Benson-Lisa-Paper 2014 - eCommons@Cornell

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Surgical Treatment of Vaginal Leiomyosarcoma in a Mixed Breed Dog
Lisa Benson
Advisors: Dr. James Flanders and Dr. Kelly Hume
Senior Seminar Paper
Cornell University College of Veterinary Medicine
4/16/14
Key Words: Leiomyosarcoma, Leiomyoma, Vagina, Canine, Pubic Osteotomy
Abstract
An 11 year old mixed breed spayed female dog was presented to the Cornell
University Hospital for Animals Soft Tissue Surgery Service with a two week history of
tenesmus and cough. A mass localized to the colon by her primary veterinarian via
external abdominal palpation was first detected four months prior and had rapidly grown
in size. During the same time period, rapidly progressive right hind limb lameness
developed.
Digital rectal palpation revealed an intrapelvic mass, which effectively obstructed
her rectum. A full body CT scan was negative for metastasis and confirmed a vaginal
mass as the cause of the patient’s tenesmus as well as the patient’s associated right hind
limb lameness.
After successful excision of the vaginal mass, histopathological analysis
confirmed a diagnosis of leiomyosarcoma and a likely curative complete excision.
Introduction
Vaginal tumors are uncommon in dogs. Tumors of the vulva and vagina account
for only 2.4 – 3% of all reported canine neoplasms. Of these, 83% are reported as benign
smooth muscle tumors, the most common being leiomyoma. Leiomyoma is usually found
in intact females with an average age of 10.8 years1. The incidence of leiomyoma is
higher in intact nulliparous bitches2. Several studies present data which indicate that
vaginal leiomyoma growth is affected by sex steroids, as it has been documented in
human literature2,3,4,5,6,7. Leiomyosarcoma is the most common malignant canine vaginal
neoplasia, and distant metastases have been reported. It is more commonly found in the
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gastrointestinal tract than the vagina, and generally has a moderate metastatic risk
depending on the primary location of the tumor8.
Vaginal leiomyosarcoma is less common in dogs compared to gastrointestinal or
splenic leiomyosarcomas. Unlike the benign vaginal leiomyoma, which is seen in intact
females, it has been reported in spayed females. Leiomyosarcoma is a malignant soft
tissue sarcoma of smooth muscle origin8. It appears grossly similar to the benign smooth
muscle tumor, leiomyoma. Definitive diagnosis differentiating between these two
requires histopathological analysis. The differentiation between the two diagnoses may
be challenging due to a lack of cases and is generally based on severity of mitotic index,
necrosis, ischemic change, invasiveness, and cellular atypia7.
This paper describes the clinical signs, diagnosis, and surgical treatment of a vaginal
leiomyosarcoma in a spayed mixed breed dog.
Case History
An 11 year old female spayed mixed breed dog weighing 29.3 kg (64.5 lb) was
presented to the Cornell University Hospital for Animals Soft Tissue Surgery Service
with the following problems listed in chronological order: chronic, mild, bilateral hind
limb lameness, a four month history of a mass localized by the referring veterinarian via
external abdominal palpation to the colon, a four month history of progressive right hind
limb lameness, a two week history of severe tenesmus which prompted the presentation
to the soft tissue surgery service, and a two week history of cough. The tenesmus had not
improved despite oral lactulose administration (15 ml PO TID = 341 mg/kg PO TID) for
the three days prior to presentation.
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The chronic, mild, bilateral hind limb lameness had not progressed or interrupted
the patient’s daily activities or energy level, and had not historically been a concern to the
referring veterinarian or the client. The key presenting complaint of primary concern to
all was a two week history of severe tenesmus.
Four months prior to presentation, the referring veterinarian had palpated an
approximately 2 cm diameter mass, which was localized to the colon via external
abdominal palpation. Diagnostic imaging was not pursued at this time, however a
complete blood count and blood chemistry were performed at that time by the referring
veterinarian and were unremarkable. During the course of the ensuing four months the
mass had grown in diameter to approximately 5 cm. This same mass was presumably the
cause of the patient’s tenesmus.
The owner also noted progressive right hind limb lameness over the course of the
four months prior to presentation. At the time of presentation to the soft tissue surgery
service, the owner complained of marked tenesmus, right hindlimb lameness, and cough.
The patient had no previous history of illness before the presentation of the mass
four months prior, nor did she experience complications with the ovariohysterectomy
performed over 10 years prior to presentation, when she was less than six months old.
Clinical Findings
At presentation, the patient appeared severely anxious and was reactive to touch,
or the anticipation of touch to the caudal half of the trunk and hind limbs. No external
swelling or mass was visible at the rectum, vulva, perineum, or abdomen. The right hind
limb laterally deviated on ambulation, which appeared as “swinging” the leg laterally at
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the walk and the jog, as well as holding the leg away from the trunk cranio-laterally when
sitting and recumbent. A round, firm, mobile subcutaneous mass 3 cm in diameter, was
palpated at the caudal aspect of the left hind limb. No coughing was noted at the time of
the physical examination. Complete blood count and blood chemistry were unremarkable.
At this time, the differential diagnoses list for this patient is extensive, including
an abscess or neoplasia arising from any of the normal anatomy of the pelvis. Examples
of differential diagnoses include granuloma, as the result of a stump pyometra (ovarian
remnant syndrome), carcinoma, adenocarcinoma, fibroma, fibrosarcoma, mast cell tumor,
leiomyoma, leiomyosarcoma, transmissible venereal tumor, hemangioma,
hemangiosarcoma, squamous cell carcinoma, and malignant lymphoma. Many of these
examples are uncommon for this location in canines. Nevertheless, the list of differential
diagnoses could not be reduced without further diagnostics including advanced imaging
to help localize and characterize the mass.
The patient was anesthetized for a full body computed tomography (CT) scan,
which confirmed a large, focal, well-defined, intrapelvic mass as the cause of the
patient’s inability to defecate. It was found to displace and compress the rectum leftdorsally, displace the urethra ventrally, and was continous with the vagina. The mass
appeared to arise from the vagina, not the colon or rectum. Sciatic nerve compression was
noted as a potential source for right pelvic limb pain. Bilateral hip osteoarthrosis was
noted as mild and provided an explanation for the patient’s chronic, mild bilateral hind
limb lameness, but was considered to be an unlikely cause of the more severe pain noted
at presentation. The subcutaneous mass of the left thigh was found to be an incidental
lipoma.
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While under general anesthesia, digital rectal palpation was performed and
revealed a large, rounded, firm mass along the right ventro-lateral aspect of the pelvic
canal, which effectively obstructed her rectum. The left ischium was also immediately
palpated at the left aspect of her pelvic canal, demonstrating the previously noted
deviation of the lumen of the rectum as the result of the presence of the large intrapelvic
vaginal mass. A biopsy of her mass, obtained through the lumen of the rectum during
digital rectal examination was also performed at this time and was inconclusive on
preliminary cytology.
Prior to further diagnostics, an extensive list of differential diagnoses included an
abscess or neoplasia arising from any of the normal anatomy of the pelvis: the rectum, the
vagina, the bony pelvis, and the urethra. Following localization of the mass to the vagina
via computed tomography, primary differential diagnoses were reduced to two forms of
neoplasia: either the benign leiomyoma or the malignant leiomyosarcoma,. The primary
inflammatory differential diagnosis, a granuloma resulting from “stump pyometra”, was
unlikely due to the fact that the patient was spayed by six months of age, over 10.5 years
prior, with no signs of ovarian remnant in the time since her ovariohysterectomy. Thus,
the primary differential diagnoses were limited to leiomyoma or meiomyosarcoma. The
final definitive diagnosis required histopathological analysis.
The treatment of choice for each primary differential diagnosis is the same:
surgical mass excision. Due to the unremarkable blood work, lack of metastases, and
well-defined nature of the reconstructed images of the intrapelvic mass, the patient was
considered a good candidate for surgery and surgical mass excision was planned for the
following day.
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Treatment
Surgery began with an episiotomy, in an effort to excise the mass with minimal
trauma to the nerves and other tissue of the pelvis in as minimally invasive an approach
as possible. The patient was surgically prepared for an abdominal approach as well,
should the mass require an abdominal laparotomy and pubic osteotomy to remove the
intrapelvic mass.
A standard approach to an episiotomy was performed with a standard full
thickness incision9. The caudal aspect of the mass was located and partially visualized in
the vaginal canal. However, the mass was located too far cranially to be removed using
this approach. The episiotomy incision was closed in standard three layer fashion and the
patient was then placed in dorsal recumbency and prepared in standard sterile fashion for
an abdominal laparotomy.
A standard caudal abdominal approach was made, after which the bladder,
ureters, uterine stump, and associated nerves were visualized. The mass was localized
and surrounding tissue was dissected away to confirm the mass was within the lumen of
the vagina and of vaginal origin. However, it was apparent that a pubic osteotomy was
required to provide access to the full mass and enable the complete excision of the mass.
The adductor and gracilis muscles were transected at their point of origin along
the pubic symphysis, and the right and left arms of the pubic bone were then carefully
transected. The cranial aspect of the pubic symphysis was then transected in a
perpendicular line to the original two transections, and the central portion of the pubic
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bone including the pubic symphysis was reflected caudally. Within the pelvis, the ventral
vaginal wall was incised and reflected to reveal the mass.
The mass was carefully excised from the vaginal wall. Attention was given to
attempt to avoid causing trauma to the associated nerves of the pelvis. The hypogastric,
pelvic, and pudendal nerves as well as the pelvic plexus were visualized. All together,
these nerves supply the sympathetic and parasympathetic innervation to the bladder,
urethra, and external urethral sphincter10. The tissue surrounding these nerves associated
with the mass were meticulously dissected in an attempt to prevent potentially permanent
post surgical complications including urinary or fecal incontinence.
After excision of the mass, the remaining defect in the vaginal wall as well as a
small defect in the rectal serosa was repaired before the pubic bone was realigned and
closed with 22 gauge orthopedic wire using the circlage technique. The adductor and
gracilis muscles were reattached to the pubic symphysis and the abdomen was flushed
with warm lavage before closing in standard fashion. The patient recovered from
anesthesia without complication and the mass was submitted for histopathological
analyisis.
After surgery, the patient received standard post surgical care in the intensive care
unit. This included intravenous antibiotic (clindamycin 11 mg/kg BID) as well as pain
management. Antibiotic medication was indicated as a prophylactic post-laparotomy
measure in the event of potential rectal wall perforation. Though we did not visualize any
gut wall perforations during the surgery, we could not confirm this until we concluded
surgery. Furthermore, we had been dissecting tissue surrounding and including the wall
of the rectum throughout the surgery. Some of this rectal serosal tissue had already been
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compromised prior to surgery by the presence of the tumor. Antibiotic administration was
begun in this patient prior to surgery and continued perioperatively until two weeks post
surgery. Clindamycin was chosen for it’s good coverage of anaerobic bacteria, which are
of particular concern in the event of rectal wall compromise. Pain management included:
intravenous fentanyl CRI 2 mcg/kg/hr, intravenous dexmedetomidine (0.5 mcg/kg) as
needed q 4 hours) and a one time subcutaneous 24 hour dose of carprofen (4.4 mg/kg). A
75 mcg fentanyl patch was placed post operatively so that it would be active the next day.
Once the patient was eating, oral pain medications were administered which
included carprofen (2 mg/kg PO BID), gabapentin (3 mg/kg PO BID), and tramadol (3
mg/kg PO as needed q 8 hours). The patient was weaned off of intravenous medications.
Throughout the patient’s recovery beginning directly after surgery, additional
supportive care included intravenous fluids, icing of the incision, checking the bandage
every 6 hours, and regularly monitoring the patient for pain or other abnormalities
including abnormalities in urination. The primary concern for this patient post operatively
was the surgical complication of urinary incontinence. However, within 24 hours the
patient produced a steady, controlled stream of urine and demonstrated good bladder
control. She was discharged to her owners 24 hours after surgery with the oral pain
medications (described above) as well as a prescription for two weeks of the antibiotic
clindamycin (7.7 mg/kg PO BID).
Pathological Findings
A moderately cellular, well-demarcated, expansile mass was described
histopathologically. The mass was composed of spindle cells which were often
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arranged at irregular, acute angles, thus creating a generalized disorganization
which is consistent with the irregular orientation of neoplastic cells. Cellular
pleomorphism, including anisocytosis and anisokaryosis were noted. Areas of
necrosis and ischemic change were also noted. The mitotic index was originally read
out at 1 mitotic figure per 10 high powered fields, but later was re-examined and
determined to be approximately 3 mitotic figures per 10 high powered fields. While
this remains a relatively low mitotic index, it is subjectively higher than the typical
mitotic indexin a benign leiomyoma. Cytologic features such as pleomorphism, rate
of mitosis, and invasiveness help in determining whether a tumor is the benign
leiomyoma or the malignant leiomyosarcoma7.
The mitotic index, areas of necrosis and ischemic change, and the cellular
atypia were the basis for the diagnosis of leiomyosarcoma. Data is limited for
vaginal leiomyosarcomas and therefore an assessment is also partially dependent
on the experience of the pathologist. In this case, the combination of mitotic activity,
cellular atypia and large areas of ischemic change and necrosis warranted a diagnosis of a
low grade leiomyosarcoma. Despite these factors, the mass appeared well demarcated.
The presence of normal muscle cells identified along the entire circumference of the
tumor demonstrated a likely complete excision.
Outcome/Discussion
Two weeks post surgery, the owners reported that the patient was
experiencing tenesmus . This patient was no longer receiving oral lactulose at the
time. After administration of lactulose (341 mg/kg PO BID), and supplementing the
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diet with canned pumpkin, the tenesmus resolved. One episode of diarrhea
followed an accidental overdose of lactulose, but the patient has had no subsequent
issues and has urinated and defecated normally throughout the eight weeks since
this episode. The owners report that the patient has a good appetite and energy
level, with no signs of pain or illness. The owners also report that the patient is able
to maintain bladder control for 7 hours at a time. Her current lactulose dose of one
teaspoon every 12 hours (0.11 mg/kg PO BID) is most likely unnecessary, but is
administered due to owner preference.
As previously stated, canine vaginal leiomyosarcomas are uncommon.
Gastrointestinal and splenic leiomyosarcomas are more commonly seen., Biologic
behavior seems to vary by location. For example, canine leiomyosarcoma of the liver
is considered to have a 100% risk of metastasis while a dermal leiomyosarcoma is
considered to have a very low risk of metastasis2. Not enough data exists to provide
a figure specifically describing the risk for metastasis of vaginal canine
leiomyosarcoma.
For other cancer types, a moderate risk of metastasis is generally associated
with larger tumors. Radiation therapy and chemotherapy may be pursued as post
surgical adjuvant therapies dependent upon whether or not the tumor was
completely excised, the location and size of the tumor, mitotic index and other
histological characteristics. There is no standard protocol in dogs regarding
radiation therapy or chemotherapy for vaginal leiomyosarcoma, although
doxorubicin based protocols are commonly used for other sarcomas in dogs Due to
limited data, the impact of these therapies on the outcome for vaginal
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leiomyosarcoma is unknown. Adjuvant therapy would have been recommended if
the patient’s histopathology report indicated incomplete excision or more
aggressive signs of malignancy. In this case, a complete excision seems to have been
attained and there is optimism that surgery was likely curative.
References
1. Thacher, CT and Bradley RL. "Vulvar and vaginal tumors in the dog: a retrospective
study." J Am Vet Med Assoc. 1983; 183.6: 690-692.
2. Klein, MK. Tumors of the female reproductive system. In: Withrow, SJ, and Vail, DM,
eds. Withrow & Macewen's Small Animal Clinical Oncology. 4th ed. St. Louis: Saunders
Elsevier, 2007. 610-618
3. Brodey, RS, Roszel JF. Neoplasms of the canine uterus, vagina, and vulva: a
clinopathologic survey of 90 cases. J Am Vet Med Assoc. 1967; 151:1294-1307.
4. Kydd DM, Burnie AG. Vaginal neoplasia in the bitch: a review of 40 clinical cases. J
Small Anim Pract. 1986; 27: 255-263.
5. Maruo, T, Ohara N, Wang, J, et al. Sex steroidal regulation of uterine leiomyoma
growth and apoptosis. Human reprod update. 2004;10(3): 207-220
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6. Reed, SD, Cushing-Haugen KL, Daling, JR et al. Postmenopausal estrogen and
progestogen therapy and the risk of uterine leiomyomas. Menopause. 2004;11(2): 214-22.
7. Schlafer DH, Miller RB. Female genital system. In: Maxie, MG, ed. Jubb, Kennedy,
and Palmer's Pathology of Domestic Animals. Vol.3 Edinburgh: Elsevier Saunders. 2007;
429-564
8. Liptak, JM, Forrest, LJ. Soft tissue sarcomas. In: Withrow, SJ, and Vail, DM, eds.
Withrow & Macewen's Small Animal Clinical Oncology. 4th ed. St. Louis: Saunders
Elsevier, 2007. 425-454.
9. Tobias, KM. Episiotomy. In: Tobias, KM. Manual of Soft Tissue Surgery. Ames:
Wiley-Blackwell. 2010; 265-268.
10. Evans, HE, de Lahunta, A., eds. The urogenital system. In: Miller's Anatomy of the
Dog. 4th Ed. St. Louis: Elsevier Saunders. 2013; 361-405.
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