B- and T-cell neoplasm features and fine points

Hairy cell leukemia is the classic one for morphology (Fig. 6). In his experience, he said, “hairy cell leukemia is a lot less exciting on a blood smear than the book images lead you to believe.”

“When I was first learning this, I saw the beautiful images of the big hair-like projections.” When he started to see cases, he said, “it was hard to find cells that have those wonderful projections.”

It’s more common to see “a ruffled or frilly kind of border to the cytoplasm,” he said, adding that paying attention to the nuclear features is important. “I know the cytoplasm and hair-like projections get all the press, but the nuclear features are also somewhat distinctive in hairy cell. The nuclei are generally oval, or may be kidney-bean shaped, and eccentrically placed, because there is some moderate amount of cytoplasm.”

Patients are frequently cytopenic in hairy cell leukemia, Dr. Bradley said, and usually the abnormal cells are “few and far between. There’s not that many of them because there’s pancytopenia, including lymphopenia.”

Monocytopenia is a characteristic feature. “So if you can’t find a monocyte, or a very low zero to one percent monocytes, that’s typical for hairy cell leukemia, and relatively specific among lymphoid malignancies in the blood. Splenomegaly is typical, and essentially every case will have a BRAF V600E mutation.”

Hairy cell leukemia variant (Fig. 7) is not a variant of hairy cell leukemia, “but it does share some features, which is why it originally got that name,” Dr. Bradley said. “If I see something that looks like hairy prolymphocytes, that’s likely hairy cell leukemia variant.”

He explains: “They have prolymphocyte-like nuclei with prominent nucleoli. These are not a feature of typical hairy cell leukemia, but then the cytoplasm has features that are typical for hairy cell leukemia with that ruffled and hair-like projection.”

Other features of hairy cell leukemia variant are a usually normal monocyte count, a significant increase in the white count, absence of the BRAF V600E mutation, and the possible presence of MAP2K1 mutations. Biologically, hairy cell leukemia variant is unrelated to HCL. “They share some phenotypic characteristics and some morphological characteristics,” he said, “which is why it has the name it has.”

For follicular lymphoma (Fig. 8), pathologists usually get a staging bone marrow, and while the marrow is ordinarily involved, blood involvement is rare. The centrocyte morphology is small to medium-size cells with a nuclear cleft. “And these will have the translocation (14;18) IGH-BCL2 in most cases.”

Blood involvement is more common (25 to 50 percent of cases) in mantle cell lymphoma (Fig. 9), but the lymphocyte morphology is variable, often with irregular nuclear contours. The translocation (11;14) IGH-CCND1 can be evaluated to help make the diagnosis, he said.

Dr. Bradley turned to T-cell neoplasms with interesting morphologic features, the first of which is T-cell prolymphocytic leukemia (Fig. 10). “The characteristic feature is cytoplasmic blebs. Very distinctive, though sometimes they’re more subtle.”

“You may see some nucleoli. They do have a name of prolymphocyte, but it’s variable how much you’ll see the nucleoli,” he said, urging pathologists to consider T-cell prolymphocytic leukemia when they see cytoplasmic blebs and a T-cell phenotype. “The white count in these cases is usually markedly elevated, often greater than 100. A 300 or 400 white count is not uncommon at all in T-PLL.” To help solidify the diagnosis: “Recognize that on chromosomes, about 80 percent of cases will have an inversion 14, and that’s relatively specific for this diagnosis,” Dr. Bradley said.

The classic finding in adult T-cell leukemia/lymphoma, or ATLL (Fig. 11), is flower cells, which are cells with flower-like nuclei with many nuclear convolutions and lobes (lower box, cell on left). “This is one where you would want your clinicians to do HTLV-1 virus testing by serology,” he said, “because there is a very high association between that virus leading to this disease.”

Last is plasma cell leukemia (Fig. 12). “There are some things to be aware of when you’re evaluating smears and suspicious for plasma cell leukemia,” Dr. Bradley said. Fig. 12 is a typical case: “There’s probably anemia, and there is a high lymphocyte or plasma cell count in this case, with lymphoid or lymphoplasmacytic cells,” some of which have typical plasma cell features. “Yet there are no beautiful classic plasma cells like you see in tissue or in bone marrow aspirates.”

“The plasma cells will look much more lymphocyte-like and much less impressive.” (Fig. 13). Pathologists need to be aware of that, he said, because if they are asked to evaluate for plasma cell leukemia and look for typical plasma cells, they won’t find them in most cases.

 

Karen Lusky is a writer in Brentwood, Tenn.