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.
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- MATERIALS AND METHODS
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 aspects||Pathologic features|
|Age range (yrs)||Anatomic site||Usual cytologic features||Nuclear pleomorphism||Immunohistochemical/ molecular profile|
|Myxofibrosarcoma||50–80||Dermal/subcutaneous, extremities||Myxoid granular film, individually dispersed tumor cells, variable vascularity||Usually significant, often marked||Vimentin positive/complex karyotype (nondiagnostic)|
|Myxoid/round cell liposarcoma||40–70||Deep soft tissues, extremities||Myxoid stromal fragments, individually dispersed ovoid tumor cells, arborizing blood vessels. Round cell component comprised of larger, sometimes epithelioid, cells||Minimal, if round cell component is present, may be significant||Vimentin positive S-100 variable/t(12;16)(q13;q11) CHOP-TLS|
|Myxoid chondrosarcoma||40–70||Deep soft tissues, extremities||Myxoid stromal fragments, spindled to round tumor cells arranged in anastomosing cords, nests, and clusters; absence of vascularity||Minimal to absent||Vimentin 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.