There are many types of histiocytic diseases. Some are benign cancers, some are malignant, and some are not neoplastic (cancer) at all. This article will focus on the three types of malignant histiocytic diseases: disseminated histiocytic sarcoma, localized histiocytic sarcoma, and hemophagocytic histiocytic sarcoma.
Disseminated Histiocytic Sarcoma
Who Is At Risk: The average age of onset for this form of histiocytic sarcoma (HS) is 8 years. Twenty-five percent of all Bernese Mountain dogs will develop this form of HS. In fact, one study of 800 Bernese Mountain dogs revealed an oligogenic mode of inheritance (more than one gene controls inheritance) with 78% of dogs with HS having relatives with HS and 40% of affected dogs having a relative with a different type of cancer. Rottweilers are also more likely to develop HS than other breeds.
Signs of Disseminated HS: Signs of this disease are usually non-specific and include anorexia, lethargy and weight loss. This is an aggressive disease. Patients can progress to feeling quite sick (very lethargic and complete anorexia) within a short amount of time (few weeks).
Which Organs Are Involved: "Disseminated" implies that multiple organs are affected by the disease at the same time. If HS is found in only one organ after a complete work up, the patient does not have the disseminated form.
The most common organs involved in disseminated HS are typically lungs, spleen, lymph nodes, liver and bone marrow. However, virtually ANY organ can be involved (bladder, kidney, brain etc).
Recommended Work-Up: The work-up helps determine which organs are affected and characterize the overall health of the patient. This typically includes: 3-view thoracic radiographs (read by a radiologist), abdominal ultrasound, CBC, chemistry, urinalysis.
Making A Diagnosis: These days a diagnosis can often be made using a fine needle aspirate and cytology, but in many cases we request special stains (on either biopsy or cytology samples) as well. This disease is not always easy to diagnose.
Due to the rapid progression of the disease, we must act quickly to complete tests, request a rush (STAT) on all lab tests, and sometimes initiate treatment based on preliminary results (we never want a dog to die because test results were taking too long to process). We treat these cases as emergencies.
Treatment: First line treatment for disseminated HS is oral CCNU (lomustine) chemotherapy. This is given every 3 weeks for as long as it is effective. According to one study, 46% of dogs respond to this treatment. Dogs that respond (CCNU successfully stabilizes or improves cancer) are expected to have a MST (median survival time = half live longer and half do not live as long) of 5.7 months. Dogs that did not respond to chemotherapy in the study (their disease continued to progress) had a MST of 2 months.
Other treatment options include zoledronate plus doxorubicin or vincristine, epirubicin and CCNU, and Palladia.
Localized Histiocytic Sarcoma:
Who Is At Risk: The following breeds have an increased risk for developing the localized form of HS: Labrador and golden retrievers, flat-coated retrievers, Rottweilers, Bernese Mountain dogs. Dogs are typically middle-aged at diagnosis.
One study showed that localized HS accounted for 36% of all malignant cancer affecting flat-coated retrievers. None of the dogs in the study developed the disseminated form of the disease.
One study showed that dogs with dogs with previous joint disease were 5.4 times more likely to develop localized HS (in a joint) than those with healthy joints.
Signs of Localized HS: The localized form starts in just one organ, but commonly metastasizes (spreads) to a lymph node or possibly other organs.
Signs of this disease are dependent on the location of the tumor. If the disease is located in a joint, the dog might simply be lame. If the disease is in a joint and is advanced, there might be a mass or swelling around the joint and/or an enlarged lymph node nearby. Often these patients are sent to the orthopedic service for a suspected cruciate (ACL) tear, only to find out that it's actually cancer.
If the disease is in the spleen causing the spleen to become enlarged, there might not be any signs - this might be an incidental finding on a physical exam or x-rays. The same is true if the disease is in the lungs.
If the disease is in the skin or subcutaneous tissues, then you would just see a skin mass, which would probably look like all of your dog's other skin masses.
Which Organs Are Involved: Basically any organ can be affected by localized HS. The most common are probably bone, skin and subcutaneous tissues, joints, lung, spleen.
Recommended Work-Up: These patients need to be completely staged in order to figure out if the disease has spread to a lymph node, and if you're dealing with the localized or disseminated form of HS. This will help inform treatment options and prognosis.
Most patients (68%) will have metastasis at diagnosis, so we have to perform a thorough work-up if we want to be able to recommend appropriate treatment options.
Necessary Tests: Limb radiographs if limping, 3-view thoracic radiographs read by a radiologist, CT scan if lung is involved (if the family is considering surgery), abdominal ultrasound performed by a very competent ultrasonographer, ultrasound-guided aspiration of any abnormal abdominal organs, needle aspirate of nearest lymph node (if possible), CBC, chemistry panel, urinalysis.
Making A Diagnosis: Obtaining a diagnosis typically involves sampling the tumor using fine needle aspiration and sending the sample to the lab for a cytologic diagnosis. If the lab cannot "call it" on cytology, we can sometimes request special stains on cytology (called immunocytochemistry). Other times a biopsy with special stains (immunohistochemistry) is needed.
Treatment: Patients with localized HS will live the longest if we are able to achieve "local control", if there is no obvious evidence of metastasis, and if we follow surgery with chemotherapy.
Local control means eliminating all cancer cells at the primary tumor site. If a patient has localized HS confined to the spleen, this means removing the spleen. If the disease is present in a single lung lobe (confirmed with CT scan), they would undergo lung lobectomy (removal of the affected lung lobe). If the disease is in the elbow joint, they would have the leg amputated. If they had a skin mass on their hip that was HS (and the local lymph node was affected), they might need surgical removal of the mass and the lymph node followed by radiation treatment of both sites.
On average, if we can achieve local control using surgery (and radiation if needed) then follow with CCNU oral chemotherapy (every 3 weeks for 6 treatments), patients will have a median survival time (half live longer and half don't live as long) of 13-19 months.
If surgery is not performed, then we can give CCNU every 3 weeks for as long as it helps to keep the tumor is stable or smaller; this is usually about 4-6 months.
One study showed that dogs with the periarticular (joint) form of localized HS had a MST of 8 months if there was metastasis at diagnosis, vs 33 months if there was no evidence of metastasis (these patients were given treatment). Another study showed that patients live 6 months if they have metastasis and 15 months if they don't have metastasis at diagnosis.
One study described the outcome for dogs affected with the pulmonary (lung) form of localized histiocytic sarcoma. Patients that received surgery (lung lobectomy) followed by chemotherapy had an overall survival of 374 days, while those that received chemotherapy alone had an overall survival of 131 days.
Hemophagocytic Histiocytic Sarcoma
This is the most aggressive of the three types of histiocytic malignancies and one of the most aggressive types of cancer that dogs can develop, period. It most commonly affects Bernese Mountain dogs, golden retrievers, Labrador retrievers, Rottweilers, and schnauzers. Dogs from ages 2.5 to 13 years are reported to have been affected.
Dogs that have hemophagocytic HS (HPHS) typically appear extremely sick. They are often extremely lethargic (in part due to severe anemia), very pale, often unwilling to eat, and might have evidence of bleeding (red/purple spots on gums or abdomen).
I've only seen one patient with this disease that did not present "sick" at diagnosis; the patient looked completely normal. During her dock diving competitions she was not performing as well, so her incredibly astute owner took her in for an evaluation; she knew this meant that something was "off". A mild anemia was noted and an abnormal spleen was found on ultrasound later that day; the spleen was removed and a diagnosis was obtained. In 99.99% of cases the disease is not caught that early. Most people are not that proactive.
The work up includes 3-view thoracic radiographs read by a radiologist, abdominal ultrasound, CBC, chemistry and urinalysis. Most patients will have a regenerative anemia, low platelet count, low albumin, and low cholesterol.
These lab work changes in addition to the finding of a mass involving the spleen would increase our suspicion for the disease. These patients usually need blood transfusions and intensive care in the hospital. An effective treatment has not been found. If the patient is stable enough for surgery, we could remove their spleen, to hopefully improve their prognosis, (this is also how we usually make the definitive diagnosis) and follow with CCNU chemotherapy. Reported survivals are from 2 to 32 weeks, with an average of 7 weeks.
Other things to note:
For histiocytic sarcoma in general, there is evidence that the use of steroids may shorten survival. Based on this information, I would only recommend their use if your dog was feeling quite sick due to his disease, and steroids were being used as a palliative measure (towards the end) to help improve appetite. Steroids are not a treatment for this disease.
Although the outcome for the disseminated form seems quite bleak, chemotherapy does improve survival. It's also encouraging that dogs that have the localized form, if treated appropriately (achieve local control and follow with CCNU) can live for quite a long time (33 months!) if they're free of metastasis at diagnosis.
These are great cases to have an oncologist involved, in order to make sure that an accurate diagnosis is made as quickly as possible and you're given all of the appropriate treatment options.
Have questions about this article? Reach out!
Dr. Lori Cesario
Board Certified Veterinary Oncologist
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