Clinical history: 76 year old man with decreased level of consciousness. Prior history of lymphoma.
What is the diagnosis?
Lymphoproliferative disorder, consistent with metastatic lymphoma.
Cerebrospinal fluid, when normal, is a hypocellular fluid with scattered lymphocytes and monocytes and possibly red blood cells as a result of the needle puncture. Lymphoma or leukemia of the CSF is readily suspected by the high cellularity of the specimen. The type of lymphoma or leukaemia cannot usually be diagnosed by morphology alone unless there is a known history of lymphoma or leukaemia. Subtyping should be done by flow cytometry. Lymphoproliferative disorders may be metastatic to the CSF or may be primary at that site.
In general, lymphoproliferative disorders are characterized by single cells with few areas where the cells are touching each other. The cells may be the size of normal lymphocytes if a small cell disorder or may be larger and more pleomorphic if a large cell disorder. Typically, lymphocytes have minimal cytoplasm but the large B-cell and myeloid types may have more. Generally, chromatin is irregularly distributed and clumpy appearing. The degree of nuclear membrane irregularity varies with subtype. Some disorders show cleaved cells and others do not. Myeloid leukaemias may show azurophilic granules in the cytoplasm.
A common differential diagnosis is with small cell carcinoma. Small cell carcinoma also has dyscohesive cells but there are typically some areas of cohesion and it is here that nuclear moulding may be appreciated. Additionally, small cell carcinoma usually has hyperchromatic nuclei with smudgy or salt and pepper type chromatin whereas lymphoproliferative disorders usually show clumpy chromatin.