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Uterine Leiomyosarcoma in a 14 month filly
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Rullán-Mayol Alberto J, VMD, Reed S. DVM, DABVP, Johnson Jill R. DVM, MS, DACVIM, DABVP, Eilts B. E, DVM, MS,. DACT

Case Description: A 14 month old Quarter Horse was evaluated for colic, hematuria and vaginal bleeding of seven days duration.

Clinical findings: Results of a physical examination showed mild tachycardia and bloody vaginal discharge. Hematological analysis showed mild hypoalbuminimea and mildly prolonged clotting times. Transrectal and transabdominal ultrasound revealed a large irregular cystic mass which extended from the vagina to mid abdomen. Based on biopsy it was determined the mass to be leiomyosarcoma.

Treatment and outcome: The owner declined to attempt treatment with ovariohysterectomy. The filly died 20 days after discharge from the hospital. Post mortem examination revealed a 16 kg irregular, multiloculated, cystic mass originating from the uterine bifurcation.

Clinical relevance: Uterine leiomyosarcoma can occur in young fillies, can be invasive and can be fatal.

Case History:
A 14 month old Quarter Horse filly with a primary complaint of colic, hematuria and vaginal bleeding of seven days duration. The filly had been kicked in the abdomen 5 months prior to presentation, resulting in a laceration in the flank that healed without complications. The referring veterinarian had attempted to treat the recent urogenital bleeding with trimethoprim sulfamethoxazole without response.

At presentation, the body condition score was 6/9. An approximately 6cm scar was observed on the right body wall. The heart rate was 60 beats per minute, the respiratory rate was 32 breaths per minute and the rectal temperature was 38.7C A small amount of bloody discharge was noted coming from the vagina. A vaginoscopic exam revealed what was believed to be a large blot clot laying on the floor of the vagina. The filly was rested overnight in order to avoid possible bleeding from the mass. Hematological analysis revealed hypoproteinemiaof 4.7g/dl (reference range 6.1-8.1g/dl), and hypoalbuminimia of 2.3g/dl (3.0-4.1gm/dl). A coagulation profile showed a pro-thrombin time of 12.3 seconds (8-10seconds), and a partial thromboplastin time of 51 seconds (32-42 seconds).

Abdominocentesis yielded a clear fluid with total a protein less than 2.5gm/dl, nucleated cells less than 2500 cells/µl with 64% non-degenerative neutrophils, 2% small mature lymphocytes and 34% macrophages with occasional leukophagocytosis.

A more thorough vaginoscopic examination revealed an irregular mass covered with unclotted blood in the cranial vagina. The cervix and fornix could not be visually identified. Palpation per rectum identified an enlarged, firm uterus (approximately the size of a 3 month old pregnancy). Neither the uterine horns nor the ovaries could be readily distinguished. Manual examination of the cranial vagina revealed a very large, fragile, irregular mass, surrounded by fluid, presumed to be blood. The vaginal wall felt roughened and irregular. The mass appeared to be attached to, or pass through, the cervix. A biopsy of the mass was submitted for histopathology.

Transrectal ultrasound of the mass showed a heterogenous, fluid filled structure that appeared to extend from the cranial vagina into the uterus. The cranial border of the uterus could not be identified. Multiple hypoechoic structures surrounded by heterogenous fluid were observed (Figure 1). A homogeneous hyperechoic structure was seen in the left uterine horn (figure 2). Transabdominal ultrasound revealed a large heteroechoic mass with multiple hypoechoic structures extending cranially on both right and left flanks (Figure 3).

Differential diagnosis of the mass included blood clot due to uterine vessel rupture, bleeding due to urolithiasis, varicose veins, urinary tract trauma or neoplasm.

Based on the biopsy, the histopathologic and immunohistochemical diagnosis of the mass was leiomyosarcoma.

The owner declined to attempt treatment with ovariohysterectomy. The filly died 20 days after discharge from the hospital.

Post mortem examination revealed a 16 kg irregular, multiloculated, cystic mass originating from the uterine bifurcation and filling the uterine lumen (Figures 4 and 5). The mass extended from inside the uterus caudally into the vagina and into the vestibule.

Gross pathologic description:
Grossly, the neoplasm appeared to emanate from the dorsal wall of the uterine body just caudal to the bifurcation of the uterine horns. The mass filled most of the uterine lumen, extended through the cervix, and filled the vaginal vault. Dimensions were approximately 30-40 cm in diameter by approximately one meter long. The mass was variable in shape and consistency; in most areas it was moist, rubbery and conformed to the dimensions of the uterine lumen; but also in other areas multilocular cysts were present. The portion of the tumor filling the vaginal vault was drier, firmer, and less pliable. Most of the intrauterine mass was tan, whereas the portion extending through the cervix and occupying the vaginal vault was mottled red to black.

Histopathologic description:
Histologically, the neoplasm was composed of large areas of hemorrhage and disorganized neoplastic spindle to oval cells with variable amounts of eosinophilic or non-staining cytoplasm. The majority of the mass had a disorganized reticular appearance (the cells having large amounts of non-staining vacuolated cytoplasm); however there were densely packed areas of cells with eosinophilic cytoplasm that formed haphazard interlacing fascicles. The cell borders were indistinct and the nuclei were paracentral to peripherally located. The nuclei were elongated, elliptical, or fusiform and had hyperchromatic chromatin without distinctive nucleoli. There were 1-2 mitotic figures per high powered field. Minimal stromal tissue consisted of moderate numbers of blood vessels with scant fibrous connective tissue. Occasional vessels were thrombosed with fibrin clots. Immunohistochemical staining of the neoplasm was positive for vimentin, desmin and smooth muscle actin (consistent with leiomyosarcoma).



Discussion:
Uterine leiomyosarcoma is a rare neoplasm in horses[1]. Equine leiomyosarcomas have been reported to occur in the testicles, lungs, mouth, stomach, rectum and uterus. [1-8]. Other malignant uterine tumors in mares include rhabdomyosarcomas, lymphosarcomas and adenocarcinomas [9]. Uterine leiomyosarcomas have not been previously reported in horses younger than 7 years. Hinojosa et al reported two cases involving small extraluminal masses that were detected upon palpation per rectum in two adult mares (ages 7 and 15 years old). Surgical excision was thought to be curative for both cases. Santschi and Slone reported a case with a discrete extraluminal uterine leiomyoma causing infertility that regained reproductive soundness after partial hysterectomy. However, reproductive performance may be negatively affected by uterine leiomyosarcoma (Lofstedt TM, Grant). Prognosis after surgical removal of small uterine tumors has been reported to be good [4, 9-12].

Vaginal bleeding was the first indication of disease, however colic was the reason the horse was ultimately presented, at which time the condition was quite advanced. Differential diagnoses for vaginal bleeding and/or hematuria in mares include urolithiasis, urinary tract trauma or neoplasms [13], vaginal varicosities [14], uterine vessel rupture, uterine neoplasm [15]. Neoplasia was not highly suspected in this animal due to age, however, this case shows that uterine tumors can occur in young animals, can be locally invasive and can ultimately be fatal. Perhaps early tumor detection and resection could have been curative in this case, however the clinical signs and the non-breeding age of the filly made early detection of this tumor improbable.

References:

1. Allison, N. and R.B. Moeller, Jr., Bilateral testicular leiomyosarcoma in a stallion. J Vet Diagn Invest, 1999. 11(2): p. 179-82.

2. Rossdale, P.D., et al., Pulmonary leiomyosarcoma in a 13-year-old Thoroughbred stallion presenting as a differential diagnosis to recurrent airway obstruction. Equine Veterinary Education, 2004. 16(1): p. 21-28.

3. MacGillivray, K.C., T.D. Graham, and E.J. Parente, Multicentric leiomyosarcoma in a young male horse. Journal of the American Veterinary Medical Association, 2003. 223(7): p. 1017-1021+986.

4. Hinojosa, A.M., et al., Theriogenology question of the month. Journal of the American Veterinary Medical Association, 2003. 223(6): p. 786-788.

5. Hollerrieder, J. and J. To?th, Minimal invasive surgery of a bleeding uterine tumor in a mare using a wire cerclage. Minimal invasive entfernung eines blutenden uterustumors bei einer stute mittels drahtcerclage ein fallbericht, 2002. 30(6): p. 404-407.

6. Boy, M.G., et al., Gastric leiomyosarcoma in a horse. Journal of the American Veterinary Medical Association, 1992. 200(9): p. 1363-1364.

7. Mair, T.S., F.G.R. Taylor, and P.J. Brown, Leiomyosarcoma of the duodenum in two horses. Journal of Comparative Pathology, 1990. 102(1): p. 119-123.

8. Clem, M.F., R.M. DeBowes, and H.W. Leipold, Rectal leiomyosarcoma in a horse. Journal of the American Veterinary Medical Association, 1987. 191(2): p. 229-230.

9. McCue, P.M., Neoplasia of the female reproductive tract. Vet Clin North Am Equine Pract, 1998. 14(3): p. 505-15.

10. Janicek, J.C., D.H. Rodgerson, and B.L. Boone, Use of a hand-assisted laparoscopic technique for removal of a uterine leiomyoma in a standing mare. J Am Vet Med Assoc, 2004. 225(6): p. 911-4, 880.

11. Quinn, G.C. and N.S. Woodford, Infertility due to a uterine leiomyoma in a Thoroughbred mare: Clinical findings, treatment and outcome. Equine Veterinary Education, 2005. 17(3): p. 150-152.

12. Berezowski, C., Diagnosis of a uterine leiomyoma using hysteroscopy and a partial ovariohysterectomy in a mare. Canadian Veterinary Journal, 2002. 43(12): p. 968-969.

13. Fischer Jr, A.T., et al., Neoplasia of the equine urinary bladder as a cause of hematuria. Journal of the American Veterinary Medical Association, 1985. 186(12): p. 1294-1296.

14. White, R.A., et al., Persistent vaginal haemorrhage in five mares caused by varicose veins of the vaginal wall. Veterinary Record, 1984. 115(11): p. 263-264.

15. Brandstetter, L.R., P.S. Doyle-Jones, and H.C. McKenzie Iii, Persistent vaginal haemorrhage due to a uterine leiomyoma in a mare. Equine Veterinary Education, 2005. 17(3): p. 156-158.