Erythropoietin-producing tubercle granuloma in a hemodialysis patient

Abstract

Background: We describe a case of a fever of unknown etiology that was caused by a caseating tubercle granuloma which produced erythropoietin. To our knowledge, this is the first report of an erythropoietin- producing granuloma.

Case presentation: A 48-year-old Japanese man with a 5-year history of maintenance hemodialysis for diabetic nephropathy presented with an intermittent fever over a few months. During febrile periods he developed erythema nodosum on his legs. Computed tomography showed axillary lymph node enlargement and this was further corroborated by a gallium scan that revealed high gallium uptake in these nodes. A Mantoux test was positive and an interferongamma release assay for tuberculosis diagnosis was also positive. Lymph node tuberculosis was suspected and the patient underwent lymphadenectomy. Histological analysis of the lymph nodes revealed a caseating granuloma that showed positive results on an acid-fast bacteria stain and a Mycobacterium tuberculosis polymerase chain reaction test. After lymphadenectomy, however, the patient's hemoglobin levels rapidly decreased from 144 to 105 g/L, and this was further compounded by a decrease in serum erythropoietin from 223 mIU/mL to 10.7 mIU/mL by postoperative day 21. We suspected the tubercle to be a source of the erythropoietin and this was further confirmed by in situ hybridization.

Conclusions: We report for the first time ectopic erythropoietin production by a tuberculous lymph node. Our observations are substantiated by a postoperative decline in his erythropoietin level and a clinical requirement for erythropoietin treatment.

Figure 1

Images of right axillary lymph node tuberculosis. Images of computed tomography (A) and gallium scanning (B). (A) Non-enhanced computed tomography scan showing enlarged right axillary lymph nodes (arrow). (B) Gallium scan showing abnormal uptake in axillary lymph nodes (arrow).

Figure 2

Pathological images of tubercle granuloma. Pathological findings (A) and acid-fast bacteria stain (B) of resected axillary lymph node. (A) Histopathological findings of the resected specimen include caseous necrosis and an epithelioid granuloma with Langhans giant cells (arrow) (PAS staining, ×100). (B) Microphotograph of the resected axillary lymph node stained with Ziehl-Neelsen stain (×400) showing acid-fast stain-positive bacilli within the tissue (arrow).

Figure 3

Epo expression in tubercle granuloma.In situ RNA hybridization of the resected axillary lymph node (A) and immunohistochemistry for CD68 (B), CD20 (C), and CD8 (D). (A) In situ hybridization revealing the expression of Epo mRNA in non-epithelioid cells in lymph nodes. Methods are described in the Additional file 1. Positive signals were observed in the granuloma (arrow) (×200). (B) CD68-positive cells were observed in the granuloma (arrow) (×200). (C, D) CD20- and CD8-positive cells were rarely observed in the granuloma (arrow) (×200).