PMC3916803_01
Chest X-ray and computed tomography scan images on admission. (A) Chest X-ray showing minimal bilateral hilar lymphadenopathy with clear lung fields. (B) Chest computed tomography scan clearly showing mild bilateral hilar lymphadenopathy (arrows) without pulmonary infiltrates.
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A chest X-ray showed minimal bilateral hilar lymphadenopathy (BHL); however, a chest computed tomography (CT) scan clearly revealed mild BHL without pulmonary infiltrates (Figure 1).
Positron emission tomography-computed tomography images on admission. (A) Coronal and sagittal positron emission tomography images on admission showing 18F-fluorodeoxyglucose uptake in peripharyngeal, axillary, mediastinal, hilar, iliac and inguinal lymph nodes and spleen. An arrow indicates 18F-fluorodeoxyglucose uptake at submandibular dental roots, suggesting submandibular periodontitis. (B) Fused positron emission tomography-computed tomography image showing left hilar lymph node swelling with moderate 18F-fluorodeoxyglucose uptake. (C) Fused positron emission tomography-computed tomography image showing remarkable 18F-fluorodeoxyglucose uptake in the spleen.
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In addition, remarkable FDG uptake at her submandibular dental roots wearing ceramic crowns was observed, suggesting chronic periodontitis (Figure 2).
Histopathology of the lymph node. (A) Langhans giant cells with various degrees of eosin stainability are seen. One giant cell (black arrow) shows moderately eosinophilic condensed cytoplasm, and another one (blue arrow) has a remarkably eosinophilic condensed cytoplasm with multiple condensed nuclei. Hematoxylin and eosin stain (underx20 magnification objective). (B) The sarcoid granuloma consisting of epithelioid cells is somewhat ill defined from surrounding tissue. Lymphocytes are seen surrounding the sarcoid granuloma, which is reminiscent of cellular immune reaction. Hematoxylin and eosin stain (underx40 magnification objective).
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A right inguinal lymph node biopsy specimen, which was obtained 9 days after the initiation of CAM treatment, showed non-caseating epithelioid cell granulomas with abundant multinucleated giant cells (Langhans giant cells) in the background of epithelioid cells, macrophages, lymphocytes and plasma cells (Figure 3A). In the present case, the sarcoid granulomas were somewhat diminished in size and number, and ill defined from surrounding tissue (Figure 3B). In addition, some of the giant cells showed condensed heterochromatin (pyknosis; Figure 3A), multiple fragmented nuclei (apoptotic bodies; Figure 4A) and multiple nuclear remnants with indistinct nuclear configurations in the eosinophilic condensed cytoplasm (Figure 4B).
Histopathology of the lymph node. (A) Multiple fragmented condensed nuclei (apoptotic bodies) are seen in the eosinophilic degenerated giant cell (arrow) with fibrotic configuration. Hematoxylin and eosin stain (underx40 magnification objective). (B) Two eosinophilic degenerated giant cells (blue and black arrows) showing indistinct nuclear configurations, which are probably in the advanced stage of degeneration. One cell (blue arrow) shows fibrotic configuration. Yellow arrows indicate relatively intact giant cells. Hematoxylin and eosin stain (underx20 magnification objective). (C) Black arrows indicate three eosinophilic homogenous degenerated substances (hyaline-like degeneration) with fibrotic configuration. Nuclear remnants are barely visible. Morphological transition from degenerating/degenerated giant cells to hyaline-like degeneration is shown. Hematoxylin and eosin stain (underx20 magnification objective). (D) A degenerating giant cell (black arrow) and a degenerated giant cell (blue arrow) showing increased periodic acid-Schiff stainability. Periodic acid-Schiff stain (underx20 magnification objective).
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In addition, some of the giant cells showed condensed heterochromatin (pyknosis; Figure 3A), multiple fragmented nuclei (apoptotic bodies; Figure 4A) and multiple nuclear remnants with indistinct nuclear configurations in the eosinophilic condensed cytoplasm (Figure 4B). These degenerated giant cells appeared to have transformed into eosinophilic homogenous substances with fibrotic configuration (that is, hyaline-like degeneration; Figure 4C). The degenerating/degenerated giant cells showed slightly increased stainability with periodic acid-Schiff (Figure 4D).
Propionibacterium acnes within sarcoid granulomas in the lymph node. Hematoxylin and eosin staining (left) and immunostaining with PAB antibody specific to Propionibacterium acnes (counterstained with hematoxylin) (right) are shown pairwise. (A, B) Square indicates an eosinophilic homogenous degenerated substance (hyaline-like degeneration). Positive reaction products (brown dots) are located preferentially in the hyaline-like degeneration (underx40 magnification objective). (C, D) In the sarcoid granuloma, a small positive dot is seen in an epithelioid cell (red arrow). Some fine reaction products are sparsely scattered in the sarcoid granuloma. A black arrow indicates a Langhans giant cell (underx40 magnification objective). Abbreviations: HE, hematoxylin and eosin; P., Propionibacterium.
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Small positive dots were scattered sparsely in the sarcoid granulomas (Figure 5).
Immunohistochemical staining of the lymph node for immunoglobulin G, immunoglobulin D and immunoglobulin G4. (A) Degenerating giant cells (yellow arrows) and degenerated homogenous substance, possible hyaline-like degeneration (black arrows), are moderately positive for immunoglobulin G. By contrast, an intact giant cell (white arrow) is negative for immunoglobulin G. Infiltrated plasma cells are distinctly positive for immunoglobulin G (underx20 magnification objective). (B) The giant cell (arrow) is faintly positive for immunoglobulin D (underx20 magnification objective). (C) The giant cells are negative for immunoglobulin G4. The immunoglobulin G4-positive plasma cells are sporadic in frequency (underx20 magnification objective). Abbreviations: IgD, immunoglobulin D; IgG, immunoglobulin G; IgG4, immunoglobulin G4.
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IgA, IgM, IgD and IgG4 to dispel the possibility of IgG4-related disease (Figure 6). Infiltrated plasma cells were positive for IgG, IgA, IgM, IgD and IgG4 at different degrees. Some of the giant cells and degenerated homogenous substances were positively stained with anti-IgG antibody, and the reaction was more intense in degenerating/degenerated giant cells than in intact ones (Figure 6A). The giant cells were faintly stained with anti-IgD antibody (Figure 6B) but not with anti-IgA (not shown), anti-IgM (not shown) and anti-IgG4 (Figure 6C) antibodies.
Clinical course during admission. After the initiation of clarithromycin treatment, the fever subsided within 1 week. The elevated levels of C-reactive protein returned to normal within 2 weeks and elevated soluble-interleukin-2 receptor levels were remarkably depressed within 3 weeks. Abbreviations: CAM, clarithromycin; CRP, C-reactive protein; s-IL2R, soluble-interleukin-2 receptor.
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The elevated levels of CRP returned to normal within 2 weeks and elevated s-IL2R levels were remarkably decreased within 3 weeks (Figure 7).
Positron emission tomography and fused positron emission tomography-computed tomography images 2 months after admission. Drastic resolution in axillary, mediastinal, iliac and inguinal lymph nodes is shown. The spleen (yellow arrow) shows no 18F-fluorodeoxyglucose uptake. However, submandibular dental roots (blue arrow) and peripharyngeal lymph nodes (black arrow) still show 18F-fluorodeoxyglucose uptake.
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The FDG uptake in her spleen also disappeared (Figure 8).