A 26-year-old man has noted lumps in his neck that have been enlarging for the past 6 months. On physical examination, he has a group of enlarged, nontender right cervical lymph nodes. A biopsy of one of the lymph nodes microscopically shows macrophages, lymphocytes, neutrophils, eosinophils, and a few plasma cells. There are scattered CD15+ large cells with multiple nuclei or a single nucleus with multiple nuclear lobes, each with a large inclusion-like nucleolus. What is the most likely cell of origin with infectious agent for these large cells?

**Core Concept**
The patient's presentation of enlarged, nontender cervical lymph nodes with a mixed cellular infiltrate, including scattered large cells with characteristic nuclear features, suggests a diagnosis of Hodgkin lymphoma (HL). The presence of CD15+ large cells with multiple nuclei or a single nucleus with multiple nuclear lobes, each with a large inclusion-like nucleolus, is a hallmark of Reed-Sternberg cells, the malignant cells of HL.

**Why the Correct Answer is Right**
The large cells in question are Reed-Sternberg cells, which are the malignant cells of Hodgkin lymphoma. These cells are characterized by their distinctive nuclear morphology, including multiple nuclei or a single nucleus with multiple nuclear lobes, each containing a large inclusion-like nucleolus. Reed-Sternberg cells are typically CD15+ and can also express CD30, a member of the tumor necrosis factor receptor family. The presence of these cells in the biopsy is diagnostic of Hodgkin lymphoma. The exact cell of origin for Reed-Sternberg cells is still a topic of debate, but it is thought to be a germinal center B cell that has undergone malignant transformation.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because it does not accurately describe the cell of origin for the large cells in question. While lymphocytes are present in the biopsy, the large cells are not lymphocytes.
**Option B:** This option is incorrect because it does not accurately describe the cell of origin for the large cells in question. While macrophages are present in the biopsy, the large cells are not macrophages.
**Option C:** This option is incorrect because it does not accurately describe the cell of origin for the large cells in question. While plasma cells are present in the biopsy, the large cells are not plasma cells.

**Clinical Pearl / High-Yield Fact**
Reed-Sternberg cells are the hallmark of Hodgkin lymphoma and are characterized by their distinctive nuclear morphology. The presence of these cells in a lymph node biopsy is diagnostic of HL. It is worth noting that Hodgkin lymphoma can be divided into two main types: classical HL and nodular lymphocyte-predominant HL (NLPHL). Reed-Sternberg cells are characteristic of classical HL.

**Correct Answer:** D. Reed-Sternberg cells are the malignant cells of Hodgkin lymphoma.

✓ Correct Answer: A. B lymphocyte, Epstein-Barr virus