To be a great veterinarian is one thing, but the ability to maintain compassion and caring sets you apart from the rest.
A 10 year 6 month old, FS, German shepherd, initially presented to her primary veterinarian for vomiting yellow liquid 2-3 times per week for the past 1-2 months. Also, she was straining to defecate with no production when going on walks but was having normal bowel movements in the yard prior to going on walks. On physical examination she was noted to have a 1-2 cm mass in the left anal sac. Abdominal radiographs (not available for review) and a FNA of the anal sac mass were performed. Cytology results revealed an anal sac adenocarcinoma and referral to an oncologist was recommended.
She was evaluated by the oncology service at Hope Veterinary specialists 10 days later. Complete blood work was performed which was unremarkable. Three view thoracic radiographs revealed no evidence of metastasis and abdominal ultrasound showed an enlarged left sublumbar lymph node that measured 1.75 x 4.19 cms (Figure 1) and was normoechoic with diffusely heterogenous parenchyma.
Treatment options were discussed including the most aggressive option of surgery followed by adjuvant treatment such as radiation +/- chemotherapy vs. a palliative approach including radiation to the mass and lymph nodes with systemic therapy; either Palladia or chemotherapy.
The owners opted to pursue surgery and a left anal sacculectomy/mass resection and left sublumbar lymph node excision were performed without complications. Histopathology results revealed an anal sac adenocarcinoma with lymphatic invasion and narrow excision. The left medial iliac lymph node showed metastatic anal sac adenocarcinoma.
A follow-up appointment with the surgery service for suture removal and with the oncology service was performed at 16 days postop. The sutures were removed and chemotherapy (carboplatin IV q 3 weeks x 4-6 cycles) +/- radiation to the draining lymph nodes was discussed. The owner opted for chemotherapy alone and carboplatin was started that day. A recheck CBC in one week had no concerning findings. A recheck examination was performed by the oncology service 3 weeks after receiving her first dose of carboplatin and the owner reported that the first dose had affected her appetite slightly for a few days but had since resolved. A CBC had no concerning findings and the second dose of carboplatin was administered and maropitant citrate was prescribed. A recheck ultrasound to evaluate her lymph nodes is to be performed after two cycles of Carboplatin.
Tumors of the anal sac are uncommon and represent a small percentage of all tumors in dogs (<1%). The most common malignant tumor of the perianal region is the anal sac (gland) carcinoma accounting for 16.5% of all perianal tumors. These tumors are locally invasive and metastasize early in the course of disease. There does not appear to be a breed or sex predilection for this tumor and no consistent etiology has been noted.
In many cases these tumors are noted as an incidental finding on a routine rectal examination and can range in size from very small to very large before clinical signs occur. In dogs with clinical signs, perianal swelling, straining to defecate, licking at the perianal region, and bleeding were most commonly seen and are a result of a large anal sac tumor or severely enlarged regional lymph nodes. In other cases the increased drinking and urination was noted as a result of high calcium in the blood. This paraneoplastic syndrome is associated with release of the parathyroid related protein (PTHrp) which elevates the blood calcium, in some cases leading to significant kidney damage. It has been shown that up to 25% of dogs with anal sac tumors will have elevated calcium levels in the blood.
A diagnostic workup for anal sac adenocarcinoma includes; bloodwork (CBC, serum chemistry), urinalysis, chest radiographs, abdominal ultrasound and aspirates of the tumor or regional lymph nodes (if enlarged). A definitive diagnosis is obtained either by aspirates of the tumor or lymph node or biopsy of the tumor. Metastasis is relatively common with this tumor and may be present in 36-96% of the dogs.
Once a diagnosis has been obtained therapy will be determined based upon the size of the tumor and ability of the surgeon to remove the tumor without complications. Surgery offers the only chance for a cure and involves removing the anal sac and regional lymph nodes if affected. In cases where surgery is not complete, then radiation therapy offers good local control. At the same time radiation therapy is also directed at the regional lymph nodes (sublumbar) prophylactically.
The benefits of chemotherapy for this cancer are unknown, however, chemotherapy is added to most protocols due to the high chance of metastasis by the time therapy is instituted. Commonly used chemotherapy agents include Carboplatin
In some cases multimodality therapy are used (surgery, chemotherapy, radiation therapy) in the treatment of dogs with anal sac carcinoma and in one study of dogs treated with surgery, radiation therapy (15 treatments) and chemotherapy (mitoxantrone) a median survival of > 900 days was noted. Although the survival was quite favorable, significant radiation therapy induced side effects were noted in majority of dogs.
Lastly, a novel class of drugs exist called “signal blockers ” which have been shown to have efficacy against this cancer (Palladia). It inhibits signals used by the tumor to create new blood vessels and thus can be used against a variety of tumors, including anal sac adenocarcinomas. In a study of dogs receiving Palladia nearly a 70% response rate was noted and the response duration was ~23 weeks.
Submitted by Dr Lauren May VMD, DACVS
Ultrasound image showing an enlarged left medial iliac lymph node (1.75 x 4.2 cms).
A 13-year-old spayed female Beagle presented to a medical oncologist for a lingual mass. On physical exam, there was a 1 cm, slightly lobular, slightly ulcerated mass found in the middle of the tongue surface. The mass bled upon fine needle aspirate. The patient also had a history of an adrenal mass, a retroperitoneal mass, unspecified liver changes on an abdominal ultrasound, and possible Cushing’s disease. No evidence of metastatic disease was found upon chest radiographs. A fine needle aspirate was obtained and submitted for cytologic evaluation.
Submitted slides were moderately to very highly cellular and consist of many red blood cells and a nucleated cell population predominated by individual round cells with very low numbers of neutrophils and small lymphocytes. These round cells have a moderate amount of basophilic cytoplasm that occasionally contains a perinuclear clear area/prominent Golgi. The nuclei are most commonly eccentric, round to oval to rarely indented, and have a densely clumped to finely stippled chromatin pattern and indistinct nucleoli. Anisokaryosis is moderate. Binucleation is commonly noted; the two nuclei are typically eccentrically located together in the cell. Multinucleation (3-5 nuclei) are also occasionally found. The cytologic diagnosis was plasma cell tumor. See photos below.
Contrary to common misconception, definitive diagnosis of round cell tumors is typically easier with cytology in comparison to histopathology. The morphologic detail that differentiates mast cell tumors, histiocytomas, plasma cell tumors, lymphoma, and transmissible venereal tumors, is more apparent in cytologic preparations. The same round cell tumors can be differentiated histologically, but this commonly requires immunohistochemical or special stains.
The diagnosis was plasma cell tumor. This patient likely had a solitary extramedullary plasmacytoma, which is largely considered a benign neoplasm that can be cured with complete excision or radiation therapy (these tumors are typically cutaneous, but can arise from mucous membranes and essentially anywhere in the body). However, a metastatic lesion that is part of a more systemic, malignant plasma cell tumor originating from the bone marrow (multiple myeloma), cannot be ruled out. Further, even though most extramedullary plasmacytomas are considered benign, the potential for disseminated disease does exist. Lastly, the malignant potential of these cells cannot be determined based on their cytomorphology. As in this case, many benign solitary plasmacytomas exhibit multiple criteria malignancy (anisokaryosis, multinucleation); and, many of the plasma cells found in the marrow of multiple myeloma cases are very uniform in appearance. Therefore, when a plasma cell tumor is diagnosed, it is always prudent to evaluate the patient for metastasis via imaging and evaluation of serum globulins. If a hyperglobulinemia is present, a serum protein electrophoresis should be performed to determine if a monoclonal gammopathy is present.
Submitted by Casey J. LeBlanc, DVM, PhD, DACVP of KDL VetPath
These days, if you read any news article about human health, the words “personalized medicine” likely appear somewhere in the story.
What is personalized medicine? Is it really that revolutionary? How can personalized medicine be useful to veterinary medicine?
Personalized medicine is defined according to Wikipedia as “a medical model that proposes the customization of healthcare – with medical decisions, practices, and/or products being tailored to the individual patient.” This approach often entails the use of specialized diagnostic tests-often employing genomics, proteomics, or other –omics to help guide the clinician. The results of these tests can lead to a more accurate diagnosis, help the medical professional determine the underlying genetic or molecular basis for the disease, and ultimately tailor the therapy based upon these results.
Hasn’t medicine always been personal?
To some extent, doctors and veterinarians always personalize the medical care they deliver. We treat Chihuahuas differently than Great Danes, we treat sight hounds differently than bulldogs, and Greyhounds differently than Rottweilers. Personalized medicine takes this level of customization to a completely different level. For example, instead of just changing a dose based upon your patient’s weight or breed, imagine a veterinarian prescribing a different medication based upon a pet’s gene expression. Genes regulate metabolism, determine a pet’s susceptibility to cancer and by what mechanism that cancer grows, as well as affecting how a pet will react to chemotherapy.
Personalized medicine and veterinary oncology.
With the publishing of the canine genome, veterinary medicine has truly entered the genomic age. In veterinary oncology, the traditional way to diagnose and categorize malignancies was by evaluating their histology. This information along with staging tests such as radiographs, ultrasounds, bone marrow aspirates, lymph node evaluation among others, allowed as to assign a clinical stage and a grade to most malignancies. We are on the verge of changing this paradigm, categorizing cancers by their genetic signature. To some extent we have already “personalized” therapy for dogs with mast cell tumors. We routinely recommend evaluating mast cell tumors for the presence of a c-kit mutation. This information does influence how we treat that patient.
Although the number of genes and therefore the number of potential mutations is exceedingly large, there is evidence to suggest that cancer-causing mutations affect only 12 basic cellular pathways (http://www.sciencedirect.com/science/article/pii/S1090023315000088). This information may allow therapies to be personalized based upon which pathway(s) are altered rather than on the more onerous task of basing therapy on the genetic variations of each tumor.
Veterinary oncology is rapidly moving into the genomic era. We still need to genetically characterize most of the common cancers that affect both dogs and cats, but I am incredibly excited about the prospect of making therapeutic recommendations based upon the genetic signature of a patient’s tumor. When this change occurred for lung cancer in people, survival times dramatically improved (http://18.104.22.168/biochem/biochem230/papers2005/week5/2129.pdf) and I am hopeful that this will happen for our patients as well.
We are thrilled to have Brian Bretz, DVM, DACVS join the surgical team at Hope this June. He will see appointments on Tuesdays and be available for surgery on Mondays.
Dr. Brian Bretz received his DVM degree from the University of California, Davis School of Veterinary Medicine in 2005 and completed a one year rotating internship in small animal medicine and surgery at Garden State Veterinary Specialists. He went on to complete a residency in small animal surgery at Tufts University and the Angell Animal Medical Center in Boston. Following his residency, he joined a private practice in the northern Philadelphia region before joining HOPE.
Dr. Bretz is a Diplomate of the American College of Veterinary Surgeons. His clinical interests include orthopedic, soft tissue, oncologic, and neurologic surgery. He has also performed multiple types of minimally invasive surgery (arthroscopy, laparoscopy, and thoracoscopy) over the last 9 years and has co-authored several journal articles in peer reviewed journals. From 2012-2014 Dr. Bretz served as co-chairman of the medical advisory board for Pet Partners,LLC providing medical support and guidance to over 30 general practices across the country. He enjoys lecturing on all aspects of surgery. He is currently enrolled in an Executive MBA program at the University of Chicago, Booth School of Business.
He lives in Malvern with his wife, a veterinary radiation oncologist, a dog and two cats. In his spare time, Dr. Bretz enjoys running, scuba diving and travelling.
We would like to also introduce to you to Dr. Sarah Muhrer. She joined our emergency team in May and we couldn’t be happier she is on board with us!
Dr. Sarah Muhrer attended Earlham College in Richmond Indiana where she completed her Bachelors of Arts Major in Biology with honors in 2005. She then attended Cornell University where she obtained her Doctorial Veterinary degree in 2009. Thereafter, she completed a one-year rotating medicine and surgical internship at Metropolitan Veterinary Associates in Valley Forge, Pennsylvania. For the past five years, she has done Emergency Medicine at a specialty hospital in Clarks Summit, PA.
Dr. Muhrer’s special interests include treating toxicities, urethral obstructions, and neonatal medicine. She also loves international veterinary medicine and spent four months in Tanzania Africa studying wildlife protection in the Serengeti and 4 weeks in the Bahamas studying Iguanas. Her personal hobbies include doing agility with her Border collie mix, cross-country skiing, kayaking, and traveling.
Cancer in Pets
Cancer affects all of us, whether through a family member, a close friend, a teacher or a beloved pet. There are approximately 165 million dogs and cats at risk for cancer in the United States. This translates into nearly 4 million dogs and 4 million cats developing cancer each year. It is estimated that nearly 50%of all dogs and 32% of all cats over the age of 10 will develop cancer, making it the leading cause of death in our pets.
The term cancer describes a large number of diseases with the common feature of uncontrolled cell growth. The development of cancer depends on multiple factors. Environmental and genetic contributions often result in an accumulation of errors in the cell leading to uncontrolled growth. Breed, gender, and environmental factors all play a role in the development of cancer.
Warning Signs of Cancer in Pets
Early cancer detection is associated with best outcomes and in many cases a cure. It is important for owners to accurately recognize possible “warning signs” of cancer in their pets. If noted, it is important to contact the primary care veterinarian for a thorough examination.
10. Lumps and Bumps
Not all lumps and bumps on or under the skin are cancerous. It is important to bring this to the attention of your primary care veterinarian to further investigate. A needle aspirate or biopsy are routine procedures to help determine benign from malignant. Needle aspirates are painless, typically do not require sedation or anesthesia, and often reveal the underlying cause of the skin lump. In some cases, a needle aspirate cannot be performed and a biopsy under light sedation or general anesthesia may be recommended.
- Abnormal Odors
Offensive odors from your pet’s mouth, ears, or any other part of the body, should be checked out. Oftentimes cancers of these regions can cause foul odors as a result of secondary infections. Tumors, unlike normal tissue, are more susceptible to infection especially when located in certain areas of the body such as the mouth, the ears and around the anus. A thorough physical examination can often determine the location and cause of the odor.
- Abnormal Discharges
Abnormal fluid discharge from any part of your pet’s body should be checked out by your veterinarian. Some cancers may produce fluid while others may put pressure on the normal drainage system in the body leading to a back up fluids. A thorough physical examination can often determine the location and cause of the discharge.
- Non-Healing Wounds
If your pet has wounds or sores that are not healing, it could be a sign of infection, skin disease, or cancer. Unlike normal tissue which has the ability to heal itself, tumors do not contain this property and to the pet owner, this may appearas a non-healing wound. An examination and tissue sample can often determine the underlying cause.
- Weight Loss
Cancer can cause weight loss in a pet. If sudden weight loss is noted in your pet this should be evaluated by a veterinarian. Cancer may prevent normal intake of food or cancer can compete with the body for important nutrients, leading to weight loss. A thorough physical examination, routine laboratory diagnostics and in some cases imaging (radiographs or ultrasound) may be required to determine the underlying cause.
- Change in Appetite
Pets generally do not stop eating without an underlying reason. A recent lack of appetite could be a result of an underlying cancer and should be evaluated. Cancer may affect normal intake of food through either the development of nausea or the physical presence of the tumor (oral cavity of gastrointestinal tract).
- Coughing or Difficulty Breathing
Coughing or changes in breathing can be a result of heart disease, lung disease, or cancer. If this is noted your pet should be evaluated by your veterinarian. Cancers located within the respiratory system can affect the normal respiration process, resulting in changes in breathing and/or cough. A thorough physical examination with special emphasis on the respiratory system through auscultation is warranted. In some cases chest x-rays may be required to visualize the chest cavity in more detail.
- Lethargy or Depression
If you notice your pet is less active, sleeping more, or less interactive, these can be signs of cancer and should be evaluated further. Cancer, depending upon the type and where it is located, may result in minor discomfort or affect normal exercise which may manifest as lethargy and/or depression.
- Changes in Bathroom Habits
Changes in your pet’s urinary or bowel habits may be potential signs of cancer. Straining to urinate or defecate, blood in the stool or urine, more or less frequent eliminations, are some symptoms of cancers located in the urinary or gastrointestinal system. An examination, routine diagnostics and often more advanced imaging such as an ultrasound is often required to properly assess the cause of these symptoms.
- Evidence of Pain
Limping or other evidence of pain is generally more likely associated with arthritis or muscular injury, but it can also be a sign of cancer (especially cancer of the bone) and should be evaluated by your veterinarian. A routine physical examination and gait evaluation can often localize the region of the body from which the lameness is occurring. Radiographs of the affected area can often help elucidate the underlying case.