We regard sialolipoma as a distinct variant of salivary gland lipoma that can occur in both the major and minor salivary glands. Superficial parotidectomy, or surgical resection in the case of palatal tumours, is an appropriate treatment for this benign tumour.

Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated" carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.

Hybrid carcinomas of the salivary gland are a recently defined and rare tumor entity, consisting of two histologically distinct types of carcinoma within the same topographic area. In this study, we examined nine such cases, which mainly arose in the parotid gland (seven cases), with an additional one each from submandibular and lacrimal glands, and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The prevalence of hybrid carcinomas was 0.4% among the 1863 cases of parotid gland tumors in our series. The nine patients comprised five men and four women, ranging in age from 40 to 81 years (mean, 62 y). Tumor size ranged from 2 to 10 cm (mean, 4.2 cm). Of the seven patients who were followed up, two were alive with disease and five were alive with no evidence of disease, although the follow-up period was short. Three cases had cervical lymph nodal metastases. The combinations of carcinoma components in our hybrid carcinomas were as follows: epithelial-myoepithelial carcinoma and basal cell adenocarcinoma in two cases, epithelial-myoepithelial carcinoma and squamous cell carcinoma in one case, salivary duct carcinoma and adenoid cystic carcinoma in two cases, myoepithelial carcinoma and salivary duct carcinoma in one, acinic cell carcinoma and salivary duct carcinoma in one, and squamous cell carcinoma and salivary duct carcinoma in two. Although the proportion of each carcinoma component in a tumor mass varied from case to case, the minor component always represented >10% of the area. Differences in cellular composition were studied by immunohistochemistry and electron microscopy. The Ki-67-labeling index apparently differed between the two carcinoma elements in five cases. Diffusely positive p53 immunoreactivity was observed in four cases, restricted to the more aggressive component in each pair. Furthermore, p53 gene alteration analysis of these p53-positive cases revealed that all and three cases demonstrated loss of heterozygosity at p53 microsatellite loci and p53 gene point mutations, respectively, which were detected only in the p53-immunoreactive carcinoma component. Therefore, there is the possibility that such molecular-genetic events take an integral part for inducing the transformation from histologically lower to higher grade tumor during the hybrid carcinoma genesis of the salivary glands.

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Background. Although there have been a few reports dealing with the sarcomatous changes of intrahepatic cholangiocarcinoma, its clinicopathologic features as well as immunohistochemical nature remain obscure. Methods. Among 155 cases of intrahepatic cholangiocarcinoma, 7 cases of sarcomatous cholangiocarcinoma were chosen. Immunohistochemical studies using the avidin‐biotin‐peroxidase complex method were performed on these cases. Results. The tumor showed both mucin‐producing adenocarcinoma areas and sarcomatous areas, the latter being predominant in three cases and focal in the other four. All the sarcomatous areas consisted of atypical spindle cells arranged in sheets or bundles. Pleomorphic giant cells were observed in some sarcomatous components in five cases. Immunohistochemical staining for keratin and epithelial membrane antigen revealed apparent positivity in the sarcomatous components of five cases. The patients with these tumors showed aggressive intrahepatic spreading and widespread metastasis of the sarcomatous cells, and demonstrated poorer prognosis than those with ordinary cholangiocarcinoma, with one exception, a patient who remained disease‐free for 3 years after surgery. Conclusions. These findings favor the possible epithelial origin of sarcomatous cells. Radical operation would be necessary for patients with this special type of cholangiocarcinoma.

Nine cases of biliary cystadenocarcinoma of the liver were studied, with emphasis on its clinicopathologic features, mucin profiles, and immunohistochemical characteristics. In general, the cystic tumors had protrusions that consisted of well‐differentiated papillary adenocarcinoma cells with or without benign‐appearing epithelial elements. In invading or metastatic foci, the carcinoma cells tended to show distinctive anaplastic changes. Tumor growth was confined to the cystic lesions in five cases (noninvasive type), whereas in four cases it extended to the hepatic parenchyma or neighboring organs (invasive type). There was a considerable difference between the two groups in terms of prognosis. In fact, the patients included in the group with the noninvasive type had no sign of tumor recurrence after an appropriate surgical procedure. With mucin histochemical and immuno‐histochemical approaches, positive reactions with car‐cinoembryonic antigen, tissue polypeptide antigen, carbohydrate 19‐9, and Dupan‐2 and the predominance of sialomucin were observed in most cases of biliary cysta‐denocarcinoma, indicating a similar cellular nature of cholangiocarcinoma. Cancer 1992; 69:2426‐2432.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a newly proposed clinicopathologic entity; a few cases of LCNEC have been reported in other sites, such as the uterine cervix and the thymus. In the salivary glands, LCNEC is extremely rare and is not recognized as a specific entity in the World Health Organization classification. We retrospectively reviewed from our files 1675 cases of surgically resected primary parotid gland tumors and found 2 cases of LCNEC that fulfilled the criteria of pulmonary LCNEC. These cases occurred in 72-and 73-year-old men who had short histories of enlarging parotid gland tumors. The tumors were composed of large cells that exhibited organoid, solid, trabecular, and rosette-like growth patterns with a high mitotic rate and a conspicuous tendency for necrosis. The tumor cells were polygonal and characterized by a moderate nuclear:cytoplasmic ratio, coarse chromatin, and conspicuous nucleoli. Immunohistochemical examination revealed that the tumor cells were positive for six general neuroendocrine markers, cytokeratin, p53, bcl-2, epidermal growth factor receptor, and cyclin D1. Markedly reduced expressions of p21 Waf1 and p27 Kip1 were also noticed. The Ki-67 labeling index was more than 50% in both cases. One case showed loss of heterozygosity at TP53 accompanied by a p53 gene point mutation. Loss of heterozygosity at chromosome 9p21 was detected in both cases; one was accompanied by a p16 gene silent point mutation.Both patients died of the disease, with recurrence 5 months and 4 years after surgery, respectively. These findings indicate that LCNEC is a rare but distinct salivary gland tumor with highly aggressive biologic behavior. Multiple alterations of cell cycle regulators and tumor suppressor genes may play an important role in presenting the biologic characteristics of this rare parotid gland tumor.KEY WORDS: bcl-2, Cyclin D1, K-ras, Large-cell neuroendocrine carcinoma, p16, p27 Kip1

Benign salivary gland tumors composed of purely squamous cells are quite unusual and are not included in the World Health Organization classification. We have seen two benign parotid gland tumors characterized by multicystic spaces with stratified squamous linings and focal solid epithelial nests. Seifert et al. recently described such a case as a choristoma; we, however, herein propose a new designation, keratocystoma, for this unique tumor group, because of its distinctive histological features. These tumors occurred in men aged 18 and 38 years with enlarging parotid gland tumors. Both had largely similar gross and histological features, with some variations. The epithelium lining of the cysts showed apparent keratinization through a parakeratotic or orthokeratotic pathway without forming a granular cell layer. Stratification of the epithelium was always regularly oriented from the outer basal to the inner keratotic cell layer. Focally, the outer layer had bud-like protrusions. In some areas, solid squamous cell islands surrounded by basement membrane were enclosed within the collagenous stroma. These cystic and solid structures were randomly distributed, showing no definite lobular architecture. All of the tumor cells had uniform, bland nuclei and abundant eosinophilic cytoplasm. Scattered mitotic figures were observed, limited to the outer epithelial layer, and showed no abnormal patterns. Transformation from the parotid ductal epithelium to the tumor cells is evident.Foci of foreign-body reactions against keratin materials were present. Immunoreactivities for cytokeratins reconfirmed the nature of squamous differentiation of the tumor cells. Ki-67-positive cells were confined along the outer basal layer of the tumor epithelium. Tests for ␣-smooth muscle actin and S-100 protein were completely negative. Both patients had no evidence of recurrence 3 and 2 years after subtotal parotidectomy, respectively, without any additional therapy. We believe that this lesion represents a benign cystic neoplasm rather than a malignant tumor or pseudoneoplastic metaplastic condition. It is important to recognize that this peculiar benign tumor does originate from the salivary gland.