Hypothesis 3: Neoplasia disrupting cranial cruciate ligament

Damage to the cranial cruciate ligament is the primary focus of the diagnostic 
workup since the left stifle demonstrates a positive cranial drawer sign, a test that is 
indicative of a partial or complete cranial cruciate ligament rupture.  In addition to this 
test result, there is no palpable pain or abnormality in the patella, collateral ligaments of 
the stifle or the hip joint.  Although the cranial drawer of the right stifle was reported as 
<2mm, this is considered normal and will not be investigated further.  However, an obese 
large-breed dog is predisposed to degenerative joint disease and other joint injury so the 
owner should be observant of any gait changes in the future.

Due to Bonnie's age, neoplasia should be considered as a cause of the cranial 
cruciate damage.

Two types of neoplasia are located in joints: synovial osteochondroma and 
synovial sarcoma.  With synovial sarcoma, the synovial membrane produces islands of 
cartilage that become separated from the membrane and float freely in the joint.  This 
neoplasm arises from synovial metaplasia.  Synovial sarcomas, on the other hand, 
originate from mesenchymal precursor cells outside of the synovial membrane of joints 
and bursa.  Although this form of cancer is uncommon in the dog, it is usually seen in 
middle-aged, large-breed dogs.  The joints most commonly affected by synovial sarcoma 
are the stifle and elbow.  The sarcoma grows slowly and is first identifiable as a soft 
tissue mass around the joint.  In dogs, synovial sarcoma invades the adjacent bone and 
erodes the cortical bone adjacent to the joint.  This could erode the insertion or origin of 
the cranial cruciate ligament, resulting in its rupture or avulsion.  Cancellous bone is also 
destroyed on either side of the joint.  Unlike osteochrondromas, synovial sarcomas are 
invasive and do metastasize.
Any cancer residing in the joint cavity or the vicinity has the potential to affect 
the cranial cruciate ligament.  Some tumors cause bone lysis, which can affect the 
attachments of the ligament and cause it to separate from the bone.  Like a rupture, the 
detachment would allow the tibia to move cranially and cause the cranial drawer sign.  
Also, a tumor in the joint cavity would incite an inflammatory reaction that would initiate 
the release of cytokines, prostaglandins and lysosomal enzymes from neutrophils.  These 
inflammatory mediators alter the biochemical environment of the joint and disrupt the 
stability of the collagen within the ligament.  As the collagen fibers are weakened, the 
cranial cruciate ligament is susceptible to damage from relatively minor trauma.  In 
addition to the mechanisms described above, a tumor, simply by its space occupying 
nature, can disrupt the ligament's architecture and cause it to break.
Neoplasia arises from a nonlethal genetic mutation that allows a cell to replicate 
without cellular control.  The stimulus for the mutation can be an inherited defect, a virus, 
radiation or chemicals.  The genes responsible for the cell's aberrant multiplication are 
known as oncogenes and they include genes responsible for apoptosis, growth 
suppression, DNA repair and growth promotion.  Multiple mutations are required for the 
development of cancer due to the intricate regulation of the cell cycle.  If a neoplastic cell 
escapes the detection of the immune system, it will multiply to form a clinically 
detectable tumor.