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.

The diagnosis of synovial sarcoma is typically made based on histology and is confirmed by the presence of t(X;18) chromosomal translocation.

Two cell types can be seen microscopically in synovial sarcoma. One fibrous type, known as a spindle or sarcomatous cell, is relatively small and uniform, and found in sheets. The other is epithelial in appearance. Classical synovial sarcoma has a biphasic appearance with both types present. Synovial sarcoma can also appear to be poorly differentiated or to be monophasic fibrous, consisting only of sheets of spindle cells. Some authorities state that, extremely rarely, there can be a monophasic epithelial form which causes difficulty in differential diagnosis. Depending on the site, there is similarity to biphenotypic sinonasal sarcoma, although the genetic findings are distinctive.

Like other soft tissue sarcomas, there is no universal grading system for reporting histopathology results. In Europe, the Trojani or French system is gaining in popularity while the NCI grading system is more common in the United States. The Trojani system scores the sample, depending on tumour differentiation, mitotic index, and tumour necrosis, between 0 and 6 and then converts this into a grade of between 1 and 3, with 1 representing a less aggressive tumour. The NCI system is also a three-grade one, but takes a number of other factors into account.

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.

It can be detected by magnetic resonance imaging (MRI), but a biopsy is required for the definitive diagnosis. MRI findings typically show a well-circumscribed mass that is dark on T1-weighted images and bright on T2-weighted images. Central necrosis is often present and identifiable by imaging, especially in larger masses.

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.

Dermatofibrosarcoma protuberans is diagnosed with a biopsy, when a portion of the tumor is removed for examination. In order to ensure that enough tissue is removed to make an accurate diagnosis, the initial biopsy of a suspected DFSP is usually done with a core needle or a surgical incision.

ASPS is an extremely rare cancer. While sarcomas comprise about 1% of all newly diagnosed cancers, and 15% of all childhood cancers, ASPS comprises less than 1% of sarcomas. According to the American Cancer Society, about 9530 new cases of soft tissue sarcoma will be diagnosed in the USA in 2006. This predicts under 100 new cases of ASPS. Such low numbers of occurrence seriously impede the search for a cure by making it hard to gather any meaningful statistics about the disease. As a result, finding the best treatment option often involves making a lot of educated guesses.

Sarcomas are given a number of different names based on the type of tissue that they most closely resemble. For example, osteosarcoma resembles bone, chondrosarcoma resembles cartilage, liposarcoma resembles fat, and leiomyosarcoma resembles smooth muscle.

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

Surgery is important in the treatment of most sarcomas. Limb sparing surgery, as opposed to amputation, can now be used to save the limbs of patients in at least 90% of extremity tumor cases. Additional treatments, including chemotherapy and radiation therapy, may be administered before and/or after surgery. Chemotherapy significantly improves the prognosis for many sarcoma patients, especially those with bone sarcomas. Treatment can be a long and arduous process, lasting about a year for many patients.

- Liposarcoma treatment consists of surgical resection, with chemotherapy not being used outside of the investigative setting. Adjuvant radiotherapy may also be used after surgical excision for liposarcoma.

- Rhabdomyosarcoma is treated with surgery, radiotherapy, and/or chemotherapy. The majority of rhabdomyosarcoma patients have a 50–85% survival rate.

- Osteosarcoma is treated with surgical resection of as much of the cancer as possible, often along with neoadjuvant chemotherapy. Radiotherapy is a second alternative although not as successful.

Prognosis depends on the primary tumor grade (appearance under the microscope as judged by a pathologist), size, resectability (whether it can be completely removed surgically), and presence of metastases. The five-year survival is 80%.

The only reliable way to determine whether a soft-tissue tumour is benign or malignant is through a biopsy. There are two methods for acquisition of tumour tissue for cytopathological analysis;

- Needle Aspiration, via biopsy needle

- surgically, via an incision made into the tumour.

A pathologist examines the tissue under a microscope. If cancer is present, the pathologist can usually determine the type of cancer and its grade. Here, 'grade' refers to a scale used to represent concisely the predicted growth rate of the tumour and its tendency to spread, and this is determined by the degree to which the cancer cells appear abnormal when examined under a microscope. Low-grade sarcomas, although cancerous, are defined as those that are less likely to metastasise. High-grade sarcomas are defined as those more likely to spread to other parts of the body.

For soft-tissue sarcoma there are two histological grading systems : the National Cancer Institute (NCI) system and the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system.

Soft tissue sarcomas commonly originate in the upper body, in the shoulder or upper chest. Some symptoms are uneven posture, pain in the trapezius muscle and cervical inflexibility [difficulty in turning the head].

The most common site to which soft tissue sarcoma spreads is the lungs.

Although KS may be suspected from the appearance of lesions and the patient's risk factors, definite diagnosis can be made only by biopsy and microscopic examination. Detection of the KSHV protein LANA in tumor cells confirms the diagnosis.

In differential diagnosis, arteriovenous malformations, pyogenic granuloma and other vascular proliferations can be microscopically confused with KS.

Blood tests to detect antibodies against KSHV have been developed and can be used to determine whether a person is at risk for transmitting infection to their sexual partner, or whether an organ is infected prior to transplantation. However, these tests are not available except as research tools, and, thus, there is little screening for persons at risk for becoming infected with KSHV, such as people following a transplant.

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.

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.

NMC when viewed microscopically, are poorly differentiated carcinomas which show abrupt transitions to islands of well-differentiated squamous epithelium. This tumor pattern is not specific or unique to NUT midline carcinoma, but this pattern is most suggestive of the diagnosis. The neoplastic cells will show a positive reaction with various cytokeratins, p63, CEA, and CD34 immunohistochemistry. However, the NUT antibody confirms the diagnosis (although only available in a limited number of laboratories).

The differential diagnosis is quite wide, but it is important to consider this tumor type when seeing a poorly differentiated tumor that shows abrupt areas of keratinization. Other tumors included in the differential diagnosis are sinonasal undifferentiated carcinomas, Ewing sarcoma/Primitive neuroectodermal tumor, leukemia, rhabdomyosarcoma, and melanoma. When NUT midline carcinoma is seen in the head and neck, the squamous lining of the cavities may be entrapped by the neoplastic cells, and so it is important to document the carcinoma cells in the rest of the tumor by a variety of stains (including cytokeratin or p63). One of the most helpful and characteristic findings is the focal abrupt squamous differentiation, where stratification and gradual differentiation are absent, resembling a Hassall corpuscle of the thymus.

The defining feature of NMCs is rearrangement of the "NUT" gene.

Most common is a translocation involving the BRD4 gene and NUT gene (t(15;19)(q13;p13.1)).

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.

Tissue biopsy is the diagnostic modality of choice. Due to a high incidence of lymph node involvement, a sentinel lymph node biopsy is often performed. A common characteristic of epithelioid sarcoma (observed in 80% of all cases) is the loss of function of the SMARCB1 gene (also termed BAF47, INI1, or hSNF5). Immunohistochemical staining of INI1 is available and can be used for the diagnosis of epithelioid sarcoma. MRI is the diagnostic modality of choice for imaging prior to biopsy and pathologic diagnosis, with the primary role being the determination of anatomic boundaries.

Ancillary testing for fibrosarcoma includes IHC, where vimentin is positive, cytokeratin and S100 are negative, and actin is variable.

Treatment is primarily surgical, with chemotherapy and radiation therapy sometimes used.

The NCCN guideline recommends CCPDMA or Mohs surgery for the best cure rate of DFSP. Mohs surgery can be extremely effective. It will remove the tumor and all related pathological cells without a wide-area excision that may overlook sarcoma cells that have penetrated muscle tissue.

The standard of care for patients with DFSP is surgery. Usually, complete surgical resection with margins of 2 to 4 cm (recommended) is performed. The addition of adjuvant radiotherapy (irradiation) improves local control in patients with close or positive margins during the surgery. A special surgical technique, the "Mohs micrographic surgery" (MMS), can be employed in patients with DFSP. MMS is technically possible if the DFSP is in an anatomically confined area. A high probability of cure of DFSP can be attained with MMS as long as the final margins are negative. Patients who have a recurrent DFSP can have further surgery, but the probability of adverse effects of surgery and/or metastasis is increased in these patients. The Mohs surgery is highly successful.

Imatinib is approved for treatment. As is true for all medicinal drugs that have a name that ends in "ib," imatinib is a small molecular pathway inhibitor; imatinib inhibits tyrosine kinase. It may be able to induce tumor regression in patients with recurrent DFSP, unresectable DFSP or metastatic DFSP. There is clinical evidence that imatinib, which inhibits PDGF-receptors, may be effective for tumors positive for the t(17;22) translocation.

Evidence is conflicting on the prognostic significance of chloromas in patients with acute myeloid leukemia. In general, they are felt to augur a poorer prognosis, with a poorer response to treatment and worse survival; however, others have reported chloromas associate, as a biologic marker, with other poor prognostic factors, and therefore do not have independent prognostic significance.

The staging for epithelioid sarcoma takes into account size and location of the primary tumor, lymph node involvement, presence and location of metastasis, and histologic grade (a measure of disease aggressiveness)

MCACL has a much more favorable prognosis than most other forms of adenocarcinoma and most other NSCLC's. Cases have been documented of continued growth of these lesions over a period of 10 years without symptoms or metastasis. The overall mortality rate appears to be somewhere in the vicinity of 18% to 27%, depending on the criteria that are used to define this entity.