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Hemophagocytic Histiocytic Sarcoma in Dogs

 

Hemophagocytic histiocytic sarcoma in dogs is a form of malignant cancer that is not very common in dogs, although it occasionally shows up every now and then in pathology reports. Diagnosis may not arrive in a timely manner due to the vagueness of symptoms. This condition is often confused with immune-mediated hemolytic anemia (IMHA) or more specifically with Evan’s syndrome. An ultrasound and fine need aspiration is usually the first way hemophagocytic histiocytic sarcoma in dogs is tentatively diagnosed.

Hemophagocytic Histiocytic Sarcoma

There are various histiocytic disorders affecting dogs which include histiocytoma, localized histiocytic sarcoma (HS) and disseminated HS (malignant histocytosis). These latter disorders principally share in common the proliferation of dendritic cells (DC) of either Langerhans cell or interstitial DC lineage. Hemophagocytic histiocytic sarcoma (HHS) is distinctive as it’s an aggressive cancer of macrophage origin (containing specialized cells that engulf and destroy target cells).

The term hemophagocytic is composed by the words “hemo” meaning blood and the term phagocytosis, which depicts the process by which living cells known as phagocytes engulf other cells or particles.

The term histiocytic derives from histiocytes, a special type of cell found in animals which plays a role in the dog’s immune system. Histiocytes are immune cells that originate from the dog’s bone marrow. Once released from the bone marrow, these cells travel into the dog’s bloodstream initially as monocytes which mature into histiocytes only once they have entered different tissues. There are three main subtypes of histiocytes: dendritic cells, macrophages, and Langerhans cells.




The term sarcoma, on the other hand, derives from the Greek word sarx, meaning “flesh.” Sarcomas are given various different names based on what type of tissue they originate from and resemble. For instance, osteosarcomas are sarcomas that resemble bone, liposarcomas are sarcomas that resemble fat, chondrosarcomas resemble cartilage, leiomyosarcomas resemble smooth muscles. Histiocytic sarcomas are sarcomas instead that originate from histiocytes.

Hemophagocytic Histiocytic Sarcoma in Dogs

Hemophagocytic Histiocytic Sarcoma in Dogs
Hemophagocytic Histiocytic Sarcoma in Dogs

Several dogs breeds are predisposed to histiocytic types of cancer including Bernese mountain dogs, golden retriever, Rottweilers and Labrador retrievers. Symptoms may be vague and include loss of appetite, lethargy, weakness, weight loss and pale mucous membranes.

On bloodwork, according to a study findings include Coombs negative responsive anemia in 94 percent in dogs, thrombocytopenia (low blood platelet count) in 88 percent,  hypoalbuminemia (low albumin) in 94 percent and hypocholesterolemia (low cholesterol) in 69 percent.

On ultrasound, dogs typically present with an enlarged spleen and masses.When fine-needle aspirates were taken, histiocytes were found to be markedly erythrophagocytic (engulfing other cells or particles) and were accompanied by foci of extramedullary hemopoiesis (production of blood cells taking place outside the bone marrow). While phagocytosis may be evident in other forms of histiocytic sarcomas,  it has been found to be much more profound in hemophagocytic HS.

According to the book “Diagnostic Cytopathology in Clinical Oncology,” the presence of neoplastic macrophages are a “wolf in sheep’s clothing” considering that these cells look similar to the phagocytic macrophages found in inflammatory lesions and therefore seldom exhibit criteria of malignancy. It’s therefore important to point out that rarely a definitive diagnosis of HHS can be made cytologically and therefore a biopsy is required.

Dogs affected by hemolytic anemia who are not responding to immunosuppressive therapy, should be evaluated for  HHS. In the absence of the presence of defined masses, a histologic diagnosis may also be difficult.




 Differential diagnosis (other disease processes that produce similar signs of HHS)  include reactive macrophage proliferations secondary to other tumors or other inflammatory processes (hemophagocytic syndrome).

The organs mostly involved in this HHS cancer include  spleen, liver, bone marrow, and lung. This cancer has a tendency to spread from it’s primary site to secondary site (metastasis).

In a study it was found that hemophagocytic histiocytic sarcoma involved the spleen and bone marrow at the same time and then later spread to the dog’s liver and lungs in an insiduos manner, but with minimal mass formation.

“The unique pattern of organ infiltration evident in canine HS with prominent hemophagocytosis differs markedly from HS of DC (dendritic cells) origin. It should also be mentioned for completeness that mixed histiocytic tumors have been observed rarely, i.e., dogs that have hemophagocytic HS occurring in the context of HS of DC origin.”~Veterinary Pathology

Prognosis of Hemophagocytic Histiocytic Sarcoma in Dogs

Of all the types of histiocytic sarcomas, the hemophagocytic form unfortunately carries the worst prognosis with a median survival time of only 4 weeks and a mean survival time of  7 weeks following diagnosis. The poor outcomes are due to the development of severe anemia and coagulopathy (prolonged/excessive bleeding) as the disease progresses.

A presentation by Dr. Meredith Gauthier, a board-certified veterinarian specializing in oncology, features a case study involving a 6-year old Rottweiler. The ultrasound with fine needle aspiration revealed malignant histiocytes with hemophagocytosis.

In this case, unfortunately, a splenectomy would not have helped resolve the anemia or symptoms of lethargy and poor appetite. Because of ongoing rupture or destruction of red blood cells, a transfusion would have only provided only temporary relief. Euthanasia was therefore sadly elected.

What if a treatment such as chemo was instituted though to treat hemophagocytic histiocytic sarcoma in dogs? Unfortunately, even then things don’t get much better.  In a study involving dogs presenting with low albumin levels and low platelets, the chemo oral drug lomustine (CCNU) provided a survival time of less than one month (versus the 106 days for dogs without these abnormal values).


References:

    • Vet Pathol. 2006 Sep;43(5):632-45.Canine hemophagocytic histiocytic sarcoma: a proliferative disorder of CD11d+ macrophages.Moore PF1, Affolter VK, Vernau W.
    • A Review of Histiocytic Diseases of Dogs and Cats , P. F. Moore, BVSc, PhD, Dip ACVP Veterinary Pathology  Vol 51, Issue 1, pp. 167 – 184 First PublishedJanuary 6, 2014

    • Diagnostic Cytopathology in Clinical OncologyWithrow and MacEwen’s Small Animal Clinical Oncology (Fifth Edition)

    • Integumentary System, Elizabeth A. Mauldin, Jeanine Peters-Kennedy, in Jubb, Kennedy & Palmer’s Pathology of Domestic Animals: Volume 1 (Sixth Edition), 2016

    • J Vet Intern Med. 2007 Jan-Feb;21(1):121-6.CCNU for the treatment of dogs with histiocytic sarcoma.
      Skorupski KA1, Clifford CA, Paoloni MC, Lara-Garcia A, Barber L, Kent MS, LeBlanc AK, Sabhlok A, Mauldin EA, Shofer FS, Couto CG, Sørenmo KU.
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