Splenic sarcoidosis: An unusual aetiology of agranulocytosis

Abstract

A 18-year-old French Caribbean male with no medical past history was referred for night sweats and severe neutropenia (absolute neutrophil count <0.2 G/L). There was no fever or wasting, and physical examination was unremarkable. There was no atypical cell or excess of large granular lymphocytes on peripheral blood smear and peripheral blood immunophenotyping found a normal lymphocytes subpopulations count. Bone marrow smear and bone marrow biopsy disclosed a mild granulocytic hypoplasia with a normal representation of granulocytic progenitors at all stages of differentiation without malignant cells. Antineutrophil antibodies were negative. Serologies for human immunodeficiency virus, human T-cell leukemia virus-1, cytomegalovirus, and B and C hepatitis virus were negative and Epstein-Barr virus serology was of IgG-type. Total body computerized tomography scan revealed a mild splenomegaly (15 cm height) with diffuse nodular lesions, with no lymph node enlargement. (18)F-fluoro-2-deoxy-D-glucose positron emission tomography showed an intense splenic uptake. A laparoscopic splenectomy was therefore performed ( Image 1). The spleen weighted 480 g; on gross sections besides the clearly discernable white pulp, several nodules measuring 1–3 cm, were randomly scattered. These reddish nodules were more easily observed after formalin fixation. On histology, the white pulp was normal with reactive germinal centers without lymphoma infiltration. The reddish nodules were made of multiple epithelioid and giant-cell granulomas (black arrow); fibrinoid necrosis was rarely observed. Comparable granulomas were present in splenic hilar lymph nodes. Special stains for acid-fast bacilli and fungi were negative. The diagnosis of sarcoidosis was supported by the pathological findings. Exhaustive explorations found no other organ involvement and serum calcium and angiotensin convertase enzyme levels were normal. Serum protein electrophoresis disclosed a polyclonal hypergammaglobulinemia (22 g/L) with no monoclonal component on immunofixation. The patient's status did not require any further therapy, as night sweats did not recur and neutrophil count recovered completely some weeks after splenectomy. Sarcoidosis is an unusual etiology of agranulocytosis [1, 2]. In the absence of lung or other systemic involvement, splenic sarcoidosis can mimic more ominous neoplastic or infectious disease [3] and in this context only splenectomy allows to establish the diagnosis. Interestingly, splenectomy may also allow the total and rapid resolution of agranulocytosis, as it was observed for our patient. This observation supports clear evidence that sarcoidosis granulomas are involved in the occurrence agranulocytosis, probably through either a direct or indirect secretion of mediators of neutropenia.