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Year : 2019  |  Volume : 36  |  Issue : 2  |  Page : 118-123
Core needle biopsy versus fine needle aspiration cytology in bone and soft tissue tumors

Department of Surgical Pathology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India

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Date of Web Publication8-Mar-2019


Fine needle aspiration cytology (FNAC) for diagnosis of musculoskeletal tumors is well discussed and debated. The current evidence restricts its application in recurrent and metastatic lesions, with core needle biopsy as the acceptable technique/gold standard for the primary diagnosis of these challenging tumors. However, there are several studies showing reasonable sensitivity and specificity in primary diagnosis of bone and soft tissue tumors, especially in differentiating benign from malignant tumors. There is an acceptable limitation in the exact subtyping of soft tissue tumors, based on cytology smear examination, in the absence of ancillary techniques. Nonetheless, cytology constitutes an optimal material for triaging cases for ancillary techniques, such as immunocytochemistry, immunohistochemistry, molecular cytogenetics, and molecular diagnosis, in the form of smears and cell block preparations. This review focuses on the strengths and limitations of cytology versus core needle biopsy in the diagnosis of bone and soft tissue tumors, with the current evidence in the form of published studies, including the authors' experience.

Keywords: Fine needle aspiration cytology of bone and soft tissue tumors, immunocytochemistry, immunohistochemistry of sarcomas

How to cite this article:
Rekhi B. Core needle biopsy versus fine needle aspiration cytology in bone and soft tissue tumors. J Cytol 2019;36:118-23

How to cite this URL:
Rekhi B. Core needle biopsy versus fine needle aspiration cytology in bone and soft tissue tumors. J Cytol [serial online] 2019 [cited 2023 Mar 23];36:118-23. Available from:

   Introduction Top

Bone and soft tissue tumors constitute as one of the diagnostically challenging groups of tumors. The reasons include rarity, leading to a limited access of these tumors to a routine pathologist, along with a remarkable heterogeneity and overlap within the several tumor entities, especially within soft tissue tumors. More than 100 soft tissue tumors and more than 80 sarcomas have been described.[1] While core needle biopsy is the time-honored gold standard for diagnosis of these challenging tumors, fine needle aspiration cytology (FNAC) has its value in certain scenarios.

FNAC constitutes an inexpensive, quicker, safe, technique with an opportunity for an immediate assessment of specimen adequacy.[2] In expert hands, this has been purported to show high diagnostic accuracy and predictive value with results comparable to those obtained by needle core biopsy, mostly in differentiating benign from malignant tumors.[3] There are a considerable number of published studies, including from our country regarding cytological diagnosis of soft tissue tumors, with sensitivity ranging from 84% to 100%; specificity from 83% to 97%, and a positive predictive value of 84% to 98%, in differentiating benign from malignant tumors. However, there is a limitation in subclassification. An accurate subtyping was possible in 25%–47% cases, as per these studies.[4],[5],[6],[7],[8] Furthermore, there have been attempts toward grading sarcomas on cytology samples with a higher cytohistological concordance in high-grade sarcomas, when compared with low-grade sarcomas.[9],[10]

Current evidence states the diagnostic role of FNAC, essentially in recurrent and metastatic lesions of soft tissues and bones. It can also be useful in identifying metastatic tumors and myeloma, which present as lytic or sclerotic bony lesions.[3],[11] Its role in the primary diagnosis of musculoskeletal tumors has been reasonably discussed and debated.[12] Our recent analyses of 400 cases of soft tissue tumors have unraveled significant discrepancies between diagnosis from a general (nonspecialist) and a specialist pathologist, routinely engaged in reporting musculoskeletal tumors. One of the reasons for the discrepancies was an attempt to primarily diagnose soft tissue tumors on FNAC, especially from a nonspecialist, possibly with limited access to ancillary techniques.[13] Nonetheless, FNAC is very useful for triage, including for ancillary testing.[14],[15],[16] It provides more access to mass lesions, when compared to a core biopsy. In cases of bone tumors, a cytological access from the soft tissue component can be useful for a timely diagnosis (e.g., a pleomorphic sarcoma), especially in limited resource settings and for further triage. A guided FNAC, especially with positron emission tomogram and magnetic resonance imaging, can enhance the amount of representative material.

   Prerequisites Top

While evaluating a bone and soft tissue mass, one needs to use a correct needle (preferably 22–25 gauge needles) and follow the right approach. A basic understanding of oncology practice, in the form of a multidisciplinary approach, is imperative.[17] This may be combined with an algorithmic approach and further morphology-based analysis. While on plain radiograph imaging, well-defined, geographic, lytic lesions with a narrow zone of transition are more commonly associated with benign bone tumors; “moth-eaten” and permeative lesions with a wide zone of transition and significant periosteal reaction are more commonly seen in malignant bone tumors. Typical examples include “sun burst” pattern in an osteosarcoma and a lamellated or “onion skin” type of periosteal reaction in Ewing sarcoma. The latter appearances can also be seen in inflammatory lesions, including tubercular osteomyelitis. It is also helpful to know which tumors frequently occur in a particular part of a bone, for example, giant cell tumor occurs as an expansile, epimetaphyseal-based tumor.[18]

The other prerequisites for evaluation of a soft tissue and also a bony mass include clinical history and parameters, such as age, gender, duration of the lesion, and growth pattern, along with association of the lesion with pain and or trauma. During clinical examination, it is important to know the size (clinicoradiological) and site of the lesion (superficial/deep). There might be a single or multiple lesions, for example, in setting of neurofibromatosis with café au lait spots. At the time of FNAC procedure, in case the patient feels a strong wince, there could be a possibility of a neurogenic tumor. It is also significant to know whether there is association with skin, any previous scar, and lymph nodes. There can be help for available biochemical investigations, for example, tumor marker levels in suspected germ cell tumor at sites such as retroperitoneum.

   Bone Tumors Top

Bone tumors have specific cytomorphological appearances, such as multinucleated, osteoclast-like giant cells, along with mononuclear cells in a giant cell tumor of bone [Figure 1], and polygonal cells with intranuclear grooves in a chondroblastoma [Figure 2].[19],[20] Cytomorphological appearances in malignant bone tumors include pleomorphic sarcomatous cells in a conventional high-grade osteosarcoma [Figure 3] and abundant chondroid matrix in a chondroid tumor, including a chondrosarcoma and round cells in Ewing sarcomas and non-Hodgkin's lymphomas, the latter invariably associated with several lymphoglandular bodies.[21],[22],[23],[24] At all times, the findings need to be correlated with clinicoradiological findings. For example, in a case of multiple bone and soft tissue lesions in a pediatric patient, one should consider a possibility of a hematolyphoid neoplasm.[23] There have been instances of identifying sarcomatous component on cytology specimens, in cases of a giant cell tumor of bone.[25]
Figure 1: (a) Case of a giant cell tumor of bone, displaying clusters and singly scattered osteoclastic giant cells with intervening mononuclear cells. Papanicolaou (Pap) 400×. (b) Corresponding histopathologic section showing features of a giant cell tumor of bone. Hematoxylin and eosin (H and E), 200×

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Figure 2: Case of a 19-year-old male with an epimetaphyseal lesion in distal femur. (a) Smear showing few clusters of cells, with scattered osteoclastic giant cells (upper inset). Mononuclear cell showing intranuclear grooves (lower inset). Pap, 400×; cytologic diagnosis: suspect chondroblastoma. (b) Histopathologic section (same case diagnosed as a chondroblastoma) showing scattered osteoclastic giant cells and scattered cells with intranuclear grooves. H and E, 200×. (c) “Chicken wire”-like calcification with chondroid differentiation. H and E, 200×

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Figure 3: Case of a 9-year-old girl with a destructive lesion in the lower end humerus along with soft tissue extension and solid periosteal reaction. (a) Cytologic smear showing markedly pleomorphic sarcomatous cells, consistent with a high-grade osteosarcoma. May Grunwald Giemsa (MGG) 400×

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   Soft Tissue Tumors Top

While evaluating smears in cases of soft tissue masses, it is necessary to have familiarity with normal structures, such as mesenchymal stroma (appears metachromatic on Romanowsky-stained smears), adipose tissue, neural tissue, and muscle fibers. A tumor composed of a rather banal-looking nuclei arranged in the form of a neural structure could be a benign nerve sheath tumor [Figure 4]. The degree of cellularity and atypia, including mitotic figures, tumor giant cells, and background necrosis, are other features that need to be carefully assessed. A pragmatic approach while evaluating a soft tissue lesion on cytology is to identify whether the lesion or the tumor is composed of predominantly spindle-shaped cells, polygonal/epithelioid, round cells, or pleomorphic cells. The other categories/subtypes include adipocytic and myxoid-rich tumors.[6],[12] While round cell tumors can be fairly diagnosed on cytology with ancillary techniques in certain cases and pleomorphic sarcomas can be identified timely, spindle cell, epithelioid, and myxoid tumors are challenging. It is noteworthy that round cell tumors need to be accurately subtyped, in view of specific chemotherapy regimens for tumors, including Ewing sarcoma, rhabdomyosarcoma, non-Hodgkin's lymphoma, and neuroblastoma [Figure 5],[Figure 6],[Figure 7]. Within the realm of spindle cell sarcomas, synovial sarcomas can be diagnosed, in a clinical context [Figure 8].[26] Epithelioid tumors such as an epithelioid sarcoma can be difficult to diagnose on cytology smears, in view of their superficial location and a histopathological spectrum, leading to a challenge in differentiating this tumor from a metastatic carcinoma and other epithelioid tumors, including a melanoma (amelanotic type). The diagnosis can be possible if the results are combined with immunostaining results, including INI1/SMARCB1.[27] In the subgroup of myxoid tumors, while chordomas and, to some extent, extraskeletal myxoid chondrosarcomas have been diagnosed with the help of FNAC, low-grade fibromyxoid sarcomas are difficult to diagnose by FNAC.[16],[28],[29] FNAC has been reported to be useful in uncovering rare morphological variants within soft tissue sarcomas.[30] Within the subgroup of epithelioid-cell-rich lesions, diagnosis of Langerhans cell histiocytosis should be kept in mind, in case of lytic lesions in bones and in lymph nodes in pediatric patients, wherein smears show polygonal cells admixed with eosinophils [Figure 9].[31]
Figure 4: Case of a young male with a 3-cm-sized nodule in the forearm. (a) and (b) FNAC smears showing elongate cells with wavy nuclei, arranged in a neural-like pattern. Cytological diagnosis was suggestive of a benign nerve sheath tumor. MGG 400×. Histopathologic diagnosis was a schwannoma

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Figure 5: Case of Ewing sarcoma. (a) Cellular smear showing cohesive clusters of malignant round cells displaying fine chromatin. Pap 400×. (b) Classic rosette formation with cells containing scant, finely vacuolated cytoplasm. MGG 400×. (c) Cell block preparation showing malignant round cells arranged in a diffuse pattern. H and E, 200×. (d) Tumor cells displaying diffuse, cytoplasmic membranous positivity for MIC2/CD99, reinforcing a diagnosis of Ewing sarcoma. Diaminobenzidine (DAB), 400×

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Figure 6: Multiple views of a case of Ewing sarcoma, displaying EWSR1 rearrangement (red-green split signals) by fluorescent in situ hybridization (FISH) technique, tested on a cell pellet preparation. DAPI, 1000×

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Figure 7: A 15-year-old male with a nasal tumor and cervical lymph node. (a) FNAC from the cervical lymph node showing a malignant round cell tumor, including binucleate forms against a “Tigroid” background. MGG, 400×. (b) Malignant round cells with prominent nuclei and multinucleate forms. Pap 400×. (c) Histopathologic section of the nasal tumor, showing features of a rhabdomyosarcoma (solid variant). A “wreath-like” giant cell (arrow head) (d). Tumor cells displaying desmin positivity. DAB, 400×. (e) Diffuse intranuclear MyoD1 positivity. DAB, 400×

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Figure 8: Case of a 26-year-old male with a recurrent soft tissue tumor in his elbow. Synovial sarcoma. (a) Cellular tumor displaying prominent branching vascular pattern. Pap 200×. (b) Higher magnification showing scattered cells with oval to short spindle-shaped atypical nuclei. Pap, 400×. (c) Cohesive cluster of polygonal to short spindly cells (biphasic). MGG, 400×. (d) Cluster of malignant cells with polygonal and spindle-shaped nuclei, displaying significant atypia, arranged in a pseudoacinar pattern. Pap, ×400

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Figure 9: Case of a 4-year-old child with a lytic lesion in the scalp and lymph node (a and b). (a) Moderately cellular smear composed of round to polygonal cells, with characteristic intranuclear grooves, indicative of Langerhans cell histiocytosis (LCH). Pap, 400×. (b) Polygonal cells with moderate amount of cytoplasm. MGG, 400×. (c) Biopsy confirming a diagnosis of LCH. H and E, 200×. (d) CD1a reinforcing a diagnosis of LCH. DAB, 400×

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At all times, one needs to be aware of lesions, such as myositis ossificans, aggressive fibromatosis, and nodular fasciitis [Figure 10], which can mimic sarcomas and therefore constitute as diagnostic pitfalls.[6],[15] There can be a considerable difficulty in differentiating an enchondroma from a well-differentiated chondrosarcoma and chondrosarcoma from a chondroblastic osteosarcoma.[22] Sclerotic lesions are difficult to evaluate on cytology. These cases are subjected to a biopsy in case of a negative cytology result and persistent clinicoradiological suspicion or an equivocal result.
Figure 10: Case of a young male with a 3-cm-sized soft tissue lesion in his neck. Nodular fasciitis. (a) Cellular smears showing metachromatic myxoid matrix. MGG 400×. (b) Spindle-shaped fibroblastic cells with banal-looking nuclei. MGG 400×. (c) Cluster of spindle cells with innocuous-looking nuclei. Pap 400×. (d). Spindle cells with an interspersed multinucleate giant cell. Pap 400×. Inset: Histopathologic section showing corresponding features of nodular fasciitis. H and E 200×

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To summarize, FNAC has a significant role in the diagnosis of bone and soft tissue tumors. It is complimentary to a biopsy, for preoperative decisions and triage. FNAC of musculoskeletal tumors should be practiced at specialized centers, dealing with high volume of such cases, in a multidisciplinary approach. It is imperative to incorporate radiological findings during the diagnosis of bone tumors. FNAC can be useful in sorting out pleomorphic and round cell tumors, timely. Spindle cell and epithelioid tumors are particularly difficult and challenging. It is an excellent material for ancillary techniques. While immunohistochemistry/immunocytochemistry is essential for subclassification of round cell tumors, molecular and/molecular cytogenetic techniques are useful in an exact diagnosis of certain round and spindle cell tumors.

Smears and cell blocks are useful for ancillary techniques in cytology. Various cytomorphological clues guide in primary diagnosis of certain tumors and for the choice of ancillary techniques. A correct diagnosis has a remarkable impact, especially in pediatric round cell tumors. The importance of interpretation of cytomorphological findings, including ancillary test results in a clinicoradiological context, cannot be overemphasized.

While benign and malignant tumors can be differentiated on cytology and certain subtypes of sarcomas can be correctly diagnosed, with ancillary testing, grading of sarcomas, on cytology, especially low-grade sarcomas, remains a challenge.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

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Correspondence Address:
Dr. Bharat Rekhi
Room Number 818, Department of Surgical Pathology, 8th Floor, Annex Building, Tata Memorial Hospital, Dr E.B. Road, Parel, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JOC.JOC_125_18

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]

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