This lymph node from a 77-year-old woman with suspected metastatic tonsil cancer showed a diffuse proliferation (panel A: hematoxylin and eosin [H&E] stain, original magnification ×100) of small- to medium-sized mature lymphoid cells with scant cytoplasm (panel B: Giemsa stain, original magnification ×400), intermixed with prolymphocytes and paraimmunoblasts (panel B inset: Giemsa stain, original magnification ×640) in proliferation centers. Areas of coagulation necrosis (panel C: H&E stain, original magnification ×100) contained cells with eosinophilic nuclear inclusions intermixed with debris and granulocytes (panel D: H&E stain, original magnification ×800). The lymphoid cells expressed CD20, CD5, LEF1, and, focally, CD23, consistent with a diagnosis of small lymphocytic leukemia (SLL); showed increased proliferation (panel E: MIB1 stain, original magnification ×200); showed strong positivity for p53 (panel F: P53 stain, original magnification ×200) with confirmed TP53 mutation; and interspersed Epstein-Barr virus (EBV)+ and LMP1+ cells (panel G: EBV-encoded small RNAs in situ hybridization, original magnification ×100). The nuclear inclusions in the necrosis were positive for herpes simplex virus (HSV) (panel H: HSV I and II stain, original magnification ×200).
This case highlights the propensity for local reactivation of latent viral infections in the background of chronic lymphocytic leukemia (CLL)/SLL, due to immune dysregulation even in untreated patients. Neoplastic B cells in CLL act as HSV antigen-presenting cells and are readily infected. HSV lymphadenitis is an exceedingly rare finding, but characteristically shows rapid lymph node enlargement and is an important differential diagnosis for Richter transformation, recommending a low threshold for HSV staining in the setting of necrosis.
This lymph node from a 77-year-old woman with suspected metastatic tonsil cancer showed a diffuse proliferation (panel A: hematoxylin and eosin [H&E] stain, original magnification ×100) of small- to medium-sized mature lymphoid cells with scant cytoplasm (panel B: Giemsa stain, original magnification ×400), intermixed with prolymphocytes and paraimmunoblasts (panel B inset: Giemsa stain, original magnification ×640) in proliferation centers. Areas of coagulation necrosis (panel C: H&E stain, original magnification ×100) contained cells with eosinophilic nuclear inclusions intermixed with debris and granulocytes (panel D: H&E stain, original magnification ×800). The lymphoid cells expressed CD20, CD5, LEF1, and, focally, CD23, consistent with a diagnosis of small lymphocytic leukemia (SLL); showed increased proliferation (panel E: MIB1 stain, original magnification ×200); showed strong positivity for p53 (panel F: P53 stain, original magnification ×200) with confirmed TP53 mutation; and interspersed Epstein-Barr virus (EBV)+ and LMP1+ cells (panel G: EBV-encoded small RNAs in situ hybridization, original magnification ×100). The nuclear inclusions in the necrosis were positive for herpes simplex virus (HSV) (panel H: HSV I and II stain, original magnification ×200).
This case highlights the propensity for local reactivation of latent viral infections in the background of chronic lymphocytic leukemia (CLL)/SLL, due to immune dysregulation even in untreated patients. Neoplastic B cells in CLL act as HSV antigen-presenting cells and are readily infected. HSV lymphadenitis is an exceedingly rare finding, but characteristically shows rapid lymph node enlargement and is an important differential diagnosis for Richter transformation, recommending a low threshold for HSV staining in the setting of necrosis.
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![This lymph node from a 77-year-old woman with suspected metastatic tonsil cancer showed a diffuse proliferation (panel A: hematoxylin and eosin [H&E] stain, original magnification ×100) of small- to medium-sized mature lymphoid cells with scant cytoplasm (panel B: Giemsa stain, original magnification ×400), intermixed with prolymphocytes and paraimmunoblasts (panel B inset: Giemsa stain, original magnification ×640) in proliferation centers. Areas of coagulation necrosis (panel C: H&E stain, original magnification ×100) contained cells with eosinophilic nuclear inclusions intermixed with debris and granulocytes (panel D: H&E stain, original magnification ×800). The lymphoid cells expressed CD20, CD5, LEF1, and, focally, CD23, consistent with a diagnosis of small lymphocytic leukemia (SLL); showed increased proliferation (panel E: MIB1 stain, original magnification ×200); showed strong positivity for p53 (panel F: P53 stain, original magnification ×200) with confirmed TP53 mutation; and interspersed Epstein-Barr virus (EBV)+ and LMP1+ cells (panel G: EBV-encoded small RNAs in situ hybridization, original magnification ×100). The nuclear inclusions in the necrosis were positive for herpes simplex virus (HSV) (panel H: HSV I and II stain, original magnification ×200).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/136/26/10.1182_blood.2020008950/1/m_bloodbld2020008950f1.png?Expires=1765916894&Signature=Yh9xOxrw1XU~RW~vLGxE0~5QYn5N33eZKAuavi8FJHdBcv37khDdVPekTn834v-M2A4YTFyG3Z9n-Y2DCGKPlVvfLHuj6gXBeOrxkN~Otw4akLxcLvN67U2B2hlUt5dxrPosgzk-G1srhyBmWufjmbD-k9fQdBsz1-kNwPl05HRYLoQR0aVHGPXjb1NVrO-1YMC2mFpcCBukiYVF4V9LBASck0S1OOsninB9bCNTdCHAkx3Z3e9MVWMHMCriiCNl-m6Ns3SD5U9fLm~tXIlPAQs-3meM9Vi119JYJhAmnjIzh-UlVhXeWjU~4kmEZuRH5lISOhB65W95esJBGeWPiw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
![This lymph node from a 77-year-old woman with suspected metastatic tonsil cancer showed a diffuse proliferation (panel A: hematoxylin and eosin [H&E] stain, original magnification ×100) of small- to medium-sized mature lymphoid cells with scant cytoplasm (panel B: Giemsa stain, original magnification ×400), intermixed with prolymphocytes and paraimmunoblasts (panel B inset: Giemsa stain, original magnification ×640) in proliferation centers. Areas of coagulation necrosis (panel C: H&E stain, original magnification ×100) contained cells with eosinophilic nuclear inclusions intermixed with debris and granulocytes (panel D: H&E stain, original magnification ×800). The lymphoid cells expressed CD20, CD5, LEF1, and, focally, CD23, consistent with a diagnosis of small lymphocytic leukemia (SLL); showed increased proliferation (panel E: MIB1 stain, original magnification ×200); showed strong positivity for p53 (panel F: P53 stain, original magnification ×200) with confirmed TP53 mutation; and interspersed Epstein-Barr virus (EBV)+ and LMP1+ cells (panel G: EBV-encoded small RNAs in situ hybridization, original magnification ×100). The nuclear inclusions in the necrosis were positive for herpes simplex virus (HSV) (panel H: HSV I and II stain, original magnification ×200).](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/136/26/10.1182_blood.2020008950/1/m_bloodbld2020008950f1.png?Expires=1765916895&Signature=NspeH5mt3UfZGJG2IFkvv46BvvfbJ~pppmTWUaNKPjlj9Y6kL-1rmJiTJedmvVYOEpBClv3hFEpDw8gifgHdYtj~9u2h1837n0zoIzlKKLARlrXLCokC51Rw80Md0cbYqOx7Bg1GqPOHNH9kMfik8TPSthMkHT8YdnSU3CV0luj81swt-dHVrL7JmnKykklWnSmrUDO0clY2HMnzHUUgRfPx~RTp4oyaNpYE3kza8AVqZqImW1J6li3fYtvDcKNB9ia4uvelNvX~055L9bwlUtHWAh2aWdEMgoCFX7npNGWaJ1XJZ70mgFAhG91BYtuV6r6koh0Ma9KwhgEPoVm86A__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)