Note the massively enlarged cervical lymph nodes in this five-year-old ferret with
lymphocytic lymphosarcoma
This eight-month-old ferret exhibits multicentric lymphoblastic lymphosarcoma with marked organ infiltration (thymus, liver, spleen).
Note the massively enlarged cervical lymph nodes in this five-year-old ferret with
lymphocytic lymphosarcoma
This eight-month-old ferret exhibits multicentric lymphoblastic lymphosarcoma with marked organ infiltration (thymus, liver, spleen).
General.
Lymphosarcoma is the most common hematopoetic neoplasm in the ferret as
well as in most other animal species, and in ferrets, the most common malignancy.
While there's a fair amount of literature available on this disease, we actually know
very little, and unfortunately, save few cases.
This neoplasm certainly appears to be on the rise. Practitioners and pathologists alike report an increased incidence of lymphosarcoma over the last few years - up to one to two cases weekly in some practices. While the increased incidence of lymphosarcoma and occasional clustering of cases has led to speculation of a viral cause to date, a causative agent has not been isolated.
Types of lymphosarcoma.
First, let's take a look at the varied forms that lymphosarcoma can take. There
are basically two clinical presentations of lymphosarcoma in the ferret - a rapidly
progressive lymphoblastic form which is most common in ferrets under 2 years of age,
and a more chronic lymphocytic form which affects ferrets 5-7 years of age.
The "classic" form of lymphosarcoma, which causes marked enlargement of the peripheral nodes, is seen in older animals and has the more prolonged course of the two syndromes. In this disease, an infiltrate of small mature lymphocytes expands the peripheral and mesenteric nodes, eventually effacing nodal architecture. Late in the course of disease, neoplastic lymphocytes infiltrate visceral organs (including the liver, kidney, lungs, and spleen) resulting in organ failure and death. This disease is usually insidious, resulting in little clinical debility until extensive infiltration of visceral organs has occurred.
The lymphoblastic form, which affects ferrets from one to two years, is quite different. In this disease, large immature lymphocytes quickly infiltrate the viscera, including the thymus, spleen, liver, and many other organs. Little to no lymph node replacement is seen in these cases, a finding which results in a high rate of misdiagnosis by clinicians without extensive ferret experience. This form can take a myriad of clinical appearances depending on which organs are involved. One of the more common presentations results in dyspnea and is often diagnosed as cardiomyopathy or pneumonia. The lesion in this syndrome is actually a rapidly growing thymic mass which compresses the lungs. Less commonly, extensive hepatic infiltration by neoplastic lymphocytes may result in marked hepatic enzyme increases and icterus suggesting fulminant liver disease, and so on. Lymphoblastic lymphosarcoma should always be ruled out when dealing with any serious illness in young ferrets.
Finally, leukemic forms, in which neoplastic lymphocytes circulate within the peripheral blood, may be seen in the latter stages of either form, but are generally uncommon.
Diagnosis.
Lymphosarcoma in many cases is not an easy diagnosis. Definitive diagnosis
requires interpretation of a lymph node aspirate or biopsy. While the presence of a
monomorphic population of immature lymphocytes on a lymph node aspirate is highly
suggestive of this disease, the opinion of a pathologist with ferret experience should be
sought in all cases. Alternatively, a diagnosis may be made on biopsies of visceral
organs in animals with disseminated disease, with the spleen probably yielding the
highest number of positive aspirates or biopsies.
Over the last few years, a disturbing trend in diagnosis of this disease has been emerging - the interpretation of elevated lymphocyte counts as evidence of lymphosarcoma in the ferret. While many cases of lymphosarcoma may exhibit a lymphocytosis on the CBC, similar changes in the differential may be seen in any number of chronic smoldering infections, most notably gastric Helicobacter mustelae infection. The prudent practitioner requires a diagnosis by aspirate or surgical biopsy before any treatment is started.
Treatment.
Several protocols have been published for the treatment of lymphosarcoma in
the ferret; however, a poor prognosis should be given to the owner before instituting
any type of chemotherapy. A protocol consisting of prednisone at 1 mg/kg PO SID will
cause initial clinical improvement and a marked decrease in the size of peripheral
nodes, but the vast majority of these animals will return within 4-6 weeks with
disseminated disease which is refractory to further prednisone treatment. The most
popular aggressive protocol consists of a combination of intravenously-administered
chemotherapeutic agents - vincristine, asparaginase, cyclophosphamide and
doxorubricin (coupled with daily oral prednisone) over a 14 week period. Aggressive
treatment appears to have a higher rate of remission than the less aggressive
protocols.
Summary.
In summary, practitioners who treat ferrets are certain to encounter
lymphosarcoma on a regular basis. You should remember several things when such
cases are presented for evaluation and treatment. The younger the ferret at
presentation, the more rapid the disease progression, and the less favorable the
prognosis. Young ferrets often present with signs of heart failure or respiratory disease
due to the presence of a rapidly growing thymic mass. The diagnosis of
lymphosarcoma is based on the presence of a monomorphic population of blastic
lymphocytes on a fine needle aspirate or surgical biopsy of a lymph node or, less
commonly, a visceral organ, and NOT changes seen on a complete cell count. While
prednisone may result in initial clinical improvement, more aggressive forms of
chemotherapy increase the chances of inducing remission. Finally, all ferrets with
lymphosarcoma should be given a poor prognosis before any treatment protocol is
initiated.
References:
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