PMC10061130_01
Computed tomography (CT) scans show an occupation in the right middle mediastinum (white arrow), with a CT value of 20-80 Hu (A). The resected mass is well-demarcated, and exhibits a solid and lobulated appearance in cut surface (B).
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The maximum diameter was about 10cm ( Figure 1A ). It was solid and nodular in cut surface and tenacious to soft in texture ( Figure 1B ). By contrast, in other areas they exhibited enlarged and hyperchromatic nuclei, increased mitotic activity (5 per 10 high power fields), and atypical mitoses ( Figure 3B ,  Supplementary Figure 1 ). The morphologic transition could be perceived between the mild and dysplastic cellular areas ( Figure 3C ,  Supplementary Figure 1 ).
The mass generally exhibits a histologic structure of Castleman disease of hyaline-vascular type (HVCD). Beneath the capsule (white arrow), the lymphoid follicles are unevenly distributed and the follicles are generally atrophied (black arrow) (A). The germinal centers are characterized by a depletion of lymphoid cells and proliferation of follicular dendritic cells (black arrow). The mantle zone lymphocytes are concentrically arranged and impart an onion-skin-like appearance (B, C). Toward the central region, the interfollicular areas are widened by storiform-arranged spindle cells under low power (back arrow) (D). Those spindle cells illustrate long, slender cytoplasm and vesicular to fine chromatin nuclei. No distinctive nuclear atypia is perceived in these fields (E, F).
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Microscopically, the lymphoid follicles were unevenly distributed under the capsule ( Figure 2A ). The hyperplastic follicular dendritic cells in germinal center and concentrically-arrayed lymphocytes in mantle zone could be easily observed ( Figures 2B, C ). The interfollicular fields were dominated by the compact plump spindle cells with a fascicular and storiform arrangement ( Figure 2D ). No obvious nuclear atypia or pleomorphism was presented ( Figures 2E, F ,  3A ). Neoplastic necrosis was observed focally ( Supplementary Figure 2 ). Those lymphocytes illustrated oval nuclei, darkly-stained chromatin and inconspicuous nucleoli ( Figures 2E, F ).
Apart from the cells with a bland appearance (A), some of the spindle cells demonstrate remarkably pleomorphism. Abnormal mitoses (white arrow) and multinucleated tumor cells (black arrow) could be observed (B). There exists a morphological transition between the bland (left side of the dot line) and atypical cellular regions (right side of the dot line). The high power fields of the red square and the yellow square are corresponding to (A, B), respectively (C).
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No obvious nuclear atypia or pleomorphism was presented ( Figures 2E, F ,  3A ). By contrast, in other areas they exhibited enlarged and hyperchromatic nuclei, increased mitotic activity (5 per 10 high power fields), and atypical mitoses ( Figure 3B ,  Supplementary Figure 1 ). The morphologic transition could be perceived between the mild and dysplastic cellular areas ( Figure 3C ,  Supplementary Figure 1 ). In addition, proliferated small vessels were found tightly intermixed with the stromal cells ( Supplementary Figure 3 ).
Comparison of the immunostaining features of the bland (A, C, E, G, I) and atypical spindle cells (B, D, F, H, J). They are focally immunoreactive with SMA (C, D) and CD68 (E, F). However, the staining of p53 is negative in the former (G), while strongly expressed in the latter (H). In addition, an increased ki-67 index is noticed in the atypical spindle cells (I, J).
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SMA and CD68 ( Figures 4A-F ). Strong P53 staining and increased Ki-67 index (20%) was detected in regions with notably cellular atypia, while negative P53 staining and low Ki-67 index (10%) was presented in spindle cells with benign morphology ( Figures 4G-J ). On the other hand, they were uniformly negative for CD21, CD23, CD35, SSTR2, D2-40, and CXCL13 ( Supplementary Figure 4 ).
A moderate number of small lymphocytes are unevenly infiltrated inside the interfollicular regions (A). They are variably immunostained with CD3 (B), CD10 (C), and TdT (D).
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The interfollicular small lymphocytes were immunoreactive with CD3 and CD5, and some of them were positive for TdT and CD10 ( Figures 5A-D ).