Overview of  histiocytic disease in the dog

Diseases which originate from histiocytic proliferation range from benign self-limiting lesions to malignant, life-threatening sarcomas and they include newly discovered disease of spleen and bone marrow macrophages.

At least three well defined syndromes that originate from histiocytic proliferation are described in the dog. These are cutaneous histiocytoma, reactive histiocytosis (skin and systemic) and histiocytic sarcoma (localized and disseminated). Malignant fibrous histiocytoma until recently was grouped here, but more recent studies suggest that it refers to soft tissue sarcomas.

Origin of histiocytes

Most histiocytes proliferate from CD34 + stem cells in bone marrow to macrophages and one of the three types of dendritic cells: epithelial (or Langerhans) cells in the skin, interstitial dentdritni cells in many organs and antigen presenting cells (APC) located in the T cell area in the peripheral lymphoid organs. There is no data that the APC cells lead to disease. The proliferation of CD34 + stem cells is influenced by the cytokines, and specific combinations of them.

Histiocytoma

Histiocytoma are benign skin tumors , most often in young dogs and constitute from 3% to 14% of skin tumors in this species. Their prevalence is highest in animals under 3 years of age. There is breed predisposition in boxers, dachshunds, cocker spaniels, German Danes, Shetland Sheepdog and Bullterriers . There is no evidence of sexual predisposition

Histiocytoma are skin lesions <2-3 cm. In diameter, with rapid growth. Most often localized on the limbs , head, ears and neck. Despite their rapid growth they are benign. Some dogs have multiple lesions and rarely affect regional lymph nodes (most common in Shar – Pei).

Diagnosis is based on cytological and histological. The differentiation from other histiocytic diseases is made by using cell surface markers and immunohistochemical studyes.

Treatment: in most cases , the tumors regress spontaneously within 3 months. Rarely they metastase in regional lymph nodes. When there are multiple lesions and metastases, the course of the disease is protracted with frequent recurrences of regressing lesions. It is expected spontaneous regression of all lesions. Surgical treatment is usually curative. Adjunctive therapy (corticosteroids) generally is not necessary.

The prognosis for individual skin lesions is excellent. The prognosis for patients with multiple lesions and/ or metastases in regional lymph nodes is good

Reactive histiocytosis

This disease has two forms: cutaneous and systemic.

• Cutaneous histiocytosis is a proliferative disease limited to the skin and subcutaneous tissue rarely involves regional lymph nodes. They often affect the face, ears, nose, neck, limbs, perineum and scrotum. Mid- adult to adult dogs are affected more often. There is no breed or age predisposition.
• Systemic histiocytosis is a disseminated form of the skin form, that affects the skin, ocular, nasal mucosa and peripheral lymph nodes. Lesions can also develop in the lungs, spleen, liver or bone marrow. Clinical signs are non-specific (weight loss, anorexia, conjunctivitis, stertor). Systemic histiocytosis is described for the first time in young to mid-adult Bernese mountain dogs and polygenic type of inheritance is proven. Breed predisposition is documented and Rottweiler, Golden and Labrador retrievers.

Diagnosis is cytological and histological. Immunohistochemistry may help to distinguish the disease from granulomatous process and cutaneous lymphoma. Cell surface markers are also used in diagnosis.

Treatment: both forms of reactive histiocytosis tend to regress spontaneously in the initial phase of  the disease. Typical for the disease is partial remission with subsequent relapse. About 50% of the dogs showed partial to complete remission with immunosuppressive therapy (corticosteroids, cyclosporin, leflunomide and doxorubicin HCl). In general, long-term prognosis is poor, with most patients disease progression leads to a lack of response to therapy.

Histiocytic sarcoma

Histiocytic sarcoma is presented in localized and disseminated form. The localized neoplasia affects one place, usually the extremities. Disseminated sarcoma is a disease with systemic nature.

It was first described in the Bernese Mountain Dog. There is a breed predisposition for Rottweiler breeds and Retrievers. No evidence of sexual predisposition.

Usually it is a fast – growing localized soft tissue mass. Most commonly affecting the extremities near the joint, since the tumor cells are derived from dendritic cells in the synovial line. Primary lesions can develop further into the stomach, spleen, liver, lung, pancreas or central nervous system. Most dogs are middle to old age. The clinic is nonspecific (anorexia, weight loss, lethargy), unless they are related to affected organ systems: lameness and swelling of the affected limb; cough and shortness of breath ( respiratory system); convulsions and paralysis (central nervous system). Common laboratory findings in a presentation include: anemia, thrombocytopenia, hypoalbuminemia and mild to moderate increase in liver enzymes. Hyperferritinemia is typical.

Diagnosis is based on clinical presentation, cytology of the mass or effusion of  body cavity and histology. Full clinical feature of the disease is made with radiographs of the abdomen, chest and axial skeleton, ultrasound of the abdomen and thorax.

Treatment: а combination of radiotherapy , chemotherapy and supportive care are recommended for this disease. New options for therapy include T- cell therapy and Lomustin.

Hemophagocytic histiocytic sarcoma

Individual subtype of histiocytic sarcomas, characterized with hemophagocytosis and Coombs negative regenerative anemia.

Hemophagocytic histiocytic sarcoma shares many common features with histiocytic sarcomas including breed predisposition, clinical signs , affected organ systems and the aggressive clinical course.

Unlike histiocytic sarcomas, which is derived from proliferating interstitial dendritic cells, hemophagocytic sarcoma is derived from splenic macrophages of red pulp and bone marrow.

The multiorgan involvement (typical of other histiocytic diseases in dogs), combined with the unique feature of hemophagocytosis and regenerative anemia, defines hemophagocytic histiocytic sarcoma as a separate nosological unit.

Other clinicopathological features include thrombocytopenia, hypoalbuminemia and hypocholesterolemia in 88%, 94% and 69% of the cases respectively.

The therapy is similar to that of histiocytic sarcoma.

THE CASE OF TERES

Teres is  a male dog, 4 months old Cane Corso. The dog comes to the clinic with complaint of otitis externa treated unsuccessfully to date with eardrops. Owners reported itching in the ear , head-shaking and general weakness of the dog.

During examination the dog was contact and in good condition. Pulse, respiratory rate – normal. Mucous membranes – pink . No evidence of dehydration. Temperature – normal. CRT- normal. In otoscopy in the right ear establish some soft tissue nodules with pink smooth surface. Detailed examination of the inside of the ear canal is impossible. Fine needle biopsy was preformed.

 

The diagnosis is histiocytoma. Therapy was  not initiated at this stage.

In the course of the disease nodes increased in number and size, and started to become inflamed. The dog showed constant itching in the area. Otitis externa has developed due to localization of the neoplastic process.

Secondary complications were controlled with topical medication, weekly wash the ear canal with saline , twice a course of amoxicillin/ clavulanic acid at a dose of 13 mg/ kg for 2 weeks of the third week of the diagnosis of disease, and the 10th week from the diagnosis of the disease.

Monitoring during course of the disease

The patient fully recovered from the disease!

During that time the patient was treated surgically by prolapse of the gland of the third eyelid (“Cherry eye”) and conservative of traumatic rupture of one testicle. These diseases have no clinically relevant to the above problem.