Case Study: Lymphoproliferative Disorder of Natural Killer-Cells

Among the rare group of natural killer-cell (NK-cell) malignancies, there are two which primarily involve the peripheral blood and bone marrow: aggressive NK-cell leukemia (ANKL) and chronic lymphoproliferative disorder of NK-cells (CLPDNK). Distinguishing chronic lymphoproliferative disorder of natural killer (NK) cells from aggressive NK-cell leukemia is critical because they have distinct clinical course and management.

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Min Shi, M.D., Ph.D.

Mayo Clinic researchers, first author Min Shi, M.D., Ph.D., reported an unusual case of NK-cell neoplasm having an immunophenotype similar to that associated with ANKL but with clinical and laboratory features typical of the much more indolent CLPDNK. The case was published in Clinical Case Reports

The patient is a 65-year-old Caucasian male with a 16-year history of leukopenia and neutropenia. He was completely asymptomatic, denying fevers, night sweats, or unexplained weight loss and had no documented history of neutropenic infection. An ultrasound revealed an enlarged spleen without focal masses. No hepatomegaly or lymphadenopathy was found. The patient had not received therapy for this condition.

The peripheral blood smear showed an increase in granular lymphocytes with bland nuclei and abundant pale-staining cytoplasm containing fine to coarse azurophilic granules. No nuclear atypia, such as enlargement, folding, or open chromatin, was noted. Peripheral blood flow cytometric immunophenotyping revealed significantly increased NK-cells.

 Immunophenotypic, morphologic, and immunohistochemical features of the case. (A) Immunophenotying by flow cytometric analysis on peripheral blood showed a distinct population of surface CD3-negative NK-cells (in red) with partial loss of CD7. They were positive for CD56, and negative for CD8, CD16, and CD57. They had uniform strong expression of CD94 and NKG2A and they completely lost the expression of KIRs, such as CD158a, CD158b, and CD158e. (B) Wright-Giemsa-stained peripheral blood smear showed a population of lymphocytes with intermediate-sized reticulated chromatin and azurophilic granules in abundant amounts of pale cytoplasm (original magnification ×1000). (C–E) Immunohistochemical studies on the bone marrow biopsy revealed a linear (or intrasinusoidal/intravascular) distributed neoplasm cells that were positive for CD3 (C), Granzyme B (D) and TIA-1 (E).
Immunophenotypic, morphologic, and immunohistochemical features of the case. (A) Immunophenotying by flow cytometric analysis on peripheral blood showed a distinct population of surface CD3-negative NK-cells (in red) with partial loss of CD7. They were positive for CD56, and negative for CD8, CD16, and CD57. They had uniform strong expression of CD94 and NKG2A and they completely lost the expression of KIRs, such as CD158a, CD158b, and CD158e. (B) Wright-Giemsa-stained peripheral blood smear showed a population of lymphocytes with intermediate-sized reticulated chromatin and azurophilic granules in abundant amounts of pale cytoplasm (original magnification ×1000). (C–E) Immunohistochemical studies on the bone marrow biopsy revealed a linear (or intrasinusoidal/intravascular) distributed neoplasm cells that were positive for CD3 (C), Granzyme B (D) and TIA-1 (E).

The diagnosis of NK-cell leukemia is challenging for practicing pathologists because NK-cells lack a singular lineage defining antigen and are phenotypically similar to normal cytotoxic T-cells. Due to this, flow cytometric immunophenotyping is a primary laboratory tool as it allows for the accurate identification of NK-cells through combined assessment of antigens.

For more information, read the full case history and discussion.

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Kelley Schreiber

Kelley Schreiber is a Marketing Channel Manager at Mayo Medical Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her new kitten, and exploring new foods.