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Prognosis and Surgical Treatment of the Urethra Embedding Leiomyosarcoma in a Dog
Ji-Hyun Kim, Jun-Am Lee, Ill-Hwa Kim, Dong-Woo Jang and Hyun-Gu Kang1
College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Korea (Accepted: June 18, 2014)
Abstract : A 16-year-old female Shih-Tzu, weighing 5 kg, presented with clinical symptoms of abdominal distension and urinary and fecal incontinence. Abdominal palpation detected a large mass. According to the radiographic findings, the bladder had been moved to the umbilicus by the mass and a large abdominal mass was confirmed in the lower abdominal area. Ultrasonography indentified a large heterogeneous mass with heterogeneous parenchyma and a focal anechoic area in the lower abdominal area. The complete blood count abnormalities suggested thrombocytosis and mild neutrophilia, and the serum chemistry indicated an elevated alkaline phosphatase value. During laparotomy, a firm mass that measured 10.5× 9.6 cm was found between the uterine cervix and urinary bladder. The urethra was embedded in the mass. A diagnosis of leiomyosarcoma was established based on histopathology and histochemistry.
One week after surgery, urinary retention symptoms that did not appear to be related to mechanical obstruction presented suddenly, but they did not respond to several drug treatments, thus long-term conservative therapy was adopted. The urinary symptoms disappeared on day 27 and the patient started to void large quantities of urine in a smooth and frequent manner. This case report describes the serial changes in the patient’s status and the response after surgical remove of the urethra embedding leiomyosarcoma.
Key words : dog, leiomyosarcoma, urinary incontinence, micturition disorder after surgery.
Introduction
Leiomyosarcomas are malignant tumors that occur within smooth muscles, which account for 10% of all smooth mus- cle tumors (6,7). In addition, it is known that their benign counterparts, leiomyomas, can undergo malignant transforma- tion. Leiomyosarcomas represents only a very small proportion of urinary system tumors and they occur most commonly in the genitalia (3,4,7,15,24,25).
The clinical signs that are commonly associated with urinary system leiomyosarcoma are hematuria and/or dysuria, anorexia, lethargy, and an acute painful abdomen, but if they are suffi- ciently large they can be obstructive, with azotemia, uremia, or pelvic limb edema (3,4,11). Tumors in the genital system may also cause reproductive failure or urinary or colonic obstruc- tion (3,7,9,13).
Micturition disorders can be divided into urinary inconti- nence, which presents as involuntary leakage of urine, and urinary retention, which is defined as the failure to void, thereby leading to frequent and unsuccessful attempts to uri- nate (10,14,17,23). Micturition disorders may be related to multiple factors, such as halothane anesthesia, glycopyrrolate administration, anal purse-string suture, and surgical pain in postoperative dogs (7,10,17).
This report describes the case of a dog with leiomyosar- coma of unknown origin in the abdominal cavity and the micturition symptoms that presented after surgery.
Case
A 16-year-old female Shih-Tzu, weighing 5 kg, presented at the Chungbuk National University, Veterinary Teaching Hospital with a history of fecal and urinary incontinence. On physical examination, the respiratory rate and pulse rate of the patient were within the normal range, but the oral mucosa was dry and sticky. Palpation detected a large caudal abdominal
1Corresponding author.
E-mail: [email protected]
Table 1. Hematological values
Items Values Reference range
White blood cells (cells/µL) 17,800 6,000~17,000 Monocyte (cells/µL) 178 200~2,000 Lymphocyte (cells/µL) 890 1,000~4,800 Neutrophil (cells/µL) 16,732 3,000~11,800 Eosinophil (cells/µL) 0 100~1,300
Basophil (cells/µL) 0 0~500
Red blood cells (× 106cells/µL) 5.40 5.5~8.5
Hemoglobin (g/dL) 12.8 12~18
PCV (%) 37.1 37~55
MCV (fL) 68.7 60~74
MCH (pg) 23.7 19.5~24.5
MCHC (g/dL) 34.5 31~36
Platelet (× 103/µL) 961 200~500
·PCV = packed cell volume, MCV = mean corpuscular volume, MCH = mean corpuscular hemoglobin, MCHC = mean corpuscu- lar hemoglobin concentration.
mass near the bladder, which was round and firm. In addition, there were 3 cm and 1 cm diameter mammary tumors in the 3rd mammary gland on the left and the 4th mammary gland on the right, respectively. There was no enlargement of the superficial lymph nodes.
The complete blood count detected thrombocytosis (961× 103/µL, reference range: 200-500× 103/µL) and mild neutro- philia (16,732 cells/µL, reference range: 3,000-11,800 cells/µL).
The lymphocyte and monocyte levels were mildly elevated (Table 1). According to the serum biochemistry, the sodium and chloride levels were within the reference limits. How- ever, severe elevation of alkaline phosphatase was detected (Table 2).
Radiographic examination of the caudal part of the abdomen indentified a well-circumscribed, homogeneous shaded mass
that measured 10.5× 9.6 cm in diameter. The mass was located between the umbilicus and pelvic inlet, and the descending colon deviated to the right dorsolateral side.
Excretory urography was performed to examine the ure- ters, urethra, and bladder. Radiographic images were obtained at 20 min after injecting the contrast medium, which showed that both kidneys were dislocated to the front. The left renal pelvis exhibited mild to moderate enlargement and the distal ureter had a normal diameter but was deviated toward the bladder craniolaterally by the mass at the L5 level. The blad- der also deviated toward the umbilicus level due to the mass and the caudal side appeared to be the shape of a half-moon because of extraluminal suppression (Fig 1).
According to ultrasonography, there was a caudal abdomi- nal mass with mixed echogenicity. The mass appeared to be well marginated from the peripheral tissues and the cortex of the mass was thin (Fig 2). The renal size, echogenicity, tex- ture, and corticomedullary definition were normal. Hypere- choic calcification was detected in the renal diverticulum and the margin of the left kidney was irregular. Based on color Doppler, there was no detectable blood flow within the mass.
Laparotomy was performed. A round and firm mass that measured approximately 10 cm was excised from the front part of the pelvic cavity (Fig 3). The mass adhered to the bladder in a forward direction and the urethra was enclosed along the mass (Fig 3B). All of the components were cov- ered broadly with a thick sheath. The mass was separated readily from its location by blunt dissection because the mass had only embedded the serosal layers of the urethra (Fig 3C).
The urethra was elongated by approximately 10 cm due to the growth of the mass, but it was not expected to require any surgical treatment due to spontaneous repair. Lumpectomy was also performed.
Histopathological examination (Fig 4) of the abdominal mass detected a malignant soft tissue tumor, which was assumed to be a leiomyosarcoma or fibrosarcoma. Using Masson’s tri- chrome stain, the mass was diagnosed as a leiomyosarcoma.
After surgery, the urethral catheter was removed on day 7, but urinary retention was detected on day 8. The vacuation Table 2. Serum biochemical profiles of the patient
Items Values Reference range
Total protein (g/dL) 6.8 5.4~7.1
Albumin (g/dL) 2.6 2.6~3.3
Globulin (g/dL) 4.2 2.7~4.4
A/G ratio 0.62 0.59~1.11
ALT (IU/L) 83 21~102
BUN (mg/dL) 17.5 7~25
Creatinine (mg/dL) 1.0 0.5~1.5
Glucose (mg/dL) 106 65~118
Total bilirubin (mg/dL) 0.1~0.5
ALP (IU/L) 703 29~97
GGT (IU/L) 6 1.2~6.4
Sodium (mmol/L) 154 141~152
Potassium (mmol/L) 4.9 4.37~5.35
Chloride (mmol/L) 116 105~115
Calcium (mg/dL) 10.2 9~11.3
Phosphorus (mg/dL) 2.9 2.6~6.2
·ALT = alkaline phosphatase, BUN = blood urea nitrogen, ALP = alanine aminotransferase, GGT = gamma-glutamyl transpeptidase.
Fig 1. Right lateral (A) and ventrodorsal (B) radiographs. The viscera were displaced by the well-circumscribed intra-abdominal mass.
In the lower abdomen, the shaded rounded mass is visible at L5 near to the pelvic inlet. The white arrows indicate the abdominal mass and the black arrow indicates the contrast-enhanced urinary bladder.
Fig 2. Transverse (A) and longitudinal (B) ultrasonographic images of the abdominal mass. The abdominal mass appears as heter- ogeneous parenchyma and there is a focal anechoic area.
Fig 3. Photographs of the abdominal mass. (A) Macroscopic appearance of the urinary bladder and abdominal mass. The white arrow indicates the urinary bladder. The black arrow indicates the abdominal mass. (B) Macroscopic appearance of the abdominal mass with urethra embedded by viscera. The white arrow indicates the embedded urethra. (C) Gross appearance of the extracted mass with the urethra separated from the abdominal mass. The white arrow indicates the urethra and the black arrows indicate the mass.
Fig 4. Microscopic appearance of the abdominal mass. (A) The tumor primarily comprised spindle cells with elongate nuclei, granular chromatin, and eosinophilic cytoplasm, thereby suggesting a smooth muscle tumor. The fascicles exhibit a basket weave pattern in many areas of the tumor (× 100). (B) Pleomorphic tumor cells with irregular nucleoli and mitotic figures (black arrows) (× 400). (C) The red areas are cytoplasm, keratin, or muscle fibers, and the blue areas are collagen tissues. Although there are large fibrous com- ponents, the diagnosis should be leiomyoma or leiomyosarcoma provided smooth muscle is present (× 100). (D) Coagulative tumor cell necrosis. The hyperchromatic necrotic tumor cell nuclei on the left are characteristic of those in tumor cell necrosis (× 400). A, B, and D = stained with hematoxylin-eosin. C = stained with Masson’s trichrome.
function and perineal reflex were normal. Ultrasonographic examination showed that the bladder was severely distended.
Both the renal pelvis and proximal ureters were enlarged (2.5 mm), but the corticomedullary definition and the parenchyma margin were normal. A urinary catheter was advanced easily via the urethra into the urinary bladder. According to com- plete blood count, the white blood cell (32,700/µL, reference range 6,000-17,000/µL) and segmented neutrophil (28,776/
µL, reference range 3,000-11,800/µL) counts were elevated, and red blood cell regeneration was observed.
On day 15, manual urination was attempted. The bladder was rigid and the patient felt pain when the bladder was compressed manually. The patient adopted a urination pos- ture for prolonged periods, but only voided small drops of urine. The results of a urothrogram (Fig 5) showed that the elongated urethra was twisted and the urethral diameter was irregular. A filling defect had occurred at the bladder neck and the diameter of the proximal urethra was narrow com- pared with the other part. However, the urinary symptoms, which suggested complete obstruction, were too severe to be caused by this problem alone. We considered that the cause was not physical obstruction due to the displacement of the elongated urethra and we assumed that a neurological prob- lem might have been affecting the urethral sphincter, bladder muscle, or urethral muscle.
Thus, we started prazosin (Prazocin®, 0.06 mg/kg, PO, BID, Hanbul, Korea) treatment on day 16. The next day, the patient voided a small amount of urine when the urinary catheter was removed. However, dysuria reoccurred soon after and the urinary catheter was inserted again. On day 19, diaz- epam (Diazepam®, 4 mg/kg, IV, GuJu, Korea) and betha- nechol (Besacolin®, 5 mg/day, PO, CJ Cheiljedang, Korea) treatment were instituted, but there was no improvement. On day 20, an evaluation using cystometry (Urodynamics) showed that the bladder function was normal but the relaxation pat- tern of the outer urethra was not confirmed. On day 23, dan- trolene (Dantrolene®, 2 mg/kg, IV, BID, Korea Orphan Center, Korea) treatment was started and manual expression was attempted, but it failed. Vomiting symptoms appeared due to
dantrolene’s adverse reaction with the gastrointestinal tract, thus an antiemetic drug was also prescribed.
We decided to perform exploratory laparotomy on day 27, but the urinary symptoms suddenly disappeared on the next day and the patient started to void large quantities of urine in a smooth and frequent manner. The urine analysis showed that the urine pH was moderately high (9.0), whereas the other values were normal. The CBC, serum chemistry, and electrolyte values were also normal, except for ALP (210 IU/
L, reference range: 29-97 IU/L). Follow-up veterinary evalu- ation was not performed.
Discussion
Leiomyosarcomas of the urogenital system may affect the vagina, vulva, uterus, ureter, prostate, or kidney in dogs (3,4, 19,24,25). This is the first case of a urethral embedded lei- omyosarcoma in a dog. In this case, the origin of the tumor was unknown and the mass adhered to the bladder in a for- ward direction while the urethra was enclosed along the mass.
The mass was separated readily from its location by blunt dis- section because the mass had only invaded the serosal layers of the bladder and urethra. The gross features of the cross- sections of leiomyosarcoma masses are pale grey, firm, and fleshy, with a nodular or bosselated surface (16,19,20). Simi- lar gross features were observed in the present case.
The clinical signs associated with urogenital system leiomy- osarcoma are hematuria and/or dysuria, anorexia, lethargy, acute painful abdomen, azotemia, uremia, pelvic limb edema, reproductive failure, and urinary or colonic obstruction (3,7,9,11,13). Similar clinical signs (fecal and urinary incon- tinence) were observed in the present case.
Histopathologically, the characteristic features of leiomyo- sarcomas may vary depending on the degree of differentiation.
Densely packed homogeneous spindle cells similar to normal smooth muscle cells and pleomorphic spindle to ovoid or round cells with variable histological patterns may be present (7,12,16,19). It is sometimes difficult to distinguish leiomyo- sarcoma from leiomyoma, but the three features, mitotic index, evidence of invasion, and areas of tumor necrosis, are most useful for detecting malignancy (7,12,19). In our case, the presence of a necrotic mass and mitotic changes were confirmed by hematoxylin-eosin staining, thus we diagnosed a malignant tumor. Using Masson’s trichrome stain, the tumor was finally confirmed as a leiomyosarcoma (Fig 4). In addi- tion, we found that the masses in the mammary glands were carcinosarcomas, which were not associated with the abdom- inal mass.
Normal urination is a spinal reflex function, which is medi- ated by the caudal brain stem. Urination is facilitated by relax- ation of the bladder neck and proximal urethra via the inhibition of α-adrenergic sympathetic neurons (10). The dog’s urinary dysfunction may have been caused by multiple fac- tors such as bupivacain and glycopyrrolate administration, halothane anesthesia (1,5,21,22), surgical pain and stress, and increased bladder distention (2,18,22). Urinary retention is caused by urinary obstruction or bladder atony. Mechanical or functional causes can lead to urinary obstruction, and failure of the detrusor muscle due to a neurological or muscular defect Fig 5. Image of excretory urography on day 20. The diameter of
the urethra was irregular but it was not obstructed completely.
can lead to bladder atony (8,10,23). Bethanechol, which is a cholinergic drug, and alpha-adrenergic blockers are gener- ally used to treat bladder atony (8,23). Thus, in the follow- ing order, we provided prazosin treatment to attempt to relax the urethral muscle, bethanechol treatment with diazepam to stimulate the urinary bladder, and dantrolene treatment to facilitate muscle relaxation. None of the treatments were fully effective. Thus, we concluded that neurogenic damage to the bladder or urethra was not the cause of the urinary reten- tion. We also obtained a urothrogram to confirm whether there was mechanical obstruction of the ureter, which showed that mechanical obstruction was not the direct cause (Fig 5). Uri- nary retention disappeared suddenly on day 27 and the patient voided normally. As a result, we conclude that this case was related to surgical pain or stress rather than neurogenic dam- age and mechanical obstruction.
In conclusion, this case shows that urinary symptoms can occur without urethral obstruction or neurogenic problems after surgical treatment of the urogenital system. In such cases, it is appropriate to assess the effects following surgery and to provide long-term conservative therapy. In addition, the deci- sion about whether to remove an elongated urethra should only be made after careful consideration.
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개에서 요도를 포매한 평활근육종의 수술적 처치 및 예후
김지현·이준암·김일화·장동우·강현구1
충북대학교 수의과대학 동물의료센터
요 약 : 충북대학교 동물의료센터에 16년령 암컷 시츄견이 복부팽만과 배뇨, 배변곤란을 주증으로 내원하였다. 신체검
사 시 복부에서 10cm가량의 종양이 촉진되었으며 방사선 상에서 확인되었고, 방광은 종양에 의해 배꼽 쪽으로 변위
되어 있었다. 초음파 상에서 종양은 불균질한 실질과 국소적으로 무에코성 영역을 가지고 있었다. 혈액검사 소견상 혈 소판증가증과 약한 호중구증가증이 나타났으며, 혈액화학치 검사 결과 ALP 상승을 확인할 수 있었다. 개복술을 시행 하여 자궁경과 방광 사이의 10.5 × 9.6 cm 크기의 단단한 종양이 요도를 포매하고 있는 것을 확인하고 주위조직과 둔 성분리 후 절제하였다. 조직병리학적 검사와 면역화학 적 검사 결과 종양은 평활근육종으로 진단되었다. 수술 후 일주 일 뒤 배뇨곤란을 주증으로 재 내원하였다. 배뇨곤란의 원인을 찾기 위하여 요도조영술을 실시하였으나 물리적인 폐 색 등 특별한 원인을 찾을 수 없었다. 방광근과 방광조임근에 작용하는 몇몇 약물요법 등을 시행하였지만 반응이 없 어 중장기의 보존요법이 지시되었으며 배뇨곤란 증상은 술 후 27일차에 갑작스럽게 호전되어 환자는 원활한 배뇨를 하게 되었다. 본 증례는 요도를 포매하고 있는 복강 내 종양의 수술 후 예후와 배뇨곤란과 같은 후유증을 나타낼 수 있음을 시사하고 있다.
주요어 : 개, 평활근육종, 배뇨곤란, 수술 후 합병증
