Merkel cell carcinoma of the parotid gland associated with Warthin tumour: report of two cases.

AIMS: Two cases of Merkel cell carcinoma occurring simultaneously and in close association with a Warthin tumour of the parotid gland are reported. METHODS AND RESULTS: The patients were a 65-year-old man and a 70-year-old man, respectively. The Merkel cell carcinoma component was immunoreactive for chromogranin and keratin 20 and contained neuroendocrine-type granules at the ultrastructural level. CONCLUSIONS: The histogenesis of this heretofore undescribed combination is discussed.

Mucoepidermoid carcinoma arising in Warthin's tumour of the parotid gland: report of two cases with histopathological, ultrastructural and immunohistochemical studies.

AIMS: Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland. METHODS AND RESULTS: Two cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and SalylTn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT. CONCLUSIONS: Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.

Immunocytochemical study of pituitary oncocytic adenomas.

Using immunocytochemistry we have analyzed 8 pituitary oncocytomas, 14 null cell adenomas, and 2 oncocytomas of the parotid gland (Warthin's tumor). The proportions of adenoma cells that are positive for mitochondrial protein (MP), cytochrome oxidase (COX), and manganese-superoxide dismutase (Mn-SOD) were significantly higher in pituitary oncocytomas than in null cell adenomas (MP P < 0.001, COX P < 0.001, Mn-SOD P < 0.05). In pituitary oncocytomas, MP-positive cells were distributed unevenly but in clusters or in islets admixed with some MP-negative cells, and corresponded to COX-positive cells. In contrast, almost all of the oxyphilic epithelial cells of Warthin's tumor were positive for MP, COX, and Mn-SOD. On the other hand, both pituitary tumors displayed similar findings with regard to the proportion of adenoma cells immunoreactive for copper/zinc-SOD and adenohypophysial hormones, the Ki-67 (MIB-1) proliferating cell index, and the mean number of argyrophilic nucleolar organizer regions. It was confirmed that immunocytochemical identification of MP and COX is useful for distinguishing pituitary oncocytomas from null cell adenomas. Although it remains to be determined whether oncocytomas originate from oncocytic changes of tumor cells or from neoplastic transformation of oncocytic cells, it appears that tumorigenesis of pituitary oncocytomas differs from that of Warthin's tumor.

Cystadenolymphoma of the parotid gland an immunohistochemical study of the epithelial component of twenty cases.

Carcinoembryonic antigen, epithelial membrane antigen, Keratin, Desmin, Vimentin, CD30, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 protein, somatostatin and glucagon were looked for using immunohistochemical methods in the epithelial component of 20 parotid gland cystadenolymphomas and 20 normal parotid glands. Carcino-embryonic antigen, ephithelial membrane antigen, S-100 protein, and somatostatin were found in the epithelial cells of most of the cystadenolymphomas. In normal parotid tissue, carcinoembryonic antigen, epithelial membrane antigen, Keratin, alpha 1-antitrypsin, alpha 1-antichymotrypsin, and S-100 protein were found in all three types of ductal cells, somatostatin only in intercalated and striated ductal cells, and lysozyme only in acinar and intercalated ductal cells. Desmin and CD30 were found in the epithelial component of seven of the 20 tumors versus none of the 20 normal parotid glands. Glucagon and Vimentin were negative both in tumor epithelial cells and in normal parotid ductal cells. Our results support the theory that cystadenolymphomas arise from epithelial cells. The presence of lysozyme in the epithelial tumor cells and in the intercalated ductal cells of normal parotid tissue suggest that cystadenolymphomas may arise from the intercalated ducts. The presence of S-100 and somatostatin may indicate that the tumor derives from neuroendocrine structures, but further studies are needed to clarify this point.

Epidermoid carcinoma arising in Warthin's tumour: a case study.

We present a case of epidermoid carcinoma arising in Warthin's tumour of parotid gland in an 80-year-old woman. Light microscopy revealed small foci typical of benign Warthin's tumour with transition to epidermoid carcinoma. Immunohistochemical and ultrastructural observations confirmed the epidermoid features of the malignant cells. The differential diagnosis of a metastasis from an epidermoid carcinoma to the stroma of Warthin's tumour and also of the so-called metaplastic variant of Warthin's tumour is discussed.

Luminal epithelium of Warthin's tumours: a scanning electron microscopic study.

Three cases of papillary cystadenoma lymphomatosum were examined by light and scanning electron microscope to declare the morphology of the luminal epithelial surface. It was found that ciliated cells were present in one case. This finding explains the origin of ciliated cells as a development included in the neighbouring lymph node with a tendency of metaplastic change and exfoliation.

Rare expression of the c-erbB-2 oncoprotein in salivary gland tumors: an immunohistochemical study.

An immunohistochemical study of c-erbB-2 oncoprotein expression was carried out on 201 cases of primary salivary gland tumors, using a polyclonal antibody, raised to the intracytoplasmic domain of the c-erbB-2 oncogene product. An intense membrane reactivity was observed in one case of sialocarcinoma transformed from pleomorphic adenoma (n = 8) and one case of mucoepidermoid carcinoma (n = 22). A comparative histopathologic evaluation of c-erbB-2 positive tumors showed marked variation in cell size, nuclear pleomorphism, multinucleation, a high mitotic rate and increased lymphoid cell infiltration and an aggressive clinical course with poor survival. The results indicate that c-erbB-2 oncoprotein is rarely expressed in malignant salivary gland tumors. However, the overexpression appears to have a distinct histopathologic feature, but a larger study incorporating histopathology and clinical data would be necessary to correlate the significance of c-erbB-2 oncogene product in salivary malignant tumors.

False aneuploidy in benign tumors with a high lymphocyte content: a study of Warthin's tumor and benign thymoma.

The quality of results of flow cytometric DNA content analysis of formalin-fixed, paraffin-embedded tissue may be affected by a number of preanalytical variables. We performed flow cytometric DNA content analysis on two types of benign tumors to investigate the effect of a prominent lymphocytic component: Warthin's tumor (N = 20) and benign thymoma (N = 8). Malignant tumors (N = 23) were included as DNA aneuploid controls. All tissues studied were archival material processed using Hedley's technique either without prolonged rehydration in water (day 0 samples) or with 24- or 48-hour rehydration (day 1 and day 2 samples, respectively). Image cytometric DNA ploidy analysis was also performed on most cases. Eight cases (40%) of Warthin's tumor and five cases (63%) of benign thymoma showed either hyperdiploid peaks or marked asymmetry on the day 0 DNA histograms; nine of the malignant tumors were aneuploid. The DNA histogram abnormalities of the benign tumors could be gated out by excluding the lymphocyte nuclei. None of the DNA indices of the benign tumors corresponded with expected deviations based on published chromosomal studies. All of the DNA histogram abnormalities of the benign tumors disappeared and/or fused with the main peaks on the day 1 or day 2 samples, except for one case of benign thymoma. All the DNA aneuploid peaks on the malignant tumors persisted with prolonged rehydration. Image cytometric DNA analysis showed a diploid pattern in all benign tumors. We conclude that a high lymphocyte content may be a cause of false aneuploidy in these benign tumors. Furthermore, the degree of rehydration appears to be an important factor in achieving optimum fluorochrome staining of DNA.

Malignant Warthin's tumour: a case study.

Malignant transformation of a benign Warthin's tumour (adenolymphoma) is extremely rare. The light microscopic and ultrastructural features of an adenocarcinoma arising in a Warthin's tumour in the parotid gland are described. Light microscopy demonstrated a transition zone from the benign to the malignant component, and the malignant cells revealed oncocytic features by both light- and electronmicroscopy.

Nuclear ultrastructure of human parotid gland tumors with special focus on nuclear bodies.

The purpose of our study was to determine the morphology and the proportion of NB in 20 human parotid gland tumors. Types I and III NB were observed in benign as well as malignant tumors. Some atypical forms ("onion-like" NB and NB with lipidic inclusions) were found in benign tumors. The proportion of nuclear profiles containing one and more NB varied from 0 to 60% in the benign tumors, and from 4 to 50% in the malignant tumors. Nuclei containing 3 and more NB were observed as well in the benign as in the malignant tumors. The NB ratio cannot be taken for a malignancy criteria.

[Ultrastructural study of adenolymphoma].

Ultrastructure of 10 adenolymphomas of parotid gland were studied. The neoplastic epithelium consists of "oncocytes" which are arranged in pseudostratified pattern. Their cytoplasm is almost totally packed with a large numbers of hypertrophic mitochondria showing a variety of peculiar forms. The amount and alteration of the mitochondria gradually increase in the order of pyramidal cell, common columnar cell and degenerated columnar cell. This might be a process of transposition representing degeneration due to metabolic disorder in the tumor. The obvious alterations of mitochondria are found in the cases with not only "hot" nodule but also "cold" nodule shown in the studies of 99mTc scintigraphy. There seems no relationship between "hot" nodule and alteration of mitochondria.

Ultrastructural study of mitochondria in oncocytes.

A number of mitochondria in oncocytes show pleomorphism by conventional electron microscopy. In an investigation of their stereostructure, specimens were obtained from 11 patients with Warthin's tumor, parts of which were used in the preparation of serial thin sections. It was revealed that cup-shaped and concentric ring forms of mitochondria resulted from invagination and that aberrant cristae such as the sheaflike and vesicular types were both derived from laminated cristae with vesicular structure.

Warthin's tumour in Jamaica. Incidence, electron microscopy and immunoenzyme studies.

Warthin's tumour has traditionally had a strong male association, and has been said to be rare in Blacks. Current studies describe a new trend; a rise in females, strongly linked to cigarette smoking. The tumour has eosinophilic epithelial cells packed with distinctive mitochondria, and a lymphoid stroma. Immunological investigations have demonstrated polyclonal B cells, T cells and macrophages. Views differ as to whether B or T cells predominate. Between 1958 and 1989, the Jamaica Cancer Registry recorded 491 benign and malignant salivary gland tumours. There were 18 cases of Warthin's tumour (3.7%), with a male: female ratio of 5:1. The low proportion of females is similar to the trend for female lung cancer in Kingston & St. Andrew. A case of Warthin's tumour was studied by light and electron microscopy and immunoenzyme methods. The epithelial cells contained numerous mitochondria with stacked cristae, as previously described. Similar morphology occurs in oncocytic tumours; riboflavin-deficient rats and mice; rats given non-lethal doses of hypoglycin; dogs treated with annatto extracts; and hibernating or starving frogs. The mitochondrial changes may be an adaptive response. The immunoenzyme studies utilized newly available monoclonal antibodies: UCHL1, L26, 4KB5, MT1 and LN2. The reaction patterns indicate a distribution of B and T cells in a manner expected in a lymph node. The interaction between mitochondrial changes, adaptive metabolic pathways, the immune cells and tobacco raises some interesting questions.

Coexpression of intermediate-sized filaments in sialadenoma papilliferum and other salivary gland neoplasms.

The neoplastic cells present in a sialadenoma pappiliferum were found by immunoperoxidase method and immunofluorescent staining technique to co-express 3 different types of intermediate-sized filaments (IFs) defined by monoclonal antibodies to cytokeratin, vimentin and desmin. When other salivary gland tumors such as 18 pleomorphic adenomas, 15 adenolymphomas, 2 oxyphilic adenomas, 7 mucoepidermoid tumors, 5 acinic cell tumors, 8 adenoid cystic carcinomas and 6 adenocarcinomas were examined immunohistochemically for the expression of IFs, no tumors with all 3 types of IFs observed in sialadenoma papilliferum were found.

Basal membrane associated substances in human salivary glands and salivary gland tumours.

Human salivary gland tissue was analysed with respect to the distribution of basal membrane associated substances. Collagen type IV and laminin were studied on the basis of monoclonal antibodies, fibronectin was analysed with polyclonal antibodies. The structure of the basal membrane was well preserved in normal salivary gland tissue. There was a continuous staining of the basal membrane around the acini and the ducts. The labelling for these substances appeared to be associated with the myoepithelial cells. Pleomorphic adenomas exhibited a heterogeneous pattern for the basal membrane substances. Focally, there was an augmentation of collagen IV and laminin, as well as of fibronectin. This was observed in the neighbourhood of myoepithelial like cells. Other parts of pleomorphic adenomas showed an interruption of the basal membrane. Adenoid cystic carcinomas displayed a clear staining of the basal membrane associated substances in the pseudocysts. Stromal trabeculae were stained in an irregular manner. Acinic cell tumours, adenocarcinomas, mucoepidermoid tumours and squamous cell carcinomas (for comparison taken from other regions in the head and neck area) presented a clear destruction of the basal membrane as visualized by antibodies against collagen IV and laminin. The study of the basal membrane substances may be helpful for identifying special features of salivary gland tumours and for grading the amount of invasive behaviour in the malignant tumours.

Warthin's tumor: an ultrastructural and immunohistochemical study of basilar epithelium.

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.

Scanning electron microscopic study of Warthin's tumor.

Three cases of Warthin's tumors were studied with a scanning electron microscope. The free surface of the epithelium was composed mainly of round or ovoid dome-like structures bearing microvilli and apocrine protrusions. Ciliated epithelial cells were detected in 2 of the tumors. The tumor epithelium encircled various amounts of cellular debris resembling degenerate lymphoid cells. A few tiny cystic spaces were also found. Within the lymphoid stroma, tightly packed lymphocytes, a meshwork of reticulum cells and medullary cord-like structures were observed. Our findings support the concept that Warthin's tumors develop from heterotopic salivary gland ducts within pre-existing lymph nodes.