Following diagnosis and histopathological analysis, the patient will usually undergo magnetic resonance imaging (MRI), ultrasonography, and a bone scan in order to determine the extent of local invasion and metastasis. Further investigational techniques may be necessary depending on tumor sites. A parameningeal presentation of RMS will often require a lumbar puncture to rule out metastasis to the meninges. A paratesticular presentation will often require an abdominal CT to rule out local lymph node involvement, and so on. Patient outcomes are most strongly tied to the extent of the disease, so it is important to map its presence in the body as soon as possible in order to decide on a treatment plan.

The current staging system for rhabdomyosarcoma is unusual relative to most cancers. It utilizes a modified TNM (tumor-nodes-metastasis) system originally developed by the IRSG. This system accounts for tumor size (> or <5 cm), lymph node involvement, tumor site, and presence of metastasis. It grades on a scale of 1 to 4 based on these criteria. In addition, patients are sorted by clinical group (from the clinical groups from the IRSG studies) based on the success of their first surgical resection. The current Children's Oncology Group protocols for the treatment of RMS categorize patients into one of four risk categories based on tumor grade and clinical group, and these risk categories have been shown to be highly predictive of outcome.

Urine catecholamine level can be elevated in pre-clinical neuroblastoma. Screening asymptomatic infants at three weeks, six months, and one year has been performed in Japan, Canada, Austria and Germany since the 1980s. Japan began screening six-month-olds for neuroblastoma via analysis of the levels of homovanillic acid and vanilmandelic acid in 1984. Screening was halted in 2004 after studies in Canada and Germany showed no reduction in deaths due to neuroblastoma, but rather caused an increase in diagnoses that would have disappeared without treatment, subjecting those infants to unnecessary surgery and chemotherapy.

Rhabdomyosarcoma is often difficult to diagnose due to its similarities to other cancers and varying levels of differentiation. It is loosely classified as one of the “small, round, blue-cell cancer of childhood” due to its appearance on an H&E stain. Other cancers that share this classification include neuroblastoma, Ewing sarcoma, and lymphoma, and a diagnosis of RMS requires confident elimination of these morphologically similar diseases. The defining diagnostic trait for RMS is confirmation of malignant skeletal muscle differentiation with myogenesis (presenting as a plump, pink cytoplasm) under light microscopy. Cross striations may or may not be present. Accurate diagnosis is usually accomplished through immunohistochemical staining for muscle-specific proteins such as myogenin, muscle-specific actin, desmin, D-myosin, and myoD1. Myogenin, in particular, has been shown to be highly specific to RMS, although the diagnostic significance of each protein marker may vary depending on the type and location of the malignant cells. The alveolar type of RMS tends to have stronger muscle-specific protein staining. Electron microscopy may also aid in diagnosis, with the presence of actin and myosin or Z bands pointing to a positive diagnosis of RMS. Classification into types and subtypes is accomplished through further analysis of cellular morphology (alveolar spacings, presence of cambium layer, aneuploidy, etc.) as well as genetic sequencing of tumor cells. Some genetic markers, such as the "PAX3-FKHR" fusion gene expression in alveolar RMS, can aid in diagnosis. Open biopsy is usually required to obtain sufficient tissue for accurate diagnosis. All findings must be considered in context, as no one trait is a definitive indicator for RMS.

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.

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.

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.

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.

The prognosis of patients with FA as a whole is considered to be better than that of most other forms of non-small cell carcinoma, including biphasic pulmonary blastoma.

Another way to detect neuroblastoma is the mIBG scan (meta-iodobenzylguanidine), which is taken up by 90 to 95% of all neuroblastomas, often termed "mIBG-avid." The mechanism is that mIBG is taken up by sympathetic neurons, and is a functioning analog of the neurotransmitter norepinephrine. When it is radio-ionated with I-131 or I-123 (radioactive iodine isotopes), it is a very good radiopharmaceutical for diagnosis and monitoring of response to treatment for this disease. With a half-life of 13 hours, I-123 is the preferred isotope for imaging sensitivity and quality. I-131 has a half-life of 8 days and at higher doses is an effective therapy as targeted radiation against relapsed and refractory neuroblastoma.

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.

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.

Patients who have been diagnosed with ARMS often have poor outcomes. The four year survival rate without remission for local ARMS tumors is 65 percent, while the four year survival rate with metastatic ARMS is only 15 percent. Patients who have metastatic ARMS positive with PAX3-FOXO1 fusion often have a poorer outcome than patients positive with PAX7-FOXO1 fusion, with a four-year survival rate of 8 percent and 75 percent respectively. Other variables affect the four year survival rate, such as, primary tumor site, size of primary tumor, amount of local invasion, number of distal lymph nodes spread to, and whether metastasis has occurred. Prognosis for patients who have primary tumor sites within the bones often have higher survival rates and respond well to treatment options. While patients who have primary tumor sites within the nasopharynx region with metastases to the breast have very poor outcomes. Patients who are fusion protein negative with low risk clinical features should be treated with reduced therapy, while patients who are fusion protein positive with low risk clinical features should be treated as an intermediate risk and have more intensive therapy regimens.

On conventional radiographs, the most common osseous presentation is a permeative lytic lesion with periosteal reaction. The classic description of lamellated or "onion-skin" type periosteal reaction is often associated with this lesion. Plain films add valuable information in the initial evaluation or screening. The wide zone of transition (e.g. permeative) is the most useful plain film characteristic in differentiation of benign versus aggressive or malignant lytic lesions.

Magnetic resonance imaging (MRI) should be routinely used in the work-up of malignant tumors. It will show the full bony and soft tissue extent and relate the tumor to other nearby anatomic structures (e.g. vessels). Gadolinium contrast is not necessary as it does not give additional information over noncontrast studies, though some current researchers argue that dynamic, contrast-enhanced MRI may help determine the amount of necrosis within the tumor, thus help in determining response to treatment prior to surgery.

Computed axial tomography(CT) can also be used to define the extraosseous extent of the tumor, especially in the skull, spine, ribs, and pelvis. Both CT and MRI can be used to follow response to radiation and/or chemotherapy. Bone scintigraphy can also be used to follow tumor response to therapy.

In the group of malignant small round cell tumors which include Ewing's sarcoma, bone lymphoma, and small cell osteosarcoma, the cortex may appear almost normal radiographically, while permeative growth occurs throughout the Haversian channels. These tumours may be accompanied by a large soft-tissue mass while almost no bone destruction is visible. The radiographs frequently do not shown any signs of cortical destruction.

Radiographically, Ewing's sarcoma presents as "moth-eaten" destructive radiolucencies of the medulla and erosion of the cortex with expansion.

Other entities with similar clinical presentations include osteomyelitis, osteosarcoma (especially telangiectatic osteosarcoma), and eosinophilic granuloma. Soft-tissue neoplasms such as pleomorphic undifferentiated sarcoma (malignant fibrous histiocytoma) that erode into adjacent bone may also have a similar appearance.

The prognosis varies depending on the site of origin, the type of cancer cell, the tumor size, the depth, and proximity to lymph nodes. Well-differentiated liposarcomas treated with surgery, intra-operative distilled water lavage and radiation have a low recurrence rate (about 10%) and rarely metastasize.

Five-year survival rates vary from 100% to 56% based on histological subtype.

ARMS usually occurs in the skeletal muscle tissue of the extremities, but it is still very common in the torso, head, and neck regions. The primary tumor often presents itself as a soft mass of tissue that is painless, but the tumor can be detected if it starts to put pressure on other structures in the primary site. A large fraction of patients who are diagnosed with ARMS, roughly 25-30 percent, will have metastases at the time of diagnosis. The standard sites for metastases to form are the bone marrow, the bones, and distal nodes. Typical treatment options for patients who have been diagnosed with ARMS include standard surgery, radiation therapy, and intensive chemotherapy.

Current consensus is that the long-term prognosis of c-SCLC patients is determined by the SCLC component of their tumor, given that "pure" SCLC seems to have the worst long-term prognosis of all forms of lung cancer. Although data on c-SCLC is very sparse, some studies suggest that survival rates in c-SCLC may be even worse than that of pure SCLC, likely due to the lower rate of complete response to chemoradiation in c-SCLC, although not all studies have shown a significant difference in survival.

Untreated "pure" SCLC patients have a median survival time of between 4 weeks and 4 months, depending on stage and performance status at the time of diagnosis.

Given proper multimodality treatment, SCLC patients with limited disease have median survival rates of between 16 and 24 months, and about 20% will be cured. In patients with extensive disease SCLC, although 60% to 70% will have good-to-complete responses to treatment, very few will be cured, with a median survival of only 6 to 10 months.

Some evidence suggests that c-SCLC patients who continue to smoke may have much worse outcomes after treatment than those who quit.

Genetic changes are very high in SCLC and LCNEC, but usually low for TC, intermediate for AC.

The diagnosis of SCLC, TC and AC can be made by light microscopy without the need for special tests in most cases, but for LCNEC it is required to demonstrate NE differentiation by immunohistochemistry or electron microscopy.

The diagnosis is established by histologic examination of the tissue, i.e., biopsy or excision. Lipoblasts are often present; these are cells with an abundant clear multi-vacuolated cytoplasm and an eccentric darkly staining nucleus that is indented by the vacuoles.

All in all, small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.

In "limited-stage" disease, median survival with treatment is 14–20 months, and about 20% of patients with limited-stage small-cell lung carcinoma live 5 years or longer. Because of its predisposition for early metastasis, the prognosis of SCLC is poor, with only 10% to 15% of patients surviving 3 years.

The prognosis is far more grim in "extensive-stage" small-cell lung carcinoma; with treatment, median survival is 8–13 months; only 1–5% of patients with extensive-stage small-cell lung carcinoma treated with chemotherapy live 5 years or longer.

The prognosis for rhabdomyosarcoma has improved greatly in recent decades, with over 70% of patients surviving for five years after diagnosis.

Cancer screening uses medical tests to detect disease in large groups of people who have no symptoms. For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life. This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%). High risk people are those age 55–74 who have smoked equivalent amount of a pack of cigarettes daily for 30 years including time within the past 15 years.

CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment. For each true positive scan there are about 19 falsely positives scans. Other concerns include radiation exposure and the cost of testing along with follow up. Research has not found two other available tests—sputum cytology or chest radiograph (CXR) screening tests—to have any benefit.

The United States Preventive Services Task Force (USPSTF) recommends yearly screening using low-dose computed tomography in those who have a total smoking history of 30 pack-years and are between 55 and 80 years old until a person has not been smoking for more than 15 years. Screening should not be done in those with other health problems that would make treatment of lung cancer if found not an option. The English National Health Service was in 2014 re-examining the evidence for screening.

Removal of the mast cell tumor through surgery is the treatment of choice. Antihistamines, such as diphenhydramine, are given prior to surgery to protect against the effects of histamine released from the tumor. Wide margins (two to three centimeters) are required because of the tendency for the tumor cells to be spread out around the tumor. If complete removal is not possible due to the size or location, additional treatment, such as radiation therapy or chemotherapy, may be necessary. Prednisone is often used to shrink the remaining tumor portion. H2 blockers, such as cimetidine, protect against stomach damage from histamine. Vinblastine and CCNU are common chemotherapy agents used to treat mast cell tumors.

Toceranib and masitinib, examples of receptor tyrosine kinase inhibitors, are used in the treatment of canine mast cell tumors. Both were recently approved by the U.S. Food and Drug Administration (FDA) as dog-specific anticancer drugs.

Grade I or II mast cell tumors that can be completely removed have a good prognosis. One study showed about 23 percent of incompletely removed grade II tumors recurred locally. Any mast cell tumor found in the gastrointestinal tract, paw, or on the muzzle has a guarded prognosis. Previous beliefs that tumors in the groin or perineum carried a worse prognosis have been discounted. Tumors that have spread to the lymph nodes or other parts of the body have a poor prognosis. Any dog showing symptoms of mastocytosis or with a grade III tumor has a poor prognosis. Dogs of the Boxer breed have a better than average prognosis because of the relatively benign behavior of their mast cell tumors. Multiple tumors that are treated similarly to solitary tumors do not seem to have a worse prognosis.

Mast cell tumors do not necessarily follow the histological prognosis. Further prognostic information can be provided by AgNOR stain of histological or cytological specimen. Even then, there is a risk of unpredictable behavior.

Because of its extreme rarity, there have been no controlled clinical trials of treatment regimens for FA and, as a result, there are no evidence-based treatment guidelines. Complete surgical resection is the treatment of choice in FA, as it is in nearly all forms of lung cancer.

Anecdotal reports suggest that FA is rarely highly sensitive to cytotoxic drugs or radiation. Case reports suggest that chemotherapy with UFT may be useful in FA.