Every once in a while we discover a syndrome that has not been seen before, or rediscover an old disease that has apparently laid dormant for a number of years. Here are a few of them that you will probably see in your practice.

Histiocytosis of Golden Retrievers:

In the mid-1980s, there was a series of papers describing cutaneous, systemic, and malignant histiocytosis in Bernese mountain dogs. The disease would present as anything from multiple histiocytic cutaneous nodules to widespread histiocytic visceral malignancy, with particularly prominent lung involvement. In 1995, there was a single paper describing a case of malignant, multi-organ histiocytosis in a young golden retriever. Since that time, I have received specimens from 17 cases of histiocytosis in this breed.

The age of affected dogs, when first presented for diagnosis, has ranged from 1.5 to 10 years, with a mean of 5.7 years and a median and mode of 5 years. Ten of 17 dogs were 5 years old or less at the time of diagnosis. Males and females have been affected with equal frequency. In 13 of 17 cases, the initial complaint has been one or more cutaneous nodules which have been refractory to standard antibiotic or anti-inflammatory therapy, and which have grown more numerous. Four dogs had visceral involvement, without observed skin nodules, at the time of first presentation.

The microscopic lesion is a nodular, deep dermal and subcutaneous proliferation of atypical histiocytic cells, often with nuclear gigantism and bizarre nuclear shapes.

At the moment, our understanding of the biologic behavior is still rudimentary. In some dogs, the multiple nodules undergo spontaneous and apparently permanent remission over the several weeks or months after the diagnosis. In other cases, there is temporary remission followed by reappearance of the nodules, which then remain until euthanasia. In the majority of cases, the nodules are progressive, becoming larger and more numerous. No chemotherapy has been effective (prednisone, vincristine, COP), but this information comes from a retrospective series of individual cases with no uniformity in therapeutic protocols. At the moment, I suggest a very guarded prognosis because the majority of cases seem to eventually progress to involve hundreds of unsightly cutaneous nodules. Visceral involvement appears to be uncommon but few cases have had necropsy follow-up. The microscopic lesions can be distinguished from the syndrome of multiple benign cutaneous histiocytosis that occurs sporadically in various breeds by the greater cellular pleomorphism and the presence of atypical, large hyperchromatic histiocytes.

Update on Feline Post-vaccinal Sarcomas:

There has been a 38% decrease in the prevalence of post-vaccinal sarcomas as a percentage of all feline submissions to Histovet thus far in 1997. Whether this is a genuine trend or just a transient blip remains to be seen. One can imagine things like less frequent and more selective vaccination as possible explanations.

To briefly re-iterate information contained in a previous Oracle (Fall 1994), we see these aggressive spindle cell sarcomas developing at sites of vaccination in cats anywhere from 16 weeks to 16 years old, with no particular age predilection. They may occur as quickly as 3 weeks after the very first vaccination. We still do not know what the carcinogen is, or whether there is a single shared carcinogen among all the incriminated vaccines. Virtually all vaccines have been incriminated, and so it appears not to be the antigen itself. Overall, sarcomas are most prevalent at sites of rabies vaccination, but the strongest direct epidemiologic link is to the less-frequently administered feline leukemia vaccines. The risk of developing a sarcoma at a vaccine site varies somewhere between 1 in 1,000 vaccinations (Vancouver data) to 1 in 10,000 (American data).

The most familiar pattern for the disease is the gradual emergence of an aggressive, invasive sarcoma a month or two after vaccination, arising from the proliferating fibroblasts within the post-vaccinal granuloma. However, I have recently had several cases in cats that had not been vaccinated for 5-6 years. There had been no persistent nodule at the site, and the sarcomas appeared to have arisen de novo. Considering that the interval between carcinogen exposure and eventual clinical malignancy in human beings may be 20 or 30 years, this delay in onset should not come as a big surprise.

Sadly, the aggressive clinical behaviour seems not to have improved at all. Recurrence rate is still at least 60% despite greater recognition by practitioners and very aggressive initial surgery. It is also frequent to see the recurring tumors at sites that represent gravitational drainage of vaccine vehicle, such as the lateral thorax or above the hock. Occasionally, the primary tumor occurs at such atypical (gravitational) locations.

Metastatic disease appears to be very infrequent, but that may reflect relatively early euthanasia of cats with recurring, ever-deepening sarcomas. Very few of these cases receive a complete post mortem.

Familial Liver Disease in Dogs:

A huge topic, but here is a quick overview. Breed-associated familial liver disease comes in three main types: vascular abnormalities leading to portosystemic shunting, copper storage disease, and other, non- copper associated, fibrosing liver diseases. The classification of developmental hepatic shunts is a mess, related to our confusion in distinguishing primary lesions versus secondary lesions. It is a specific topic unto itself and will be discussed in a future Oracle.

Copper storage disease is, of course, very familiar to you as a disease of Bedlington terriers and various other breeds. It is well described in any of the clinical textbooks. I will not go into it further, other than to mention that there is now a new test for the defective gene, which may prove to be much more valuable and certainly less labourious than liver biopsy and quantitative chemical assay for copper (VetGen, Ann Arbor, MI; Fax 313-669-8441; www.vetgen.com). As is typical of any new test, there already are debates about sensitivity and specificity based upon apparent discordance between expected results based upon pedigree information and the actual test results.

Copper storage disease has been reported in a variety of breeds other than Bedlington terriers, including Doberman pinschers, West Highland White terriers, and Airedale terriers. There is considerable debate, however, about the validity of this claim because many sick livers will accumulate copper and other metabolic debris. In Dobermans, the disease is a chronic active periportal hepatitis seen primarily (90%) in middle-aged females. Clinical progression usually is very slow, but response to therapy is disappointing (and hard to assess in a slow moving disease!). It appears that the copper storage is purely secondary. In West Highland White terriers, there are in fact two familial liver diseases. One is copper storage (although never as severe as in the Bedlington) and the other is a progressive, fibrosing liver disease that it is not copper associated. The two can be distinguished by histopathology and, of course, by quanititative copper measurement on liver biopsies.

Finally, we see a progressive familial liver disease in American cocker spaniels, usually affecting male dogs at 4-7 years of age. The histologic lesion is characteristic, with periportal fibrosis and massive biliary proliferation. Because of the great reserve of liver function, clinically-affected dogs will usually have very advanced disease, and survival time after diagnosis has typically been a matter of months. As far as I know, there has been no investigation of the mode of inheritance. Interestingly, in contrast to the generally high level of breeder awareness of familial liver disease in the three above-mentioned breeds, there seems to be little interest/awareness among breeders about this disease in cockers.

Gingival Alveolar Squamous Cell Carcinoma in Cats:

Beware of the solitary loose tooth with alveolar bone lysis! The majority of such lesions are submitted to me because the cat does not have generalized gingivitis or other dental disease to explain the tooth loss, and there is the presumption of alveolar osteomyelitis. Virtually all such cases turn out to be osteolytic alveolar squamous cell carcinoma. The prognosis appears to be the same as for other gingival squamous cell carcinomas in cats: very poor. I admit that my impression may be greatly biased by sample selection, and perhaps only the alveolar lesions that look a bit "strange" are submitted for my attention. However, the number of such squamous cell carcinomas that I diagnose every year is enough to justify this note of caution.

Canine Viral Papillomatosis:

All medicine and pathology textbooks contain descriptions of oral papillomatosis in young dogs, but in fact it has been a very uncommon disease over the past 20 years. Within the last year, several diagnostic laboratories across the country have seen a dramatic increase in the prevalence of oral and cutaneous viral papillomas in dogs. I have seen more cases within the past year than in the previous 20 years combined. Examination of our records from 40 recent cases reveals that the lesions have been oral in 16 dogs. Six of the remaining 24 cutaneous cases have affected the digit. Age of affected dogs has ranged from 0.5 to 9 years, with a mean of 3.6 years. The majority of the affected dogs (31 of 40) have been under 4 years of age. The lesions are typical papillomas, consisting of papillary proliferation of vacuolated epithelial cells supported by long, thin fibrous stalks. I have not sought any follow-up information, but historically such lesions have undergone spontaneous remission because of immune recognition of the papillomaviral antigen within such tumors. Remission usually requires several weeks or months, and many veterinarians find it more expedient to excise such lesions if they are causing the dog discomfort.

It is not unusual for infectious disease to undergo periodic cycling within wild populations, reflecting the gradual disappearance of immune animals following a previous epizootic, and the emergence of a large, fully-susceptible population. Epidemiologic evidence suggests that immunity following papillomavirus infection is lifelong, so it would be logical to see small epizootics of papilloma infection every 10-15 years. I have not noted any particular geographic clustering in the current outbreak.