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International Journal of Laboratory Hematology

The Official journal of the International Society for Laboratory Hematology

ORIGINAL ARTICLE INTERNAT IONAL JOURNAL OF LABORATO RY HEMATO LOGY

ICSH recommendations for the standardization of nomenclature


and grading of peripheral blood cell morphological features
L. PALMER*, C. BRIGGS , S. MCFADDEN , G. ZINI , J. BURTHEM , G. ROZENBERG**,
M. PROYTCHEVA , S. J. MACHIN

*Haematology Laboratory, S U M M A RY
Middlemore Hospital, Auckland,
New Zealand These guidelines provide information on how to reliably and con-

University College London sistently report abnormal red blood cells, white blood cells and
Hospitals, London, UK

McFadden Consulting, platelets using manual microscopy. Grading of abnormal cells,


Columbus, OH, USA nomenclature and a brief description of the cells are provided. It is

Universita Cattolica del Sacro important that all countries in the world use consistent reporting of
Cuore, Rome, Italy
blood cells. An international group of morphology experts have
Institute of Cancer Sciences,
University of Manchester, decided on these guidelines using consensus opinion. For some red
Manchester, UK blood cell abnormalities, it was decided that parameters produced
**SEALS Randwick, Prince of by the automated haematology analyser might be more accurate
Wales Hospital, Randwick,
NSW, Australia
and less subjective than grading using microscopy or automated
image analysis and laboratories might like to investigate this fur-
University of Arizona Medical
Center, Tucson, AZ, USA ther. A link is provided to show examples of many of the cells dis-
cussed in this guideline.
Correspondence:
Lynn Palmer, Haematology
Laboratory, Middlemore
Hospital, Private Bag 93311,
Otahuhu, Auckland 1640,
New Zealand.
Tel.: +64 9 2760167;
Fax: +64 9 2704761;
E-mail: Lynn.Palmer@
middlemore.co.nz

doi:10.1111/ijlh.12327

Received 26 August 2014;


accepted for publication 10
December 2014

Keywords
Blood, morphology, RBC,
platelets, WBC

2015 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 287303 287
288 L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY

pated in a survey on blood film morphology and grad-


INTRODUCTION
ing routinely used in their respective laboratories. The
The presence of qualitative flags and/or quantitative results of this survey were discussed at a full day
abnormal results may indicate the need for peripheral meeting in New Orleans USA (May 2011).
blood (PB) film review and/or a manual differential This preliminary meeting resulted in a consensus
count. The examination of a well made and stained agreement on red cell, white cell and platelet nomen-
PB film coupled with the complete blood count infor- clature (with a suggestion to include a short descrip-
mation and the ability and skill of the reviewer adds tion of these cells and morphological abnormalities),
qualitative and/or quantitative information and is an and a proposal to develop a grading system for these
essential part of the diagnostic work-up. Abnormal cell types. One important recommendation was to
morphologic findings are reported in various ways: (i) encourage the use of grading some cell morphology
a simple description, (ii) the use of terms such as pres- using analyser parameters which can be generated
ent or absent, (iii) a semi-quantitative determination, with a higher level of accuracy and precision com-
mild (+), moderate (++), marked (+++), (iv) a quanti- pared with observer use of the optical light micro-
tative percentage of the morphological abnormalities: scope, for example red cell size abnormalities mean
normal (<5%), mild (525%), moderate (2550%), cell volume (MCV) for microcytosis and macrocytosis,
marked (>50%) although certain morphological and mean cell haemoglobin (MCH) for hypochromia
abnormalities, for example schistocytes, will have a and hyperchromia. However, it is important that the
greater significance at lower percentage numbers than laboratory establishes policies to review peripheral
other abnormalities such as hypochromia and this is blood smears for abnormalities when the full blood
reflected in the proposed grading criteria. count (FBC) data contain test results that indicate
Worldwide, there is a marked variation in blood pathologies which must be investigated.
film evaluation, reporting practices and morphology Laboratories that do not have advanced haematolo-
terminology with recommendations in the literature gy analysers which produce morphology grading will
[1, 2] and in local regional publications from a num- need to establish their own guidelines for when to
ber of different national societies including the College examine the peripheral blood smear for morphological
of American Pathologists (CAP), the United Kingdom elements.
National External Quality Assessment Service (UK The writing Committee collected all available data
NEQAS), the Japanese Society for Laboratory Hema- and after an exhaustive review and analysis of the lit-
tology and the Royal College of Pathologists of Aus- erature, the preliminary draft was circulated among
tralasia Quality Assessment Programs (RCPA QAP). the members, and a final draft was fully agreed on by
Although there is no evidence that one reporting the committee. The Working Group communicated by
system is superior to the others, it has become evident internet e-conferencing. Moreover, the in-progress
that there is a need to develop a global consensus drafts of this guideline were discussed and finalized
guideline for the grading of blood film abnormalities during the ICSH General Assembly meetings in Octo-
and blood film reporting as part of good laboratory ber 2013 (Gerrards Cross, UK) and May 2014 (The
and clinical practice and for use by laboratory accredi- Hague, the Netherlands). In addition to this document,
ting agencies. The aim of the ICSH committee on it was agreed that an IP address for a link to the mor-
Standardization of Peripheral Blood Cell Morphology, phological image web database of Manchester Metro-
Nomenclature and Grading was to provide a guideline politan University, UK, and ICSH.org be provided to
for the nomenclature and grading of red cell, white offer reference images for some of the cell types and
cell and platelet abnormalities. morphological abnormalities included in this docu-
ment. The images may also be found as additional sup-
porting information (supplementary images) with the
M AT E R I A L S A N D M E T H O D S
online version of the manuscript. An ad hoc meeting
An international group of pathologists, haematologists in Manchester was organized to select the images.
and scientists with blood film morphology expertise It is not the purpose of this guideline to provide
from Europe, America, Australasia and Asia partici- recommendations for standardized blood film prepara-

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L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY 289

tion, staining and examination or an exhaustive


Table 1. Morphology Grading Table
description of blood cell morphology. For these
aspects, the authors recommend reference to existing Grading System
ISLH/ICSH guidelines and standard morphology text-
Mod/2+, Many/3+,
books [15]. Nor is it the purpose of this guideline to Cell Name Few/1+ % %
provide diagnostic criteria for the classification and
diagnosis of haematological malignancies or other dis- RBC
Anisocytosis N/A 1120 >20
ease states.
Macrocytes N/A 1120 >20
There were a number of differences in opinion on Oval macrocytes N/A 25 >5
nomenclature and practice between different world Microcytes N/A 1120 >20
regions evident from the initial meeting in New Hypochromic cells N/A 1120 >20
Orleans and the committee members acknowledge Polychromasia N/A 520 >20
this. This document reflects a consensus agreement on Acanthocytes N/A 520 >20
Bite cells N/A 12 >2
nomenclature and grading between the participating
Blister cells N/A 12 >2
committee members and is intended as a guideline Echinocytes N/A 520 >20
only. We come from laboratories of different sizes and Elliptocytes N/A 520 >20
scopes of practice, serving different populations and Irregularly N/A 12 >2
types of patients. One reporting system probably would contracted cells
Ovalocytes N/A 520 >20
not fit all and there should be some degree of flexibility
Schistocytes <1% 12 >2
in the way laboratories report. This may to some extent Sickle cells N/A 12 >2
be dictated by the limitations of the different Labora- Spherocytes N/A 520 >20
tory Information Systems and middleware in use. Stomatocytes N/A 520 >20
Target cells N/A 520 >20
Teardrop cells N/A 520 >20
G R A D I N G O F M O R P H O L O G I C A L F E AT U R E S Basophilic stippling N/A 520 >20
Howell-Jolly bodies N/A 23 >3
The grading of morphology elements should provide Pappenheimer bodies N/A 23 >3
the clinician with useful information regarding the WBC
status of any abnormality in the peripheral blood. This Dohle bodies N/A 24 >4
means that it is the responsibility of the laboratory to Vacuolation N/A 48 >8
(neutrophil)
provide information to assist in the differential diag-
Hypogranulation N/A 48 >8
nosis instead of providing bits of data that are not (neutrophil)
clinically significant. Therefore, the morphology grad- Hypergranulation N/A 48 >8
ing table included contains a two-tiered grading sys- (neutrophil)
tem, for 2+ (moderate) and 3+ (many). The Platelets
designation for 1+ (few/rare) is reserved only for Giant Platelets N/A 1120 >20
schistocytes, as the observation even in small numbers
is clinically significant. Each laboratory and laboratory generate instrument flags that should be confirmed
system should have policies in place to ensure the by optical microscope. In a stained PB film, normal
consistent application of the grading criteria (Table 1). RBC are on average 7.5 lm in diameter and round
or slightly oval in shape with an area of central pal-
lor occupying approximately the middle third of the
RED BLOOD CELLS
cell. Microscopic slide review of red cells and the
Automated analyser peripheral blood (PB) counts identification of abnormalities in size, shape and
provide accurate and precise red blood cell (RBC) staining and the presence of inclusions, remains a
counts and red cell indices, information on RBC fundamental way of identifying morphological abnor-
population distribution, size and haemoglobin con- malities useful in the diagnostic work-up. According
tent less than one minute after sample aspiration. to the R umke table distribution [6], a minimum of
Abnormalities in one or more of these parameters 1000 RBC should be evaluated to provide a precise

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290 L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY

percentage of the cells having a particular morpho- and follow-up of thrombotic thrombocytopenic pur-
logical abnormality. pura (TTP) and haemolytic uraemic syndrome (HUS)
As a general recommendation, the ICSH group rec- [7]. There is wide variation in red cell nomenclature
ommends providing only a qualitative report for those in common use and a table showing the recom-
presenting with RBC abnormalities; however, a schis- mended nomenclature and common red cell syno-
tocyte count may be of clinical value for the diagnosis nyms has been provided (Table 2).

Table 2. Common red cell synonyms

Recommended Common clinical conditions


Nomenclature Synonym associated with

Acanthocyte acanthoid cell, astrocyte, burr cell, prickle cell, Liver disease, vitamin E deficiency,
pyknocyte, star cell, spur cell, thorn cell postsplenectomy, abetalipoproteinaemia,
McLeod RBC phenotype
Basophilic punctate basophilia Lead poisoning, haemoglobinopathies,
stippling thalassaemia, abnormal haem synthesis
Bite cell keratocytes G6PD deficiency
Blister cell puddle cell, eccentrocyte Oxidative haemolysis, G6PD deficiency
Echinocyte berry cell, burr cell, crenated cell, Liver and renal disease, pyruvate kinase
mulberry cell, poikilocyte, pyknocyte, deficiency, storage artefact
spiculated cell, spur cell, sputnik
cell, star cell
Elliptocyte bacillary cell, cigar or rod shaped cell, Hereditary elliptocytosis, iron deficiency
ovalocyte, pencil cell
Howell-Jolly body Hyposplenism, postsplenectomy, haemolytic
anaemia, megaloblastic anaemia
Hypochromic cell anulocyte, pessary form, ring form Iron deficiency, thalassaemia
Irregularly G6PD deficiency, haemoglobinopathies
contracted cell
Macrocyte macronormocyte, megalocyte B12/folate deficiency, liver disease, MDS
Microcyte micronormocyte Iron deficiency, thalassaemia
Ovalocyte bacillary cell, cigar or Hereditary elliptocytosis, iron deficiency
rod shaped cell, elliptocyte
Pappenheimer Sideroblastic anaemia, haemoglobinopathies,,
bodies hyposplenism
Poikilocyte burr cell, irregular shaped
cell, irregularly contracted
cell, pyknocyte, spur cell
Polychromatic cell polychromatophilic cell Haemolytic anaemia, haematinic treatment
RBC erythrocyte, normocyte,
discocyte
Schistocyte burr cell, helmet cell, Microangiopathic haemolytic anaemia,
horn cell, keratoschistocyte, TTP, HUS, DIC,
pincer cell, poikilocyte, renal disease
prickle cell, red cell
fragment, schizocyte,
thorn cell, triangular cell
Sickle cell drepanocyte, holly leaf cell Sickle cell anaemia and other sickle cell diseases
Spherocyte spherical cell Hereditary spherocytosis, ABO and warm AIHA,
Clostridium perfringens sepsis, burns
Stomatocyte cup cell, knizocyte, slit cell Alcoholic liver disease, hereditary stomatocytosis
Target cell codocyte, leptocyte Liver disease, haemoglobinopathies, thalassaemia
Teardrop cell dacrocyte, pear-shaped cell myelofibrosis

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L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY 291

Irregular distribution of RBC on the blood film Hypochromia


Hypochromia is a reduction in RBC staining with an
Agglutination
increase in central pallor to greater than one-third of
Agglutination is the irregular clumping of red blood the RBC diameter. The MCH will be decreased as will
cells into grape-like clusters, usually indicating the the MCHC in severe hypochromia. Clinical conditions
presence of a cold reactive anti-RBC antibody. A fal- causing hypochromia will often have an associated
sely increased MCV and falsely reduced RBC count microcytosis. Hypochromia may also be seen in red
will be obtained from the analyser leading to an erro- cells that are thinner than normal but have normal
neous elevation in the MCH and mean cell haemoglo- haemoglobin concentration and volume.
bin concentration (MCHC). It is recommended that the analyser generated
The recommendation is to report the presence of MCH be used to gauge hypochromia rather
agglutination when observed. than grading by visual microscopic examination but
grading criteria have also been included in the table
for hypochromic cells for those laboratories who
Rouleaux formation
prefer to grade hypochromia using direct visual
Rouleaux formation (red cells stacked up like a pile of inspection.
coins) usually occurs when plasma protein concentra-
tions are high.
The recommendation is to report the presence of Macrocytes
rouleaux when observed. Macrocytes are enlarged red cells with a diameter
greater than 8.5 lm, (MCV > 100 fL). The MCV will
Abnormalities of RBC size and/or colour be elevated but the MCH will be normal or elevated if
there is a significant increase in MCV. They may be
Anisocytosis round or oval in shape which can have diagnostic sig-
nificance. It is noteworthy that red cells in premature,
Anisocytosis is an increased variability in RBC size. It newborn babies and neonates are physiologically lar-
is nonspecific and will be reflected in an increased red ger than in adults. Reticulocytosis may also cause an
cell distribution width (RDW) in automated analyser elevated MCV.
counts. It is recommended that the more accurate analyser
The recommendation is to use and report the RDW generated MCV be used to gauge red cell size (degree
as a measure of the degree of variation in red cell size. of macrocytosis) rather than grading by visual micro-
However, anisocytosis can be graded if an RDW is scopic examination but grading criteria have also been
unavailable. included in the table for macrocytes for those labora-
tories that do not have these advanced analysers. An
Dimorphism abnormal RDW or red cell histogram that suggests the
presence of macrocytes even though the MCV is nor-
Dimorphism is the presence of two distinct RBC popu- mal may also prompt slide review and grading of mac-
lations which may be clearly seen on an analyser red rocytes by visual microscopic examination. However,
cell histogram with a corresponding increase in RDW. if oval macrocytes are present, it is recommended that
The term is most often used when there is a popula- these be graded.
tion of microcytic, hypochromic cells and another
population of normochromic cells which may be
Microcytes
normocytic or macrocytic, but could also be used to
describe coexisting macrocytic and normocytic popula- Microcytes are small red blood cells with a diameter
tions of cells. of less than 7 lm (MCV < 80 fL). They may be associ-
The recommendation is to report the presence of ated with decreased amounts of haemoglobin (hypo-
dimorphism and describe the two populations. chromia). It should also be noted that moderate

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numbers of target cells will falsely lower the MCV mias and mechanical damage to the red cells may
due to their increased surface area to volume ratio produce morphologically identical cells (keratocytes),
[8]. which are formed by the rupture of peripheral
As previously mentioned, the red cells of newborns pseudovacuoles and subsequent fusion of the red cell
and neonates are larger than in adults but the red membrane.
cells of healthy children are physiologically smaller The recommendation is to grade bite cells.
than in adults so it important that red cell size be
interpreted in the context of the age of the subject.
Blister cells
It is recommended that the more accurate analy-
ser generated MCV be used to gauge red cell size Supplementary image S3.
(degree of microcytosis) rather than grading by visual Blister cells are red cells in which the haemoglobin
microscopic examination but grading criteria have appears retracted into one half of the cell to form a
also been included in the table for microcytes for dense mass leaving the remainder of the cell as an
those laboratories that do not have these advanced empty membrane.
analysers. An abnormal RDW or red cell histogram The recommendation is to grade blister cells.
that suggests the presence of microcytes even though
the MCV is normal may also prompt slide review
Echinocytes (burr cell)
and grading of microcytes by visual microscopic
examination. Supplementary image S4.
Echinocytes are red cells that have lost their disc
shape and are covered with 10-30 short blunt projec-
Polychromasia
tions or spicules of fairly regular form.
Polychromasia refers to immature red cells that are The recommendation is to grade echinocytes.
pinkish blue-grey in appearance due to residual ribo-
somal RNA. They are larger in size than normal
Elliptocytes and ovalocytes
mature red cells.
The recommendation is to grade polychromasia Supplementary image S5.
and perform a reticulocyte count if necessary. Elliptocytes are cells with an elliptical shape (the
long axis is more than twice the short axis), while
ovalocytes have an oval shape (the long axis is less
Abnormalities of RBC shape
than twice the short axis). The recommendation is to
grade elliptocytes and ovalocytes.
Acanthocytes (spur cell)
Supplementary image S1.
Irregularly contracted cells
Acanthocytes are round, hyperchromic red
cells with 2-20 irregularly spaced projections or Supplementary image S6.
spicules of variable length, thickness and shape. Irregularly contracted cells are smaller and denser
Some spicules have club-shaped rather than pointed RBC which lack an area of central pallor but are not
ends. as regular in shape as spherocytes.
The recommendation is to grade acanthocytosis. The recommendation is to grade irregularly con-
tracted cells.

Bite cells
Poikilocyte
Supplementary image S2.
Bite cells are RBC with peripheral single or multi- A poikilocyte is a red cell of abnormal shape. Poikilo-
ple arcuate defects (bites) caused by the removal of cytosis is a non-specific abnormality but poikilocytes
Heinz bodies by the spleen and are a feature of oxi- of specific shapes may be associated with a particular
dant haemolysis. Microangiopathic haemolytic anae- disorder e.g. elliptocytes in hereditary elliptocytosis.

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L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY 293

The recommendation is to report the abnormal spe- the stomatocytes may have two stomas per cell which
cific cell shape rather than use poikilocytosis. may be longitudinal, transverse, V or Y shaped.
The recommendation is to grade stomatocytes.

Schistocyte
Target cells
Supplementary image S7.
Schistocytes are fragments of red blood cells pro- Supplementary image S11.
duced by extrinsic mechanical damage within the circu- Target cells are thin cells with an increased surface
lation and are a diagnostic feature of microangiopathic area to volume ratio that have an area of increased
haemolytic anaemia (MAHA). Schistocytes are always staining which appears in the middle of the area of
smaller than intact red cells and can have the shape of central pallor.
fragments with sharp angles and straight borders, small The recommendation is to grade target cells.
crescents, helmet cells or keratocytes. Microspherocytes
may also be a feature of MAHA [7].
Teardrop cells
The recommendation is to grade schistocytes. A
schistocyte count may be of value when schistocytes Supplementary image S12.
are the dominant feature ( polychromasia, NRBC, Teardrop cells are red cells that are pear or teardrop
thrombocytopenia) for the diagnosis and follow-up of in shape.
MAHA. The recommendation is to grade teardrop cells.

Sickle cells Inclusions in RBC

Supplementary image S8.


Basophilic stippling
Sickle cells are red cells that become crescent or
sickle-shaped with pointed ends as a result of poly- Supplementary image S13.
merization of HbS. Basophilic stippling describes the occurrence of
The recommendation is to grade sickle cells. A fine, medium, or coarse blue granules due to abnor-
sickle screen or haemoglobinopathy screen may be mally aggregated ribosomes, uniformly distributed
recommended. throughout the RBC.
The recommendation is to grade basophilic stip-
pling.
Spherocytes
Supplementary image S9.
Howell-Jolly bodies
Spherocytes are of small diameter (<6.5 lm) and
are dense spheroidal RBC with a normal or decreased Supplementary image S14.
MCV and an absence of central pallor. They may be Howell-Jolly bodies are usually single, small
formed as a consequence of an abnormality of the (1 lm), dense, perfectly round basophilic inclusions
RBC cytoskeleton and membrane, immune and mi- that are fragments of nuclear material (DNA).
croangiopathic haemolysis and direct damage to the The recommendation is to grade Howell-Jolly
red cell membrane. bodies.
The recommendation is to grade spherocytes.

Intracellular haemoglobin crystals


Stomatocytes
Crystalline aggregates of haemoglobin may be seen in
Supplementary image S10. HbC and HbSC disease. These crystals stain densely,
Stomatocytes are uniconcave cup-shaped red blood vary in size and have straight edges with pointed ends.
cells that appear on a stained blood film with a slit-like The recommendation is to report the presence of
area of central pallor. In South East Asian ovalocytosis, intracellular haemoglobin crystals when observed.

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294 L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY

well-stained peripheral blood film for accurate white


Micro-organisms in RBC
cell differentiation and classification.
Micro-organisms may be seen free between or within White cell differentiation involves the classification
RBC in patients with bacterial, fungal, protozoan or of white cells based on size, nuclear shape, chromatin
parasitic infections. pattern and cytoplasmic appearance and content [11,
The recommendation is to report their presence 12]. Morphological qualitative abnormalities of the
when observed. cell nucleus or cytoplasm and/or the size of the white
Malarial species identification should be made and cells can be congenital or acquired in the course of
reported. For patients with malaria, determination of various diseases.
parasite density is useful in clinical management and The 2008 World Health Organisation (WHO) Clas-
in monitoring a patients response to treatment, par- sification of Tumours of Haemopoietic and Lymphoid
ticularly in Plasmodium falciparum and Plasmodium Tissues recommends a 200 white cell peripheral blood
knowlesi [9]. cell differential be performed as part of the diagnostic
work-up [13] in acute myeloid leukaemia (AML) and
myelodysplastic syndromes; however, a 100 white cell
Pappenheimer bodies
differential is more usual in the routine haematology
Supplementary image S15. laboratory.
Pappenheimer bodies are ferritin aggregates in red
cells, visible in Romanowsky stained PB films as mul- Normal myeloid development and morphology
tiple basophilic inclusions of variable size, shape and
distribution usually in a limited cytoplasmic area. Myeloblast
They stain positively for iron (Perls Prussian blue reac-
tion). Blast cells in normal myeloid maturation have a diam-
The recommendation is to grade Pappenheimer eter of 1220 lm and a relatively large round or oval
bodies. nucleus with a fine chromatin pattern and one or
more distinct nucleoli. The cytoplasm is basophilic
with an absent Golgi zone and granules may or may
Nucleated Red Blood Cell (NRBC) not be present.
Supplementary image S16.
A nucleated red blood cell is a red cell precursor Promyelocyte
and is used to describe an erythroblast in the periph-
Normal promyelocytes are 1525 lm in diameter, have
eral circulation.
an oval or round nucleus with fine/intermediate chro-
The recommendation is to report NRBCs as an
matin and a usually visible and prominent nucleolus.
absolute count within the differential with the WBC
The cytoplasm is basophilic and contains blue-violet
corrected for the presence of NRBCs, or, count and
and red (primary) granules. A pale area equating to the
report the number of NRBC per 100 WBC.
Golgi zone is present adjacent to the nucleus.

WHITE BLOOD CELLS Myelocyte


In nearly all cases, modern haematology analysers pro- The myelocyte is slightly smaller than the promyelo-
vide accurate white cell counts and white cell differen- cyte (1018 lm) with a round or oval nucleus which
tials. The differential may be suppressed or inaccurate may be eccentrically placed. The nuclear chromatin
when there are abnormal white cell populations pres- shows a moderate degree of coarse clumping and
ent but this will cause abnormal flags to be triggered nucleoli are not seen. There is a moderate amount of
[10]. Automated instruments cannot enumerate and blue-pink cytoplasm which contains numerous
classify abnormal white cell populations or recognize red-violet granules. As the myelocyte matures, the sec-
many significant morphological abnormalities necessi- ondary granules develop definite neutrophilic, eosino-
tating the microscopic examination of a well made and philic or basophilic characteristics.

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Metamyelocyte Basophil
The metamyelocyte is smaller than the myelocyte A basophil is 1016 lm in diameter with pale blue
with an indented or kidney-shaped nucleus. Nucleoli cytoplasm containing purple-black secondary gran-
are not observed. The cytoplasm is usually clearly ules. These granules are water soluble and may dis-
pink and contains granules that are clearly differenti- solve on staining leaving clear areas in the cytoplasm.
ated as neutrophilic, eosinophilic or basophilic. The nucleus is segmented but is often obscured by
N.B. Immature granulocytes (promyelocytes, myel- basophilic granules which may vary in number, size
ocytes and metamyelocytes) are not usually seen in and shape.
normal peripheral blood.

Monocyte
Band neutrophil
Monocytes are the largest cell in the peripheral blood,
Band neutrophils are 1014 lm in diameter and have variable in size but usually 1522 lm in diameter.
a nucleus that is nonsegmented or has rudimentary The nucleus is irregular in outline (often kidney
lobes that are connected by a thick band rather than a shaped), and the chromatin is arranged in fine strands
thread. Cytoplasm is abundant, pink and contains with sharply defined margins. The cytoplasm is light
many small violet-pink neutrophilic or secondary blue-grey and contains numerous fine dust-like gran-
granules distributed evenly throughout the cell. ules. Some cells may contain a small number of red-
Many laboratories do not report band neutrophils violet granules. Vacuolation may be present.
on adult patients or children due to interobserver var-
iation in band neutrophil classification; this is a well
Normal lymphocyte development and morphology
recognized and acceptable practice.
It is recommended that band neutrophils be
Lymphoblast
counted as segmented neutrophils in the differential.
Appropriate comments may be made if increased The lymphoblast has a diameter of 820 lm. The
numbers are seen in the blood film. nucleus is round or oval with fine granular chromatin
and one or more indistinct nucleoli. The cytoplasm is
scanty and basophilic, and cytoplasmic granules are
Segmented neutrophil
absent. It cannot be reliably distinguished from some
A granulocyte that is 1014 lm in diameter with a types of undifferentiated or minimally differentiated
lobulated nucleus (usually 34 lobes, but small myeloblasts and therefore should be counted as a blast
numbers of 2 and 5 lobed neutrophils may also be cell.
seen) connected by a thin thread of chromatin. The
chromatin is coarse, stains violet and is arranged in
Prolymphocyte
clumps. Small nuclear appendages may be seen. There
is abundant pink cytoplasm with many small second- The nucleus is round and contains a single prominent
ary granules. nucleolus. It has more cytoplasm than a lymphoblast
and the chromatin is more condensed.
N.B. Lymphoblasts and prolymphocytes are not
Eosinophil
usually seen in the normal peripheral blood.
The diameter of the eosinophil is 1217 lm. The
nucleus usually only has 2 lobes with coarsely
Lymphocyte
clumped, violet-staining chromatin. There is abundant
cytoplasm containing many eosinophilic (orange) sec- Lymphocytes seen in the peripheral blood are pre-
ondary granules that are larger than neutrophil gran- dominantly small (1012 lm), or, less frequently large
ules and more uniform in size. (1216 lm).

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Small lymphocytes are usually round in outline, Each laboratory should establish their own refer-
and the nucleus is round with coarse, densely staining ence ranges as these will vary depending on popula-
chromatin. Cytoplasm is scanty. tion, laboratory, instrumentation and methods used.
Large lymphocytes are usually irregular in outline, It is recommended that the automated analyser
and the nuclear chromatin is not as coarse as in small WBC differential count be reported in patients with
lymphocytes. Cytoplasm is abundant and tends to be normal cell populations in the absence of analyser flags
light sky blue in colour. or abnormal cell populations that cannot be reliably dif-
Large granular lymphocytes (LGLs) are of the same ferentiated and classified by automated instruments.
appearance as large lymphocytes but the cytoplasm The automated differential may also be reported after
contains prominent small red-violet granules. These viewing a blood film due to flags or other indicators
cells can comprise up to 1020% of the peripheral where the automated values are found to be accurate.
blood lymphocytes in normal subjects. LGLs are not
routinely counted as a separate lymphocyte popula-
Qualitative abnormalities in myeloid cells
tion.
Supplementary image S17.
Cytoplasmic abnormalities
It is recommended that LGLs be counted as lym-
phocytes but may be commented on if they are pres- Auer rod. Supplementary image S18.
ent in increased numbers. This may prompt further A sharply defined red rod or needle-like cytoplas-
investigations such as flow cytometry. mic inclusion formed by abnormal primary granule
N.B. Lymphocytes predominate in the blood films development. Found mainly in leukaemic myeloblasts
of infants and children until 4 years of age. These or abnormal promyelocytes, they stain positively for
lymphocytes are more pleomorphic than those seen in myeloperoxidase and are a specific marker for myeloid
normal adult blood films. lineage neoplasms. There may be several in a cell and
may be arranged in bundles (faggots).
The recommendation is to report the presence of
Quantitative abnormalities
Auer rods when seen.
Neutrophilia, neutropenia, lymphocytosis, lymphope-
nia, monocytosis, monocytopenia, eosinophilia, eosin- Dohle body. Pale light blue or grey, single or multiple,
openia, basophilia, basopenia. cytoplasmic inclusions found near the periphery of
WBC differential counts can be performed by auto- the neutrophil. D ohle bodies are a non-specific
mated analysers or manual microscopic visual exami- reactive change but may also indicate May-Hegglin
nation of a blood film. Automated analysers use anomaly if associated with thrombocytopenia and
multiple parameters and methods such as impedance giant platelets. D
ohle bodies may also be seen in
technology and fluorescence flow cytometry to differ- patients on growth factor therapy such as granulocyte
entiate and count the 5 major white cell types found colony-stimulating factor (G-CSF).
in the peripheral blood neutrophils, lymphocytes, The recommendation is to grade D ohle bodies
monocytes, eosinophils and basophils. Many modern when seen.
analysers also now provide a 6 part differential with
the enumeration of immature granulocytes (promyel- Hypergranulation neutrophil, (toxic granulation).
ocytes, myelocytes and metamyelocytes). Supplementary image S19.
The automated WBC differential count is less time- Coarse, purple staining primary (azurophilic) neu-
consuming and expensive than the manual method trophil cytoplasmic granules which occur as a
and as an analyser counts thousands of cells compared response to infection and inflammation. A non-spe-
to the usual 100200 WBC by the microscopic cific reactive change, it is a result of abnormal primary
method, it will also be more precise in the absence of granule maturation with retention of their azurophilic
abnormal cell populations. Very low or high white cell staining properties.
counts may also cause the manual differential to be The recommendation is to grade hypergranulation
less accurate and reproducible. when seen.

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L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY 297

Hypogranulation neutrophil. Supplementary image It is recommended that hyposegmented neutrophils


S20. be counted and reported as mature segmented neu-
Reduced or absent neutrophil granulation causing trophils but with a suitable interpretive comment.
the cytoplasm of mature neutrophils to appear blue-
grey. Myeloid cells in haematological neoplasms
The recommendation is to grade hypogranulation
when seen. Leukaemic myeloblasts. Supplementary image S22.
Leukaemic myeloblasts vary in appearance. They
Vacuolation neutrophil. Neutrophil cytoplasmic can be large or small in size. Some may have a
vacuolation in infection is due to granule fusion with high N:C ratio, uncondensed chromatin and usually
a phagocytic vacuole and release of lysosomal one or more prominent nucleoli. Others may have
contents to kill bacteria. This vacuolation may appear a lower N:C ratio and a few red-purple granules or
as pin-hole vacuolation small, discrete vacuoles, Auer rods. Nuclear and cytoplasmic irregularities
but the vacuoles may be larger. Other causes of may be present, for example nuclear folding, cyto-
neutrophil vacuolation include alcohol toxicity and plasmic basophilia and cytoplasmic blebbing or
prolonged exposure to EDTA anticoagulant (storage pseudopods.
artefact). The recommendation is to count these as blasts
The recommendation is to grade neutrophil vacuo- and describe them in the film report with a suitable
lation when seen. interpretive comment.

Abnormal promyelocytes in acute promyelocytic


Nuclear abnormalities leukaemia (APL). Supplementary images S23 and
Hypersegmented neutrophils. Normal
neutrophils S24.
usually have 34 lobes (occasionally 2 and 5 lobes). The promyelocytes in the hypergranular variant of
Hypersegmented neutrophils have an increased APL have nuclei that vary in size and shape and are
number of distinct nuclear lobes with increased often kidney shaped or bilobed. The cytoplasm is
numbers of neutrophils having 5 or more nuclear packed with large coalescent pink-purple granules and
segments. may contain Auer rods. These may be grouped in
Neutrophil hypersegmentation is defined as any bundles or faggots within the cytoplasm.
neutrophil having 6 or more lobes or more than 3% In the hypogranular or microgranular variant, the
of neutrophils having 5 lobes, when 100 neutrophils nuclear shape is usually bilobed but the cytoplasm
are examined. contains few or no granules.
The recommendation is to comment on the pres- The recommendation is to count these abnormal
ence of hypersegmented neutrophils when seen. promyelocytes as blast equivalents in the differential
but it is important that a suitable description of the
Hyposegmented neutrophils hypolobated neutrophils abnormal promyelocytes and an interpretive comment
(Pelger-Huet neutrophils). Supplementary image S21. is added to the film report and a likely diagnosis of
Hyposegmented neutrophils are marked by the fail- APL communicated directly to the clinician.
ure of normal nuclear lobe development during termi-
nal differentiation and have coarse clumped nuclear Monoblasts. Supplementary image S25.
chromatin. Monoblasts are larger than myeloblasts (20-
It is important that these hyposegmented neu- 30 lm), with a round/oval nucleus, fine chromatin
trophils not be confused with myelocytes, metamyelo- and one or two prominent nucleoli. The cytoplasm is
cytes or band neutrophils. They are mature basophilic and usually lacks granules.
neutrophils and can be differentiated by their smaller The recommendation is to count these as blasts
nucleus and lower nuclear: cytoplasmic ratio (N:C and describe them in the film report with a suitable
ratio) and condensed nuclear chromatin [14]. interpretive comment.

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298 L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY

Promonocytes. Supplementary image S26.


Qualitative abnormalities in lymphoid cells
Promonocytes may be rarely seen in the peripheral
blood in reactive conditions as well as in some leukae- Lymphocyte morphology is subject to wide variability
mias. They are large cells with a nucleus that is con- due to various immunological stimuli both in inflamma-
voluted/indented with a delicate, lace-like chromatin tory and infectious diseases (particularly viral) as well as
pattern and prominent nucleolus. The cytoplasm is in neoplastic disorders (leukaemias and lymphomas),
blue-grey and may contain a small number of fine resulting in circulating lymphocytes with morphological
red-violet granules. abnormalities in various quantities. Terminology for
The recommendation is to count promonocytes in these lymphocytes has been varied and confused with
the differential and comment on their presence with a many different terms being used to describe the same
suitable interpretive comment. Leukaemic promono- thing including variant, reactive, abnormal, activated
cytes should be summated with blast cells when mak- and atypical lymphocytes, Downey cells Type13, Turk
ing a diagnosis of AML. cells, immunoblasts and even combinations of cells, for
example monocytoid lymphocytes. This highlights a
Abnormal monocytes. Monocytes produced under need to simplify this terminology.
conditions of bone marrow stress or stimulation, for It is recommended that reactive lymphocyte is used to
example infections, growth factor (GM-CSF) describe lymphocytes with a benign aetiology and
administration, show an increased N:C ratio, a more abnormal lymphocyte with an accompanying description
delicate chromatin pattern, nucleoli and increased of the cells is used to describe lymphocytes with a sus-
numbers of vacuoles. Granulation and cytoplasmic pected malignant or clonal aetiology.
basophilia may also be increased. Reactive lymphocytes (atypical lymphocyte, suspect
Abnormal monocytes can be seen in a number of reactive European LeukemiaNet classification) [15].
haematological neoplasms. In contrast to monoblasts Supplementary image S27.
and promonocytes, the abnormal monocytes are Abnormalities include increased cell size, immatu-
larger, have irregular nuclei and increased cyto- rity of the nucleus including a visible nucleolus and
plasm. lack of chromatin condensation, irregular nuclear out-
The recommendation is to count these as mono- line or lobulation, cytoplasmic basophilia and vacuola-
cytes with a comment on their morphology and a tion and irregular cell outline. The cytoplasm may be
suitable interpretive comment. abundant with staining varying from pale blue to
markedly basophilic especially at points of contact
Dysplastic changes. Dysplasia refers to morphologically with adjacent cells.
abnormal cells or tissues that are due to abnormal cell The recommendation is to comment on the pres-
development and maturation. Examples of dysplasia ence of reactive lymphocytes. They may be counted
include abnormally large or small cells, nuclear as a separate population in the differential if they are
hyposegmentation (hypolobation), nuclear hyperseg- present in significant numbers.
mentation, hypogranulation, hypergranulation and Abnormal lymphocytes (atypical lymphocyte, sus-
abnormal granulation (large fused granules, Auer pect neoplastic European LeukemiaNet classifica-
rods). tion) [15].
The recommendation is to comment on the pres- A comprehensive classification and description of
ence of dysplasia with a suitable interpretive com- lymphocytes in malignant lymphoid neoplasms is
ment. beyond the scope of this article. For this, the reader is
It should be noted that the diagnosis and classifica- advised to refer to the WHO Classification of Tumours
tion of myelodysplastic syndrome as per the WHO of Haematopoietic and Lymphoid Tissues, Fourth Edi-
classification 2008 requires a percentage count of dys- tion [13].
plastic changes per lineage. This, however, is not rou- It is recommended that abnormal lymphoid cells
tinely performed by the scientist reviewing the that can be identified as a particular neoplastic cell
peripheral blood film. Further investigations and clini- type (as described below), for example hairy cells,
cal correlation by the clinician is required. lymphoma cells and prolymphocytes (based on dis-

2015 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 287303
L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY 299

tinctive morphology and confirmed by immunophe- cytes and some cells may appear blastic with cleft
notyping), and plasma cells in plasma cell myeloma or or irregular nuclei and a prominent nucleolus.
other plasma cell dyscrasias be included in the differ- Burkitt lymphoma These lymphoma cells are
ential as that cell class. Other abnormal lymphoid cells large with dispersed nuclear chromatin, one or
can be described in the film comment and counted as more prominent nucleoli and moderately abun-
a separate population of abnormal lymphocytes in dant, deeply basophilic and vacuolated cytoplasm.
the differential if present in significant numbers. Sezary syndrome S ezary syndrome is a mature T-
The use of this nomenclature underlines the limited cell lymphoma with neoplastic T lymphocytes in
diagnostic value of morphology in the lymphoprolifer- the peripheral blood. The cells are present in vari-
ative neoplasms where the final diagnosis is deter- able numbers ranging from a few cells to a frankly
mined by immunophenotyping by flow cytometry. leukaemic picture with a marked leucocytosis. The
cells may be large or small but the nuclear mor-
Hairy cells phology, classically described as cerebriform, is the
characteristic cytological feature of both cell types.
Supplementary image S28. The nucleus has deep narrow clefts with superim-
Hairy cell leukaemia is a chronic B cell lineage leu- posed and folded lobes giving it a very convoluted
kaemia with morphologically distinctive neoplastic appearance.
cells. Hairy cells are larger than normal lymphocytes Adult T-cell leukaemia/lymphoma (ATLL) ATLL
and have abundant pale blue-grey cytoplasm with is characterized by a broad spectrum of cytological
fine hair-like projections. The nucleus varies in shape features but the characteristic ATLL cells have been
and may be round, oval, bean-shaped or bilobed. described as flower cells with many nuclear con-
It is recommended that hairy cells are counted as volutions and lobules.
abnormal lymphocytes on first presentation with a It is recommended that lymphoma cells are
detailed description of the cells included in the film counted as abnormal lymphocytes on first presenta-
comment. After immunophenotyping, the cells may tion with a detailed description of the cells included
be counted as hairy cells in the WBC differential. in the film comment. After immunophenotyping,
the cells may be counted as lymphoma cells in the
Lymphoma cells WBC differential.

Lymphoma is a neoplasm of B, T or Natural Killer


(NK) lymphocytes and is more often found in tissues Plasma cells
other than bone marrow and peripheral blood. Lym-
Supplementary image S30.
phoma may have a leukaemic phase, however, in
A plasma cell is larger than a normal small lym-
which morphologically abnormal cells appear in the
phocyte, has deeply basophilic cytoplasm, an eccentric
peripheral blood. A comprehensive classification of
round or oval nucleus, coarsely clumped chromatin
lymphoma is beyond the scope of this document, but
and a pale Golgi zone or perinuclear halo adjacent to
some specific examples include the following:
the nucleus.
Follicular lymphoma These lymphoma cells are It is recommended that plasma cells be counted as
often small with scanty, weakly basophilic cyto- a separate population in the WBC differential.
plasm and have nuclei with notches or deep nar-
row clefts. Sometimes the cells are larger and more
Prolymphocytes
pleomorphic with small but distinct nucleoli and
nuclear clefts or notches. B-prolymphocytes are twice the size of a lymphocyte
Supplementary image S29 and have a round nucleus, moderately condensed
Mantle cell lymphoma These lymphoma cells are nuclear chromatin, a prominent central nucleolus and
pleomorphic varying in size and N:C ratio. Chro- a relatively small amount of faintly basophilic cyto-
matin condensation is less than in CLL lympho- plasm.

2015 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 287303
300 L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY

Supplementary image S31.


P L AT E L E T S
T prolymphocytes are smaller and more pleomor-
phic than B prolymphocytes. Nuclei are irregular or Platelets are small, blue-grey granular fragments
lobulated. The cytoplasm is scanty and moderately derived from megakaryocytic cytoplasm, containing
basophilic and cytoplasmic blebs may be present. many small, reddish-purple granules.
Nucleoli are usually not as large or prominent as B-
lineage prolymphocytes.
Qualitative abnormalities
It is recommended that prolymphocytes be counted
as a separate population in the WBC differential.
Platelet size
Platelet size is of diagnostic significance particularly
Smudge cells (smear cells)
when considered in relation to the platelet count.
Smudge cells result from shearing forces on the cells A normal platelet measures 1.53 lm in diameter.
during the spreading of blood films. They are the dis- Large platelets measure 37 lm (roughly the diameter
rupted nuclei of fragile cells. A repeat film made with of a normal sized red cell), whilst giant platelets, (sup-
one part albumin added to four parts blood may pre- plementary image S33), are larger than normal sized
vent cell disruption and allow identification of the red cells at 1020 lm in diameter and are flagged by
fragile cells and their inclusion in the WBC differen- automated analysers. In a normal person, usually less
tial. than 5% of the platelets appear large. Platelet size
When the nature of the smear cell is apparent, it is increases gradually during storage in EDTA anticoagu-
recommended that they should be counted as the cell lated venipuncture tubes.
from which they are derived. Large numbers of It is recommended that giant platelets be graded.
smudge cells may be seen in CLL PB films (supple- A comment about the platelet count and the pres-
mentary image S32). It is recommended that the ence of small, large and/or giant platelets can be made
automated differential be reported if available in this with an additional interpretive film comment if appro-
instance but the presence of smudge cells may be priate.
commented on in the film report. Hypogranular platelets, (supplementary image
S34), exhibit little, if any, of the purple-red granules
found in normal platelets.
Leukaemic lymphoblasts
It is recommended that a comment about the pres-
Leukaemic lymphoblasts range from those with a high ence of hypogranular platelets be made if seen in the
N:C ratio, clumped chromatin, inconspicuous nucleoli PB film.
and scanty basophilic cytoplasm to those that are het- Megakaryocytes and megakaryoblasts are rarely
erogeneous in appearance and have a nuclear chro- seen in normal peripheral blood. Small megakaryo-
matin pattern varying from finely dispersed to blasts may be indistinguishable from lymphoblasts
coarsely condensed. The nuclear outline may be irreg- whereas larger ones will have a nucleus with a diffuse
ular and nuclear clefting, indentation and folding are chromatin pattern and a variable amount of basophilic
common. Nucleoli vary in size and number but are cytoplasm which may form blebs.
often indistinct. A small number of lymphoblasts may Abnormal megakaryocytes, megakaryoblasts and
have more abundant cytoplasm containing coarse azu- bare megakaryocyte nuclei may be seen in the PB in
rophilic granules. pathological conditions. Micromegakaryocytes, (sup-
Lymphoblasts cannot be reliably distinguished from plementary image S35), are seen in some patients
myeloid blasts, lymphoma cells and sometimes, reac- with haematological neoplasms. The micromegakaryo-
tive lymphocytes. Additional information from cyto- cyte is defined as a megakaryocyte approximately the
chemical stains or immunophenotyping may be size of a promyelocyte or smaller with a nonlobated
required to make an accurate diagnosis. or a bilobed nucleus and a variable amount of weakly
The recommendation is to count and report these basophilic cytoplasm. The nucleus may appear bare
as blasts and describe them in the film report. but a small rim of cytoplasm can be demonstrated by

2015 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 287303
L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY 301

electron microscopy. The cytoplasm is weakly baso- Peripheral Blood Cell Morphology Nomenclature and
philic. Cytoplasmic vacuolation and variable numbers Reporting in accordance with the basic aim of the ICSH
of granules may be present, and there may also be to achieve reliable and reproducible results in laboratory
small cytoplasmic protrusions or blebs. Platelets may analysis and, in particular, diagnostic haematology. The
appear to be budding from the surface. existence of traditional and geographical differences in
It is recommended that a comment about the pres- nomenclature is recognized and accepted, thus favouring
ence of megakaryoblasts, megakaryocytes and micro- some flexibility in the suggested methods of reporting for
megakaryocytes be made if seen in the PB film. a number of parameters.
Links for examples of cells discussed. (i) http://
www.morphology.mmu.ac.uk, (ii) www.icsh.org.
CONCLUSION
These recommendations deal with the need for a glo-
AC K N OW L E D G E M E N T S
bal standard in naming, grading and reporting abnor-
mal cells or morphological abnormalities which are We would like to thank the Morphology Workshop
observed at the time of the PB film review and man- Sponsors: Abbott Diagnostics, Beckman Coulter, Hori-
ual differential count. ba Medical Diagnostics, Mindray, Nihon Kohden, Sie-
Their primary goal is to produce clear guidelines mens, Sysmex Corporation. We would like to thank
for scientists who perform analysis of haematology John Burthem and Michelle Brereton at Central
samples. This issue is becoming more important as Manchester and Manchester Childrens University
hospitals and laboratories join with others, forming Hospital, UK for compiling the images. Images have
large hospital and laboratory systems, with physicians been provided by John Burthem, Michelle Brereton,
practicing at multiple sites and with patients able to Gina Zini and Gillian Rozenberg. Gillian Rozenbergs
gain access to the healthcare system from multiple images have been reproduced by permission from
sites. There are also laboratories which are crossing Elsevier Australia from Gillian Rozenberg; Microscopic
international borders. Laboratory services can now haematology: a practical guide for the laboratory 3e
span multiple countries. The need for consistent 2011, Sydney, Elsevier Australia.
nomenclature and appropriate grading standards are
therefore more important than ever.
CONFLICT OF INTEREST
This document is the result of an exhaustive and com-
prehensive review, analysis and consensus agreement by All authors declare that they have no conflict of inter-
the ICSH ad hoc Committee on Standardization of ests.

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Lab Hematol. 2015;37:17. strated Field Guide Based on Proficiency ning RD, Borowitz MJ, Porwit A, Harris

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NL, Le Beau MM, Hellstrom-Lindberg E, tional Agency for Research on Cancer, Terpos E, Tichelli A, Vallesp T, Woessner
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APPENDIX

APPENDIX. ICSH Morphology Panel Members


Stefanie McFadden McFadden Consulting, Columbus, OH, USA stefhem@aol.com
Maria Proytcheva University of Arizona Medical Center, MProytcheva@medadmin.arizona.edu
Tucson, AZ, USA
Bernie Fernandes Mt Sinai Hospital, Dept. of Pathology & Lab bfernandes@mtsinai.on.ca
Medicine, Toronto,
ON, Canada
Gini Bourner Gamma Dynacare Medical Laboratory, gbourner@rogers.com
Brampton, ON, Canada
Carol Briggs University College London Hospitals, carolbriggs@hotmail.com
London, UK
Keith Hyde United Kingdom External Quality Keith.Hyde@nhs.net
Assessment Scheme for
General Haematology [UK NEQAS(H)],
Manchester, UK
Josep Jou Hospital Clinic, Barcelona, Spain JMJOU@clinic.ub.es
JL Vives Corrons Hospital Clinic, Barcelona, Spain jlvives@clinic.ub.es
Jean Francois Lesesve Centre Hospitalier Universitaire de Nancy jf.lesesve@chu-nancy.fr
et de Nantes, Nancy,
France
Gina Zini Universita Cattolica del Sacro Cuore, Rome, Italy recamh@rm.unicatt.it
Yutaka Nagai Nihon Kohden, Japan; JSLH ynagai@ic.daito.ac.jp
Yohko Kawai Japanese Society for Laboratory Hematology yohko@iuhw.ac.jp
Gillian Rozenberg SEALS Randwick, Prince of Wales Hospital, gillian_rozenberg@yahoo.com
Randwick NSW,
Australia
Lynn Palmer Middlemore Hospital, Auckland, New Zealand Lynn.Palmer@middlemore.co.nz
Anne Kornreich Grand H^ opital de Charleroi, Brussels, Belgium ankornre@ULB.AC.BE
A.A. Ermens Amphia Hospital, Breda, Netherlands aermens@amphia.nl

Supporting Information Image S1. acanthocytes


Image S2. Three bite cells
Additional Supporting Information may be found in
Image S3. blister cells
the online version of this article:
Image S4. echinocytes
Supplementary Images: ICSH Recommendations for Image S5. ovalocytes and elliptocytes
Peripheral Blood Cell Morphology Standardization Image S6. irregularly contracted cells
and Grading Image S7. schistocytes

2015 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 287303
L. PALMER ET AL. | NOMENCLATURE AND GRADING OF PERIPHERAL BLOOD CELL MORPHOLOGY 303

Image S8. sickle cells Image S22. leukaemic myeloblasts


Image S9. spherocytes Image S23. abnormal promyelocytes in APL (1)
Image S10. stomatocytes Image S24. abnormal promyelocytes in APL (2)
Image S11. target cells (Copyright: Microscopic haematology: a practical guide for
Image S12. tear drop cells the laboratory 3e (c) 2011, Sydney, Elsevier Australia)
Image S13. basophilic stippling Image S25. monoblasts
Image S14. Howell-Jolly bodies Image S26. abnormal promonocytes
Image S15. Pappenheimer bodies (Copyright: Micro- Image S27. reactive lymphocytes
scopic haematology: a practical guide for the laboratory 3e Image S28. hairy cells
(c) 2011, Sydney, Elsevier Australia) Image S29. follicular lymphoma cells
Image S16. nucleated red blood cell Image S30. plasma cells
Image S17. large granular lymphocyte Image S31. prolymphocytic leukaemia cells
Image S18. Auer rods Image S32. chronic lymphocytic leukaemia cells
Image S19. hypergranulation (neutrophils) Image S33. giant platelets
Image S20. hypogranulation (neutrophils) (Copyright: Image S34. hypogranular platelets
Microscopic haematology: a practical guide for the labora- Image S35. micromegakaryocytes
tory 3e (c) 2011, Sydney, Elsevier Australia)
Image S21. Pelger Huet neutrophils

2015 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2015, 37, 287303

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