A 28-year-old woman presents with painless cervical lymphadenopathy and B symptoms. Excisional lymph node biopsy is performed. Histology reveals a polymorphous inflammatory background with scattered large cells. The structure marked **A** in the diagram shows a large binucleated cell with prominent eosinophilic nucleoli giving an 'owl-eye' appearance. Immunohistochemistry shows this cell is CD15+, CD30+, and CD20−. Which of the following best describes the cell lineage and diagnostic significance of the structure marked **A**?
A. Mummified apoptotic cell with retained CD20 expression, characteristic of nodular sclerosis subtype
B. Histiocytic cell of monocytic origin with CD30 activation, seen in reactive lymphadenopathy
C. B-cell-derived malignant cell that has lost B-cell surface antigens, diagnostic of Hodgkin lymphoma
D. T-cell-derived neoplastic cell with aberrant CD15 expression, indicating nodular lymphocyte-predominant subtype
Explanation
Why B-cell-derived malignant cell that has lost B-cell surface antigens, diagnostic of Hodgkin lymphoma is right
The structure marked A is the classic Reed-Sternberg (R-S) cell, the pathognomonic diagnostic hallmark of Hodgkin lymphoma. According to Robbins & Cotran and WHO 5th edition, R-S cells are derived from germinal centre B-cells but characteristically lose B-cell surface antigens (CD20−, CD45−) while retaining CD15 and CD30. The binucleated morphology with prominent eosinophilic inclusion-like nucleoli ('owl-eye' appearance) in a polymorphous inflammatory background is diagnostic of classical Hodgkin lymphoma. This immunophenotype (CD15+, CD30+, CD20−) is the defining feature that distinguishes R-S cells from other lymphoid malignancies.
Why each distractor is wrong
T-cell-derived neoplastic cell with aberrant CD15 expression, indicating nodular lymphocyte-predominant subtype: R-S cells are B-cell-derived, not T-cell-derived. Nodular lymphocyte-predominant HL contains L&H ('popcorn') cells, which are CD20+, CD15−, and CD30−—the opposite immunophenotype of classic R-S cells.
Histiocytic cell of monocytic origin with CD30 activation, seen in reactive lymphadenopathy: R-S cells are neoplastic, not reactive histiocytes. While CD30 is positive, the CD20− phenotype and loss of B-cell antigens indicate malignant transformation, not reactive inflammation.
Mummified apoptotic cell with retained CD20 expression, characteristic of nodular sclerosis subtype: Mummified cells are apoptotic R-S cell variants but are not the classic diagnostic form. Retained CD20 expression is not typical of classic R-S cells; they are characteristically CD20−. This describes a different morphological variant.