We herein describe a case of sacral mass which was diagnosed as anaplastic chordoma on fine needle aspiration cytopathology (FNAC) and was later confirmed by histopathology and immunohistochemistry. Such anaplastic chordomas need to be differentiated early from chondrosarcomas on preoperative aspiration cytopathology.
FNAC from the mass yielded blood-stained mucoid material. The smears were highly cellular and composed of tumor cells medium to large in size with a rounded well demarcated cytoplasm and central nucleus. The cytoplasm was abundant and foamy to bubbly in appearance (classical physaliphorous cell) (Figure 2). Many binucleated cells and multinucleated giant cells were also seen (Figure 2, inset), along with few pleomorphic spindle cells. Some of the cells had prominent nucleoli. The cells were arranged in groups with abundant magenta colored stroma in the background encircling individual cells (Figure 3). Mitotic figures were not seen. The diagnosis of anaplastic chordoma was considered on the basis of clinical, radiological and predominantly, cytopathological findings.
An open excision biopsy was performed. Histopathology from the mass lesion showed a lobulated tumor separated by fibrous strands. The cells were arranged in sheets, lobules and cords, dispersed in abundant myxoid stroma. Typical physaliphorous cells were present, along with scattered highly pleomorphic cells with large bizarre nuclei (Figure 4).
Binucleated and multinucleated tumor giant cells were also seen. Mitosis was infrequent (<2/10 high power field). The tumor was locally infiltrative, invading the left paravertebral muscles. Left lateral resection margin was involved by the tumor. Immunohistochemistry (IHC) for pan-cytokeratin showed strong positivity. The histopathology and IHC hence confirmed our cytopathological diagnosis. The patient received radiation therapy of 6000 cGy over 5 weeks, and is now on regular follow-up with no recurrence at 8 months post surgery.
Subsequent histopathological examination in our case showed the characteristic architecture of chordoma, bearing lobules and cords of cells embedded in a myxoid matrix. In addition to physaliphorous cells, the aggressive nature of cells seen in cytology smears was also confirmed in histopathology. Mitotic figures were absent in the aspiration cytology smears from the tumor. In a study by Crapanzano et al mitotic figures were rarely observed in cytology smears of chordoma[9]. Ng et al reported a case of dedifferentiated or sarcomatoid sacral chordoma, where spindle and pleomorphic cells were mitotically inactive[6]. Other than cytological features of dedifferentiation, adverse prognostic factors are represented by large tumor size, positive surgical margins, necrosis and high proliferative activity[10]. In our case the tumor size was 8 x 8.2 cm, with invasion of paravertebral muscles and destruction of the sacrum, along with positive resection margins. However, necrosis was absent and assessment of proliferative activity was not possible in our setup although it would have been useful. Immunohistochemically the neoplastic cells are reactive for S 100 protein, cytokeratin and epithelial membrane antigen, but usually negative for carcinoembryonic antigen[3]. In the present case, we have excluded adenocarcinoma by cytopathology and histopathological examination of the resected tumor. Strong positivity for cytokeratin in this case excluded the possibility of chondrosarcoma and other myxoid sarcomas.
The main differential diagnosis in our case was from a welldifferentiated chondrosarcoma. Other tumors that should be considered in differential diagnosis on cytopathology include metastatic clear cell carcinoma, especially renal cell carcinoma or mucin producing adenocarcinoma, myxoid liposarcoma and myxoid malignant fibrous histiocytoma (MFH)[2,11]. In low-grade chondrosarcoma, the aspiration cytology smears show cells in lacunae in a cartilaginous matrix, along with binucleation, multinucleation and few pleomorphic, hyperchromatic nuclear forms. The diagnosis of chordoma was preferred over chondrosarcoma in this patient as the physaliphorous cells were identified, and in a few areas the myxoid matrix was seen encircling the tumor cells individually (Figure 3). Abundant ground substance of chordoma may be inconspicuous in hematoxylin and eosin or Papanicolaou-stained smears and the epithelial like tumor cells may give a false impression of an epithelial neoplasm[11]. Giemsa-stained smears of this case showed deep magenta colored myxofibrillary ground substance, that excludes the possibility of a clear cell adenocarcinoma (Figure 2). FNAC has proven to be a useful tool in the diagnosis of adult myxoid sarcomas[12]. Myxoid liposarcoma show characteristic lipoblasts with scalloped nuclei and vacuolated cytoplasm along with a delicate branching capillary network against a myxoid background[13,14]. The myxoid variant of MFH displays a mixture of atypical spindle cells, pleomorphic histiocyte-like cells and multinucleated cells in an abundant myxoid background, often containing a curved vessel fragment[15,16]. These features were not present in our case.
To conclude, the cytomorphological features of chordoma allow accurate diagnosis by FNAC. Features associated with dedifferentiation or anaplasia include increasing pleomorphism, a prominent nucleolus, binucleation and presence of multinucleated bizarre giant cells. Recognition of these anaplastic features helps to expand the morphological spectrum of chordoma and differentiate from chondrosarcoma, clear cell adenocarcinoma or other myxoid sarcomas at the preoperative stage.
1) Bohra M, Mogra N, Patni A, Sujnani S: Diagnostic aspiration
cytology of sacral chordoma. J Cytol 2007, 24:60
2) Akerman M: Benign and Malignant Tumours of Bone. In Gray W,
Mckee GT. (Eds): Diagnostic Cytopathology. 2nd ed., Edinburgh,
Elsevier Churchill Livingstone, 2003, 924-925
3) Rone R, Ramzy I, Duncan D: Anaplastic sacrococcygeal
chordoma. Fine needle aspiration cytologic findings and
embryologic considerations. Acta Cytol 1986, 30:183-188 [ Özet ]
4) Nijhawan VS, Rajwanshi A, Das A, Jayaram N, Gupta SK: Fineneedle
aspiration cytology of sacrococcygeal chordoma. Diagn
Cytopathol 1989, 5:404-407 [ Özet ]
5) Lin O, Zakowski MF: Cytology of Soft Tissue, Bone and Skin. In
Bibbo M, Wilbur D. (Eds): Comprehensive Cytopathology. 3rd
ed., Philadelphia, Elsevier Saunders, 2008, 493-500
6) Ng WK, Tang V: Crush preparation findings of “sarcomatoid”
chordoma of the sacrum: report of a case with histologic,
immunohistochemical, and ultrastructural correlation. Diagn
Cytopathol 2001, 25:406-410 [ Özet ]
7) Layfield LJ, Liu K, Dodd LG, Olatidoye BA: “Dedifferentiated”
chordoma: a case report of the cytomorphologic findings on fineneedle
aspiration. Diagn Cytopathol 1998, 19:378-381 [ Özet ]
8) Hanna SA, Tirabosco R, Amin A, Pollock RC, Skinner JA,
Cannon SR, Saifuddin A, Briggs TW: Dedifferentiated
chordoma: a report of four cases arising ‘de novo’. J Bone Joint
Surg Br 2008, 90:652-656 [ Özet ]
9) Crapanzano JP, Ali SZ, Ginsberg MS, Zakowski MF: Chordoma:
a cytologic study with histologic and radiologic correlation.
Cancer 2001, 93:40-51 [ Özet ]
10) Rosai J: Rosai and Ackerman’s Surgical Pathology. 9th ed., St.
Louis, Missouri, Elsevier Mosby, 2004, 2183-2185
11) Akerman M: Bone. In Orell SR, Sterrett GF, Whitaker D. (Eds):
Fine Needle Aspiration Cytology. 4th ed., Edinburgh, Elsevier
Churchill Livingstone, 2005, 441-442
12) Kilpatrick SE, Ward WG, Bos GD: The value of fine-needle
aspiration biopsy in the differential diagnosis of adult myxoid
sarcoma. Cancer 2000, 90:167-177 [ Özet ]
13) Akerman M, Rydholm A: Aspiration cytology of lipomatous
tumors: a 10-year experience at an orthopedic oncology center.
Diagn Cytopathol 1987, 3:295-302 [ Özet ]
14) Walaas L, Kindblom LG: Lipomatous tumors: a correlative
cytologic and histologic study of 27 tumors examined by fine
needle aspiration cytology. Hum Pathol 1985, 16:6-18 [ Özet ]
15) Walaas L, Angervall L, Hagmar B, Säve-Söderbergh J: A
correlative cytologic and histologic study of malignant fibrous
histiocytoma: an analysis of 40 cases examined by fine-needle
aspiration cytology. Diagn Cytopathol 1986, 2:46-54 [ Özet ]
16) Merck C, Hagmar B: Myxofibrosarcoma: a correlative cytologic
and histologic study of 13 cases examined by fine needle aspiration
cytology. Acta Cytol 1980, 22:137-144 [ Özet ]