|Year : 2015 | Volume
| Issue : 4 | Page : 1028
Langerhans cell histiocytosis diagnosed by FNAC of lymph nodes
Shashikant C.U. Patne1, Saloni Dwivedi1, Richa Katiyar1, Vineeta Gupta2, Aditya K Gupta2
1 Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
|Date of Web Publication||15-Feb-2016|
Shashikant C.U. Patne
Department Of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Langerhans cell histiocytosis (LCH) is a rare clonal disorder of unknown etiology and characterized by the proliferation of dendritic cells. LCH most commonly involves the bone followed by the skin and the lymph nodes. Recently, only a few cases of LCH with predominant lymph node involvement have been diagnosed by fine-needle aspiration cytology (FNAC). A 2-year-old boy presented with generalized lymphadenopathy, fever, and cough. The patient had hepatosplenomegaly, anemia, and lytic lesions in the skull. FNAC from the largest submandibular lymph node showed features of LCH. The large cells of LCH showed positive immunostaining for S-100 protein on FNAC smears. Later, lymph node biopsy and immunohistochemistry against S-100 protein and CD1a confirmed the diagnosis of LCH. The patient was treated with chemotherapy and he is under regular follow-up. This case report highlights the importance of FNAC as a rapid and accurate investigation in the diagnosis of lymph node predominant LCH.
Keywords: Cytology, CD1a, eosinophilic granuloma, lymphoma, Letterer-Siwe disease
|How to cite this article:|
Patne SC, Dwivedi S, Katiyar R, Gupta V, Gupta AK. Langerhans cell histiocytosis diagnosed by FNAC of lymph nodes. J Can Res Ther 2015;11:1028
| > Introduction|| |
Langerhans cell histiocytosis (LCH) is a rare disorder of unknown etiology, wherein clonal proliferation of the dendritic cells occurs. , In children, the estimated incidence of LCH is eight to nine cases a million each year.  LCH may occur in any tissue within the body; however, bone is the most common site of involvement, followed by the skin and the lymph nodes.  Recently, there are only a few reports establishing diagnosis of LCH by fine-needle aspiration cytology (FNAC) of lymph nodes. ,,, Here, we report FNAC diagnosis of LCH in a child with primary involvement of lymph nodes.
| > Case report|| |
A 2-year-old boy brought by his parents to the pediatric outpatient department with generalized lymphadenopathy since 5 months, fever since 15 days, and cough since 2 days. Examination of the boy showed pallor and generalized lymphadenopathy. He had multiple bilateral cervical, submandibular, axillary, and inguinal lymph nodes. The largest submandibular lymph node was 10 × 8 cm [Figure 1]. The liver was 8 cm in midclavicular line and the spleen measured 4 cm along the long axis. There was extensive seborrheic dermatitis of the scalp. Provisional clinical diagnosis was lymphoma. Except for hemoglobin 5.6 g/dl, all other hematological investigations were within the normal limits. Computed tomography scans of the thorax revealed patchy soft-tissue opacity in the right upper lobe of lung and the right perihilar region, suggesting a possibility of infective pathology. Mantoux and QuantiFERON-TB gold tests were negative. There were many enlarged periportal and parasplenic lymph nodes on ultrasonography examination. FNAC of bilateral cervical and submandibular lymph nodes was air dried and fixed in 90% ethanol for Giemsa and Papanicolaou staining, respectively. Microscopic examination showed cellular smears with many scattered large polygonal cells having complex, irregularly folded nuclei, prominent nuclear grooves and clefts, infrequent visible nucleoli, and abundant cytoplasm [Figure 2]a]. These cells were admixed with eosinophils, lymphocytes, foamy histiocytes, and multinucleate giant cells. Mitotic figures were few. For immunocytochemistry, repeat FNAC smears were spread over a slide precoated with 10% poly-L-lysine, and after spread immediately fixed in chilled acetone at 4°C for 30 min. After 30 min, the slides were brought to room temperature and standardized steps of immunostaining were done. There was strong nuclear and cytoplasmic staining for S-100 protein [Figure 2]b] and negative staining for CD20 in the large cells. The findings of cytomorphology and immunocytochemistry were in favor of LCH. After diagnosis of LCH on cytology, the skull X-ray showed osteolytic lesions; while magnetic resonance imaging revealed extensive calvarial lytic bony lesions with soft-tissue involvement of the pineal gland. For diagnostic confirmation, excision biopsy of the submandibular lymph node was done. Histopathology sections showed complete effacement of lymph node architecture and diffuse infiltrate of sheets of large polygonal cells with irregularly folded nuclei, prominent nuclear grooves, and plentiful cytoplasm. There were admixture of eosinophils, osteoclast-like giant cells, histiocytes, and lymphocytes [Figure 2]c]. Immunohistochemistry was performed, which showed strongly positive S-100 protein and CD1a [Figure 2]d] in the large cells, while CD20 and CD3 were negative. Pathological findings were diagnostic of LCH. The final clinical diagnosis was Letterer-Siwe variant of LCH. Patient responded well to the initial four cycles of chemotherapy regimen comprising of prednisolone and vinblastine. At present, he is under regular follow-up.
|Figure 1: Photograph of the child with enlarged right submandibular lymph node (arrow)|
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|Figure 2: (a) Fine-needle aspiration cytology (FNAC) smear showing cellular clusters of the large cells of Langerhans cell histiocytosis (LCH) with prominent nuclear grooves (arrows) along with scattered lymphocytes and an occasional eosinophil (Papanicolaou stain, ×400). (b) Immunocytochemistry done on FNAC smear showing strongly positive nuclear and cytoplasmic expression of S-100 protein in the large cells of LCH (S-100 protein immunostain, × 400). (c) Diffuse sheets of the large cells of LCH admixed with osteoclastic-type giant cells, eosinophils, and lymphocytes (hematoxylin and eosin stain, ×400). (d ) Strong membranous expression of CD1a in the large cells of LCH (CD1a immunostain, × 400)|
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| > Discussion|| |
LCH represents a spectrum of disorders with varied clinical presentation. Based on disease severity, classification of LCH is: (a) The gravest form, Letterer-Siwe disease, (b) a less serious form, Hand-Schuller-Christian disease, and (c) the mildest form, eosinophilic granuloma. Letterer-Siwe disease is most commonly seen in infant and children less than 3 years of age and clinically presents with fever, weight loss, otitis media, papular rash, exophthalmos, hepatosplenomegaly, lymphadenopathy, and generalized skeletal involvement.  Unfortunately, our patient had the most severe Letterer-Siwe disease variant of LCH.
The lymph node involvement in LCH presents with adjacent bone lesions in one-third patients.  The lymph node involvement can occur either as a part of systemic disease or as an isolated manifestation.  The dendritic cells of LCH migrate from the epidermis to regional lymph nodes through efferent lymphatics. However, upon arrival in the lymph node, they lose their capability of antigen presentation. 
Cytology and histology examinations of LCH reveal the characteristic large cells of around 12 μm diameter with irregular convoluted nuclei, nuclear clefts and grooves, one or more small nucleoli, fine chromatin, and abundant amount eosinophilic cytoplasm. , These large cells are usually admixed with varying proportions of eosinophils, osteoclast-type giant cells, neutrophils, and lymphocytes. By inducing osteoclast-derived enzymes, these giant cells are responsible for the destruction of architecture in both osseous and nonosseous lesions of LCH. 
Histiocyte Society Writing group (1987) has defined the criteria for the diagnosis of LCH, according to which the presence of Birbeck granules on electron microscopy or demonstration of CD1a on immunohistochemistry confirms the diagnosis of LCH in a typical histology.  Strong expression of CD1a was the diagnostic marker of LCH in our case. Recently, Langerin (CD207), a novel C-type lectin, has been shown to induce the formation of Birbeck granules; thus, immunohistochemical demonstration of Langerin is the marker of Birbeck granules in LCH. 
In this case, the earliest diagnostic findings of LCH were obtained by FNAC. This case report highlights usefulness of immunocytochemistry in diagnosis of LCH without the use of cellblock or liquid-based cytology. The procedure is satisfactory on the FNAC smears, provided the person doing FNAC is experienced enough, smear is well spread over a small area, and the slide is immediately fixed in chilled acetone. Thus, a provisional clinical diagnosis of lymphoma was found to be LCH on cytological smears. Later, radiological examinations revealed osteolytic lesions and the diagnosis was confirmed by histopathology and immunohistochemistry.
Currently, accepted treatment of LCH includes surgery, chemotherapy, and radiotherapy. While patients of LCH with disseminated bony lesions are candidates for low dose radiotherapy, chemotherapy is the treatment for systemic involvement with dysfunction of organs like liver, lungs, spleen, or bone marrow.  Our patient is receiving chemotherapy and he is under regular follow-up.
| > References|| |
Abla O, Egeler RM, Weitzman S. Langerhans cell histiocytosis: Current concepts and treatment. Cancer Treat Rev 2010;36:354-9.
Pinkus GS, Lones MA, Matsumura F, Yamashiro S, Said JW, Pinkus JL. Langerhans cell histiocytosis immunohistochemical expression of fascin, a dendritic cell marker. Am J Clin Pathol 2002;118:335-43.
Buckwalter JA, Brandser E, Robinson RA. The variable presentation and natural history of Langerhans cell histiocytosis. Iowa Orthop J 1999;19:99-105.
Lee LY, Kang CJ, Hsieh YY, Hsueh S. Diagnosis of nodal Langerhans cell histiocytosis by fine needle aspiration cytology. Chang Gung Med J 2005;28:735-9.
Pohar-Marinsek Z, Us-Krasovec M. Cytomorphology of Langerhans cell histiocytosis. Acta Cytol 1996;40:1257-64.
Sajjad SM, Osborne B. Lymph node involvement by histiocytosis X. Arch Pathol Lab Med 1982;106:96-8.
Akhtar M, Ali MA, Bakry M, Sackey K, Sabbah R. Fine needle aspiration biopsy of Langerhans histiocytosis (histiocytosis-X). Diagn Cytopathol 1993;9:527-33.
Edelweiss M, Medeiros LJ, Suster S, Moran CA. Lymph node involvement by Langerhans cell histiocytosis: A clinicopathologic and immunohistochemical study of 20 cases. Hum Pathol 2007;38:1463-9.
da Costa CE, Annels NE, Faaij CM, Forsyth RG, Hogendoorn PC, Egeler RM. Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. J Exp Med 2005;201:687-93.
Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, et al
. Langerin, a novel C-type lectin specific to Langerhans cell, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 2000;12:71-81.
[Figure 1], [Figure 2]