Original Research Article

Study of fine needle aspiration cytology and histopathological co-relation of soft tissue lesions in pediatric patients at tertiary health care institute in western Maharashtra

J Juvekar1, S G Surase2*, K A Deshpande3, M S Wadhi4, S V Thavare5

1,4,5Speciality Medical Officer, NMMC, Vashi, Mumbai, Maharashtra, INDIA. 2,3Associate Professor, Department of , Grant Government Medical College and Sir J.J. Group of Hospitals, Mumbai, Maharashtra. Email: [email protected]

Abstract Background: The field of soft tissue tumours (STT) is enormously vast, and yet, as cytologically relatively undiscovered. Due to the rarity of primary tumours of soft tissue and a large range of different types of tumours, the diagnosis and classification of STTs become most difficult areas in and absence of recognizable tissue architectural patterns in cytological preparation makes a diagnosis by FNAC even more difficult.1 Objectives: •To study and analyse the spectrum of soft tissue tumours in our tertiary care hospital by FNAC. •To correlate the cytoarchitectural features observed with histopathological parameters. Material and Methods: Present prospective study was conducted in the Pathology Department of GMC and JJ Hospital, Mumbai, Maharashtra, over a period of two years. Study included all the patients in the pediatric age group which were referred to the FNAC outpatient department with soft tissue swelling. The result of FNAC was further correlated with the histopathological diagnosis from paraffin-embedded sections wherever available. Data obtained was analysed for the histopathological correlation and statistical significance. Results: A total of 57 cases were included in the study of which 45 were found to be benign and 12 were malignant on cytology. Cyto-histo correlation was available in 45 cases. The overall sensitivity, specificity and efficiency of FNAC was found to be 90.09 %, 94.1 % and 93.33 % respectively. Conclusion: FNAC has an absolute role in the diagnosis of STT’s in primary lesions, for a timely management. It is a simple, rapid, cost-effective and well-tolerated procedure in well trained and experienced hands. Key words: Cyto-histopathology correlation, FNAC, Sensitivity, Specificity, Soft tissue tumors

*Address for Correspondence: Dr.S.G.Surase, Associate Professor, Department of Pathology, Grant Government Medical College and Sir J.J. Group of Hospitals, Byculla, Mumbai - 400008, Maharashtra Email: [email protected] Received Date: 21/09/2019 Revised Date: 10/10/2019 Accepted Date: 06/11/2019 DOI: https://doi.org/10.26611/10512210

field of STTs is enormously vast and yet, as cytologically Access this article online relatively undiscovered. The rarity of primary tumours of Quick Response Code: soft tissue and a large range of different types of tumours, Website: the diagnosis and classification of STTs become most

www.medpulse.in difficult areas in surgical pathology and absence of recognizable tissue architectural patterns in cytological preparation makes a diagnosis by FNAC even more difficult.1 Soft tissue arises from the non-epithelial extra- Accessed Date: skeleton connective tissue exclusive of the 24 November 2019 reticuloendothelial system, glia and supporting tissue of 2 various parenchymal organs. FNAC as a diagnostic modality for STTs is increasingly being used. Their INTRODUCTION morphologic overlap and biological heterogeneity pose a FNAC is a safe, reliable and cost-effective tool that is significant diagnostic challenge.3 Advantage of FNAC of used in the diagnosis of lesions in various organs. The STT over core needle biopsy is the sampling of material

How to cite this article: J Juvekar, S G Surase, K A Deshpande, M S Wadhi, S V Thavare. Study of fine needle aspiration cytology and histopathological co-relation of soft tissue lesions in pediatric patients at tertiary health care institute in western Maharashtra. MedPulse International Journal of Pathology. November 2019; 12(2): 113-119. https://www.medpulse.in/Pathology/ MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 12, Issue 2, November 2019 pp 113-119 from different parts of large tumours to diagnose tumour 3. Spindle cell tumours-the predominance of spindle cells heterogenicity. The final diagnosis of STT by FNAC is with fusiform or ovoid nuclei and elongated uni- or based on a combined evaluation of clinical data, patient bipolar cytoplasm. age, site, duration, radiographic and cytological study, 4. Pleomorphic pattern- the cells show marked variation also it requires interaction between pathologist, surgeon in cell and nuclear size and shape. and radiologist.4 The true frequency of soft tissue lesions 5. Myxoid pattern-when the background matrix is the is difficult to estimate, as most of the non-neoplastic and standout component of a tumour and is myxoid i.e. blue benign lesions are not removed. A conservative estimate or blue-violet in MGG and faintly pink in HandE and is that benign tumours outnumber their malignant faintly green in PAP. The cells maybe spindle, round or counterpart tumours by a ratio of about 100:1 in hospital pleomorphic. population and their annual incidence is approximately 6. Round cell pattern- small round to oval, relatively 300 per 1,00,000 population.5,6,7,8 With the above undifferentiated cells, with a variable amount of background, the present study was undertaken to increase cytoplasm. our understanding about STTs, the accuracy of FNAC in 7. Epithelioid cell pattern-rounded or polygonal cells with their diagnosis, its cytoarchitectural features and to distinct cytoplasmic borders, abundant cytoplasm, and compare these findings with histopathological diagnosis. rounded, ovoid or irregular nuclei. Accurate subtyping was done and the nature of the lesion MATERIALS AND METHODS was mentioned. The present study was a prospective study, carried out in The surgical specimens were received for the Department of Pathology, GMC and JJ hospital for a total histopathological confirmation of the diagnosis. period of 2 years. All the patients in the pediatric age Specimens were processed in automated tissue processing group which were referred to the FNAC outpatient unit and staining was performed with routine H and E department with soft tissue swelling were included. staining. The result of FNAC was correlated with the Detailed history was taken and clinical examination of histopathological diagnosis wherever available. Data patient was carried out. Relevant past, family and obtained was analysed for the histopathological treatment history if any was taken. The patient’s relatives correlation and statistical significance. were informed about the procedure and informed consent was obtained from parents/ guardians before subjecting to RESULTS FNAC. FNAC was performed under all aseptic A total of 57 cases were included in the study of which 45 precautions as OPD procedure with the help of 22-24 were found to be benign and 12 were malignant on gauge needle and disposable 5ml/10ml syringes. Smears cytology. A total number of 12 cases were lost because were prepared, fixed in 95% ethyl alcohol and then were histological examination was not available. The age stained with Haematoxylin and Eosin (HandE) or distribution of the STTs as diagnosed by FNAC showed Papanicolaou (PAP) stain. The slides meant for Giemsa benign tumours were more common amongst 5 years to 8 staining were air dried and stained with Giemsa stain. The years, while malignant tumours were relatively evenly interpretation of the slides was done by the distributed among all the age groups.Male patients cytopathologist. outnumbered the female patients in both benign and After assessing for adequacy, the majority of STTs were malignant categories. Cytological categories of total classified into 7 groups - aspirates - Among the various cytomorphological 1. Vascular pattern-showing a predominantly a categories, maximum i.e. 21 cases (36%) were of vascular haemorrhagic background and a paucicellular aspirate tumours, followed by 14 (24%) cases of spindle cell type. showing few spindle cells. (Table 1). 2. Adipocytic pattern-tumours showing a predominance of mature adipocytes. Table1: Cytological categories of total aspirates Sr. No Lesion category No. of cases Percentage 1 Adipocytic tumours 6 10.52% 2 Vascular tumours 21 36.84% 3 Spindle cell tumours 14 24.56% 4 Small round blue cell tumours 9 15.7% 5 Pleomorphic tumours 1 1.75% 6 Myxoid tumours 1 1.75% 7 Miscellaneous 5 8.77% TOTAL 57 100%

MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 12, Issue 2, November 2019 Page 114 J Juvekar, S G Surase, K A Deshpande, M S Wadhi, S V Thavare

The cytological diagnoses included 'terms' like benign vascular lesion-haemangioma, spindle cell lesion-neurogenic, malignant small round cell tumour- highly suggestive of , benign adipocytic tumour-lipoma, lipoblastoma, benign spindle cell lesion, spindle cell lesion-probably benign, suggestive of lymphangioma, giant cell tumour (GCT), malignant mesenchymal tumour, pleomorphic cell , malignant mesenchymal tumour-highly suggestive of myxoidliposarcoma. On FNAC, 12 cases were labelled as malignant and 45 cases were labelled as benign. (Table 2) Table2: Cytological categories of total aspirates Sr. no Lesion category Cytological diagnosis No. of cases Percentage Lipoma 4 7.0% 1 Adipocytic tumours Lipomatosis 1 1.7% Lipoblastoma 1 1.7% Benign vascular lesion- haemangioma 18 31.5% 2 Vascular tumours Lymphangioma 3 5.2% Fibromatosis Colli 1 1.7% Benign spindle cell lesion- neurogenic 9 15.7% 3 Spindle cell lesions Benign spindle cell tumour 1 1.7% Spindle cell lesion-probably benign 3 5.2% Small round blue cell tumour- highly suggestive of 7 12.2% 4 Small round blue cell rhabdomyosarcoma Small round blue cell tumour -highly suggestive of Ewings/ PNET 2 3.5% 5 Pleomorphic lesions Pleomorphic cell sarcoma 1 1.7% 6 Myxoid Malignant mesenchymal tumour- suggestive of myxoidliposarcoma 1 1.7% Giant cell lesion 4 7.0% 7 Miscellaneous Malignant mesenchymal tumour 1 1.7% TOTAL 57 100%

Frequency of distribution of different categories of lesions According to age Age group 5-8 years showed the maximum number of cases, of which 19 were benign and 4 were malignant. Age groups 1-4 years and 9-12 years were equally affected in the present study with an equal number of cases (17). (Table 3)

Table 3: Agewise distribution of lesions Sr. No Lesion category 1-4 yrs 5-8 yrs 9-12yrs No. of cases 1 Adipocytic tumours 2 0 4 6 2 Vascular tumours 10 10 1 21 3 Spindle cell lesions 1 8 5 14 4 Small round blue cell 3 4 2 9 5 Pleomorphic lesions 0 0 1 1 6 Myxoid 0 0 1 1 7 Miscellaneous 1 1 3 5 Total 17 23 7 57

Site wise distribution of total lesions The chest, back and trunk were the most common sites of involvement by soft tissue out of which 17 were benign and 3 were malignant. The benign soft tissue were most common on the chest, back and trunk area. The malignant soft tissue neoplasms were most common in the lower extremities. (Table 4)

Table 4: Site wise distribution of total lesions Sr.no Site Benign Malignant Total 1 Head and neck 8 3 11 2 Upper extremity 12 1 13 3 Lower extremity 8 5 13 Chest, back and 4 17 3 20 trunk Total 45 12 57

Copyright © 2019, Medpulse Publishing Corporation, MedPulse International Journal of Pathology, Volume 12, Issue 2 November 2019 MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 12, Issue 2, November 2019 pp 113-119

Cyto-histological correlation (Table 5) Out of a total 57 cases on which were reported on FNAC, 45 cases were followed up with histopathological examination. Remaining cases were lost to follow up. Hence correlation was done in 45 cases.

Table 5: Cyto-histological correlation Sr. No Cytological Category No of cases of cytology No of cases with histological examination Percentage 1 Adipocytic tumours 6 6 100 2 Vascular tumours 21 16 76.19 3 Spindle cell lesions 14 10 71.42 4 Small round blue cell 9 8 88.88 5 Pleomorphic lesions 1 1 100 6 Myxoid 1 1 100 Miscellaneous 6 5 3 60

TOTAL 57 45 78.9

Statistical Significance 1 Gupta N. et al15 (2017) 1:1.5 D. Y. Kachanov et al16 Out of the 45 benign cases of reported on FNAC, 33 were 2 1.52:1 confirmed by histopathology. Two cytology smears (2011) which were diagnosed as benign were later found to be 3 Das Bet al17 (2017) 1:1.30 Chandrashekhar et malignant on histopathology. These are false negative 4 18 1.16:1 cases. Out of the 12 malignant cases reported on FNAC, al (2015) 4 Present study (2017) 3:1 11 were confirmed by histopathology. One cytology Thus, our study showed a greater ratio of the incidence of smear which was diagnosed as malignant was later found soft tissue in males as compared to other to be benign on histopathology. This is a false negative studies. case. Distribution according to the nature of tumours

Out of 57 cases, present study showed a predominance of DISCUSSION benign lesions (45) over the malignant (12) ones. The STTs have usually been diagnosed with the 'time- percentage of benign and malignant lesions was honoured' histopathology that is recognized as the 'gold comparable to Vidyabharathi et al4 (2015) and Beg et standard' for their evaluation. However, in the current era, al15(2017). The proportion of benign and malignant cases where 'needle is preceding the scalpel' and the biopsy may vary widely between institutions depending upon the material is getting limited, it would be prudent to discuss evaluation protocol followed by them, the level of the role and scope of FNAC in diagnosing STTs. The role hospital care being provided and the competence and of FNAC has mostly been noted in soughting recurrent 16 9-11 skillset of the physicians available. Rekhi et al stated and metastatic STT cases. Nevertheless, there are the reason for the increased number of overall malignant studies indicating its role in the primary diagnosis of 12-14 vs. benign cases in their series due to the predominance of these tumours. The present study was carried out to referral cases, including a greater proportion of sarcomas highlight the various aspects of cytological diagnosis of that their centre receives. This may explain the variation STTs and confirms the accuracy and the clinical utility of in the proportion of cases. FNAC in diagnosing soft tissue neoplasms in the Distribution of soft tissue sarcomas according to site pediatric age group. To our best knowledge, our work Our study showed the most common site of STTs to be represents the first study in the cytological literature the lower limbs, as opposed to the studies carried by comparing the accuracy of cyto-histological correlation of Chandrasekhar et al17 and D.Y. Kachanov et al.18 STTs in pediatric age group. The results are being Subtyping of benign STTs compared to similar studies done in general population. The present study showed vascular tumours comprising 16 of the total benign STTs (33) in pediatric age group. Sex-specific incidence rate of soft tissue The percentage of vascular tumours in our study is sarcomas in pediatric age group comparable to Chakrabartiet al.19 Hemangiomas being the most common STT in the present study, which concurs Table 6: Sex-specific incidence rate of soft tissue sarcomas in with most studies on STTs in pediatric age group. pediatric age group Subtyping of malignant tumours Sr. Male: Authors no female ratio Rhabdomyosarcoma as the most common STS in the pediatric age group. The percentage of

MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 12, Issue 2, November 2019 Page 116 J Juvekar, S G Surase, K A Deshpande, M S Wadhi, S V Thavare rhabdomyosarcoma in our study is comparable to that of ganglion cells, stellate cells and metachromatic fibrillary D. Y. Kachanov et al.18 Loeb et al20 aptly state material.27 The only myxoid tumour in our study was rhabdomyosarcoma represents 50% of all STSs in the labelled as myxoid liposarcoma which turned out to be children <15 years of age. myxoid liposarcoma on histopathology thus giving us 100 Cyto-histological correlation in adipocytic tumours percent concordance which was comparable to P Arul et In the present study, we came across 6 tumours of the al.24 Wong NL28 in his article on FNAC of myxoid adipocytic type and were able to make an accurate lesions stated that the diagnostic accuracy of FNAC was diagnosis in all of them, thus getting a concordance of nearly 100 % in differentiating benign and malignant 100 %, which is comparable to Soni et al21.Chaturaet al3 myxoid lesions of soft tissues and coordinate rate to had recorded a very low concordance with respect to histopathology diagnosis of myxoid lesions of soft tissue lipomatous tumours. Mary K. Sidawy22 rightfully stated is71.4 % in benign and 80 % in malignant myxoid soft that atypical lipomatous tumours / well-differentiated tissue lesions. liposarcomas may consist predominantly of mature Cyto-histological correlation in spindle cell tumours adipose tissue and therefore, atypical adipocytes and The spindle cell tumours form the most heterogeneous of lipoblasts may be rare in these aspirates thus mimicking a the STTs and are a frequent cause of diagnostic pitfalls as lipoma. Furthermore, cells of lipomas are identical to it is difficult to distinguish benign tumours with high non-neoplastic subcutaneous fat and therefore the cellularity from low-grade sarcomas. The criteria for possibility of sampling the subcutaneous fat must be malignancy as described by Kilpatrick SE et al13 was that entertained when smear contains mature adipocytes and the aspirate is designated as a sarcoma when the smear especially if clinical history has not been provided. shows moderate to high cellularity, hyperchromatic nuclei Akerman et al23 also concluded that preoperative FNAC in almost all the sampled cells and ill-defined edges of the of lipomatous tumours is of value in the management of neoplastic fragments. In the present study, the two false these tumours. negative aspirates belonged to the spindle cell category. Cyto-histological correlation in vascular tumours One case of was labelled as benign Vascular tumours in the present study included 21 spindle cell tumour on cytology because of the presence tumours, 16 of which were confirmed on histopathology, of fewer spindle cells in a background of blood. One case all were accurately diagnosed and comprised of of low-grade malignant peripheral nerve sheath tumour hemangioma(12), lymphangioma(3) and arteriovenous (MPNST) was labelled as schwannoma in our study malformation (1) thus, giving us a concordance of 100 % because the cytology smears showed predominantly which was comparable to P Arul et al24(2016) and Soni et spindle cells with questionable pleomorphism and nuclear al.21 Perez-Guillermo et al25 stated that the hyperchromasia which was attributed to ancient change. cytopathological findings of vascular tumours, evaluated Therefore, in the present study, the accuracy of in the context of clinical findings are sufficiently diagnosing spindle cell neoplasms on FNAC was 80%, characteristic to be able to make a definitive diagnosis. which was comparable to Chatura et al3 (2015) Awasthi26 concluded that a confident diagnosis of Cyto-histological correlation in miscellaneous STTs lymphangioma can usually be made on cytology. In the present study, there was a single case of Cyto-histological correlation in small round cell pleomorphic sarcoma which was diagnosed accurately on tumours FNAC thus showing 100% concordance which was The round cell category generally comprises of high- comparable to Rekhi et al16 and Beg et al.29 The grade tumours. Cytological findings of special interest miscellaneous category comprises the tumours which include rhabdomyoblasts, atypical lipoblasts, neuroblast cannot be accurately fit into the above 6 categories. In the rosettes and intracytoplasmic glycogen.27 Categorisation present study, 3 cases were included in this category viz. is difficult in absence of specific features. The present giant cell tumour of tendon sheath(GCT) (2) and one case study included 9 cases of small round blue cell tumour, of inflammatory myofibroblastic tumour (IMT) which out of which 8 were confirmed on histopathological was reported as a malignant mesenchymal tumour on examination and included 6 cases of rhabdomyosarcoma FNAC. This was the single false positive case in the and 2 cases of Ewings/PNET thus giving 100 present study. The cytology of GCT of the tendon sheath %concordance which was comparable with P Arul et al24, is very characteristic and along with the clinical details, Rekhi et al16 and Vidyabharathi et al.4 the diagnosis of GCT is fairly possible. The FNAC Cyto-Histological correlation in myxoid tumours smears of IMT showed some clusters of spindle cells, Tumours rich in myxoid matrix have soft consistency and admixed with occasional inflammatory cells and foamy aspiration generally yields varying amount of viscous histiocytes, most of the spindle cells showed mild material. Special attention should be paid to lipoblasts, anisonucleosis and prominent nucleoli and was

Copyright © 2019, Medpulse Publishing Corporation, MedPulse International Journal of Pathology, Volume 12, Issue 2 November 2019 MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 12, Issue 2, November 2019 pp 113-119 interpreted as malignant mesenchymal tumour. False Comparison of statistical analysis between studies positive diagnosis of Inflammatory myofibroblasic tumor (Table 7.) (IMT) can be attributed to the interpretation of The sensitivity, specificity, positive predictive value and anisonucleosis and prominent nucleoli as malignant and negative predictive value is comparable to those studies because of limited experience and limited cytological which are done in general population, confirming that literature on IMT. Shukla et al30 concluded that FNA FNAC is indeed an invaluable tool in the diagnosis of cytology is not very helpful in distinguishing IMT from STTs in pediatric age group. malignant lesions, especially STSs.

Table 7: Comparison of statistical analysis between studies Sr.no Authors Sensitivity Specificity PPV NPV 1 Layfield et al12 (1986) 95 95 - - 2 Wakely et al31 (2000) 100 97 - - 7 Nagira et al1(2002) 92 97 - - 3 Dey et al14 (2004) 91.5 92.5 95.5 - 5 Domanski et al32(2005) 98.7 96.2 97.5 98 10 Rekhi et al16 (2007) 100 87 98 100 4 Ng et al80 (2009) 89.2 89.8 96.1 98.1 6 Kasraeian et al33 (2010) 79.2 72.7 67.9 82.8 1 Beg et al15 (2012) 98.1 96.7 97.2 - 2 Soni et al21 (2014) 70 100 97.9 100 11 P Arul et al24 (2016) 91.7 97.7 84.6 98.9 12 Presentstudy (2017) 90.09% 94.1% 83.33% 96.6%

Table 8: The discordant cases on histology and their cause Sr.no Cytological diagnosis Histopathological diagnosis Nature Reason for discordance 1 Schwannoma Low-grade MPNST False negative Interpretation error 2 Benign spindle cell tumour Synovial sarcoma False negative Sampling error 3 Malignant mesenchymal tumour Inflammatory myofibroblastic tumour False positive Interpretation error As mentioned in the above discussion we attribute the cause for one of our false negative case and our only false positive case on interpretation error and the reason for the other false negative case as sampling error.

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