Fine-Needle Aspiration Cytology of Carcinosarcoma of the Parotid Gland: Cytohistological and lmmunohistochemical Findings Manuel de la Torre, M.D., and Erik Larsson, M.D.

Carcinosarcoma or true malignant mixed tumor of salivary glands is a very rare neoplasm which shows malignant features of the epithelial and mesenchymal components. We hereby present cytological, pathological, and immunohistochemical findings of one such case, first examined by fine-needle aspiration cytology.

The aspirate was cell-rich and consisted of large cell clusters which at low magnijication showed an arrangement reminiscent of a jigsaw puzzle. An amorphous substance was observed in the middle of some of these clusters. There were also numerous dis- sociated cells which ofen displayed marked atypia. Histology showed a tumor with malignant epithelial and mesenchymal com- ponents. The carcinomatous areas consisted of cells arranged in solid nests or glandular structures. The sarcomatous areas showed osteosarcoma, low-grade chondrosarcoma, and undiyerentiated components. On immunohistochemistry, the tumor coexpressed epithelial and mesenchymal markers. Cytokeratin, keratin, and epithelial membrane antigen were mainly localized to the car- cinomatous portion, whereas vimentin and neuron-specijic enolase were restricted to the sarcomatous areas. S-100 protein was posi- tive in both. Our findings support previous views that this tumor may be related to pleomorphic adenoma. Diagn Cytopathol 1995;12:350-353. @ 1995 Wiley-Liss, Inc.

Key Words: Salivary glands; Needle aspiration; Immunohisto- chemistry

Fine-needle aspiration cytology (FNA) is routinely used in Scandinavia as a preoperative diagnostic method in tumors of the salivary glands. Carcinosarcoma (CS) or true malignant mixed tumor of the salivary glands is a very rare neoplasm which makes up only 0.2% of all malignant lesions of the salivary glands. ' The term malig- nant mixed tumor has usually been applied to neoplasms

Received October 29, 1993. Accepted May 5, 1994. From the Department of Pathology, University Hospital of Uppsala,

Uppsala, Sweden. Address reprint requests to Manuel de la Torre, M.D., Department of

Pathology, University Hospital of Uppsala, S-75 1 85 Uppsala, Sweden.

in which only the epithelial component shows malignant features. These neoplasms are commonly known as car- cinomas ex-pleomorphic adenoma. CS is a mixed heterologus neoplasm in which both the epithelial and the mesenchymal components display malignant features. Chondrosarcoma is the sarcomatous element which has most often been observed, and the epithelial component is a ductal carcinoma. 3-5

To our knowledge, there has been only one previous study in which cytologic findings in CS were illustrated. We hereby present cytological findings in a case of CS, along with a thorough immunohistochemical (IMH) anal- ysis.

Case Report An 83-yr-old woman reported to the ear, nose, and throat (ENT) department complaining of a rapidly enlarging right parotid tumor for the last 3 mo. She recalled having a small nodule in the same area for about 30 years. She gave no history of radiation to this region or weight loss. ENT exploration remained without any positive findings. Physical examination of the right parotid gland region revealed a 10 x 8-cm soft nodule. FNA of the mass was performed. Smears were air-dried and stained by May-Griinwald-Giemsa (MGG) method. Surgical exci- sion of the lesion was performed. The tumor was extir- pated along with surrounding tissues. The patient recov- ered uneventfully but died of the tumor 1 yr after the surgical intervention. The patient had local recurrence of the tumor and lung metastasis, as evidenced by roent- genography.

FNA Findings The FNA aspirate contained a very cellular material con- sisting of large clusters which at low magnification showed an arrangement reminiscent of a jigsaw puzzle. An amor-

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phous substance was observed in the middle of some clus- ters. Many isolated dissociated atypical cells showing large irregular nuclei were also seen (Figs. 1,2). The cyto- logical diagnosis was consistent with malignancy.

differentiated fibrosarcoma or neurofibrosarcoma were ob- served. The undifferentiated areas were predominantly in the sarcomatous portion and showed abundant mitotic activity. No remnants of benign pleomorphic adenoma were found.

Pa thology The tumor was received in two pieces. The largest mesured 10 X 8 X 5 cm and the smallest 3 X 3 X 3 cm. The tumor was poorly circumscribed, had a gelatinous appearance and a gray or yellow cut surface with hemor- rhagic foci. By microscopic examination, the tumor showed a polymorphous picture, composed of intermin- gled carcinomatous and sarcomatous areas (Fig. 3). The carcinomatous portion consisted of well-defined adeno- carcinoma elements showing tubular structures with open luminae. There were also solid nests of malignant cells often with central necrosis and intercellular bridging, but without convincing keratin production.

Immunohistochemistry The immunohistochemical (IMH) data are summarized in Table I. The IMH study was performed on formalin-fixed, paraffin-embedded tissue sections using a panel of mono- clonal or polyclonal antibodies, including cytokeratin, keratin, epithelial membrane antigen (EMA), neuron-spe- cific enolase (NSE), protein S- 100, a,-antitrypsin (A- 1-A), 1 ysozyme, carcinoembryonic antigen (CEA), desmin, my- oglobin, smooth muscle actin (SMA), and vimentin. The antibodies were all obtained from Dakopatts with the ex- ception of keratin (Boehringer-Mannheim) and myoglo- bin (Sigma, St. Louis, MO).

The sarcomatous portion was diverse in composition. Osteosarcoma (Fig. 3), low-grade chondrosarcoma (grade I or 11), and undifferentiated areas reminiscent of poorly

Immunohistochemical Findings The epithelial markers, including cytokeratin, keratin, and EMA, were extensively expressed in the car-

Fig. 1. Carcinosarcoma aspirate showing part of a cell cluster with rather loose stromal core. Some cells with anisokaryosis can be seen in the periphery (MGG, X400).

Fig. 2. Cytologic smear ofcarcinosarcorna: Note some dissociated atypi- cal cells with large irregular nuclei (MGG, ~ 4 0 0 ) .

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Fig. 3. Carcinosarcoma section. A: Undifferentiated sarcomatous component. B: A malignant infiltrating gland surrounded by compact dense stroma. C Malignant cells intermingled with rather dense osteoid substance (H&E, ~ 4 0 0 ) .

cinomatous portion of the tumor (Fig. 4). EMA was often observed at the luminal apical cell portion and inside the lumina of malignant tubuli. S-100 expression occurred both in adenocarcinomatous and chondrosar- comatous areas. Some expression of cytokeratin and keratin was observed in sarcomatous areas. The undif- ferentiated sarcomatous region expressed vimentin ex- tensively. It also showed moderate NSE immunoreac- tivity. A- 1-A staining was observed in the chondromatous stroma adjacent to the malignant glands. CEA, desmin, myoglobin, SMA, and lysozyme were all negative.

Discussion Carcinosarcoma of the salivary gland is a very rare neo- plasm. ' , * s 5 In the study of Stephen et al., which consisted of 12 cases (probably the hrgest series), the most common malignant mesechymal component was a chondrosar- coma, identified in ten cases. This has been confirmed by some other reports. 3,6-8 Other components previously de- scribed include fibrosarcoma, malignant fibrous histiocy- toma, and/or myxosarcoma. The occurrence of osteo- sarcoma in CS has previously been documented in three histological reports. 9-1 In the present study, we observed some areas with malignant cells featuring immature oste- oid (Fig. 3), indicating osteosarcoma. Furthermore, some areas resembling well-differentiated chondrosarcoma and other foci showing undifferentiated sarcoma reminiscent of poorly differentiated fibrosarcoma or neurofibrosar- coma were also identified. The possible association of this case with pleomorphic adenoma is suggested by the clini- cal history, since no residual remnants of such tumor could be demonstrated. The value of FNA in the diagnosis

of salivary gland masses has been well established along with the primary role of FNA in the preoperative evalua- tion of these lesions. ',I2-l5

Cytological findings in CS have been illustrated, to our knowledge, on only one previous occasion. There was no IMH analysis of that case. These authors obtained a yield consisting of chondrosarcomatous cells mixed with sheets of cohesive nonkeratinizing cells with spindle-shaped or pleomorphic nuclei. The cell yield obtained in the present case may have been obtained from the predominantly un- differentiated sarcomatous component of this tumor. Re- markable individual cell atypia warranted a diagnosis of malignancy. According to the cytological picture observed

Table I. Irnmunohistochemical Data

Carcinomatous Sarcomatous

Adenoca. Solid Chondro. Osteo. Undiff

Cytokeratin Keratin EMA CEA NSE s-100 A- 1 -A Lysozyme Desmin Myoglobin - - - - -

SMA - - - - -

3 Vimentin -

aSymbols and abbreviations: The positively immunostained cells for each particular histological area were represented in percentages as follows: 1, 1-10%; 2, 11-30%; 3, 31-60%; 4, more than 60% positive cells. f, A- 1 -A was focally positive in the stroma surrounding carcinomatous glands; SMA, smooth muscle actin.

- - -

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in this case, the differential diagnosis one has to consider includes primary sarcoma or secondary malignancy.

IMH investigation of this case showed coexpression of epithelial and mesenchymal markers. Positive vimentin immunoreactivity was observed only in the “undifferenti- ated” sarcomatous areas. The carcinomatous nests re- acted positively to cytokeratin but not to vimentin. In one of three previous reports of CS with osteosarcoma, IMH investigation was performed. Those authors observed that the epithelial component stained for keratins and the sarcomatous areas for vimentin, whereas neither compo- nent reacted for S - 100 protein.

The IMH findings of the present study (coexpression of epithelial and mesenchymal markers, the distribution of EMA in the luminal part of the malignant glands, and the distribution of S-100 in both the carcinomatous and sar- comatous areas) are in accordance with the IMH observa- tions by others, 1,3,4,16 who have suggested that this tumor may be derived from pleomorphic adenoma.

Acknowledgments We are indebted to Mrs. Ewa Wahlund and Maj-Lis Book for excellent technical assistance and to Dr. Ahmad Ata for linguistic revision.

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