Canine synovial lipomatosis: Clinicopathologic findings and HGMA2 immunohistochemistry in 4 cases

Abstract

Synovial lipomatosis is an uncommon, intra-articular, fat-containing, proliferative lesion with unknown etiology that is rarely reported in dogs. A retrospective study spanning 13 years was conducted to search for cases of canine synovial lipomatosis. Among 188 synovial biopsies of major diarthrodial joints (ie, shoulder, elbow, carpus, hip, stifle, and tarsus) from 186 dogs, 4 cases (2.1%) of synovial lipomatosis were identified. One case occurred in a stifle with chronic lateral patellar luxation. The other 3 cases had microscopic evidence of synovitis (eg, synovial hyperplasia, lymphoplasmacytic infiltrates, hemosiderin-laden macrophages, myxomatous changes, fibrosis, and increased vascularity) but lacked a clinical history of arthritis. Immunohistochemistry for HMGA2 was negative, suggesting canine synovial lipomatosis is a non-neoplastic proliferative lesion, yet the cause remains unknown.

Synovial lipomatosis is an intra-articular, fat-containing, proliferative “tumor-like” lesion. ¹⁴ It has been documented in single case reports and case series in human medicine.^1,6,9,14,17 This condition is also known as lipoma arborescens in humans and most commonly affects the knee with less predilection for other joints.^4,17 It is commonly associated with arthritic conditions, particularly osteoarthritis, and hence, it is hypothesized to be a reactive response to chronic inflammatory or traumatic stimuli.^1,14 However, the exact etiology remains unknown, and other causes, including rheumatologic, developmental, and neoplastic processes, have been implicated.^3,7 Synovial lipomatosis in multiple joints has also been reported in a human patient with short bowel syndrome, which may have been related to abnormal fat deposition due to reduced fat absorption. ¹⁶ An immunohistochemical study of HMGA2 (high mobility group AT hook 2) supports a non-neoplastic basis for synovial lipomatosis in humans. ¹¹

To the authors’ knowledge, there are only 3 case reports of synovial lipomatosis in dogs.^2,13,15 To enhance understanding of this rare condition in dogs, canine synovial biopsy cases diagnosed at the University of Missouri’s Veterinary Medical Diagnostic Laboratory between 2011 and 2024 were retrieved and examined. Among 188 synovial biopsies of major diarthrodial joints (ie, shoulder, elbow, carpus, hip, stifle, and tarsus) from 186 dogs, 4 cases (2.1%) of synovial lipomatosis were identified. The cases included a 5-year-old, 30.0 kg, neutered pit bull mix (right elbow) with body condition score (BCS) 5/9; a 7-year-old, 28.9 kg, neutered Australian shepherd dog (right tarsus) with BCS 5/9; a 4-year-old, 22.9 kg, spayed English Springer Spaniel (right tarsus) with BCS 5/9; and an 11-month-old, 48.5 kg, neutered Newfoundland dog (left stifle) with BCS 4/9. The mean age was 4.2 years, and the mean body weight was 32.5 kg. Incisional biopsies had been obtained via an open joint approach in these cases. Five-micrometer-thick sections stained with hematoxylin and eosin were prepared from formalin-fixed paraffin-embedded specimens and were examined.

The 5-year-old pit bull mix (case 1) was presented for evaluation of right forelimb lameness with a 7 cm (medial-lateral) × 7.7 cm (cranial-caudal) × 3.3 cm (proximal-distal) irregular, immobile, subcutaneous soft mass with poorly defined margins extending circumferentially around the right elbow. Standard radiographs showed a soft tissue swelling around the elbow with no underlying bony changes. The differential diagnosis included articular histiocytic sarcoma, synovial myxosarcoma, and soft tissue sarcoma. Histologically, the lesion consisted of variably sized papillae and nodules of mature adipose tissue (Fig. 1a). The adipose tissue was covered by synovial intima with plump synovial lining cells (synoviocytes) ranging up to 6 cell layers thick (synovial hyperplasia). In the subintima among the sheets of mature adipocytes, there were areas of myxomatous change (perivascular and interstitial), fibrosis, small numbers of lymphocytes and plasma cells, occasional small perivascular lymphoid aggregates, scattered hemosiderin deposits and hemosiderin-laden macrophages, and an increased number of small blood vessels (>10 per 0.237 mm²). The specimens also contained areas of villous proliferation of the synovial intima lined by hyperplastic synoviocytes with small numbers of lymphocytes and plasma cells in the fibrovascular and/or adipose subintimal stalks (hyperplastic synovitis) (Fig. 1a). The owner opted to hold off on treatment apart from oral carprofen (50 mg, S.I.D.) and 100 mg of tramadol as needed to ease discomfort of the right forelimb. Eight months after the biopsy diagnosis of synovial lipomatosis, the lesion had grown to 8.5 cm × 7.4 cm × 10.9 cm. On physical examination, the elbow joint had a decreased range of motion with pain on elbow flexion. The antebrachium distal to the mass was swollen with edema to the level of the metacarpus and decreased flexion of the carpal joint. A computed tomography (CT) scan of the right elbow and a repeat incisional biopsy were performed. The CT examination revealed a large, heterogeneously contrast-enhancing, lobulated, circumferential mass centered on the right elbow joint (Fig. 1b). The mass was characterized by mixed fat, fluid, and soft tissue attenuation, with fat being the predominant component. The lesion extended beyond the joint, reaching proximally to the mid-humerus and distally to the mid-antebrachial region. There was no bone involvement on CT. The histologic findings of the repeat biopsy were identical to those from the initial biopsy. Therapeutic options, including synovectomy, were discussed, but the owner declined further treatment, and the patient was lost to follow-up.

Figure 1.

Synovial lipomatosis in dogs. (a) Synovial subintima expanded by mature adipose tissue and lined by hyperplastic synovial lining cells; lymphoplasmacytic infiltrates, myxomatous change, fibrosis, and increased vascularity are present. The synovium occasionally exhibits villous hyperplasia. Case 1. Hematoxylin and eosin (HE). (b) Computed tomography image shows a large mass with mixed fat, fluid, and soft tissue attenuation associated with the right elbow (arrowheads). Case 1. (c) Synovial subintima expanded by mature adipose tissue; hyperplastic synovial lining cells are present. Case 2. HE. (d) Ulcerated synovial lining covered by aggregates of blood and fibrin; subintimal fibrosis; myxomatous change; scattered lymphocytes, plasma cells, and hemosiderin-laden macrophages; and a perivascular lymphoplasmacytic aggregate. Case 2. HE. (e) Synovial subintima expanded by mature adipose tissue; hyperplastic synovial lining cells with areas of villous hyperplasia are present. Case 3. HE. (f) Nodular proliferation of mature adipocytes with hyperplastic synovial lining cells. Case 4. HE.

The lesion of the 7-year-old Australian shepherd dog (case 2) was initially identified as an approximately 2.5 cm, soft, flocculent swelling on the medial aspect of the right tarsus, but no diagnostic investigation or treatment intervention was undertaken at that time. Eight months later, although the size of the mass was unchanged, the owner requested surgical removal. While a subcutaneous mass was suspected clinically, at surgery, there was abundant tissue resembling adipose within the tarsal joint. Histologic examination revealed variably sized papillae and nodules of mature adipose tissue covered by hyperplastic synovial lining cells (Fig. 1c). The synovial lining was focally extensively ulcerated and covered by abundant fibrin and hemorrhage (Fig. 1d). The subintima adjacent to the ulceration/fibrinous adhesion was fibrotic with moderate numbers of lymphocytes and plasma cells mixed with frequent hemosiderin deposits and hemosiderin-laden macrophages (Fig. 1d). The adipose tissue adjacent to the fibrosis exhibited myxomatous change with scattered hemosiderin-laden macrophages (Fig. 1d). Increased vascularity was also present. No follow-up information was available, leaving the clinical outcome unknown.

The 4-year-old English Springer Spaniel (case 3) was presented for a slow-growing (6-month duration), approximately 2 cm, soft nodular mass on the right tarsus, which was thought to be subcutaneous until surgery, where it was discovered to be synovial. The biopsy specimens consisted of variable-sized papillae and nodules of mature adipose tissue covered by hyperplastic synovial lining cells (Fig. 1e). Small numbers of lymphocytes and plasma cells and some hemosiderin-laden macrophages were present in the subintima, along with increased vascularity and occasional areas of mild myxomatous change and fibrosis. The specimen also contained villous proliferations of the synovium lined by layers of plump synovial lining cells with small numbers of lymphocytes and plasma cells in the fibrovascular and/or adipose subintimal tissue (Fig. 1e). There was no follow-up information.

The 11-month-old Newfoundland dog (case 4) had chronic lateral patellar luxation of the left stifle with swelling. Irregularly thickened synovium was noted during the surgical repair of patellar luxation, and biopsies of the abnormally thickened synovium were taken for histologic examination. Histologically, the specimens comprised multiple, up to 0.7 cm in diameter, nodular proliferations of mature adipocytes covered by hyperplastic synovial lining cells with occasional short frond-like projections (Fig. 1f). The affected subintima exhibited moderate myxomatous change, mild fibrosis, increased vascularity, small numbers of lymphocytes and plasma cells, and small aggregates of hemosiderin-laden macrophages. Follow-up information was unavailable.

In the previous case reports of canine synovial lipomatosis, the lesions developed in a stifle joint of a 6-year-old, neutered, overweight (65.5 kg) Central Asian shepherd dog with a partial cranial cruciate ligament rupture; ¹³ in a stifle joint of a 2-year-old, neutered, bullmastiff with a partial cranial cruciate ligament rupture and radiographic evidence of osteoarthritis (eg, osteophytes); ² and in a tarsal joint of a 3-year-old, neutered, Eurasian dog, concurrently with spinal epidural lipomatosis after prolonged use of immunosuppressive dosages of prednisolone. ¹⁵ Clinical information of these cases suggests that canine synovial lipomatosis may develop in response to local or systemic insults. An association with chronic joint inflammation or abnormal lipid metabolism has also been speculated in human synovial lipomatosis. ¹⁴ In this study, only 1 dog (case 4) had documented chronic joint disease (ie, lateral patellar luxation), whereas the other 3 dogs had no documentation of arthritis or joint injury in the affected joint. None of the dogs in the present study were obese or had a reported history of prolonged steroid use.

To investigate whether the lesions are neoplastic proliferations of adipocytes within the joint, immunohistochemistry for HMGA2 (AF3184 R&D systems, 1:100 dilution, Supplemental Table S1) was conducted using the antibody validated for canine research. ¹⁸ In humans, the HMGA2 gene encodes a protein that alters chromatin structure. ⁵ Although not validated in dogs, its involvement in adipocytic tumors has been demonstrated in humans.^5,10 The HMGA2 is detectable by immunohistochemistry in formalin-fixed paraffin-embedded adipocytic tumors (eg, cutaneous lipomas, intramuscular lipomas, and liposarcomas), whereas normal mature adipose tissue does not express HMGA2. ⁵ In a human study, all examined synovial lipomatosis tissues (n = 17) were negative for HMGA2 by immunohistochemistry. ¹¹ In the present study, an intramuscular lipoma from a 6-year-old, neutered Labrador retriever and a cutaneous lipoma from a 7-year-old, spayed Labrador retriever were used as positive controls, both showing positive nuclear immunolabeling for HMGA2 (Fig. 2a). Consistent with the human study, ¹¹ none of the 4 canine synovial lipomatosis lesions labeled positively for HMGA2 (Fig. 2b), supporting the hypothesis that synovial lipomatosis in dogs is a non-neoplastic condition.

Figure 2.

(a) An intramuscular lipoma (positive control) has adipocyte nuclei that are immunoreactive for HMGA2 (arrows). HMGA2 immunohistochemistry (IHC) (b) Nuclei of adipocytes in synovial lipomatosis are not immunoreactive for HMGA2. Case 1. HMGA2 IHC.

Although only 1 dog in this report had clinical evidence of chronic local joint disease (case 4, lateral patellar luxation), the possibility of underlying subclinical or non-documented arthritis and/or joint trauma in the other 3 cases cannot be excluded in this retrospective study. Hyperplastic synovitis (synovial lining hyperplasia with or without inflammatory infiltrates) present in all 4 cases in this study is chronic and not specific diagnostically. However, synovial hyperplasia with lymphoplasmacytic inflammation often develops in canine osteoarthritic joints, such as stifles with cranial cruciate ligament rupture. ⁸ Hemosiderin-laden macrophages, often seen in the synovium in post-traumatic osteoarthritis, ⁸ were also noted. Myxomatous change, fibrosis, and increased vascularity in the subintima are common histologic features of synovitis associated with arthritis.^8,12 Fibrin adhesion on the ulcerated synovial surface present in case 2 is a feature of high inflammatory arthritis ¹² and may suggest acute trauma superimposed on preexisting chronic synovitis or rheumatoid joint disease (eg, immune-mediated arthritis), although rheumatoid joint disease is uncommon in dogs. Repetitive trauma associated with chronic lateral patellar luxation may have contributed to synovial lipomatosis in case 4. Despite microscopic evidence of concurrent synovitis in all 4 cases, this study was unable to identify the underlying condition(s) that may have provoked synovitis and/or synovial lipomatosis in the other 3 cases. Synovitis may be a contributing factor in synovial lipomatosis; however, it may also be a result of abnormal joint motion, pressure, and friction associated with the lesion. Synovial lipomatosis is rare, even though arthritis is prevalent in both humans and dogs. This suggests that there may be a yet unknown factor that is necessary to induce synovial lipomatosis, possibly in the context of traumatic or inflammatory joint conditions. Nonetheless, the present study supports the contention that canine synovial lipomatosis is a non-neoplastic proliferative lesion of synovial subintimal adipose tissue.

Limitations inherent to the retrospective nature of this study also include the limited use of imaging modalities for characterizing the affected joint, the absence of a systemic disease evaluation including serum lipid profiles, and the lack of prognostic information. In humans, treatment of synovial lipomatosis typically consists of synovectomy of the lesion via arthrotomy or arthroscopy with generally a good prognosis.^9,14 This may also apply to canine patients. However, treatment may need to be directed toward eliminating any underlying insults if this condition is indeed reactive in nature. In addition, the clinical and biological behaviors of the lesion in case 1 in this study indicate that, despite being a non-neoplastic condition, it does not always have a favorable prognosis. Further investigation into underlying precipitating factors and effects of treatment options is warranted.

Supplemental Material

sj-pdf-1-vet-10.1177_03009858241306404 – Supplemental material for Canine synovial lipomatosis: Clinicopathologic findings and HGMA2 immunohistochemistry in 4 cases

Supplemental material, sj-pdf-1-vet-10.1177_03009858241306404 for Canine synovial lipomatosis: Clinicopathologic findings and HGMA2 immunohistochemistry in 4 cases by Keiichi Kuroki, Katelin Dark, Jimmy C. Lattimer and Gayle C. Johnson in Veterinary Pathology