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CLINICAL

Cutaneous Lymphoma
case report
SPECIES: BREED: AGE: SEX: COLOUR: WEIGHT: Equine Thoroughbred 4 year old Mare (not in foal) Brown 520kg

By Jo Park, AVN, Dip VN (Surgical)

Cutaneous Lymphoma is a neoplastic disorder of lymphoid tissue. It can exist as a primary disease limited to skin and subcutaneous tissues or concurrently with visceral involvement. Horses of all ages have been diagnosed with lymphoma, with the majority being between the ages of 4 and 9 years. No clear age, sex or breed predisposition has been identified, however there have been reports of a higher incidence in mares. The most common form of Cutaneous Lymphoma is T-cell rich, B cell lymphoma within subcutis and dermis.

On the 20th of June 2006, the mare was presented to another veterinary clinic for a routine vaccination schedule of EHV1, Salmonella, Tetanus and Strangles. On examination she had been fully clipped except on the legs. Three, firm non-painful subcutaneous lumps were found in the long hair on the right front medial knee region. These were approx 1.5cm to 5cm in diameter and protruding about 2.5cm. On the 26th of June 2006, an excision biopsy of the smallest lump was taken by the other veterinary clinic and sent away for tests. On the 7th July 2006, a routine blood screen was performed whilst awaiting the results of the biopsy as the stud manager had noticed that the mare was quiet and mildly lethargic. The results revealed that there were no abnormal circulating lymphoid cells.

HISTORY

On the 14th July 2006, histopathology results were completed. These found neoplastic cells present in biopsy sample. Owners were advised of options by the other veterinary clinic and decided to refer the mare to Scone Veterinary Clinic. On the 19th of July 2006, the mare was referred to Scone Veterinary Hospitals Clovelly Intensive Care Unit for further evaluation.

ADMISSION

Before the mares arrival to the Clovelly Intensive Care Unit her paperwork had been filled out including Admission form and Consent form. All of her referral paperwork was put into her folder along with Intensive Care Flow Sheets and Progressive Clinical Note Sheets. A straw box had been made ready for her with water and lucerne hay.

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Upon arrival it was noted that the mare had three rugs. An identification label was placed on them and a note was made on her Clinical Note sheet. She walked in and settled well into her box. She was left for a while to be observed before a thorough clinical examination was performed. It was decided not to prescribe any medication for her at this time until all diagnostic test have been completed. She was placed on a 24 hour ICU check where her vitals were taken every 24 hours. Her rugs were taken off in the morning and placed on again at night. She was eating, drinking, urinating and passing manure normally. After 3 days she was placed into a small paddock during the day and put back into her box at night.

Physical examination, laboratory data, ultrasonographic and radiographic findings revealed no evidence of systemic involvement of the cutaneous lesions. However, these diagnostic tests cannot preclude the presence of a small mass or the beginning of systemic involvement. There is the potential for systemic / multicentric involvement and this form carries a guarded prognosis, however the cutaneous form carries a good prognosis. The cutaneous masses can regress and reoccur and remission has been associated with pregnancy, hormone fluctuations or supplement administration. Pathology Report HAEMATOLOGY WBC x 109/L RBC x 1012/L HAEMOGLOBIN g/L PCV L/L MCV fl MCH pg MCHC g/L NEUTROPHILS LYMPHOCYTES MONOCYTES PLASMA PROTEIN g/L FIBRINOGEN g/L BIOCHEMISTRY AST (GOT) U/L ALP U/L GAMMA GT U/L CK U/L GLUCOSE U/L CREATINE umol/L UREA mmol/L T.BILIRUBIN umol/L SERUM PROTEIN g/L ALBUMIN g/L GLOBULINS g/L CALCIUM g/L PHOSPHATE mmol/L SODIUM mmol/L RESULTS 8.0 10.31 155 0.48 46 15.1 326 68 - 5.44 (x 109/L) 26 - 2.08 (x 109/L) 6 - 0.48 (x 109/L) 65 2 RESULTS 295 176 18.9 217 5.7 146 6.0 48 57 31 26 2.93 0.93 135 EQUINE TB 6.0 - 12.0 6.0 - 12.0 130 - 174 0.35 - 0.47 38 - 49 13 - 16 300 - 390 2.47 - 7.00 1.63 - 4.40 0 - 0.72 55 - 70 2-4 EQUINE TB < 350 < 200 < 22.0 < 350 4.5 - 6.3 87 - 160 3.7 - 7.0 17 - 48 55 - 65 29 - 37 13 - 37 2.78 - 3.32 0.92 - 1.36 136 - 142

POTASSIUM mmol/L CHLORIDE mmol/L TOTAL CO2

3.5 96 36

3.1 - 4.4 95 - 106 27 - 32

Ultrasononographic examination of the uterus, ovaries, thorax and abdomen revealed no significant findings. Abdomniocentesis was attempted, however no fluid was obtained. Radiographs taken of her thorax detected no abnormalities.

PRESENTATION

On arrival the mare was bright and alert, in good body condition with a normal appetite and manure production. A full physical examination was performed on the mare. Physical Examination TIME TEMPERATURE HEART RATE PULSE QUALITY MUCOUS MEMBRANE COLOUR CAPILLARY REFILL TIME RESPIRATION RATE LUNGS GUT SOUNDS URINE FAECES APPETITE ATTITUDE 2pm 37.6 40 Strong Pink <2 16 OK OK None Normal OK BAR

DIAGNOSIS

The differential diagnosis for Cutaneous Lymphoma include a range of nodular skin diseases. Definitive diagnosis requires histopathologic or cytologic confirmation. Histologic examination of a biopsy specimen from affected tissue can be useful. An excisional biopsy was performed by the other veterinary clinic. Tests revealed that neoplastic cells had infiltrated the associated fascial tissue. A diagnosis of T-cell rich B cell lymphoma was made. These usually develop slowly and can also go through spontaneous rapid growth as well as episodes of partial to full remission.

TREATMENT
Glucocorticoids remain the mainstay of treatment of Cutaneous T-cell-rich B cell lymphoma. Tumor regression is typically noted following the systemic administration of Dexamethasone or Prednisolone. Intralesional injections of Betamethasone or Triamcinolone can also be performed with success. However, this may be impractical when presented with a large number of cutaneous lesions. Progestogens may demonstrate a decrease in production of the tumors. Surgical removal may be beneficial if there is a large number of masses. Radiation therapy and systemic chemotherapy could also be used, however more investigation and research as to the effectiveness in the management of equine patients is needed.

Two masses were palpated on the right fore no associated pain. The two masses measured approx 3cm and 2cm in diameter. There were also a number of smaller masses on the inside of both hind legs dorsal to the stifle joint. No other cutaneous lesions were found and no abnormalities were found on a detailed physical examination. A rectal exam was performed and no abnormalities were detected.

ASSESSMENT

Further diagnostic workup included laboratory test Haematology, CBC and Biochemistry; ECG; abdominal and thoracic ultrasonography and thoracic radiography. Additionally each mass was palpated and evaluated ultrasonography to document and characterise the masses anatomical relations. The majority were well defined, discrete and encapsulated ranging in size from 0.5cm to 3cm in diameter.

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On the 25th of July 2006, a thorough physical and ultrasound examination was performed on the mare. All limbs and the body were investigated and this found 8 separate areas where subcutaneous masses were present. A total of sixteen lumps were identified all located on the legs. All four legs had masses on them ranging in size from 1cm to 6cm in diameter. A small area around the masses was clipped for better viewing. These areas were the right front upper medial forearm, left front and right front distal lateral forearm, left hind and right hind upper medial thigh, left hind and right hind distal lateral gaskin and left hind caudal gaskin. The masses did not appear to enter vital structures such as the carpal joint or tarsal sheath but they were immediately adjacent to them. A rough diagram of each leg was made with reference to each lump. identified masses and that post-operative hormone therapy (i.e progesterone) and pregnancy may prevent further growth or the development of other masses. Considering the size, number and the location of the masses, surgery was to be undertaken by three surgeons. Consent was organised for surgery to be performed the following day. Transport was pre-booked with a livestock transport company to take her up to the Large Animal Surgery section of Scone Veterinary Hospital. A NO FEED sign was placed on the mares door at midnight and she was prohibited from eating anything. Water was left for her to drink. After an hour a halter and lead were placed on her and she was held for the anaesthetist to check her vitals: Heart Rate 42, Pulse Rate 42, Respiration Rate 14, Temperature 37.2, MM colour pink, Capillary Refill Time - < 2, Anaesthetic Risk 2, Surgery Risk 2.5. She then had her mouth washed out with water to remove any debris that may cause her to choke when anaesthetised. She was led down to a concrete area just outside the induction box where her feet were cleaned out and her legs (mid cannon to upper leg) were clipped using a size 40 blade prior to surgery. She was sedated for this with 5.2ml (1.0mg/ kg) of Xylazine IV and 0.5ml (0.01mg/kg) of Butorphonol IV. Once clipped she was led into the induction box and the outside doors were closed and the bars put on. The mare was given pre-operative antimicrobials 12g of Benzylpenecillin IV, 35ml (6.6mg/kg) of Gentamicin sulphate plus antiinflammatories 10ml (4.4mg/kg) of Phenylbutazone IV. She was also given a Tetanus Antitoxin. Due to the time it took to clip her legs she was topped up with another 1ml of Xylazine before induction. Induction involves pushing the mare into the wall and 4 people standing along the length of the mare to assist her to slide down the wall. Due to the mare being placed in dorsal recumbency on the surgery bed she was placed on the wall that would enable her to be right side up.

SURGERY PREPARATION

On the 26th of July 2006, the mare was transported from Clovelly to surgery where she was placed into a yard to settle for approx an hour. During this time everything was prepared for surgery. The anaesthetist set up the equipment consisting of the Large Animal circle anaesthetic machine using Halothane /Oxygen combination, the monitoring equipment ECG, Pulse Oximeter and Capnograph plus fluids 5L bags of Hartmans. The nurses set up the theatre area bed was positioned in dorsal recumbency, leg stands, gross scrub buckets and towels, 2 lights one on each side of the room, 2 x fluids on stands 1L bags of Hartmans were used, sterile scrub bowls - 1 with straight Hexawash, 1 with Alcohol, and 1 for final Chlorhexidine 70% alcohol prep. Two surgery tables needed to be set up due to the 3 surgeons working around the mare. These were set up in an aseptic manner and covered. The following equipment was placed on each table : Table cover (disposable) Minor Kit: - 1 x Mayo Hegar Needle Drivers - 1 x Metzenbaum Straight Scissors - 1 x Sharp Sharp Suture Scissors - 1 x Rat-tooth Forceps - 2 x No. 3 Scalpel Handles - 2 x Straight Mosquito Heamostats - 4 x Backhaus Towel Clamps - Quantity of swabs All wrapped in blue paper (double layer) and then placed in a medi-pack. Single Cysto set Disposable gowns for each vet 2 sets of gloves for each vet. Quantity of scalpel blades, size 10 and 15 Extra sterile swabs On one of the tables was placed 8 sterile material drapes and 6 sterile blue waterproof polydrapes. Each surgeon has their own preference for suture material. Therefore 2 PDS, 2.0 PDS, 2.0 Monocryl and 2.0 Prolene were used.

After investigation by the equine surgeon and consultation with the owners it was decided the best course of action was to surgically remove all the masses. The surgeon advised the owners this would be beneficial for the following reasons: the masses all appeared of sufficient size and location to allow removal, the mare was at a good stage of her breeding career to allow removal without the complication of pregnancy, it was hoped that surgery could offer total removal of the

Anaesthesia was induced using 13ml (2.6mg/ kg) of Ketamine and 6ml (0.06mg/kg) of Diazepam combination. No catheter was placed to induce. Once the mare was on the floor she was connected to the anaesthetic machine via a size 26 endotracheal tube and the Halothane (flow rate 5) and Oxygen (flow rate 5L/min) was turned on. The anaesthetist placed a 14g short term Terumo catheter into the right jugular vein after a 3 time prep of Hexawash and Alcohol. The nurses performed an initial gross prep using moist medi-sponges and moist wipes to remove surface dirt and hair from the patients legs, which were then patted dry with a towel. She was then connected to the hoist and moved to the surgery bed.

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Once on the bed she was placed into position and her legs were extended on stands. This was to enable the surgeons to work independently and gain access to the numerous surgical sites. The anaesthetist set up her monitoring equipment and fluids were also connected by a single cysto set. Two nurses worked on the mare to prepare her for surgery. Gloves were placed on her feet and a body drape was put over her. A 3 time Hexawash / Alcohol scrub was performed using sterile gauze swabs working from the sites outwards. Chorhexidine 70% alcohol was used as a final prep, the nurses, wearing sterile gloves wiped the area with soaked sterile swabs. Six people were involved in the surgery 3 surgeons, 1 anaesthetist and 2 nurses. All wore scrubs, hats and masks, the surgeons also wore disposable gowns and 2 sets of gloves, 1 set was removed after draping. While the nurses were preparing the mare, the surgeons were scrubbing, gowning and gloving for surgery. E a ch surgeon worked systematically around the mare each starting on a different leg. A mid-line incision was made over each mass, this varied in size depending on the mass. The masses varied in their characteristics, with some being obviously circumscribed and others adhered to surrounding soft tissue. Each mass was sharply excised, care was taken not to disturb the mass ensuring complete removal of neoplastic cells as far as possible and no vital structures were penetrated. Some were deep to fascial planes and required a two layer closure. Closure was with absorbable and non-absorbable (2.0 Prolene) suture material in a continuous suture pattern. The majority required skin closure only. Proximal masses were only partially closed allowing drainage of serous fluid post operatively. The surgical wounds were either fully or partially sutured depending on their location and the ability to bandage the surgical sites. removed and a nasotrach tube was placed, Oxygen was administered at 15L/min during recovery. She was also given 1ml of Xylazine to delay recovery from anaesthesia. She was not assisted due to her size and weight. The doors were closed and bolted. Lights were turned off and noise was kept to a minimum to reduce the stimulation. It took approximately 50 minutes for the mare to stand, in which time she was watched to ensure there were no complications. During recovery she knocked the nasotrach tube out, so the anaesthetist turned the Oxygen off as it was no longer needed. Once up she stood quietly and was left for a further 15 minutes until she was steady enough to move to a yard. Her catheter and bandages were checked to ensure they were in order. There was no sign of myositis when she was moved to a yard. She was placed in a rubber yard to minimise contamination to her bandages, the water was removed. After a further 10 minutes of observation her water was returned and she was booked out with transport to return to the Clovelly Intensive Care Unit. While waiting for transport she was checked periodically for any signs of distress. Approximately 2 hours after surgery she was transported down to Clovelly and placed in her straw box, where she had access to lucerne hay and water.

SURGERY

The anaesthetist maintained the patient on Halothane/ Oxygen combination with top-ups of 1ml of Xylazine at intervals prior to incisions on each leg. The mare was monitored during surgery with the following equipment: Electrocardiogram (ECG) Pulse Oximeter Capnograph Direct Blood Pressure using a pressure transducer an intra-arterial catheter was placed in the transverse facial artery to record BP.

POST-OPERATIVE CARE
Once each leg was finished with they were lowered from their extension to prevent the build up of lactic acid. Surgery time was shortened due to the 3 surgeons working on her and they were able to complete the removal of all 16 masses in 2 hours. This shortened the mares anaesthetic time and prevented any complications that may have arisen if she had remained on the operating table for numerous hours. Once surgery was completed and all drapes removed, the mare had all four legs bandage with sterile combine wraps, Co-flex and Elastoplast. Both hind legs and right fore were bandaged from the upper leg down to the foot, the left fore had a knee bandage. She was then placed on the hoist and lowered into recovery in right lateral recumbency, catheter up and bottom front limb extended out. The endotracheal tube was deflated and

Fluid therapy was maintained throughout surgery using Hartmans IV at the rate of 10ml/kg/hr, it was delivered via a single cysto set from 5L bags. T h e mare was draped in ro u t i n e fa s h i o n en sur i n g al l su rfaces we re cove re d .

On arrival at Clovelly the mare was bright and alert. She was very stiff on her hind limbs and slightly sore in front. She settled in well and began eating. She was initially checked every hour and TPR performed an hour after arrival revealed normal parameters. Nabudone P (Phenylbutazone) was administered to aid in pain relief . The mare was expected to stay at Clovelly for 8 days post surgery. Initially her ICU checks were performed every 6 hours, all her vitals were recorded and these were all within normal limits. TPR was reduced to every 12 hours 2 days post surgery. She was observed on a regular basis and checked when her medication was administered. Post-op medication included antimicrobials 12g of Benzylpenicillin IV every 6 hours (QID) for 4 days, 33ml of Gentamicin sulphate IV every 24 hours (SID) for 5 days, plus antiinflammatories 10ml of Phenylbutazone IV every 24 hours (SID) for 5 days, Butorphanol 0.4ml was given for pain relief SID for 4 days. Post-op day 4, 12mls of Regumate was introduced and Benzylpenicillin was replaced by Depocillin 25ml every 12 hours (BID) IV. On day 5 Depocillin was stopped and Oral Bute was then administered - 10mls per Os every 24 hours (SID) until discharge. Post operative care included: - regular monitoring, - observing fluid intake (buckets of water measurements),

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Continuing Professional Development Questions and Answers can be found on page 26

nutrition requirements lucerne hay, bran mash (day 1), chaff mix and grass pick, wound care monitored discharge and swelling, daily bandage changes, clean discharging wounds with sterile saline swabs, re-apply new bandage, changes decreased to every second day on day 3, exercised hand walked and allowed to pick at fresh grass, patient comfort cleaned bedding twice daily, added fresh straw every morning, needed rugs at night for warmth as mare was fully clipped, rugs were placed on without hind legs straps done up as surgical sites may have been injured, top doors on box were left open and mare was hand walked to relieve boredom; catheter care checked for patency every time intra-venous meds were administered, removed on day 5.

of the masses. As the mare is intended for breeding purposes, this will be able to be discontinued whilst she is being served, however it is recommended that it is reinstituted after the mare has ovulated and been served. The owners were warned that multiple surgical procedures may be required if the masses reappear in numbers and size. The owners are to ensure that their own veterinarian removes the sutures and contact their own veterinarian if they are worried about the mare at any time in regards to this condition.

CONCLUSION

DISCHARGE

After 8 days the mare was discharged from the Scone Veterinary Hospitals Clovelly Intensive Care Unit. Her surgical sites had healed well and those which were open and draining were improving. The discharge instructions outlining aftercare and medications were faxed through to the owners and the medicine specialist spoke to the owners to reiterate instructions given. The mare was to be kept in a small grass covered yard during the day and boxed overnight for 10 days. Her sutures were to be removed in a further 8 days 15 days post surgery. Her right foreleg was to be kept bandaged and changed every third day until suture removal. She was placed on 12mls of Regumate (Altronogest) per Os SID (once a day). The prognosis for the mare is guarded. The veterinarians report reads:It is unknown whether the cutaneous lymphoma will reoccur. There is limited information available in the literature on the long term outcome on horses affected with this condition. There are reports that horses with cutaneuos lymphoma show spontaneous resolution or the masses increase or decrease in size associated with different hormonal status of the horse. The mare was placed on Regumate (oral progesterone supplement) in an attempt to decrease the recurrence

Cutaneous Lymphoma is rarely reported on in Equine patients. Some of the treatments available have not been widely researched for use in horses radiation therapy and chemotherapy. Due to the intention of using the mare for breeding purposes, the preferred treatment of Glucocorticoids (Dexamethasone) would prove to be a problem. The prolonged therapy required may have interfered with her reproductive cycles, leading to difficulty in getting her in-foal and preclude her use as a brood mare for this season. A combination of surgery and progesterone therapy was the mares best option. Due to reported regression of masses being attributed to a rise in plasma progesterone levels, pregnancy may help to suppress any remaining neoplastic cells or undetected masses. The life expectancy for horses with primary cutaneous lymphoma is unknown with many patients showing signs of reoccurrence.

BIBLIOGRAPHY
Brown C.M and Bertone J.J. The 5-Minute Veterinary Consult. 2002, Lippincott, Williams and Wilkins. Coumbe K.M. Equine Veterinary Nursing Manual. 2001, Blackwell Publishing. Robinson N.E. Current Therapy in Equine Medicine 5, Chapter 4.12. 2003, Saunders.

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