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A 28-year-old previously healthy man comes to the office due to episodic fevers, night sweats, and weight loss for several months.  He emigrated from Kenya with his family at age 14.  He does not use tobacco, alcohol, or illicit drugs.  The patient works as a driving instructor and volunteers at a homeless shelter.  His temperature is 37.2 C (99 F).  Physical examination is normal with the exception of cervical lymphadenopathy.  A lymph node biopsy is performed, and histopathologic findings are shown in the image below.

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Which of the following is the most likely diagnosis?

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This patient most likely has classic Hodgkin lymphoma (HL).  The typical presentation is either nontender lymphadenopathy or lymphadenopathy incidentally detected on routine chest x-ray.  Many patients develop associated systemic B symptoms (fevers, night sweats, weight loss).  HL has a bimodal age distribution with a peak in the 20s (or younger in some countries) and another in the 60s.  The complete blood count and peripheral blood smear are usually unremarkable.

A lymph node biopsy can distinguish HL from benign causes of lymphadenopathy.  The key to diagnosing classic HL is detecting the characteristic Reed-Sternberg (RS) cell on hematoxylin and eosin preparation.  RS cells have ample cytoplasm, a multilobed nucleus or multiple nuclei, and inclusion-like nucleoli.  RS cells are seen against a background of lymphocytes, histiocytes, and eosinophils in classic HL.

(Choice A)  Burkitt lymphoma often presents as a mass in the abdomen/pelvis (or the jaw in the endemic [African] form, which has a peak incidence in boys around age 5).  However, histology would show a monotonous population of medium-sized lymphoid cells with many tingible body macrophages, giving a "starry sky" appearance.  High numbers of mitotic cells and apoptotic bodies would be seen.

(Choice B)  Follicular lymphoma shows aggregates of closely packed, neoplastic lymph node follicles.  Two major cell types, centrocytes (small cleaved cells) and centroblasts (large noncleaved cells), are observed.  Older adults tend to be affected.  Waxing and waning painless lymphadenopathy (typically without B symptoms) is common.

(Choice D)  Large B-cell lymphoma is characterized by diffuse sheets of large, atypical lymphoid cells with nuclei at least 5 times the size of small lymphocytes.  RS cells against a background of mixed inflammation is not a characteristic histologic feature of large B-cell lymphoma.

(Choice E)  Multiple myeloma, a plasma cell dyscrasia characterized by proliferation of clonal plasma cells, is predominantly a disease of the elderly.  It is characterized by osteolytic lesions, although spread to nodal and extranodal sites can occur.

(Choice F)  Tuberculosis is on the differential diagnosis for this patient, who is from Kenya, volunteers at homeless shelters, and has had night sweats and weight loss.  However, histology in tuberculosis would show caseating granulomas, not RS cells.

Educational objective:
The presence of Reed-Sternberg (RS) cells on lymph node biopsy is a diagnostic feature of classic Hodgkin lymphoma.  RS cells have abundant cytoplasm, a multilobed nucleus or multiple nuclei, and inclusion-like nucleoli.