| Abstract|| |
Background: Histological diagnosis of soft tissue sarcomas is a difficult job not only for diverse architecture of different variants but also for variability in picture among different parts of a single tumor. Thus, cytodiagnosis of these tumors is one of the most challenging jobs.
Aims: To evaluate the role of fine needle aspiration cytology in diagnosis of soft tissue malignancies and discuss the false-positive cases with particular reference to causes of misdiagnosis and possible ways of correction.
Materials and Methods: In the present study, we used cytology for categorization of 59 soft tissue malignancies according to predominant cell type and also on the basis of differentiation.
Results: Out of 59 cytodiagnosed malignant soft tissue tumors, 36 were classified as high grade and rest as low grade. Spindle cell sarcoma was the commonest diagnosis, followed by pleomorphic variant. Histological correlations were performed in 47 cases showing consistency in 41 cases. Rest six cases with disparity were further discussed to ascertain causes of failures and to chalk out possible plans to evade these pitfalls in future.
Conclusions: Overall our study established the role of cytology in diagnosis of soft tissue sarcomas with good cytohistological correlation rate (87.2%).
Keywords: Cytodiagnosis; pitfall; soft tissue sarcomas.
|How to cite this article:|
Sengupta S, Mondal SK, Mallick MG, Biswas P, Basu N. Role of cytology in diagnosis of soft tissue sarcomas with special reference to false positive cases. J Cytol 2009;26:15-9
|How to cite this URL:|
Sengupta S, Mondal SK, Mallick MG, Biswas P, Basu N. Role of cytology in diagnosis of soft tissue sarcomas with special reference to false positive cases. J Cytol [serial online] 2009 [cited 2021 Mar 8];26:15-9. Available from: https://www.jcytol.org/text.asp?2009/26/1/15/54862
| Introduction|| |
Extra-skeletal supporting tissue of body is known as soft tissue. It includes fat, fibrous tissues, voluntary and involuntary muscles, blood vessels and also peripheral nerves. Different kinds of tumors, both benign as well as malignant, can arise from these tissues and are named according to their apparent resemblance to mature tissues. Soft tissue tumors can involve any part of the surface of the body as well as retroperitoneum and mediastinum. 
Malignant soft tissue tumors i.e. soft tissue sarcomas (STSs) are rare and account for less than 1% of total malignancies. However, diagnosis of these tumors is a challenging job for histopathologists because of extreme histological diversity. Interpretation from a small biopsy sample is particularly difficult as there may be variability in appearances in different parts of a single tumor. ,
Naturally, the role of cytology in the diagnosis of STSs is well debated. 
A lot of workers discouraged fine needle aspiration cytology (FNAC) in this field and argued that it should be restricted for assessment of metastatic and recurrent lesions. , Limitations of FNAC in diagnosis of STSs, as mentioned by various authors include: ,
(1) Failure to obtain adequate specimen particularly from deep seated or necrotic or cystic lesions. (2) Misdiagnosis over specimens drawn from the surrounding reactive zones. (3) Failure to specially typify majority of the STSs. (4) Failure to interpret rare variants. (5) Lack of adequate cytological diagnostic criteria of newly discovered/classified entities.
However, recent workers clearly established the role of cytology in this field with highly sensitive and specific tumor detection rate in their study group. ,,, FNAC has also got some distinct advantages over a small biopsy sample for primary pre-operative assessment of STSs such as: ,, (1) Needle aspiration is associated with minimum chance of tumor spread. (2) Multiple aspirations from different parts of a large heterogeneous tumor can be more informative than a small biopsy sample.
FNAC, being a simple, cheap and quick procedure, is also considerably more cost effective.
However, we must understand that FNAC should be used in this field as a complement rather than a competitor to histopathology. 
With this background, we used cytology for diagnosis of STSs in the present study. The aim and objectives of our study were: (1) To evaluate the role of FNAC in diagnosis of soft tissue malignancies. (2) To discuss the false-positive cases with particular reference to causes of misdiagnosis and possible ways of correction in future.
| Materials and Methods|| |
Present study was performed in the Department of Pathology of our institute over a period of five years (1 st April 2002 to 31 st March 2007). During this period, all the cases that were diagnosed on cytology as primary STSs were included in the study group. Metastatic tumors presenting as a soft tissue mass or malignancies of nearby structures involving soft tissue by extension (like osteosarcoma or fibrosarcoma of bone) were excluded. Histology confirmed soft tissue malignancies were not included in our study group, if previous needle biopsies failed to detect either malignant nature or soft tissue origin of the lesions.
Aspirations were performed with 22G disposable needles fitted to 20 cc disposable syringes using recommended criteria.  Multiple aspirations were attempted from different parts of the tumors, particularly from the larger malignancies. Cytological smears were examined in the context of available clinical-radiological findings. All smears were classified according to the predominant cell type into one of the four groups namely spindle cell sarcoma, round cell sarcoma, pleomorphic sarcoma and myxoid sarcoma.
We also classified all these smears into high-grade or low-grade malignancies using criteria to be discussed later. So, the final cytodiagnosis of a tumor was high-grade pleomorphic sarcoma or low-grade spindle cell sarcoma or likewise. No attempt was made for specific identification of tumors on cytology.
Histological samples were processed and studied using standard procedures in cases with available biopsy specimens. Light microscopic diagnosis of slides were performed following the recommendation of experts.  Cytohistological correlations was attempted considering histological diagnosis as final. Cytological diagnosis was taken as consistent when histology confirmed a diagnosis of STS, irrespective of specific type. The cases with histological diagnosis other than STSs were regarded as inconsistent and dealt in detail.
| Results|| |
During the study period, a total of 14 863 cases were aspirated with adequate aspiration in 14 496 cases. Among these cases 4374 cases (30.2%) were cytodiagnosed as malignant. Soft tissue sarcomas accounted for 1.34% of malignancies (59 cases).
[Table 1] shows that among these 59 cytodiagnosed STS cases, male case outnumbered females. Commonest age group affected was 41-60 years and majority of the tumors arose from trunk followed by inferior extremities. Out of 59 STS cases, majority (36) were high-grade tumors.
Spindle cell sarcomas were the commonest variant (22 out of 59), followed by pleomorphic sarcomas [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Table 2].
Biopsy materials for histopathological examinations were available in 47 cases. Histology confirmed diagnosis of STS in 41 cases. There were six false-positive cases. Commonest histological diagnosis was rhabdomyosarcoma followed by fibrosarcoma and small round cell tumors [Table 3].
[Table 4] deals with cases showing cytohistological disparity.
| Discussion|| |
Soft tissue sarcomas accounted for 1.34% of malignancies in our study. This is slightly higher in comparison to less than 1% rate, reported by other workers. , Inclusion of false-positive cases might be responsible for this higher rate. Different workers reported higher number of male cases and more number of elderly cases in their series as experienced by us. , Maximum number of cases have been reported from trunk followed by inferior extremity and head-neck region as reported by others. 
Specific cytological diagnostic criteria for few STSs are already established.  However, as most of the sarcomas cannot be accurately cytodiagnosed, standard approach is to categorize tumors into predominant cell type, i.e. spindle cell, round cell, myxoid and pleomorphic sarcoma. Some authors recommended a fifth group polygonal cell sarcoma. But we categorized all tumors of our study group into four groups, following standard recommendation. , Spindle cell tumors accounted for majority of the cytodiagnosed cases in our series. High-grade malignancies were more frequent than low-grade sarcomas. These are also standard findings of others. ,,
Standard 3 tier or 4 tier histological grading system for STSs is proposed by many authors.  But grading of these tumors on cytology is considerably difficult. ,,, Different authors attempted cytological grading depending upon cellularity of the smears, differentiation of the cells, mitotic rate and amount of necrosis, if present. ,, The predominant cell type is also important as round cell tumors are commonly taken as high-grade lesions. Pleomorphic sarcomas usually fall into high grade and myxoid sarcomas into low grade. , For easy reproducibility, we adopted a two-tier system. We utilized following cellular and nuclear features as proposed by other workers, for classification of the tumors of our series into low-grade and high-grade lesions, such as cellularity (low-to-moderate v/s moderate-to-high), architecture of aspirate (more cohesive v/s more single cell), predominant cell type (myxoid v/s pleomorphic or round cell variant), necrosis (absence v/s presence), mitotic rate (low v/s moderate to high with atypical form), cellular pleomorphism (mild-to-moderate v/s moderate-to-severe), nuclear membrane (regular v/s irregular), chromatin pattern (homogeneous v/s clumped), nucleoli (inconspicuous v/s prominent) and nuclear lobulation (unusual v/s common). 
Rhabdomyosarcoma was the commonest histological subtype of STSs in our series, similar to experience of other workers. 
In our series, cytohistological correlation rate was 87.2%. Akerman M and Willιn H  in their largest series of 517 cases of soft tissue tumors, cytodiagnosed 202 STSs. They were able to differentiate benign from malignant lesions in 94% cases. Brosjo et al.  reported 88% conclusive diagnosis on cytology in their series of 342 soft tissue tumors. Liu et al. ,  on the other hand, reported considerable improvement in diagnostic accuracy of cytodiagnosis (from 0.19-0.44 to 0.48-0.66) of soft tissue tumors, if clinical findings were made available to the examining pathologists.Rekhi et al.  and Kumar et al.  during assessment of 127 and 72 cases of soft tissue tumors in their respective series, reported more than 90% diagnostics accuracy of FNAC for detection of soft tissue sarcomas.
Out of six false-positive STS cases in our series, two cases were proven to be fibromatosis, though cytodiagnosis was low-grade spindle cell sarcoma. This is a commonly reported mistake and occurs due to high cellular yield, pleomorphism and increased mitotic rate of the aspirates from fibromatosis. , For correct diagnosis of fibromatosis, more stress should be given to the myxoid background, presence of inflammatory cells and binucleate or trinucleate ganglion cells, pale wispy cytoplasm of spindle cells with relatively bland, homogeneous chromatin pattern. Clinical features are also helpful in diagnosis. But immunocytochemistry has got little role. ,
Another case of ancient schwannoma was misdiagnosed cytologically as low-grade pleomorphic sarcoma. It is also a commonly reported mistake.  Hypercellularity of the smears and presence of large bizarre cells with hyperchromatic irregular nuclei were causes for misinterpretation. For cytodiagnosis of ancient schwannoma, following findings must be looked for-more cohesive architecture, low mitotic rate, homogeneous and pyknotic chromatin pattern and relative sparsity of tumor giant cells. S-100 positivity of tumor cells also strongly indicates towards a benign neurogenic tumor. 
We also misinterpreted a case of malignant melanoma as high-grade pleomorphic sarcoma. Presence of bizarre pleomorphic cells in smears and frequent absence of demonstrable melanin pigment in cells are causes behind this type of confusion. Without proper clinical history, this distinction is often difficult. Immunostaining particularly for HMB-45 can confirm melanoma cells. 
Two cases of diffuse large cell non Hodgkin's lymphoma (NHL) were wrongly interpreted as high-grade round cell sarcomas. Distinction of these two entities is quite difficult, particularly where clinical findings are misleading. Cytodiagnosis of NHL can be achieved with demonstration of lymphoglandular bodies, if present, more dyscohesive cellular architecture, prominent pleomorphism and presence of prominent nucleoli and nuclear grooving in few cases. Immunocytochemistry has got a very important role. ,
| Conclusion|| |
In the present study, the success of FNAC in the field of pre-operative diagnosis of STS cases is established. Cytological categorization of these malignancies according to differentiation and predominant cell type will definitely help in early formulation of effective management protocol. Causes of failures are also discussed in the study to attain possible remedies. We are concluding our work with the hope of further intensified research in this field of diagnostic pathology to establish more accurate and precise criteria for cytodiagnosis of STSs.
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Santosh Kumar Mondal
"Teenkanya Complex", Flat 1B, Block B, 204 R N Guha Road, Dumdum, Kolkata - 700 028
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]