Topics include:

• Initial assessment and management of the patient
• Imaging of spinal cases
• CSF analysis
• Rehabilitation after spinal injury.

Speakers

• Damien Bush MA VetMB CertSAS MRCVS
• Elisa Best BVSc Cert SAS MRCVS
• Emily Hellewell BSc BVSc MACVSc(SAM) MRCVS
• Samantha Bell BSc RVN MBVNA

Arrangements

• Venue: The Bristol Golf Club [web site] [map]
• Date: Thursday, 3rd November 2011
• Time: 7.30pm hot and cold buffet served. 8pm lectures start.

How to book

Please print and return a booking form or register below:

fig.1 - Fine needle aspiration of a solitary cutaneous lesion on the flank of a Rhodesian Ridgeback.

17-21% of all skin tumours are diagnosed as MCT.  There is no single, pathognomonic presentation for MCT.  Therefore, they should be considered as a possible differential diagnosis with any cutaneous nodule.

Breed predispositions have been reported, with more than 50% of MCT presenting in Boxers and Boston Terriers. No gender predilection is reported. The mean age at presentation is 7.5-9 years.  MCT mostly affect the trunk, followed by the extremities and the head and neck.  They are more commonly found towards the caudal part of the trunk than cranially.  They commonly present as solitary cutaneous lesions though 5-25% of dogs are affected by multiple lesions.

No single factor has been identified as a consistent prognostic indicator in dogs with mast cell disease.  However, MCT located in the nail bed, oral cavity, muzzle, inguinal region, preputial region, perineal region or at the mucocutaneous junction are associated with a worse prognosis than masses at other sites.  Ulceration, erythema or pruritus associated with the lesion is also considered a poor prognostic indicator.

Systemic clinical signs associated with the visceral form of the disease such as anorexia, vomiting, haematochezia, melaena, anaemia, abdominal pain, GI perforation and peritonitis indicate a poor prognosis.  35-83% of dogs with mast cell tumours demonstrated associated visceral lesions at necropsy.  These lesions are caused by vascular damage and H2 receptor stimulation resulting in increased gastric acid production.

MCT in Boxers tend to present at a younger age, with a lower histological grade than other breeds and are associated with a better prognosis.  Rapidly growing masses tend to be associated with a poorer prognosis as do masses that are large in size on presentation.

Metastatic disease

fig.2 - A well-differentiated MCT identified on cytology (grading was performed on a subsequent, histological sample).

Well-differentiated MCT have a metastatic rate of less than 10%. Intermediate grade tumours are of low to moderate metastatic potential.  55-96% of undifferentiated tumours metastasise.  The variability in this figure may be due to the subjective nature of MCT grading criteria.  Disseminated mastocytosis is usually preceded by an undifferentiated, primary cutaneous mast cell tumour.  Mast cell tumours initially metastasise to local lymph nodes, then the spleen, liver or other viscera.  Lung involvement is rare in mast cell disease.

Paraneoplastic syndromes and complications of granule release

• Delayed wound healing – due to proteolytic enzyme and vasoactive amine release.
• Bleeding – likely to be due to coagulation defects caused by heparin release.  Rarely uncontrollable.
• GI ulceration
• Collapse – due to massive histamine release from neoplastic cells.  This is a potential complication of manipulation and/ or surgery.

Diagnostic work-up

The aims of this process are to establish a definitive diagnosis, to provide clinical staging of the disease and to document paraneoplastic clinical signs.

Tumour cytology

• This should always be performed prior to surgery.

FNA (see fig 1) yields a diagnosis in 92-96%

Figure 2 shows a discrete, round cell population with a moderate amount of cytoplasm containing purplish-red cytoplasmic granules of variable number and size.  The cells have ovoid nuclei which may be masked by granules.

Further diagnostic work-up

Minimum pre-operative work-up for staging is FNA of draining lymph nodes even if they are normal in size, and abdominal ultrasound to include the sublumbar lymph nodes.  Suspicious visceral lesions should be aspirated. Thoracic radiographs are seldom indicated, unless looking for concurrent disease in older animals, as metastasis to this site is rare.  The value of screening of the buffy coat is disputed as mastocytaemia is more common in inflammatory conditions than in MCT.  Bone marrow biopsy is no longer recommended for routine staging if mast cell disease is not evident in regional lymph nodes or abdominal organs. Visceral MCT carries a grave prognosis and the presence of neoplastic mast cells in bone marrow rarely alters treatment decisions.

Staging

WHO staging system

• Stages 0 and I have a better prognosis than higher stage disease.
• No significant difference has been reported in single v multiple masses of the same histological grade.  As a result, it has been suggested that each mass should be staged individually to avoid unnecessarily aggressive treatment based on the limitations of the WHO staging system.
• Up to 44% of dogs cured of previous MCT will develop de novo MCTs which require individual staging and grading.

Histology

fig.3 - A grade I, well-differentiated MCT. These masses are well circumscribed but not encapsulated. Cells are round with a central, small nucleus. Abundant, highly granulated cytoplasm is seen. MCT of this grade are usually confined to the dermis but may also invade the subcutaneous tissue.

fig.4 - A grade III MCT. These masses are poorly circumscribed and poorly differentiated. The cells are highly pleomorphic and can be confused with the appearance of other round cell tumours. The cells have large, irregularly shaped nuclei and contain numerous mitotic figures.

Grading is based on histology, not cytology.  Margin assessment should also be performed on excisional biopsy.

Patnaik et al (1984) described the histopathological classification most frequently used to differentiate between well-differentiated, intermediate grade and undifferentiated MCT.  Grade does not correlate well with behaviour in intermediate grade masses as they may behave in a benign manner, recur or metastasize.  More than 40% of all canine MCT are described as intermediate grade.  The subjective parameters used for grading result in variation between pathologists using identical grading systems.

Intermediate (Grade II) MCT

These masses are less well circumscribed and contain closely packed cells with distinct cell borders.  They have an increased nuclear:cytoplasmic ratio and fewer granules. Small numbers of mitotic figures are seen.

Grading based on markers

Mitotic Index – marker of morphology

• Studies have demonstrated a prognostic value of MI in canine MCT.
• Median survival for MI<5=70 months v MI>5=2 months regardless of histological grade.
• Difficult to assess in highly granulated MCT.
• Objective measure with strong prediction of prognosis with regard to survival time.
• Impact of MI on rate of recurrence is controversial.

AgNOR – marker of proliferation. 

• Indicated regions in the nucleus associated with proteins that bind silver molecules that can be visualised by light microscopy using a silver-based immunohistochemical stain.

• Quantity of AgNORs per nucleus is proportional to the rate of cell doubling time in vitro and rate of tumour growth in vivo.
• Higher AgNOR counts in MCT are associated with increased mortality, local recurrence and metastasis.

Ki67 – marker of proliferation.

• Nuclear protein expressed in all active phases of the cell cycle but not present in quiescent cells.
• The number of Ki67 positive cells is used to determine the relative number of cells actively involved in the cell cycle; the growth fraction.
• High Ki67 is associated with increased mortality, increased rate of local recurrence and metastasis.
• Ki67 is considered better than AgNOR for identifying MCT associated with decreased survival.
• AgNOR is considered superior for identifying MCT with a decreased disease free interval.

Treatment

Visceral metastatic disease

Local control should be accompanied by systemic treatment

• Cytotoxic chemotherapy

Þ Prednisolone/Vinblastine

Þ Prednisolone/Vinblastine/Cyclophosphamide

Þ Prednisolone/Vinblastine/Lomustine

Þ Comparative efficacy studies are still

pending.

• Ancillary treatment to decrease systemic side- effects of MCT granule release

Þ H1 and H2 blockers

Þ Proton pump inhibitors

Þ Sucralfate in cases of GI ulceration

• Radiation therapy

Recommended for post-op residuals and microscopic/subclinical disease if further resection is not possible. It has also been employed pre-operatively to reduce tumour size.

• Masitinib (Mastivet)
  • Novel, targeted therapy for use in mast cell tumours and other inflammatory diseases.
  • Targets and inhibits a limited number of key kinases including c-Kit.
  • c-Kit, a mast/stem cell growth factor receptor, demonstrates mutations in 20-30% of canine mast cell tumours. This mutation correlates with a higher histological grade.
  • When used as first-line therapy in dogs (grade II or III cutaneous MCT) with both mutant and wild-type forms of c-Kit, masitinib significantly increased time to progression (TTP) of mast cell tumours when compared to a placebo.
  • Masitinib is a p-glycoprotein substrate and the effectiveness of the drug can be compromised by activation of the MDR-1 gene. Dogs that developed resistance to other chemotherapeutic agents did benefit from masitinib treatment. TTP was only increased by masitinib when the MCT expressed c-Kit mutation.
  • Utilisation of masitinib as part of a multidrug chemotherapy protocol is not yet recommended due to an absence of evidence and the similar toxicity profiles of masitinib and other chemotherapeutic agents.
  • Care should be taken in incorporating masitinib into protocols containing cimetidine and vinblastine as competition between these drugs on cytochrome P450 enzymes could reduce metabolic clearance of these drugs resulting in toxicity.
  • Side effects include vomiting and diarrhoea of mild-moderate intensity and transitory nature. Improved tolerance of the drug is possible over long-term treatment regimens. Protein loss has also been reported resulting in hypoalbuminaemia from which dogs recover and do not relapse after discontinuation of masitinib therapy.
  • Contraindications:
    • Þ Renal dysfunction
    • Þ Hepatic dysfunction
    • Þ Anaemia
    • Þ Neutropaenia
    • Þ Administration to pregnant or lactating bitches
    • Þ Dogs less than 6-months of age or less than 3.4kg body weight.

Further reading

1. Thamm DH, Vail DM (2007) Mast Cell Tumors in Withrow & MacEwan’s Small Animal Clinical Oncology p402-424 Saunders Elsevier, Missouri.

2. Welle MM, Bley CR, Howard J, Rufenacht S (2008) Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment. Vet Dermatol 19(6): 321-39.

3. Hahn KA, Ogilvie G, Rusk T, Devauchelle P, Leblanc A, Legendre A, Powers B, Leventhal PS, Kinet JP, Palmerini F, Dubreuil P, Moussy A, Hermine O (2008). Masitinib is safe and effective for the treatment of canine mast cell tumours. J Vet Intern Med. 22(6):1301-9.

fig.2 - lateral skull radiograph. There is a metallic-density foreign body located within the ethmoturbinates.

fig. 1 - preoperative photo showing discrete soft-tissue-swelling over the nasal planum

A 15-year-old male, neutered DSH cat presented with a two-week history of right, unilateral epistaxis with concurrent swelling of the nasal planum (see fig. 1).

The cat had been in the owner’s possession for twelve years, with no known history of trauma during that time.  The referring veterinary surgeon’s radiographs revealed a metallic-density foreign body, located within the right side of the nasal cavity, resembling an air-gun pellet (see figs. 2&3) .  Clinical examination failed to identify an entry wound, but there was a faint, mature scarring of the skin over the fluctuant, non-painful swelling on the nasal planum..

.

.

Treatment

fig.3 - dorsoventral radiograph of the skull showing a metallic object resembling an air-gun pellet, lodged within the nasal cavity.

fig.4 — intraoperative photograph showing pellet after removal via dorsal rhinotomy.

Surgical exploration of the swelling revealed a small, granulation tract, less than 1mm in diameter, running through the right frontal bone, leading to an area of turbinate necrosis within the nasal cavity rostral to the ostium of the right frontal sinus; this tissue was found to contain the embedded object.  The tract was enlarged to facilitate debridement of all non-viable tissue and removal of the air-gun pellet (see fig.4).  The nasal cavity was lavaged before primary wound closure; the frontal bone deficit was left unfilled.  Overlying soft tissues were closed primarily.

Bacteriology yielded a light growth of Klebsiella ozaenae, sensitive to all antimicrobials tested.  The patient made an unremarkable recovery and there has been no recurrence of facial swelling or epistaxis in the two months since surgery..

.

Discussion

This case shows that nasal foreign bodies may be asymptomatic for many years before clinical signs become apparent.  Dorsal rhinotomy is tolerated relatively well in the feline patient.

Examination revealed ataxia of all four limbs.  Claws on all limbs appeared scuffed.  There was reduced conscious proprioception of the thoracic limbs and brisk spinal reflexes in all limbs.  Mentation and cranial nerve testing were considered normal, consistent with a spinal cord lesion in the C1-5 segments. 

ALT levels were found to be elevated 429 (0-110)U/l, but resting/ post-prandial bile acids and albumin were found to be within the normal range.  Ultrasound examination of the abdomen, including the liver and associated vessels revealed no structural abnormalities or shunting vessels.  Ultrasound-guided, fine needle aspirates of the liver were normal, with no evidence of microvascular dysplasia.  A haematocrit of 31(37-55)% and cytology of fresh smears were consistent with mild, non-regenerative anaemia.  Coagulation testing was within normal limits.

fig.1 - preoperative, transverse T1W slice at level of subarachnoid cyst, showing right, lateralised fluid-filled space (dark grey) extending ventrally into cord parenchyma

MR-scans of the cervical spine revealed a widening of the cerebrospinal fluids space bordering the right dorsolateral limit of the spinal cord at the level of the Ce2 vertebral body, extending ventrally to compress the cord parenchyma (see fig. 1).  In addition, there was evidence of central canal dilatation/ syringomyelia further caudally consistent with chronic obstruction to the normal flow of CSF.

Treatment

S-Adenosylmethionine (Hepatosyl) was started q24h P.O. to manage non-specific hepatitis.  Repeat biochemistry one week later revealed improvement in ALT levels.  Six weeks later, marsupialisation was performed to drain the cyst;

A right, lateral pediculectomy at C2 was used to access the dura over the cyst.  Durotomy was performed to raise a flap of tissue, which was sutured to the surrounding tissues in an attempt to create a permanent drainage route.  The wound was closed routinely, and the patient made an unremarkable recovery from anaesthesia.  The patient was ambulatory a few hours after surgery and he remained bright and comfortable.

Follow up

Ataxia appeared slightly worse over the following few days.  However, five weeks after surgery, re-examination revealed no further scuffing of the claws and normal thoracic limb proprioception.  There were persistent, mild deficits in the right pelvic limb. 

fig. 2 - five-week post-operative, transverse, T1W slice at level of pediculectomy, showing reduction in size of cyst and increased cross-sectional area of the remaining cord parenchyma as compared to fig. 1

Repeat MR-scans (see fig.2), at the level of the pediculectomy revealed an increase in the cross-sectional area of the cord parenchyma, suggesting surgery was successful in decompressing the cord.

Discussion

The most frequent location for sub-arachnoid cysts is within the limits of the C2 vertebra.   Familial patterns suggest a genetic component so owners should be advised not to breed from affected animals. 

If cysts result in signs early in life, they will often progress over time to compromise the patient significantly as they age.  Corticosteroids at anti-inflammatory doses may be used to slow down the rate of progression but the condition may be managed surgically with the aim of establishing permanent drainage.  However, scarring may limit the long-term effectiveness of surgery and recurrence of signs is possible.

The liver disease present in this case was not thought to be related to the patient’s neurological condition, but nevertheless the patient’s liver biochemistry remains under review.

fig.1 — mediolateral radiograph of left shoulder, showing mineralised mass at the caudal rim of the glenoid

The referring veterinary surgeon had detected pain on manipulation of the left shoulder.  Radiology had revealed a mineralised mass at the caudal limit of the glenoid (see fig 1) consistent with un-united caudal glenoid. 

There had been a good response to rest and meloxicam therapy.

Orthopaedic examination revealed no evidence of muscle atrophy or lameness on gait analysis, but there was consistent and repeatable resentment of extension of the left shoulder. 

Treatment

Exploratory arthrotomy was performed via a standard caudolateral approach to the left shoulder. 

Probing of the caudal glenoid revealed a loose, bony fragment which was removed.  The humeral head was inspected for signs of abnormalities but was found to be normal.  The joint was flushed and closed routinely. 

The patient was confined to short lead walks for six weeks postoperatively before progressive increase in exercise was allowed.  Three months after surgery, there has been no recurrence of the lameness and the shoulder remains pain-free on manipulation.

Discussion

Un-united caudal glenoid is a rare manifestation of osteochondrosis, seen mostly in large breed dogs as a chronic, low-grade lameness.  It results from a failure of fusion of the main body of the glenoid and the separate centre of ossification of the caudal rim.  Mineralisation of this junction should normally be complete by nine months of age.  Such radiographic findings may be incidental, so it is important to exclude other, more common causes of lameness with a thorough orthopaedic assessment which may require further imaging of other joints in the limb where appropriate.  However, any patient with a lameness referable to the shoulder joint with this characteristic radiographic appearance is a candidate for surgical assessment – either  arthroscopically or via arthrotomy. Loose fragments should be debrided as they would otherwise continue to act as a free body within the joint, causing synovitis and pain.  Long term sequelae are minimal, but a degree of osteoarthritis is inevitable.

On presentation, the dog was bright and comfortable with no visible lameness.  General physical examination revealed a large, firm, fixed, non-painful mass over the right hemipelvis extending as far caudally as the ischial tuberosity and 3cm cranial to the greater trochanter. Rectal examination was unremarkable. There was no pain or discomfort associated with manipulation of the limb.

fig.1 - T1W dorsal slice of proximal femur: a large, lobular, high signal intensity mass is visible lateral to the greater trochanter, extending into the intertrochanteric fossa.

MR-scans of the area (fig.1) revealed a large, lobulated mass, with a high T1W signal intensity, infiltrating into the surrounding muscle tissue, bisecting the biceps femoris muscle throughout most of its length distally, consistent with fatty tissue.  The mass did not appear contiguous with the sciatic nerve.  However, given its infiltrative nature, a provisional diagnosis of malignant liposarcoma was offered. 

In the first instance, local excision was planned, with radical resection (amputation/ hemipelvectomy) a reserve option if adequate margins were not achieved.  The lateral aspect of the right hemipelvis was exposed and the mass dissected away from its attachments (fig. 2). The surgical findings closely mirrored those of the MRI as the mass appeared to have originated from the ischial tuberosity.   Tissue was submitted for surgical margins.  An active drain was placed and the wound was closed routinely.

The dog was hospitalised until drain removal three days later, after which it was discharged on a regime of restricted exercise to minimise the risk of seroma formation.

Histopathology identified the mass as an infiltrative lipoma, an uncommon neoplasm that histologically resembles a lipoma but behaves more like a sarcoma.

Although distant metastasis was considered unlikely, local recurrence was a strong possibility.  Due to the nature of the tissue, it was hard to determine surgical margins histologically.  The risk of damage to intrapelvic structures with follow-up radiotherapy was considered to be low, but the owners declined further treatment.  Follow-up was conducted by telephone four months post surgery, which suggested no evidence of recurrence to date.

Discussion

fig.2 - intraoperative photograph showing dissection of the mass away from the biceps femoris, vastus and gluteal muscle groups.

Tumours of adipose tissue can be divided into benign (lipomas) and malignant neoplasms (liposarcomas). Although they may resemble one another macroscopically, they are histopathologically distinct.¹ Lipomas normally occur subcutaneously but can also occur in the abdominal or thoracic cavity as well as other areas of the body.²  As with other soft tissue sarcomas, liposarcomas tend to be locally invasive and metastasis is rare.  Infiltrative lipomas are uncommon tumours that histologically resemble lipomas but behave like liposarcomas in that they are locally invasive and aggressive.²  There appears to be some controversy regarding nomenclature of these tumours and it has been suggested that these masses should be called well differentiated liposarcomas based on their biological behaviour.³

CT-imaging of infiltrative lipomas has been described in the literature but differentiation from normal fatty tissue can be problematic.⁷ Precise anatomical location is therefore not easily described.  Reports detailing MR-imaging of these masses are scant in the literature but from our experience, this form of imaging is very helpful in precisely identifying the tumour’s location, extent and proximity to vital structures such as, in this case, the sciatic nerve.

Surgical removal is the treatment of choice for these tumours with local recurrence being a common problem.⁴  A reported recurrence rate of 36% and a median time to recurrence of 239 days is cited in one paper.⁵  Radiotherapy does appear to have some benefits either alone, for non-resectable masses or in combination with surgery.⁶  A reported median survival time of 40 months is given for the combined approach; hence why it was considered in this case.

Although there has been no reports of re-growth so far, this case remains under regular review.

 References

1. Baez JL, Hendrick MJ, Shofer FS, Goldcamp C and Sorenmo KU (2004) Liposarcomas in dogs: 56 cases(1989-2000). JAVMA 224 887-891

2. Liptak JM and Forrest LJ (2007) Soft tissue sarcomas. In Withrow SJ and Vail DM Small animal clinical oncology, Missouri, WB Saunders.

3. Saik JE, Diters RW and Wortman JA. (1987) Metastasis of a well-differentiated liposarcomas in a dog and a note on nomenclature of fatty tumours. J Comp Pathol. 97 369-73

4) McChesney AE, Stephens LC, Lebel J, Snyder S and Ferguson HR (1980) Infiltrative lipoma in dogs. Vet Pathol. 17 316-22

5) Bergman PJ, Withrow SJ, Straw RC and Powers BE (1994) Infiltrative lipoma in dogs: 16 cases (1981-1992) JAVMA 205 322-4

6) McEntee MC, Page RL, Maudlin GN and Thrall DE (2000) Results of irradiation of infiltrative lipoma in 13 dogs. Vet Radiol Ultrasound 41 554-6

7) McEntee MC and Thrall DE (2001) Computed tomographic imaging of infiltrative lipoma in 22 dogs. Vet Radiol Ultrasound 42 221-5

Examination 

On presentation, the dog was bright and comfortable. He was ambulatory with a 5/10 lameness of the left thoracic limb.  General physical examination revealed an enlarged, left, prescapular lymph node.  Cervical spinal pain was evident on both left and right lateral flexion of the neck. Neurological examination was normal.  Orthopaedic examination revealed discomfort on palpation of both digits 3 and 4 of the left manus, but no gross lesions were detected.

Further Investigations

Routine blood-testing showed mild increases in haematocrit, ALT and TBIL, but was otherwise unremarkable.

fig.1 - dorsal STIR slice of manus at level of proximal margin of digital pads; there is increased signal strength within the soft tissues between digits 3 & 4.

On the basis of the above, it was thought possible that the pedal discomfort might be due to nerve root signature secondary to a C6-T2 lesion; MR-scans of the cervico-thoracic spine, left brachial plexus and brain were performed, which were all found to be unremarkable.   Given the clinical finding of resentment to palpation of the digits, the left manus was subsequently scanned.  An area of increased signal intensity on T2W and STIR sequences (fig. 1) was found , extending from the pads of digits 3and 4, along the interdigital soft tissues and tracking proximally along the abaxial side of the third digit. The foot was clipped to facilitate closer examination of the skin but again, no sign of inflammation, penetrating wounds or other lesions was apparent. A cisternal CSF tap was performed and the prescapular lymph node was aspirated for cytology and bacteriology.  The dog was placed on broad spectrum antimicrobials (amoxiclav) pending results.

The dog made an uneventful recovery from anaesthesia and was hospitalised for repeat assessment the following day.  At this time, the 5/10 left thoracic limb lameness was still present, but the neck pain had resolved. The foot was still painful on examination especially in the distal interdigital area between digits 3 and 4. The dog was discharged with a continuing course of antimicrobials and NSAID analgesia, pending results of the CSF and lymph node aspirate.

Results

fig.2 - Haematoxylin & eosin x400 - shows keratinocytes (hexagonal cells on right) expanded by a grey/blue fibrillary cytoplasm . There is peripheralisation of the nuclear chromatin caused by intranuclear inclusion material (pale pink) evidencing a viral cause.

CSF analysis was found to be unremarkable.  Lymph node cytology was consistent with reactive change possibly due to inflammation in the distal limb.

The dog was re-examined approximately one week later: the referring vet had noticed a small circular lesion which had appeared on the palmar aspect of the distal interdigital skin between digits 3 and 4. Although this area was not part of the pad per se, it was contiguous with both pads of P3 and P4 and was of the same consistency.  The area had been probed to investigate the possibility of the presence of a sinus tract but there was no evidence of extension into the soft tissues of the foot. The lesion comprised a circular, hard area of hyperkeratosis which appeared macroscopically to resemble a corn.  The surrounding area was thickened and painful when palpated.

The interdigital lesion was excised en bloc and submitted for histopathology. Closure was routine and a light dressing was applied to enclose the manus.

Subsequent to surgery, the lameness initially improved but recurred a few days later. This was ascribed to minor wound dehiscence, which was managed conservatively and the dog has since made a full recovery, with no further recurrence of the lesion or lameness.

Histopathology revealed a papilloma with mild secondary furunculosis.  Excision appeared to be complete and a viral aetiology was confirmed by the multifocal presence  of large amphophilic intranuclear inclusion bodies (fig. 2).

Discussion

Viral papillomas are usually multiple and frequently affect the oral cavities of young dogs.  They have also been described in adult, immuno-suppressed individuals (e.g. those undergoing chemotherapy).^1,2  Lesions commonly appear 4-8 weeks after viral inoculation, initially, as small pale smooth elevated areas that subsequently develop into the classic cauliflower-like lesion.  These spontaneously regress after a further 4-8 weeks in most cases. Papillomatosis is normally considered a benign disease although there have been reports of transformation to malignant squamous cell carcinoma.  In addition, there is some evidence to demonstrate the presence of the virus in de novo squamous cell carcinomas, although in this situation, there remains the possibility that a primary lesion may have been missed clinically.³

Cutaneous papillomatosis is less common and although also viral in origin, it affects a broader age range and regression is often prolonged.  Lesions may occur anywhere on the body, but the digits do not appear to be a predilection site; they have however been described as causing lameness in an adult Siberian husky, successfully treated by digital amputation⁴.

A rare form of cutaneous papillomatosis has also been described in greyhounds, in which the lesion occurs in the interdigital area of the pads as in this case.⁵  In contrast, keratomas arising within the digital pads of greyhounds are termed ‘corns’.   They are most commonly found within pads 3 and 4 of the manus.   A proposed aetiology is the excessive forces generated within the tissues during racing, but there is also some evidence to suggest that foreign body penetration may cause these lesions to form.  Electron microscopy of corns has however, failed to find any evidence of a viral aetiology.⁶

Treatment of viral papillomas is often unnecessary due to spontaneous regression; but in cases where clinical signs have persisted, sharp excision, cryo- or laser surgery have all proved successful.  Interferon has also been tried with some success, as have live vaccines although these have the potential to cause squamous cell carcinomas at their injection sites.  Azithromycin is an azalide subclass macrolide antibiotic used for the treatment of papillomatosis in humans.  It has been trialed in dogs with reported success.  The mechanism of action in treating this disease is however, still unclear.²

Although surgical excision in this case was successful, had the papilloma recurred,  the use of azithromycin might be considered as an alternative to repeat surgery.

At the time of writing, there has been no evidence of recurrence.  Should lesions re-form, further investigation of possible underlying immunosuppression would be warranted.

References

1  Macy DW (2007): Tumor- causing viruses of dogs in Small Animal Clinical Oncology Withrow SJ and Vail DM, editors: , Missouri, , WB Saunders.

2 Yagci BB, Ural K, Ocal N and Haydar Edeoglu AE (2008): Azithromycin therapy of papillomatosis in dogs: a prospective, randomized, double-blinded, placebo-controlled clinical trial. Veterinary Dermatology  19(4) 194-8

3  Zuagg N, Nespeca G, Hauser B, Ackermann M and Favrot C (2005): Detection of novel papillomaviruses in canine mucosal, cutaneous and in situ squamous cell carcinomas. Vet Dermatology 16(5): 290-8

4  Plattner BL and Hostetter JM (2009): Cutaneous viral papilloma with local extension and subungual cyst formation in a dog. J Vet Diagn  Invest  21(4) 551-4

5  Davis PE, Huxtable CRR, Sabcine M (1976): Dermal papillomas in the racing greyhound. Australasian Journal of Dermatology 17 13-16.

6 Guillard MJ, Segboer I and Shearer DH (2010): Corns in dogs; Signalment, possible aetiology and response to surgical treatment. JSAP 51(3):162-168

fig.1 - parasagittal T1W slice of lumbosacral spine showing an incidental finding of an extradural cyst immediately cranial to the lumbosacral disc. Note: the L7-S1 disc is degenerate and S1 appears transitional.

Age of onset is usually middle-age, but juveniles and geriatrics are occasionally affected.  There appears to be no sex predilection.

Signs are often insidious in onset, initially presenting as a reluctance to jump or with progressive exercise intolerance.  Owners may describe nerve-root signs such as intermittent, poorly localisable lameness or licking and chewing of the pelvic region or the distal limb.  Signs are usually exacerbated by vigorous exercise.  The vast majority of cases presenting here have bilateral pelvic limb involvement which can sometimes make gait abnormalities harder to detect.  Advanced cases may develop a combination of the following; atrophy of the hamstring muscle group, mono- or para-paresis, loss of voluntary movement of the tail and urinary/ faecal incontinence.

Diagnosis

fig.2 - transverse T2W slice at level of a normal lumbosacral disc for comparison. Note the presence of fat signal throughout both intervertebral foramen.

It is important that patients undergo a full clinical (including rectal), orthopaedic and neurological examination to determine their health status and rule out other differentials such as prostatic, urethral or anal sac disease.  CSF analysis may also be used to eliminate primary inflammatory CNS disease. 

Mildly affected cases may not display overt lameness, but will sometimes adopt a characteristic ‘tucked-up’ posture at rest.

Palpation of the hamstring muscle groups may reveal a degree of atrophy .  Hypersensitivity of the sciatic nerve may also be demonstrable on deep palpation of the nerve through the biceps femoris muscle.

The most reliable clinical finding is discomfort on palpation or manipulation of the lumbosacral joint.  Stoic or mildly affected cases may not respond initially, but repeat examinations will usually identify the locus of pain accurately.  A useful manipulation is to place the examiner’s chin over the L7-S1 joint so as to free up both hands to clasp the proximal pelvic limbs; by exerting a proximal force vector along the axis of the limbs the lumbosacral joint is extended without extension of the hips; occult hip pain might ……………………………….otherwise confuse localisation of the problem.

fig.3 - sagittal T2W slice showing dorsoventral stenosis of the neural canal.

Neurological testing is often unremarkable in the early stages of the disease.  Advanced cases may develop pelvic limb proprioceptive deficits, poor hock flexion on withdrawal and pseudohyperreflexia of the patella reflex due to loss of hamstring muscle tone.

Imaging

fig.4 - transverse T2W slice at level of the L6-7 disc - there is left lateral deformation to compress the L6 outflow tract.

fig.5 transverse T2W slice at level of lumbosacral disc - there is bilateral deformation to compress both L7 outflow tracts.

Survey radiology of the lumbosacral joint may reveal degenerative changes, including disc space narrowing, spondylosis across the disc space or around the facet joints, as well as end-plate sclerosis.  Transitional vertebrae may also be encountered, which often prove significant in this region of the spine.  Bone loss at the end-plates may be seen in advanced cases of discospondylitis.  However, many cases affected by lumbosacral disease will show minimal radiographic changes.  Conversely, the presence of marked radiographic changes is not a reliable marker of clinical disease.  Stressed, flexed and extended lateral views of the caudal lumbar spine may be useful to demonstrate ………………………………………………………………..instability or subluxation of the joint.

Myelography and ‘discography’ are not helpful (even where the dural sac extends caudal to the L7-S1 disc) as more often than not, compression of neural structures occurs within the exit (abaxial)-zone of the intervertebral foramen; such lesions would be missed with these imaging techniques – leading to a high incidence of false negatives.

fig.6 - parasagittal 3D T1W slice showing loss of fat signal around the L7 nerve root due to impingement - compare to L5 & 6 foramen.

CT may be used to outline changes to the L7-S1 intervertebral disc and identify narrowing of the neural canal and/ or the intervertebral foramen, but this imaging modality will not give sufficient information regarding subtle changes to the soft tissues to provide a complete assessment of the condition. 

It is well established that the gold standard for the definitive diagnosis of lumbosacral disease is MRI.  This modality has inherent advantages in eliminating other differentials, characterised by soft-tissue pathological processes such as tumours and extradural cysts which can mimic lumbosacral disease but are difficult to rule out by other means (see fig.1).

Several MRI sequences are routinely acquired when assessing patients for this condition:

• Standard T1 & T2W sagittal and transverse slices will allow accurate assessment of degenerative changes to the intervertebral discs, facet joints and will localise sites of compression along the nerve root outflow tracts so as to characterise the condition as central, uni– or bi-lateral (figs. 2-5). 
• 3D (thin) parasagittal slices are also helpful to further characterise foraminal entrapment, impingement or claudication of the nerve roots (fig. 6).
• Dorsal STIR slices are also used to identify pre-stenotic hyperplasia of affected nerve roots.  This is a reliable marker for clinical disease (fig. 7).

Management

fig.7 dorsal STIR slice showing enlarged, right L7 nerve root pre-stenosis. Left nerve root also appears enlarged as compared to L6 nerve roots.

With few exceptions, lumbosacral disease is a progressive condition.  Owners who elect for conservative therapy (modification of exercise regime, including targeted physiotherapy and analgesia) should be advised that long-term compression of neural structures eventually results in irreversible malacia; those animals presenting with end-stage disease (severe paraparesis and/ or incontinence) may not benefit significantly from surgery.  However, the majority of cases would be expected to show a significant clinical improvement in the short-to-medium term with non-surgical treatment.  Combinations of gabapentin, tramadol and anti-inflammatory doses of steroid may be used to reduce pain associated with acute flare-ups.  However, owners should be further advised that cases will often relapse once exercise levels are increased.

Given that many patients present relatively late in the course of the disease – once they can no longer cope with their previously active life-style – recommendations involving indefinite restriction of their pet’s exercise are understandably unpopular with owners; a discussion of the benefits of surgical therapy may therefore be appropriate as soon as the diagnosis has been confirmed. 

Surgery should also be considered where response to conservative management has been poor.

Surgical management of lumbosacral disease is controversial.  Reported procedures advocate removal of the dorsal annulus of the L7-S1 disc (possibly combined with fenestration of the nucleus pulposus, and debridement of the soft tissues around the facet joints) prior to stabilisation of the joint(s) with implants.  However, it is our experience that patients can expect to achieve a sustained clinical improvement without the need to stabilise the joint, provided sufficient decompression has been achieved; we routinely perform dorsal laminectomy of the L7-S1 joint, extended bilaterally to remove the caudal articular processes of L7 so as to ‘de-roof’ the foramen and permanently relieve the pressure along the nerve-root outflow tracts.  Long-term follow-up of such cases suggests the majority of patients can resume their active life-styles with minimal signs of recurrence. 

Of further note is the continued evolution of foraminal surgery due to on-going concerns regarding chronic instability of the L7-S1 joint.  A dorsolateral foraminotomy technique has been proposed in an attempt to address these concerns¹.

References/ Further Reading:

1.  Goedde T., Steffen F. (2007) Surgical Treatment of Lumbosacral Foranimal Stenosis Using a Lateral Approach in Twenty Dogs with Degenerative Lumbosacral Stenosis. Vet Surg 36(7) 705-13.

2. Sharp NJ & Wheeler SJ (2005) Lumbosacral Disease in Small Animal Spinal Disorders.  Diagnosis and Surgery p.181-209 Elsevier Mosby, London.

fig. 1 - lateral radiograph of lumbar spine. There is extensive, bridging spondylosis of ventral spine with evidence of loss of mineralisation within the L7-S1 bridging bone ventrally, but the corresponding vertebral body end-plates appear intact.

fig. 2 - ventrodorsal radiograph showing moderate degenerative changes to the hips

A three-year-old male, neutered, Basset Hound presented to the referring veterinary surgeon with a history of spinal pain and pelvic limb weakness.  Signs were first noted one week previously as sudden onset exercise intolerance with concurrent loss of appetite. There was an initial, partial response to meloxicam 2.5mg q24h P.O. and diazepam 2mg q8h P.O. However, over the course of the following week signs worsened again; by the morning of presentation, the left pelvic limb was non-weight bearing lame.

On clinical examination, the patient was able to stand and walk slowly, but subdued and reluctant to move. There was generalised inflammation of the skin which emitted a characteristic ‘yeasty’ odour.  Mild, generalised lymphadenopathy was noted. There was resentment to palpation and manipulation of the caudal lumbar spine lateralised to the left.  Neurological examination revealed slightly delayed conscious proprioceptive testing in the left pelvic limb with normal segmental spinal reflexes.  Routine biochemistry was unremarkable.  Haematology revealed a mild neutrophilia 12.27(2-12)x10⁹/l and monocytosis 2.56(0.3-2)x10⁹/l. 

Imaging

fig. 3 - sagittal T2W slice of caudal lumbar spine showing inflammatory pattern within bridging spondylosis ventral to the L7-S1 disc, which, although degenerate, does not appear inflamed itself.

Radiology was performed under general anaesthesia which revealed marked, ventral spondylosis extending from the sacrum as far cranially as T12. Orthogonal views revealed degenerative changes to both hips  (figs. 1 & 2).  MRI scans of the lumbar spine (figs. 3 & 4) revealed a focal area of increased signal intensity on T2W in the area of demineralising bone within the spondylosis ventral to L7-S1.

Corresponding T1W sequences yielded a low signal intensity with post-gadolinium contrast ring-enhancement, consistent with infection/inflammation.  In addition, there was a focal area of high signal on STIR sequences within the neural canal on the left side consistent with empyema (fig. 5).  With both the T2W and STIR sequences, the L7-S1 intervertebral disc itself did not appear grossly affected other than a slight increase in signal within the right, lateral annulus.  In addition to the changes to the spine noted above, there was a diffuse, patchy ‘irritation pattern’, indicative of cellulitis of the paraspinal soft tissues surrounding the lumbosacral region (fig. 6).

fig. 4 - T2W transverse slice through L7-S1 disc, showing inflammatory signal beneath disc.

Blood culture yielded a heavy, pure growth of Staphylococcus aureus, sensitive to a broad spectrum of antibiotics including both cefuroxime and marbofloxacin.  Urine cultures and serology for Brucella canis were both found to be negative.

Initial therapy with metronidazole 250mg q12h I.V. and cefuroxime 625mg q12h I.V. was instituted, pending bacteriology results. Analgesia was provided using a combination of lidocaine 20 ug/kg/min I.V. and ketamine 5ug/kg/min I.V. as a constant rate infusion.  In addition, meloxicam 2.5mg q24h P.O., methadone 6mg q8h I.M. and gabapentin 200mg q12h P.O. were used to control pain.

Although there was initial improvement in clinical signs, nerve root signature subsequently developed in the right pelvic limb, which failed to respond to the addition of marbofloxacin 50mg q24h I.V. to the above regime.

Further investigations and treatment, including surgical biopsy, foraminal decompression, debridement, lavage and omentalisation were discussed.  However, the owner elected not to pursue treatment and the dog was euthanased.

Discussion:

fig. 5 - STIR sagittal slice showing area of high signal within the neural canal, dorsal to the L7-S1 disc.

Spondylosis

may be defined as ankylosis of a vertebral joint and is used to describe degenerative changes of the spinal column.  It is a common, often incidental radiographic finding in the aging canine population.

Spondylitis may be defined as active infection of the vertebral bone (osteomyelitis), including any associated periarticular new bone e.g. bridging spondylosis. 

Discospondylitis describes the destructive inflammatory and proliferative process involving the intervertebral discs, their associated endplates and by extension, the vertebral bodies¹.

This case illustrates an unusual situation, where there is significant inflammation of the surrounding bone and soft tissues, yet the disc itself appears unaffected.  This phenomenon has been reported in the human literature, where paraspinal abscesses and/ or septic spondylitis have been described.  To our knowledge, there are no reports of MRI findings with septic spondylosis in the absence of associated discospondylitis in the veterinary literature.

References:

fig. 6 - STIR dorsal slice showing diffuse patchy increased signal consistent with cellulitis around the lumbar spine.

1.Carrera I et al (2010) MRI features of discospondylitis in dogs. Vet Radiol & Ultrasound in press

2.Cherubini GB et al (2004) MRI findings in a dog with discospondylitis caused by Bordetella species. JSAP 45:417-20

3.Forrester DM (2004) Infectious spondylitis. Semin Ultrasound CT MR. 25:461-73

4.Gonzalo-Orden JM et al (2000) MR, CT and radiologic findings in a dog with discospondylitis. Vet Radiol & Ultrasound 41:142-4

5.Holloway A et al (2009) MRI features of paraspinal infection in the dog and cat. Vet Radiol & Ultrasound 50:285-91

6.Stefani de A et al (2008) MRI features of spinal epidural empyema in five dogs. Vet Radiol & Ultrasound 49:135-40

7.Tali ET (2004) Spinal infections. Eur J Radiol 50:120-33

8.Thrush A; Enzmann D (1990) MR imaging of infectious spondylitis.  A J Neuroradiology 11:1171-80

9. Vorbeck F et al (1996) Infectious spondylitis in adults. Radiologe 36:795-804

fig. 1 – physical examination revealed inability to stand and a poor body condition.

On physical examination the cat was in poor body condition (BCS 1/5; fig. 1) and was weak and unable to stand. The mucous membranes were very pale and the capillary refill time could not be appreciated. The breathing was shallow and tachypnoeic (80bpm) and there was a 3/6 systolic heart murmur. The heart rate was mildly elevated at 240bpm with sinus rhythm. The pulse quality was strong and there was no pulse deficit. The rectal temperature was slightly low at 99.9^oF. The remainder of the routine clinical examination was unremarkable. The systolic blood pressure was 150mmHg and ophthalmoscopic examination was unremarkable.

The cat was assessed to be well hydrated so fluids were not administered immediately but an intravenous catheter was placed in case emergency IV access was required. Given the tachycardia oxygen supplementation was given and because of the mild hypothermia the cat was placed in an incubator. Blood was taken for baseline analysis (table 1, below) revealing severe anaemia.

Table 1: Baseline blood results

Blood smear: No evidence of aniscocytosis or polychromasia, some nucleated red blood cells present, few platelets seen.

Following an improvement in the cat’s clinical status, further blood was submitted for full haematology (table 2, below).

Table 2: Initial haematology results

Lipaemic sample gave falsely high Hb. Hb, MCH and MCHC therefore not reported. Spun PCV performed.

Film comment: Thrombocytopenia. Normocytic and normochromic anaemia. High MCV due to red cell agglutination. The nucleated red cells are intermediate and late normoblasts.

fig. 2 - blood smear cytology showing nucleated red blood cells.

This confirmed a severe, non-regenerative anaemia with a significant number of circulating nucleated red blood cells (fig. 2).

There was also marked thrombocytopenia and

a mild neutropaenia. Serum biochemistry revealed a moderate elevation in liver enzymes and creatine kinase along with mild hypoproteinaemia.  Infectious disease screening (feline infectious anaemia PCR, FIV ELISA and FeLV ELISA) was negative as was Coombs testing. Coagulation times (PT/APTT) were within normal limits and urinalysis was unremarkable. These results were highly suspicious for a primary bone marrow disorder.

A blood transfusion was performed (50ml type A whole blood) following which the haematocrit increased from 6.0% to 13.2% and the platelet count increased from 10×10⁹/l to 48×10⁹/l (table 3, below).

Table 3: Follow-up haematology results

A course of doxycyline (10mg/kg po sid) was also started in case of haemotropic mycoplasma infection whilst awaiting the infectious disease screening results. 24 hours later the cat appeared much brighter. Diagnostic imaging (lateral thoracic and lateral abdominal radiography and abdominal ultrasonography) was unremarkable so the cat was anaesthetised for bone marrow aspiration and biopsy. Bone marrow cytology and histopathology were both indicative of acute erythroblastic leukaemia and FeLV PCR of the bone marrow sample was negative.

Chemotherapy induction was instigated using cytosine arabinoside (50mg/m² iv bid for 4 days) and doxorubicin (10mg/m² iv sid for 3 days). Blood samples were taken pre-treatment and then daily during treatment for haematological monitoring. Several days into the induction marked neutropaenia was noted (0.27×10⁹/l) and the thrombocytopenia had worsened (27×10⁹/l). Chemotherapy was therefore suspended and prophylactic antibiotics were given (amoxicillin-clavulanate 50mg q12h P.O.). A week later the neutrophil count had normalised and the chemotherapy induction was completed. The PCV and platelet count remained low (10.8% and 40×10⁹/l respectively) and, following cross matching, a repeat blood transfusion was given before discharge. The maintenance chemotherapy protocol was cytosine arabinoside (50mg/m² sc – two doses 12hours apart once weekly) and doxorubicin (10mg/m² iv every 3 weeks). Blood was taken weekly for haematological monitoring.

Two weeks following discharge the haematocrit had gradually increased to 19.7% and the platelet count had improved (60×10⁹/l). The cat continued to do well clinically, remaining bright with a good appetite and the haematology results remained stable. However, two months later the cat became acutely weak and dyspnoeic. The PCV at this time was 9%. Cross matches were performed with several donor cats but strong agglutination was evident in all the samples

Since repeat transfusion was unlikely to be successful the owners opted for euthanasia at this stage.

Erythroblastic leukaemia is a myeloproliferative disease which is characterised by malignant transformation and excessive proliferation of erythroid precursors in the bone marrow. As in this patient, it generally results in severe non-regenerative anaemia with nucleated erythrocytes present in the peripheral circulation. Erythroblastic leukaemia is rare in cats. In the few published case reports, concurrent FeLV infection is a common finding but this did not appear to be an inciting factor in this cat. The prognosis for acute non-lymphoblastic leukaemias is generally poor and euthanasia is often performed at the time of diagnosis. The two-month survival time seen in this cat seems favourable compared with survival times documented in previous case reports but it is impossible to compare efficacies due to a paucity of case numbers.