LETTER TO THE EDITOR

Cytomorphological Diagnosisof Langerhans Cell Histiocytosis

Dear Dr. Bedrossian:

Langerhans cell histiocytosis (LCH) is also known as histio-

cytosis X, comprising of eosinophilic granuloma, Letterer-

Siwe disease, Hand-Schuller-Christian disease triad.

LCH is a clonal proliferation of Langerhans cells that

express an immunophenotype positive for S-100 and

CD1a and which contain cytoplasmic Birbeck granules on

electron microscopy. LCH occurs worldwide and is most

common in children aged 1–3 years although it can occur

at any age. LCH is more common in boys with a male

female ratio of nearly 2:1. In adults, there may be a slight

female preponderance.1 Annual incidence of LCH is 5.4

million children per year.2

An 8-month-old male child presented with fever for 6

months followed by formation of papules on head, neck,

back, and trunk, which were unresponsive to treatment.

After 2 months, patient developed a nasal growth extend-

ing into palate and oral cavity after along with pallor and

hepatomegaly.

Routine hematological investigations revealed mild ane-

mia. Other investigations like biochemistry, bone marrow

examination, and chest X-ray were within normal limits.

Fine needle aspiration cytology (FNAC) from palatal

growth was performed using 23G needle and 10-ml sy-

ringe. Smears were fixed in 95% ethanol and were stained

with hematoxylin and eosin stain. FNAC revealed Langer-

hans histiocytes with characteristic grooved, folded ec-

centric nuclei and abounded eosinophilic cytoplasm.

Binucleated and multinucleated giant cell were seen along

with eosinophils, lymphocytes, and neutrophils (Fig. 1).

Biopsy of palatal growth showed polymorphous popula-

tion of cells comprising of Langerhans histiocytes, lym-

phocytes, eosinophils along with atypical histiocytes, few

multinucleated giant cell, foam cells, and neutrophils.

On immunohistochemistry, S-100 antigen and CD1a

markers were positive. CD1a is a specific marker of LCH.

LCH present with three main clinical subtypes. The

unifocal variant (single system, single site) also known as

eosinophilic granuloma presents with bone involvement

(up to 80% of cases), lymph nodes or lungs.3

The second subtype—Hand-Schuller-Christian disease—

usually affects younger patients and involves several sites

in one organ system (single system, multiple sites).3

Letterer-Siwe disease is a third subtype that affects

multiple sites in multiple organ systems and is more prev-

alent in young children and infants.3

The natural history of LCH is poorly understood.

Infact, spontaneous regression has been well documented

and therefore the relative benefit of any treatment modal-

ity including surgery, radiation, or chemotherapy has not

been fully elucidated.4 However, recurrences and more

aggressive courses have also been well described.

Prognosis depends on age at the time of diagnosis and

degree of organ involvement. It is poor in children under

Fig. 1. FNAC: Langerhans cell histiocytes showing characteristic grooved,folded eccentric nuclei and abundant eosinophilic cytoplasm. Occasionalmultinucleate cell seen (H&E, 3400). [Color figure can be viewed in theonline issue, which is available at wileyonlinelibrary.com.]

*Correspondence to: Lubna Khan, M.D., Department of Pathology,GSVM Medical College, Kanpur, Uttar Pradesh, India.E-mail: lkhan1@rediffmail.com

Received 31 October 2009; Accepted 24 January 2010DOI 10.1002/dc.21367Published online 4 March 2011 in Wiley Online Library

(wileyonlinelibrary.com).

' 2011 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 39, No 5 389

2 years of age and adults older than 65 years and patients

with multisystem disease.5

A retrospective study of 55 children under the age of 2

years diagnosed with LCH, found high-fatality rate

(81.3%) in children less than 6 months of age. Presence of

organ dysfunction, thrombocytopenia, and/or respiratory

dysfunction was highly associated with fatal outcome.6

The patient in this case responded to chemotherapy and

was discharged. Mortality occurred after about 2 months

due to pancytopenia-related complications.

The present case is reported with the aim to highlight

the unusual presentation of LCH and significance of cy-

tology in the diagnosis.

Lubna Khan, M.D.*

Sapna Soni, M.D.

P. K. Singh, M.D.

Asha Agrawal, M.D.

Department of Pathology

GSVM Medical College, Kanpur

Uttar Pradesh, India

Sandeep Kaushik, M.S.

Department of ENT

GSVM Medical College, Kanpur

Uttar Pradesh, India

References1. Goodman WT, Barrett TL. Disorders of Langerhans cells and macro-

phages. In: Bolognia JL, Jorizzo JL, Rapini RP, editors. Dermatol-ogy, Vol. 2. London: CV Mosby; 2003. p 1429–1433.

2. Bhatia S, Nesbit M, Jr, Egeler RM, et al. Epidemiological study ofLangerhans cell histiocytosis in children. J Pediatr 1997;130:774–784.

3. Al-Abbadi M, Masih A, Braylan RC, et al. Soft tissue Langerhans’cell histiocytosis in an adult. Arch Pathol Lab Med 1997;121:169–172.

4. Khanna G, Sato Y, Smith RJ, Bauman NM, Nerad J. Causes of facialswelling in pediatric patients: correlation of clinical and radiologicalfindings. Radiographics 2006;26:157–171.

5. Jubran RF, Marachelian A, Dorey F, Malogolowkin M. Predictors ofoutcome in children with Langerhans cells histiocytosi. Pediatr BloodCancer 2005;45:37–42.

6. Rivera-Luna R, Alter-Molchadsky N, Cardenas-Cardos R, Martinez-Guerra G. Langherhans cell histiocytosis in children under 2 years ofage. Med Pediatr Oncol 1998;26:334–343.

KHAN ET AL.

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