Clinicopathologic Features of CD5-positive Nodal Marginal Zone Lymphoma
Clinicopathologic Features of CD5-positive Nodal Marginal Zone Lymphoma
We identified seven cases of CD5-positive NMZL representing 8.6% of all cases of NMZL diagnosed at our institution during the study interval. There were five women and two men, with a median age of 49 years (range, 36–80 years) Table 1. Lymph node excisional biopsy specimens were obtained from the cervical (n = 4), axillary (n = 2), and gastroepiploic (n = 1) regions. No patients had extranodal sites of disease or splenomegaly. One patient had B-type symptoms and one patient had concurrent hepatitis C infection. At the time of presentation, all seven patients had disseminated disease. Specifically, six patients had widespread lymphadenopathy with bone marrow involvement.
Laboratory data were reviewed from all seven patients Table 2. A complete blood count was performed in all patients and was abnormal in three: one (case 4) had a low leukocyte count of 1.5 × 10/L (normal range, 4–11 × 10/L), one (case 7) had a low hemoglobin of 9.7 g/dL (normal range, 12–14 g/dL) and a low platelet count of 91 × 10/L (normal range, 150–440 × 10/L), and a third patient (case 3) had leukocytosis (29.7 × 10/L) with an absolute lymphocytosis value of 25.3 × 10/L. One patient had a serum paraprotein of immunoglobulin G (IgG) λ type. The serum β2-microglobulin level was elevated in three of five patients assessed. No patients had an elevated serum lactate dehydrogenase level or evidence of hepatitis B or human immunodeficiency virus infection.
In all cases, the lymph node architecture was partially or near totally replaced by lymphoma that surrounded reactive follicles with active germinal centers Image 1. Four cases showed prominent follicular colonization. Mitotic figures were infrequent in all cases. Cytologically, the neoplastic cells were composed of small lymphocytes with slightly irregular nuclear contours, condensed chromatin, and moderate cytoplasm interspersed with scattered large cells with vesicular nuclear chromatin. Four cases had substantial numbers of monocytoid cells, and two tumors exhibited prominent plasmacytoid differentiation, including one neoplasm that had clusters of plasma cells containing abundant intracytoplasmic immunoglobulin (Russell bodies). Prominent follicular colonization was also present in this case. Both cases with plasmacytoid differentiation also had small lymphocytes and monocytoid cells. None of the cases showed proliferation centers.
(Enlarge Image)
Image 1.
A, Lymph node involved by CD5-positive nodal marginal zone lymphoma (H&E; ×200). B, High-power view with centrocyte-like cells, monocytoid cells, and scattered large cells (H&E; ×1,000). C, The lymphoma cells are brightly positive for CD20 (immunohistochemistry with hematoxylin counterstain; ×400). D, The lymphoma cells coexpress CD5 (immunohistochemistry with hematoxylin counterstain; ×400). E, The lymphoma cells are negative for CD3 (immunohistochemistry with hematoxylin counterstain; ×400).
The bone marrow was involved in all six patients assessed. In the aspirate smears, the lymphoid cells were predominantly of small to medium size with round to slightly irregular nuclear contours and scant cytoplasm. In biopsy specimens, the infiltrate was composed predominantly of small lymphoid cells in an interstitial (n = 3) or nodular (n = 3) pattern. The extent of involvement in the bone marrow ranged from approximately 5% to 20% of the medullary space (Table 2).
All seven cases were assessed by immunohistochemical analysis Table 3. All cases were positive for CD5 and CD20, and all cases assessed were also positive for BCL-2 (5/5) and PAX5 (1/1). In a subset of tumors, the neoplastic cells were positive for CD43 (2/4) and were dimly positive for BCL-6 (2/3). The neoplastic cells in all cases were negative for cyclin D1 (0/7), CD23 (0/6), SOX11 (0/5), and CD10 (0/4).
Flow cytometric immunophenotyping was performed on cell suspensions of lymph node specimens from five patients Table 4. The neoplastic cells in all cases were positive for monotypic surface immunoglobulin light chain (three κ and two λ), CD5, CD19, CD20 (moderate to bright), and FMC-7 (n = 3). One of three cases assessed was dimly CD23 positive. The neoplastic cells were negative for CD10 in two cases assessed. Flow cytometric immunophenotyping was performed on six positive bone marrow aspirate samples as well as four concurrent peripheral blood samples and showed similar results. All samples showed a monotypic B-cell population with aberrant expression of CD5. Conventional cytogenetic analysis performed on morphologically involved bone marrow aspirate specimens from four patients showed a diploid karyotype.
Treatment and follow-up information were available for all seven patients Table 5. The median follow-up was 32 months (range, 3–154 months), and six of seven patients were alive at last follow-up. Two patients were observed without specific therapy and were alive with disease at last follow-up. Of the three patients who received rituximab alone, two achieved complete remission and one was alive with disease. Two patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy: one was alive with disease and one died of complications from chemotherapy.
We compared the seven patients with CD5-positive NMZL with a group of 66 patients with CD5-negative NMZL. In the CD5-positive group, six (86%) of seven patients had lymphadenopathy above and below the diaphragm, and all six patients assessed had bone marrow involvement. In contrast, in the CD5-negative group, 28 (42%) of 66 patients had lymphadenopathy above and below the diaphragm as judged by radiologic imaging studies, and 36 (55%) of 66 had bone marrow involvement. These differences between the CD5-positive and CD5-negative NMZL patients were statistically significant (P = .045 and P = .037, respectively).
Results
Clinical Findings
We identified seven cases of CD5-positive NMZL representing 8.6% of all cases of NMZL diagnosed at our institution during the study interval. There were five women and two men, with a median age of 49 years (range, 36–80 years) Table 1. Lymph node excisional biopsy specimens were obtained from the cervical (n = 4), axillary (n = 2), and gastroepiploic (n = 1) regions. No patients had extranodal sites of disease or splenomegaly. One patient had B-type symptoms and one patient had concurrent hepatitis C infection. At the time of presentation, all seven patients had disseminated disease. Specifically, six patients had widespread lymphadenopathy with bone marrow involvement.
Laboratory data were reviewed from all seven patients Table 2. A complete blood count was performed in all patients and was abnormal in three: one (case 4) had a low leukocyte count of 1.5 × 10/L (normal range, 4–11 × 10/L), one (case 7) had a low hemoglobin of 9.7 g/dL (normal range, 12–14 g/dL) and a low platelet count of 91 × 10/L (normal range, 150–440 × 10/L), and a third patient (case 3) had leukocytosis (29.7 × 10/L) with an absolute lymphocytosis value of 25.3 × 10/L. One patient had a serum paraprotein of immunoglobulin G (IgG) λ type. The serum β2-microglobulin level was elevated in three of five patients assessed. No patients had an elevated serum lactate dehydrogenase level or evidence of hepatitis B or human immunodeficiency virus infection.
Morphologic Findings
In all cases, the lymph node architecture was partially or near totally replaced by lymphoma that surrounded reactive follicles with active germinal centers Image 1. Four cases showed prominent follicular colonization. Mitotic figures were infrequent in all cases. Cytologically, the neoplastic cells were composed of small lymphocytes with slightly irregular nuclear contours, condensed chromatin, and moderate cytoplasm interspersed with scattered large cells with vesicular nuclear chromatin. Four cases had substantial numbers of monocytoid cells, and two tumors exhibited prominent plasmacytoid differentiation, including one neoplasm that had clusters of plasma cells containing abundant intracytoplasmic immunoglobulin (Russell bodies). Prominent follicular colonization was also present in this case. Both cases with plasmacytoid differentiation also had small lymphocytes and monocytoid cells. None of the cases showed proliferation centers.
(Enlarge Image)
Image 1.
A, Lymph node involved by CD5-positive nodal marginal zone lymphoma (H&E; ×200). B, High-power view with centrocyte-like cells, monocytoid cells, and scattered large cells (H&E; ×1,000). C, The lymphoma cells are brightly positive for CD20 (immunohistochemistry with hematoxylin counterstain; ×400). D, The lymphoma cells coexpress CD5 (immunohistochemistry with hematoxylin counterstain; ×400). E, The lymphoma cells are negative for CD3 (immunohistochemistry with hematoxylin counterstain; ×400).
The bone marrow was involved in all six patients assessed. In the aspirate smears, the lymphoid cells were predominantly of small to medium size with round to slightly irregular nuclear contours and scant cytoplasm. In biopsy specimens, the infiltrate was composed predominantly of small lymphoid cells in an interstitial (n = 3) or nodular (n = 3) pattern. The extent of involvement in the bone marrow ranged from approximately 5% to 20% of the medullary space (Table 2).
Immunophenotypic and Cytogenetic Findings
All seven cases were assessed by immunohistochemical analysis Table 3. All cases were positive for CD5 and CD20, and all cases assessed were also positive for BCL-2 (5/5) and PAX5 (1/1). In a subset of tumors, the neoplastic cells were positive for CD43 (2/4) and were dimly positive for BCL-6 (2/3). The neoplastic cells in all cases were negative for cyclin D1 (0/7), CD23 (0/6), SOX11 (0/5), and CD10 (0/4).
Flow cytometric immunophenotyping was performed on cell suspensions of lymph node specimens from five patients Table 4. The neoplastic cells in all cases were positive for monotypic surface immunoglobulin light chain (three κ and two λ), CD5, CD19, CD20 (moderate to bright), and FMC-7 (n = 3). One of three cases assessed was dimly CD23 positive. The neoplastic cells were negative for CD10 in two cases assessed. Flow cytometric immunophenotyping was performed on six positive bone marrow aspirate samples as well as four concurrent peripheral blood samples and showed similar results. All samples showed a monotypic B-cell population with aberrant expression of CD5. Conventional cytogenetic analysis performed on morphologically involved bone marrow aspirate specimens from four patients showed a diploid karyotype.
Therapy and Clinical Outcome
Treatment and follow-up information were available for all seven patients Table 5. The median follow-up was 32 months (range, 3–154 months), and six of seven patients were alive at last follow-up. Two patients were observed without specific therapy and were alive with disease at last follow-up. Of the three patients who received rituximab alone, two achieved complete remission and one was alive with disease. Two patients received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy: one was alive with disease and one died of complications from chemotherapy.
We compared the seven patients with CD5-positive NMZL with a group of 66 patients with CD5-negative NMZL. In the CD5-positive group, six (86%) of seven patients had lymphadenopathy above and below the diaphragm, and all six patients assessed had bone marrow involvement. In contrast, in the CD5-negative group, 28 (42%) of 66 patients had lymphadenopathy above and below the diaphragm as judged by radiologic imaging studies, and 36 (55%) of 66 had bone marrow involvement. These differences between the CD5-positive and CD5-negative NMZL patients were statistically significant (P = .045 and P = .037, respectively).