Journal of Cytology
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CASE REPORT Table of Contents   
Year : 2008  |  Volume : 25  |  Issue : 4  |  Page : 153-156
Solitary eosinophilic granuloma of the ulna: Diagnosis on fine needle aspiration cytology


1 Department of Pathology, J.N. Medical College, A.M.U., Aligarh, India
2 Department of Orthopaedics, J.N. Medical College, A.M.U., Aligarh, India

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   Abstract 

Solitary eosinophilic granuloma is a part of the spectrum of Langerhans cell histiocytoses (LCH) which are rare diseases with varied clinical presentations. They comprise of three major overlapping syndromes: solitary eosinophilic granuloma (unifocal disease), Hand-Schueller-Christian disease (multifocal, unisystem), and Letterer-Siwe disease (multifocal, multisystem).
A case of solitary eosinophilic granuloma of the ulna is presented here for its relatively uncommon incidence and the difficulty in making an accurate diagnosis based on the radiological picture alone. We hereby, emphasize the importance of a quick and reliable diagnosis based on fine needle aspiration cytology, and the need to consider the possibility of LCH in the differential diagnoses of a slide showing a large number of histiocytes and eosinophils, as in tuberculosis, Hodgkin's disease, and other primary and metastatic bony lesions. Characteristic nuclear grooves and a large number of eosinophils help in clinching the cytological diagnosis.

Keywords: Bone; FNAC; Langerhans cell histiocytosis; ulna.

How to cite this article:
Jain A, Alam K, Maheshwari V, Jain V, Khan R. Solitary eosinophilic granuloma of the ulna: Diagnosis on fine needle aspiration cytology. J Cytol 2008;25:153-6

How to cite this URL:
Jain A, Alam K, Maheshwari V, Jain V, Khan R. Solitary eosinophilic granuloma of the ulna: Diagnosis on fine needle aspiration cytology. J Cytol [serial online] 2008 [cited 2021 Mar 5];25:153-6. Available from: https://www.jcytol.org/text.asp?2008/25/4/153/50803



   Introduction Top


Langerhans cell histiocytosis (LCH) is a rare disease involving clonal proliferation of the Langerhans cells. The disease is part of a group of clinical syndromes called histiocytoses that are characterized by an abnormal proliferation of histiocytes (an archaic term for dendritic cells and macrophages). Their manifestations range from isolated bone lesions to multisystem disease; however, neither the clinical findings nor imaging studies are sufficient by themselves to make a diagnosis in the majority of the cases. The current case had a similar nonspecific appearance clinically as well as on the radiographs, but the cytological findings clinched the diagnosis of LCH that was proved further by imprint cytology, histopathology, and immunohistochemical staining for CD1a.


   Case Report Top


A seven year-old girl presented with swelling and deformity of her left elbow of two months' duration. There was no history of fever, weight loss, or rashes. Pain and deformity were not present at any other bony site or joint and there were no other soft tissue swellings.

On examination, she was found to be of moderate build and nutrition. There was no pallor, lymphadenopathy, or hepatosplenomegaly; systemic examination yielded no remarkable results.

There was a bony swelling on the upper forearm, measuring 4.0 3.0 cm, hemispherical in shape with a smooth surface and hard consistency; the skin over the swelling appeared normal. Palpation did not raise the local temperature and the swelling was nontender. However, active range of motion at the elbow joint was only possible with difficulty because of pain.

Results of routine investigations were within normal limits except for a raised erythrocyte sedimentation rate which was 50 mm fall at the end of the first hour (Wintrobe's method). There was no M-band seen on serum protein electrophoresis. Liver enzymes, renal functions, and serum uric acid were normal; chest radiograph was unremarkable. Radiographs of the forearm revealed an osteolytic lesion involving the upper 1/3 rd of the ulna.

Fine needle aspiration cytology (FNAC) from the swelling revealed good cellularity smears composed of a mixed population of mainly histiocytoid cells with grooves in the nuclei and large number of eosinophils [Figure 1] along with occasional neutrophils and lymphocytes. The histiocytoid cells were approximately 10-15 in size, with moderate to abundant, slightly eosinophilic cytoplasm, and grooved, folded, indented, or lobulated nuclei, fine chromatin, inconspicuous nucleoli, and a thin nuclear membrane [Figure 2]. Binucleate and multinucleate forms resembling osteoclasts were seen frequently. There was only mild nuclear atypia and occasional mitoses. Therefore, a diagnosis of solitary eosinophilic granuloma (unifocal LCH) was suggested based on the FNAC, and biopsy was advised for a confirmation.

Surgical excision of the lesion was performed based on the cytology report. Imprint smear examination and histopathology showed a similar picture as cytology [Figure 3a]. The Langerhans cells stained positive with S-100 [Figure 3b] and further workup revealed no other bony lesions; bone marrow examination revealed no abnormalities. The patient is doing well postoperatively.


   Discussion Top


The incidence of LCH is about five per million with most cases occurring in childhood. [1] According to a recent study, the median age at diagnosis is 3.8 years (two months to 13.7 years) with 69% of the children having single system disease. [2] There is a predilection for males (male: female ratio 3.7: 1) and whites of Northern European descent. [3] In contrast to these findings, our patient was a seven year-old girl child.

Solitary eosinophilic granuloma accounts for the majority of LCH cases, usually involving bone and less commonly, the lymph node, skin, or lung. [3] The skull, long bones of the upper extremities, and the flat bones are affected in descending order; the problem being manifested as persistent pain, swelling, and less commonly, pathological fracture. [4]

The clinical and radiographic findings are often not specific enough to determine the diagnosis. Similar to plain radiographic studies; bone, computed tomogram, and magnetic resonance imaging scans are also not diagnostic. [5] There is diffuse osteopenia in some patients, but in others, it appears as a focal, sharply defined, osteolytic lesion involving the diaphysis or irregular destructive defects with significant reactive bone formation. [3],[5] Appearance on radiographs is variable among different patients and at different locations, and may resemble a variety of other bone lesions such as tuberculous osteomyelitis, chondroblastoma, Ewings' sarcoma, lymphoma, metastatic renal cell carcinoma, and amelanotic melanoma. [6] In the present case, there was an osteolytic lesion involving the diaphysis of the ulna. Chondroblastoma is usually epiphyseal and shows calcifications. [6] A possibility of osteomyelitis, especially of tuberculous nature, is the most important differential diagnosis particularly in our country where tuberculosis is so common.

Cytology is very helpful in arriving at the diagnosis of LCH, especially eosinophilic granuloma of the bone. Morphologically, the key feature is the identification of Langerhans cells with characteristic grooved, folded, indented nuclei in the appropriate milieu which includes variable numbers of eosinophils and histiocytes including multinucleated forms, often appearing similar to osteoclasts, or touton-like giant cells, neutrophils, and small lymphocytes. [7] Unless there are marked atypical features, a mild degree of atypia does not have any significant effect on the clinical outcome. [3]

In current practice, osteomyelitis is the most difficult diagnosis although eosinophilic infiltrate and characteristic nuclear grooves are important differentiating points. Ewing's sarcoma has characteristic, small, round cell morphology, making it easily distinguishable from LCH. The presence of eosinophils with histiocytes can mimic Hodgkin's lymphoma, but the identification of Reed Sternberg cells should be mandatory for the diagnosis of this disease. Melanoma cells typically exhibit binucleation and occasional intracytoplasmic or nuclear inclusions. Cells from metastatic renal cell carcinomas overwhelmingly exhibit a clustered cell pattern. [8]

Although the neoplastic Langerhans cells (LCs) are immunophenotypically similar to normal Langerhans dendritic cells in their consistent expression of CD1a and S-100 proteins, enzyme cytochemistry reveals that neoplastic LCs are positive whereas normal cells are negative for placental alkaline phosphatase. [3] Also, normal LCs have a different pattern of expression of cellular adhesion molecules. [3]

The cells are negative for most B cell, T cell, and specific follicular dendritic cell lineage markers. They are, however, positive for adenosine triphosphase, a-D-mannosidase, a-naphthyl acetate esterase (with variable inhibition by sodium fluoride), a-naphthyl butyrate esterase, and acid phosphatase, but negative for tartrate-resistant acid phophatase, 5'-nucleotidase, peroxidase, chloracetate esterase, and β-glucuronidase. [3]

An ultrastructural hallmark of LCs is the characteristic tennis racket-shaped Birbeck granules in the cytoplasm. [3]

The etiology of LCH is unknown and there is continuing debate whether this condition is neoplastic or nonneoplastic. Studies of the X-linked androgen receptor gene have demonstrated a monoclonal proliferation of Langerhans cells in all major clinical syndromes. [3] Senechal et al . [9] proposed that enhanced cell survival rather than uncontrolled LC proliferation as in neoplasia, is likely to play a major role in the maintenance and dissemination of these slow-growing tumors.

The clinical course is related to the number of organs affected at presentation, with an overall survival of 95% for patients with unifocal disease; 10% of patients with unifocal disease eventually progress to multisystem disease. [3] With multifocal disease, 60% have a chronic course, 30% achieve remission, and mortality is up to 10%. [10]

Hepatomegaly, blood cytopenias, and marrow involvement were found to have poor prognosis in children below 18 months of age at the time of diagnosis, [11]

Treatment is guided by the extent of disease. Solitary bone lesions may be amenable to excision or limited radiation, however, systemic disease often requires chemotherapy. Use of systemic steroids is common, singly or as an adjunct to chemotherapy. Chemotherapaeutic agents such as alkylating agents, antimetabolites, vinca alkaloids, either singly or in combination, can lead to complete remission in diffuse disease. [4] Even patients with isolated Langerhans cell skeletal histiocytosis should be followed for at least five years as other lesions may appear and recurrences have been reported in approximately 10% of the patients. [5]

 
   References Top

1.Nicholson HS, Egeler RM, Nesbit ME. The epidemiology of Langerhans cell histiocytosis. Hematol Oncol Clin North Am 1998;12:379-84.  Back to cited text no. 1    
2.Stεlemark H, Laurencikas E, Karis J, Gavhed D, Fadeel B, Henter JI. Incidence of Langerhans cell histiocytosis in children: A population based study. Pediatr Blood Cancer 2008;51:76-81.  Back to cited text no. 2    
3.Weiss LM, Grogan TM, Müller-Hermelink, Stein H, Dura T, Favara B, et al . Langerhans cell histiocytosis. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumors of haematopietic and lymphoid tissues. Lyon: IARC Press; 2001. p. 280-2.  Back to cited text no. 3    
4.Histio.org [Homepage on the Internet]. USA: Histiocyte society-Histiocytosis association of America, Inc.; c2007 Disease information; Available from: http://www.histio.org/site/c.kiKTL4PQLvF/b.1810505/k.F16D/Disease_Information.htm. [cited on 2008 Apr 28].  Back to cited text no. 4    
5.Buckwalter JA, Brandser EA, Robinson RA. Langerhans cell histiocytosis. In: Bulstrode C, Buckwalter J, Carr A, Marsh L, Fairbank J, Wilson-McDonald J, et al , editors. Oxford textbook of orthopedics and trauma. 1st ed. Oxford University Press (OUP); 2003. p. 176-9.  Back to cited text no. 5    
6.Forest M. Eosinophilic granuloma. In: Forest M, Tomeno B, Vanel D, editors. Orthopedic surgical pathology: Diagnosis of tumors and pseudotumoral lesions of bone and joints. Edinburgh: Churchill Livingstone; 1998. p. 555-66.  Back to cited text no. 6    
7.Mukhopadhyay S, Mitra PK, Ghosh S. Touton like giant cell in lymph node in a case of Langerhans cell histiocytosis. J Cytol 2007;24:191-2.  Back to cited text no. 7    Medknow Journal
8.Wakely PE. Aspiration and touch preparation cytopathology of lymph nodes. In: Atkinson BF, Silverman JF, editors. Atlas of difficult diagnoses in cytopathology. Philadelphia: W.B. Saunders Company; 1998. p. 406-7.  Back to cited text no. 8    
9.Senechal B, Elain G, Jeziorski E, Grondin V, Patey-Mariaud de Serre N, Jaubert F, et al . Expansion of regulatory T- cells in patients with Langerhans cell histiocytosis. PLoS Med 2007;4:e253.  Back to cited text no. 9    
10.Komp D, El Mahdi A, Starling K, Easley J, Vietti T, Berry D, et al . Quality of survival in histiocytosis X: A Southwest Oncology Group study. Med Pediatr Oncol 1980;8:35-40.  Back to cited text no. 10    
11.Sinha SK, Chattopadhyay S, Sen S, Basu K, Bhattacharyya A, Basumitra R, et al . Spectrum of Langerhans cell histiocytosis with prognostic parameters. J Cytol 2004;21:73-6.  Back to cited text no. 11    

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Correspondence Address:
Veena Maheshwari
Department of Pathology, JNMC, AMU, Aligarh, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9371.50803

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    Figures

  [Figure 1], [Figure 2], [Figure 3a], [Figure 3b]

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