Bone metastases are a major clinical concern that can cause severe pain, bone fractures, spinal cord compression, hypercalcemia, anemia, spinal instability, decreased mobility, and rapid degradation in the quality of life for patients. Patients have described the pain as a dull ache that grows worse over time, with intermittent periods of sharp, jagged pain. Even under controlled pain management, these periods of breakthrough pain can occur rapidly, without warning, several times a day. Pain may be worse at night and partially relieved by activity. Metastases to weightbearing bones may become symptomatic early in the course of disease as compared to metastases to the flat bones of the rib or sternum.

- Effects of bone metastasis

- severe pain

- bone fractures

- spinal cord compression

- hypercalcemia

- anemia

- spinal instability

- decreased mobility

Bone metastases, or metastatic bone disease, is a class of cancer metastases that results from primary tumor invasion to bone. Bone-originating primary tumors such as osteosarcoma, chondrosarcoma, and Ewing's sarcoma are rare. Unlike hematological malignancies that originate in the blood and form non-solid tumors, bone metastases generally arise from epithelial tumors and form a solid mass inside the bone. Bone metastases cause severe pain, characterized by a dull, constant ache with periodic spikes of incident pain.

Many patients first complain of pain that may be worse at night, may be intermittent and of varying intensity and may have been occurring for some time. Teenagers who are active in sports often complain of pain in the lower femur, or immediately below the knee. If the tumor is large, it can present as overt localised swelling. Sometimes a sudden fracture is the first symptom, because affected bone is not as strong as normal bone and may fracture abnormally with minor trauma. In cases of more deep-seated tumors that are not as close to the skin, such as those originating in the pelvis, localised swelling may not be apparent.

Initially, nearby lymph nodes are struck early. The lungs, liver, brain, and bones are the most common metastasis locations from solid tumors.

- In lymph nodes, a common symptom is lymphadenopathy

- Lungs: cough, hemoptysis and dyspnea (shortness of breath)

- Liver: hepatomegaly (enlarged liver), nausea and jaundice

- Bones: bone pain, fracture of affected bones

- Brain: neurological symptoms such as headaches, seizures, and vertigo

Although advanced cancer may cause pain, it is often not the first symptom.

Some patients, however, do not show any symptoms.

When the organ gets a metastatic disease it begins to shrink until its lymph nodes burst, or undergo lysis.

Patients usually present with pain and limited range of motion caused by tumor's proximity to the joint space. Swelling may occur, as well, if the tumor has been growing for a long time. Some patients may be asymptomatic until they develop a pathologic fracture at the site of the tumor. They usually originate from the epiphysis of long bones, but in rare cases, they may arise from anterior arc of the ribs.

The symptoms may include muscular aches and pains in arms or legs and abdominal pain. Patients may also experience nerve pain which feels like an electric shock due to weight bearing.

The most common symptom is mild to severe pain that is gradually progressive in the affected region and may be initially attributed to a minor injury or sports-related injury. Pain may be present for several weeks, months, or years. Other symptoms in order of most common to least commonly observed include swelling, a limp (when affected bone is in the lower extremity), joint stiffness, and a soft tissue mass.

Physical findings include localized tenderness and a decreased range of motion in the involved bone and nearby joint, muscle atrophy, a palpable mass, soft tissue swelling, and joint effusion in the affected area. Less commonly, pathological fractures can be found, especially in cases involving the foot. In cases involving the temporal bone, tinnitus, dizziness, and hearing loss have been reported.

In a publication by Turcotte et al. it was found that the average duration of symptoms for patients with chondroblastoma was about 20 months, ranging from 5 weeks to 16 years.

An osteosarcoma (OS) or osteogenic sarcoma (OGS) is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignant osteoid.

Osteosarcoma is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults.

Physicians grade chondrosarcoma using several criteria, but particularly on how abnormal the cancerous cells appear under the microscope, and the growth rate of the tumors themselves, both of which are directly linked to the propensity of the cancer to invade locally, and to spread widely to distant organs and sites in the body (called metastasis).

Grade 1 chondrosarcoma grows relatively slowly, has cells whose histological appearance is quite similar to cells of normal cartilage, and have much less aggressive invasive and metastatic properties. Grades 2 and 3 are increasingly faster-growing cancers, with more varied and abnormal-looking cells, and are much more likely to infiltrate surrounding tissues, lymph nodes, and organs. Some, but not all, authorities and medical facilities assign a "Grade 4" to the most anaplastic, undifferentiated cartilage-derived tumors.

The most common sites for chondrosarcoma to grow are the pelvis and shoulder, along with the superior metaphyseal and diaphyseal regions of the arms and legs. However, chondrosarcoma may occur in any bone, and are sometimes found in the skull, particularly at its base.

ICD-O codes provide a more precise classification of chondrosarcoma. These "subtypes" are derived from, and reflect, both (a) the topographical location of the tumor, (b) the histological characteristics of the cancerous cartilage cells, and (c) the makeup of the surrounding matrix material associated with the tumor:

Chondroblastoma is a rare, benign, locally aggressive bone tumor that typically affects the epiphyses or apophyses of long bones. It is thought to arise from an outgrowth of immature cartilage cells (chondroblasts) from secondary ossification centers, originating from the epiphyseal plate or some remnant of it.

Chondroblastoma is very uncommon, accounting for only 1-2% of all bone tumors. It affects mostly children and young adults with most patients being in the second decade of life, or less than 20 years of age. Chondroblastoma shows a predilection towards the male sex, with a ratio of male to female patients of 2:1. The most commonly affected site is the femur, followed by the humerus and tibia. Less commonly affected sites include the talus and calcaneus of the foot and flat bones.

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; it is typically spoken of as such spread by a cancerous tumor. The newly pathological sites, then, are metastases (mets).

Cancer occurs after cells are genetically altered to proliferate rapidly and indefinitely. This uncontrolled proliferation by mitosis produces a primary heterogeneic tumour. The cells which constitute the tumor eventually undergo metaplasia, followed by anaplasia then dysplasia, resulting in a malignant phenotype. This malignancy allows for invasion into the circulation, followed by invasion to a second site for tumorigenesis.

Some cancer cells known as circulating tumor cells acquire the ability to penetrate the walls of lymphatic or blood vessels, after which they are able to circulate through the bloodstream to other sites and tissues in the body. This process is known (respectively) as "lymphatic" or "hematogenous" spread. After the tumor cells come to rest at another site, they re-penetrate the vessel or walls and continue to multiply, eventually forming another clinically detectable tumor. This new tumor is known as a metastatic (or "secondary") tumor. Metastasis is one of the hallmarks of cancer, distinguishing it from benign tumors. Most cancers can metastasize, although in varying degrees. Basal cell carcinoma for example rarely metastasizes.

When tumor cells metastasize, the new tumor is called a "secondary" or "metastatic" tumor, and its cells are similar to those in the original or primary tumor. This means that if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called "metastatic breast cancer", not "lung cancer". Metastasis is a key element in cancer staging systems such as the TNM staging system, where it represents the "M". In overall stage grouping, metastasis places a cancer in Stage IV. The possibilities of curative treatment are greatly reduced, or often entirely removed, when a cancer has metastasized.

Chondrosarcoma is a cancer composed of cells derived from transformed cells that produce cartilage. Chondrosarcoma is a member of a category of tumors of bone and soft tissue known as sarcomas. About 30% of skeletal system cancers are chondrosarcomas. It is resistant to chemotherapy and radiotherapy. Unlike other primary bone cancers that mainly affect children and adolescents, chondrosarcoma can present at any age. It more often affects the axial skeleton than the appendicular skeleton.

Giant-cell tumor of the bone (GCTOB) is a relatively uncommon tumor of the bone. It is characterized by the presence of multinucleated giant cells (osteoclast-like cells). Malignancy in giant-cell tumor is uncommon and occurs in about 2% of all cases. However, if malignant degeneration does occur, it is likely to metastasize to the lungs. Giant-cell tumors are normally benign, with unpredictable behavior. It is a heterogeneous tumor composed of three different cell populations. The giant-cell tumour stromal cells (GCTSC) constitute the neoplastic cells, which are from an osteoblastic origin and are classified based on expression of osteoblast cell markers such as alkaline phosphatase and osteocalcin. In contrast, the mononuclear histiocytic cells (MNHC) and multinucleated giant cell (MNGC) fractions are secondarily recruited and comprise the non-neoplastic cell population. They are derived from an osteoclast-monocyte lineage determined primarily by expression of "CD68", a marker for monocytic precursor cells. In most patients, the tumors are slow to develop, but may recur locally in as many as 50% of cases.

Micrometastasis is a form of metastasis (the spread of a cancer from its original location to other sites in the body) in which the newly formed tumors are too minuscule to be detected.

Adjuvant chemotherapy and adjuvant radiotherapy are directed at killing any micrometastases, thus preventing relapse (regrowth of the cancer) and the (likely) death of the patient. Early detection of micrometastases could identify the patients who are most (and least) likely to benefit from adjuvant therapy.

The symptoms produced by metastatic breast cancer vary by the location of the metastases. For instance:

- Metastatic disease to the bone causes severe, progressive pain, and, less commonly, pathological fracture, erythema over the affected bone, and swelling.

- Metastatic breast cancer to the brain causes the following symptoms: persistent, progressively worsening headache, visual changes, seizures, nausea or vomiting, vertigo, behavioral and personality changes, and increased intracranial pressure.

- Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting

- Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest X-ray, and chest pain.

- Other nonspecific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss, and poor appetite.

Because different parts of the brain are responsible for different functions, symptoms vary depending on the site of metastasis within the brain. However, brain metastases should be considered in any cancer patient who presents with neurological or behavioral changes.

Brain metastases can cause a wide variety of symptoms which can also be present in minor, more common conditions. Neurological symptoms are often caused by increased intracranial pressure, with severe cases resulting in coma. The most common neurological symptoms include:

- New onset headaches: headaches occur in roughly half of brain metastasis patients, especially in those with many tumors.

- Paresthesias: patients often present with (hemiparesis), or weakness on only one side of the body, which is often a result of damage to neighboring brain tissue.

- Ataxia: when metastasis occurs to the cerebellum, patients will experience various difficulties with spatial awareness and coordination.

- Seizures: when present, often indicates disease involvement of the cerebral cortex.

Hemangiosarcoma is quite common in dogs, and more so in certain breeds including German Shepherd Dogs and Golden Retrievers. It also occurs in cats, but much more rarely. Dogs with hemangiosarcoma rarely show clinical signs until the tumor has become very large and has metastasized. Typically, clinical signs are due to hypovolemia after the tumor ruptures, causing extensive bleeding. Owners of the affected dogs often discover that the dog has hemangiosarcoma only after the dog collapses.

The tumor most often appears on the spleen, right heart base, or liver, although varieties also appear on or under the skin or in other locations. It is the most common tumor of the heart, and occurs in the right atrium or right auricular appendage. Here it can cause right-sided heart failure, arrhythmias, pericardial effusion, and cardiac tamponade. Hemangiosarcoma of the spleen or liver is the most common tumor to cause hemorrhage in the abdomen. Hemorrhage secondary to splenic and hepatic tumors can also cause ventricular arrythmias. Hemangiosarcoma of the skin usually appears as a small red or bluish-black lump. It can also occur under the skin. It is suspected that in the skin, hemangiosarcoma is caused by sun exposure. Occasionally, hemangiosarcoma of the skin can be a metastasis from visceral hemangiosarcoma. Other sites the tumor may occur include bone, kidneys, the bladder, muscle, the mouth, and the central nervous system.

The early lesions are usually asymptomatic. The patients presenting with an advanced stage of the disease comprises around 66-77% of the cases.

The most important signs include a lump in the neck when palpated and weight loss.

People may also present with fatigue as a symptom.

The primary tumor does not have readily discernible signs or symptoms as they grow within the tonsillar capsule. It is difficult to notice anything suspicious on examination of the tonsil other than slight enlargement or the development of firmness around the area.

The carcinoma may occur in one or more sites deep within the tonsillar crypts. It may be accompanied by the enlargement of the tonsil. The affected tonsil grows into the oropharyngeal space making it noticeable by the patient in the form of a neck mass mostly in the jugulodiagastric region.

As the tonsils consist of a rich network of lymphatics, the carcinoma may metastasise to the neck lymph nodes which many are cystic.

Extension of tumor to skull or mediastinum can occur.

The additional symptoms include a painful throat, dysphagia, otalgia (due to cranial nerve involvement), foreign body sensation, bleeding, fixation of tongue (infiltration of deep muscles) and trismus (if the pterygoid muscle is involved in the parapharyngeal space).

On the other hand, the tumor may also present as a deep red or white fungating wound growing outwards, breaking the skin surface with a central ulceration. This wound-like ulcer fails to heal (non-healing) leading to bleeding and throat pain and other associated symptoms.

During biopsy, the lesion may show three signs: Gritty texture, Firmness and cystification owing to keratinization, fribrosis and necrosis respectively.

Cervical lymphydenopathy may be present.

Presenting complaints and clinical signs are usually related to the site of origin of the primary tumor or to the presence of metastases, spontaneous tumor rupture, coagulopathies, or cardiac arrhythmias. More than 50% of patients are presented because of acute collapse after spontaneous rupture of the primary tumor or its metastases. Some episodes of collapse are a result of ventricular arrhythmias, which are relatively common in dogs with splenic or cardiac HSA.

Most common clinical signs of visceral hemangiosarcoma include loss of appetite, arrhythmias, weight loss, weakness, lethargy, collapse, pale mucous membranes, and/or sudden death. An enlarged abdomen is often seen due to hemorrhage. Metastasis is most commonly to the liver, omentum, lungs, or brain.

A retrospective study published in 1999 by Ware, "et al.", found a 5 times greater risk of cardiac hemangiosarcoma in spayed vs. intact female dogs and a 2.4 times greater risk of hemangiosarcoma in neutered dogs as compared to intact males.

A brain metastasis is a cancer that has metastasized (spread) to the brain from another location in the body and is therefore considered a secondary brain tumor. The metastasis typically shares a cancer cell type with the original site of the cancer. Metastasis is the most common cause of brain cancer, with tumors originating in the brain being less common. The most common sites of primary cancer which metastasize to the brain are lung, breast, colon, kidney, and skin cancer. Brain metastases can occur in patients months or even years after their original cancer is treated. Brain metastases have a poor prognosis for cure, but modern treatments are allowing patients to live months and sometimes years after the diagnosis.

UPS occurs most commonly in the extremities and retroperitoneum, but has been reported in other sites. Metastasis occurs most frequently in the lungs (90%), bones (8%), and liver (1%).

In the extremities, it presents itself as a painless enlarging soft tissue mass.

Roughly 70% of all patients living with advanced breast cancer have bone metastases. Very often bone metastases can be successfully managed for a long time.

Undifferentiated pleomorphic sarcoma (UPS), also undifferentiated pleomorphic sarcoma (PUS) and previously malignant fibrous histiocytoma (abbreviated MFH), is a type of cancer and soft tissue sarcoma.

It is considered a diagnosis of exclusion for sarcomas that cannot be more precisely categorized. Other sarcomas are cancers that form in bone and soft tissues, including muscle, fat, blood vessels, lymph vessels, and fibrous tissue (such as tendons and ligaments).

Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom.

All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.

Symptoms may include:

- Swelling in the extremities (arms or legs), also called peripheral edema; the swelling often is painless.

- Difficulty in moving the extremity that has the tumor, including a limp.

- Soreness localized to the area of the tumor or in the extremity.

- Neurological symptoms.

- Pain or discomfort: numbness, burning, or "pins and needles."

- Dizzyness and/or loss of balance.

Signs vary but may include bleeding from the nose, nasal discharge, facial deformity from bone erosion and tumor growth, sneezing, or difficulty breathing.