Diagnosis and treatment of canine lymphoma, MCT, and osteosarcoma
DENVER, CO − Lymphosarcoma, mast cell disease, and osteosarcoma are all common types of cancers in dogs. Understanding the prevalence, clinical signs, staging, and available therapies for each type of cancer will help veterinary technicians provide optimal care to this important patient population, explained Steven E. Suter, VMD, MS, PhD, DACVIM, speaking at the American College of Veterinary Internal Medicine Forum.
Canine lymphosarcoma (LSA) accounts for 7-24% of all canine tumours and though some breeds are more affected than others, all breeds of dogs are susceptible. Weak links have been associated between LSA and viral infections, pesticide exposure, and possibly impaired immune function. Approximately 80% of dogs with LSA present with multicentric disease, manifested via peripheral lymphadenopathy. Most dogs are asymptomatic at presentation, although 20%- 40% have a history of weight loss, lethargy, anorexia, and febrile episodes. Also, approximately 27%-34% of dogs have pulmonary infiltrates. There is also a specific type of LSA called hepatosplenic LSA. These dogs do not have any outward evidence of disease, but instead have an expansion of a specific type of T-cell, called a gammadelta T-cell. These cells tend to invade the sinusoids of the liver and spleen and eventually the bone marrow. Finally, LSA can be found in virtually any organ in the body, with and without peripheral lymphadenopathy or invasion into other organs at the same time. Dr. Suter stressed the importance of having LSA on a differential list for most physical exam findings.
The clinical signs associated with canine LSA are extremely variable depending on site of disease, extent of organ involvement, and disease progression. Dogs can present with huge peripheral lymph nodes and be completely normal clinically, and other dogs present with almost no outward evidence of disease and are quite ill. Dr. Suter said that in his hospital all dogs with LSA are treated as emergencies, since the disease can progress rapidly. Clinical staging should include complete history, physical exam, complete blood count, serum chemistry, urinalysis, thoracic and abdominal radiographs or ultrasound, bone marrow aspiration, and lymph node biopsy or cytology.
LSA diagnosis is usually fairly straightforward; on physical exam peripheral lymphadenopathy, hepatomegaly, and splenomegaly can usually be confirmed. Other findings suggestive of LSA include dyspnea/tachypnea with reduced cardiac sounds, ocular infiltrates or hyphema, chronic diarrhea, or vomiting. Abnormalities seen on the CBC should not be automatically attributed to the lymphosarcoma, but evaluated independently. The most common cause of hypercalcemia is LSA. Renal disease or liver abnormalities are not uncommon in dogs with LSA.
LSA is usually relatively easy to diagnose cytologically; PCR for antigen receptor rearrangements can be used for difficult to diagnose cases. Histologic grading may also be useful. Identification of mediastinal mass, sternal lymph nodes, and abdominal involvement aids via imaging can help identify those dogs requiring close monitoring during the post-treatment period.
LSA therapy consists mainly of systemic chemotherapy, with combination chemotherapy being generally more effective than single agent chemotherapy. The best single agent for LSA is doxorubicin. Most protocols include tapering doses of prednisone and a combination of L- asparaginase, vincristine, cytoxan, and doxorubicin. Many institutions now incorporate one-half body irradiation at various points in the chemotherapy protocol, which seems to show some improvement over chemotherapy alone. Autologous peripheral blood stem cell transplantation is currently the only protocol that may completely cure some patients with LSA; about 80%-90% of LSA patients will attain a complete remission once starting chemotherapy.
Canine mast cell disease (MCT)
Cutaneous canine MCT represents approximately 16-21% of all cutaneous tumours in dogs. Both dermal and squamous MCT are the most common types and they are usually found in older dogs. The etiology of canine MCT remains virtually unknown.
Canine MCT is generally divided into Grades I, II, and III, with Grade I tumours generally acting biologically benign. Grade III tumours are considered highly metastatic. The vast majority of canine MCT are, unfortunately, Grade II tumours, which are essentially biologically unpredictable. Muzzle, preputial/inguinal, nailbed, and mucocutaneous tumours are all anecdotally reported to be more aggressive. Solitary tumours tend to metastasize to regional lymph nodes first before spreading elsewhere.
Most tumours are solitary, but 11%-14% of patients have multiple lesions. Most more benign lesions tend to be solitary, 1-4cm in diameter, slow growing, and present for more than six months. The vast majority of dogs with cutaneous MCT are completely asymptomatic at initial presentation.
Clinical staging of canine MCT includes a complete blood count, serum chemistry, urinalysis, abdominal ultrasound, thoracic radiographs, with or without buffy coat preps if Stage IV is suspected, and with or without CT scan if surgery is indicated. MCT are generally very easy to diagnose with an FNA of the mass in question, although a biopsy is needed to determine the grade. There are a number of immunostains that are now available through some academic institutions and private labs, including Ki-67, AgNors, and c-kit.
Due to the metastatic potential of these tumours, treatment usually consists of surgery with or without irradiation. Chemotherapy historically has consisted of steroids, vinblastine, and CCNU, but some other more targeted chemotherapeutics, such as Palladia or Kinavet, are also now available. All dogs with a visible MCT tumour should be started on Benedryl and PepcidAC (or similar drugs) to decrease the chances of GI ulceration.
The prognosis for dogs with grade III cutaneous and visceral MCT remains poor, no matter what treatment option is used. In one study in dogs with GI MCT: only 40% were alive 30 days after first admission and fewer than 10% were alive at six months.
Canine osteosarcoma (OSA)
Canine OSA represents approximately 85% of all primary bone tumours and 3%-6% or all canine neoplasias. In large breed dogs the distal radius is the primary affected site, with the proximal humerus and distal femur/tibia the next most common sites. The front limbs are affected about twice as much as the hind limbs.
The etiology of some canine OSAs can be caused by foreign bodies (orthopedic implants), bone infarcts, chronic osteomyelitis, bone trauma, and occur at sites of previous radiation exposure. Other weaker links include viruses and chemicals. Breed is the most documented etiology, with large/giant breed dogs having 60 times the risk of developing OSA compared to small breeds. In fact, 90% of OSA occurs in dogs weighing more than 35 lbs.
OSA is, unfortunately, considered metastatic at diagnosis. The tumour is typically very aggressive, with extensive lysis, bone invasion and destruction. The tumour spreads mainly through the blood and most commonly affects the lungs, other bones, and abdominal organs.
Clinical signs of OSA include obviously lameness of the affected leg, swelling at the tumour site, muscle atrophy of the affected limb due to disuse, anorexia and lethargy, and possible respiratory signs due to metastatic disease. OSA of sites other than the limbs, such as oral, spinal, rib, etc., can lead to other clinical sings such as dysphagia, tooth loss, facial deformity, exophthalmos, and neurologic signs.
Staging of canine OSA incudes complete blood count, serum chemistry, urinalysis, abdominal ultrasound, thoracic radiographs, limb radiographs, and if necessary, technetium scanning. The tumour itself can be diagnosed via large bore needle FNAs or bone biopsies.
Treatment typically consists of amputation of the affected limb followed by systemic chemotherapy. Palliative radiation therapy for limb OSAs can be used to alleviate pain if amputation is not an option, although no life extension benefit exists with this treatment. There are also now a wide variety of NSAIDs available with additional drugs to augment their efficacy. Dr. Suter said that some veterinary institutions also offer a variety of limb-sparing surgeries that remove the affected part of the limb and replace it with either a piece of donor bone or a piece of patient bone, noting that this treatment will preserve leg function, but does not prolong life.CVT
