Composition and significance of splenic Gamna-Gandy bodies in sickle cell anemia

Summary

Children with sickle cell anemia may undergo acute splenic sequestration. Splenectomy is performed in an attempt to reduce further events. Histologic studies of spleens have revealed the presence of granuloma-like nodules, known as Gamna-Gandy bodies with amorphous inclusions; however, their significance is unknown. The medical case records and histologic samples of consecutive children with sickle cell anemia treated with splenectomy between 2001 and 2007 at Our Lady's Children's Hospital, Dublin, were reviewed. Seventeen patients were identified. Gamna-Gandy bodies were studied by scanning electron microscopy and x-ray fluorescence spectroscopy. Gamna-Gandy bodies were identified in 7 (41%) patients, and amorphous inclusions were always seen. Patient age correlated significantly with Gamna-Gandy bodies (P = .002). Scanning electron microscopic analysis demonstrated the crystalline nature of Gamna-Gandy bodies and the chemical composition (C 47.1%; O₂ 29.7%; P 9.0%; K⁺ 0.4%; Ca²⁺ 6.4%; Fe²⁺ 7.4%), whereas x-ray diffraction studied the structure (CaPO₄ ∙ FeOH). A crystal-formation gradient was observed, increasing from the red pulp to the white pulp. Our study shows that Gamna-Gandy bodies contain crystals and that their formation is age dependent. We also demonstrated the crystal structure and chemical composition and the relationship between Gamna-Gandy bodies and chest crises presplenectomy or postsplenectomy.

Introduction

Acute splenic sequestration occurs in children as young as 5 weeks, but it is seen most often in children between the age of 3 months and 5 years and represents a life-threatening situation in sickle cell anemia (SCA) [1], [2]. It is caused by acute pooling of blood cells in the spleen, trapping erythrocytes, and is defined by hemoglobin decrease of at least 2 g/dL, associated with elevated reticulocyte count and an acutely enlarged spleen [3]. The classic clinical signs are splenomegaly, abdominal pain, abdominal tenderness, pallor, and irritability. Treatment is based on top-up transfusion or red blood cell exchange. Transfusion delay could lead to hypovolemic shock and death [4]. Since the introduction of efficacious vaccinations against capsulated bacteria (eg, Haemophilus influenzae, Streptococcus pneumoniae, etc), splenectomy (SP) has become an accepted procedure in the management of SCA patients undergoing recurrent splenic crisis.

Histologic studies of SCA spleens have shown the presence of granuloma-like nodules, known as Gamna-Gandy bodies (GGBs) (Fig. 1). The true significance of GGBs and their inclusion is still unknown; the early hypothesis formulated by C. Gamna that GGBs originate by periarterial hemorrhage followed by fibrosis and impregnation of iron pigments is to date the most credible [5]. Several pathologic reports from the early 20th century have attempted to provide a very accurate description of this phenomenon; however, these articles are difficult to access because the PubMed database contains medical citations only from 1950 onward. In addition, the current literature is limited to a few radiologic case reports correlated with simplistic histopathologic descriptions of the phenomenon. In this study, all articles on GGB published after 1905 in several languages were reviewed.

We present a series of pediatric cases of splenic GGB in SCA. The morphological slide review was correlated with a detailed scanning electron microscopy (SEM) with x-ray fluorescence analysis (XRF) in energy dispersive spectroscopy (EDS) mode of the histopathologic samples using high and low magnification [6]. In addition, XRF by SEM allowed the identification of the chemical constituents of GGB crystals and their distribution within splenic architecture.