The value of fine-needle aspiration biopsy in the differential diagnosis of adult myxoid sarcoma


  • Scott E. Kilpatrick M.D.,

    Corresponding author
    1. Department of Pathology, University of North Carolina, Chapel Hill, North Carolina
    • Department of Pathology and Laboratory Medicine, University of North Carolina, CB# 7525, Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525
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  • William G. Ward M.D.,

    1. Department of Orthopedics, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina
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  • Gary D. Bos M.D.

    1. Department of Orthopedics, University of North Carolina, Chapel Hill, North Carolina
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The usefulness of fine-needle aspiration biopsy (FNAB) for the histologic subtyping of specific sarcomas still is somewhat controversial but is becoming increasingly popular in the U.S.


To determine the accuracy and usefulness of FNAB in the differential diagnosis of myxoid sarcoma, the authors retrospectively reviewed 18 FNAB specimens (16 primary tumors, 1 local recurrence, and 1 metastasis) in 18 patients. The study sample included myxoid/round cell liposarcoma in six patients, myxofibrosarcoma in six patients, myxoid chondrosarcoma in five patients, and myxoid leiomyosarcoma in one patient.


All but one tumor were recognized correctly as malignant. With regard to primary tumors, a specific cytologic diagnosis was rendered in 13 of 16 patients (81%). Problematic areas included the diagnosis of high grade myxofibrosarcoma with minimal amounts of myxoid stroma, myxoid liposarcoma with a predominant round cell component, and the single case of myxoid leiomyosarcoma.


FNAB represents a valuable diagnostic tool for the differential diagnosis of myxoid sarcoma, especially myxofibrosarcoma, low grade myxoid liposarcoma, and myxoid chondrosarcoma. Due to its prognostic and therapeutic significance, the presence of a predominant round cell component in myxoid liposarcoma should be documented adequately. Other sarcomas (e.g., leiomyosarcoma) rarely may exhibit a prominent myxoid stroma and therefore should be considered in the differential diagnosis of adult myxoid sarcoma. Cancer (Cancer Cytopathol) 2000;90:167–77. © 2000 American Cancer Society.

Fine-needle aspiration biopsy (FNAB) of soft tissue sarcomas remains somewhat controversial, as evidenced by the reluctance of the Association of Directors of Anatomic and Surgical Pathology to endorse the procedure fully as a viable diagnostic technique.1 Nevertheless, in experienced hands FNAB has been shown to be a highly accurate technique for the evaluation of soft tissue sarcomas, especially among pediatric patients.2–5 Recently, major surgical pathology textbooks have acknowledged the successful contribution of FNAB to the diagnosis and management of patients with soft tissue sarcomas.6, 7

Among soft tissue sarcomas, FNAB appears especially useful for adult myxoid sarcomas, with the majority appearing to be diagnosed easily based solely on their distinctive cytomorphologic features.4, 8, 9 Although the cytologic findings of the myxoid sarcoma subtypes have been described adequately, to our knowledge, little emphasis has been given to the accuracy of FNAB in distinguishing the various subtypes and the range of histologic grade in myxoid liposarcoma and myxofibrosarcoma.8–11 The cytologic features of myxoid leiomyosarcoma of soft tissue have been illustrated and described only rarely.12 We report herein our experience with FNAB of adult myxoid soft tissue sarcomas with emphasis on the range of cytomorphologic features and histologic grade as well as potential diagnostic pitfalls.


We retrospectively reviewed 18 FNAB specimens from 18 patients from the cytopathology files of Wake Forest University Baptist Medical Center (16 cases) and the University of North Carolina Medical Center (2 cases). The study cases were retrieved consecutively between 1994–1999. Sixteen cytologic samples were obtained without anesthesia using 23-gauge and 25-gauge needles by the standard manual method; two were procured by computed tomography guidance. Aspirated material was expelled onto glass slides and smeared using a second glass slide. Half of the smears were air dried and stained with Diff-Quik® (Fisher Scientific Biomedical Sciences, Inc., Swedesboro, NJ). An equal number of slides immediately were immersed in 95% ethanol for staining by the Papanicolaou method. Cell blocks were prepared from eight FNAB specimens. Hematoxylin and eosin stained histologic slides from resection specimens were reviewed in all patients. Clinical data were retrieved from the patients' medical records.


Clinical Features

The clinical and pathologic features of the study cases are summarized in Table 1. Among the entire group of adult myxoid sarcomas, the patients' ages at diagnosis ranged from 23–94 years. There were nine men and nine women. The FNAB specimens were obtained from the primary tumors in 16 cases, a local recurrence in 1 case, and pulmonary metastasis in 1 case. Among FNAB specimens obtained from the primary tumor, an accurate cytologic diagnosis was rendered in 13 of 16 patients (81%). A case of low grade myxofibrosarcoma (Case 2) initially was believed to represent an atypical lipoma, due to the abundant amount of adipose tissue and the presence of scattered spindled cells with significant nuclear atypia. A case of myxoid/round cell liposarcoma with a predominant round cell component (Case 6) was diagnosed nonspecifically as “malignant neoplasm”; the morphology initially suggested metastatic carcinoma. Due to minimal amounts of myxoid stroma, one example of high grade myxofibrosarcoma (Case 4) was diagnosed as “pleomorphic sarcoma, not otherwise specified.” In contrast, due to its rather unusual and abundant myxoid stroma, a case of myxoid leiomyosarcoma initially was misdiagnosed as myxofibrosarcoma. In none of these cases did the failure to render a specific cytologic diagnosis lead to inadequate or inappropriate therapy.

Table 1. Clinicopathologic Features of the Study Patients with Myxoid Sarcoma
Patient no.Age (yrs)GenderAnatomic siteFNACytologic DxHistologic Dx
  1. FNA: fine-needle aspiration; Dx: diagnosis; F: female; M: male; NOS: not otherwise specified.

177FRight buttockPrimaryMyxofibrosarcomaMyxofibrosarcoma
247FLeft heelPrimaryAdipose tissue with atypiaMyxofibrosarcoma
350MRight buttockPrimaryMyxofibrosarcomaMyxofibrosarcoma
440FRight thighPrimaryPleomorphic sarcoma, NOSMyxofibrosarcoma
526MLeft backRecurrenceMyxofibrosarcomaMyxofibrosarcoma
679FLeft groinPrimaryMalignant neoplasmMyxoid/round cell liposarcoma
749FLeft thighPrimaryMyxoid liposarcomaMyxoid liposarcoma
823MLeft legPrimaryMyxoid liposarcomaMyxoid liposarcoma
979MLeft shoulderPrimaryLiposarcomaMyxoid/round cell liposarcoma
1057MMediastinumPrimaryMyxoid liposarcomaMyxoid/round cell liposarcoma
1149MLeft armLungMyxoid chondrosarcomaMyxoid chondrosarcoma
1247MLeft thighPrimaryMyxoid chondrosarcomaMyxoid chondrosarcoma
1394FRight thighPrimaryMyxofibrosarcomaMyxoid leiomyosarcoma
1465FRight thighPrimaryMyxoid chondrosarcomaMyxoid chondrosarcoma
1582FLeft poplitealPrimaryMyxofibrosarcomaMyxofibrosarcoma
1671FRight thighPrimaryMyxoid chondrosarcomaMyxoid chondrosarcoma
1744MLeft thighPrimaryMyxoid liposarcomaMyxoid/round cell liposarcoma
1832MLeft anklePrimaryMyxoid chondrosarcomaMyxoid chondrosarcoma

Pathologic Findings

Cytologic smears of myofibrosarcoma in all cases were characterized by variable amounts of a myxoid granular to filamentous background containing randomly distributed, mostly single, dyscohesive tumor cells and occasional loose cellular clusters (Fig. 1). In general, the volume of the myxoid material was inversely proportional to the cellularity and grade of the tumor. Individual tumor cells frequently displayed a wide range of cell shapes and sizes, ranging from round and polygonal to spindled and stellate. Nuclei frequently were large, hyperchromatic, and pleomorphic, often containing prominent nucleoli. Cytoplasm ranged from scant and wispy to dense and tapering, sometimes vacuolated. Multinucleated tumor giant cells occasionally were observed, more frequently in the higher grade examples. With the exception of one case, low and intermediate grade myxofibrosarcomas typically were recognized more easily in the cytologic preparations. Due to its less obvious and abundant myxoid stroma, higher grade examples appeared more difficult to subtype specifically and were not distinguishable from other adult pleomorphic sarcomas (malignant fibrous histiocytoma, pleomorphic liposarcoma, etc.). Based on the resection specimens, Cases 2 and 3 were determined to be low grade, Cases 1 and 15 were determined to be intermediate grade, and Cases 4 and 5 were determined to be high grade. Curvilinear blood vessels, a distinctive feature in histologic specimens of myxofibrosarcoma, were notably absent in the vast majority of smears. However, in the aspirate from one tumor (Case 15), blood vessels were prominent.

Figure 1.

Case 15. Myxofibrosarcoma characterized by mostly solitary, round to spindled, and pleomorphic tumor cells within a background myxoid to granular film (A: Diff-Quik stain, ×100; B: Papanicolaou stain, ×600).

Unlike the diffuse myxoid granular background of myxofibrosarcoma, myxoid liposarcoma was characterized by scattered fragments of myxoid stroma, frequently containing arborizing, capillary-like blood vessels. In the absence of a round cell component, the tumor cells were remarkably uniform and ovoid to slightly spindled. Nuclei were uniform and ovoid, hyperchromatic, and contained inconspicuous to absent nucleoli (Fig. 2). Occasional univacuolated and rare multivacuolated lipoblasts were identified (Fig. 3). However, in only one case were the lipoblasts a dominant and easily recognizable feature (Case 17). The most distinctive findings in all cases of myxoid liposarcoma (except for the virtually pure round cell type [Case 6]) were fragments of myxoid stroma, an arborizing vascular pattern, and a randomly distributed population of ovoid, undifferentiated tumor cells. Cases 9, 10, and 17 represented mixed round cell and myxoid liposarcomas whereas Case 6 appeared to be mostly (> 95%) round cell. The round cell component in these tumors was characterized by a significantly larger cell population comprised of mostly round cells with hyperchromatic nuclei and occasional prominent nucleoli. Cytoplasm generally was scant and only rarely vacuolated. The round tumor cells were dispersed solitarily and in small cellular clusters (Fig. 4). Rarely, the round cell component had epithelioid features (small cohesive clusters of large tumor cells with round and hyperchromatic nuclei and surrounded by scant to eccentrically placed cytoplasm), mimicking the appearance of metastatic adenocarcinoma.

Figure 2.

Case 8. Myxoid liposarcoma characterized by a myxoid stromal fragment containing a population of mostly uniform, ovoid, and hyperchromatic tumor cells transversed by an arborizing blood vessel (Papanicolaou stain, ×200).

Figure 3.

Case 17. Myxoid liposarcoma with myxoid stromal fragments and scattered, univacuolated, and multivacuolated lipoblasts, a predominant finding in only this case (A: Diff-Quik stain, ×100; B: Papanicolaou stain, ×200).

Figure 4.

Case 10. Myxoid and round cell liposarcoma characterized by a population of larger tumor cells with ovoid to round, vesicular nuclei and prominent nucleoli (A: fine-needle aspiration biopsy specimen; Papanicolaou stain, ×400; B: resection specimen; H & E, ×200).

All cases of myxoid chondrosarcoma showed similar cytopathologic features with aggregates of myxoid stroma within which was a population of mostly uniform-appearing round to spindled tumor cells (Fig. 5). In addition to the distinctive stromal fragments, a background granular film was present in the smears of one tumor (Case 18). Within the stromal fragments, the tumor cells were arranged in cords and small clusters or nests. Blood vessels were not identified. The nuclei of the tumor cells ranged from round to ovoid and hyperchromatic with small to inconspicuous nucleoli (Fig. 6). The round to polygonal-shaped tumor cells were surrounded by a thin rim of scant to slightly vacuolated cytoplasm. The more spindle-shaped forms displayed a wispy to dense, tapering cytoplasm. Definite hyaline cartilage differentiation was not identified in any of the cytologic preparations or the subsequent histologic resection specimens.

Figure 5.

Myxoid chondrosarcoma characterized by myxoid stromal fragments comprised of a uniform population of spindled to round tumor cells arranged in cords and nests. In addition to the stromal fragment, note the background granular pinkish film in panel B (A: Case 16; Diff-Quik stain, ×100; B: Case 18; Diff-Quik stain, ×100).

Figure 6.

Case 16. Myxoid chondrosarcoma with a uniform population of rounded to ovoid tumor cells, minimal nuclear pleomorphism, and inconspicuous nucleoli (Papanicolaou stain, ×200).

Cytologic smears from the single case of myxoid leiomyosarcoma resembled low to intermediate grade myxofibrosarcoma. A diffuse granular myxoid film was accompanied by randomly distributed tumor cells arranged solitarily and in large cohesive cellular clusters (Fig. 7). The neoplastic cells ranged from ovoid to spindled. Nuclei were round to ovoid, moderately pleomorphic, and contained inconspicuous to small nucleoli. The morphologic features initially suggested myxofibrosarcoma (Fig. 8). Retrospectively, the large compact and cohesive clusters of tumor cells would have been unusual for myxofibrosarcoma but not leiomyosarcoma. The latter diagnosis was confirmed in the resection specimen (Fig. 9).

Figure 7.

Myxoid leiomyosarcoma with a large cohesive tumor fragment. Note the pinkish, background granular and myxoid film (Diff-Quik stain, ×40).

Figure 8.

Myxoid leiomyosarcoma with solitary, atypical to markedly pleomorphic tumor cells, mimicking the appearance of myxofibrosarcoma (Papanicolaou stain, ×600).

Figure 9.

Myxoid leiomyosarcoma with (A) more conventional-appearing areas of smooth muscle differentiation and (B) areas of obvious myxoid change splaying individual tumor cells apart (A: H & E, ×40; B: H & E, ×100).


The primary purpose of the current study was to report our experience regarding the accuracy of FNAB, as well as to discuss and illustrate the histologic range and grade and identify reliable cytomorphologic features among adult myxoid soft tissue sarcomas. The clinical and pathologic features of the more common adult myxoid sarcomas are listed in Table 2. Cytologically, myxofibrosarcoma, myxoid liposarcoma, and myxoid chondrosarcoma share the presence of a myxoid stroma. However, the character of the stroma, degree of cellular atypia, and the arrangement of the tumor cells allow reliable separation of these neoplasms in the majority of cases. In myxofibrosarcoma, the myxoid stroma is manifested by a diffuse granular background, covering virtually the entire surface area of the smear. Among myxoid sarcomas, the degree of cytologic atypia and nuclear pleomorphism in myxofibrosarcoma exceeds that typically observed in myxoid liposarcoma and chondrosarcoma.9 Conversely, the latter neoplasms more commonly exhibit distinct myxoid stromal fragments containing a uniform cell population, usually with minimal to no nuclear pleomorphism. In addition, the tumor cells in myxoid chondrosarcoma usually are arranged in cords and anastomosing strands and may even appear lodged in lacunae, albeit true hyaline cartilage differentiation rarely is observed histologically.8, 13 These features, coupled with the clinical data, appear highly reliable. In the current series, we were able to diagnose preoperatively 13 of 16 primary tumors accurately. Problematic areas included high grade myxofibrosarcoma and myxoid liposarcoma with a predominant round cell component. In their higher grade forms, both of these neoplasms may exhibit minimal to absent myxoid stroma on cytologic smears but easily are recognized as malignant. As a consequence, histologic subtyping may not be possible but, in our limited experience, does not generally impact therapy provided the tumor is recognized as sarcoma.

Table 2. Clinicopathologic Features of Adult Myxoid Soft Tissue Sarcomas
 Clinical aspectsPathologic features
Age range (yrs)Anatomic siteUsual cytologic featuresNuclear pleomorphismImmunohistochemical/ molecular profile
Myxofibrosarcoma50–80Dermal/subcutaneous, extremitiesMyxoid granular film, individually dispersed tumor cells, variable vascularityUsually significant, often markedVimentin positive/complex karyotype (nondiagnostic)
Myxoid/round cell liposarcoma40–70Deep soft tissues, extremitiesMyxoid stromal fragments, individually dispersed ovoid tumor cells, arborizing blood vessels. Round cell component comprised of larger, sometimes epithelioid, cellsMinimal, if round cell component is present, may be significantVimentin positive S-100 variable/t(12;16)(q13;q11) CHOP-TLS
Myxoid chondrosarcoma40–70Deep soft tissues, extremitiesMyxoid stromal fragments, spindled to round tumor cells arranged in anastomosing cords, nests, and clusters; absence of vascularityMinimal to absentVimentin positive S-100 variable/t(9;22)(q21-31;q12) EWS-CHN(TEC)

Recent morphologic and cytogenetic evidence suggests that myxoid liposarcoma and round cell liposarcoma are not separate entities but, moreover, appear to occupy a clinicopathologic spectrum of the same neoplasm.14–16 In a majority of cases, myxoid and round cell liposarcomas harbor a specific cytogenetic abnormality, t(12;16)(q13;p11) and the CHOP-TLS fusion gene product.15 Furthermore, recognizing and documenting a round cell component in myxoid liposarcoma is not just an academic observation but appears to have prognostic significance.14, 16 Although the cytologic features of myxoid and round cell liposarcoma have been described previously, to our knowledge the spectrum between the two neoplasms has been addressed only rarely, mostly by European investigators,10, 11, 17 possibly due to the fact that only recently have the tumors been widely appreciated to represent a single entity. Recent cytologic reports from American investigators did not document specifically the presence or absence of a round cell component among various series (total of 28 cases) of myxoid liposarcomas.8, 18, 19 Whether this represents a failure to identify a round cell component or an exclusion of such tumors from these studies is unclear. Nemanqani and Mourad19 mention the presence of areas of “increased cellularity” in myxoid liposarcoma but these appear to represent foci of obvious multivacuolated lipoblasts and not round cell differentiation. When the full spectrum of myxoid and round cell liposarcomas are analyzed, pure myxoid (absence of a round cell component) liposarcoma represents between 28–57% of the cases, suggesting that round cell differentiation may be more common than initially believed.14, 16 It is our impression that the round cell component of myxoid liposarcoma remains underrecognized in many cases, especially in cytologic preparations. Definite round cell differentiation clearly was present in the histologic specimens of four cases; retrospectively, these cells also were present in the cytologic smears but were not recognized initially as round cell liposarcoma. Cytologically, round cell liposarcoma is characterized by a significantly larger cell population with nuclei resembling a Ewing sarcoma or large cell lymphoma.14 Nucleoli often are present and occasionally prominent. Rarely, the tumor cells appear epithelioid, mimicking adenocarcinoma.20

Myxoid chondrosarcoma is a rare sarcoma most commonly affecting the soft tissue (and rarely bone) of the extremities.13 Recent cytogenetic evidence suggests that the majority of these tumors show a nonrandom reciprocal chromosomal translocation, t(9;22)(q21-31;q12), with the EWS-CHN(TEC) fusion gene product.13 Cytologic descriptions largely have been restricted to individual case reports.21–24 Despite the name, myxoid chondrosarcoma rarely reveals hyaline cartilage differentiation. On conventional cytologic smears, the tumor is comprised of fragments of myxoid stroma tinctorially similar to that observed in myxoid liposarcoma. However, arborizing capillaries are absent and the population of uniform round to spindled cells is arranged in nests, cords, and anastomosing strands. Among the adult myxoid sarcomas in the current series, myxoid chondrosarcoma showed the least variation from case to case. Although cytogenetic analysis may be helpful, we believe the majority of cases can be diagnosed easily by careful analysis of clinical and cytomorphologic features.

Extensive myxoid change within uterine leiomyosarcoma is a well recognized phenomenon; however, to our knowledge similar features in soft tissue leiomyosarcoma are exceedingly rare and less well known.25 Arguably, only recently has myxoid leiomyosarcoma been clearly recognized as a distinct entity and not simply an unusual finding in occasional leiomyosarcomas.26 Its behavior, outside of the genitourinary regions, does not appear aggressive. However, myxoid leiomyosarcoma often is misdiagnosed as other myxoid sarcomas.26 In the cytologic literature, rare examples of myxoid leiomyosarcoma also have been documented, emphasizing the tendency to mistake such tumors for other myxoid sarcomas, especially myxofibrosarcoma.12 We encountered one example of myxoid leiomyosarcoma in our series of adult myxoid sarcomas. The tumor initially was misinterpreted as myxofibrosarcoma. Retrospectively, the presence of large tumor cell clusters and aggregates on the cytologic smears would have been more typical of leiomyosarcoma and, in our experience, unusual in myxofibrosarcoma.9, 20

Clinical and radiologic data may be helpful but generally are nonspecific for the differential diagnosis of myxoid sarcoma. Myxofibrosarcoma, myxoid liposarcoma, and myxoid chondrosarcoma may show similar clinical, radiologic, and macroscopic features, all usually arising in the extremities of older adults and appearing myxoid and lobulated by imaging studies. Perhaps the most helpful clue may be compartmental location (e.g., cutaneous/subcutaneous vs. deep intramuscular). Most examples of myxofibrosarcoma arise in the dermal or subcutaneous tissues; myxoid liposarcoma and myxoid chondrosarcoma virtually never occur in this location.27 However, many examples of myxofibrosarcoma arise in deeper locations. Only two of the cases in the current study (Cases 2 and 5) appeared to arise from more superficial soft tissues. Consequently, such data were not especially helpful for rendering a specific diagnosis in the majority of cases in the current study.

FNAB represents a valuable diagnostic tool for the differential diagnosis of myxoid sarcoma, especially low to intermediate grade examples of myxofibrosarcoma, myxoid liposarcoma, and myxoid chondrosarcoma. Higher grade examples of myxofibrosarcoma may be difficult to subtype specifically but generally are easily recognized as sarcoma. Due to its prognostic and therapeutic significance, the presence of a predominant round cell component in myxoid liposarcoma should be recognized and documented adequately. Other sarcomas (e.g., leiomyosarcoma) rarely may exhibit a prominent myxoid stroma and therefore should be considered in the differential diagnosis of adult myxoid sarcoma.