Diagnosis of multiple myeloma in a Labrador Retriever

florinFlorin Cristian Delureanu

MRCVS, DVM

November 2021

 

History

A 12 years old intact male labrador retriever was presented to the practice in 05.03.2021 with a history of diarrhea and hyporexia. The diarrhea was present for few days and the appetite was decreased for about 2 weeks but there were moments when the patient was eating normally. The patient was up to date with the booster vaccination and was regulary using antyparasitic treatment.

 

Physical examination

At the moment of examination the patient was bright, alert, with normal temperature (38.7 °C), the palpable lymphnodes were normal in size, nothing abnormal detected in the oral cavity and thoracic ascultation unremarkable. A mass of approximate 5cm diameter with soft consistency, mobile, and without local reaction on the surrounding soft tissue was identified in the xiphoid area.

 

Investigations

Initially general blood tests including complete blood count, biochemistry, electrolytes and total T4 were performed as a routine screening in order to identify any abnormalities. The results from the haemoleucogram demonstrate mild microcytic hypochromic non-regenerative/ pre-regenrative anemia, neutropenia, monocytopenia and eosinopenia. On the biochemistry just hyperproteinaemia due to increased globulins was the single abnormality. Also the thyroid hormone was under the normal reference range (picture 1).

fig 1

Coroborating the blood results with the history and the clinical examination the following differential diagnostic list was discussed with the owner: occult chronic blood loss, iron deficiency, inflammatory/infectiouse cause, neoplastic, immune mediated disease, endocrine (anemia secondary to hypothyroidism), gammopathies.

Aditional history: the last time when the patient went to a veterinary practice was 5 months prior for the regular booster vaccination.

Because of no evident clinical symptoms the presumption of chronic blood loss due to diarrhoea or anemia secondary to hypothyroidism was suspected. After discussion with the owner the decision of repeating blood tests in 4 days was taken. The patient was discharged with oral probiotics and was put on gastro intestinal veterinary diet to treat the diarrhoea. At reevaluation blood was collected and was send to the reference laboratory for complete blood count and blood smear interpretation, SDMA, Coomb’s test and C-reactive protein and complete thyroid panel including total T4, freeT4, cTSH, thyroglobulin autoandibody

The SDMA was normal also the thyroid panel was normal and negative on thyroglobulin autoandibody. The C-reactive protein was mildly elevated and the Coomb’s test was negative. On haematology the anemia had the same characteristics but was normocytic the reticulocytes and platelets under the normal limit. There were no modifications on the leucogram compared with the one performed at the first presentation (picture 2).

fig 2

The blood film was evaluated and a mild microcytosis and no increased in polycromasia was noted. Marked rouleaux formation and occasional metarubricyte were present too and leucopenia was confirmed. Estimation of free platelets (3-8 platelets seen per HPF) suggested platelet numbers are mildly/moderately decreased with and very small platelet clumps seen was identified.

 

Based on the second blood tests (pancytopenia is observed but also marked rouleaux and occasional metarubricyte) and hyperglobulinaemia from the initial blood tests a suspicion of neoplastic disease like multiple myeloma or lymphoma less likely non-neoplastic disorders like monoclonal gammopatihes (Erlichiosis or Dirofilariasis) because the patient was regulary using antiparasitic medication and no history of travelling. In the same day results were reported to the owner and additional questions regarding the origin, travel status and lameness episodes were asked to the owner in order to find more informations. There was no history of travelling, the dog origin was United Kingdom and transitory episode of weakness were observed in the past months.

 

Further investigations

To investigate more the suspicion serum and urine protein electrophoresis, urinalysis including urine protein creatinine ratio, radiographs and bone marrow aspiration were recommended. Five days later the patient presented to the practice but the owner accepted initially just the non-invasive investigation and declined the x-rays and bone marrow aspiration. An additional in house haemoleucogram was performed at this stage to monitor the trend of the red and white blood cells (picture 3)

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The urinalysis revealed proteinuria 3+ and a pH of 8 with active sediment and no crystals or casts, the urine beign collected via urethral catheterisation. The urine protein creatinine ratio was marked elevated (picture 4).

 

fig 4-1

 

 

 

 

At serum protein electrophoresis hypoalbuminaemia was present with a mild increase in alpha 1 globulins and marked increase in gamma globulins migrating in a gamma region and a depletion of the globulins thereafter, consistent with a monoclonal band (picture 5)

fig 5

 

 

 

 

 

 

 

 

 

The urine protein electrophoresis showed that majority of the protein was presented in the alpha-beta region and this was interpreted as overflow proteinuria secondary to the marked gammopaty present at the serum protein electrophoresis. No bands consisting with Bence Jones protein were noted but this would be masked by the overflow proteinuria (picture 6).

fig 6

After these last results a highly suspicion of neoplastic disease was made. Radiography and bone marrow aspiration were recommended to confirm the disease. The owners were reluctant to put the dog under sedation because in the past he had general anesthesia and was not stable according to the previouse veterinarian. At this moment the patient was sent to a referral center to have the imagistic investigation.

 

In 09.04.2021 the patient arrived at the referral center for the last investigations. After clinical examination a firm mobile mass was noted in the caudal abdomen. Initially HLG, blood film evaluation, ionised calcium and 4Dx were performed followed by CT scan of the thorax and abdomen and fine needle aspiration of the liver, spleen and abdominal mass ultrasound guided. The ionised calcium was mild elevated (1.95 mmol/L), the 4Dx was negative. The haematology findings consist with normal white blood cell count with a slight improvement from the 5th March and a stable red blood cell count (HCT 31%) – with a mild non-regenerative anaemia. An initial review of the CT scan confirms the presence of a 4.5-5cm encapsulated mass in the caudal abdomen, with no obvious association with the intestinal wall. A small amount of free fluid is present between the liver lobes. After these investigations the patient was sent home with Fortekor as a treatment of proteinuria.

 

Seven days later the full CT report, aspirates results and blood smear interpretation were ready.

 

Cytology interpretation

 

A detailed haematology showed a mild, normocytic normochromic, poorly regenerative anaemia (HCT 36.9%, reticulocyte count 95.05×109/L). His white blood cell and platelet count were low-normal. There was no evidence to support haemolysis and leucocyte morphology was unremarkable.

Aspirates from the liver and spleen identify a population of extremely atypical plasma cells, supportive of multiple myeloma. Prominent extra medullary haematopoiesis is also noted within the spleen.

Aspirates from the caudal abdominal mass show adipocytes and a mixed inflammatory cell population, comprising of neutrophils ageing in situ and undergoing pyknosis. An atypical plasmacytoid population is identified but in low numbers, suggesting infiltration with myeloma.

 

CT findings from the report

 

Musculoskeletal:

There are multifocal osteolytic lesions throughout the entire included portion of the skeleton, including essentially all included vertebrae (thoracic, lumbar, sacral), multiple ribs, the sternebrae, the proximal humeri, the pelvis and the proximal femurs (picture 7).

 

Thorax:

No soft tissue attenuating pulmonary nodules are identified. There are multiple small (<5mm), mineral attenuating, geometrically shaped foci throughout the pulmonary parenchyma (predominately within the periphery), consistent with benign osteomata.

 

Abdomen:

An ovoid, well encapsulated mass is identified within the mesentery of the right caudal abdomen, which measures approximately 4.7cm x 4cm x 5.7cm (height x length x width) (picture 8). The mass is predominately fat attenuating, with a soft tissue attenuating rim and patchy regions of internal soft tissue attenuation (which ranges in appearance from ill-defined to linear).

 

A soft tissue attenuating (isoattenuating to the adjacent renal cortical tissue on pre-contrast), minimally contrast enhancing nodule, measuring approximately 1cm in largest diameter, is present in the right lateral renal cortex (picture 9).

 

The liver and spleen are diffusely mildly enlarged, with rounded margins, however they demonstrate normal attenuation and contrast enhancement. A mildly enlarged splenic lymph node is also present.

fig 7 fig 8 fig 9

 

 

 

Diagnosis: Multiple myeloma – advanced stage

 

Discussion

 

Multiple myeloma is a lymphoproliferative cancer arising from plasma cells and their precursors, characterised by clonal proliferation of plasma cells infiltrating the bone marrow and then affecting other organs such as the spleen. Diagnosis of MM usually follows the demonstration of bone marrow or

visceral organ plasmacytosis, the presence of osteolytic bone lesions and the presence of urine myeloma proteins. Renal disease is present in approximately one-quarter to one half of dogs with MM, and azotemia is observed in 30% to 40% of cats.

Bence Jones proteinuria was not evident in the pacient urine protein electrophoresis due to overflow proteinuria secondary to the marked gammopaty. Bence Jones proteinuria occurs in approximately 25% to 40% and hypercalcemia is reported in 15% to 50% of dogs with multiple myeloma. The clinical signs can vary from lethargy and weakness to inappetence, weight loss, lameness, polyuria/polydipsia, bleeding diathesis and central nervouse system deficits. The patient presented with a history of mild inappetence and isolated episodes of lameness.

Chemotherapy is effective at reducing malignant cell burden and to improve the quality of life of the patient. Variouse alkylating agents such as melphalan, cyclophosphamide, chlorambucil, lomustine can be used together with steroid therapy. The most common protocol is a combination between melphalan and prednisolone. This protocol is usually well tolerated by the vast majority of the dogs, the most clinically significant toxic events beign represented by myelosuppression and delayed thrombocytopenia.

 

After the last investigations performed at the referral center the patient started to deteriorate significantly this manifested by presence of a severe swelling over the left side of the face associated with pain and ptyalis. Two days later, a chemotherapeutic protocol including melphalan, cyclophosphamide orally with intravenous dexamethasone was started. Despite this, the dog developed neutropenia and pyrexia, raising concern for sepsis. As a result, a decision was made to euthanase him one day later.

 

 

 

 

 

 

 

 

 

 

 

Cerebrovascular accidents in dog

 

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Dr Svetoslav Penchev

United Veterinary Clinic

Varna,Bulgaria

 

 

Stroke or cerebrovascular accident (CVA) is the most common clinical manifestation of cerebrovascular disease, and can be broadly divided into ischemic stroke and hemorrhagic stroke. CVA are characterized clinically by a per acute or acute onset of focal, asymmetrical and non-progressive brain dysfunction. Next cases show the both type of CVA in dogs.

1st case is about 9 years old female boxer. The dog was referring to the clinic with acute onset of seizures. The results of CBC and Biochemistry were normal and MRI was performed.

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MRI findings: Intra-axial right piriform lobe and hippocampus lesion with impression of moderate swelling of these portions is present. The cerebral falx is only mildly displaced to the left. There is corresponding low T1 signal intensity in these sections of the brain suggesting edema. There is no enhancement of the lesion after contrast administration. The findings suggest that there is a non-hemorrhagic cerebrovascular accident in right forebrain of the dog.

 

The 2nd case is about  a 8 years old male Cane corso. The dog was present in the clinic with unilateral fore brain deficits and history of epileptic seizures. Biochemistry and CBC were normal and MRI was performed.

 

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MRI findings : There is a well‐delineated T1 iso- to hypointense  and T2 hypointense  mass lesion with surrounding brain edema in right piriform lobe with a thin peripheral rim of contrast enhancement. There is a mass effect, displacement of the right lateral ventricle and midline shift to the left. This imaging feature is consistent with an acute to subacute intracranial hemorrhage.

 

Conclusion:

MRI features of Hemorrhagic infarction in dogs may not be distinguishable from hematoma caused by vascular disruption. Imaging characteristics will vary depending on the size, location, and chronicity ofthe hematoma.

Hyperacute – 24 hours   T1 isointense ; T2 hyperintense

Acute         1-3 days  T1 iso- to hypointense  ; T2 hyperintense

Early subacute   >3 days  T1 hyperintense  ; T2 hypointense

Late subacute    >7 days  T1 hyperintense ; T2 hyperintense

Chronic              > 14 days   T1 hypointense ; T2 hypointense

Secondary  features :  mass effect, surrounding edema, midline shift , ventricular displacement and compression .

 

MRI features of Nonhemorrhagic Infarction in dogs include mildly T1 hypointense and T2 hyperintense  lesion with minimal  mass effect involving both gray and white matter on unenhanced MR images. These changes seen in ischemic parenchyma rely on an increase in tissue water content. Gradually, during the acute stage, the T2-weighted image becomes more hyperintense in the ischemic region, particularly over the first 24 hours. These signal changes seen in the first 24-hours are best appreciated in grey matter and are well visualized in deep grey matter structures such as the thalamus or basal ganglia, in addition to cortical grey matter. Gadolinium enhances infarcts because of vascular rupture but does not enhance ischemia or edema.

 

Meningocele and meningoencephalocele in a dog

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Dr Svetoslav Penchev

United Veterinary Clinic

Varna, Bulgaria

 

8 mounts ,female dog with congenital meningocele and hydrocephalus . The dog is with normal behavior and without neurological deficits.1113

Meningocele and meningoencephalocele of the skull are congenital deformities. These deformities, which are observed as cyst-like swellings in the median part of the skull cap, occur very rarely. The intracranial material protrudes through a spontaneous cavity, such as the anterior fontanelle , and they are classified as encephalocele, meningocele, or meningoencephalocele according to the cranial bifida.111 1122

Craniomandibular osteopathy in a young dog

421347_10151629937179640_1038846606_nDr Miroslav Todorov

Blue Cross Veterinary Hospital

Sofia, Bulgaria

Case report

40542605_382709382264902_1711454165768601600_nCraniomandibular osteopathy in a young Labrador retriever.

A 4 months old Labrador retriever was presented at the BlueCross Veterinary Hospital in Sofia, Bulgaria, with the owner complaining about painful episodes after touching the head of the animal.

Clinical examination: the dog is in a good clinical stage, no pathological heart or lung sounds.

The temperature was 39,5 C. No abdominal pain or other abnormalities.

The palpation of the skull was painful for the dog, there was slight dome shape of the cranium. The masseter muscles were atrophied. After palpation of the mandibula it was noted that the lower jaw of this dog looked enlarged. Pic 1

Considering the age, breed and the affection of the specific bones, the following list of differential diagnosis was made:

  1. Craniomandibular osteopathy
  2. Osteomyelitis
  3. Calvarial Hyperosthosis
  4. Neoplasia

We took a blood sample for CBC and biochemistry analysis.

On the CBC there was a slight decrease of the RBC – 5,36 (5.5- 8.5 x10/12/L) but this could be normal for younger animals.

On the biochemistry there was a slight decrease of the Total protein – 49 (51- 78) g/L and Albumin – 20(26- 41) g/L. Everything else was WNL.

The patient was sent for CT of the head to search for additional characteristics of the bones of the head and confirm my suspicion about the disease. We put an injection of NSAID for the pain until the test was done.

On the CT we discovered symmetrical bone proliferation of the rami of the mandubule and bone thickening of the calvarium of the animal. No underlying bone lysis was noted. Fortunately, till this moment affection of the temporomandibular joints was not discovered, but it is possible that this could happen during the next months.40574303_322560345178752_5208200230733873152_n 40589358_286835962116167_5128061020073361408_n 40589364_655681474803526_9092529697882898432_n 40623237_513632389060326_2736220804109828096_n 40764141_2203859333191397_5014338687031312384_n

There were not clear signs of neoplastic process or osteomyelitis. As a result, considering the information that we had, a diagnosis of craniomandibular osteopathy was made.

Craniomandibular osteopathy is a non neoplastic proliferative bone disease affecting immature dogs.

Usually the clinical signs start between 3 and 8 months of age. Common clinical presentation is pain episodes, fever, trouble chewing food, drooling and in more advanced cases – inability to open the mouth and eat. The etiology of this disease is unknown.40530022_1906226039680267_8977683290295107584_n

The first written description of CMO appeared in 1958.(9) It was described in five West Highland white terriers affected within a 2-year period. The most common breeds that are affected are West Highland white Terrier, Scottish Terrier, Cairn Terrier. The disease is described in other breeds – in Labradors, Boxers, Great Dane and a few more.

It is believed that this could be an inherited disease (autosomal recessive inheritance pattern) and as such it is advised for such animals to be neutered.

Commonly the affected dogs have bilaterally symmetrical enlarged mandibles and tympanic bulles, and affection of other bones of the calvarium. In severe cases those structures could fuse and this will lead to decreased range of motion of the temporomandibular joint. On examination, the temporal and masseter muscles may be atrophied.

In advanced cases, the diagnosis of craniomandibular osteopathy can be done with good positioned x-rays of the head of the animal. The advance imaging techniques, such as CT or MRI, improve the visualization and confirm the extension of the process.

On x- ray or CT increased irregular bone density is commonly observed –  symmetrical periosteal proliferation, in most of the cases primary affection of the mandibules- 84%; tymplanic bulles – 51% and in some of the cases bones of the calvarium -13%.

The treatment plan is symptomatic with painkillers and anti-inflammatory drugs – commonly used drugs are NSAID and Steoids. Such drugs are needed during pain episodes and fever. Placement of an esophagostomy or gastrostomy feeding tube may be considered in patients that have difficulty eating and their nutritional requirements are not being met. Soft or liquefied food may be easier for some patients to eat. A high protein, high caloric food should be offered in order to meet nutritional needs.

Surgery of the bone proliferated tissues is not helpful in those cases.

The prognosis for these patients depends of the extent of progression of the disease. In those cases where a severe bone proliferation develops, the result is fusion of the temporomandibular joint and the prognosis is poor. Most of those dogs are euthanized because of the extent of the disease. It has been a common observation that when the affected dog is approximately 11 to 13 months of age, the disease may become self-limiting. The growth of abnormal bone slows, often regresses, and sometimes recedes completely. This period of self-limitation coincides with the time of completion of regular endochondral bone growth and ossification.

Our patient felt great after one injection of meloxicam. He is feeling active and has no signs of pain and temperature. Unfortunately, we cannot say whether his condition will progress to the extent to affect the temporomandibular joints and lead to inability to open its mouth.

The owner will return the dog to the breeder. It was advised to watch the dog for any additional signs and painkillers were prescribed.

C2 FRACTURE AND CENTRAL CORD SYNDROME

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Dr Svetoslav Penchev

United Veterinary Clinic 

Varna, Bulgaria

 

 

 

 

Case is about a 6 months , male  cocker spaniel named  Michael.Michael was brought in the clinic from another city in very bad candition.The owners report for a trauma in cervical region.Radiography and neurological examinations were made. Results revealed –Tetraplegie and atalnto-axial instability.It was made a CBCT on cervical region.The image show C2-Fracture .3

 

 

 

 

 

 

 

 

Michael C2 fr et CCS 9Michael C2 fr et CCS 5Michael C2 fr et CCS 6Michael C2 fr et CCS 4Michael C2 fr et CCS 2It was maked a surgary to stabilize  cervical spine. Ten days after surgery Michael starts moving the pelvic limbs first and tries to stand on them. Twenty one days after surgary Micheal start to moving and thoracic limb  , but  have ataxia and destroys proprioception on his  four leg. Michael`s  recovery begin first with the hind limbs and then with the thoracic limbs .In human literature, the symptom in which the thoracic limb is in a dysfunctional state with minimal to no deficit in the pelvic limbs has been referred to as CCS (Central Cord Syndrome ). The spinal cords that travel to the pelvic limbs are minimally affected because the lesion is centralized in the cervical region, which only affects the thoracic limbs. In general, CCS has a good prognosis for functional recovery and its common etiology is traumatic disease in human medicine. CCS treatments with nonsurgical management include cervical spine restriction with a neck collar, rehabilitation followed by physical therapy and occupational therapy. Surgical management is provided for patients who cannot be treated by conservative management alone.

 

Michael C2 fr et CCS 10Michael C2 fr et CCS 8Michael C2 fr et CCS 11Michael C2 fr et CCS 12Michael C2 fr et CCS 13