Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis

J Clin Exp Hematop. 2021;61(3):173-179. doi: 10.3960/jslrt.21008.


Neoplastic programmed cell death ligand 1 (PD-L1) expression, activated by PD-L1 gene alterations, is strongly associated with classic Hodgkin lymphoma (CHL). This association enabled a diagnostic consensus for lymphocyte-depleted CHL (LD-CHL), a previously enigmatic disease. We describe two patients with LD-CHL and primary extranodal disease. One patient was a 92-year-old female (Case #1) with a large mass that involved the uterus combined with swollen lymph nodes in the pelvic cavity. The second patient was a 76-year-old female (Case #2) with human T-cell leukemia virus type 1 (HTLV-1) who initially exhibited massive bone marrow involvement without peripheral lymphadenopathies. Biopsies of these tumors from the cervix uteri and bone marrow, respectively, revealed lesions rich in Hodgkin and Reed-Sternberg (H-RS) cells and diminished populations of other cell populations. Immunohistochemistry demonstrated that these H-RS cells expressed CD30, BOB1, and fascin, but not CD15, CD20, PAX5, or OCT2. They also expressed PD-L1, which led to our preferred diagnosis of LD-CHL in both patients. Epstein-Barr virus was associated with LD-CHL in Case #1, but not in Case #2. Both patients were deemed too frail for treatment. They died of disease at 1 (Case #1) and 15 months (Case #2) after the diagnosis. These findings highlight the abnormal biological behavior of this immune-escape-related lymphoid neoplasm in patients with immunodeficiency due to immune senescence and HTLV1 infection.

Keywords: fragile elderly; lymphocyte-depleted classic Hodgkin lymphoma; primary extranodal disease; programmed cell death ligand 1.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biopsy
  • Diagnosis, Differential
  • Fatal Outcome
  • Female
  • HTLV-I Infections / complications
  • Hodgkin Disease / diagnosis*
  • Hodgkin Disease / etiology
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / therapy
  • Humans
  • Immunohistochemistry
  • Immunologic Deficiency Syndromes / complications
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • Reed-Sternberg Cells / pathology
  • Tumor Escape / immunology