Answer: Nodular sclerosis Hodgkin’s lymphoma

Histology: Histologic sections show an enlarged lymph node that is architecturally distorted by a vaguely nodular infiltrate. Some of the nodules are separated by bands of collagen fibrosis. Also, the lymph node capsule is abnormally thickened. Cytologically, the infiltrate is notable for numerous large, atypical cells in the background of small, mature lymphocytes. Most of the atypical cells demonstrate lacunar morphology and complex nuclear features consistent with Reed-Sternberg cell variants, and some demonstrate binucleation and prominent nucleoli typical of classic Reed-Sternberg cells. The background small, mature lymphocytes are morphologically unremarkable. The immunoperoxidase stain shown here demonstrates a lack of reactivity for CD45 (common leukocyte antigen) within the large, atypical Reed-Sternberg cells.

Discussion: Nodular sclerosis Hodgkin’s lymphoma (NSHL) is a subtype of classical Hodgkin’s lymphoma and is characterized by bands of collagen fibrosis and Reed-Sternberg (RS) cells and variants with lacunar morphology. NSHL accounts for approximately two-thirds of all Hodgkin’s lymphomas and is the one subtype that does not have a male predominance; the male:female ratio is about 1:1. Patients are typically young or middle-aged adults who commonly present with a mediastinal mass and/or cervical lymphadenopathy. B-symptoms (fever, night sweats, weight loss) are encountered in approximately 40% of cases. Spleen and/or lung involvement is seen in 10-20% of cases, but bone marrow involvement is rare. NSHL is generally responsive to radiation and modern chemotherapy regimens. The prognosis of NSHL is better than that of lymphocyte depleted subtype and slightly better than that of mixed cellularity subtype, but is not as good as the prognosis for lymphocyte predominant Hodgkin’s lymphoma. The relatively good prognosis is largely based on its tendency to present with low stage disease (usually stage II). Bulky mediastinal disease is an adverse risk factor.

Morphologically, the lymph nodes classically show a nodular growth pattern and an abnormal proliferation of fibrous tissue. The RS cells are highly variable in number and tend to have more polylobated nuclei and less prominent nucleoli than other subtypes of Hodgkin’s lymphoma. In formalin fixed tissues, the cytoplasm of the RS cells frequently show retraction artifact rendering them a lacunar appearance. Lacunar cells may form cellular aggregates, which are occasionally associated with necrosis. When aggregates are very prominent, the term syncytial variant of NSHL has been used. Immunophenotypically, the Reed-Sternberg cells and variants are positive for CD15 and CD30, and are negative for CD45, CD20 and CD3. The small, mature lymphocytes in the background represent a mixture of CD20-positive B cells and CD3-positive T cells.

Occasionally, anaplastic large cell lymphoma (ALCL) may resemble NS Hodgkin’s lymphoma due to the complex nuclear features of the malignant cells. However, ALCL does not typically show a nodular growth pattern and lacunar cytology. Moreover, though CD30 reactivity is common to both types of lymphoma, ALCL is positive for CD45 and negative for CD15. The immunophenotype of RS cells in the lymphocyte predominant subtype is distinctly different; these cells are positive for CD45 and CD20 and negative for CD15 and CD30.