Am J Blood Res 2012;2(2):113-118
Review Article
Subtle bone marrow involvement by large B-cell lymphoma with
pronormoblast-like morphology and prominent but not exclusive sinusoidal
distribution
Christine G Roth, Kaaren K Reichard
Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pathology, University of New Mexico,
Albuquerque, New Mexico; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. *Dr.
Reichard is currently affiliated with Mayo Clinic, Rochester
Received March 16, 2012; accepted April 1, 2012; Epub April 15, 2012; Published June 15, 2012
Abstract: Primary bone marrow presentation of diffuse large B-cell lymphoma (DLBCL) is unusual, and appreciation of the
diffuse growth pattern may be difficult in cases with low-level involvement. In particular, subtle sinusoidal and interstitial bone
marrow involvement and morphologic overlap of the tumor cells with pronormoblasts may result initially in a missed
diagnosis. We describe the clinicopathologic features of 13 cases of morphologically subtle DLBCL involving the bone
marrow, which were only identified with the aid of immunohistochemistry. The overwhelming majority of cases (12/13, 92%)
presented with cytopenias, and 5 of 7 cases, with available information, had splenomegaly. The morphology of the tumor cells
in the aspirate smears overlapped with pronormoblasts (immature erythroid precursors) in 12 of 13 cases. Similarly, in
histologic sections, the tumor cells in virtually all cases (12/13) demonstrated round nuclear contours and oblong nucleoli,
mimicking pronormoblasts. A CD20 immunohistochemical stain was essential in identifying the neoplastic infiltrate in all
cases. The majority of cases (73%, 10/13) showed low-level bone marrow involvement by lymphoma, 10% or less. CD20
immunohistochemistry highlighted individually dispersed and small clusters of large lymphoid cells in a sinusoidal and/or
interstitial growth pattern. Most of the cases that were assessed showed a non-germinal center phenotype (CD10-, BCL6-/+,
IRF4/MUM1+). There was an aggressive disease course with a median overall survival of 6 months. We would recommend
performing a CD20 immunostain in patients who present with unexplained cytopenias and/or splenomegaly. Further
investigation is warranted to better describe the features of this unique and aggressive variant of DLBCL. (AJBR1203002).
Keywords: Diffuse large B cell lymphoma, bone marrow, immunohistochemistry, CD20, pronormoblast-like
Address all correspondence to:
Dr. Christine G Roth
200 Lothrop Street-UPMC-PUH, Suite G300
Division of Hematopathology, Department of Pathology
Pittsburgh, PA 15213, USA.
Tel: 412 647-5191; Fax: 412-647-6332
E-mail: garciac@upmc.edu
Review Article
Subtle bone marrow involvement by large B-cell lymphoma with
pronormoblast-like morphology and prominent but not exclusive sinusoidal
distribution
Christine G Roth, Kaaren K Reichard
Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Pathology, University of New Mexico,
Albuquerque, New Mexico; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. *Dr.
Reichard is currently affiliated with Mayo Clinic, Rochester
Received March 16, 2012; accepted April 1, 2012; Epub April 15, 2012; Published June 15, 2012
Abstract: Primary bone marrow presentation of diffuse large B-cell lymphoma (DLBCL) is unusual, and appreciation of the
diffuse growth pattern may be difficult in cases with low-level involvement. In particular, subtle sinusoidal and interstitial bone
marrow involvement and morphologic overlap of the tumor cells with pronormoblasts may result initially in a missed
diagnosis. We describe the clinicopathologic features of 13 cases of morphologically subtle DLBCL involving the bone
marrow, which were only identified with the aid of immunohistochemistry. The overwhelming majority of cases (12/13, 92%)
presented with cytopenias, and 5 of 7 cases, with available information, had splenomegaly. The morphology of the tumor cells
in the aspirate smears overlapped with pronormoblasts (immature erythroid precursors) in 12 of 13 cases. Similarly, in
histologic sections, the tumor cells in virtually all cases (12/13) demonstrated round nuclear contours and oblong nucleoli,
mimicking pronormoblasts. A CD20 immunohistochemical stain was essential in identifying the neoplastic infiltrate in all
cases. The majority of cases (73%, 10/13) showed low-level bone marrow involvement by lymphoma, 10% or less. CD20
immunohistochemistry highlighted individually dispersed and small clusters of large lymphoid cells in a sinusoidal and/or
interstitial growth pattern. Most of the cases that were assessed showed a non-germinal center phenotype (CD10-, BCL6-/+,
IRF4/MUM1+). There was an aggressive disease course with a median overall survival of 6 months. We would recommend
performing a CD20 immunostain in patients who present with unexplained cytopenias and/or splenomegaly. Further
investigation is warranted to better describe the features of this unique and aggressive variant of DLBCL. (AJBR1203002).
Keywords: Diffuse large B cell lymphoma, bone marrow, immunohistochemistry, CD20, pronormoblast-like
Address all correspondence to:
Dr. Christine G Roth
200 Lothrop Street-UPMC-PUH, Suite G300
Division of Hematopathology, Department of Pathology
Pittsburgh, PA 15213, USA.
Tel: 412 647-5191; Fax: 412-647-6332
E-mail: garciac@upmc.edu
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