by Barbara Bouyet
“Malignant histiocytosis,”
(MH) was the diagnosis from the oncologist after receiving the
results of the biopsy. That information was not only vital to my
peace of mind, but it was extremely important for the Leonberger
because that type of cancer had never been recognized in the breed.
Histiocytes are macrophages, cells produced in the bone marrow
which play a vital part in the body’s immune system. They assist in
recognizing invading bacteria and parasites, and are necessary for
lymphocytes to produce antibodies. Histiocytes are normally found
in skin, connective tissue, liver, lung, gut, lymphatic glands,
spleen, bones and parts of the brain. Any of these sites can be
affected by the disease.
With the exception of the
Bernese Mountain Dog and the Flat-Coated Retriever, MH is uncommon
in most other breeds, occurring only rarely. There are subtle
differences between the types of MH in these two breeds, however it
is a common cancer that takes a toll on both breeds. For this
reason, it is believed to be inherited, probably with a polygenic
mode of inheritance.
MH is believed to be rare in
the Leonberger but one in every 5 Berners will die from the cancer.
Because of the high incidence in the Bernese Mountain dog, their
club has become active in researching this cancer.
Pat Long of the Bernese Mountain Dog Club of
America (BMDCA) writes: “Malignant histiocytosis (MH) is a very
aggressive form of cancer that is usually already widespread before
any symptoms are noted. Symptoms usually include loss of appetite
(anorexia), weight loss, lethargy, weakness, and poor general
condition. There could be difficulty breathing, coughing, shortness
of breath, or abnormal lung sounds. Radiographs may show single or
multiple tumors in the lungs, or enlargement of the spleen or liver
(splenomegaly or hepatosplenomegaly). The lymph nodes may be
enlarged. Blood chemistry may be normal; it may show anemia; it may
show a decrease in the number of platelets (thrombocytopenia); or it
may show high liver enzyme activity. This cancer affects the spleen,
lymph nodes, lungs, and/or bone marrow, but can also affect the
liver, central nervous system, kidneys, skeletal muscle, stomach,
and adrenal glands.”
“But malignant histiocytosis is a disease that
attacks many organs simultaneously, or that metastasizes rapidly, so
the dog eventually succumbs from the involvement of the other
organs.”
“MH is generally so far spread throughout the
organs at the time of diagnosis as to preclude surgical excision as
a viable treatment option. To date, no treatment has been found to
be effective long-term. Survival from time of diagnosis may vary
from hours, days, perhaps weeks, and very rarely months. The mean
age at onset is 7 years. “
We lost Magnum December 18, 2002—he was 8 years old. About 3
years ago Magnum developed some hot spots and his blood tests
indicated hypothyroid disease, another surprise in the Leo. Damage
to the thyroid gland can occur because of constant exposure to
biocides, chemicals that block re-uptake of iodine. Though we have
never used any chemicals on our Leos, I know the area parks are
polluted making exposure to these biocides unavoidable. Magnum was
put on Soloxin. In August, Magnum began suffering heat intolerance
to such an extreme that we stopped taking him out during the
daytime. He was walked in the morning and in the evening. (We
learned how to compensate to keep him comfortable.) At the same
time, he began secreting clear fluid from his nose. There were days
when the amount of fluid under his face was alarming but his
veterinarian felt it was “allergies,” and he was given benedryl
which I used infrequently.
Because Soloxin can cause a slight intolerance to heat, I thought
perhaps his thyroid levels were too high and we did a complete
thyroid panel and blood chemistry. His T4 was exactly where it
should be. One of his vets thought perhaps he had laryngeal
paralysis and that his clear secretions were simply condensation
from his breathing problem. We were not convinced because when he
slept, he appeared to have little discomfort. Another of his
veterinarians said he lacked the labored breathing sounds typical of
LP.
In October 2002, during a routine examination, his
veterinarian discovered that one testicle appeared to have
atrophied. Because Magnum had perfect Leo temperament and was a
“Category I, Very Good,” we wanted to breed him to our female. We
could not delay neutering him—an atrophied testicle could signal a
malignancy or an injury. We believed it was an injury because
8-months earlier, Magnum had fallen on a slippery floor and
sustained a groin injury. Still, an injury could trigger a
malignancy. We decided to collect his sperm to bank and went ahead
with our plan after an ultrasound showed the testicle was simply
atrophied.
During the next month, Jazzie came into heat which always caused
Magnum to stop eating. (Usually, he lost about ten pounds during
this time of forced celibacy.) Magnum’s collections at the
reproductive specialist were successful and his appetite picked up
enough for him to gain back 4 pounds.
Another blood panel was done before surgery as part of his
pre-surgical work-up. This time it showed an elevated ALT.
ALT is an enzyme involved in the metabolism of the
amino acid alanine. ALT is found in a number of tissues but it is in
highest concentrations in the liver. Injury to the liver results in
release of the enzyme into the blood. An elevated value is not
clinically significant when all other liver enzymes appear normal,
we were assured.
Shortly after his surgery, he stopped eating and began to lose
weight. We began taking him in for vitamin shots and began testing
him for every tick disease, blood borne parasite--anything and
everything we could imagine, including the Coombs test for
autoimmunity. His daily walks were very short, and he appeared
exhausted after a short walk, another alarming symptom; Magnum loved
going for walks more than anything on earth.
His blood tests indicated a low-grade anemia. Thinking perhaps
his thyroid levels were dropping his medication (Soloxin) was
increased, and we began to give him herbal iron supplements. Within
a week his chest began to fill with fluid. My perfect friend was
dying, it was obvious to my husband and me, but we did not know what
to do. After phone calls to a dear friend, Dr. Jean Dodds, she
arranged for Magnum to see an internist that evening. An ultrasound
showed a diffused mass in his chest next to his heart. We brought
him home and nursed him until his appointment with an oncologist a
few days later. He was on lasix to keep fluid build-up down, but we
had him to the pet emergency hospital the next night for an
emergency aspiration. That was one more nightmare to haunt us—that
Magnum had to suffer through these awful aspirations to allow his
lungs to fill with oxygen by removing the fluid that was crushing
him.
The oncologist explained that only surgery could tell us what was in
his chest and so we decided to do the surgery. I always believed we
could remove the tumor and have Magnum back home—even for a month it
would have been worth everything. They asked to keep him that night
to put him on a morphine drip, and drain fluid to make him
comfortable. We agreed, and I will regret that for the rest of my
life because his last hours were spent without us. On the operating
table, they opened his chest and saw he had cancer throughout his
chest, into his spleen, liver and stomach. They phoned us to say it
was hopeless and we allowed him to go--again I regret bitterly that
I was not there to see his soul enter the light. I pray constantly
that he passed over knowing how much we loved him. I had the
presence of mind to ask that they take some tumor for a biopsy--I
had to know what the cancer was because Magnum was raised
homeopathically. We used minimal vaccines, organic food,
supplements to support immune function and detoxify against
pollution; we never sprayed chemicals, we never applied chemicals to
his body, and yet my Leonberger was dead at the age of 8, his body
filled with malignancy. The cancer took on a life of its own and I
had to have a name for it. It was an enemy.
When the biopsy came back, “malignant histiocytosis,” I began to
research this cancer and posted the information to the LeoList. I
learned that Magnum’s littermate, Gage, another boy with the same
wonderful temperament and a laundry-list of obedience titles, died
of the same cancer. Thanks to his owner, Beth O’Conner, Gage’s
tumor was also biopsied and confirmed as MH. Two confirmed cases of
MH in the same litter pointed to more than coincidence. Magnum’s
breeder had also lost another littermate to cancer 3 months
earlier—squamous cell carcinoma—and she encouraged me to go forward
with this article in hopes of saving lives in the future. Another
littermate, a female, had been found dead 6 months earlier when her
owner returned from work. Her death was attributed to “unknown
causes.” She could have died from MH; as the oncologist explained,
dogs can be found dead by owners and no one would know they died
from MH a cancer that can rupture the spleen causing death by blood
loss. If her remains had been autopsied, we would have another
piece to the puzzle. Many other Leos may have died from this cancer
but without a confirmation from a biopsy, their deaths remain a
mystery.
The wonderful honesty apparent in Leonberger owners and breeders
led to the discovery that another case of confirmed MH had occurred
in a 7 year old male a few years ago. That male was a cousin to
Magnum and Gage. More recently, I learned that a 5 year old female
related to Magnum (a niece) died from MH, also confirmed through a
biopsy. Two Leonbergers in the Mid-West died from confirmed MH
years ago but we have not located their owners, which means we
cannot confirm their familial link to Magnum’s line.
Research and MH
For years, the Bernese Mountain Dog Club and the Flat-Coated
Retriever Club have been funding research into the genetics of MH in
their breeds. In the FCR, research is focused on the p53
tumor-suppressor gene; a tumor registry has been set-up at The Ohio
State University.
The BMDCA has a study ongoing at UC Davis to “evaluate MH tumor
specimens for mutations in genes that may contribute to the
development of this devastating cancer. The genes of interest are
those that code for proteins known as growth factor receptors.” The
BMDCA study underway at the Fred Hutchinson Cancer Research Center
in Washington is a broader study with more ambitious goals.
The Dog Genome Project is a collaborative study involving many
scientists and universities including Fred Hutchinson Cancer
Research Center in Washington. When completed, the canine genome
will show a map of all the chromosomes in dogs which can be used to
locate the genes causing disease and those controlling morphology
and behavior.
Colleen Hacker of the BMDCA explains the importance of the
research by Dr. Heidi Parker, working in Dr. Elaine Ostrander’s
laboratory at the Fred Hutchinson Cancer Research Center. Dr.
Parker’s goal is to find DNA markers associated with this disease in
the Berner and the actual gene mutations that cause MH. “Heidi and
colleagues in the Ostrander lab are taking the genome-wide scanning
approach to identify the DNA variants that cause MH. This approach
makes no assumptions up front about what genes contribute to the
disease. The whole genome scan will be conducted using a subset of
markers from the 3,400 marker map that are evenly distributed across
the dog genome. DNA isolated from blood samples of dogs affected
with MH and unaffected normal controls will be tested for these
markers to determine which marker alleles or combination of alleles
is associated with MH. Once an association is found, the team will
perform a deeper screen of the surrounding region using a more dense
set of markers in order to more precisely define the region of the
dog genome that is associated with MH. Once the region is defined,
they will look for nearby genes either from the 10,000 genes
currently being mapped or from comparisons with human DNA sequence,”
said Colleen.
A list
of genes in the associated region will be compiled, “and the genes
ranked in order of which ones are most likely to cause MH based on
what is known about each gene function. (For instance, an oncogene,
such as p53, would be ranked high on the list). Starting with the
most likely gene candidate, they will then begin searching each
affected and control dog for mutations in the gene. Meanwhile, the
genome scan will continue, searching for other associated markers
and mutations that contribute to developing the disease.”
The
Leonberger and MH
To give
meaning to such a hollow death, I often think that Magnum died so
other Leonbergers could live. I carefully packaged up a swab of his
DNA taken when the sperm collection started last October. I had
frozen sperm if necessary, though it would never be used for
breeding, only as a source of more DNA to fight this disease.
Through
Pat Long of BMDCA, I had arranged for the Leonberger to participate
with the Berner in Dr. Parker’s study. An appeal for unrelated
blood samples to be sent to Dr. Parker was met with an overwhelming
response from Leo folks and I am relieved to report that the
Leonberger is minimally included in this study, though we have not
contributed funds, only DNA. Dr. Parker believes she will be able to
determine if the genetic sequencing is the same in the Leonberger as
it is in the Berners. With that knowledge, we will have to decide
on the next step—hopefully, funding research to find a genetic test
to screen for carriers. Imagine a world with healthy Leonbergers
who live long, satisfying lives!
Different dog breeds suffer
from different types of cancers. For example, some giant breeds,
including the Bernese Mountain dog, Irish Wolfhound, Great Dane and
the Leonberger suffer a high incidence of osteosarcoma. German
shepherds appear to be predisposed to hemangiosarcoma; Bull mastiffs
to lymphosarcoma, Golden Retrievers are prone to fibrosarcoma,
familial lymphoma occurs in Saint Bernards, and Boxers are
predisposed to mast cell tumors. Veterinary geneticists and
researchers believe these breed susceptibilities are important and
are related to the high incidence of autosomal recessive diseases in
dogs arising from selective breeding for desired traits.
The complexity of
canine cancer is tremendous. For example, a growing body of
evidence links exposure to common lawn pesticides with non-Hodgkins
lymphoma, childhood cancers, multiple myeloma, leukemias, breast,
prostate, ovarian, pancreatic cancers, and birth defects. A
case-control study of canine malignant lymphoma reports a positive
association with an owner’s use of the popular crabgrass killer
2,4-D and their dog’s chances of getting cancer.
There are four forms of lymphoma that may develop in the dog and
the primary symptoms are fatigue, weight loss, anorexia, fluid
build-up, and difficulty breathing. With subtle differences, these
are the same symptoms as malignant histiocytosis, hemangiosarcoma,
leukemia, and many other canine cancers. Knowing who the enemy is
allows you to prepare a battle plan. We cannot avoid breeding dogs
with possible genetic cancers unless you know the causes of death of
the dogs in that breed. How many Leonbergers have died of cancer?
The LCA Health Committee tells us it is the number one killer of all
Leonbergers, a statistic that applies to all breeds of dog.
The only way to compile statistics on the incidence of a
particular canine cancer is by biopsies when tissue is available,
and by a necropsy or postmortem on a dog that dies of unknown
causes. Yes, it does cost money but we spent $6,000 trying to learn
why Magnum was dying and we have nothing to show for that expense
except the cause of his death, which gives us all an opportunity to
work toward prevention.
Many people have an aversion to doing these invasive tests and I
can understand because I loved Magnum with all of my heart. Learning
from the death of a beloved dog is more important than our
aversions. Colleen Hacker writes: “When
Pat Long’s dog, Maggie, got sick, Pat “knew” that Maggie had
MH based on diminished appetite, swollen liver, and abdominal fluid.
The vet who examined Maggie suspected that cause as well. Pat
insisted on necropsy, and they were both shocked to learn that the
diagnosis was hepatocellular carcinoma, a liver cancer that affects
many older dogs. Had Pat not insisted on confirmation, writes
Colleen, the use of a sample from Maggie could have complicated the
painstaking research into the cause of MH.”
How many Leonbergers died from
true lymphoma and how many have died from malignant histiocytosis,
the least treatable most fatal canine cancer? How many Leonbergers
were confirmed by biopsy with hemangiosarcoma? We really need to
know. We need to know how often a cancer occurs so that research
efforts and eventually, funding can be put to use in the right
order—starting with the most prevalent cancer. The LCA Health,
Education and Research Committee does not see malignant
histiocytosis as a significant cancer in Leonbergers, therefore,
they have not pursued the research started at Fred Hutchinson Cancer
Center and will not go forward with any research into this cancer.
For that reason, your help is vital--if we are to count the cases of
malignant histiocytosis in the Leonberger, we will have to do that
as individuals joined together. PLEASE, do a necropsy and have
your vet send tissue samples in for pathology. We know too
many Leonbergers die from cancer, but we need to know if this always
fatal cancer can be avoided by breeding away from carriers, was it a
fluke in one line of Leos, is it rare, is it common????
I had to ask myself—would Magnum
have wanted me to treat his disease ravaged body as
sacrosanct? Would he have wanted me
to ignore my responsibility to determine the cause of his death, why
his life was cut off in its prime? If he could have understood
those concepts, he would have wanted me to use that empty vessel to
better understand what destroyed him.
After Magnum’s cremated remains
came home, my husband and I heard the distinct sound of his big feet
pushing off the wall by the front door to roll over. We heard the
sound on three occasions and now we hear only silence.
PLEASE fill out the Cause of Death Registry form to participate in
understanding and some day preventing diseases that kill our
Leonbergers.
Click here:
A NEED FOR BIOPSIES AND
AUTOPSIES 
