Reactive disorders of histiocytic origin
This tumor type is typically classified as a reactive disorder of Langerhans cells, although also has been classified as a
malignant disease. They are most commonly seen in dogs younger than 3 years old but can be seen in dogs of any age. The most
common location is the head or pinnae (Photos 1 and 2). These tumors are considered solitary, but there are reports of dogs
with multiple histiocytomas (Shar Peis) as well as migratory (metastatic) disease to lymph nodes (
http://www.histiocytosis.ucdavis.edu/). The diagnosis of multiple histiocytomas can be misdiagnosed as cutaneous histiocytosis because of the similar clinical
presentation. It is speculated that these tumors are due to dysregulation of the immune system. In the majority of cases,
there is no treatment required since they will spontaneously regress within three months, although dogs with multiple tumors
can have delayed regression. Regression of migratory disease has been reported, which supports the diagnosis of histiocytomas
being a reactive disorder.
Photo 1: Cutaneous histiocytoma in a dog.
Cutaneous histiocytosis (CH) and systemic histiocytosis (SH)
Both of these diseases are considered a reactive disorder of Langerhans cells. The histologic appearance of CH and SH is identical,
which suggests they may be the same disease process (Moore 2000). Collies, Shetland Sheep dogs and Bernese Mountain dogs appear
to be predisposed to CH, while SH is seen mainly in male Bernese Mountain dogs. Both entities have been seen in other dog
breeds as well. In Bernese Mountain dogs, it is felt that there is a genetic abnormality that predisposes them to this disease.
It has been postulated that CH and SH are caused by abnormal interactions between dendritic cells and T lymphocytes (Moore
Photo 2: Aspirate of a histiocytoma.
The clinical presentation can be variable and often has a waxing and waning course. With SH, clinical signs can include weight
loss, anorexia and respiratory signs, depending on the organ systems involved. Clinical signs of both diseases include multiple,
erythematous rapidly growing dermal or cutaneous plaques that are found anywhere on the body (Photo 3). Involvement of the
nasal planum and mucosa can be seen. CH can also involve lymph nodes. In SH, other organ systems (lung, liver, spleen, bone
marrow) are involved, as are cutaneous and mucosal lesions. CH does not always require treatment; but for SH and progressive
cases of CH, immunomodulatory drugs such as prednisone, azathioprine, chlorambucil, cyclosporine and leflunomide have shown
to be beneficial. Response to treatment is variable, with SH being more aggressive and less responsive to treatment.
Photo 3: Multiple, erythematous plaques are often seen in CH and SH.
Described in both dogs and cats, this syndrome is considered a reactive process. The diagnosis is based on the finding of
histologically normal histiocytes, which are phagocytosing myeloid and erythroid precursors. This syndrome is secondary to
other causes such as infectious, neoplastic or metabolic diseases.
Malignant diseases of histiocyticorigin (histiocytic sarcoma complex)
Malignant histiocytosis (MH) and Diffuse histiocytic sarcoma (DHS)
MH was originally recognized in Bernese Mountain dogs, but it has been reported in other breeds including Flat Coated Retrievers,
Golden Retrievers, Labradors and Rottweilers. There may be a male predisposition for MH. Given the strong breed association,
it is thought that there is a genetic determinant of this disease. Research is being done to identify the specific genetic
abnormality(ies), since this may identify dogs at risk, as well as provide a therapeutic target.
Photo 4: Bone marrow aspirate with malignant histiocytic cells present.