Case Report

Amee Soni *, Chandni Gadara*, Preeti Jhaveri**, Anjali Goyal***, C. K. Shah ****

Hairy Cell Leukemia- A Case Report

* Resident

** Assistant Professor

*** Associate Professor

**** Professor and Head, Pathology Department, Smt. N.H.L

Municipal Medical College, Ahmedabad, Gujarat, India

Correspondence : Dr. Amee Soni

E-mail : ameesoni37@gmail.com

Introduction :

Hairy cell leukemia is recognized as an entity by the

world health organization (WHO 2008) and the 2016

revision of the WHO classification of lymphoid

neoplasm.HCL is rare chronic B-cell disorder,

accounting for 2% of Non- Hodgkin lymphomas and

occurs more frequently in men with an overall incidence

of 2.9 per million per year for men and 0.6 per million (1)per year for women in the united states. The etiology

of HCL is unknown, although case control studies have

identified possible relationships to farming (including

exposure to farm animals, commercial herbicides

and/or pesticides) and an inverse correlation with (1)smoking. More recently it has been demonstrated that

most hairy cells contain a mutated active form of the

BRAF gene(V600E) which may be used as a diagnostic (2)tool and a potential target for therapy. Complete

blood count and careful review of the peripheral blood

smear are the first step in very characteristic

morphological identification of hairy cells. Diagnosis is

achieved by studies on peripheral blood including flow

cytometry and review of peripheral blood smear along

with bone marrow biopsy. The flow cytometry markers

positive in hairy cell leukemia include CD 11c, CD 25,

Abstract :

Hairy cell leukemia is rare chronic B cell malignancy that involves the bone marrow, spleen and peripheral blood.

Median age of diagnosis is approximately 55 years with significant higher incidence in Men and male to female

ration of 4:1. The disease is characterized by the presence of typical hairy cells in peripheral blood and bone

marrow, pancytopenia and a variable degree of splenomegaly. Classically patient present with weakness,

fatigue, symptoms related to pancytopenia and splenomegaly. The etiology of hairy cell leukemia not well

elucidated. However previous exposure to various chemicals may play a role in it's development. Most cases are

postulated to be derived from V600E BRAF gene mutation of late activated memory B cell.

Key Words : B-cell lymphoid leukemia, Hair like projection, Hairy cell leukemia, V600E BRAF mutation

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CD 103, along with typical B- cell marker such as CD19, (2)CD20 or CD22. Hairy cells can be identified in

Romanowsky-stained peripheral blood films from

approximately 90% of patients as mononuclear cells

that are usually 1 to 2 times the size of mature

lymphocyte.

Case report:

An old female patient, aged 40 years, presented to out-

patient department with chief complain of abdominal

pain since 2 years. Patient was relatively asymptomatic

before 2 years. Then she develops abdominal pain

which was diffuse, insidious in nature and associated

with nausea, constipation, vomiting and intermittent

fever. On clinical examination spleen was palpable. USG

findings showed hepatosplenomegaly. On peripheral

blood smear WBC series showed lymphocytosis with

large atypical lymphocytes showing irregular cell

membrane and moderate basophilic cytoplasm. Many

cells show hair-like cytoplasmic processes and few show

polar villous cyoplasmic processes. Nuclei are round to

oval with clumped chromatin and indistinct nucleoli.

Patient also has anemia and thrombocytopenia.

Findings are suggested possibility of hairy cell leukemia.

Bone marrow biopsy was performed which shows

hypercellular marrow. Occasional megakaryocytes were

seen. It shows significantly increased lymphoid cells,

approximately 58% with many showing hairy cell

projection. Erythroid series show normoblastic

maturation. Granulocytic series is suppressed. And the

diagnosis of hypercellular marrow involved by hairy cell

leukemia was made.

GCSMC J Med Sci Vol (IX) No (I) January-June 2020

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Discussion:

As a lymphoproliferative neoplasm, Hairy cell leukemia

is a clonal disorder. The relatively recent discovery of the

presence of the V600E BRAF gene mutation in vast

majority of cases of classic Hairy cell leukemia has

suggested that the pathogenesis of this disorder lies in ( 2 , 3 )the RAS-RAF-MAPK signaling pathway.

Constitutive activity of this pathway leads to increased

cellular proliferation and survival and ultimately

malignancy. A recent study also found CDKN1B (3)inactivation in 16% of patient with classical HCL. It is

the second most commonly mutated gene in HCL.

Classically patient present with weakness, fatigue and

other symptoms related to pancytopenia and

splenomegaly. Patient commonly present with

pancytopenia at presentation, which is multifactorial in

nature and related to marrow infiltration, cytokines

induced myelosuppression with myelofibrosis and (4)splenic sequestration. Pyogenic infections account for

50 % of infectious episodes, gram-negative and gram-

positive bacteria are identified with approximately equal (4)frequency. Infectious complication are common due to

both the underlying immunosuppresion from

cytopenias and myelosuppressive therapy. Clinical

manifestation secondary to various autoimmune

disorders are being recognized with increasing

frequency in patients with HCL. Hairy cell are

frequently present on examination of a peripheral blood

film and demonstrate a characteristic monocytoid

appearance with pale blue-gray cytoplasm,

circumferential fine villous projection and cell diameter (4, 5)in the range of 10 to 25 µm. Marrow infiltration is

demonstrable in trephine biopsies of more than 99% of

patient. Over all marrow cellularity appears increased.

The bone marrow aspiration may be difficult in HCL,

with a “Dry tap” or exceedingly hemodilute aspirates

obtained in approximately 50% cases secondary to a

diffuse reticulin fibrosis produced by the hairy cell

infiltrate through autocrine production and (5)multimerization of fibronectin. Immunophenotyping

has proved very useful in assisting in the diagnosis of

HCL and in differentiating it from variants and other B-

cell malignancies. Immunophenotype includes bright

CD 11c expression with CD 103, CD25, CD123 and

AnnexinA1(ANXA 1) coexpression along with typical

B-cell markers such as CD 19, CD20 or CD22. ANXA1

is regarded as the most specific tumor marker for HCL,

(6)as it is absent on other B-cell lymphomas. Positive

immunostaining for tartrate resistant acid (6)phosphatase(TRAP) , is also a diagnostic tool for HCL.

Treatment for HCL is reserved for symptomatic

patients. Cladribine and pentostatin, 2 purine analogs

are the first line treatment for hairy cell leukemia. Either

of these two drugs is highly effective in inducing high

rate of complete remission for prolonged duration, they

have replaced alpha- interferon and splenectomy as (6, 7)first line therapy in HCL.

Figure 1: Peripheral smear of hairy cell leukemia

Figure 2: Bone marrow biopsy of hairy cell leukemia.

Soni A. et al. : Hairy cell leukemia...

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The pattern of bone marrow involvement is typically an

interstitial infiltration becoming diffuse, creating

“Honeycomb” or “Fried egg” appearance with the

nucleus of each hairy cell surrounded by a halo of

cytoplasm.

Conclusion:

Hairy cell leukemia is rare type of leukemia , which may

be considered in the presence of pancytopenia

associated with splenomegaly , presence of atypical

lymphoid cells with irregular cytoplasm projections in

peripheral blood, bone marrow and unique

immunophenotypic features. Cladrabine is regarded as

a first line chemotherapy due to its favorable toxicity

profile. Prolong survival is possible with current modes

of therapy, thus prognosis is good.

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GCSMC J Med Sci Vol (IX) No (I) January-June 2020