langerhans cell histiocytosis ( lch ) is a rare disease affecting predominantly children and young adults but can be found in any age group .
the disorder is characterized by abnormal , clonal proliferation and accumulation of antigen - presenting dendritic cells , the langerhans cells ( lcs ) , associated with immunosurveillance and immune regulation .
the peculiar cytomorphological , immunohistochemical , immunophenotypic , ultrastructural , and functional properties of these cells allow them to be identified amid various cells of the monocyte - macrophage lineage .
the spectrum ranges from unifocal disease with excellent survival to multifocal disease with single system or multisystem involvement associated with poor prognosis .
the skin , bone , lymph node , lungs , liver , spleen , thymus , and central nervous system may be involved .
the varied disease manifestations mandate different treatment modalities , which range from minimal therapy to aggressive multidrug chemotherapeutic regimens .
the present study was undertaken to study the cytomorphological features of lch , along with the differential diagnoses so that a rapid and accurate diagnosis on fine - needle aspirates can be made .
seven cases of lch diagnosed on fine - needle aspiration ( fna ) over a period of 10 years ( 2004 - 2013 ) were retrieved from the archives .
the clinical data from the cytology forms and case files of the patients were collected .
the clinical parameters including the age , sex , and signs and symptoms with emphasis on the type of lesions were evaluated .
fna was performed by the cytopathologist using 23-gauge needle fitted to a 10 ml disposable syringe mounted on syringe holder .
the smears were air - dried for may - grnwald - giemsa ( mgg ) and wet - fixed in 95% alcohol for hematoxylin and eosin ( h and e ) and papanicolaou staining .
the age of the patients ranged from 25 days to 11 years and the male - to - female ratio was 1:1.3 .
all the seven cases were confined to the head and neck region , which included three cases of lymphadenopathy , three cases of scalp swelling , and one case of orbital swelling as shown in table 1 .
clinically , the diagnoses suggested were tuberculosis , abscess , and malignancy in cases with enlarged lymph nodes . the scalp swelling was thought to be tuberculosis in one case and this patient also had cervical lymphadenopathy . the clinical possibility of a retrobulbar inflammatory lesion was kept in the case with orbital swelling .
clinical and cytomorphological findings in langerhans cell histiocytosis ( n = 7 ) the cytological findings are summarized in table 1 .
the cytologic smears in all the cases were cellular showing isolated lcs with low nuclear : cytoplasmic ratio , many having large , pale , bland ovoid vesicular  coffee - bean  nuclei with grooves and indentations , along with ample eosinophilic granular cytoplasm [ figure 1a  c ] .
areas of necrosis were seen in one case and staining for acid - fast bacilli done in this case was negative ( case 2 ) . on cytology , the diagnosis rendered was lch in all the cases .
langerhans cell histiocytosis ( a ) cytological smear showing langerhans cells ( lcs ) with a few binucleate and multinucleate forms in a polymorphic infiltrate with a preponderance of eosinophils ( mgg , 100 ) ( b ) aspirate smear showing lcs with grooved folded nuclei ( arrows ) ( h and e , 400 ) ( c ) an occasional lc showing mitosis ( arrow ) ( h and e , 200 ) ( d ) histological section showing diffuse infiltration by sheets of lcs ( h and e , 400 ) .
inset shows nuclear and cytoplasmic positivity for s-100 immunostain in lcs ( immunoperoxidase , 400 ) histopathologic confirmation was performed in all the cases .
paraffin sections showed sheets and islands of dense mixed infiltrate composed of lcs , eosinophils , and lymphocytes [ figure 1d ] .
in all the cases , immunohistochemistry for s-100 antibody showed nuclear and cytoplasmic staining in lcs [ figure 1d ] .
the cytologic smears in all the cases were cellular showing isolated lcs with low nuclear : cytoplasmic ratio , many having large , pale , bland ovoid vesicular  coffee - bean  nuclei with grooves and indentations , along with ample eosinophilic granular cytoplasm [ figure 1a  c ] .
areas of necrosis were seen in one case and staining for acid - fast bacilli done in this case was negative ( case 2 ) . on cytology , the diagnosis rendered was lch in all the cases .
langerhans cell histiocytosis ( a ) cytological smear showing langerhans cells ( lcs ) with a few binucleate and multinucleate forms in a polymorphic infiltrate with a preponderance of eosinophils ( mgg , 100 ) ( b ) aspirate smear showing lcs with grooved folded nuclei ( arrows ) ( h and e , 400 ) ( c ) an occasional lc showing mitosis ( arrow ) ( h and e , 200 ) ( d ) histological section showing diffuse infiltration by sheets of lcs ( h and e , 400 ) .
inset shows nuclear and cytoplasmic positivity for s-100 immunostain in lcs ( immunoperoxidase , 400 )
paraffin sections showed sheets and islands of dense mixed infiltrate composed of lcs , eosinophils , and lymphocytes [ figure 1d ] .
in all the cases , immunohistochemistry for s-100 antibody showed nuclear and cytoplasmic staining in lcs [ figure 1d ] .
the disparate group of diseases with variable nomenclatures  histiocytosis x , eosinophilic granuloma , letterer - siwe disease , hand - schuller - christian syndrome , hashimoto - pritzker syndrome , self - healing histiocytosis , pure cutaneous histiocytosis , langerhans cell granulomatosis , type ii histiocytosis , and nonlipid reticuloendotheliosis are now collectively referred to as lch .
the clonal proliferation of the antigen presenting dendritic cells , the langerhans cells , supports neoplastic nature of lch . for a long time
it may be a viral infection induced or a defect in t cell macrophage interaction and/or a cytokine - mediated process , involving interplay of tumor necrosis factor , interleukin 11 , and leukemia inhibitory factor .
the multifocal unisystem disease almost always occurs in the bone usually involving the skull , spine , pelvis , ribs , and mandible in more than half of the cases .
the multifocal multisystem disease involves multiple organs  the bone , liver , spleen , hematopoietic system , skin , and lymph node .
lytic lesions in the skull bones having a punched out appearance was seen in one case .
the differential diagnoses of skull lesions clinically include ewing 's sarcoma , non - hodgkin lymphoma , and osteomyelitis .
ewing 's sarcoma and non - hodgkin lymphoma are characterized by a monotonous population of malignant small round cells . in acute osteomyelitis
, there is a neutrophilic predominance while chronic osteomyelitis shows numerous plasma cells and lymphocytes .
the cytological smears in lch are almost always cellular , composed of sheets and scattered lcs with interspersed polymorphous population of eosinophils , neutrophils , lymphocytes , plasma cells , and multinucleated giant cells . in fna ,
the cellularity of the smears and proportion of various cells correlate with the stages of lesions in lch .
further , with increasing duration fibrosis sets in ; the lcs and eosinophils become an occasional finding .
the cytologic differential diagnoses of lch include dermatopathic lymphadenitis , parasitic infection , kimura 's disease , cat - scratch disease , sinus histiocytosis with massive lymphadenopathy , and hyperplastic lymph nodes .
the cytomorphological features in the presence of relevant clinical and radiological findings are sufficient for reaching a correct diagnosis and ancillary studies are not mandatory in all the cases .
in diagnostic difficulties , ancillary techniques such as immunostaining and electron microscopy are of help .
the birbeck granules  pentalaminar structures with prominent central cross striations seen on electron microscopy is the ultrastructural hallmark , which is present in 2 - 69% of the cases .
to conclude , fna procedure , which is rapid , quick , and easy may be helpful in the early identification of lch patients so that appropriate therapeutic measures are instituted .
a high index of suspicion , awareness of cytological features of lch , and the diagnostic pitfalls hold the key to an accurate diagnosis .
 background : langerhans cell histiocytosis ( lch ) is a rare intricate pediatric neoplasm with varied clinical manifestations and multiple treatment modalities.aim:to study the cytological features of lch and the differential diagnoses on fine - needle aspiration ( fna).materials and methods : fna was performed using a 23-gauge needle fitted to a 10 ml syringe mounted on syringe holder . 
 lch was diagnosed on fna smears in seven cases confined to the head and neck region , which included three cases of lymphadenopathy , three cases of scalp swelling , and one case of orbital swelling.results:the age of the patients ranged from 25 days to 11 years and male - to - female ratio was 1:1.3 . 
 clinically , the diagnoses suggested were tuberculosis , inflammatory lesion , abscess , and malignancy . 
 the cytologic findings included high cellularity , isolated langerhans cells ( lcs ) with prominent nuclear indentation , grooves and abundant vacuolated cytoplasm , multinucleated giant cells , eosinophils , and lymphocytes . 
 areas of necrosis were noted in one case . 
 histopathology , along with positive s-100 immunohistochemistry , confirmed the diagnosis of lch.conclusions:lch is a rare disease occurring predominantly in children and can be diagnosed with ease on fna cytology by the presence of characteristic langerhans cells . 
 the s-100 positivity aids in suggesting a diagnosis of lch . 