Mesenteric rheumatoid nodules masquerading as an intra-abdominal malignancy: a case report and review of the literature
© Thinda and Tomlinson; licensee BioMed Central Ltd. 2009
Received: 23 March 2009
Accepted: 15 July 2009
Published: 15 July 2009
Rheumatoid nodules are the most common extra-articular findings in patients with rheumatoid arthritis. They occur most commonly at pressure points such as the extensor surfaces of the forearms, fingers, and occiput, but have also been reported to occur in unusual locations including the central nervous system, pericardium, pleura, and sclera. We present the unusual case of rheumatoid nodules in the small bowel mesentery masquerading as an intra-abdominal malignancy.
A 65-year-old-male with a known history of longstanding erosive, nodular, seropositive rheumatoid arthritis was incidentally found to have a mesenteric mass on computed tomography (CT) exam of the abdomen. This mass had not been present on prior imaging studies and was worrisome for a malignancy. Attempts at noninvasive biopsy were nondiagnostic but consistent with a "spindle" cell neoplasm. Laparotomy revealed extensive thickening and fibrosis of the small bowel mesentery along with large, firm nodules throughout the mesentery. A limited bowel resection including a large, partially obstructing, nodule was performed. Pathology was consistent with an unusual presentation of rheumatoid nodules in the mesentery of the small bowel.
Rheumatoid nodules should be considered in the differential diagnosis of a patient who presents with an intra-abdominal mass and a history of rheumatoid arthritis. Currently, no tests or imaging modality can discriminate with sufficient accuracy to rule out a malignancy in this difficult diagnostic delimma. Hopefully, this case will serve as impetus for further study and biomarker discovery to allow for improved diagnostic power.
In addition to the classic symptom of chronic inflammatory arthritis, RA is also associated with many extra-articular findings, including rheumatoid nodules, pyoderma gangrenosum, pericarditis, pleuritis, felty's syndrome, interstitial lung disease, glomerulonephritis, peripheral neuropathy, scleritis, episcleritis, and vasculitis[1, 3]. Rheumatoid nodules are the most common extra-articular findings, occurring in about 25% of patients with RA. Rheumatoid nodules occur most commonly at pressure points such as the extensor surfaces of the forearms, fingers, occiput, ischial areas, and the Achilles tendon. They may also occur within internal tissues of the body: central nervous system, heart, pericardium, lungs, pleura, peritoneum, bones, vocal cords, and sclera. Pulmonary nodules have been associated with pleural effusions, pneumothoraces, and fibrosis. Cardiac nodules may be noted on echocardiogram and can cause symptoms of heart block and syncope[5, 6]. There have been no reports of rheumatoid nodules within the mesentery, and as is exemplified by our case, this entity has the potential to masquerade as a malignancy.
Given a nondiagnostic core needle biopsy but suggestive of malignancy, along with symptoms of intermittent obstruction, an exploratory laparotomy was undertaken. At exploration, the patient was noted to have extensive thickening and fibrosis of the entire small bowel mesentery along with centimeter sized, firm nodules throughout the mesentery. One nodule measuring approximately 2 × 2 cm was causing severe narrowing of the small bowel. This nodule along with 10 cm of the involved small bowel were resected and sent to pathology for frozen section analysis, which revealed acute and chronic inflammation, extensive necrosis, and foci of partial fibrinoid granulomas. Given the extensive nature of this disease process, no further attempts at resection were made as this disease process was incompatible with complete resection.
Rheumatoid arthritis is associated with many extra-articular manifestations, of which rheumatoid nodules are the most common, occurring in approximately 25% of patients with RA. Rheumatoid nodules are more common in Caucasian males and occur more frequently in patients who are RF positive. Rheumatoid nodules occur most commonly at pressure points such as the extensor surfaces of the forearms, fingers, occiput, ischial areas, and the Achilles tendon, but may also occur within internal tissues of the body: central nervous system, heart, pericardium, lungs, pleura, peritoneum, bones, vocal cords, sclera, and the mesentery.
From a histological standpoint, rheumatoid nodules are characterized by a central area of necrosis that includes collagen fibrils, fibrin, and proteins. Surrounding this central area are palisading epithelioid cells and chronic inflammatory cells. Fibroblasts are also present within the nodule and produce significant quantities of metalloproteases. Similarly, histology from our case demonstrated extensive mesenteric fat necrosis, chronic inflammation and fibrosis. Immunohistochemical staining of rheumatoid nodules has shown positive staining of epithelioid cells for HLA-DR, CD68, lysozyme, MMP-2, MMP-3, MMP-9 and Ki67. These markers are helpful but may not provide adequate discrimination to rule out a malignancy as many tumors are also positive for MMPs.
Accelerated rheumatoid nodulosis
There have been numerous reports of accelerated rheumatoid nodulosis, defined as a significant increase in the size and number of rheumatoid nodules, secondary to the use of methotrexate[1, 10, 11]. RF seropositivity seems to be a risk factor for the development of these accelerated nodules, and they usually favor the hands, but can also occur in various other anatomic locations. Most of these accelerated nodules are histologically identical to the classic rheumatoid nodules described earlier[1, 11]. In addition to methotrexate, azathioprine has also been associated with this phenomenon of accelerated rheumatoid nodulosis.
Our seropositive patient actually had a history of methotrexate use and this may have been the etiological agent responsible for the accelerated rheumatoid nodulosis evident in his small bowel mesentery. This medication was completely discontinued and the patient was instead started on etanercept and low dose prednisone, allowing for good control of his RA and moderate regression of the abdominal rheumatoid nodules.
Rheumatoid nodules should be included in the differential diagnosis of a patient who presents with an intra-abdominal mass and a history of RA. Special attention should be paid to the medication regimen of a patient with RA, as some of these agents have been shown to exacerbate the growth of rheumatoid nodules.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors would like to thank the VAGLA pathology department and specifically Dr. G.H. Pez for providing the histological images and insightful discussions regarding the preoperative differential diagnosis as well as the final diagnosis being consistent with RA nodules.
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