Q. I’m now studying for USMLE and have something which is really confusing, I’m hoping you might be able to help! I see the term “Owl’s eye” thrown around for both Reed Sternberg cells of Hodgkin’s Lymphoma as well as for CMV. Based on the pictures I find on the internet it seems that the two are a bit different histologically. The CMV cells seem to have a clearing around the dark round nucleus whereas the RS cells seem to have more of an ovoid nucleus without clearing. If they are in fact different I think it’s quite confusing that the same terminology is used for both!

A. Yeah – you’re right – it is confusing!!

Sometimes in pathology a term will be used exclusively for one situation, and that’s it. Two phrases that come to mind are “starry sky pattern” (Burkitt lymphoma) and “cerebriform nucleus” (mycosis fungoides/Sezary syndrome).

Other times, a single term will be used to describe different things. The term “myeloid” is like this. It can mean either “of the marrow” (referring to any hematopoietic cell that is born and grows up in the marrow – red cells, white cells, or platelets) or “of the neutrophil lineage” (referring to any of the cells of that lineage from myeloblasts to promyelocytes to neutrophils). Confusing.

“Owl’s eye” belongs to the latter category. It can be used to describe the nuclei of cells infected by CMV (above, left), and it can also be used to describe the nuclei of Reed-Sternberg cells (above, right).

The intranuclear inclusions in CMV-infected cells are large (at least half the diameter of the cell) and deep purple in color. There is usually some clearing around the inclusion, as you noted, and the chromatin tends to condense around the periphery of the nucleus.

The nucleoli of Reed-Sternberg cells look very similar. They are reddish-purple and large (often as big as the nuclei of surrounding lymphocytes!). They can have a clear perinucleolar halo, and there is usually an accentuated nuclear membrane. A classic Reed-Sternberg cell has two nuclei (but some variants have one nucleus or more than two).

There are a few size differences between the two cells. First, CMV-infected cells are often (but not always) larger than Reed-Sternberg cells. Second, the intranuclear inclusions in CMV-infected cells are often (but not always) larger than the nucleoli in Reed-Sternberg cells. These size differences are not drastic or consistent enough, however, to be useful diagnostically.

One morphologic feature that may be helpful in distinguishing between the two cells is the presence of cytoplasmic inclusions in some cases of CMV. When present, these inclusions are purplish and granular (not big blobs like the intranuclear inclusions). Reed-Sternberg cells don’t have this type of cytoplasmic appearance.

In pathology, when you get stuck on a single cell, or group of cells, one thing that you should always do is look around at the surrounding tissue. Sounds simple – but it is surprisingly easy to get fixated on one thing and forget to systematically evaluate the entire slide. In this instance, if you have a big cell with owl’s eye nuclei and it is in a lymph node from a young male, and there are rare other cells like it within a background of neutrophils, eosinophils, plasma cells and histiocytes, then Hodgkin disease would be a likely diagnosis. If the cell is in a lung biopsy from a patient with HIV, CMV would be more likely.

A final caution: watch out when evaluating lymph nodes. There are cases of CMV lymphadenitis that can mimic Hodgkin disease. Sometimes, patients with Hodgkin disease in remission may contract CMV infection due to their immunosuppressed state. Or, patients with Hodgkin disease may harbor CMV in their lymph nodes (and if you misinterpret it as Hodgkin disease, then the patient would get staged inappropriately). Such cases could be difficult even for pathologists! If you happen to get a case like this, find a patient pathologist (there are lots of them) and sit down at the scope to pick his/her brain. Often, immunohistochemical stains can help make a definitive diagnosis.