March 2014 - Dr. Shaheed W. Hakim
Clinical history: 35 year old female with enlarged supraclavicular lymph node.
Classical Hodgkin Lymphoma is a monoclonal neoplasm that is composed of mononuclear Hodgkin cells and multinucleated Reed-Sternberg cells. These cells are surrounded by a mixed infiltrate composed of small lymphocytes, eosinophils, neutrophils, histiocytes, plasma cells, fibroblasts, and collagen fibres. There are four histological subtypes that are based on the characteristics of the infiltrate as well as the morphology of the Reed-Sternberg cells. These are: (1) lymphocyte rich classical Hodgkin lymphoma, (2) nodular sclerosis classical Hodgkin lymphoma, (3) mixed cellularity classical Hodgkin lymphoma and (4) lymphocyte depleted classical Hodgkin lymphoma.
Nodular sclerosis classical Hodgkin lymphoma accounts for around 70% of the classical Hodgkin lymphomas in both Europe and USA. It is more common in the resource rich areas, highest among those with higher socioeconomic statuses. The incidence is the same between males and females and peaks at ages 15-34 years. It most commonly involves the mediastinum (80% of cases), as bulky disease (54%), in the spleen and/or lung (8-10%), bone involvement (5%), bone marrow (3%) and liver involvement (2%). B-symptoms are encountered in approximately 40% of the cases.
Grossly, these lymph nodes characterized by a thickened capsule, fish-flesh appearance on cut surface with a prominent nodularity, and dense fibrotic bands.
Histologically, the lesion is characterized by a nodular growth pattern, with collagen bands surrounding the nodules. The lymphoma tends to contain a variable number of Reed-Sternberg cells, designated as the lacunar type. These cells have lobated nuclei with small lobes, less prominent nucleoli, and a large amount of cytoplasm. There is a retraction of the cytoplasmic membrane (in formalin fixed tissues) that gives the impression that the cell seems to be sitting in a lacunae, hence the term, lacunar cell. These cells may form aggregates, and when prominent, are designated as a ‘syncytial variant’.
Immunophenotypically, the malignant cells demonstrate positive staining for CD 30, CD15, MUM1 and show negative staining for CD45. PAX5 has a characteristic weak ‘blush-like’ staining for the neoplastic cells, than the reactive B-cells. Epstein Bar Virus (demonstrated by EBER or EBV) is positive in 10-40% of cases. CD20 is positive in 30-40% of cases.
Nodular sclerosis Hodgkin lymphoma has a better prognosis overall than that of other types of classical Hodgkin lymphoma. Treatment is tailored to disease type, stage and assessment of the risk for resistant disease. It is considered a curable malignancy, but therapies can have significant long term toxicity. The general treatment strategies include radiation therapy, induction chemotherapy, salvage chemotherapy, and stem cell transplantation.