the value of fine-needle aspiration cytology in the evaluation of pediatric head and neck tumors

5
The value of fine-needle aspiration cytology in the evaluation of pediatric head and neck tumors Kiran Alam 1 , Roobina Khan 1, *, Anshu Jain 2 , Veena Maheshwari 3 , Surabhi Agrawal 4 , R.S. Chana 5 , S.H. Harris 6 The Departments of Pathology and Surgery, J.N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India 1. Introduction Aspiration cytology, a well established diagnostic tool in adult oncology, is recently gaining acceptance in pediatric population [1], as clinicians add this technique to their diagnostic armamen- tarium. FNA in children, apart from being accurate, safe and minimally invasive, has also added benefit of lack of need for sedation or general anesthesia except in selected cases. The spectrum of neoplasms in pediatric age group differs markedly from that of the adults. We have performed a comprehensive study of both benign and malignant tumors of the head and neck in children less than 15years of age with the aim to correlate their cytological and histological findings and to evaluate the effectiveness of fine-needle aspiration cytology (FNAC) in diagnosing such lesions. There are only a few studies which focus on cytological diagnosis of both benign and malignant lesions that occurs in the region of head and neck in children. [1–3] This study also reviews the diverse spectrum of lesions occurring in the head and neck region in the pediatric population. 2. Materials and methods One hundred and twenty-eight children <15 years of age presenting with head and neck lesions were reviewed over a period of 2 years. The study had the approval of the bioethical committee of the faculty of Medicine at our Institution for performing these procedures in children. Lesions related to congenital anomalies, inflammation and the thyroid gland were excluded from the study. FNAC was performed by a 23 gauge needle attached to a 10 ml syringe using the standard technique. Smears were stained with Haematoxylin & Eosin (H&E), Papanicolaou’s and May Grunwald Giemsa stains. Patients presenting with palpable anterior orbital growths were approached transcutaneously under direct vision. Posterior orbital and nonpalpable tumors were localized by computerized tomography (CT) scan of the orbit and then approached through the skin in between the eyeball and the orbital wall. Aspirations of orbital tumors were done under short general anesthesia. No anesthesia was required in other cases except in apprehensive children where needle aspirations were done after giving mild sedative. Histopathological examination was done in all the cases and the results were correlated with the cytological findings. Special and immunohistochemical stains were used for confirmation wherever required. International Journal of Pediatric Otorhinolaryngology 73 (2009) 923–927 ARTICLE INFO Article history: Received 23 October 2008 Received in revised form 11 February 2009 Accepted 15 February 2009 Available online 17 April 2009 Keywords: Pediatric Tumor Head Neck ABSTRACT Objective: To study the efficacy of fine-needle aspiration cytology (FNAC) of head and neck masses in pediatric patients. Study design: Of the 128 cases studied, FNAC was performed in 74 patients and their cyto–histological correlation done. Sensitivity and specificity of cytological diagnosis was then computed. Results: Benign lesions were found to be more common than the malignant variety, the commonest being soft tissue tumors (46.87%). Lymphomas were the commonest tumors (22.6%) in the malignant category. Cytology was done in 74 patients of whom smears from 21 patients were unsatisfactory for diagnosis. There was one false positive and two false negative cases resulting in the specificity and sensitivity of FNAC in pediatric head and neck tumors to be 95.65% and 93.3% respectively. Conclusion: FNAC is a useful and reliable tool in the diagnosis of head and neck masses with no contraindications and minimal complications even in children. ß 2009 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Hafeez Manzil, Marris Road, Aligarh, Uttar Pradesh, 202001, India. Tel.: +91 0571 2400911; fax: +91 0571 2721127. E-mail address: [email protected] (R. Khan). 1 Lecturers, Pathology. 2 Senior Resident, Pathology. 3 Professor, Pathology. 4 Ex- Senior Resident, Pathology. 5 Professor, Surgery. 6 Lecturer, Surgery. Contents lists available at ScienceDirect International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl 0165-5876/$ – see front matter ß 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijporl.2009.02.026

Upload: kiran-alam

Post on 17-Oct-2016

212 views

Category:

Documents


0 download

TRANSCRIPT

International Journal of Pediatric Otorhinolaryngology 73 (2009) 923–927

The value of fine-needle aspiration cytology in the evaluation of pediatrichead and neck tumors

Kiran Alam 1, Roobina Khan 1,*, Anshu Jain 2, Veena Maheshwari 3, Surabhi Agrawal 4,R.S. Chana 5, S.H. Harris 6

The Departments of Pathology and Surgery, J.N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, 202002, India

A R T I C L E I N F O

Article history:

Received 23 October 2008

Received in revised form 11 February 2009

Accepted 15 February 2009

Available online 17 April 2009

Keywords:

Pediatric

Tumor

Head

Neck

A B S T R A C T

Objective: To study the efficacy of fine-needle aspiration cytology (FNAC) of head and neck masses in

pediatric patients.

Study design: Of the 128 cases studied, FNAC was performed in 74 patients and their cyto–histological

correlation done. Sensitivity and specificity of cytological diagnosis was then computed.

Results: Benign lesions were found to be more common than the malignant variety, the commonest

being soft tissue tumors (46.87%). Lymphomas were the commonest tumors (22.6%) in the malignant

category. Cytology was done in 74 patients of whom smears from 21 patients were unsatisfactory for

diagnosis. There was one false positive and two false negative cases resulting in the specificity and

sensitivity of FNAC in pediatric head and neck tumors to be 95.65% and 93.3% respectively.

Conclusion: FNAC is a useful and reliable tool in the diagnosis of head and neck masses with no

contraindications and minimal complications even in children.

� 2009 Elsevier Ireland Ltd. All rights reserved.

Contents lists available at ScienceDirect

International Journal of Pediatric Otorhinolaryngology

journal homepage: www.elsev ier .com/ locate / i jpor l

1. Introduction

Aspiration cytology, a well established diagnostic tool in adultoncology, is recently gaining acceptance in pediatric population[1], as clinicians add this technique to their diagnostic armamen-tarium. FNA in children, apart from being accurate, safe andminimally invasive, has also added benefit of lack of need forsedation or general anesthesia except in selected cases.

The spectrum of neoplasms in pediatric age group differsmarkedly from that of the adults. We have performed acomprehensive study of both benign and malignant tumors ofthe head and neck in children less than 15years of age with the aimto correlate their cytological and histological findings and toevaluate the effectiveness of fine-needle aspiration cytology(FNAC) in diagnosing such lesions. There are only a few studieswhich focus on cytological diagnosis of both benign and malignantlesions that occurs in the region of head and neck in children. [1–3]

* Corresponding author at: Hafeez Manzil, Marris Road, Aligarh, Uttar Pradesh,

202001, India. Tel.: +91 0571 2400911; fax: +91 0571 2721127.

E-mail address: [email protected] (R. Khan).1 Lecturers, Pathology.2 Senior Resident, Pathology.3 Professor, Pathology.4 Ex- Senior Resident, Pathology.5 Professor, Surgery.6 Lecturer, Surgery.

0165-5876/$ – see front matter � 2009 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.ijporl.2009.02.026

This study also reviews the diverse spectrum of lesionsoccurring in the head and neck region in the pediatric population.

2. Materials and methods

One hundred and twenty-eight children <15 years of agepresenting with head and neck lesions were reviewed over a periodof 2 years. The study had the approval of the bioethical committeeof the faculty of Medicine at our Institution for performing theseprocedures in children. Lesions related to congenital anomalies,inflammation and the thyroid gland were excluded from the study.FNAC was performed by a 23 gauge needle attached to a 10 mlsyringe using the standard technique. Smears were stained withHaematoxylin & Eosin (H&E), Papanicolaou’s and May GrunwaldGiemsa stains. Patients presenting with palpable anterior orbitalgrowths were approached transcutaneously under direct vision.Posterior orbital and nonpalpable tumors were localized bycomputerized tomography (CT) scan of the orbit and thenapproached through the skin in between the eyeball and theorbital wall. Aspirations of orbital tumors were done under shortgeneral anesthesia. No anesthesia was required in other casesexcept in apprehensive children where needle aspirations weredone after giving mild sedative.

Histopathological examination was done in all the cases and theresults were correlated with the cytological findings. Special andimmunohistochemical stains were used for confirmation whereverrequired.

Table 1Distribution of cases.

Lesions No. of cases Benign Malignant

Lymph nodes 29 (22.6%) – 29

Hodgkin lymphomas 19 – 19

Non-Hodgkin lymphoma 10 – 10

Soft Tissue &Bone 60 (46.87%) 58 2

Adipose tissue 6 6 –

Lipomas 5 5 –

Angiolipomas 1 1 –

Vascular tumors 44 44 –

Haemangiomas 33 33 –

Lymphangiomas 10 10 –

Haemangiopericytoma 1 1 –

Neurofibromas 7 7 –

Embryonal 2 – 2

RhabdomyoSA – – –

Osteoma 1 1 –

Round Cell Tms 11 (8.59%) – 11

Retinoblastoma 9 – 9

Olfactory neuroblastoma 2 – 2

Salivary gland tms 10 (7.81%) 9 1

Pleomorhic adenomas 8 8 –

Warthin tm 1 1 –

Mucoepidermoid CA 1 – 1

Tms of jaw 9 (7.03%) 9 –

Ameloblastic fibromas 4 4 –

Ameloblastomas 3 3 –

Ossifying fibromas 2 2 –

Nasopharyngeal angiofibroma 9 (7.03%) 9 –

Total 128 85 (66.41%) 43 (33.59%)

K. Alam et al. / International Journal of Pediatric Otorhinolaryngology 73 (2009) 923–927924

3. Results

Age of all the 128 patients ranged from 2 months to 15 years.Maximum numbers of cases were in the age group of 11–15years. Commonest tumors in the age group of 1–10years were those arising from soft tissues, whereas nasalangiofibroma and salivary gland tumors occurred at a later age(11–15 years). Males were predominantly affected with M:Fratio being 3.2:1.

Tumors seen exclusively in males were retinoblastoma andnasopharyngeal angiofibroma, 9 patients of either variety.

Out of a total of 128 cases, 85 patients (66.4%) had benignlesions whereas 43 (33.6%) had malignancy (Table 1). Soft tissuetumors were the commonest lesions encountered (46.87%), mostof them being benign. Vascular tumors were the commonestbenign lesions among the soft tissue tumors with maximumnumber of cases being that of hemangioma.

FNAC was done in 74 of 128 cases. Of these 22 were diagnosedas benign and 31 as malignant. Twenty-one lesions wereconsidered unsatisfactory for diagnosis by FNAC (28.3%). Unsa-tisfactory smears were either hypocellular or hemorrhagic andbelonged mostly to benign soft tissue and nasopharyngeal lesions.(Table 2).

Vascular tumors: Only 2 cases of hemangioma were diagnosedon cytology on the basis of few endothelial cells seen in abackground of blood. Rest of the aspirates suspected of havinghemangioma were hemorrhagic and considered inadequate fordiagnosis. A 12 year old female patient with post aural swellingdiagnosed as round cell lesion on cytology was confirmed ashaemangiopericytoma on histopathology. Reticulin positivity waspresent outside the endothelial cells.

Pleomorphic adenoma of the salivary glands was the next mostcommon benign tumor in this age group, accounting for 8 patients.Aspirates in most cases showed cohesive epithelial cells in achondromyxoid background. Cytology here was diagnostic in all ofthe patients except one.

Tumors of jaws comprising of 9 cases were the other lesionsseen in benign category. Aspirates from the patients withameloblastoma (3 cases) showed cohesive clusters of palisadingepithelial cells along with few anastomosing squamous cells.Strands of fibrous tissue along with basoloid cell with peripheralpalisading were found in the aspirate from both the cases ofameloblastic fibroma. The other 2 cases of amelobastic fibromaalong with 2 cases of ossifying fibroma yielded either a dry tap orhemorrhage on aspiration.

Table 2Cytological & Histopathological Correlation.

Tumors No of cases FNAC done

Lymph nodes 29 24

HL 19 15

NHL 10 9

Soft tissue and bone 60 20

Adipose 6 6

Vascular 44 6

Nerve 7 5

Muscle 2 2

Osteoma 1 1

Round cell tumor 11 7

Retinoblastoma 9 5

Olf neuroblastoma 2 2

Salivary gland tms 10 10

Tms of jaw 9 9

Nasopharyngeal angiofibromas 9 4

Total 128 74

The other cases which could not be diagnosed on cytology wereone case of osteoma and 4 patients of nasopharyngeal angiofi-broma.

Overall the second commonest but largest group in malignantcategory was lymphomas, of which Hodgkin’s lymphoma (HL) wasseen in 19 whereas Non-Hodgkin lymphoma (NHL) was evident in10 patients. (Table 1) Diagnosis of HL (Fig. 1b) and NHL (Fig. 2a)was possible on FNAC in most of the cases, though the exact typingwas done only on histopathology which was later confirmed byimmunohistochemistry in few cases (Fig. 2b). Only two variants ofHodgkin lymphomas i.e., mixed cellularity (MCHL) and nodularsclerosis (NS) were reported in our study. Aspirates from HLshowed atypical mononuclear cells along with Reed-Sternberg (R-S) cells in a reactive inflammatory background. Few cases showed

Inadequate Correlation Concordant Discordant

2 22 20 2

2 13 12 1

– 9 8 1

8 12 11 1

2 3 3 –

3 3 2 1

2 3 3 –

– 2 2 –

1 – – –

2 5 5 –

2 3 3 –

– 2 2 –

1 9 9 –

4 5 5 –

4 - - –

21 53 50 3

Table 3Comparison between cytological &histological diagnosis.

Cytology Histopathology

Benign Malignant

Benign 24 22 2

Malignant 29 1 28

Total 53 23 30

K. Alam et al. / International Journal of Pediatric Otorhinolaryngology 73 (2009) 923–927 925

multilobated R-S cells. Some aspirates showed granulomatousreaction along with atypical mononuclear cells.

Variants of NHL seen were small non-cleaved lymphomas (3cases), Burkitt’s lymphomas (1 case), Lymphoblastic lymphomas (4cases). One case each of Large cell and Anaplastic large celllymphoma were also reported. Diagnosis of NHL was mostly madeby highly cellular smears showing monotonous population of cells

Fig. 2. (a) Large cell lymphoma: Variable population of lymphoid cells with irregular n

positivity of the same. (X500).

Fig. 1. (a) Embryonal rhabdomyosarcoma: Pleomorphic round to spindle shaped cells wi

lymphoma: Reed-Sternberg cells with surrounding polymorphous lymphoid populatio

with coarse chromatin and high nuclear cytoplasmic ratio (N:Cratio), and slightly irregular nuclear membrane. Abnormal mitosiswas also seen in most of these cases. A mistaken diagnosis ofreactive lymphadenitis was rendered in cytology in one case eachof Hodgkin’s lymphoma (Nodular sclerosis), due to lack of R-S cellsand NHL (Small non-cleaved lymphoma) due to presence ofdendritic reticulum cells as well as small lymphocytes in thesmear. Confirmation was later made on histopathology.

Retinoblastoma (9 patients) accounted for the second mostcommon malignant tumor of head and neck region in pediatric agegroup. Enucleation of the affected eye ball was done in all the cases.Preoperative diagnosis of retinoblastoma was made only in 3patients based on cytological evaluation. Smears showed smallround tumor cells forming Flexner-Wintersteiner rosettes atplaces. (Fig. 3) One of the patients, an 11 year old male childpresented with parotid swelling, which when aspirated showedfeature consistent with metastatic round cell lesion. Search for the

uclei and scant cytoplasm. Lymphoglandular bodies seen. (PAP X500). (b) CD-20

th course nuclear chromatin and eosinophilic cytoplasm (H&E X500). (b) Hodgkin’s

n. (MGG X250).

Fig. 3. Retinoblastoma: Small round tumor cells forming Flexner-Wintersteiner

rosettes. (H&E X500).

K. Alam et al. / International Journal of Pediatric Otorhinolaryngology 73 (2009) 923–927926

primary tumor revealed a small ill defined mass in the posteriorchamber of left eye confirming the diagnosis of a rare metastasis ofthe retinoblastoma to the parotid gland.

Embryonal rhabdomyosarcoma was the only malignant lesionin soft tissue tumor category diagnosed in two boys with a meanage of 6.5 years. Aspirates showed pleomorphic cells varying fromround to spindle in shape with atypical nuclear features suggestiveof rhabdomyosarcoma (Fig. 1a). Diagnosis was confirmed onhistopathology which showed undifferentiated round cells alongwith strap shaped rhabdomyoblasts consistent with embryonalrhabdomyosarcoma

Mucoepidermoid carcinoma of salivary gland was seen in onlyone patient where the smear showed few cohesive epithelialclusters with mild nuclear pleomorphism and prominent nucleoliin a dirty background. Few squamous cells and cells withcytoplasmic vacuolation were also seen on MGG stained smear.However, the cellular details were more evident with H&E and Papsmear.

Histopathology was done in all the cases and histo–cytologicalcorrelation done wherever possible (Table 3). Cytology was foundto be discordant in 3 cases. Two patients reported as reactivelymphadenitis on cytology turned out to be lymphomas onhistopathology, while one case of haemangiopericytoma waswrongly diagnosed as round cell tumor on cytology.

One false positive and two false negative results were found onFNAC giving needle aspiration cytology specificity and sensitivityof 95.65% and 93.3% respectively. The diagnostic accuracy of FNACwas 94% with a positive predictive value of 96% and a negativepredictive value of 92%.

Statistical analysis was done by applying the Z-test forproportion in both benign and malignant cases separately. Forbenign lesions Z = 6.8 which is highly significant (p < 0.001) andfor malignant lesions Z = 4.2, which is again highly significant(p < 0.001).

4. Discussion

FNAC has been widely used as an early diagnostic tool in adultsbut its use in pediatric population especially in head and neckregion is only slowly gaining momentum among clinicians. [1]Notably primary malignant tumors of head and neck account for5% of all pediatric neoplasms. [4] Range of lesions which can bereliably diagnosed by this method keeps on expanding. In thisseries, FNAC of the head and neck region in children was found toconfirm malignancy in a clinically suspicious lesion with a highdegree of specificity and sensitivity.

Male children were found to be more commonly affected byhead and neck tumors as compared to females with a ratio of 3.2:1.

There was marked male predominance in patients of lymphomas,retinoblastomas, and nasopharyngeal angiofibromas, similar to astudy by Kusumakumary et al. [5] who observed this to be due to agenetic difference in the immune function.

Although FNAC was done only in 74 patients, we have includedall 128 cases in our series to study the diversity of lesions occurringin the head and neck region in the pediatric population. Thecommonest lesions assessed by FNAC were from the lymph nodessimilar to those reported by Kardos et al. [6].

The commonest lesions seen in our study were from the softtissues, most of them being benign. Vascular lesions accounted forthe most common benign tumor in this category; results beingsimilar to those seen by Chaterjee et al. [7] However, FNAC of mostof these lesions were hemorrhagic giving a suggestive report. Twoof the cases of hemangiomas showed few endothelial cells inhemorrhagic background, thus helping in clinching the diagnosis[1].

Next in frequency were salivary gland tumors, of whichpleomorphic adenoma accounted for the maximum number ofcases, in concordance with the finding of Laikui et al. [8] whodescribed it to be the commonest salivary gland tumor in childrenand adolescents. One case each of warthins tumor and mucoepi-dermoid carcinoma was also diagnosed. Epithelial salivary glandtumors are very uncommon in pediatric population and havedifferent histological characteristics compared to that of adults,but with similar prognosis.[9] Clinicians should have a high level ofsuspicion when a non-inflammatory single mass lesion presents inthe parotid and submandibular region, as there is a high likelihoodof such lesions being malignant.[10]

Lesions of jaw and bone were the other benign tumors seen inthis study, most common being ameloblastic fibromas. FNAC of 2cases of ameloblastic fibroma yielded clusters of basaloid cells withpalisading of the columnar cells at the borders along with amesenchymal component that consisted of loosely arrangedspindle cells. Hypercellular stroma seen in one of these caseswas the key feature to differentiate it from other odontogenictumor, a finding similar to that noted by Bocklage et al. [11]. Needleaspirates from cases of amelobastomas comprised of cohesiveclusters of palisading epithelial cells along with few anatomisingsquamous cells. These findings have also been corroborated byGunhan [12] in his study of 10 cases of ameloblastoma.

In our study the commonest malignant lesion found werelymphomas, a finding in concordance with Kusumakumary et al.[5] who found leukemia and lymphomas to be the commonestpediatric tumor. However Chaterjee et al. [7] reported retino-blastoma to be the most frequent head and neck tumor in this agegroup.

Hodgkin lymphomas were more frequent than Non-Hodgkinlymphomas, which showed more aggressive behavior similar tothe findings of Roh et al. [13] Cervical lymphadenopathy was thecommonest presentation of these lymphomas. Similar to Urquhartand Berg [14] we too found Hodgkin lymphomas to be commonerin younger age group than Non-Hodgkin lymphomas. Nodularsclerosis was the commonest variant of Hodgkin lymphomafollowed by mixed cellularity, as seen in the study by Oliapuramet al. [15] FNAC can sometimes give a false negative result in casesof HL as was reported in one of our patient due to the presence ofmixed inflammatory cells and at times granulomas together withscarcity of R-S cells.[1] False negative results can also be obtaineddue to partial lymph node involvement or fibrosis.[16] Overall thereported sensitivity in diagnosing HL was 82% [17] whereas wefound the sensitivity to be as high as 92.3%.

The commonest variant of NHL seen in this study waslymphoblastic lymphomas with small cleaved lymphomas beingthe next common variety. Mathur et al. [18] found FNAC to beuseful not only in diagnosing but also grading NHL, with a

K. Alam et al. / International Journal of Pediatric Otorhinolaryngology 73 (2009) 923–927 927

diagnostic accuracy of 70.5%. A substantial number of theselymphomas could be sub-classified based on the FNA material. [19]However, these studies also indicated that FNA could notcompletely replace tissue biopsy, and there were still cases ofNHL that required surgical biopsy for confirmation of the diagnosis.One of the main limitations of the cytological preparations is thelack of architectural pattern.

Chintagumpala et al. [20] in their study found retinoblastoma tobe the most frequent ocular cancer in pediatric age group. Theywere the second commonest malignant lesion seen in this study.Leucoria and strabismus were the usual revealing presentation inour patients, most of them presenting unilaterally, a finding similarto that of Doz. [21] FNAC has being found to be very useful indiagnosing orbital masses along with emphasis on immune stainsfor tumor characterization. [22] The major deterrent to thewidespread use of this technique is the fear of dissemination ofthe intraocular tumor through the needle tracks. Such dissemina-tion has not been documented in any of the patients in a largeseries of 140 patients who underwent FNAC.[4] This has largelybeen proven as a safe technique. Rhabdomyosarcomas were one ofthe commonest sarcomas of head and neck region especially inchildren and adolescents, [23] but we encountered just 2 cases inour study.

Overall one false positive and two false negative resultswere found on FNAC giving a specificity and sensitivity of95.65% and 93.3% as against the finding of Rapkiewicz et al. [1]who found it to be 93% and 100% respectively. The highspecificity leads to a confident diagnosis of malignant lesions inclinically suspicious masses of head and neck among this agegroup.

We found that FNAC has a high diagnostic accuracy in head &neck lesions of pediatric age group, provided there is adequatematerial. Most of the cases with inadequate material were ofvascular or bony origin. We observed that FNAC is especially usefulin early diagnosis of malignant cases thus preventing theinadvertent delay in planning treatment modalities.

5. Conclusion

Thus we found FNAC to be having a very high diagnosticpotential in head and neck masses, even in pediatric population.Apart from reassurance of benignity, it helps in confirmingmalignancy and thus in initiating early treatment. However,expertise in performing FNAC is mandatory to obtain adequatematerial. It should always be supplemented with tissue diagnosisand immunohistochemistry.

References

[1] A. Rapkiewicz, B. Thuy Le, A. Simsir, J. Cangiarella, P. Levine, Spectrum of head andneck lesions diagnosed by fine-needle aspiration cytology in pediatric population,Cancer 111 (2007) 242–251.

[2] H.H. Ramadan, M.K. Wax, C.B. Boyd, Fine-needle aspiration of head and neckmasses in children, Am. J. Otolaryngol. 18 (1997) 400–404.

[3] E.S. Liu, J.M. Bernstein, N. Sculerati, H.C. Wu, Fine-needle aspiration biopsy ofpediatric head and neck masses, Int. J. Pediatr. Otorhinolaryngol. 60 (2001) 135–140.

[4] P.V. Dickson, A.M. Davidoff, Malignant neoplasms of the head and neck, Semin.Pediatr. Surg. 15 (2006) 92–98.

[5] P. Kusumakumary, R. Jacob, R. Jothirmay, M.K. Nair, A profile of pediatric malig-nancy–A 10 year report, Indian Pediatrics 37 (2000) 1234–1238.

[6] T.F. Kardos, S.J. Maygarden, BlumbergAK, P.E. Wakely Jr., W.J. Frable, Fine-needleaspiration biopsy in the management of children and young adults with periph-eral lymphadenopathy, Cancer 63 (1989) 703–707.

[7] S. Chaterjee, N. Basu, A. Basu, D. Nag, R. Chaterjee, M.G. Mallik, Role of FNAC indiagnosis of pediatric head and neck neoplasms, J. Cytol. 20 (2003) 185–188.

[8] L. Laikui, L. Hongwei, J. Hongbing, H. Zhixiu, Epithelial salivary gland tumors ofchildren and adolescents in west China population: a clinicopathologic study of79 cases, J. Oral Pathol. Med. 37 (2008) 201–205.

[9] M. Guzzo, A. Ferrari, I. Marcon, P. Collini, L. Gandola, N. Pizzi, et al., Salivary glandneoplasms in children: the experience of the Istituto Nazionale Tumori of Milan,Pediatr. Blood Cancer 47 (2006) 806–810.

[10] P. Bradley, L. McClelland, D. Mehta, Pediatric salivary gland epithelial neoplasms,ORL J. Otorhinolaryngol. 69 (2007) 137–145.

[11] T.J. Bocklage, T. Ardeman, D. Schaffner, Ameloblastic fibroma: a fine- needleaspiration case report, Diagn. Cytopathol. 17 (1997) 280–286.

[12] O. Gunhan, Fine-needle aspiration cytology of ameloblastoma. A report of 10cases, Acta Cytol. 40 (1996) 967–969.

[13] J.L. Roh, J. Huh, H.N. Moon, Lymphomas of the head and neck in the pediatricpopulation, Int. J. Pediatr. Otorhinolaryngol. 71 (2007) 1471–1477.

[14] A. Urquhart, R. Berg, Hodgkin’s and non-Hodgkin’s lymphoma of the head andneck, Laryngoscope 111 (2001) 1565–1569.

[15] B. Oliapuram Jose, P. Koerner, S. Bertolone, C.C. Patel, W.J. Spanos Jr., K.J. Paris,et al., Pediatric Hodgkin’s disease, J. Ky. Med. Assoc. 102 (2004) 104–106.

[16] D.C. Chhieng, J.F. Cangiarella, W.F. Symmans, J.M. Cohen, Fine-needle aspirationcytology of Hodgkin disease: a study of 89 cases with emphasis on false-negativecases, Cancer 93 (2001) 52–59.

[17] J.A. Jimenez- Heffernan, B. Vicandi, P. Lopez-Ferrer, D. Hardisson, J.M. Viguer,Value of fine-needle aspiration cytology in the initial diagnosis of Hodgkin’sdisease. Analysis of 188 cases with an emphasis on diagnostic pitfalls, Acta Cytol.45 (2001) 300–306.

[18] S. Mathur, R. Dawar, K. Verma, Diagnosis and grading of non-Hodgkin’s lympho-mas on fine-needle aspiration cytology, Indian J. Pathol. Microbiol. 50 (2007) 46–50.

[19] H.Y. Dong, N.L. Harris, F.I. Preffer, M.B. Pitman, Fine-needle aspiration biopsy inthe diagnosis and classification of primary and recurrent lymphoma: a retro-spective analysis of the utility of cytomorphology and flow cytometry, Mod.Pathol. 14 (2001) 472–481.

[20] M. Chintagumpala, P. Chevez-Barrios, E.A. Paysse, S.E. Plon, R. Hurwitz,Retinoblastoma: review of current management, Oncologist 12 (2007)1237–1246.

[21] F. Doz, Retinoblatoma: a review, Arch Pediatr. 13 (2006) 1329–1337.[22] E. Tani, S. Seregard, G. Rupp, V. Soderlund, L. Skoog, Fine-needle aspiration

cytology and immunocytochemistry of orbital masses, Diagn. Cytopathol. 34(2006) 1–5.

[23] A.T. Lyos, H. Goepfert, M.A. Luna, N. Jaffe, A. Malpica, Soft tissue sarcoma of thehead and neck in children and adolescents, Cancer 77 (1996) 193–200.