Spindle cell rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma first described by Cavazzana, Schmidt and Ninfo in 1992. This subtype has a more favorable clinical course and prognosis than usual embryonal rhabdomyosarcoma. Spindle cell rhabdomyosarcoma typically occurs in young males and most commonly occurs in paratesticular soft tissue, followed by the head and neck.

ERMS is the more common of two major subtypes of rhabdomyosarcoma, the other being alveolar rhabdomyosarcoma.

It has been informally classified as a "small round blue cell tumor" because of the characteristic microscopic appearance of its cells after histological staining with hematoxylin and eosin.

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

In the United States, about 20-30 cases are reported each year. This may be a gross underestimate of the total number of cases as few laboratories have the reagents and expertise to make the diagnosis. The symptoms are similar to other forms of cancer and dependent on the stage. While generalized symptoms (weight loss and fatigue) may be seen, site specific symptoms are also present. If the tumor involves the head and neck region (in about 35%), then pain, a mass, obstructive symptoms, among others, may be experienced. NUT midline carcinomas are not specific to any tissue type or organ.

Common sites include the head, neck and mediastinum. The median age at diagnosis is 17 years, but older patients may be affected.

RMS can occur in almost any soft-tissue site in the body; the most common primary sites are genitourinary (24%), parameningeal (16%), extremity (19%), orbit (9%), other head and neck (10%), and miscellaneous other sites (22%). RMS often presents as a mass, but signs and symptoms can vary widely depending on the site of the primary tumor. Genitourinary tumors may present with hematuria, urinary tract obstruction, and/or a scrotal or vaginal mass. Tumors that arise in the retroperitoneum and mediastinum can become quite large before producing signs and symptoms. Parameningeal tumors may present with cranial nerve dysfunction, symptoms of sinusitis, ear discharge, headaches, and facial pain. Orbital tumors often present with orbital swelling and proptosis. Extremity tumors generally present as a rapidly enlarging, firm mass in the relevant tissue. The cancer's prevalence in the head, face, and neck will often allow for earlier signs of the disease simply due to the obvious nature of tumors in these locations. Despite the varying presentation and typically aggressive nature of the disease, RMS has the potential to be diagnosed and treated early. The fourth IRSG study found that 23% of patients were diagnosed in time for a complete resection of their cancer, and 15% had resection with only minimal remnants of the diseased cells.

ASPS may exist in the patient’s body for a long time before being diagnosed. It can grow large and push aside surrounding tissues for a long time before causing any discomfort. Therefore, ASPS symptoms may either be a painless swelling, or a soreness caused by compressed nerves or muscles, affecting the range of motion in the area.

Sclerosing rhabdomyosarcoma is a rare subtype of rhabdomyosarcoma that was characterized by Folpe et al. in 2002. It is microscopically characterized by primitive round cells forming microalveoli, nests, and cords in a sclerotic background.

Although ASPS displays a relatively indolent course, the ultimate prognosis is poor and is often characterized by late metastases.

NUT carcinoma (formerly NUT midline carcinoma), is a rare genetically defined, very aggressive squamous cell epithelial cancer that usually arises in the midline of the body and is characterized by a chromosomal rearrangement in the nuclear protein in testis gene. In approximately 75% of cases, the coding sequence of "NUTM1" on chromosome 15q14 is fused to "BRD4" or "BRD3", which creates a chimeric gene that encodes the "BRD-NUT" fusion protein. The remaining cases, the fusion of NUTM1 is to an unknown partner gene, usually called "NUT"-variant.

Given the difficulty in diagnosing rhabdomyosarcoma, definitive classification of subsets has proven difficult. As a result, classification systems vary by institute and organization. However, rhabdomyosarcoma can be generally divided into three histological subsets:

- "Embryonal rhabdomyosarcoma" (ERMS) is the most common histological variant, comprising approximately 60–70% of childhood cases. It is most common in children 0–4 years old, with a maximum reported incidence of 4 cases per 1 million children. ERMS is characterized by spindle-shaped cells with a stromal-rich appearance, and the morphology is similar to the developing muscle cells of a 6–8 week old embryo. Tumors often present in the head and neck as well as the genitourinary tract. ERMS also has two defined subtypes, botryoid and spindle cell ERMS, and these subtypes are associated with a favorable prognosis.

- Subtypes of ERMS

- Botryoid ERMS is almost always found in mucosal lined organs including the vagina, bladder, and nasopharynx (although presentation in the nasopharynx typically affects older children). It often presents in patients <1 year old as a round, grape-like mass on the affected organ. Histologically, cells of the botryoid variant are defined by a dense tumor layer under an epithelium (cambium layer).

- Spindle cell rhabdomyosarcoma comprises about 3% of all RMS cases. This subtype is very similar to that of leiomyosarcoma (cancer of the smooth muscle tissue), and it has a fascicular, spindled, and leiomyomatous growth pattern with notable rhabdomyoblastic differentiation . It occurs most commonly in the paratesticular region, and the prognosis for this particular form of RMS is excellent with a reported 5 year survival rate of 95%.

- "Alveolar rhabdomyosarcoma" (ARMS) is the second most common type. ARMS comprises approximately 20–25% of RMS-related tumors, and it is equally distributed among all age groups with an incidence of about 1 case per 1 million people ages 0 to 19. For this reason, it is the most common form of RMS observed in young adults and teenagers, who are less prone to the embryonal variant. This type of RMS is characterized by densely-packed, round cells that arrange around spaces similar in shape to pulmonary alveoli, although variants have been discovered without these characteristic alveolar spacings. ARMS tends to form more often in the extremities, trunk, and peritoneum. It is also typically more aggressive than ERMS.

- "Anaplastic (undifferentiated) rhabdomyosarcoma", also known as "pleomorphic rhabdomyosarcoma", is the final variant of RMS recognized in most classification systems. Anaplastic rhabdomyosarcoma is defined by the presence of anaplastic cells with large, lobate hyperchromatic nuclei and multipolar mitotic figures. These tumors display high heterogeneity and extremely poor differentiation. The anaplastic cells may be diffuse or localized, with the diffuse variation correlating to a worse prognosis. It occurs most often in adults, rarely in children, and is often discovered in the extremities. Due to the lack of discernible separation among cancers of this type, clinicians will often label undiagnosed sarcomas with little to no discernible features as anaplastic RMS. It is the most aggressive type of RMS, and will often require intensive treatment.

There is also an extremely rare subtype of RMS that has been described as "sclerosing rhabdomyosarcoma" by "Folpe, et al", but it is not a currently recognized subtype by the NCI or WHO. This subtype has characteristic histology involving hyaline sclerosis and pseudovascular development. Its origins are unclear, but some studies have pointed to an association with embryonal RMS.

Multiple classification systems have been proposed for guiding management and treatment, and the most recent and widely used classification system is the "International Classification of Rhabdomyosarcoma" or ICR. It was created by the IRSG in 1995 after their series of four multi-institutional trials aimed at studying the presentation, histology, epidemiology, and treatment of RMS (IRSG I–IV). The ICR system is based on prognostic indicators identified in IRSG I–IV. Pleomorphic rhabdomyosarcoma usually occurs in adults rather than children, and is therefor not included in this system. Sclerosing rhabdomyosarcoma is also not included in this system due to its rare presentation and weak classification schema.

Ewing's sarcoma is more common in males (1.6 male:1 female) and usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age. It can occur anywhere in the body, but most commonly in the pelvis and proximal long tubular bones, especially around the growth plates. The diaphyses of the femur are the most common sites, followed by the tibia and the humerus. Thirty percent are overtly metastatic at presentation. Patients usually experience extreme bone pain.

Signs and symptoms include: intermittent fevers, anemia, leukocytosis, increased sedimentation rate, and other symptoms of inflammatory systemic illness. Also, depending on the type, progression, and location of the tumor, great pain may occur.

According to the Bone Cancer Research Trust (BCRT), the most common symptoms are: localized pain, swelling, and sporadic bone pain with variable intensity. The swelling is most likely to be visible if the sarcoma is located on a bone near the surface of the body, but when it occurs in other places deeper in the body, like on the pelvis, it may not be visible.

Alveolar rhabdomyosarcoma (ARMS) is a sub-type of the rhabdomyosarcoma soft tissue cancer family whose lineage is from mesenchymal cells and are related to skeletal muscle cells. ARMS tumors resemble the alveoli tissue that can be found in the lungs. Tumor location varies from patient to patient, but is commonly found in the head and neck region, male and female urogenital tracts, the torso, and extremities. Two fusion proteins can be associated with ARMS, but are not necessary, PAX3-FKHR (now known as FOXO1). and PAX7-FKHR. In children and adolescents ARMS accounts for about 1 percent of all malignancies, has an incidence rate of 1 per million, and most cases occur sporadically with no genetic predisposition.

Childhood rhabdomyosarcoma consists of three subgroups. Embryonal is the most common among children and young adults. Alveolar and anaplastic rhabdomyosarcoma occur in the teenage years.

- Embryonal rhabdomyosarcoma develops within the first seven weeks of the embryo's development. Rapid cell growth causes masses to form along the head, neck, urinary tract, and genital organs.

- Alveolar, the second most common group, is seen later in life. During the teen years, large muscle groups come under attack, including the torso and large appendages. Aggressive treatment is needed to stop or limit progression of alveolar rhabdomyosarcoma.

- Anaplastic rhabdomyosarcoma is rarely seen in children and only precise intensive lab work can identify it.

Childhood rhabdomyosarcoma is difficult to diagnose. Factors that increase the likelihood of this cancer include Li-Fraumeni syndrome, type one Neurofibromatosis, Beckwith-Wiedemann syndrome, Costello syndrome, and Noonan syndrome. Each contribute to deformations of bones, tissue, and muscles.

Ewing sarcoma or Ewing's sarcoma () is a malignant small, round, blue cell tumor. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the ribs and clavicle (collar bone).

Since a common genetic locus is responsible for a large percentage of Ewing sarcoma and primitive neuroectodermal tumors, these are sometimes grouped together in a category known as the Ewing family of tumors.

Ewing sarcoma occurs most frequently in teenagers and young adults, with a male/female ratio of 1.6:1.

Although usually classified as a bone tumor, Ewing's sarcoma can have characteristics of both mesodermal and ectodermal origin, making it difficult to classify.

James Ewing (1866–1943) first described the tumour, establishing that the disease was separate from lymphoma and other types of cancer known at that time.

There are few early warning signs that a patient has a DSRCT. Patients are often young and healthy as the tumors grow and spread uninhibited within the abdominal cavity. These are rare tumors and symptoms are often misdiagnosed by physicians. The abdominal masses can grow to enormous size before being noticed by the patient. The tumors can be felt as hard, round masses by palpating the abdomen.

First symptoms of the disease often include abdominal distention, abdominal mass, abdominal or back pain, gastrointestinal obstruction, lack of appetite, ascites, anemia, and/or cachexia.

Other reported symptoms include unknown lumps, thyroid conditions, hormonal conditions, blood clotting, kidney or urological problems, testicle, breast, uterine, vaginal, or ovarian masses.

Sarcoma botryoides or botryoid sarcoma or botryoid rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma, that can be observed in the walls of hollow, mucosa lined structures such as the nasopharynx, common bile duct, urinary bladder of infants and young children or the vagina in females, typically younger than age 8. The name comes from the gross appearance of "grape bunches" ("botryoid" in Greek).

Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.

Although rhabdoid variants of LCLC are sometimes referred to as "rhabdoid carcinomas", this particular term should be reserved for examples of "pure" rhabdoid neoplasms (i.e. those that do not contain cells containing other histological variants)

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.

A sarcoma is a cancer that arises from transformed cells of mesenchymal origin. Thus, malignant tumors made of cancellous bone, cartilage, fat, muscle, vascular, or hematopoietic tissues are, by definition, considered sarcomas. This is in contrast to a malignant tumor originating from epithelial cells, which are termed carcinoma. Human sarcomas are quite rare. Common malignancies, such as breast, colon, and lung cancer, are almost always carcinoma. The term is from the Greek "sarx" meaning "flesh".

Giant-cell carcinoma of the lung (GCCL) is a rare histological form of large-cell lung carcinoma, a subtype of undifferentiated lung cancer, traditionally classified within the non-small-cell lung carcinomas (NSCLC).

The characteristic feature of this highly lethal malignancy is the distinctive light microscopic appearance of its extremely large cells, which are bizarre and highly pleomorphic, and which often contain more than one huge, misshapen, pleomorphic nucleus ("syncytia"), which result from cell fusion.

Although it is common in the lung cancer literature to refer to histologically mixed tumors containing significant numbers of malignant giant cells as "giant-cell carcinomas", technically a diagnosis of "giant-cell carcinoma" should be limited strictly to neoplasms containing "only" malignant giant cells (i.e. "pure" giant-cell carcinoma).

Aside from the great heterogeneity seen in lung cancers (especially those occurring among tobacco smokers), the considerable variability in diagnostic and sampling techniques used in medical practice, the high relative proportion of individuals with suspected GCCL who do not undergo complete surgical resection, and the near-universal lack of complete sectioning and pathological examination of resected tumor specimens prevent high levels of quantitative accuracy.

The tumor largely affects children under 15 years of age and about 20% only are found in adults with nearly 60% involving males and 40% females (1). The most frequent locations are head and neck (orbit and nasopharynx), central nervous system, abdomen and retroperitoneum, pelvis, perineum, scrotum and prostate(1). Clinical symptoms are not specific and usually caused by local tumor compression and infiltration.

The differential diagnosis of LCLC-RP includes secondary metastatic lesions, melignant melanoma of the lung with rhabdoid phenotype, mucinous adenocarcinomas (particularly those featuring signet-ring cells), rhabdomyosarcoma, epitheloid angiosarcoma, pleural mesothelioma, and plasmacytoma.

Myosarcoma is a malignant muscle tumor. People with myosarcoma often wake up with the feeling as if they had a cramp during their sleep.

Leiomyosarcoma is sarcoma of smooth muscle, and rhabdomyosarcoma is sarcoma of striated muscle. However, the term myosarcoma itself still appears in the literature.

Desmoplastic small-round-cell tumor is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones.

The tumor is classified as a soft tissue sarcoma. It is considered a childhood cancer that predominantly strikes boys and young adults. The disease rarely occurs in females, but when it does the tumors can be mistaken for ovarian cancer.

In dogs, mast cell tumors are the most frequent round cell tumor.