title: Spleen histology in children with sickle cell disease and hereditary spherocytosis: hints on the disease pathophysiology.
abstract: Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histologic and morphometric features of HS and SCD spleens, to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS, and control patients, the following parameters were considered: (i) macroscopic features, (ii) lymphoid follicle (LF) density, (iii) presence of perifollicular marginal zones, (iv) presence of Gamna-Gandy bodies, (v) density of CD8-positive sinusoids, (vi) density of CD34-positive microvessels, (vii) presence/distribution of fibrosis and smooth muscle actin (SMA)-positive myoid cells, and (viii) density of CD68-positive macrophages. SCD and HS spleens had similar macroscopic features. SCD spleens had lower LF density and fewer marginal zones than did HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than did controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, most HS spleens clustered with controls, whereas SCD grouped separately. A multiparametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS, and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.
authors: Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, 35121 Padova, Italy.
authors: Marco
authors: M
authors: Pizzi
authors: Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, M5G 1X8 Ontario, Canada.
authors: Fabio
authors: F
authors: Fuligni
authors: Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, 35121 Padova, Italy.
authors: Luisa
authors: L
authors: Santoro
authors: Hematopathology Unit, Sant'Orsola/Malpighi Hospital, 40138 Bologna, Italy.
authors: Elena
authors: E
authors: Sabattini
authors: Pediatric Surgery Unit, Department of Woman and Child Health, University of Padova, 35128 Padova, Italy.
authors: Martina
authors: M
authors: Ichino
authors: Department of Pathology, Bambino Gesù Children's Hospital, 00146 Rome, Italy.
authors: Rita
authors: R
authors: De Vito
authors: Nuclear Medicine Service, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Pietro
authors: P
authors: Zucchetta
authors: Clinic of Pediatric Hematology/Oncology, Department of Woman and Child Health, University of Padova, 35128 Padova, Italy.
authors: Raffaella
authors: R
authors: Colombatti
authors: Clinic of Pediatric Hematology/Oncology, Department of Woman and Child Health, University of Padova, 35128 Padova, Italy.
authors: Laura
authors: L
authors: Sainati
authors: Pediatric Surgery Unit, Department of Woman and Child Health, University of Padova, 35128 Padova, Italy.
authors: Piergiorgio
authors: P
authors: Gamba
authors: Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padova, 35121 Padova, Italy. Electronic address: ral@unipd.it.
authors: Rita
authors: R
authors: Alaggio
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D006461:Hemolysis; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D055806:Microvessels / Q000473:pathology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013103:Spherocytosis, Hereditary / Q000150:complications / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D013154:Spleen / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D013156:Splenectomy
chemical_list: D015415:Biomarkers
keywords: Hereditary spherocytosis; Sickle cell disease; Spleen; Splenic pathophysiology; Vasculopathy