Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Family physicians and orthopedists rarely see a malignant bone tumor (most bone tumors are benign). The route to osteosarcoma diagnosis usually begins with an X-ray, continues with a combination of scans (CT scan, PET scan, bone scan, MRI) and ends with a surgical biopsy. A characteristic often seen in an X-ray is Codman's triangle, which is basically a subperiosteal lesion formed when the periosteum is raised due to the tumor. Films are suggestive, but bone biopsy is the only definitive method to determine whether a tumor is malignant or benign.
Most times, the early signs of osteosarcoma are caught on X-rays taken during routine dental check-ups. Osteosarcoma frequently develops in the mandible (lower jaw); accordingly, Dentist are trained to look for signs that may suggest osteosarcoma. Even though radiographic findings for this cancer vary greatly, one usually sees a symmetrical widening of the periodontal ligament space. If the dentist has reason to suspects osteosarcoma or another underlying disorder, he or she would refer the patient to an Oral & Maxillofacial surgeon for biopsy. A biopsy of suspected osteosarcoma outside of the facial region should be performed by a qualified orthopedic oncologist. The American Cancer Society states: "Probably in no other cancer is it as important to perform this procedure properly. An improperly performed biopsy may make it difficult to save the affected limb from amputation." It may also metastasise to the lungs, mainly appearing on the chest X-ray as solitary or multiple round nodules most common at the lower regions.
Amputation is the initial treatment, although this alone will not prevent metastasis. Chemotherapy combined with amputation improves the survival time, but most dogs still die within a year. Surgical techniques designed to save the leg (limb-sparing procedures) do not improve the prognosis.
Some current studies indicate osteoclast inhibitors such as alendronate and pamidronate may have beneficial effects on the quality of life by reducing osteolysis, thus reducing the degree of pain, as well as the risk of pathological fractures.
The initial evaluation involves radiographs (X-rays) of the affected site, but the only way to confirm the diagnosis is by sampling the tissue via biopsy or needle aspiration.
As soon as a tumor is detected, diagnosing the type of cancer remains a primary objective, as it helps determine the best possible treatment by the analysis of the structure of the tumor and cancer cells.
Standard X-rays are still acceptable and readily accessible imaging tools but their resolution and level of anatomical detail are not as good as for computed tomography (CT) scan. In order to definitively confirm cancer in the nasal cavity, a tissue biopsy should be obtained.
Treatments of cancer in cats usually consists of diagnosis and observation of the tumor to determine its type and size, the development of a treatment plan, the associated goals on the part of the treatment methods, and the regular evaluation of the overall health of the pet.
Depending on the pet's unique condition, there are several treatment options, including surgery, chemotherapy and radiation therapy. Treating the pain adequately is also of crucial importance to improve the pet's quality of life, especially if amputation is not performed.
Hemangiosarcoma can cause a wide variety of hematologic and hemostatic abnormalities, including anemia, thrombocytopenia (low platelet count), disseminated intravascular coagulation (DIC); presence of nRBC, schistocytes, and acanthocytes in the blood smear; and leukocytosis with neutrophilia, left shift, and monocytosis.
A definitive diagnosis requires biopsy and histopathology. Cytologic aspirates are usually not recommended, as the accuracy rate for a positive diagnosis of malignant splenic disease is approximately 50%. This is because of frequent blood contamination and poor exfoliation. Surgical biopsy is the typical approach in veterinary medicine.
Treatment options vary and depend on the type and stage of cancer. Common treatments include surgery, chemotherapy, radiation therapy, amputation, and immunotherapy. A combination of therapies may be used. Knowledge and treatment of cancer have increased significantly in the past three decades. Survival rates have also increased due to the increase prevalence of canine cancer treatment centers and breakthroughs in targeted drug development. Canine cancer treatment has become an accepted clinical practice and access to treatment for owners has widely expanded recently. Cancer-targeting drugs most commonly function to inhibit excessive cell proliferation by attacking the replicating cells. However, there is still a prevalent pharmacy gap in veterinary oncology.
There is one canine tumor vaccine approved by the USDA, for preventing canine melanoma. The Oncept vaccine activates T-cell responses and antibodies against tumor-specific tyrosinase proteins. There is limited information about canine tumor antigens, which is the reason for the lack of tumor-specific vaccines and immunotherapy treatment plans for dogs.
Success of treatment depends on the form and extent of the cancer and the aggressiveness of the therapy. Early detection offers the best chance for successful treatment. The heterogeneity of tumors makes drug development increasingly complex, especially as new causes are discovered. No cure for cancer in canines exist.
Some dog owners opt for no treatment of the cancer at all, in which case palliative care, including pain relief, may be offered. Regardless of how treatment proceeds following a diagnosis, the quality of life of the pet is an important consideration. In cases where the cancer is not curable, there are still many things which can be done to alleviate the dog's pain. Good nutrition and care from the dog's owner can greatly enhance quality of life.
VAS appears as a rapidly growing firm mass in and under the skin. The mass is often quite large when first detected and can become ulcerated or infected. It often contains fluid-filled cavities, probably because of its rapid growth. Diagnosis of VAS is through a biopsy. The biopsy will show the presence of a sarcoma, but information like location and the presence of inflammation or necrosis will increase the suspicion of VAS. It is possible for cats to have a granuloma form after vaccination, so it is important to differentiate between the two before radical surgery is performed. One guideline for biopsy is if a growth is present three months after surgery, if a growth is greater than two centimeters, or if a growth is becoming larger one month after vaccination.
X-rays are taken prior to surgery because about one in five cases of VAS will develop metastasis, usually to the lungs but possibly to the lymph nodes or skin.
Some myeloma centers now employ genetic testing, which they call a “gene array.” By examining DNA, oncologists can determine if patients are high risk or low risk of the cancer returning quickly following treatment.
Cytogenetic analysis of myeloma cells may be of prognostic value, with deletion of chromosome 13, non-hyperdiploidy and the balanced translocations t(4;14) and t(14;16) conferring a poorer prognosis. The 11q13 and 6p21 cytogenetic abnormalities are associated with a better prognosis.
Prognostic markers such as these are always generated by retrospective analyses, and it is likely that new treatment developments will improve the outlook for those with traditionally "poor-risk" disease.
SNP array karyotyping can detect copy number alterations of prognostic significance that may be missed by a targeted FISH panel. In MM, lack of a proliferative clone makes conventional cytogenetics informative in only ~30% of cases.
1. Virtual karyotyping identified chromosomal abnormalities in 98% of MM cases
2. del(12p13.31) is an independent adverse marker
3. amp(5q31.1) is a favorable marker
4. The prognostic impact of amp(5q31.1) over-rides that of hyperdiploidy and also identifies patients who greatly benefit from high-dose therapy.
Array-based karyotyping cannot detect balanced translocations, such as t(4;14) seen in ~15% of MM. Therefore, FISH for this translocation should also be performed if using SNP arrays to detect genome-wide copy number alterations of prognostic significance in MM.
Typically, either cytologic or histopathologic analysis of the suspected mass is done prior to initiating treatment. The commonly used diagnostic procedures for skin tumors are fine-needle aspiration cytology and tissue biopsy.
Cytology is an important tool that can help the veterinarian distinguish a tumor from inflammatory lesions. The biopsy technique used will largely depend on the tumor's size and location. Small masses are usually completely excised and sent to the pathology lab to confirm that the surrounding healthy tissues that were excised along with the tumor do not contain any cancer cells. If the tumor is larger, a small sample is removed for analysis and depending on the results, appropriate treatment is chosen. Depending on the tumor type and its level of aggressiveness, additional diagnostic tests can include blood tests to assess the pet’s overall health, chest X-rays to check for lung metastasis, and abdominal ultrasound to check for metastasis to other internal organs.
New vaccine protocols have been put forth by the American Association of Feline Practitioners that limit type and frequency of vaccinations given to cats. Specifically, the vaccine for feline leukemia virus should only be given to kittens and high risk cats. Feline rhinotracheitis/panleukopenia/calicivirus vaccines should be given as kittens, a year later and then every three years. Also, vaccines should be given in areas making removal of VAS easier, namely: as close as possible to the tip of the right rear paw for rabies, the tip of the left rear paw for feline leukemia (unless combined with rabies), and on the right shoulder—being careful to avoid the midline or interscapular space—for other vaccines (such as FVRCP). There have been no specific associations between development of VAS and vaccine brand or manufacturer, concurrent infections, history of trauma, or environment.
Radiation therapy has become the preferred treatment. Its advantage is that it treats the entire nasal cavity together with the affected bone and has shown the greatest improvement in survival. The radiation therapy is typically delivered in 10-18 treatment sessions over the course of 2–4 weeks.
Radiation therapy has a multitude of accompanying side effects and should be recommended on a case-by-case basis. Dogs in which nose bleeds are observed have an average life expectancy of 88 days. In instances where nosebleeds are not seen, the prognosis is slightly less grim. On average, a dog with nasal cancer has a life expectancy of 95 days.
Treatment includes chemotherapy and, where practical, removal of the tumor with the affected organ, such as with a splenectomy. Splenectomy alone gives an average survival time of 1–3 months. The addition of chemotherapy, primarily comprising the drug doxorubicin, alone or in combination with other drugs, can increase the average survival time to 2-4 months, or more.
A more favorable outcome has been demonstrated in recent research conducted at University of Pennsylvania Veterinary School, in dogs treated with a compound derived from the Coriolus versicolor (commonly known as "Turkey Tail") mushroom:
“We were shocked,” Cimino Brown said. “Prior to this, the longest reported median survival time of dogs with hemangiosarcoma of the spleen that underwent no further treatment was 86 days. We had dogs that lived beyond a year with nothing other than this mushroom as treatment.”There were not statistically significant differences in survival between the three dosage groups, though the longest survival time was highest in the 100 mg group, at 199 days, eclipsing the previously reported survival time.
The results were so surprising, in fact, that the researchers asked Penn Vet pathologists to recheck the dogs’ tissue biopsies to make sure that the dogs really had the disease.
“They reread the samples and said, yes, it’s really hemangiosarcoma,” Cimino Brown said.
Chemotherapy is available for treating hemangiosarcoma, but many owners opt not to pursue that treatment once their dog is diagnosed.
“It doesn’t hugely increase survival, it’s expensive and it means a lot of back and forth to the vet for the dog,” Cimino Brown said. “So you have to figure in quality of life.”
This treatment does not always work. So, one should always be prepared for their pet to have the same survival time as a dog who is untreated.
Visceral hemangiosarcoma is usually fatal even with treatment, and usually within weeks or, at best, months. In the skin, it can be cured in most cases with complete surgical removal as long as there is not visceral involvement.
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.
The diagnostic examination of a person with suspected multiple myeloma typically includes a skeletal survey. This is a series of X-rays of the skull, axial skeleton and proximal long bones. Myeloma activity sometimes appears as "lytic lesions" (with local disappearance of normal bone due to resorption), and on the skull X-ray as "punched-out lesions" (pepper pot skull). lesions man also be sclerotic which is seen as radiodense. Magnetic resonance imaging (MRI) is more sensitive than simple X-ray in the detection of lytic lesions, and may supersede skeletal survey, especially when vertebral disease is suspected. Occasionally a CT scan is performed to measure the size of soft tissue plasmacytomas. Bone scans are typically not of any additional value in the workup of myeloma patients (no new bone formation; lytic lesions not well visualized on bone scan).
A bone marrow biopsy is usually performed to estimate the percentage of bone marrow occupied by plasma cells. This percentage is used in the diagnostic criteria for myeloma. Immunohistochemistry (staining particular cell types using antibodies against surface proteins) can detect plasma cells which express immunoglobulin in the cytoplasm and occasionally on the cell surface; myeloma cells are typically CD56, CD38, CD138, CD319 positive and CD19 and CD45 negative. Cytogenetics may also be performed in myeloma for prognostic purposes, including a myeloma-specific FISH and virtual karyotype.
Historically, the CD138 has been used to isolate myeloma cells for diagnostic purposes. However, this antigen disappears rapidly ex vivo. Recently, however, it was discovered that the surface antigen CD319 (SLAMF7) is considerably more stable and allows robust isolation of malignant plasma cells from delayed or even cryopreserved samples.
Other useful laboratory tests include quantitative measurement of IgA, IgG, IgM (immunoglobulins) to look for immune paresis, and beta-2 microglobulin which provides prognostic information. On peripheral blood smear, the rouleaux formation of red blood cells is commonly seen, though this is not specific.
The recent introduction of a commercial immunoassay for measurement of free light chains potentially offers an improvement in monitoring disease progression and response to treatment, particularly where the paraprotein is difficult to measure accurately by electrophoresis (for example in light chain myeloma, or where the paraprotein level is very low). Initial research also suggests that measurement of free light chains may also be used, in conjunction with other markers, for assessment of the risk of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma.
This assay, the serum free light chain assay, has recently been recommended by the International Myeloma Working Group for the screening, diagnosis, prognosis, and monitoring of plasma cell dyscrasias.
The prognosis varies widely depending upon various risk factors. The Mayo Clinic has developed a risk-stratification model termed Mayo Stratification for Myeloma and Risk-adapted Therapy (mSMART) which divides people into high-risk and standard-risk categories. People with deletion of chromosome 13 or hypodiploidy by conventional cytogenetics, t(4;14), t(14;16) or 17p- by molecular genetic studies, or with a high plasma cell labeling index (3% or more) are considered to have high-risk myeloma .
Appearance and location of the tumor is enough to identify it as a mammary tumor. Biopsy will give type and invasiveness of the tumor. In addition, newer studies showed that certain gene expression patterns are associated with malignant behaviour of canine mammary tumors.
Surgical removal is the treatment of choice, but chest x-rays should be taken first to rule out metastasis. Removal should be with wide margins to prevent recurrence, taking the whole mammary gland if necessary. Because 40 to 50 percent of dog mammary tumors have estrogen receptors, spaying is recommended by many veterinarians. A recent study showed a better prognosis in dogs that are spayed at the time of surgery or that had been recently spayed. However, several other studies found no improvement of disease outcome when spaying was performed after the tumor had developed. Chemotherapy is rarely used.
Biopsy of affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-rays, ultrasound and bone marrow biopsy reveal other locations of the cancer. There are now a range of blood tests that can be utilised to aid in the diagnosis of lymphoma. Flow cytometry detects antibodies linked to tumour cell surface antigens in fluid samples or cell suspensions. Polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR) identifies circulating tumour cells based on unique genetic sequences. The canine Lymphoma Blood Test (cLBT) measures multiple circulating biomarkers and utilises a complex algorithm to diagnose lymphoma. This test utilises the acute phase proteins (C-Reactive Protein and Haptoglobin). In combination with basic clinical symptoms, it gives in differential diagnosis the sensitivity 83.5% and specificity 77%. The TK canine cancer panel is an indicator of general neoplastic disease. The stage of the disease is important to treatment and prognosis. Certain blood tests have also been shown to be prognostic.
The stage of the disease is important to treatment and prognosis.
- Stage I - only one lymph node or lymphoid tissue in one organ involved.
- Stage II - lymph nodes in only one area of the body involved.
- Stage III - generalized lymph node involvement.
- Stage IV - any of the above with liver or spleen involvement.
- Stage V - any of the above with blood or bone marrow involvement.
Each stage is divided into either "substage a", those without systemic symptoms; or "substage b", those with systemic symptoms such as fever, loss of appetite, weight loss, and fatigue.
Cancer prevalence in dogs increases with age and certain breeds are more susceptible to specific kinds of cancers. Millions of dogs develop spontaneous tumors each year. Boxers, Boston Terriers and Golden Retrievers are among the breeds that most commonly develop mast cell tumors. Large and giant breeds, like Great Danes, Rottweilers, Greyhound and Saint Bernards, are much more likely to develop bone cancer than smaller breeds. Lymphoma occurs at increased rates in Bernese Mountain dogs, bulldogs, and boxers. It is important for the owner to be familiar with the diseases to which their specific breed of dog might have a breed predisposition.
The specific treatment will depend on the tumor's type, location, size, and whether the cancer has spread to other organs. Surgical removal of the tumor remains the standard treatment of choice, but additional forms of therapy such as radiation therapy, chemotherapy, or immunotherapy exist.
When detected early, skin cancer in cats and dogs can often be treated successfully. In many cases, a biopsy can remove the whole tumor, as long as the healthy tissues removed from just outside the tumor area do not contain any cancer cells.
Medical imaging techniques such as X-rays, ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) are often used in evaluating animals with suspected liver tumors. Ultrasound-guided fine-needle aspiration or needle-core biopsy of liver masses are useful diagnostic tools that are minimally invasive to obtain samples for histopathological analysis.
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.
The veterinarian will typically perform a series of tests such as blood tests and imaging studies. The most definitive way to confirm/rule out intestinal tumors is to perform a medical procedure called endoscopy to visualize the organ and do a tissue biopsy.
Anal sac adenocarcinomas are often suspected due to location (palpable masse in anal sac) and behavior, but a biopsy and histopathology is necessary for a definitive diagnosis. Fine needle aspiration and cytology is a common first step. Cytopathology reveals clusters of cells with uniform round nuclei. These cells do not have many of the features usually associated with malignancy, such as a high nucleus to cytoplasm ratio or prominent nucleoli. Ultrasonography and radiography are performed to look for metastasis.