An autopsy case of pneumococcal Waterhouse-Friderichsen syndrome with possible functional asplenia/hyposplenia

Abstract

We report an autopsy case of rapid progressive Waterhouse-Friderichsen syndrome (WFS) associated with Streptococcus pneumonia infection in a previously healthy man. Although he once visited a hospital about 6 hours before death, the both physical and serological examination did not show any sign of overwhelming infection. Autopsy showed massive adrenal hemorrhage without inflammation, and showed proliferation of gram positive cocci and microthrombosis in the vessels of many organs. The pathological change of respiratory tract was extremely minimal. Size and weight of the spleen possible decreased than normal. However, histological examination showed that obscuration of germinal center and decreasing the immunological cells of mantle and marginal zone. Immunohisitochemically, marked decreasing the marginal zone macrophages, which are positive for specific intercellular adhesion molecule grabbing nonintegrin receptor-1 (SIGN-R1) and macrophage receptor with collagenous structure (MARCO), were decreased comparing with age-matched control case. Polymerase chain reaction (PCR) assay using each DNA, extraction from formalin-fixed paraffin-embedded specimen (FFPE) samples of lung, adrenal gland, heart, spleen, and kidney showed positive the ply gene and the lytA gene specific for Streptococcus pneumonia. Present case showed possible acquired atrophy of spleen, especially decreasing marginal zone macrophage may correlate with rapid progression of sepsis of Streptococcus pneumonia with massive adrenal hemorrhage. In addition, present case showed the usefulness of PCR using FFPE for the postmortem diagnosis of WFS.

Keywords: Asplenia/hyposplenia; Streptococcus pneumonia; Waterhouse-Friderichsen syndrome; autopsy.

Figure 1

Pathological findings of the Waterhouse-Friderichsen syndrome. (A) Gross appearance of adrenal gland, (B) Low power view of adrenal gland. Massive hemorrhage can be seen. (C) Moderate power view of adrenal hemorrhage, (D) Proliferating gram positive cocci (Gram staining), (E) Fibrin thrombi were found in capillaries of glomeruli (phosphotungstic acid-hematoxylin staining). Scale bar = 1 mm (A); 100 μm (B); 50 μm (C); 20 μm (D, E).

Figure 2

Pathological findings of the spleen in Waterhouse-Friderichsen syndrome. (A) Low power view of the spleen shows a decreased volume of white pulp. Germinal center of lymph follicle cannot be seen (hematoxylin and eosin stain). (B) Decreasing number of cells in the subcapsular region with fine fibrosis. (Masson trichrome staining), (C-H) Immunohistochemical analysis of WFS (C-E, G) and the control case (F, H). Fewer CD21 positive follicular dendritic cells (C) and CD5 positive mantle zone lymphocytes (D) are evident. Decreased MARCO (E) and SIGN-R1 (G) positive cells are also evident compared to the control case (F, H). Scale bar = 100 μm (A); 20 μm (B-H).

Figure 3

Results of PCR analysis. Presence of Streptococcus pneumoniae is shown in the lung and the adrenal gland of the patient by PCR analyses. Specific targets were amplified by real-time PCR using the ply and the lytA gene from S. pneumonia and β-actin as an internal control, showing detection of the 225-, the 272-, and the 150-bp products, respectively. M; marker, C1; control case 1, C2; control case 2.