This document summarizes causes of eosinophilia, including:
1) It classifies causes of eosinophilia as primary (clonal, idiopathic) or secondary. Secondary causes include infections, tissue invasion by parasites, drugs, allergies, autoimmune diseases, and malignancies.
2) Common primary causes include hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), and myeloproliferative neoplasms associated with eosinophilia such as those involving FIP1L1-PDGFRA, PDGFRB, FGFR1, and KIT mutations.
3) Secondary causes discussed include parasitic infections, fungal infections, HIV, drugs
General Medicine Interest Group
千葉大学医学部医の学生が主体となり、身体診察スキルとトレーニングする学部公認のサークルです。全8回のセッションを半期で行います。興味のある方は、ご一報ください。
連絡先:千葉大学医学部附属病院 総合診療科 鋪野紀好
メール:kshikino@gmail.com
General Medicine Interest Group
千葉大学医学部医の学生が主体となり、身体診察スキルとトレーニングする学部公認のサークルです。全8回のセッションを半期で行います。興味のある方は、ご一報ください。
連絡先:千葉大学医学部附属病院 総合診療科 鋪野紀好
メール:kshikino@gmail.com
Образ госслужащего в современной России: 25.05.2011ВЦИОМ
25 мая - Валерий Федоров выступил с докладом на тему «Образ госслужащего в современной России» на пленарном заседании IX Международной конференции «Государственное управление в XXI веке: традиции и инновации»
AML:ACUTE MYELOID LEUKAEMIA
for medical colleges teaching faculty and students as well. it includes AML causes , histopathological slides of subclasses of Acute myeloid leukemia, classification , diagnosis, management modalities, complications .Acute leukemias are stem cell disorders characterized by malignant neoplastic proliferation and accumulation of immature and non functional hematopoietic cells in the bone marrow.
The neoplastic cells show increased proliferation and/or decreased apoptosis.
If the defect primarily affects the common myeloid progenitor (CMP) then it is called Acute myeloid leukemia.
Acute myeloid leukemia (AML) is a neoplastic disease characterized by infiltration of the blood, bone marrow, and other tissues by proliferative, clonal undifferentiated cells of the hematopoietic system.
AML is the result of a sequence of somatic mutations in a multipotential primitive hematopoietic cell or, in some cases, a more differentiated progenitor cell.
It can be slow growing or rapidly fatal.
AML is the predominant form of leukemia during the neonatal period
Incidence : 1.5/100,000/year in infants decreases to approximately 0.4 per 100,000 children ages 5 to 9 years, increases gradually to 1.0 persons per 100,000 until age 25 years, and thereafter increases exponentially until the rate reaches approximately 25/100,000 persons.
AML accounts for 15 to 20 percent of the acute leukemias in children and 80 percent of the acute leukemias in adults.
Men > Women (4.5 : 3)
HEREDITY
1) Chromosomal aneuploidy like Trisomy 21 noted in Down syndrome
2) Defective DNA repair, e.g., Fanconi anemia, Bloom syndrome, and Ataxia telangiectasia
3) Congenital neutropenia ie Kostmann syndrome
4) Germline mutations of CCAAT/enhancer-binding protein α (CEBPA), runt-related transcription factor 1 (RUNX1), and tumor protein p53 (TP53) have also been associated with a higher predisposition to AML
RADIATION
Peaks after 5 to 7 yrs of exposure.
Therapeutic radiation alone seems to add little risk of AML but can increase the risk in people also exposed to alkylating agents.
CHEMICAL AND OTHER EXPOSURES
Exposure to benzene, plastic, rubber, petroleum products, paint, ethylene oxide, herbicides and pesticides can increase the risk.
Smoking can also increase the risk
DRUGS
Anticancer drugs are the leading cause of therapy-associated AML.
Alkylating agent–associated leukemias occur on average 4–6 years after exposure, and affected individuals have aberrations in chromosomes 5 and 7.
Topoisomerase II inhibitor–associated leukemias occur 1–3 years after exposure, and affected individuals often have aberrations involving chromosome 11q23.
Other agents like Chloramphenicol, phenylbutazone, and, less commonly, chloroquine and methoxypsoralen.
SYMPTOMS :
Present with nonspecific symptoms initially.
Fatigue is the first symptom
Fever with or without infection will be present in approximately 10% patients
Bleeding, easy bruising
occasional
Plasma cell disorders is a difficult topic where most residents and students confuse with regarding to differentiating between various types of para-proteinemias or plasma cell dyscrasias. This simple presentation will highlight the key points in differentiating, diagnosing these orders. Initial management principles are discussed as well.
multiple myloma
By: Nader Amir Al-assadi
Supervised by : Dr/ Ghazi Alariqe
taiz university
Multiple myeloma (MM) is a plasma cell malignancy in which monoclonal plasma cells proliferate in bone marrow, resulting in an over abundance of monoclonal para protein (M protein), destruction of bone, and displacement of other hematopoietic cell lines.
The precise etiology of MM has not yet been established.
Roles have been suggested for a variety of factors, including genetic causes, environmental or occupational causes,radiation, chronic inflammation, and infection .
Bone Marrow Histology is a Pathognomonic Clue to Each of the JAK2V617F, MPL,5...asclepiuspdfs
According to the World Health Organization and Clinical Laboratory Molecular and Pathological criteria bone marrow pathology in JAK2V617F mutated trilinear myeloproliferative neoplasm (MPN) patients essential thrombocythemia (ET) and polycythemia vera are indistinguishably featured by clustered medium to large pleomorphic megakaryocytes and increased cellularity (60–90%) due to increased erythropoiesis and megakaryopoiesis. MPL515 mutated ET is the second distinct clonal MPN characterized by thrombocythemia in a normocellular bone marrow showing clustered increased large to giant mature megakaryocytes with staghorn-like hyperlobulated nuclei. Calreticulin (CALR) mutated hypercellular thrombocythemia associated with prefibrotic megakaryocytic, granulocytic myeloproliferation (MGM) recently became the third distinct MPN featured by dense clusters of immature megakaryocytes with cloud-like nuclei. Bone marrow pathology in newly diagnosed MPN patients appears to be a pathognomonic clue for diagnostic differentiation between JAK2V617F mutated trilinear MPN, MPL515 normocellular thrombocythemia, and CALR thrombocythemia with MGM characteristics followed by secondary reticulin fibrosis. Their natural histories clearly differ featured by an increase of erythro/granulopoiesis and cellularity in JAK2V617F, decrease of erythropoiesis and cellularity in MPL515 and increase of dual megakaryo/granulopoiesis and cellularity in CALR mutated MPN.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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9. HESの分類 (Hypereosinophilic Diseases Working Group 2005)
9
Hypereosinophilic syndromes (HES) classification
FIP1L1-PDGFRA FIP1L1-PDGFRA
positive
Myeloproliferative HES Lymphocytic HES
Undefined
HES
Associated
HES
With a defined
diagnosis
Churg-
Strauss,
mastocytosis,
inflammatory
bowel disease,
sarcoidosis,
HIV and other
diseases
Overlap
HES
Associated
with organ-
restricted
eosinophilic
disorders (may
not meet all 3
criteria),
eosinophil-
associated
gastrointestinal
disorders,
eosinophilic
pneumonia,
eosinophilia
myalgia
syndrome
Familial
HES
Family
history of
documented
persistent
eosinophilia
of unknown
cause
Benign
No
organ
involve-
ment
negative
Episodic
Cyclical
angioedema
and
eosinophilia
Complex
Organ dysfunction
but not
myeloproliferative
or lymphocytic
variant
Aetiology unknown
Clonal eosinophils* or 4
or more of:
Dysplastic eosinophils,
High serum B12,
High serum tryptase,
Anaemia,
Thrombocytopenia,
Hepatosplenomegaly,
Marrow hypercellularity,
Spindle-shaped mast cells
and/or myelofibrosis
Monitor for T-cell clonality or other cytogenetic abnormalities
Chronic
eosinophilic
leukaemia
(CEL)
Cytogenic
abnormalities
and/or blasts
Eosinophils ≥ 1.5 × 109/l
Persistent eosinophilia and/or end organ damage/dysfunction
Exclusion of secondary causes of eosinophilia
Clonal T cells
*Clonality analysis based on the digestion of genomic
DNA with methylation-sensitive restriction enzymes
followed by PCR amplification of the CAG repeat at the
human androgen receptor gene (AR) locus on the X
chromosome
Review
10. 骨髄増殖性のHES
Chronic Eosinophilic Leukemia, SM with Eosinophiliaが代表的
圧倒的に男性例が多い.
FIP1L1-PDGFRA陽性例は極 かな例外を除いて全て男性例.
iHESと同じように心血管障害も多い. Loefflar endocarditisを呈する.
CELはCMLの1 typeでありImatinibが有効.
特にFIP1L1-PDGFRA陽性例は著効し, 投与量も100mg/dの低用量でOK
HESのうち, FIP1L1-PDGFRA陽性例は4-12.5%と母集団により様々.
10
British Journal of Haematology, 2009;145:271–285
12. 骨髄 刺所見による鑑別.Review
British Journal of Haematology, 2009;145:271–285
PDGFRβ (+): PDGFRB-rearranged eosinophilic leukemia/
Chronoic Myelomonocytic leukemia
FGFR1 (+): FGFR1-rearranged (stem cell leukemia and
lymphoma syndrome with 8p11 translocations)
Cancer J 2007;13: 384–391
13. CEL vs SM with Eoの鑑別.
Score >0ではFIP1L1/PDGFRA陽性 CELを示唆,
Score <0ではKIT D816V陽性 SM with Eoを示唆する.
他にEo上昇をしめす骨髄増殖性疾患は,
Acute leukemia associated with eosinophilia
MDS associated with eosinophilia
他のMPD associated with eosinophilia
Table II. Risk factor scores to distinguish eosinophilia due to separate mutations.
Score Risk factor for FIP1L1/PDGFRA eosinophilia Score Risk factor for KIT D816V eosinophilia
+3 Absolute eosinophil count/tryptase > 100 )3 Absolute eosinophil count/tryptase £100
+3 Dense mast cell aggregates in bone marrow absent )3 Dense mast cell aggregates in bone marrow present
+3 Peak absolute eosinophil count > 10,000
+2 Serum B12 increased
)2 Gastrointestinal symptoms
)2 Urticaria pigmentosa
+1 Pulmonary symptoms
)1 Female gender
+1 Cardiac symptoms
)1 Thrombocytosis
Positive total score denotes FIL1L1/PDGFRA-associated hypereosinophilic syndrome or chronic eosinophilic leukaemia. Negative total score denotes
KIT D816V-associated systemic mastocytosis with eosinophilia.
Modified from J Allergy Clin Immunol, 120, Maric, I., Robyn, J., Metcalfe, D.D., Fay, M.P., Carter, M., Wilson, T., Fu, W., Stoddard, J., Scott, L.,
Hartsell, M., Kirshenbaum, A., Akin, C., Nutman, T.B., Noel, P. & Klion, A.D. KIT D816V-associated systemic mastocytosis with eosinophilia and
FIP1L1/PDGFRA-associated chronic eosinophilic leukaemia are distinct entities, 680-687. Copyright 2007, with permission from Elsevier. The absolute
eosinophil count is given as eosinophils/mm3
and the tryptase level is given as ng/ml to maintain the correct ratios presented in the original article.
ª 2009 Blackwell Publishing Ltd, British Journal of Haematology, 145, 271–285 275
British Journal of Haematology, 2009;145:271–285
Cancer J 2007;13: 384–391
14. Systemic
Mastcytosis
WHOではSMを7つに分類.
WHOのSM診断Criteria
Major 1つ+ Minor 1つ
もしくはMinor 3つで診断.
14
Cancer J 2007;13: 384–391
TABLE 3. “B” Findings: Indication of High Mast Cell Burden
1. Infiltration grade (mast cells) in Ͼ30% in bone marrow on histologic examination and serum total tryptase levels Ͼ200 ng/mL
2. Hypercellular marrow with loss of fat cells, discrete signs of dysmyelopoiesis without substantial cytopenias or WHO criteria for
syndrome or myeloproliferative disorder
3. Organomegaly: palpable hepatomegaly, splenomegaly, or lymphadenopathy (on computed tomography scan or ultrasound) Ͼ2 cm
function
Data from Ref. 65.
TABLE 4. “C” findings: Indication of Impaired Organ Function Attributable to Mast Cell Infiltration66
1. Cytopenia(s): absolute neutrophil count Ͻ1,000/L, or hemoglobin Ͻ10g/dL, or platelets Ͻ100,000/L
2. Hepatomegaly with ascites and impaired liver function
3. Palpable splenomegaly with hypersplenism
4. Malabsorption with hypoalbuminemia and weight loss
5. Skeletal lesions: large-sized osteolysis or severe osteoporosis causing pathologic fractures
6. Life-threatening organopathy in other organ systems that definitively is caused by an infiltration of the tissue by neoplastic mast c
Data from Ref. 66.
TABLE 5. WHO Criteria for Diagnosis of SM*
Major
Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organ sections (Ͼ15 mast cells aggregating)
Minor
a. Ն25% mast cells in tissue sections or bone marrow aspirate smear are spindle shaped or have atypical morphology
b. c-kit point mutation at codon 816V
c. Expression of CD2 and/or CD25 by mast cells
d. Baseline serum tryptase persistently Ͼ20 ng/mL (not valid in presence of another non–mast cell clonal disorder)
al residual disease after imatinib therapy can be as-
by quantitative molecular analysis.44
PDGFRB rearrangement was first characterized in the
of a fusion tyrosine kinase encoding regions of
RB and the ets-like gene, ETV6 [ETV6-PDGFRB,
(q33;p13)].46 At present, several other PDGFRB fu-
anscripts are known to exist and are associated with
nt myeloproliferative neoplasm (MPN) phenotypes
ted with eosinophilia.47–55 As has been seen in indi-
with PDGFRA-rearranged MPNs, imatinib therapy
es complete hematologic remission in PDGFRB-rear-
clonal eosinophilia.48,49,51,55–57
FGFR1 translocations are usually associated with a clin-
enotype with features of both an aggressive, eosinophilia-
ted MPN and T cell lymphoblastic lymphoma.58 The
site syndrome is known as either the 8p11 myeloprolif-
syndrome or stem cell leukemia lymphoma syndrome
molecularly characterized by fusion of various 5Ј partner
o the 3Ј part of FGFR1, making it constitutively active.
utation is present in both myeloid and lymphoid lineage
–63 Clinically, 8p11 myeloproliferative syndrome/stem
kemia lymphoma syndrome has an aggressive clinical
with a rapid transformation into acute leukemia. At
, drug therapy is ineffective and allogeneic stem cell
antation should be considered as soon as the particular
sis is established.
ation and Management of
hoproliferative Variant Idiopathic
ophilia
The lymphoproliferative variant of HES is a poorly
number and/or function (Table 2).65 Accordingly, 7 disease
variants are considered, including cutaneous mastocytosis, indo
lent systemic mastocytosis (ISM), SM with an associated clona
hematologic non–mast cell disorder (SM-AHNMD), aggressive
systemic mastocytosis (ASM), mast cell leukemia, mast cel
sarcoma, and extracutaneous mastocytoma.
The WHO classification of mastocytosis mandates a
TABLE 2. WHO Variants of Mastocytosis65
1. Cutaneous mastocytosis (CM)
a. Maculopapular CM
b. Diffuse CM
c. Mastocytoma of skin
2. Indolent systemic mastocytosis (ISM)
a. Smoldering systemic mastocytosis (SSM)
b. Isolated bone marrow mastocytosis
3. Systemic mastocytosis with an associated clonal hematological non–
mast cell lineage disease (SM-AHNMD)
a. SM-myelodysplastic syndrome
b. SM-myeloproliferative disorder
c. SM-chronic eosinophilic leukemia
d. SM-chronic myelomonocytic leukemia
e. SM-non-Hodgkin lymphoma
4. Aggressive systemic mastocytosis (ASM)
With eosinophilia (SM-eo)
5. Mast cell leukemia (MCL)
Aleukemic MCL
6. Mast cell sarcoma
7. Extracutaneous mastocytoma
15. 肥満細胞の活性化の評価には “B”症状の評価,
肥満細胞浸潤による臓器障害は “C”症状で評価する.
SMによるEosinophiliaでは皮膚症状が多い.
肥満細胞クローンはCD25+ and/or CD2+最も多い.
また, 血中Tryptase<20ng/mLはSMを除外し得る.
KITD816V mutaionが代表的な遺伝子異常. 15
TABLE 3. “B” Findings: Indication of High Mast Cell Burden
1. Infiltration grade (mast cells) in Ͼ30% in bone marrow on histologic examination and serum total tryptase levels Ͼ200 ng/mL
2. Hypercellular marrow with loss of fat cells, discrete signs of dysmyelopoiesis without substantial cytopenias or WHO criteria for myelodysplastic
syndrome or myeloproliferative disorder
3. Organomegaly: palpable hepatomegaly, splenomegaly, or lymphadenopathy (on computed tomography scan or ultrasound) Ͼ2 cm without impaired organ
function
Data from Ref. 65.
TABLE 4. “C” findings: Indication of Impaired Organ Function Attributable to Mast Cell Infiltration66
1. Cytopenia(s): absolute neutrophil count Ͻ1,000/L, or hemoglobin Ͻ10g/dL, or platelets Ͻ100,000/L
2. Hepatomegaly with ascites and impaired liver function
3. Palpable splenomegaly with hypersplenism
4. Malabsorption with hypoalbuminemia and weight loss
5. Skeletal lesions: large-sized osteolysis or severe osteoporosis causing pathologic fractures
6. Life-threatening organopathy in other organ systems that definitively is caused by an infiltration of the tissue by neoplastic mast cells
Data from Ref. 66.
TABLE 5. WHO Criteria for Diagnosis of SM*
Major
Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organ sections (Ͼ15 mast cells aggregating)
Minor
a. Ն25% mast cells in tissue sections or bone marrow aspirate smear are spindle shaped or have atypical morphology
b. c-kit point mutation at codon 816V
c. Expression of CD2 and/or CD25 by mast cells
d. Baseline serum tryptase persistently Ͼ20 ng/mL (not valid in presence of another non–mast cell clonal disorder)
*Major plus one minor or three minor criteria.
The Cancer Journal • Volume 13, Number 6, November/December 2007 HES, CEL, and MCD
Cancer J 2007;13: 384–391
17. 骨髄, リンパ増殖性のHES vs iHESの鑑別OSINOPHILIC SYNDROME AND CLONAL EOSINOPHILIA
Peripheral blood screening
for FIP1L1-PDGFRA
using FISH or RT-PCR
Bone marrow biopsy
with cytogenetics
Peripheral blood lymphocyte
phenotyping and TCR
gene rearrangement studies
First step
Second step
Third step
Mutation
present
Idiopathic eosinophilia
including HES
“Lymphocytic” variant
hypereosinophilia
5q33 translocation
present
8p11 translocation
present
Other abnormalities
or excess blasts present
All the above negative
FIP1L1-PDGFRA–
associated
clonal eosinoplilia
PDGFRB-rearranged
clonal eosinophilia
FGFR1-rearranged
clonal eosinophilia
CEL-NOS or
other WHO-defined
myeloid neoplasm
Abnormal or clonal
lymphocytes present
Mayo Clin Proc. 2010;85(2):158-164
18. HESの分類 (Hypereosinophilic Diseases Working Group 2005)
18
Hypereosinophilic syndromes (HES) classification
FIP1L1-PDGFRA FIP1L1-PDGFRA
positive
Myeloproliferative HES Lymphocytic HES
Undefined
HES
Associated
HES
With a defined
diagnosis
Churg-
Strauss,
mastocytosis,
inflammatory
bowel disease,
sarcoidosis,
HIV and other
diseases
Overlap
HES
Associated
with organ-
restricted
eosinophilic
disorders (may
not meet all 3
criteria),
eosinophil-
associated
gastrointestinal
disorders,
eosinophilic
pneumonia,
eosinophilia
myalgia
syndrome
Familial
HES
Family
history of
documented
persistent
eosinophilia
of unknown
cause
Benign
No
organ
involve-
ment
negative
Episodic
Cyclical
angioedema
and
eosinophilia
Complex
Organ dysfunction
but not
myeloproliferative
or lymphocytic
variant
Aetiology unknown
Clonal eosinophils* or 4
or more of:
Dysplastic eosinophils,
High serum B12,
High serum tryptase,
Anaemia,
Thrombocytopenia,
Hepatosplenomegaly,
Marrow hypercellularity,
Spindle-shaped mast cells
and/or myelofibrosis
Monitor for T-cell clonality or other cytogenetic abnormalities
Chronic
eosinophilic
leukaemia
(CEL)
Cytogenic
abnormalities
and/or blasts
Eosinophils ≥ 1.5 × 109/l
Persistent eosinophilia and/or end organ damage/dysfunction
Exclusion of secondary causes of eosinophilia
Clonal T cells
*Clonality analysis based on the digestion of genomic
DNA with methylation-sensitive restriction enzymes
followed by PCR amplification of the CAG repeat at the
human androgen receptor gene (AR) locus on the X
chromosome
Review
26. HESの分類 (Hypereosinophilic Diseases Working Group 2005)
26
Hypereosinophilic syndromes (HES) classification
FIP1L1-PDGFRA FIP1L1-PDGFRA
positive
Myeloproliferative HES Lymphocytic HES
Undefined
HES
Associated
HES
With a defined
diagnosis
Churg-
Strauss,
mastocytosis,
inflammatory
bowel disease,
sarcoidosis,
HIV and other
diseases
Overlap
HES
Associated
with organ-
restricted
eosinophilic
disorders (may
not meet all 3
criteria),
eosinophil-
associated
gastrointestinal
disorders,
eosinophilic
pneumonia,
eosinophilia
myalgia
syndrome
Familial
HES
Family
history of
documented
persistent
eosinophilia
of unknown
cause
Benign
No
organ
involve-
ment
negative
Episodic
Cyclical
angioedema
and
eosinophilia
Complex
Organ dysfunction
but not
myeloproliferative
or lymphocytic
variant
Aetiology unknown
Clonal eosinophils* or 4
or more of:
Dysplastic eosinophils,
High serum B12,
High serum tryptase,
Anaemia,
Thrombocytopenia,
Hepatosplenomegaly,
Marrow hypercellularity,
Spindle-shaped mast cells
and/or myelofibrosis
Monitor for T-cell clonality or other cytogenetic abnormalities
Chronic
eosinophilic
leukaemia
(CEL)
Cytogenic
abnormalities
and/or blasts
Eosinophils ≥ 1.5 × 109/l
Persistent eosinophilia and/or end organ damage/dysfunction
Exclusion of secondary causes of eosinophilia
Clonal T cells
*Clonality analysis based on the digestion of genomic
DNA with methylation-sensitive restriction enzymes
followed by PCR amplification of the CAG repeat at the
human androgen receptor gene (AR) locus on the X
chromosome
Review
33. Evaluate for secondary causes
Drug history
Travel history
Stool for ova and parasites
Other tests if indicated
Clonal eosinophilia
with a molecular
target for imatinib
Clonal eosinophilia
without a molecular
target for imatinib
Hypereosinophilic
syndrome
Hydroxyurea
Vincristine
Cladribine
Allogeneic transplant
Imatinib, 100 mg / d Consider treatment
option that is optimal
to the underlying
clonal disorder
Interferon alfa with or
without prednisone
No response
No response Imatinib, 400 mg / d
Evaluate for clonal eosinophilia
Bone marrow examination with tryptase stains
Cytogenetic studies
FISH or RT-PCR to detect FIP1L1-PDGFRA mutation
Mayo Clin Proc. 2005;80(1):75-83