Regardless of location, all rhabdoid tumours are highly aggressive, have a poor prognosis, and tend to occur in children less than two years of age.

The histologic diagnosis of malignant rhabdoid tumour depends on identification of characteristic rhabdoid cells—large cells with eccentrically located nuclei and abundant, eosinophilic cytoplasm. However, the histology can be heterogeneous and the diagnosis of MRT can often be difficult. Misclassifications can occur.

In MRTs, the INI1 gene (SMARCB1)on chromosome 22q functions as a classic tumour suppressor gene. Inactivation of INI1 can occur via deletion, mutation, or acquired UPD.

In a recent study, SNP array karyotyping identified deletions or LOH of 22q in 49/51 rhabdoid tumours. Of these, 14 were copy neutral LOH (or acquired UPD), which is detectable by SNP array karyotyping, but not by FISH, cytogenetics, or arrayCGH. MLPA detected a single exon homozygous deletion in one sample that was below the resolution of the SNP array. SNP array karyotyping can be used to distinguish, for example, a medulloblastoma with an isochromosome 17q from a primary rhabdoid tumour with loss of 22q11.2. When indicated, molecular analysis of INI1 using MLPA and direct sequencing may then be employed. Once the tumour-associated changes are found, an analysis of germline DNA from the patient and the parents can be done to rule out an inherited or de novo germline mutation or deletion of INI1, so that appropriate recurrence risk assessments can be made.

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.

Cytogenetics is the study of a tumor’s genetic make-up. Fluorescent "in situ" hybridization may be able to help locate a mutation or abnormality that may be allowing tumor growth. This technique has been shown to be useful in identifying some tumors and distinguishing two histologically similar tumors from each other (such as AT/RTs and PNETs). In particular, medulloblastmas/PNETs may possibly be differentiated cytogenetically from AT/RTs, as chromosomal deletions of 17p are relatively common with medulloblastoma and abnormalities of 22q11.2 are not seen. However, chromosomal 22 deletions are very comomon in AT/RTs.

In importance of the "hSNF5/INI1" gene located on chromosomal band 22q11.2 is highlighted, as the mutation’s presence is sufficient to change the diagnosis from a medulloblastoma or PNET to the more aggressive AT/RT classification. However, this mutation is not present in 100% of cases. Therefore, if the mutation is not present in an otherwise classic AT/RT immunohistochemical and morphologic pattern then the diagnosis remains an AT/RT.

Medulloblastomas affect just under two people per million per year, and affect children 10 times more than adults. Medulloblastoma is the second-most frequent brain tumor in children after pilocytic astrocytoma and the most common malignant brain tumor in children, comprising 14.5% of newly diagnosed cases. In adults, medulloblastoma is rare, comprising fewer than 2% of CNS malignancies.

The rate of new cases of childhood medulloblastoma is higher in males (62%) than females (38%), a feature which is not seen in adults. Medulloblastoma and other PNET`s are more prevalent in younger children than older children. About 40% of medulloblastoma patients are diagnosed before the age of five, 31% are between the ages of 5 and 9, 18.3% are between the ages of 10 and 14, and 12.7% are between the ages of 15 and 19.

The cumulative relative survival rate for all age groups and histology follow-up was 60%, 52%, and 47% at 5 years, 10 years, and 20 years, respectively. Patients diagnosed with a medulloblastoma or PNET are 50 times more likely to die than a matched member of the general population.

The most recent population-based (SEER) 5-year relative survival rates are 69% overall, but 72% in children (1–9 years) and 67% in adults (20+ years). The 20-year survival rate is 51% in children. Children and adults have different survival profiles, with adults faring worse than children only after the fourth year after diagnosis (after controlling for increased background mortality). Before the fourth year, survival probabilities are nearly identical. Longterm sequelae of standard treatment include hypothalamic-pituitary and thyroid dysfunction and intellectual impairment. The hormonal and intellectual deficits created by these therapies causes significant impairment of the survivors.

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.

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.

On ultrasound, a sertoli cell tumour appears as a hypoechoic intratesticular lesion which is usually solitary. However, the large cell subtype might present as multiple and bilateral masses with large areas of calcification. An MRI may also be conducted, but this typically is undefinitive.

Microscopy and immunohistochemistry are the only way to give a definitive diagnosis, especially when there is a suspected seminoma.

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.

Due to the difficulty in identifying the tumour using imaging techniques, an orchiectomy is often performed. The majority of sertoli cell tumours are benign, so this is sufficient. There is no documented benefit of chemotherapy or radiotherapy.

Imaging studies such as X-rays, computed tomography scans, or MRI may be required to diagnose clear-cell sarcoma together with a physical exam. Normally a biopsy is also necessary. Furthermore, a chest CT, a bone scan and positron emission tomography (PET) may be part of the tests in order to evaluate areas where metastases occur.

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.

LCLC-RP are considered to be especially aggressive tumors with a dismal prognosis. Many published cases have shown short survival times after diagnosis. Some studies suggest that, as the proportion of rhabdoid cells in the tumor increases, the prognosis tends to worsen, although this is most pronounced when the proportion of rhabdoid cells exceeds 5%. With regard to "parent" neoplasms other than LCLC, adenocarcinomas with rhabdoid features have been reported to have worse prognoses than adenocarcinomas without rhabdoid features, although an "adenocarcinoma with rhabdoid phenotype" tumor variant has not been specifically recognized as a distinct entity under the WHO-2004 classification system.

Interestingly, there are case reports of rhabdoid carcinomas recurring after unusually long periods, which is unusual for a fast-growing, aggressive tumor type. One report described a very early stage patient whose tumor recurred 6 years after initial treatment. Although rapidly progressive, fulminant courses seem to be the rule in this entity, long-term survival has also been noted, even post-metastectomy in late stage, distant metastatic disease.

Although reliable and comprehensive incidence statistics are nonexistent, LCLC-RP is a rare tumor, with only a few hundred cases described in the scientific literature to date. LCLC's made up about 10% of lung cancers in most historical series, equating to approximately 22,000 cases per year in the U.S. Of these LCLC cases, it is estimated that about 1% will eventually develop the rhabdoid phenotype during tumor evolution and progression. In one large series of 902 surgically resected lung cancers, only 3 cases (0.3%) were diagnosed as LCLC-RP. In another highly selected series of large-cell lung carcinoma cases, only 4 of 45 tumors (9%) were diagnosed as the rhabdoid phenotype using the 10% criterion, but another 10 (22%) had at least some rhabdoid cell formation. It appears likely, therefore, that LCLC-RP probably comprises between 0.1% and 1.0% of all lung malignancies.

Similar to nearly all variants of lung carcinoma, large cell lung carcinoma with rhabdoid phenotype appears to be highly related to tobacco smoking. It also appears to be significantly more common in males than in females.

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.

It is classified into two types, based on location in the body: peripheral PNET and CNS PNET.

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.

Malignant germ cell tumors of the mediastinum are uncommon, representing only 3 to 10% of tumors originating in the mediastinum. They are much less common than germ cell tumors arising in the testes, and account for only 1 to 5% of all germ cell neoplasms.

Syndromes associated with mediastinal germ cell tumors include Hematologic Neoplasia and Klinefelter's syndrome.

A needle aspiration biopsy of the tumor will typically show a large number of mast cells. This is sufficient to make the diagnosis of a mast cell tumor, although poorly differentiated mast cells may have few granules and thus are difficult to identify. The granules of the mast cell stain blue to dark purple with a Romanowsky stain, and the cells are medium-sized. However, a surgical biopsy is required to find the grade of the tumor. The grade depends on how well the mast cells are differentiated, mitotic activity, location within the skin, invasiveness, and the presence of inflammation or necrosis.

- Grade I – well differentiated and mature cells with a low potential for metastasis

- Grade II – intermediately differentiated cells with potential for local invasion and moderate metastatic behavior

- Grade III – undifferentiated, immature cells with a high potential for metastasis

However, there is a significant amount of discordance between veterinary pathologists in assigning grades to mast cell tumors due to imprecise criteria.

The disease is also staged according to the WHO system:

- Stage I - a single skin tumor with no spread to lymph nodes

- Stage II - a single skin tumor with spread to lymph nodes in the surrounding area

- Stage III - multiple skin tumors or a large tumor invading deep to the skin with or without lymph node involvement

- Stage IV – a tumor with metastasis to the spleen, liver, or bone marrow, or with the presence of mast cells in the blood

X-rays, ultrasound, or lymph node, bone marrow, or organ biopsies may be necessary to stage the disease.

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.

The peripheral PNET (pPNET) is now thought to be virtually identical to Ewing sarcoma:

"Current evidence indicates that both Ewing's sarcoma and PNET have a similar neural phenotype and, because they share an identical chromosome translocation, they should be viewed as the same tumor, differing only in their degree of neural differentiation. Tumors that demonstrate neural differentiation by light microscopy, immunohistochemistry, or electron microscopy have been traditionally labeled PNETs, and those that are undifferentiated by these analyses have been diagnosed as Ewing's sarcoma."

Treatment depends upon the site and the extent of the disease. Clear cell sarcoma is usually treated with surgery in the first place in order to remove the tumor. The surgical procedure is then followed by radiation and sometimes chemotherapy. Few cases of clear cell sarcoma respond to chemotherapy. Several types of targeted therapy that may be of benefit to clear cell sarcoma patients are currently under investigation.

Many types of blastoma have been linked to a mutation in tumor suppressor genes. For example, pleuropulmonary blastomas have been linked to a mutation of the coding for p53. However, the mutation which allows proliferation of incompletely differentiated cells can vary from patient to patient and a mutation can alter the prognosis. In the case of retinoblastoma, patients carry a visibly abnormal karyotype, with a loss of function mutation on a specific band of chromosome 13. This recessive deletion on the rb gene is also associated with other cancer types and must be present on both alleles, for a normal cell to progress towards malignancy.

Staging of c-SCLC patients is usually performed in an analogous fashion to patients with "pure" small cell lung carcinoma.

For several decades, SCLC has been staged according to a dichotomous distinction of "limited disease" (LD) "vs." "extensive disease" (ED) tumor burdens. Nearly all clinical trials have been conducted on SCLC patients staged dichotomously in this fashion. LD is roughly defined as a locoregional tumor burden confined to one hemithorax that can be encompassed within a single, tolerable radiation field, and without detectable distant metastases beyond the chest or supraclavicular lymph nodes. A patient is assigned an ED stage when the tumor burden is greater than that defined under LD criteria — either far advanced locoregional disease, malignant effusions from the pleura or pericardium, or distant metastases.

However, more recent data reviewing outcomes in very large numbers of SCLC patients suggests that the TNM staging system used for NSCLC is also reliable and valid when applied to SCLC patients, and that more current versions may allow better treatment decisionmaking and prognostication in SCLC than with the old dichotomous staging protocol.