Bone marrow aspirate shows only 3% plasma cells with normal morphology. Immunostains performed on bone marrow biopsy show no evidence of light chain restriction.

CLINICAL INFORMATION:

65 year old female with history of HTN, gastric ulcer, anemia, elevated IgG level and beta 2 microglobulin level. No data on serum/urine protein electrophoreses or immunofixation are available for review. Bone marrow was requested to rule out multiple myeloma or MGUS.

SPECIMEN SUBMITTED:

Bone marrow aspirate, biopsy, and touch preps (obtained by Pathology), immunoperoxidase stains (kappa and lambda)

MICROSCOPIC DESCRIPTION:

CBC results show: RBC 4.11, Hgb 12.6, Hct 35.6, MCV 86.5, MCH 30.6, MCHC 35.3, Platelets 212 K, WBC 7.7. WBC differential shows 46% PMNs, 47% lymphocytes, 6% monocytes, and 1% eosinophils.

Examination of blood smear shows mild normochromic normocytic anemia, no polychromasia; normal number of leukocytes with a few reactive lymphocytes, normal platelet count with a few clumps and a few large platelets.

Bone marrow biopsy (decalcified) is 0.9 cm in length, with touch preps. A bone marrow cellularity of 40% is estimated from biopsy. No evidence of granuloma, fibrosis, or clusters of plasma cells are seen. Iron stores are decreased. Immunostains (kappa and lambda light chains) performed on bone marrow biopsy show no evidence of light chain restriction.

Bone marrow aspirate is hypocellular with few spicules. Bone marrow cell differential shows 1% blasts, 2% promyelocytes, 12% myelocytes, 2% metamyelocytes, 45% PMNs, 1% eosinophils, 14% lymphocytes, 3% plasma cells, 20% erythroids, with M:E ratio of 3:1. Bone marrow aspirate, touch preps and clot section show adequate granulopoiesis, megakaryopoiesis, and erythropoiesis. Iron stores are decreased. Plasma cells show normal cytological features.

++++++++++++++++++++++++++++++++++++++++++

2. BONE MARROW: PLASMA CELL MYELOMA

Peripheral blood:

-Normochromic normocytic anemia with rouleaux formation

Bone marrow:

-Plasma cell myeloma

-Adequate iron stores

COMMENT:

Marked plasmacytosis (31% of bone marrow cells) and monoclonal gammopathy by SPEP and UPEP are consistent with a diagnosis of plasma cell myeloma. Bone marrow aspirate was sent for cytogenetics (see separate report).

CLINICAL INFORMATION:

58 year old AA male with history of HTN, DM, nephrotic syndrome, Hep C infection, pneumonia and anemia. SPEP and UPEP results showed evidence of monoclonal gammopathy.

SPECIMEN SUBMITTED:

Bone marrow aspirate, biopsy, and touch preps (obtained by Pathology)

MICROSCOPIC DESCRIPTION:

CBC results show: RBC 3.19, Hgb 9.3, Hct 28.3, MCV 88.9, MCH 29.3, MCHC 33.0, Platelets 426 K, WBC 11.8. WBC differential shows 76% PMNs, 17% lymphocytes, 5% monocytes, 2% eosinophils.

Examination of blood smear shows normochromic normocytic anemia with rouleaux formation, no polychromasia; mild leukocytosis with a few reactive PMNs, slight thrombocytosis with a few large platelets.

Bone marrow biopsy (decalcified) is 0.9 cm in length, with touch preps. A bone marrow cellularity of 40% is estimated from biopsy. Iron stores are adequate.

Bone marrow aspirate shows adequate spicules. Bone marrow cell differential shows 1% blasts, 2% promyelocytes, 8% myelocytes, 3% metamyelocytes, 14% bands, 20% PMNs, 2% monocytes, 5% lymphocytes, 31% plasma cells, 14% erythroids, with M:E ratio of 5.6:1. Bone marrow aspirate, touch preps and clot section show adequate granulopoiesis and megakaryopoiesis, decreased erythropoiesis. Marked increase in plasma cells (31% ) is seen, many with immature cytological features. Iron stores are adequate.

++++++++++++++++++++++++++++++++++++++

3. BONE MARROW: PLASMACYTOSIS

Peripheral blood:

-No pathological changes

Bone marrow:

-Normocellular for age

-Plasmacytosis (see comment)

COMMENT:

Bone marrow aspirate shows 14% plasma cells, many with immature cytological features. This finding is insufficient for a diagnosis of multiple myeloma. Other data would be needed for this purpose: serum and urine protein electrophoresis with immunofixation, quantitative serum immunoglobulins, and imaging studies for lytic lesions. Since this bone marrow was performed in 2001, a repeated bone marrow is suggested at this time if clinically indicated.

CLINICAL INFORMATION:

61 year old male with history of plasmacytosis in bone marrow (2001). No data on serum/urine protein electrophoreses or immunofixation are available for review. Bone marrow was sent from Medical Pathology Laboratory for review.

SPECIMEN SUBMITTED:

Peripheral blood, bone marrow aspirate, clot, and biopsy.

MICROSCOPIC DESCRIPTION:

CBC results are not available for review.

Examination of blood smear shows normochromic normocytic RBCs, no polychromasia; normal number of leukocytes with normal morphology, normal platelet count with a few clumps. Due to the short length of blood smear, rouleaux formation cannot be assessed.

Bone marrow biopsy (decalcified) is 0.8 cm in length. A bone marrow cellularity of 40% is estimated from biopsy. No evidence of granuloma or fibrosis is found. Small clusters of plasma cells are seen.

Bone marrow aspirate is adequate with spicules. Bone marrow cell differential shows 2% blasts, 6% myelocytes, 1% metamyelocytes, 17% PMNs and bands, 2% eosinophils, 2% monocytes, 21% lymphocytes, 14% plasma cells, and 35% erythroids. Many plasma cells show immature cytological features (large nuclei with prominent nucleoli).

Bone marrow aspirate, clot section, and biopsy show adequate granulopoiesis, megakaryopoiesis, and erythropoiesis.

++++++++++++++++++++++++++++++++++++

4. BONE MARROW: SLL/CLL

DIAGNOSIS:

Peripheral blood:

- Small lymphocytic lymphoma/ chronic lymphocytic leukemia

Bone marrow:

- Small lymphocytic lymphoma/ chronic lymphocytic leukemia

CLINICAL INFORMATION:

82 year old woman diagnosed with diffuse small lymphocytic lymphoma in
March, 2004 (S2696-04).

SPECIMEN SUBMITTED:

Received from Alliance Pathology Associates, Pasadena, TX, for consultation:

- 2 paraffin blocks labeled "3743-BX, -clot"

- 10 glass slides labeled "S2004-3743 (x6); -smear-P; -BX; -clot;

iron"

- A one-page letter from Dr. Robin Brunnemann dated 05-04-04

- A one-page surgical pathology report specimen "BM:S-3743-04"

ADDITIONAL TECHNIQUES (from block 3743-BX):

CD3, CD5, CD20, CD23

GROSS DESCRIPTION:

See Alliance Pathology report S3743-04.

MICROSCOPIC DESCRIPTION:

No CBC results are available for peripheral blood. WBC differential shows 39% PMNs, 52% lymphocytes,5% monocytes, 1% eosinophils, 2% basophils, 1% metamyelocytes. Examination of blood smear shows normochromic normocytic erythroids with slight anisopoikilocytosis, lymphocytosis with the presence of a few smudge cells, platelets with normal number (estimated in blood smear)

and morphology.

Bone marrow aspirate shows adequate spicules. Bone marrow cell differential shows 1% blasts, 4% myelocytes, 3% metamyelocytes, 19% neutrophils, 1% eosinophils, 58% lymphocytes, 1% plasma cells, and 13% erythroids. Clot sections show multiple foci of lymphocytic aggregates. The lymphocytes in

aggregates are small with mature morphological features. Iron stain (clot section) shows decreased iron stores.

Bone marrow biopsy is 0.5 cm in length with 60% cellularity (hypercellular for age). Multiple foci of lymphocytic aggregates are seen in biopsy. The lymphocytes have mature cytological feature. Adequate number of megakaryocytes are present.

IMMUNOPEROXIDASE:

Immunohistochemical stains, with adequate controls, show positivity of CD5, CD20, and CD23 for the lymphocytic aggregates in the biopsy. Scattered T cells with positivity for CD3 are also seen.

++++++++++++++++++++++++++++++++++

5. ADDENDUM FOR CYTOGENETICS (REFRACTORY ANEMIA)

~~~~~ DISCUSSION AND JUSTIFICATION:

Addendum to report cytogenetic results of bone marrow and correlation with previous morphological findings

~~~~~ ADDENDUM DIAGNOSIS:

Bone marrow: Chromosome results show deletion of 7q and 20q, together with previous findings of increased erythropoiesis and dysplasia, are consistent with myelodysplasia (refractory anemia), see comment

~~~~~ ADDENDUM CANCER REGISTRY:

Y-Malignant neoplasm or neoplasm of uncertain malignant potential or behavior

~~~~~COMMENT~~~~~

Cytogenetic results from LabCorp were dated 12/27/07. ++++++++++++++++++++++++++++++++++++++++++++++++++++++++

6. ADDENDUM FOR CYTOGENETICS (CML)

~~~~~ DISCUSSION AND JUSTIFICATION:

Addendum to report cytogenetic and FISH results (bcr/abl) of bone marrow.

~~~~~ ADDENDUM DIAGNOSIS:

Bone marrow: Chromosome analysis shows normal male chromosome with no clonal abnormalities. FISH study for (bcr/abl) shows no evidence of bcr/abl gene rearrangement, see comment ~~~~~ ADDENDUM CANCER REGISTRY:

Y-Malignant neoplasm or neoplasm of uncertain malignant potential or behavior

~~~~~COMMENT~~~~~

Cytogenetic and FISH results from LabCorp were dated 12/28/07

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

7. BM: AML-M7

DIAGNOSIS:

Peripheral Blood: Microcytic hypochromic anemia

Presence of 21% blasts

Bone Marrow: Acute megakaryoblastic leukemia, AML-M7 (see comment)

Marked reticulin fibrosis

Decreased iron stores

COMMENT:

Immunophenotyping of peripheral blood leukocytes by flow cytometry shows a

myeloblast population that is positive for CD34, CD13, CD33, CD117, HLADR,

CD41a (86% of the blasts), and CD61 (78% of the blasts). These blasts are

negative for CD14, CD16, CD56, CD19, CD20, CD10, CD64, and TdT. These

findings are consistent with megakaryoblasts.

Cytogenetics and immunophenotyping of bone marrow by flow cytometry are
not available due to dry tap (secondary to marked fibrosis). Attempt to use a
bone marrow core biopsy for flow cytometry study was unsuccessful (inadequate

number of cells were extracted from the fibrotic biopsy).

Immunohistochemical stains, with adequate controls, performed on bone marrow

biopsy for c-kit, factor VIII-related antigen, and CD34 show scatterd

positivity of c-kit and CD34. Factor VIII-related antigen stain shows weak

positivity in megakaryocytes.

Even though an accurate percentage of blasts cannot be obtained from bone

marrow due to marked reticulin fibrosis, the presence of 21% megakaryoblasts

in peripheral blood smear in this patient (a consistent finding throughout the

hospital stay), and histology of bone marrow biopsy are consistent with acute

megakaryoblastic leukemia.

Review of recent bone marrow report (Ben Taub, 1/31/08, diagnosis: refractory

cytopenia with multilineage dysplasia) shows that patient did not have blasts

in peripheral blood at that time. The bone marrow was hypercellular with about

5% blast. The current findings in this patient indicates transformation from

myelodysplasia to acute myeloid leukemia.

CLINICAL HISTORY:

70 year old female with recent diagnosis of MDS (bone marrow at Ben Taub in

1/08), now with many blasts in peripheral blood.

BONE MARROW AND PERIPHERAL BLOOD REPORT

PERIPHERAL BLOOD BONE MARROW DIFFERENTIAL

(not representative due to fibrosis)

------------------------------------------------

RBC: 2.77 WBC count: 9.3 Myeloblasts: 2

Hgb: 7.8 Seg: 45 Promyelocytes: 3

Hct: 21.5 Band: 3 Myelocytes: 18

MCV: 77.8 Lymph: 14 Metas: 7

MCH: 28.0 Mono: 6 Bands & PMN's: 2

MCHC: 36.0 Eos: _____ Eos: 6

Retic %: 1.1__ Baso: 1 Baso: 3

Atyp Lymph: _____ Monos: 1

Meta: 7 Lymphs: 10

Platelets: 242,000 Myelo: 3 Plasma cells: 1

Promyelo: _____ Erythroids: 26

Blasts: 21 Other: 0

________________________________________________________________

PERIPHERAL BLOOD:

Erythrocytes: Microcytic hypochromic anemia with slight

polychromasia

White cells: Normal in number

Granulocytes: Left shift with 21% blasts

Lymphocytes: Normal morphology

Monocytes: Normal morphology

Platelets: Normal in number with moderate number of giant

forms

BONE MARROW ASPIRATE, TOUCH PREP, BIOPSY, CLOT SECTION:

Specimen: Obtained by pathology

Core: Decalcified biopsy, 1.7 cm with touch preps

Aspirate: Not successfully obtained. Cell differential is

performed on touch preps (not represntative due

to fibrosis)

Cellularity: 95%

Megakaryopoiesis: Increased, predominantly small megakaryocytes and

a few dysplastic forms

Erythropoiesis: Decreased with dyserythropoiesis

Iron Content: Decreased iron stores

Granulopoiesis: Increased in blasts found in biopsy

Lymphocytes: Normal morphology

Plasma Cells: Normal morphology

Other: Reticulin stain shows marked reticulin fibrosis

in bone marrow biopsy. Trichrome stain shows

focal collagen fibrosis. Iron stores are

decreased.

++++++++++++++++++++++++++++++++++++

8. BONE MARROW- POSSIBLE MDS (RA)

Diagnosis:

Peripheral blood: Pancytopenia

Bone marrow: Normocellular for age

Increased megakaryopoiesis and erythropoiesis with mild dysplasia

(see comments)

Adequate iron stores with no increase in ringed-sideroblasts

Comments:

Myelodysplasia (refractory anemia) cannot be ruled out with current morphological findings. Follow-up of patient and correlation with cytogenetics are suggested to rule out myelodysplasia

Microscopic:

CBC results show: Hgb 10.0, Hct 29.0, MCV 101, Platelets 74 K, WBC 1.4 K

Examination of blood smear shows macrocytic anemia with anisopoikilocytosis, minimal polychromasia; decreased number of leukocytes and platelets with normal morphology. No hypersegmented PMNs are found. Blasts are not seen.

Bone marrow biopsy (decalcified) is 0.6 cm in length, with touch preps. A bone marrow cellularity of 50% is estimated from biopsy. No evidence of granuloma, fibrosis, or abnormal cellular infiltrates is seen. Iron stores are adequate with no increase in ringed-sideroblasts.

Bone marrow aspirate is adequate with presence of spicules. Erythropoiesis is increased with a few dysplastic forms. Megakaryocytes are increased with normal maturation. Granulopoiesis is adequate with normal maturation. No increase in blasts is seen. Plasma cells are slightly increased with normal cytological features.

Immunophenotyping of aspirate by flow cytometry was reportedly showing no abnormalities. Cytogenetics is still pending.

++++++++++++++++++

9. BONE MARROW- SUBOPTIMAL BM

Diagnosis:

Peripheral blood: Pancytopenia

Bone marrow: Suboptimal for morphological evaluation (see comments)

Decreased iron stores

Comments:

Correlation with cytogenetics is suggested to rule out myelodysplasia. Morphological examination is limited by the small number of cells in aspirate and suboptimal marrow area in biopsy.

Microscopic:

The provided CBC data show: Hgb 7.9, Hct 23.2, MCV 112, Platelets 57 K, WBC 2.4 K

Examination of blood smear shows macrocytic hypochromic anemia with anisopoikilocytosis, slight polychromasia; decreased number of leukocytes and platelets with normal morphology. No immature cells or hypersegmented PMNs are found.

Bone marrow biopsy (decalcified) is 0.8 cm in length, with touch preps. The biopsy only has a small area of marrow medulla, the rest is muscle and cortical bone. Bone marrow cellularity cannot be evaluated due to lack of marrow area. Touch preps show presence of a few dysplastic erythroids. Iron stores are decreased.

Bone marrow aspirate is hypocellular with no spicules. Morphological evaluation is limited by inadequate number of cells.

Immunophenotyping of aspirate by flow cytometry was reportedly showing an atypical myeloid maturation. Cytogenetics is pending.

++++++++++++++++++

10. ADDENDUM FOR MDS, NOS (with abnl cytogenetics)

Addendum Diagnosis

Bone marrow: Myelodysplastic syndrome, N.O.S. (see comment)

Comment

Cytogenetic results from bone marrow aspirate (Dynagene/Lab Corp report dated 8/22/08) show a normal cell line in 18 cells and an abnormal cell line in 3 cells with interstitial deletion of 20q (long arm of chromosome 20). This finding, together with histological findings in bone marrow (dysplastic megakaryocytes and erythroids with nuclear-cytoplasmic dysynchrony), are consistent with myelodysplasia. Since the patient presents with thrombocytopenia but not anemia, this case is best classified as myelodysplastic syndrome, not otherwise specified (NOS).

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

11. Addendum for abnl cytogenetics in a pedi BM with normal morphology

Addendum Diagnosis

Bone marrow: Chromosome results of bone marrow aspirate (Dynagene report, dated 8/26/08) show an abnormal cell line (5 cells out of 20) with a small interstitial deletion of 20q, see comment

Comment

Del 20q is most often associated with myeloid disorders in adults (typically myelodysplasia). It has also been reported in some cases of lymphoblastic leukemia.

In light of this new finding, this case was reviewed (also with intradepartmental consultation with Dr. L. Chen on 9/3/08) and findings in previous final report were confirmed. No evidence of hematologic malignancy is found.

Findings were discussed with Dr. D. Brown (pediatric hematologist) on 9/3/08. Our concensus is that patient will need to be followed up closely and and a repeated bone marrow is likely to be needed in 1-2 months to rule out progression of bone marrow to a leukemic process.

++++++++++++++++++++++++++++++++++++++++++++++++++++++

12. Chronic LPD of NK cells (Reactive NK cell lymphocytosis)

Peripheral Blood:

Normochromic normocytic anemia

Mild leukopenia with moderate number of NK cells

Bone Marrow:

Hypocellular for age

Increase in NK cells in bone marrow (see comment)

Increased iron stores

Comment

-Immunophenotyping of bone marrow aspirate by flow cytometry shows approximately 50% of the lymphocytes expressing marker profile consistent with NK cell lineage (positive for CD2, CD56, CD7; and negative for CD5, CD3, CD57). These NK cells account for about 8-10% of the bone marrow cells.

Immunohistochemical stain for CD56, with adequate controls, on biopsy shows scattered positivity consistent with a small number of NK cells.

EBER-1 (insitu hybridization) on biopsy is pending. The result will be issued in addendum when available.

-In light of the relatively low number of NK cells in bone marrow (8-10%), lack of lymphocytic aggregates in biopsy, and the lack of hepatosplenomegaly and lymphadenopathy, the current findings are most consistent with a reactive change rather than aggressive NK cell leukemia/lymphoma. Reactive NK cell lymphocytosis is typically transient. An indolent variant of NK cell disorder (chronic NK cell lymphocytosis ) has also been described. Clinical follow-up with repeated CBCs and peripheral blood smear review is recommended.

-Bone marrow hypocellularity may be due to medication effect (Prograf, or antiviral medications), or viral infection. Clinical correlation is suggested.

-Bone marrow aspirate was sent for cytogenetics (see separate report)

Addendum Diagnosis

Bone marrow biopsy: negative for EBER (in-situ hybridization), consistent with an indolent NK cell disorder , see comment

Comment

Negative finding for EBER is most consistent with an indolent NK cell disorder. Note that aggressive NK cell leukemia/lymphoma is typically positive for EBER. This indolent NK cell lymphoproliferative disorder (also known as chronic NK cell lymphocytosis) has a nonaggressive course. Only exceptional cases were reported to transform to an aggressive phase. Some cases even have a transient presentation suggestive of a reactive process. In light of these findings, follow-up of patient with repeated CBCs and peripheral blood smear examination is recommended.

+++++++++++++++++++++++++++++++++++++++++++++++++

13. BM: SPLENIC MZL

Diagnosis

Peripheral blood:

- Microcytic hypochromic anemia

- Leukopenia

Bone Marrow:

- Involvement by marginal zone lymphoma (see comment)

- Increased iron stores

Comment

-Immunophenotyping of bone marrow aspirate by flow cytometry shows a T cell population (about 46% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers, an abnormal B cell population (about 48% of the cells analyzed) that is positive for CD19, CD20, CD22, surface kappa light-chain restriction. These B cells are negative for CD5, CD10, CD11c, CD25, and CD103. These B cells have small nuclear size (based on forward-scatter signal).

-Immunohistochemical stains, with adequate controls, are performed on block 1A for bcl-1, CD3, CD5, CD20, and CD23. The lymphoma cells are positive for CD20 and negative for bcl-1, CD5, CD23. Scattered T cells (positive for CD3 and CD5) are also seen.

-The immunophenotype results by flow cytometry and immunohistochemical stains, together morphological findings in bone marrow, are most consistent with marginal-zone lymphoma. Not that hairy cell leukemia is ruled out with negative expression for CD11c, CD25, and CD103.

-No peripheral lympadenopathy is found per documented H&P. This finding and patient's splenomegaly, together with marginal zone lymphoma in bone marrow, are most consistent with splenic marginal zone lymphoma.

-Bone marrow aspirate was sent for cytogenetics (see separate report)

++++++++++++++++++++++++++++

14. ADDENDUM FOR CYTOGENETICS (CML)

~~~~~ DISCUSSION AND JUSTIFICATION:

Addendum to report cytogenetic result of bone marrow.

~~~~~ ADDENDUM DIAGNOSIS:

Bone marrow: Chromosome analysis shows t(9;22), consistent with morphological diagnosis of chronic myelogenous leukemia (CML) ~~~~~ ADDENDUM CANCER REGISTRY:

Y-Malignant neoplasm or neoplasm of uncertain malignant potential or behavior ~~~~~COMMENT~~~~~

Cytogenetic result from LabCorp, dated 4/10/2009

++++++++++++++++++++++++++++++++++

ADDENDUM FOR NORMAL CYTOGENETICS

Bone marrow:

- Normal male chromosome analysis (46, XY); no clonal abnormalities seen (see comment)

Comment

LabCorp-Dynagene report (dated 9/8/10)

++++++++++++++++++++++++++++++++++++++

15. ADDENDUM FOR CYTOGENETICS AND FISH (residual APL cells)

ADDENDUM DIAGNOSIS:

Bone marrow: Chromosome analysis shows normal cytogenetic result (46, XY). However, FISH analysis shows presence of an abnormal clone positive for PML/RARA gene rearrangement.

COMMENT:

Addendum to report cytogenetic result and FISH testing result of bone marrow (Dynagene report, dated 5/11/09). The findings are consistent with the presence of a very small number of residual leukemic cells which are typically detected by FISH analysis but not by cytogenetic analysis (due to difference in sensitivity of detection).

+++++++++++++++++++++++

16. ADDENDUM FOR PCR PML-RARA (residual APL cells)

ADDENDUM DIAGNOSIS:

Bone marrow: Quantitative PCR for PML/RARA shows residual PML/RARA mRNA transcripts. The level in this patient represents a 3.41 log reduction from an average patient’s level at diagnosis.

COMMENT:

Mayo Clinic Lab report, dated 11/16/2010

++++++++++++++++++++++++++

17. ADDENDUM FOR AML WITH COMPLEX KARYOTYPE

Bone marrow:

Acute myeloid leukemia with myelodysplasia-related features (see comment)

Comment

Chromsome study (LabCorp-Dynagene, report dated 10/15/10) shows female chromosome 46, XX with complex karyotype as following:

der(10)t(10;12)(p12;q15), -12, del(17)(p12), add(18)(q2), +mar[20].

This complex karyotype is consistent with acute myeloid leukemia with myelodysplasia-related features.

FISH testing (LabCorp Dynagene) is negative for the following:

t(9;22), t(8;21), and inv(16)

++++++++++

18. BM: INADEQUATE SAMPLES (BX/CLT ONLY) FOR DX, AML-M6 POST CHEMOTX

Diagnosis:

Bone marrow biopsy and clot section:

Samples are insufficient to rule out residual leukemia (see comment)

Comment:

Our archived files show that patient had a bone marrow performed at Memorial Hermann Hospital on 2/27/09 with a final diagnosis of acute erythroid leukemia. The bone marrow aspirate at that time shows 52% normoblasts and 22% myeloblasts (45% of non-erythroid cells). Additional samples would be required for assessment of this post-chemotherapy bone marrow: peripheral blood smear with CBC, bone marrow aspirate, and biopsy touch preps. Immunophenotyping data for aspirate would also be useful. Findings on the biopsy and the need for additional samples were discussed with Dr. Quesada on 6/23/09.

Microscopic description:

Bone marrow biopsy (decalcified) is 1.3 cm in length, without touch preps. A bone marrow cellularity of 60% is estimated from biopsy. No evidence of granuloma or fibrosis is seen. The cells in the bone marrow biopsy are heterogeneous with increase in megakaryocytes. Myeloblasts cannot be reliably differentiated from other early bone marrow precursors in H&E stains.

+++++++++++++++++++++++++++++++++++++++++++++++

19. BM: ASPRATE ONLY, NO INCREASE IN BLASTS, AML S/P CHEMOTX

Diagnosis:

Bone marrow aspirate:

No increase in myeloblasts seen, suggesting remission (see comment)

Comment:

Our archived files show that patient had a bone marrow performed at Memorial Hermann Hospital on 1/27/09 with a final diagnosis of acute myeloid leukemia with t(8;21). Post-chemotherapy bone marrow on 2/27/09 showed remission with normal cytogenetics. Patient has been subsequently treated with chemotherapy in Mexico. The current aspirate sample was obtained in Mexico on 6/15/09. This aspirate shows no increase in blasts, suggesting remission in the patient at this time. No other materials (blood smear, bone marrow biopsy) were submitted for examination. However, the following information is described in patient’s report for bone marrow biopsy: hypocellular (10%) with dyserythropoiesis, no evidence of t(8;21) or inv(16) by cytogenetics and RT-PCR.

Findings were discussed with Dr. Quesada on 6/26/09.

Microscopic description:

Bone marrow aspirate is adequate with spicules present. Bone marrow cell differential shows 1% blasts, 4% promyelocytes, 1% myelocytes, 6% metamyelocytes, 28% PMNs/bands, 2% eosinophils, 4% monocytes, 14% lymphocytes, 40% erythroids. Bone marrow aspirate shows normal maturation in granulopoiesis, megakaryopoiesis, and erythropoiesis. Normoblasts are relatively increased in number with a few dysplastic forms (presumably secondary to chemotherapy). No increase in myeloblasts is seen.

+++++++++++++++++++++++++++++++++++++++++++++++

20. BM: del(5q) in 18 cells /20

Addendum Diagnosis

Bone marrow:

Refractory cytopenia with multilineage dysplasia (see comment)

Comment

Chromosome analysis of 20 cells from bone marrow aspirate (Dynagene, report dated 6/26/09) shows 18 cells with interstitial deletion of 5q as the only abnormality, and 2 cells with both del(5q) and t(4;22). These chromosome abnormalities are supportive of a diagnosis of myelodysplasia in this patient whose bone marrow shows dysplasia in erythroids and megakaryocytes. According to the WHO criteria, this case is best classified as refractory cytopenia with multilineage dysplasia. However, this case has many features of myelodysplastic syndrome with isolated del (5q): normal platelet count, increased in megakaryocytes with small size and hypolobated nuclei, 18 out of 20 cells in cytogenetic study show isolated del(5). Given the fact that myelodysplastic syndrome with isolated del (5q) responds well to Thalidomide analogues, a trial of Thalidomide analogues such as Lenalidomide may be considered in this patient if clinically indicated.

Findings were discussed with Dr. H. Juneja on 6/26/09.

+++++++++++++++++++++++++++++++++++

21. BM: NK/T CELL LYMPHOMA

Diagnosis

Peripheral Blood: Leukocytosis with reactive PMN's, hypochromic normocytic anemia.

Bone Marrow: NK/T-cell lymphoma involvement in bone marrow (see comment).
Increased iron stores

Comment

Immunophenotyping of bone marrow leukocytes by flow cytometry shows a T cell population (about 40% of the cells analyzed) with no aberrant loss or aberrant expression of T cell markers. Approximately 41% of the lymphocytes express a marker profile consistent with NK cell lineage (positive for CD2, CD56; and negative for CD3, CD7). Thes results indicate increased number of NK cells in bone marrow.

Immunohistochemical stains, with adequate controls, are performed on block 2A for CD2, CD7, and CD56. Many lymphocytes are postive for CD56 and CD2 indicating the presence of NK cells in bone marrow. CD7 shows normal number of benign T cells.

The morphology, together with flow cytomery and immunostain findings, are consistent with lymphoma involvement in bone marrow of this patient with recent diagnosis of nasal NK/T-cell lymphoma

+++++++++++++++++++++++++++

22. BM: MULTIPLE MYELOMA WITH ONLY 0.5% PLASMA CELLS IN BM

Peripheral blood:

- Hypochromic, normocytic anemia with rouleaux formation

Bone marrow:

- Normocellular for age.

- A small number (0.5%) of monoclonal plasma cells (see comment).

- Decreased iron stores.

Comment

Immunophenotyping of bone marrow aspirate by flow cytometry shows a T cell population (76% of the cells gated) with no aberrant loss or aberrant expression of T cell markers, a B cell population (17% of the cells gated) that is negative for CD5, CD10, also no surface light-chain restriction. Plasma cells account for about 0.5% of the cells analyzed and show cytoplasmic kappa light chain restriction. They are positive for CD38, CD56 and negative for CD19. These findings are consistent with the presence of monoclonal plasma cells (0.5%) in bone marrow.

Review of patient's medical records shows: elevation of IgG (2,200 mg/dl), decreased IgA (59.6 mg/dl), and decreased IgM (31.8 mg/dl). Patient recently had a diagnosis of plasmacytoma (L4 spine lesion), and has multiple lytic lesions. Even though a small number of monoclonal plasma cells are found in bone marrow, the overall clinical and laboratory findings are supportive of a diagnosis of multiple myeloma.

++++++++++++++++++++++++++++++++++++++++++++++

23. BONE MARROW: CMML-1

Peripheral blood:

- Normochromic normocytic anemia

- Monocytosis

- Thrombocytopenia

Bone marrow:

- Chronic myelomonocytic leukemia, CMML-1, see comment

COMMENT:

Peripheral blood and bone marrow aspirate show monocytosis. CBC reportedly showed anemia, thrombocytopenia, with normal WBC. Minimal dysplasia of normoblasts is seen in bone marrow. Blast count in bone marrow is 4%. Patient’s cytogenetics from bone marrow showed del(X) and immunophenotyping of aspirate by flow cytometry showed no abnormalities per conversation with Dr. Robin Brunnemann on 1/28/2010. The overall findings are consistent with chronic myelomonocytic leukemia, CMML-1.

CLINICAL INFORMATION:

51 year old female with history of HTLV-1 positivity, oral herpes, splenomegaly, anemia, thrombocytopenia, and monocytosis.

SPECIMEN SUBMITTED:

Peripheral blood smear, aspirate smear, clot

MICROSCOPIC DESCRIPTION:

CBC results reportedly show: Hgb 11.8, Platelets 53 K, WBC 6.4. WBC differential on the provide blood smear shows 32% PMNs, 24% lymphocytes, 43% monocytes, and 1% myelocytes.

Examination of blood smear shows mild normochromic normocytic anemia, slight polychromasia; normal number of leukocytes with many monocytes, and decreased in platelets. No blasts are seen.

Bone marrow aspirate is cellular with adequate spicules. Bone marrow cell differential shows 4% blasts, 0% promyelocytes, 9% myelocytes, 8% metamyelocytes, 29% PMNs, 1% eosinophils, 20% monocytes, 14% lymphocytes, 2% plasma cells, and 13% erythroids. Bone marrow aspirate shows increase in monocytes, adequate granulopoiesis, megakaryopoiesis, and slightly decreased erythropoiesis. Minimal dysplasia is seen in erythroids. No increase in blasts is seen.

Very few bone marrow cells are seen in clot section. Cellularity cannot be estimated from clot section. Iron stores are adequate. Bone marrow biopsy was not performed.

++++++++++++++++++++++++++++++++++++++++++

24. BONE MARROW- POSSIBLE MDS (RA)

Diagnosis:

Peripheral blood: Pancytopenia

Bone marrow:

Hypercellular for age

Increased megakaryopoiesis and erythropoiesis with megakaryocytic dysplasia (see comments)

Adequate iron stores with no increase in ring-sideroblasts

Comments:

Myelodysplasia (refractory anemia) cannot be ruled out with current morphological findings. Follow-up of patient and correlation with cytogenetics are suggested to rule out myelodysplasia.

Microscopic:

Examination of blood smear shows macrocytic hypochromic anemia with marked anisopoikilocytosis, slight polychromasia; decreased number of leukocytes and platelets with presence of reactive PMNs (cytoplasmic vacuoles). No hypersegmented PMNs are found. Blasts are not seen.

CBC results reportedly show: Hgb 8.4-10.2, MCV 104, Platelets 64-80 K, WBC 2.4-3.5 K. Serum iron panel, B12, and folate are reportedly normal.

Bone marrow biopsy (decalcified) is 0.3 cm in length, with touch prep. A bone marrow cellularity of 60-70% is estimated from biopsy. Increase in erythroids is seen in biopsy. Increase in megakaryocytes is also seen in biopsy, many with hypolobated nuclei. No evidence of granuloma, fibrosis, or abnormal cellular infiltrates is seen.

Bone marrow aspirate is adequate with presence of spicules. Trilineage representation and adequate maturation are seen. No increase in blasts is seen.

Iron stores from clot section are adequate with no increase in ring-sideroblasts.

Immunophenotyping of aspirate by flow cytometry (Applied Diagnostics) was reportedly showing no abnormalities. Cytogenetics was not available.

++++++++++++++++++++

25. MPN suggestive of CML with neg cytogenetic and FISH for bcr-abl

Diagnosis:

Peripheral Blood: Myeloproliferative Neoplasm (see comment)

Bone marrow: Myeloproliferative Neoplasm (see comment)

Comment:

The morphological findings in peripheral blood and bone marrow are most consistent with chronic myelogenous leukemia (CML). However, cytogenetics and FISH testing for bcr/abl mutation were reportedly negative. PCR testing for bcr/abl (using peripheral blood collected in purple-top tube) is suggested to rule out CML with cryptic bcr/abl mutation that may have been missed by cytogenetics and FISH testing. Gleevec would be the treatment of choice in that case (positive bcr/abl mutation). However, if the result of this PCR test is negative, then the overall findings would be best described as Myeloproliferative Neoplasm, NOS.

Microscopic description:

CBC results show: RBC 4.94, Hgb 13.4, Hct 41.4, MCV 84.0, MCH 27.1, MCHC 32.3, Platelets 281 K, WBC 97.7.

Examination of blood smear shows normochromic normocytic erythroids with slight polychromasia, rare NRBCs. Leukocytes are markedly increased with left shift including a few myeloblasts, eosinophilia and basophilia. PMNs show no evidence of reactive changes. Platelets are normal in number with a few giant platelets.

Bone marrow biopsy (decalcified) is 0.6 cm in length with a cellularity of 90%. Megakaryocytes are increased with small size and hypolobated nuclei. Layers of granulocytic precursors are increased in paratrabecular area. Granulocytes are markedly increased.

Bone marrow aspirate is hypercellular with adequate spicules. Bone marrow cells show marked increase in granulocytic precursors with decrease in erythroids. Eosinophils and basophils are increased. Blasts are less than 2%. No evidence of dysplasia is seen. Clot section shows similar morphology as in biopsy. Iron stores are decreased (stain done on clot section)

Other reported results:

Chromosome analysis (NeoGenomics) reportedly showed normal result (46, XY) with no clonal abnormalities. FISH testing for bcr/abl mutation (NeoGenomics) reportedly showed no evidence of this mutation.

+++++++++++++++++

26. BM: Addendum for normal cytogenetics

Bone marrow:

Normal male chromosome 46, XY with no clonal abnormalities observed (see comment)

Normal female chromosome 46, XX with no clonal abnormalities observed (see comment)

Comment:

Labcorp-Dynagene report (dated xx/xx/2010)

+++++++++++++++++++++++++++

27. BONE MARROW- Acute Erythoid Leukemia (AML-M6)

Diagnosis:

Peripheral blood: Pancytopenia with numerous myeloblasts

Bone marrow:

Acute Erythoid Leukemia (AML-M6)

Comments:

Patient has a history of lymphoma. Chemotherapy for lymphoma has been known to be associated with therapy-induded myelodysplastic syndrome and acute myeloid leukemia. Clinical correlation is suggested.

Microscopic:

Examination of blood smear shows normocytic hypochromic anemia with anisopoikilocytosis, slight polychromasia, a few NRBCs, decreased number of leukocytes and platelets with presence of numerous myeloblasts.

CBC results reportedly show: Hgb 9.5, MCV 98, Platelets 40 K, WBC 1.7. Manual differential on the peripheral blood smear shows 29% blasts, 5% myelocytes, 33% PMNs, 5% eos, 2% monos, 26% lymphs.

Bone marrow aspirate is hypercellular with presence of spicules. Erythroids are markedly increased (53%) with marked dysplasia, megakaryocytes are decreased. Myeloblasts are increased at 34%, many with basophilic cytoplasm. Differential shows 34% myeloblasts, 1% promyelocytes, 5% myelocytes, 2% bands, 1% basos, 3% mono, 1% lymph, 53% normoblasts.

Iron stores from clot section are adequate with no increase in ring-sideroblasts.

Immunophenotyping of aspirate by flow cytometry (Applied Diagnostics, dated 9/21/10) reportedly showed increase in myeloblasts (positive for CD34, CD117, CD13, and CD45). Cytogenetics is pending.

The immunophenotype and morphology are consistent with acute erythoid leukemia (AML-M6)

+++++++

28. BM: neg for congo red

Addendum Diagnosis

Bone marrow biopsy:

-Negative for amyloid deposit with Congo red stain (see comment)

Comment

Congo red stain was examined under polarized light. Request for Congo red was made by Dr. Quesada (patient's oncologist)

+++++++

29. BONE MARROW- Acute Myeloid Leukemia, therapy related

Diagnosis:

Peripheral blood: Pancytopenia with numerous myeloblasts

Bone marrow:

Acute Myeloid Leukemia, therapy-related (see comments)

Comments:

- Patient has a history of rectal cancer 7 years prior, s/p chemotherapy and radiation. Erythroids in bone marrow show dysplastic changes. Cytogenetics reportedly shows complex chromosome abnormalities.

- These findings are most supportive of therapy-related acute myeloid leukemia. Clinical correlation is suggested.

- Findings were discussed with Dr. Wei Feng on 5/5/2011

Microscopic:

Examination of blood smear shows pancytopenia, normocytic hypochromic RBCs with anisopoikilocytosis, slight polychromasia, and the presence of numerous myeloblasts (19%)

CBC results reportedly show: Hgb 9.3, MCV 90.4, Platelets 45 K, WBC 1.1. Our manual differential on the peripheral blood smear shows 19% blasts, 33% PMNs,11% monos, and 37% lymphs.

Bone marrow aspirate is hypocellular with suboptimal stain. Erythroids show moderate dysplasia, megakaryocytes are decreased. Differential shows 8% myeloblasts, 12% PMN/bands, 1% eos, 6% mono, 65% lymph, 8% normoblasts. We noted that the actual percentage of myeloblasts must be higher than 8% and most of the counted lymphocytes are likely myeloblasts (due to suboptimal stain). This conclusion is supported by the high percentage of blasts in peripheral blood of 19% (blasts in bone marrow must be equal or higher than those in peripheral blood). Also, flow cytometry analysis shows 25% myeloblasts in aspirate.

Bone marrow biopsy is markedly hypocellular (5% cellularity) with no evidence of fibrosis or granuloma.

Iron stores from aspirate and clot section are decreased with no increase in ring-sideroblasts.

Immunophenotyping of aspirate by flow cytometry (Quest Diagnostics, dated 4/29/2011) reportedly showed 25% myeloblasts (positive for MPO, CD34, CD117, CD13, CD56, and HLA-DR).

The immunophenotype and morphology are consistent with acute myeloid leukemia.

++++

30. BONE MARROW- Macrocytic Anemia

Diagnosis:

Peripheral blood: Macrocytic hypochromic anemia and neutrophilia with many hypersegmented PMNs

Bone marrow:

Normocellular for age

Increased erythropoiesis with mild dyserythropoiesis (see comments)

Increased iron stores with no increase in ring-sideroblasts

Comments:

The morphological findings are suggestive of B12 and/or folate deficiency. Serum B12 is reportedly normal and folate is reportedly elevated. To completely rule out B12 and folate deficiency, the following tests are suggested: Homocysteine, Methylmalonic Acid, and RBC folate levels.

Myelodysplasia (refractory anemia) cannot be completely ruled out with current morphological findings. Follow-up of patient and correlation with cytogenetics are suggested to rule out myelodysplasia.

Microscopic:

Examination of blood smear shows macrocytic hypochromic anemia with marked anisopoikilocytosis, slight polychromasia; normal number and morphology of platelets; neutrophilia with presence of many hypersegmented PMNs. Blasts are not seen.

CBC results were not available. Serum B12 is reportedly normal, and folate is reportedly elevated.

Bone marrow aspirate is adequate with presence of spicules. Trilineage representation and adequate maturation are seen. No increase in blasts is seen. Erythroids are slightly increased with a few dysplastic forms seen.

Bone marrow biopsy is not available. A bone marrow cellularity of 30% is estimated from clot section. No evidence of granuloma, or abnormal cellular infiltrates is seen in clot section.

Iron stores from clot section are increased with no ring-sideroblasts.

Immunophenotyping of aspirate by flow cytometry was reportedly showing no abnormalities. Cytogenetics is pending.

+++++

31. BONE MARROW: Diffuse myelofibrosis with increase in mast cells

Diagnosis:

Bone marrow: Diffuse myelofibrosis with increase in mast cells (see comments)

Comments:

Peripheral blood smear is not available for review. However, CBC reportedly shows WBC 11.4, Hgb 8.3 and platelet 383k. In light of increased WBC and normal platelet counts, myelofibrosis in this bone marrow biopsy may represent a focal finding rather than a systemic bone marrow finding. According to Dr. D. Willis, a repeated bone marrow is pending.

In light of the increase in mast cells and diffuse marrow fibrosis, systemic mastocytosis cannot be ruled out. Serum Tryptase is suggested (a sustained level above 20 ng/mL is consistent with systemic mastocytosis). For repeated bone marrow, flow cytometric analysis of mast cells with CD2 and CD25 is recommended (co-expression of these markers is consistent with systemic mastocytosis and not seen in normal mast cells).

Myelofibrosis associated with myeloproliferative neoplasms is ruled out in this case due to the lack of abnormal megakaryocytes in biopsy.

Microscopic:

Bone marrow aspirate is hypocellular with no spicules. Morphological evaluation is limited by inadequate number of cells. However, no increase in blasts or presence of abnormal cells is found.

Bone marrow biopsy (decalcified) is 1.0 cm in length. The biopsy shows diffuse fibrosis. Cytochemical stain trichrome shows diffuse collagen fibrosis throughout biopsy section. Immunohistochemical stains Mast cell tryptase, CD117 (C-Kit), and Pan CK were performed on biopsy. Pan CK is negative for presence of epithelial cells. Mast cells are identified with positive Mast cell tryptase and CD117. The number of mast cells appears moderately increased even though no clusters of mast cells are seen.

Immunophenotyping of aspirate by flow cytometry was reportedly showing no abnormalities (specimen was described as hemodilute).

++++++

32. BONE MARROW: Increased erythropoiesis with mild dysplasia

Diagnosis:

Peripheral blood: Pancytopenia

Bone marrow: Normocellular for age

Increased erythropoiesis with mild dysplasia

(see comments)

Adequate iron stores with no increase in ring-sideroblasts

Comments:

Myelodysplasia (refractory anemia) cannot be ruled out with current morphological findings. Follow-up of patient and correlation with cytogenetics are suggested to rule out myelodysplasia. Further testing and correlation with B12/folate levels are also suggested to rule out vitamin deficiency.

Microscopic:

CBC results reportedly show: Hgb 13.4, Hct 40.8, MCV 100, Platelets 100 K, WBC 2.8 K

Examination of blood smear shows macrocytic hypochromic anemia with anisopoikilocytosis, minimal polychromasia; decreased number of leukocytes and platelets. A few pseudo Pelger-Huet cells are found. Blasts are not seen.

Bone marrow biopsy (decalcified) is 0.2 cm in length. A bone marrow cellularity of 30% is estimated from biopsy. No evidence of granuloma, fibrosis, or abnormal cellular infiltrates is seen.

Bone marrow aspirate is adequate with presence of spicules. Erythropoiesis is increased (50% of nucleated bone marrow cells) with a few dysplastic forms (nuclear-cytoplasmic dyssynchrony). Megakaryopoiesis is adequate with normal maturation. Granulopoiesis is adequate with normal maturation. No increase in blasts is seen.

Iron stores (clot section) are adequate with no increase in ringed-sideroblasts.

Immunophenotyping of aspirate by flow cytometry was reportedly showing no abnormalities. Cytogenetics is still pending.

++++++

33. BM: AML

Diagnosis:

Peripheral blood:

-Leukocytosis with 5% blasts

-Hypochromic normocytic anemia

Bone marrow:

-Acute Myeloid Leukemia (see comments)

Comments:

-The morphological findings in peripheral blood and bone marrow do not support acute promyelocytic leukemia.

-Immunophenotyping of aspirate by flow cytometry (Applied Diagnostics, dated 8/30/2011) reportedly showed a myeloblast population (positive for CD13, CD33, CD34, CD38, and CD45). They have dim expression for HLA-DR and CD11b. They are also negative for CD4 and CD14 (monocytic markers).

-The immunophenotypic results and morphology are consistent with acute myeloid leukemia.

- Bone marrow aspirate was reportedly sent for cytogenetics.

Microscopic:

Examination of blood smear shows normocytic hypochromic anemia with anisopoikilocytosis, slight polychromasia, normal number and morphology of platelets, leukocytosis with a few blasts.

CBC results reportedly show: Hgb 11.6, MCV 94.3, Platelets 168 K, WBC not provided. Differential shows 49% PMNs, 30% lymphs, 14% mono, 1% baso, 1% meta, 5% myelo, and 5% blasts.

Bone marrow aspirate is hypercellular with adequate spicules. Myeloblasts are markedly increased (40%). Mature monocytes (10%) have normal morphology. Eosinophils are slightly increased with normal morphology. Many granulocytic cells show hypogranular cytoplasm. Erythroids are decreased, a few with irregular nuclear contour. Megakaryocytes are adequate in number, a few with hypolobated nuclei.

Bone marrow clot section is markedly hypercellular (80% cellularity) with marked increase in myeloblasts. A small benign lymphoid aggregate is also seen in clot section. Bone marrow biopsy is 0.5 cm in length with suboptimal bone marrow area for evaluation.

Iron stores in clot section are adequate with no increase in ring-sideroblasts.

++++++++

34. BM: anemia with marked polychromasia, no evidence of MDS

Diagnosis:

Peripheral blood: Normocytic hypochromic anemia with moderate-marked polychromasia

Bone marrow: Increased erythropoiesis with no evidence of dysplasia

(see comments)

Adequate iron stores with no increase in ring-sideroblasts

Comments:

Myelodysplasia (refractory anemia) is unlikely with increase in reticulocytes in this patient (6%). This increase in reticulocytes and increase in erythroids in bone marrow are consistent with appropriate response of bone marrow to anemia. The morphological findings in peripheral blood and bone marrow are suggestive of effective treatment of iron deficiency and/or B12 deficiency (patient was reportedly having a low B12 level and a low iron level). Another clinical scenario is bone marrow recovery after an acute episode of red cell aplasia (such as due to Parvo virus B19 infection). Clinical correlation and follow-up of patient are suggested.

Microscopic:

CBC results reportedly show: Hgb 7.8, Hct 22.2, MCV 95, Platelets 237 K, WBC 6.7 K

Examination of blood smear shows normocytic hypochromic anemia with slight anisopoikilocytosis, moderate-marked polychromasia; normal number and morphology of platelets and leukocytes. Blasts are not seen.

Bone marrow biopsy was not obtained. A bone marrow cellularity of 30% is estimated from clot section. No evidence of granuloma, or abnormal cellular infiltrates is seen in clot section.

Bone marrow aspirate is adequate with presence of spicules. Erythropoiesis is increased (43% of nucleated bone marrow cells) with no evidence of dysplasia. Megakaryopoiesis is adequate with normal maturation. Granulopoiesis is adequate with normal maturation. No increase in blasts is seen.

Iron stores (clot section) are adequate with no increase in ring-sideroblasts.

Immunophenotyping of aspirate by flow cytometry (Applied Diagnostics) was reportedly showing no abnormalities. Cytogenetics is still pending.

++++++

35. BM: cHL metastasis, rare HRS cells

Diagnosis

Peripheral blood:

- Normocytic hypochromic anemia and slight thrombocytopenia.

Bone marrow:

- Involvement of bone marrow with Hodgkin lymphoma.

- Adequate iron stores.

10/13/2011 10:35 BC/bt

Comment

- Bone marrow biopsy shows abnormal infiltrates with rare HRS cells admixed with mixture of lymphocytes and histiocytes. Immunohistochemical stains, with adequate controls, are performed on block 2A for CD3, CD15, CD20, CD30, and PAX-5. The stains show mixture of T lymphocytes (CD3-pos), histiocytes (CD15-pos), and a few B lymphocytes (CD20-pos, PAX5-pos). CD30 is negative. HRS cells cannot be definitively identified with stains, most likely due to paucity of these cells in biopsy.

-Reticulin stain for biopsy shows diffuse reticulin fibrosis, typically seen in Hodgkin lymphoma metastasis in bone marrow.

+++++++

36. BM: No Evidence of MDS

Peripheral blood:

-Hypochromic normocytic anemia

Bone marrow:

-Normocellular for age

-No histological evidence of myelodysplastic syndrome, see comments

-Presence of a small benign lymphoid aggregate

-Adequate iron stores with no ring-sideroblasts

COMMENT:

Immunophenotyping of aspirate by flow cytometry (Applied Diagnostics, dated 10/25/11) reportedly showed no abnormal immunophenotypes and no increase in blasts. Cytogenetics is pending. Correlation with cytogenetics is suggested to definitively rule out myelodysplastic syndrome.

MICROSCOPIC DESCRIPTION:

CBC results reportedly show: Hgb 8.6, Hct 27.1, MCV 97, Platelets 147 K, WBC 4.6.

Examination of blood smear shows hypochromic normocytic anemia, slight polychromasia; normal number of leukocytes with normal morphology, normal platelet count with normal platelet morphology.

Bone marrow aspirate is adequate with presence of spicules. Bone marrow cell differential shows 1% blasts, 2% promyelocytes, 9% myelocytes, 6% metamyelocytes, 46% PMNs and bands, 2% eosinophils, 9% lymphocytes, 1% plasma cells, 25% erythroids, with M:E ratio of 2.5. Bone marrow aspirate, and clot section show adequate granulopoiesis, megakaryopoiesis, and erythropoiesis. No evidence of dysplasia is found. Iron stores are adequate with no ring-sideroblasts.

A bone marrow cellularity of 30% is estimated from clot section. No evidence of granuloma is seen in clot section. A small benign lymphoid aggregate is seen in clot section that consists of small lymphocytes with mature cytological features. Bone marrow biopsy was not obtained.

++++++

37. BM: CML in accelerated phase-Addendum on cytogenetics and PCR for bcr/abl1

Addendum Diagnosis

Bone marrow:

- Chronic myelogenous leukemia, in accelerated phase (see comments)

Comment

- CYTOGENETIC RESULT (Dynagene/Lab Corp) for bone marrow aspirate showed the following:

46,XY,t(9;22)(q34;q11.2)[8]

47,idem,+der(22)t(9;22)[cp2]/

46,XY,der(9)t(9;22)(q34;q11.2),

ider(22)(q10)t(9;22)[cp10]

All GTG banded metaphases analyzed demonstrated a balanced translocation between chromosome 9 and 22 characteristic of CML. In addition, clonal secondary changes were noted in 12 cells. Evolution of additional clonal alterations, together with morphological findings in bone marrow, are consistent with accelerated phase of chronic myelogenous leukemia in this patient.

- BCR/ABL mRNA level analysis (p210 fusion form) for peripheral blood (sent to Mayo Clinic lab) was POSITIVE.

BCR/ABL p210 mRNA transcripts were detected and estimated to represent 100% of total abl (%bcr/abl(p210):abl).

++++++

38. BM:AML-Addendum on cytogenetics and PCR tests

Addendum Diagnosis

Bone marrow:

- Acute Myeloid Leukemia, normal cytogenetics results, negative NPM1, negative FLT3, positive for a single CEBPA variant of unknown significance

Comment

The following test results for bone marrow aspirate:

-Cytogenetics (Dynagene, Lab Corp): normal chromosome 46, XX

FISH testing negative for: bcr/abl, t(8;21), t(15;17), CBFB

-FLT3 (ITD, and D835), Mayo Clinic: negative

-NPM1 (Mayo Clinic): negative

-CEBPA: a single CEPA variant (c.667G>A, p.Gly233Ser), of unknown significance, not typically seen in AML

++++

39. BM: AMML, initial diagnosis with flow, notes on cytogenetics, FISH and PCR sent-outs

Peripheral blood:

- Acute myelomonocytic leukemia

Bone marrow:

- Acute myelomonocytic leukemia, see comment

- Decreased iron stores

Comment

- Immunophenotyping of peripheral blood leukocytes by flow cytometry shows a normal lymphocytic population in gate #2 (normal T cell and B cells). Analysis of cells in gate #1 shows a predominant blast population that is positive for CD13, CD33, CD4, CD117, HLA-DR, CD34, CD64, CD56, MPO, CD38, CD15, and partial positivity for CD14. These blasts are negative for CD16, CD19, CD20, CD10, and TdT. Bone marrow aspirate shows increased monoblasts/promonocytes (60%) with 10% monocytes. These findings, together with flow cytometric results, are most consistent with acute myelomocytic leukemia. The morphology and flow cytometric results do not support acute promyelocytic leukemia.

- Bone marrow aspirate was sent for cytogenetics and FISH testing for: t(15;17), inv(16) or t(16;16), t(8;21) , t(9;22) ; also PCR testing for Flt3 and NPM1

- Findings were discussed with Dr. A. Rios on 12/8/11

+++

40. BM: Classical Hodgkin lymphoma

Peripheral blood:

- Pancytopenia.

Bone marrow:

- Classical Hodgkin lymphoma, see comment.

- Diffuse reticulin fibrosis.

- Special stains for acid-fast bacilli and fungi are negative for organisms.

- Decreased iron stores.

Comment

-Bone marrow biopsy shows a few large foci of abnormal lymphoid tissue. They contain aggregates of large atypical cells with prominent nucleoli, some with binucleated / multinucleated form and lacunar form. These cells are admixed with an inflammatory background of small lymphocytes, macrophages, eosinophils, and neutrophils.

Immumohistochemical stains, with adequate controls, are performed on block 2A for CD3, CD15, CD20, CD30, Pax5, and CD45. The large atypical cells are positive for CD30 (with a membrane-Golgi pattern) and Pax5 (weak). Only a few large cells are positive for CD15. They are negative for CD3, CD20, and CD45. These results are consistent with the pattern of Hodgkin and Reed-Sternberg cells.

The morphology and immunophenotypes of the abnormal cells are consistent with classical Hodgkin lymphoma. Note that subtype of Hodgkin lymphoma cannot be determined from bone marrow biopsy.

- Reticulin stain shows diffuse reticulin fibrosis throughout biopsy section.

- Special stains for acid-fast bacilli (AFB) and fungi (GMS) are negative for organisms.

- Bone marrow aspirate was sent for microbiology cultures, see separate report

+++++++

41. BM: CML-Addendum on cytogenetics and bcr/abl1 results, consistent with accelerated phase

Addendum Diagnosis

Bone marrow:

- Chronic myelogenous leukemia, with cytogenetics and PCR (bcr/abl1) results consistent with accelerated phase (see comments)

Comment

- CYTOGENETICS RESULT (Dynagene/Lab Corp) for bone marrow aspirate showed the following:

46,XY,t(9;22)(q34;q11.2), i(17)(q10)/46, XY

Evolution of additional clonal alterations, are consistent with accelerated phase of chronic myelogenous leukemia in this patient.

- BCR/ABL mRNA level analysis (p210 fusion form): POSITIVE (Mayo Clinic Lab).

BCR/ABL p210 mRNA transcripts were detected and estimated to represent 25.0 % of total abl (%bcr/abl(p210):abl).

- Note that bone marrow aspirate shows only 3% blasts with morphological examination. However, cytogenetics and PCR results for bcr/abl1 are most consistent with CML in accelerated phase. Dr Juneja was notified of this finding on 1/18/2012

+++++

42. BM: CMML in accelerated phase

Diagnosis

Peripheral blood:

- Hypochromic normocytic anemia

- Leukocytosis with left shift

- Thrombocytopenia

Bone marrow;

- Myeloproliferative neoplasm in accelerated phase (15% blasts, see comment)

- Decreased iron stores

Comment

-Immunophenotyping of aspirate by flow cytometry shows a blast population that is positive for CD13, MPO, CD33, CD11b, CD4, CD117, and CD15. They are negative for CD34, CD14, CD64, CD56, CD19, CD10, and TdT. The blasts account for about 15% of bone marrow cells. Review of the aspirate smear shows 15% blasts, and 20% monocytes.

-The morphological findings (marked leukocytosis on admission with presence of 8% blasts, monocytosis in peripheral blood, no eosinophilia, no basophilia; current bone marrow with 15% blasts, 20% monocytes) are most consistent with chronic myelomonocytic leukemia (CMML) in accelerated phase.

-Bone marrow aspirate was sent for cytogenetics and FISH testing for: t(15;17), inv(16) or t(16;16), t(8;21) , t(9;22) ; also PCR testing for Flt3 and NPM1

-Dr Quesada (Oncology) was notified of the diagnosis on 5/17/2012

Clinical Information

Leukemia.

60 year old female who was admitted with WBC 92 k , monocyte 22%, blasts 8%, Hgb 10.5, Plt 63 k. Patient underwent leukopheresis after admission. Patient had also been started on Hydroxyurea before admission. Bone marrow as request for diagnosis of a hematologic disorder. Patient's CBC at outside hospital reportedly showed WBC 147 k, Plt 125 k

++++