ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral...
-
Upload
sherilyn-chase -
Category
Documents
-
view
219 -
download
4
Transcript of ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral...
![Page 1: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/1.jpg)
ICCS e- Newsletter CSI ICCS e- Newsletter CSI Summer 2013Summer 2013
Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral
Division of HematopathologyFUNDALEU - Buenos Aires - ARGENTINA
![Page 2: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/2.jpg)
Clinical History - Presentation Clinical History - Presentation
Previously healthy 63 y/o female, presenting with chills asthenia , constipation and weight loss of 14 kg (30 lbs) in one month.
Abdominal ultrasound & CT scan revealed multiple retroperitoneal and supraclavicular lymphadenopathies.
![Page 3: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/3.jpg)
Complete blood count & Laboratory results Complete blood count & Laboratory results CBC parameter Result Units
Reference range
WBC 10,40 x109/L 4.6-10.2
RBC 3,20 x1012/L 4.0-5.48HGB 8,90 g/dl 12.2-16.2HCT 27,00 % 37.7-47.9MCV 85,00 fl 80-97MCH 28,00 pg 27-31MCHC 32,80 gm/dl 31.8-35.4RDW 13,50 % 11-14PLT 309,00 142-424
WBC differential %Neutrophils 89 50-68Lymphocytes 7 21-30Monocytes 4 4-8Eosinophils 0 2-4Others 0 0
ESR 70 mm 0-15LDH 667 UI/l 260-460
![Page 4: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/4.jpg)
Work – up and EvaluationWork – up and EvaluationLymph node biopsy was submitted for morphology and flow cytometry, for initial evaluation.
Flow Cytometry analysis:
Selected files (8-color antibody tubes) are provided for review:Tubes #1 - 4 tested in Lymph node ; Tube BM : tested in Bone marrow aspirate
Data Acquisition : FACS CANTO II and DIVA softwareData Analysis: Infinicyt (Cytognos)
FITC PE PerCP-Cy5 PE Cy7 APC APC H7 V 450 V500
Tube #1 LAMBDA KAPPA CD5 CD19 CD38 CD10 CD20 CD45
Tube #2 CD23 CD7 CD5 CD123 CD2 CD3 HLA DR CD45
Tube #3 CD4 CD13 CD5 CD123 CD33 CD3 HLA DR CD45
Tube #4 CD36 CD64 CD34 CD117 IREM CD14 HLA DR CD45
Tube BM CD4 CD7 CD5 CD56 CD2 CD8 CD3 CD45
![Page 5: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/5.jpg)
FITC PE PerCP-Cy5 PE Cy7 APC APC H7 V 450 V500
LAMBDA KAPPA CD5 CD19 CD38 CD10 CD20 CD45
Tube #1 : B cell markers
In this first tube , an abnormal population of LARGE CELLS (in grey) is identified . Cells are NEGATIVE for all B cell markers tested; and also for CD5 and CD10. Very bright CD45 intensity and dim/neg CD38 exclude plasmacytic differentiation.
![Page 6: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/6.jpg)
FITC PE PerCP-Cy5 PE Cy7 APC APC H7 V 450 V500
Tube #2 CD23 CD7 CD5 CD123 CD2 CD3 HLA DR CD45
Tube #2 : T cell markers / Lymphoplasmacytoid DC
ABNORMAL POPULATION is shown here in RED
br HLA DR++ and dim/interm CD123+CD7, CD2 and CD3 are NEGATIVE
LYMPHOPLASMACYTOID DENDRITIC CELLS (DC2) are CD123++ HLA DR++
1
![Page 7: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/7.jpg)
Tube #3 : Myeloid markers & CD4 CD56 HLA DR
FITC PE PerCP-Cy5 PE Cy7 APC APC H7 V 450 V500
Tube #3 CD4 CD13 CD5 CD123 CD33 CD3 HLA DR CD45
ABNORMAL CELLS are br HLA DR+++ and br CD33+++ br CD4++ and dim CD13+ CD56 NEGATIVE (additional tube)
MONOCYTES are distinguished from large abnormal cells, showing normal FSC/ SSC features ; br CD13++ and dim CD4 expression
![Page 8: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/8.jpg)
FITC PE PerCP-Cy5 PE Cy7 APC APC H7 V 450 V500
Tube #4 CD36 CD64 CD34 CD117 IREM CD14 HLA DR CD45
e CSI Tube #4 : Monocytic maturation. Immature markers
Bright CD64+ expression allows the identification of MONOCYTIC LINEAGE.In this case, mature monocytes:CD36++ CD14++ and IREM-2 ++.
ABNORMAL CELLS are:CD64dim+ CD14neg/dim+ CD36neg/dim+Additional tube demonstrates that MPO is NEGATIVE
![Page 9: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/9.jpg)
Abnormal cells : CD45++ CD33++ HLA DR++ CD123+ CD4++ ,dimCD64+ ,dim/variable CD14+ , dim/variable CD36+ , IREM neg/dim+ MPOneg CD15neg CD56neg Lymph node (and BM , see below plots on the right) infiltrated by large / pathological cells , with phenotypic features that suggests monocytic / monocytic-related dendritic cell subset.
LYMPH NODE BM ASPIRATE
Summary - Immunophenotypic findings (FCM) Summary - Immunophenotypic findings (FCM)
![Page 10: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/10.jpg)
LYMPH NODE
Lymph node biopsy demonstrates a diffuse proliferation of pleomorphic large cells. The nuclei are irregular, often folded, with occassional nucleoli. The cytoplasm is abundant and eosinophilic.
Reactive eosinophils were observed in the background.
![Page 11: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/11.jpg)
Immunophenotype Immunophenotype
CD45 + MPO -
![Page 12: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/12.jpg)
CD68 +
(KP-1 Clone, stains also
myeloid cells)
CD68 +
(PGM-1 Clone)
VIMENTIN +
(Intermediate filament protein
present in cells of mesenchymal
origin)
KI67 - 75%
(high proliferation
index)
CD163 +
CD43 +
(Sialoglycoprotein on the surface of
monocytes)
Histiocytic markers
Unspecific staining
![Page 13: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/13.jpg)
BONE MARROW
Bone marrow core biopsy demonstrates marrow infiltration by neoplastic cells with similiar features as observed in lymph node.
![Page 14: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/14.jpg)
CD45 + CD43 +
MPO -CD163 +
![Page 15: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/15.jpg)
Preliminary DiagnosisPreliminary Diagnosis
LYMPH NODE & BONE MARROW involvement :
Hematologic malignancy with expression of Mono/Histiocytic markers.
![Page 16: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/16.jpg)
Given this immunophenotypic profile….Given this immunophenotypic profile….Lineage Assignment possibilitiesLineage Assignment possibilities
Immunohistochemistry
CD45 + CD43 + CD68 + CD163 +
MPO - CD34 - CD20 - CD3 -
Immunohistochemistry
CD45 + CD43 + CD68 + CD163 +
MPO - CD34 - CD20 - CD3 -
Flow cytometry:
HLA DR+++, CD33+++,CD123+,CD4+,CD64+w, CD14+w.
NG2 -, T y B -, CD13 -, CD1a -, MPO – CD56 --
Flow cytometry:
HLA DR+++, CD33+++,CD123+,CD4+,CD64+w, CD14+w.
NG2 -, T y B -, CD13 -, CD1a -, MPO – CD56 --
MYELOID STEM CELL
MYELOID STEM CELL
PLASMOCYTOID DENDRITIC CELL (DC2)
INTERSTITIAL DC
LANGHERHANS DC
MACROPHAGE
MYELOID DENDRITIC CELL (DC1)
CD14-CD11c+CD1a+CLA+
MonocyteCD14+CD11c+CD68+CD1a-CLA-
CD4+CD56+CD123+CD13+CD33+CD14+CD15+MPO+/-LISOZIMA+BDCA3+
CD14+CD11c+CD1a-BDCA2+CD123+BDCA4+
![Page 17: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/17.jpg)
Differential DiagnosisDifferential Diagnosis• HISTIOCYTIC SARCOMA.- Must express two or more monocyte/macrophage lineage antibodies (CD14, CD11c, CD13, CD68,
CD163).- CD4 (cytoplasmic), CD15, CD43, CD45, CD45RO, CD33, lysozyme +/-- WHO 2008 definition: Express monocyte/macrophage markers. Myeloid lineage antibodies (CD33,
CD13) MUST BE NEGATIVE.
• AML WITH MONOCYTIC DIFFERENTIATION/ MYELOID SARCOMA.- > = 20% myeloid blasts, with less than 20% of cells with monocytic differentiation.
AML M4; M5. - M4: The PB or BM has more than 20% blast (including promonocytes), neutrophils and their
precursors and monocytes and their precursors.- M5: Myeloid leukaemia in which 80% or more of the leukaemic cells are monocytic lineage including
monoblast, promonocytes and monocytes; a minor neutrophil component, <20%, may be present.
• PLASMACYTOID DENDRITIC CELL NEOPLASM/ BLASTIC NK-CELL LYMPHOMAHEMATODERMIC NEOPLASM.
- Expression of CD4, CD56 and CD123 antigens with concomitant negativity for other myeloid and lymphoid associated markers.
• ACUTE MYELOID DENDRITIC CELL LEUKAEMIA.- Expression of CD4, CD56 and CD123 antigens with concomitant positivity for myeloid markers
(CD13,CD33, CD64, 7.1, IREM).
![Page 18: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/18.jpg)
ACUTE MYELOID DENDRITIC CELL LEUKAEMIAACUTE MYELOID DENDRITIC CELL LEUKAEMIA
• Acute dendritic cell leukemias are very uncommon and have a lymphoplasmacytoid dendritic cell (DC2) phenotype more often than a myeloid dendritic cell phenotype (DC1).
• Myeloid dendritic cell leukaemia is exceptional, and it would differentiate from plasmacytoid dendritic cell leukaemia by the expression, as well as of CD4, CD56 and CD123, of some myeloid makers [CD13, CD14, CD15, CD33, myeloperoxidase (MPO), lysozyme] and specific myeloid dendritic cell antigens (BDCA3) instead of plasmacytoid dendritic cell antigens (BDCA2, BDCA4).
• Spontaneously occurring acute myeloid dendritic cell leukemia is very infrequent. It has been estimated, based on the study of 392 cases of AML, that 0.8% of cases had overt features of a dendritic cell malignancy.
• Anemia, thrombocytopenia, and blood, marrow, and skin involvement with dendritic-like blast and more mature appearing dendritic cells are characteristic findings. Lymph node and spleen enlargement from leukemic cell infiltration usually is present.
![Page 19: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/19.jpg)
• Blast cells do not display myeloperoxidase or esterases by cytochemistry.
• The main differential diagnosis of acute myeloid dendritic cell leukaemia is acute myeloid leukaemia (AML). In fact, some authors consider myeloid dendritic cell leukaemia as a morphological variant of AML. AML blast cells frequently express the dendritic cell-associated marker CD86, especially among acute monocytic leukaemia cells. Dendritic cell features can be found in AML cells after chemotherapy. In addition, using cytokines and CD40 ligands, a dendritic cell phenotype strikingly similar to the blast cells of myeloid dendritic cell leukaemia can be induced from AML blast cells.
ACUTE MYELOID DENDRITIC CELL LEUKAEMIAACUTE MYELOID DENDRITIC CELL LEUKAEMIA
![Page 20: ICCS e- Newsletter CSI Summer 2013 Bioq. Mariela B Monreal Dra. Marina Narbaitz Dra. Cecilia Cabral Division of Hematopathology FUNDALEU - Buenos Aires.](https://reader036.fdocuments.in/reader036/viewer/2022062421/56649d205503460f949f494e/html5/thumbnails/20.jpg)
ReferencesReferences
• Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: (IARC; 2008).
• Marshall A. Lichtmana, b, George B. Segelc Uncommon phenotypes of acute myelogenous leukemia: Basophilic, mast cell, eosinophilic, and myeloid dendritic cell subtypes: A review. Blood Cells Mol Dis.2005 Nov-Dec;35(3):370-83
• Martín-Martín L, Almeida J, Hernández-Campo PM, Sánchez ML, Lécrevisse Q, Orfao A Br J Dermatol Immunophenotypical, morphologic, and functional characterization of
maturation-associated plasmacytoid dendritic cell subsets in normal adult human bone marrow. Transfusion 2009 Aug;49(8):1692-1708
• M. Ferran, F. Gallardo, A.M. Ferrer,A. Salar, E. Perez-Vila,N. Juanpere, R. Salgado, B. Espinet, A. Orfao,–L. Florensaand R.M. Pujol Acute myeloid dendritic cell leukaemia with specific cutaneous involvement: a diagnostic challenge. Br J Dermatol 2008 May;158(5):1129-33.
• Orfao A. Neoplasias of dentritic cells: are they the counterpart of one or more cell lineages? Lab Hematol 2004;10(3):171.
• Elizabeth L Courville, Yue Wu, Jihen Kourda, Christine G Roth, Jillian Brockmann, Alona Muzikansky, Amir T Fathi, Laurence de Leval, Attilio Orazi and Robert P Hasserjian Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia modern Pathology , (11 January 2013)
• Rollins-Raval MA, Roth CG. The value of immunohistochemistry for CD14, CD123, CD33, myeloperoxidase and CD68R in the diagnosis ofacute and chronic myelomonocytic leukaemias. Histopathology. 2012 May;60(6):933-42.