ISSUE23

ISSUE

March2022

This issue
Last Month’s Slides P.1
Monthly Digital Case study P.1-2
Cell Quiz P.2
Rare Lymphoid clonal disorders P2-3

Last Month’sSlides
Slide 1
Lymphocytosis /Atypicallymphs? Monomorphic
hyperlymphocytosis
associated with a large
number of naked nuclei.
Immunophenotyping of
circulating lymphocytes
requested. Expert comment:
Probable CLL.

Slide 2
See case study on right.

Slide 3
Intensive care unit andpreoperative medicine.
Multiple analyser alarms.
Anisocytosis (++).
Microcytosis (++).
Macrocytosis (++). RBCtargets (+). Expert comment:
RBC targets: Underlying
hepatic disorder. Nomicrocytes.

Slide 4
Anisocytosis (++).
Eosinophilia. Discretebasophil: Nothing to report.

Monthly Digital Case Study
February 2022, Slide 2
Presentation
Male, 84 years old. Leucocytosis anderythroblastosis

FBC Results
WBC 84.2 (10^3/mm3)
RBC 2.82 (10^6/mm3)
HGB 8.0 (g/dL)
HCT 24.3 (%)
MCV 86.0 (fL)
MCH 28.4 (pg)
MCHC 32.9 (g/dL)
PLT 54 (10^3/mm3)
Neutrophils 10.6
Lymphocytes 39.0
Monocytes 2.4
Eosinophils 1.6
Basophils 0.8

Slide 5

Erythroblast

Blast cell

Hyperleukocytosis. Balancedmyelemia. Basophilia
Presence of erythroblasts.
Probable myeloproliferative
syndrome (CML?).

Slide Review

Slide 6AML is the most common type of acute leukaemia in adults, andprogresses quickly if left undiagnosed. AML results when myeloid
stem cells develop into immature white cells called MYELOBLASTS.
The myeloblasts in AML are abnormal and do not develop into healthy cells.

Nothing to report.

Anisocytosis (++). Poikilocytosis (+). Echinocytes (+). Hypogranulation of neutrophils(+). Blast population estimated at 40% of leukocytes. To be compared with the restof the clinical assessment. Expert comment: Indicative of AML.

Cell Quiz:
What is the feature within thered cell:

These leukaemic cells build up in the bone marrow and blood, preventing
healthy WBC’s platelets doing their job. This results in infection, anaemia andbleeding tendency.

There are sub-types of AML, which are based on the maturity of the leukaemic
cells at the time of diagnosis, and their variation from normal cells.
Acute Promyelocytic Leukaemia is a sub-type of AML which occurs when thereis a switching of the gene on chromosome 15 with genes on chromosome 17,
resulting in an abnormal gene, called PML-RARA. This abnormal gene sends amessage which stops promyelocytes maturing.

Rare Lymphoid Clonal Abnormalities
Hairy Cell Leukaemia (HCL)A) Howell Jolly Body
B) Ring form of P.
FalciparumC) Platelet

Last Month’s CellQuiz:

HCL is a rare clonal chronic lymphoproliferative disorder of B Cell Lymphocyte
origin which accounts for about 2% of all leukaemias. In the 1920’s it was
originally described as histiocytic leukaemia, malignant reticulosis andlymphoid myelofibrosis. The disease was first officially described in 1958 bycancer researcher Bertha Bouroncle from the Ohio state University USA. Theterm Hairy Cell Leukaemia was first used to describe the appearance of hairlike projection of the mononuclear cells in the disorder in 1966 by Shrek andDonelly. See below:

The film below is from apatient with Haemolytic
Anaemia. What feature do yousee?
Hairy Cells showing fine cytoplasmic projections, larger than anormal
lymphocyte, weakly basophilic cytoplasm.

A) Target cellsB) SpherocytosisC) Poikilocytosis
Answer: B
The film shows
SPHEROCYTOSIS, and is from apatient with haemolytic
anaemia. Spherocytes appear
as round red cells that lack thecentral area of pallor. They
appear darker and smaller
than a normocytic red cell. A
raised MCHC is noted in theFBC result.

The incidence of HCl is most common in elderly males (median age atdiagnosis 55), the commonest clinical symptoms being Pancytopenia andSplenomegaly (Splenomegaly due to extramedullary haematopoiesis) without
lymphadenopathy are the common clinical presentation. Monocytopenia isalmost always present, few abnormal lymphocytes may be present in theblood film. The abnormal cell population has slightly basophilic cytoplasm, andthe cell nucleus is round slightly indented, or reniform, nucleoli are indistinct
or absent. Bone marrow biopsy and Immunophenotyping is essential forcorrect diagnosis. Marrow aspiration may not be possible because ofincreased reticulin fibrosis. The recently identified mutation BRAFV600E has
been identified in 100% of classical HCL patients.

HCL VariantHCL Variant (HCL-V) accounts for about 10 % of all HCL cases and has featuresof both HCl and B-Prolymphocytic Leukaemia (B-PLL), the WBC is usually
elevated as in B-PLL with abnormal cells having the cytoplasmic projection asin HCL but with the addition of a prominent central nucleolus similar to that in
B-PLL, abnormal cells are often numerous in number, the BRAF V600E
mutation is absent in variant HCL. Presenting symptoms are similar to those ofclassical HCL.

Splenic Lymphoma with Villous Lymphocytes (SLVL)SLVL is a rare disorder accounting for less than 1% of lymphoid neoplasms. It is
the leukemic counterpoint of splenic marginal zone lymphoma (SMZL) and ischaracterised by splenomegaly, often with no lymphadenopathy moderate
lymphocytosis and the presence of villous (hairy), like lymphocytes in the blood
film. The morphology of the cells is slightly different to HCL in that the nucleus
is round with chromatin clumping, the cytoplasm is scanty to moderate inamount and weakly to moderate basophilic. The cytoplasmic projections arelocated at the poles of the cell (see below):

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Bibliography
https://www.sciencedirect.
com/topics/nursing-andhealth-professions/hairycell-leukemia
BJH Guidelines fordiagnosis and managementof HCL and HCL-V

Differential Diagnosis
Essential Haematology
A.V .Hoffbrand & J.E.Pettit

HCL

HCL-V

SMZL (SLVL)Gender M:F

4:!

M>F1:1

Age

Median : 55

Middle Aged elderly> 60 yrs

Immunophenotype

CD20 bright +CD20 bright +CD20 bright +CD103+

CD103 +

CD103 -CD25 +CD25-

CD25 -/+

CD27 -

CD27 +

CD27 +

CD11c+

CD11c+

CD11c +/-

CD123+

CD123-

CD123-

About us

DBA 44+

DBA44 +DBA44 +

Annexin A1+

Annexin A1-Annexin A1-

BRAF V600 E
mutation

BRAF V600E notmutated.
MAP2KImutations

Del7q (40%),
NOTCH2 andKLF2 mutations

HORIBA UK Limited
Kyoto Close
Moulton Park
Northampton, UK
NN3 6FL

Molecular Genetics

Prognosis and treatment of HCL, HCL-V and SLVL
Generally HCL is a less aggressive disease than is HCL-V with 95% of HCL patientssurviving for more than 5 years post diagnosis. SLVL has a median overall mediansurvival of 10 years, approx. 30% of these patients will develop an aggressive
form which greatly reduces the median survival. Treatment can take the form of– watchful waiting with regular medical reviews, chemotherapy (Cladribine andPentostatin), immunotherapy (recombinant interferon alpha-2b), targeted
therapy (Monoclonal antibody Rituximab, Moxetumomab pasudotox-tdfk ifrelapsed), and surgery (removal of enlarged spleen).

Editorial Team
Kelly Duffy
Andrew Fisher

HORIBA MedicalParc Euromédecine, 390
Rue du Caducée, 34790,
Francewww.horiba.com/medical