European Society of Toxicologic Pathology (ESTP)
    European Society of Toxicologic Pathology
Guess What! - ESTP Case 11

The case shows pictures of H&E-stained knee joints from two male Wistar rats about 10 weeks of age. No gait abnormalities or gross findings were reported.

Click on the images below for a larger view.
Case 11, Fig. 1
Fig. 1: Knee joint rat 1, H&E, x1.6
Case 11, Fig. 2
Fig. 2: Knee joint rat 1, H&E, x20
Case 11, Fig. 3
Fig. 3: Knee joint rat 2, H&E, x1.6
Case 11, Fig. 4
Fig. 4: Knee joint rat 2, H&E, x10
Case 11, Fig. 5
Fig. 5: Knee joint rat 2, H&E, x5

Morphologic Description

Case # 11 showed two examples of alterations of the synovial tissue of the popliteal region in young male rats. They are characterized by thrombosis of subsynovial arterioles and capillaries. In animal 1 (fig.2), the occluded vessels are more prominent and the adjacent synovial tissue is fibrotic and contains basophilic extracellular material (fig.3). In animal 2, besides remnants of occluded vessels the synovial tissue is avascular and shows chondroid metaplasia (fig. 4) or marked fibrosis and a cystic structure which is probably a residue of former vasculature (fig.5). In the affected tissue only few or no inflammatory cells are present.

Proposed Diagnosis
Fibrosis and chondroid metaplasia of the synovialis in response to thrombosis of (sub)synovial vasculatur

In a brief communication by Sasaki et al. 1998, similar changes at cruciate ligaments and surrounding connective tissue in the knee joint of young adult rats were termed synoviitis.


Nine contributions were received for this case:
In the responses, the localization of the alteration was correctly given either as synovialis or cruciate ligament.
The contributors recognized synovial fibrosis and cartilagineous (syn. chondroid) metaplasia. Thrombosis of the small vessels was not mentioned and is difficult to discover in the H&E stain since the vessels contain mostly erythrocytes and fibrin is less prominent. However, the endothelium is lacking in the affected vessels but visible in a patent empty vessel in the same section shown in fig. 2. With phosphotungstic hematoxylin staining (PTAH), intravascular fibrin (arrows) could be confirmed (additional image 6 from animal No. 2).

Synovial (membrane) hyperplasia, fibrodysplasia, chondromucinous degeneration, joint ankylosis or idiopathic arthropathy were given by the contributors as more general terms for the condition. The difficulty of the decision whether this change is more degenerative or inflammatory in nature is reflected by the diagnoses of synovial membrane hyperplasia with pannus formation, osteoarthritis (contributors), and synoviitis (article by Sasaki et al.).

Orientation within the knee joint of rats is difficult since varying levels are cut even when standard procedures are applied. The focal predilection sites at the borders of the cruciate ligaments are not contained in every section and this may be one reason - besides genetic factors and holding conditions - why in some laboratories the change is seen more frequently than in others (frequency according to Sasaki et al. in four week-studies in male Wistar rats for vascular changes 67.5%, chondroid metaplasia in males 50% and fibroplasia 7.5%).

Suggestions of the contributors regarding the pathogenesis were either an idiopathic condition, bone malformation, trauma (possibly rupture of the menisci), or mutation. Sasaki et al. 1998 assumed that rapid body weight gain and housing conditions may have caused a microcirculatory disturbance causing joint instability. Resulting mechanical damage of the synovium may then have caused fibrosis and chondroid metaplasia of the synovial tissue. Considering the predominant presence in male rats and the focal occurrence at the caudal side of the knee joint suggest an influence of body weight and lack of exercise with flexed position of the knee joint as likely contributing factors.

Click on the image below for a larger view.
Case 11, Fig. 6
Fig. 6: Knee joint rat 2, PTAH, x10


  • Greaves P (2007) Musculoskeletal System. In: Histopathology of preclinical toxicity studies. Elsevier Inc. Amsterdam, pp 160 - 214
  • Levick JR (1995) Microvascular architecture and exchange in synovial joints. Microcirculation 2: 217-233
  • Sasaki S, Nagai H, Mori I, Kandori H, Anayama H (1998) Spontaneous synovitis in Wistar rats. Toxicol Pathol 26: 687-690