Download Some Things Your Physician Has Never Seen

Some Things Your Physician Has Never Seen
D. Glen Esplin, DVM, PhD
Diplomate, American College of Veterinary Pathologists
Animal Reference Pathology Division
ARUP Laboratories
500 Chipeta Way
Salt Lake City, UT 84108
Since the bodies of pets and their owners are made up of basically the same types of cells, tissues
and organs, animals and man suffer from many of the same diseases and neoplasms. However,
our animal patients experience some tumors that are unique to the animal kingdom.
Treating a physician-owned pet can create a special challenge. These clients often request, or
even demand, a detailed explanation of diagnosis, prognosis and proposed therapeutics. A
physician’s knowledge of medical terminology can be an aid in communication, but when
terminology differences exist between human and veterinary medicine or when dealing with one
of the animal unique neoplasms, the physician’s knowledge can be a hindrance. The following
describes a few tumors your physician has never seen.
Canine Histiocytomas
Canine histiocytomas are dome or button shaped lesions which occur most commonly in the skin
of young dogs (<3years) but they can occur at any age. Occasionally in older dogs more
aggressive round cell tumors such as cutaneous lymphomas or histiocytic sarcomas may
histologically resemble histiocytomas. Recent immunohistochemical and ultrastructural studies
have shown that canine histiocytomas arise from Langerhans cells. They often become
infiltrated with lymphocytes and undergo spontaneous regression leading some to refer to them
as “surgical emergencies”—they must be removed quickly before they regress.
Histiocytic neoplasms occur in man but apparently there is not an exact counterpart to the canine
histiocytoma. Histologically canine histiocytomas have an aggressive appearance. When
examined by pathologists unfamiliar with animal tumors they are often misclassified as some
type of cutaneous lymphoma or malignant melanoma.
Mast Cell Tumors
Mast cell tumors are very common in dogs but rare in man. The history accompanying mast cell
tumors often reports that individual lesions vary in size, getting larger and smaller over time.
This is likely due to degranulation of mast cells within the tumor releasing histamine, heparin
and other vasoactive amines. This leads to not only localized edema and inflammation
immediately around the tumor but it can cause more systemic effects such as GI ulceration and
bleeding.
Although the average age at which canine mast cell tumors occur is 8-9 years, these tumors have
no respect for age and have been seen in dogs as young as 4 months. These tumors are, perhaps,
the main reason that skin nodules in young dogs should be removed, or at least evaluated, and
not assumed to be histiocytomas that will undergo spontaneous regression.
Classification of mast cell tumors into Grade I (well-differentiated), Grade II (intermediate) and
Grade III (poorly differentiated) categories has prognostic significance. Most dogs with well
differentiated tumors (80% to 90%) and approximately 75% of dogs with moderately
differentiated tumors experience long-term survival after complete surgical excision. Dogs with
undifferentiated tumors treated surgically typically die of their disease within 1 year as a result of
local recurrence or metastasis. Location of the tumor may also be an important factor. Lesions
located in the oral cavity, preputial/inguinal area, scrotum, nail bed and perineum may exhibit
more aggressive behavior. Mast cell tumors of the GI tract warrant a poor prognosis.
In cats, the vast majority of cutaneous mast cell tumors will follow a benign clinical course with
excision. The canine grading system does not apply to cats. Different types of mast cell tumors
are described in cats (well-differentiated, poorly differentiated and histiocytic) but there are
conflicting reports as to whether biologic behavior can be predicted for these different forms.
Following splenectomy , cats with splenic mast cell tumors can experience prolonged survival,
even in the face of bone marrow and peripheral blood involvement. As in dogs, intestinal mast
cell tumors in cats warrant a poor prognosis.
Mast cell tumors also occur in horses but there is some question as to whether they represent true
neoplasms. There are reports of multiple mast cell tumors in foals that spontaneously regress.
Equine mast cell tumors are almost invariably benign with only rare reports of regional
metastasis. Widespread metastasis has not been reported.
Mast cell cancer is rare in humans. The most common form of mast cell lesion in man is referred
to as urticaria pigmentosa and is associated with multiple cutaneous lesions. It arises in infancy
or early childhood and tends to spontaneously regress at the onset of puberty. It may be similar
to the multifocal mast cell tumors reported foals.
Equine/Feline Sarcoids
Cutaneous lesions referred to as sarcoids have long been recognized in horses. These
proliferative spindle cell lesions have been grossly divided into 4 morphological types—
verrucous, fibroblastic, mixed and flat. More recently similar lesions have been described in the
feline species. In both species sarcoids have been associated with bovine papillomavirus. The
lesions may occur anywhere on the body but in both species many of the lesions occur on the
head and lips. The lesions are locally infiltrative and frequently recur following surgical
excision but metastasis has not been reported. Improved therapeutic results are seen with
cryosurgery in both species. Immunotherapy has also been reported to be effective in horses.
Equine/feline sarcoids are not related to the generalized granulomatous diseases in man referred
to as sarcoids or sarcoidosis.
Tumors of the Perianal Area
Perianal Gland Tumors
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Perianal gland tumors arise from modified sebaceous glands in the perianal area of dogs.
Ectopic perianal gland tissue is also located in the preputial area and along the tail resulting in
less frequent perianal gland tumors in those locations. These tumors are sometimes referred to as
hepatoid gland tumors because, histologically, the tumor cells resemble hepatocytes. Most
perianal gland tumors are classified as adenomas but epitheliomas and carcinomas also occur.
Growth of perianal gland adenomas is influenced by hormones. Castration removes the
androgen influence causing many adenomas to regress. Perianal gland carcinomas typically
show no response to castration.
Perianal gland tumors have no counterpart in man or other non-canine species. I have seen
perianal gland tumors misclassified as squamous cell carcinomas by pathologists unfamiliar with
animal neoplasms.
Adenocarcinomas of Anal Sac Apocrine Glands
The anal sacs are surrounded by apocrine glands that drain into the anal sacs. Adenocarcinomas
arising from these glands are very aggressive lesions that exhibit high potential for metastatic
spread, most often to sacral and sublumbar lymph nodes. They are also capable of infiltration
into the pelvic canal. Hypercalcemia is often associated with these tumors due to production of
parathyroid hormone-related protein by the neoplastic cells. This hypercalcemia can be used to
monitor success of therapy. The hypercalcemia returns to normal upon removal of the tumor.
Return of the hypercalcemia usually signals recurrence of the tumor or establishment of the
tumor at a metastatic site.
Adenocarcinomas of anal sac apocrine glands have no counterpart in man.
Transmissible Venereal Tumors
Transmissible venereal tumors (TVTs) are a truly transmissible tumor. They result from transfer
of tumor cells from an infected dog to a susceptible dog. The tumor in the new host develops
from proliferation of the transferred tumor cells and not by recruitment of cells from the host.
Transmission usually occurs during sexual contact resulting in lesions on the genitalia.
However, lesions can occur at other sites such as the head, lips and nose through breaks in the
skin secondary to rubbing or licking.
TVTs are mesenchymal in origin but, even though they have been recognized for over 175 years,
the exact cell of origin is still unknown. Previous studies have suggested a histiocytic origin but
some more recent studies indicate TVTs are composed of immature leukocytes, likely of myeloid
origin. TVTs from all over the world have some unique cellular characteristics suggesting a
common origin. Tumor cells in a TVT typically have 59 chromosomes compared to the 78
chromosomes in normal dog cells. All TVTs have similar cell surface antigens. They also have
a unique genetic marker associated with the c-myc onocogene.
Many naturally acquired TVTs may undergo spontaneous remission but some reports indicate
that regression without therapy is unlikely if the tumor has been present for 6 months or longer.
These tumors are capable of metastasis, especially in immunodeficient animals or young
puppies. Thus treatment of TVTs seems appropriate. Surgery is effective in selective cases but
recurrence is common. TVTs are very responsive to chemotherapy (vincristine) and radiation
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therapy. Dogs which undergo spontaneous regression develop humoral and cellular immunity
that protects against development of subsequent tumors.
Fortunately there is no counterpart to TVTs in humans.
Conclusion
As a veterinary pathologist, I would encourage veterinarians to utilize veterinary pathologists to
read their animal tissue biopsies because they are members of your profession and have a special
understanding of the problems of animals. If you do use a physician pathologist, or, when
communicating with your physician clients, be sure that the terms being used have the same
meaning for both of you. Remember, our animal patients get a few things that your physician
has never seen!
Sources and Additional Reading
Equine Dermatology. By Scott and Miller. Saunders, 2003.
Skin Diseases of the Dog and Cat, 2nd Edition. By Gross, Ihrke, Walder and Affolter. Blackwell
Publishing, 2005.
Small Animal Clinical Oncology, 4th Edition. By Withrow and Vail. Saunders, 2007.
Tumors in Domestic Animals, 4th Edition. By Meuten. Iowa State Press, 2002.
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