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Hematopathology
Sunday, February 12, 2006 - 7:30 PM
Centennial I
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Moderator:
John Cousar
University of Virginia Health System
Charlottesville, VA
Disclosure: The speakers have indicated they have nothing to disclose.
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Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view
Submitted by:
Kathryn Foucar
University of New Mexico
Albuquerque, NM
This 53-year-old female with a 2-year history of neutropenia presents with an enlarged right axillary lymph node. Following lymph node biopsy, a bone marrow aspirate and biopsy were performed. The bone marrow was inaspirable.
| CBC: | | Differential count: |
| WBC | 4,100/µL | | Neutrophils | 34% |
| RBC | 4.2 x 106/µL | | Lymphocytes | 60% |
| Hgb | 13.1 g/dL | | Monocytes | 2% |
| Hct | 38% | | Eosinophils | 3% |
| MCV | 91 fl | | Basophils | 1% |
| Plt | 156,000/µL | | | |
Submitted by:
William G. Morice
Mayo Clinic
Rochester, MN
The patient is a 67 year old male who presents with a 2 year history of a "myelodysplastic syndrome with refractory anemia". The patient had little improvement with either iron and vitamin B6 or erythropoietin therapies and he had been transfusion dependent for approximately one year. The patient had not received other treatments. His only complaint at the time of presentation was fatigue, which was alleviated with transfusion. He had not experienced problems with either recurrent infections or bleeding.
CBC values at the time of presentation were:
Hemoglobin: 8.3 g/dL, Erythrocytes: 2.89 x 10(12)/L, MCV: 84 fL, RDW: 14.7%
Reticulocytes: 0.5%
WBC: 9.6 x 10(9)/L, ANC: 0.8 x 10(9)/L, ALC: 8.6 x 10(9)/L
PLT: 461 x 10(9)/L
Bone marrow examination was performed to further evaluate for the possibility of myelodysplasia. Cytogenetic studies performed on the bone marrow aspirate revealed a normal male karyotype (46,XY) in 20 analyzed metaphases.
Case 2 - Figure 1 - Review of a the peripheral blood smear reveals the majority of the lymphocytes to have small nuclei and relatively abundant cytoplasm containing variably prominent granules.
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Case 2 - Figure 2 - The bone marrow biopsy is normocellular to slightly hypercellular with decreased erythropoesis, increased granulopoesis, and unremarkable megakaryopoesis. The most evident lymphoid element on morphologic review are the bland appearing interstitial lymphoid aggregates.
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Case 2 - Figure 3 - Immunoperoxidase staining of the bone marrow biopsy reveals the interstitial lymphoid aggregates to predominantly contain CD3 positive T-cells (left) with lesser numbers of CD20 positive B-cells (right).
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Case 2 - Figure 4 - Additional immunoperoxidase stains demonstrate that the CD3 positive T-cells (left) in the lymphoid aggregates do not express the cytotoxic granule protein granzyme B (right). Note the presence of small granzyme B positive cells at the periphery of the lymphoid aggregate.
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Case 2 - Figure 5 - Increased numbers of CD3 positive T-cells were present in the marrow interstitium (stain not shown). These interstitial T-cells are CD8 positive, with clusters of CD8 positive cells present.
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Case 2 - Figure 6 - On closer examination a linear of distribution of CD8 positive cells in the bone marrow biopsy is evident. This is attributable to the presence of these cells in small vessels.
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Case 2 - Figure 7 - The intravascular T-cells are also positive for the cytotoxic granule proteins TIA-1 (top) and granzyme B (bottom).
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Case 2 - Figure 8 - Flow cytometric immunophenotyping analysis performed on the bone marrow aspirate reveals the presence of an immunophenotypically aberrant T-cell population with diminished expression of CD3 and CD7 (right, indicated by arrow). Subsets of these cells show both diminished expression and complete loss of CD5 (left, arrows).
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Case 2 - Figure 9 - Flow cytometry demonstrates the T-cells to be CD8 positive (left, arrow). These cells aberrantly coexpress CD16 (right, arrow).
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Case 2 - Figure 10 - 3-color flow cytometry allows for selective gating on the CD3 and CD16 positive T-cells (left, cells are in gate R2 and highlighted green). This technique is used to confirm that these cells coexpress CD57 (right).
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Case 2 - Figure 11 - The same gating strategy used in Figure 10 is used to demonstrate that the CD3 and CD16 positive cells show uniform expression of the KIR antigen CD158b. These cells do not express CD158a or CD158e (also known as p70).
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Submitted by:
Vishnu V.B. Reddy
University of Alabama
Birmingham, AL
This 73 year old female presented to family practice clinic in June of 2005 complaining increasing weakness and weight loss. A routine CBC showed anemia (Hgb 10.4 gm/dl), mild thrombocytopenia and mild leukocytosis (WBC 10.7 k/ul) with monocytosis (absolute monocyte count 2140 / cmm). Later, she was evaluated by hematologist and underwent bone marrow biopsy.
Case 3 - Figure 1 - Bone marrow aspirate (Wight-Giemsa) showing marrow elements and clusters of mast cells.
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Case 3 - Figure 2 - Bone marrow aspirate (Wight-Giemsa) showing marrow elements and clusters of mast cells (100x oil).
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Case 3 - Figure 3 - Bone marrow aspirate (Wight-Giemsa) containing several clusters of abnormal myeloid/monocytic precursors and some with dysgranulation and marked left-shift (blasts ~ 8%).
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Case 3 - Figure 4 - Bone marrow aspirate (Wight-Giemsa) showing focus of immature myeloid cells / left-shift.
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Case 3 - Figure 5 - Bone marrow biopsy was hypercellular (85-90%) cellular and contained mixtures of early and large hematopoietic elements in varying stages of maturation. Also, are found several collections of mast cells with central round pale nuclei and pale granular cytoplasm.
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Case 3 - Figure 6 - Bone marrow biopsy (20x Obj) shows mild para-trabecular fibrosis and mast cells / hematopoietic elements.
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Case 3 - Figure 7 - Immunohistochemical stain CD117 (c-kit) was positive in most of mast cells (10x Obj).
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Case 3 - Figure 8 - Immunohistochemical stain CD117 (k-kit) was positive in most of mast cells. High power examination (40x Obj) confirms that most are mast cells with strong membrane / cytoplasmic staining and pale nuclei. Rare myeloid precursors are staining.
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Case 3 - Figure 9 - Immunochemical stain tryptase was positive in few of the mast cells.
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Submitted by:
James W. Vardiman
University of Chicago
Chicago, IL
This 33-year old woman's chief complaint was gradually increasing fatigue for about one year. At the time she sought medical attention, the only significant physical finding was a "barely palpable" spleen. Laboratory data obtained demonstrated:
WBC=14.8 x 109/L, Hb=8.7g/dL, Platelets=1,247 x 109/L, Reticulocytes=4.3% with Reticulocyte Production Index=1.6.
A bone marrow biopsy and aspiration were performed, although the aspirate yielded only scant material.
Cytogenetic studies revealed a normal female karyotype. FISH studies showed no evidence of BCR/ABL fusion gene.
Additional laboratory studies included serum ferritin, 29ng/ml (normal range, 12-201), uric acid 7.5 mg/dL (normal range 2.0-7.5).
The blood and marrow findings were reported as "consistent with Essential Thrombocythemia (ET). The slides were referred to the University of Chicago for an additional opinion.
Case 4 - Figure 1 - Prefibrotic CIMF. Peripheral blood smear showing increased platelets, mild leukocytosis due to neutrophilia, and occasional teardrop-shaped red blood cells.
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Case 4 - Figure 2 - Prefibrotic CIMF. Representative fields from the peripheral blood smear showing segmented neutrophils with normal morphology, occasional myelocytes, and basophils. In these fields there is minimal red blood cell poikilocytosis.
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Case 4 - Figure 3 - Prefibrotic CIMF. Representative fields of the bone marrow biopsy demonstrate megakaryocytic proliferation, with the megakaryocytes in clusters.
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Case 4 - Figure 4 - Prefibrotic CIMF. Representative fields of the bone marrow biopsy demonstrate megakaryocytic proliferation, with the megakaryocytes in clusters.
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Case 4 - Figure 5 - Prefibrotic CIMF. High power fields of the biopsy demonstrate the variable size and atypia of the megakaryocytes. Naked megakaryocyte nuclei are seen, and in some the N:C ratio is abnormal. There is marked neutrophil proliferation but diminished numbers of erythroid precursors.
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Case 4 - Figure 6 - Prefibrotic CIMF. The aspirate smear is poorly cellular and cytology was not well preserved. The reticulin stain reveals only minimal increase in reticulin fibers.
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Case 4 - Figure 7 - Prefibrotic CIMF. The aspirate smear is poorly cellular and cytology was not well preserved. The reticulin stain reveals only minimal increase in reticulin fibers.
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Case 4 - Figure 8 - Prefibrotic CIMF. This figure summarizes the important findings, including the thrombocytosis in the blood, the hypercellular bone marrow biopsy with predominantly granulocytic and megakaryocytic proliferation, and the atypia of the megakaryocytes. There is a minimal increase in reticulin fibers.
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