| Session: Extramedullary manifestation of neoplastic myeloid disorder |
| Case number: 159 |
Submitter(s): Chad P. Soupir, Nancy L. Harris, Robert P. Hasserjian.
Clinical history
31 year old female presented with enlarged supraclavicular and cervical lymph nodes one week postpartum. The patient was otherwise asymptomatic.
19 years ago, she developed massive splenomegaly and thrombocytopenia associated with infectious mononucleosis and underwent a splenectomy. The spleen was felt to be involved by a chronic myeloproliferative process with extramedullary hemopoiesis and a "CD45 negative blast-like infiltrate". A bone marrow biopsy done then was felt to be consistent with a myeloproliferative process. She received no treatment. With close follow-up she remained clinically well.
Current CBC: WBC 6.4 x 109/L (47% polys, 42% lymphs, 7% monos, 2% eos, 2% basos, and numerous nRBC), Hgb 15.0 g/dL, platelets 467 x 109/L.
Medications: none.
Details of gross/microscopic pathology:
A biopsy of the right cervical lymph node (slides submitted) shows sheets of large primitive cells. These occur in association with maturing erythroid elements, some present within the lymph node sinuses. There are also focal areas of maturing myeloid cells and rare megakaryocytes (Figures 1-4).
The bone marrow biopsy is markedly hypercellular (about 95%) with large clusters of primitive cells resembling those in the lymph node. Megakaryocytes are mildly decreased in number (Figures 5-8). On the marrow aspirate smears, erythroid and myeloid elements demonstrate maturation and myeloblasts comprise <5% of the cells. Pronormoblasts are increased and some erythroids show nuclear irregularities and megaloblastoid features.
Immunophenotype (flow cytometry/immunohistochemistry):
Immunohistochemistry on the lymph node biopsy shows that the primitive cells are positive for CD43, focally positive for glycophorin (Figure 9), and weakly positive for CD117 (c-kit). The cells are negative for CD45, CD2, CD3, CD20, PAX-5, CD30, MUM1, CD79a, CD21, CD34, CD68, MPO, lysozyme, CD56, S100. The Ki67 proliferation index in the primitive cells is 100%.
Cytogenetics:
Marrow cytogenetics: 46, XX. FISH negative for BCR-ABL.
Molecular analysis:
Negative for JAK2 mutation.
Interesting feature(s) of submitted case:
This primitive-cell proliferation in both lymph node and bone marrow morphologically mimicked large cell lymphoma or myeloid sarcoma. The immunohistochemistry confirms these cells are of erythroid lineage. Prominent extramedullary hemopoiesis can occur in chronic hemolytic anemias; however, this patient was not anemic. The association of these erythroid proliferations with stress (EBV infection and, 19 years later, pregnancy) in an otherwise well patient suggests that these are reactive in nature, possibly related to an abnormal growth factor receptor or an immunodeficiency. Recognition that these primitive cells were erythroid was critical in avoiding unnecessary aggressive therapy.
Proposed diagnosis:
Lymph node: Extramedullary hemopoiesis with marked pronormoblast proliferation, likely non-neoplastic.
Bone Marrow: Markedly hypercellular marrow with prominent pronormoblast proliferation, likely non-neoplastic.
Panel diagnosis:
agree with proposed diagnosis
Comments:
Stains performed by the panel: MPO-, Glycoforin C-/+, CD117-/+ weak, NPM- (+in nuclei). Additional information from the submitter: The slides and blocks from the original spleen and bone marrow biopsy are no longer available for review. The pathology reports are all that remains. The spleen weighed 2.67 kg and measured 26 x 20.5 x 10.3 cm. Multiple splenic hilar lymph nodes, with the largest measuring 3.3 cm in greatest dimension. Fortunately, a detailed microscopic description of the cases is available. The original pathology was reviewed by Dr. Daniel G. Berntson. He gave a detailed microscopic description of the spleen and lymph nodes, which included the following: ""In multiple sections of lymph nodes...in focal areas, there is disruption of the normal architecture with thin walled vessels separated by increased numbers of large blast-like cells. These cells have a diffuse distribution and are separated by fascicles or packet-like areas by thin fibrous or fibrovascular septae. The nuclei show predominantly one to two large nucleoli. The nuclei are non-cleaved. Occasional mitotic figures are present. The malignant cells have scant to moderate amounts of cytoplasm."" ""Multiple sections of spleen...the red pulp is expanded in volume. Amidst the numerous sinusoids there are scattered aggregates of abnormal malignant cells. These cells are predominantly large with large nuclei showing vesicular chromatin patterns and predominantly one to two large nucleoli. These cells are similar to those described in the abnormal blast-like areas of the lymph nodes....Extramedullary hematopoiesis is present."" In the bone marrow ""infiltrates of large malignant cells are present. These cells show large oval nucleoli with one to two and infrequently three prominent nucleoli. These cells have moderate amounts of pale eosinophilic cytoplasm. Occasional mitotic figures are seen amongst the cells. These cells are consistent with the type of cells seen in the malignant infiltrates described in the lymph node and spleen. The distribution is focal, patchy, and diffuse rather than nodular."" The bone marrow, spleen and splenic hilar lymph node were sent to Dr. Peter Banks at the Mayo Clinic at the time in 1988 and the final diagnosis reads as follows: ""Spleen shows massive enlargement due to a chronic myeloproliferative process featuring extramedullary hematopoiesis, which involves the splenic hilar lymph nodes as well. Bone marrow bx, spleen, and splenic lymph node all show foci of blastic cells suggestive of an acute blastic leukemic transformation."" ""Paraffin sections show no reactivity for the peculiar blastic cell clusters in spleen and splenic lymph node for leukocyte common antigen as well, therefore these blastic-appearing cell forms are of uncertain cytogenesis."" While all we have are the descriptions of original material, we believe the CD45 negative blast like cells that Drs. Berntson and Banks described in 1988 are the same cells present in the recent cervical lymph node and bone marrow specimens and are consistent with a marked pronormoblast proliferation within extramedullary hematopoiesis. The most recent follow-up on this patient is from December 2006. She is currently being observed without treatment and followed at six month intervals. She remains clinically well without complaints. Physical exam reveals mild lymphadenopathy in the right posterior neck, but is otherwise unremarkable. Her most recent CBC is normal as provided with the abstract.
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