal tumors including rhabdomyosarcoma, neuroblastoma, and mesenteric carcinoid. In older patients DSRCT can resemble lymphoma, peritoneal mesothelioma, and peritoneal carcinomatosis. In males DSRCT may be mistaken for germ cell or testicular cancer while in females DSRCT can be mistaken for Ovarian cancer. DSRCT shares characteristics with other small-round blue cell cancers including Ewing's sarcoma, acute leukemia, small cell mesothelioma, neuroblastoma, primitive neuroectodermal tumor, rhabdomyosarcoma, and Wilms' tumor.

DSRCT is frequently misdiagnosed. Adult patients should always be referred to a sarcoma specialist. This is an aggressive, rare, fast spreading tumor and both pediatric and adult patients should be treated at a sarcoma center.

There is no standard protocol for the disease; however, recent journals and studies have reported that some patients respond to high-dose (P6 Protocol) chemotherapy, maintenance chemotherapy, debulking operation, cytoreductive surgery, and radiation therapy. Other treatment options include: hematopoietic stem cell transplantation, intensity-modulated radiation Therapy, radiofrequency ablation, stereotactic body radiation therapy, intraperitoneal hyperthermic chemoperfusion, and clinical trials.

A retrospective study of 83 women with sex cord–stromal tumours (73 with granulosa cell tumour and 10 with Sertoli-Leydig cell tumour), all diagnosed between 1975 and 2003, reported that survival was higher with age under 50, smaller tumour size, and absence of residual disease. The study found no effect of chemotherapy. A retrospective study of 67 children and adolescents reported some benefit of cisplatin-based chemotherapy.

Because of its rarity, there have been no randomized clinical trials of treatment of GCCL, and all information available derives from small retrospective institutional series or multicenter metadata.

Blood tests may detect the presence of placental alkaline phosphatase (PLAP) in fifty percent of cases. However, PLAP cannot usefully stand alone as a marker for seminoma and contributes little to follow-up, due to its rise with smoking. Human chorionic gonadotropin (hCG) may be elevated in some cases, but this correlates more to the presence of trophoblast cells within the tumour than to the stage of the tumour. A classical or pure seminoma by definition do not cause an elevated serum alpha fetoprotein . Lactate dehydrogenase (LDH) may be the only marker that is elevated in some seminomas. The degree of elevation in the serum LDH has prognostic value in advanced seminoma.

The cut surface of the tumour is fleshy and lobulated, and varies in colour from cream to tan to pink. The tumour tends to bulge from the cut surface, and small areas of hemorrhage may be seen. These areas of hemorrhage usually correspond to trophoblastic cell clusters within the tumour.

Microscopic examination shows that seminomas are usually composed of either a sheet-like or lobular pattern of cells with a fibrous stromal network. The fibrous septa almost always contain focal lymphocyte inclusions, and granulomas are sometimes seen. The tumour cells themselves typically have abundant clear to pale pink cytoplasm containing abundant glycogen, which is demonstrable with a periodic acid-Schiff (PAS) stain. The nuclei are prominent and usually contain one or two large nucleoli, and have prominent nuclear membranes. Foci of syncytiotrophoblastic cells may be present in varied amounts. The adjacent testicular tissue commonly shows intratubular germ cell neoplasia, and may also show variable spermatocytic maturation arrest.

POU2AF1 and PROM1 have been proposed as possible markers.

While cancer is generally considered a disease of old age, children can also develop cancer. In contrast to adults, carcinomas are exceptionally rare in children..

The two biggest risk factors for ovarian carcinoma are age and family history.

Spermatocytic seminomas are diagnosed based on tissue from orchiectomy (or partial orchiectomy), done for a lesion suspicious for cancer on medical imaging.

The macroscopic appearance of the tumour is of a mutinodular grey-white to tan coloured mass with gelatinous, haemorrhagic and necrotic areas. The tumour may extend beyond the testis.

Giant-cell lung cancers have long been considered to be exceptionally aggressive malignancies that grow very rapidly and have a very poor prognosis.

Many small series have suggested that the prognosis of lung tumors with giant cells is worse than that of most other forms of non-small-cell lung cancer (NSCLC), including squamous cell carcinoma, and spindle cell carcinoma.

The overall five-year survival rate in GCCL varies between studies but is generally considered to be very low. The (US) Armed Forces Institute of Pathology has reported a figure of 10%, and in a study examining over 150,000 lung cancer cases, a figure of 11.8% was given. However, in the latter report the 11.8% figure was based on data that included spindle cell carcinoma, a variant which is generally considered to have a less dismal prognosis than GCCL. Therefore, the likely survival of "pure" GCCL is probably lower than the stated figure.

In the large 1995 database review by Travis and colleagues, giant-cell carcinoma has the third-worst prognosis among 18 histological forms of lung cancer. (Only small-cell carcinoma and large-cell carcinoma had shorter average survival.)

Most GCCL have already grown and invaded locally and/or regionally, and/or have already metastasized distantly, and are inoperable, at the time of diagnosis.

Definitive diagnosis of these tumours is based on the histology of tissue obtained in a biopsy or surgical resection. In a retrospective study of 72 cases in children and adolescents, the histology was important to prognosis.

A number of molecules have been proposed as markers for this group of tumours. CD56 may be useful for distinguishing sex cord–stromal tumours from some other types of tumours, although it does not distinguish them from neuroendocrine tumours. Calretinin has also been suggested as a marker. For diagnosis of granulosa cell tumour, inhibin is under investigation.

On magnetic resonance imaging, a fibroma may produce one of several imaging features that might be used in the future to identify this rare tumour prior to surgery.

Pure mediastinal seminomas are curable in the large majority of patients, even when metastatic at the time of diagnosis. These tumors are highly sensitive to radiation therapy and to combination chemotherapy. However, the cardiotoxicity of mediastinal radiation is substantial and the standard treatment of mediastinal seminomas is with chemotherapy using bleomycin, etoposide and cisplatin for either three or four 21-day treatment cycles depending on the location of any metastatic disease.

Patients with small tumors (usually asymptomatic) that appear resectable usually undergo thoracotomy and attempted complete resection followed by chemotherapy.

The treatment for mediastinal nonseminomatous germ cell tumors should follow guidelines for poor-prognosis testicular cancer. Initial treatment with four courses of bleomycin, etoposide, and cisplatin, followed by surgical resection of any residual disease, is considered standard therapy.

Intratesticular masses that appear suspicious on an ultrasound should be treated with an inguinal orchiectomy. The pathology of the removed testicle and spermatic cord indicate the presence of the seminoma and assist in the staging. Tumors with both seminoma and nonseminoma elements or that occur with the presence of AFP should be treated as nonseminomas. Abdominal CT or MRI scans as well as chest imaging are done to detect for metastasis. The analysis of tumor markers also helps in staging.

The preferred treatment for most forms of stage 1 seminoma is active surveillance. Stage 1 seminoma is characterized by the absence of clinical evidence of metastasis. Active surveillance consists of periodic history and physical examinations, tumor marker analysis, and radiographic imaging. Around 85-95% of these cases will require no further treatment. Modern radiotherapy techniques as well as one or two cycles of single-agent carboplatin have been shown to reduce the risk of relapse, but carry the potential of causing delayed side effects. Regardless of treatment strategy, stage 1 seminoma has nearly a 100% cure rate.

Stage 2 seminoma is indicated by the presence of retroperitoneal metastasis. Cases require radiotherapy or, in advanced cases, combination chemotherapy. Large residual masses found after chemotherapy may require surgical resection. Second-line treatment is the same as for nonseminomas.

Stage 3 seminoma is characterized by the presence of metastasis outside the retroperitoneum—the lungs in "good risk" cases or elsewhere in "intermediate risk" cases. This is treated with combination chemotherapy. Second-line treatment follows nonseminoma protocols.

The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.

A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.

Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a cancer unit that treated the majority of these men, even though the unit treated more men with the worst prognosis.

Choriocarcinoma of the testicles has the worst prognosis of all germ cell cancers

Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis.

Carcinomas are usually staged with Roman numerals. In most classifications, Stage I and Stage II carcinomas are confirmed when the tumor has been found to be small and/or to have spread to local structures only. Stage III carcinomas typically have been found to have spread to regional lymph nodes, tissues, and/or organ structures, while Stage IV tumors have already metastasized through the blood to distant sites, tissues, or organs.

In some types of carcinomas, Stage 0 carcinoma has been used to describe carcinoma "in situ", and occult carcinomas detectable only via examination of sputum for malignant cells (in lung carcinomas).

In more recent staging systems, substages (a, b, c) are becoming more commonly used to better define groups of patients with similar prognosis or treatment options.

Carcinoma stage is the variable that has been most consistently and tightly linked to the prognosis of the malignancy.

The criteria for staging can differ dramatically based upon the organ system in which the tumor arises. For example, the colon and bladder cancer staging system relies on depth of invasion, staging of breast carcinoma is more dependent on the size of the tumor, and in renal carcinoma, staging is based on both the size of the tumor and the depth of the tumor invasion into the renal sinus. Carcinoma of the lung has a more complicated staging system, taking into account a number of size and anatomic variables.

The UICC/AJCC TNM systems are most often used. For some common tumors, however, classical staging methods (such as the Dukes classification for colon cancer) are still used.

The most common way to test someone for PPB is to take a biopsy. Other tests like x-rays, CAT scans, and MRI's can suggest that cancer is present, but only an examination of a piece of the tumor can make a definite diagnosis.

Antibodies may be used to determine the expression of protein markers on the surface of cancer cells. Often the expression of these antigens is similar to the tissue that the cancer grew from, so immunohistochemical testing sometimes helps to identify the source of the cancer. Individual tests often do not provide definitive answers, but sometimes patterns may be observed, suggesting a particular site of origin (e.g. lung, colon, etc.). Immunohistochemical testing suggests a single source of cancer origin in about one in four cases of CUP. However, there is a lack of definitive research data showing that treatment guided by information from immunohistochemical testing improves outcomes or long-term prognosis.

Unlike classical seminoma, spermatocytic seminomas rarely metastasise, so radical orchidectomy alone is sufficient treatment, and retroperitoneal lymph node dissection and adjuvant chemotherapy or radiotherapy are generally not required.

Staging is a formal procedure to determine how developed the cancer is. This determines treatment options.

The American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) recommend TNM staging, using a uniform scheme for non-small cell lung carcinoma, small-cell lung carcinoma and broncho-pulmonary carcinoid tumors. With TNM staging, the cancer is classified based on the size of the tumor and spread to lymph nodes and other organs. As the tumor grows in size and the areas affected become larger, the staging of the cancer becomes more advanced as well.

There are several components of NSCLC staging which then influence physicians' treatment strategies. The lung tumor itself is typically assessed both radiographically for overall size as well as by a pathologist under the microscope to identify specific genetic markers or to see if there has been invasion into important structures within the chest (e.g., bronchus or pleural cavity). Next, the patient's nearby lymph nodes within the chest cavity known as the mediastinum will be checked for disease involvement. Finally, the patient will be evaluated for more distant sites of metastatic disease, most typically with brain imaging and or scans of the bones.

The histology of EST is variable, but usually includes malignant endodermal cells. These cells secrete alpha-fetoprotein (AFP), which can be detected in tumor tissue, serum, cerebrospinal fluid, urine and, in the rare case of fetal EST, in amniotic fluid. When there is incongruence between biopsy and AFP test results for EST, the result indicating presence of EST dictates treatment. This is because EST often occurs as small "malignant foci" within a larger tumor, usually teratoma, and biopsy is a sampling method; biopsy of the tumor may reveal only teratoma, whereas elevated AFP reveals that EST is also present. GATA-4, a transcription factor, also may be useful in the diagnosis of EST.

Diagnosis of EST in pregnant women and in infants is complicated by the extremely high levels of AFP in those two groups. Tumor surveillance by monitoring AFP requires accurate correction for gestational age in pregnant women, and age in infants. In pregnant women, this can be achieved simply by testing maternal serum AFP rather than tumor marker AFP. In infants, the tumor marker test is used, but must be interpreted using a reference table or graph of normal AFP in infants.

Dysgerminomas, like other seminomatous germ cell tumors, are very sensitive to both chemotherapy and radiotherapy. For this reason, with treatment patients' chances of long-term survival, even cure, is excellent.

The standard work-up for AT/RT includes:

- Magnetic resonance imaging (MRI) of the brain and spine

- Lumbar puncture to look for M1 disease

- Computed tomography (CT) of chest and abdomen to check for a tumor

- Bone marrow aspiration to check for bone tumors. Sometimes the physician will perform a stem cell transplant

- Bone marrow biopsy

- Bone scan

The initial diagnosis of a tumor is made with a radiographic study (MRI or CT-). If CT was performed first, an MRI is usually performed as the images are often more detailed and may reveal previously undetected metastatic tumors in other locations of the brain. In addition, an MRI of the spine is usually performed. The AT/RT tumor often spreads to the spine. AT/RT is difficult to diagnose only from radiographic study; usually, a pathologist must perform a cytological or genetic analysis.

Examination of the cerebrospinal fluid is important (CSF), as one-third of patients will have intracranial dissemination with involvement of the CSF. Large tumor cells, eccentricity of the nuclei, and prominent nucleoli are consistent findings. Usually only a minority of AT/RT biopsies have rhabdoid cells, making diagnosis more difficult. Increasingly it is recommended that a genetic analysis be performed on the brain tumor, especially to find if a deletion in the INI1/hSNF5 gene is involved (appears to account for over 80% of the cases). The correct diagnosis of the tumor is critical to any protocol. Studies have shown that 8% to over 50% of AT/RT tumors are diagnosed incorrectly.

Women with benign germ cell tumors such as mature teratomas (dermoid cysts) are cured by ovarian cystectomy or oophorectomy. In general, all patients with malignant germ cell tumors will have the same staging surgery that is done for epithelial ovarian cancer. If the patient is in her reproductive years, an alternative is unilateral salpingoophorectomy, while the uterus, the ovary, and the fallopian tube on the opposite side can be left behind. This isn't an option when the cancer is in both ovaries. If the patient has finished having children, the surgery involves complete staging including salpingoophorectomy on both sides as well as hysterectomy.

Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin).

The survival rates for stages I through IV decrease significantly due to the advancement of the disease. For stage I, the five-year survival rate is 47%, stage II is 30%, stage III is 10%, and stage IV is 1%.

GCNIS is not palpable, and not visible on macroscopic examination of testicular tissue. Microscopic examination of affected testicular tissue most commonly shows germ cells with enlarged hyperchromatic nuclei with prominent nucleoli and clear cytoplasm. These cells are typically arranged along the basement membrane of the tubule, and mitotic figures are frequently seen. The sertoli cells are pushed toward the lumen by the neoplastic germ cells, and spermatogenesis is almost always absent in the affected tubules. Pagetoid spread of GCNIS into the rete testis is common. Immunostaining with placental alkaline phosphatase (PLAP) highlights GCNIS cell membranes in 95 percent of cases. OCT3/4 is a sensitive and specific nuclear stain of GCNIS.

Ganglioneuromas can be diagnosed visually by a CT scan, MRI scan, or an ultrasound of the head, abdomen, or pelvis. Blood and urine tests may be done to determine if the tumor is secreting hormones or other circulating chemicals. A biopsy of the tumor may be required to confirm the diagnosis.