Anatomic Pathology / SARCOMATOID SALIVARY DUCT CARCINOMA

Salivary duct carcinoma (SDC) is an uncommon, high-grade tumor. We present 8 cases of sarcomatoid SDC, which has been defined recently as a rare variant of SDC. The 8 patients (5 men, 3 women) had a mean age of 63.6 years. Histologically, all tumors were characterized by a biphasic neoplasm composed of both SDC and sarcomatoid elements. In 3 cases, sarcomatoid components showed osteosarcomatous heterologous differentiation. A residual pleomorphic adenoma was detected in 5 tumors. The sarcomatoid component showed focal immunoreactivity for cytokeratin in 4 cases and epithelial membrane antigen in all 8 cases. Diffuse p53 immunostaining was detected in 3 cases, and it was coexpressed in both components. Our observations support the histogenetic theory of a common origin of the carcinomatous and sarcomatoid populations. Of the 13 patients, including our 8, reported to have sarcomatoid SDC arising in a major salivary gland and for whom long-term follow-up data were available, 7 have died of disease (mean survival, 15.6 months). These results indicate that sarcomatoid SDC is a highly aggressive tumor, similar to conventional SDC. Salivary duct carcinoma (SDC) is an uncommon, distinctive, high-grade malignant tumor that arises predominantly in a major salivary gland.1-3 Kleinsasser et al4 originally described this entity in 1968, and it was included in the second version of the World Health Organization classification of salivary gland tumors.5 Histologically, SDC bears a striking resemblance to ductal carcinoma of the breast, with intraductal and invasive components. The intraductal component is described as a cribriform, papillary, or solid growth pattern, often with comedolike central necrosis. The invasive carcinoma consists of irregular glands and cords of cells that frequently elicit a prominent desmoplastic reaction. SDC can occur de novo or as the malignant component of carcinoma ex pleomorphic adenoma.6 Several histologic variants of SDC have been described, including documentation of their biologic behavior.7-9 Sarcomatoid SDC has been defined recently as one of these variants, characterized histologically by a biphasic neoplasm with SDC and sarcomatoid elements.9 Although only 4 cases have been reported as sarcomatoid SDC,9,10 we have identified several additional cases that were termed carcinosarcoma or true malignant mixed tumor in earlier reports.11-17 The clinicopathologic and immunohistochemical characteristics of these tumors have not been well defined. In the present study, we documented the clinicopathologic and immunohistochemical features of 8 cases of sarcomatoid SDC. In addition, we attempted to clarify the diagnostic criteria of this neoplasm and its possible histogenesis. Materials and Methods We identified 8 cases of the sarcomatoid variant of SDC from the pathology files of Mayo Clinic, Rochester, MN Anatomic Pathology / ORIGINAL ARTICLE Am J Clin Pathol 2004;122:222-231 223 223 DOI: 10.1309/5J4008QRY1HWW5W4 223 © American Society for Clinical Pathology (cases 1-3), and Tokyo Medical University Hospital, Tokyo, Japan (case 4), and the consultation files of the authors (T.N., cases 5 and 6; J.E.L., cases 7 and 8). The 8 cases fulfilled the criteria for sarcomatoid SDC defined by Henley et al,9 except for the presence of heterologous differentiation in several of our cases. Tumor tissue samples were fixed in 10% buffered formalin, processed by routine histologic techniques, and stained with H&E. From the slides available for each case, the percentage of carcinomatous and sarcomatoid zones in the primary lesion was estimated semiquantitatively and expressed as a percentage of the surface area involved. Clinical details and follow-up data were obtained when possible from medical records, referring pathologists, and treating physicians. Formalin-fixed, paraffin-embedded tissue samples from the primary tumors were available for immunohistochemical staining in 7 of 8 cases. In 1 case, only the recurrent sarcomatoid neoplasm was available for this analysis. The deparaffinized and rehydrated slides were stained immunohistochemically using the labeled streptavidin-biotin peroxidase method with an automated immunostainer (Ventana, Tucson, AZ). To enhance immunostaining, a heat epitope retrieval procedure or enzyme digestion method was performed. The primary antibodies used are listed in ❚Table 1❚. The antigen-antibody reaction was visualized with the chromogen 3,3'-diaminobenzidine. The sections were lightly counterstained with hematoxylin. The cases were regarded as positive for HER-2/neu when staining of the membrane or of both the membrane and cytoplasm was positive in more than 10% of tumor cells. A lesion was considered p53-positive when more than 10% of tumor cell nuclei showed strong reactivity. The percentage of Ki-67–positive cells was determined by counting at least 1,000 tumor cells, and the value was recorded as the “Ki-67 labeling index.”