Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.

There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI]). The CRTC1-MAML2, but not CRTC3-MAML2 was detected in 5/15 mWT-like tumors. FISH-WSI results showed that all epithelial cells harbored the MAML2 split in fusion-positive mWT-like tumors and were totally negative in fusion-negative mWT-like tumors. A review of the hematoxylin and eosin-stained slides showed that morphology of the "metaplastic" epithelium was virtually indistinguishable between fusion-positive and fusion-negative tumors. However, oncocytic bilayered tumor epithelium, characteristic to typical WT, was always found somewhere in the fusion-negative tumors but not in the fusion-positive tumors. This distinguishing histologic finding enabled 5 pathologists to easily differentiate the 2 tumor groups with 100% accuracy. The age and sex distribution of fusion-positive mWT-like tumor cases was similar to that of fusion-positive MEC cases and significantly different from those of fusion-negative mWT-like tumor and typical WT cases. In addition, only fusion-positive mWT-like tumors possessed concurrent low-grade MECs. In conclusion, a subset of mWT-like tumors were positive for the CRTC1-MAML2 fusion and had many features that are more in accord with MEC than with WT. The term Warthin-like MEC should be considered for fusion-positive mWT-like tumors.

A more appropriate clinical classification of benign parotid tumors: investigation of 425 cases.

CONCLUSIONS: It is appropriate to clinically classify benign parotid tumors into three groups, i.e. superficial tumors, deep tumors, and lower pole tumors. OBJECTIVE: It is important to classify benign parotid tumors based on location when deciding the surgical strategy and conducting clinical research. In this study, we examined a classification of benign parotid tumors that was useful for clinical practice. METHODS: We studied 425 patients with benign parotid tumors who underwent surgery at our hospital. Their age, gender, tumor histopathology, maximum tumor diameter, postoperative facial nerve paresis, operating time, and blood loss were investigated after classifying the tumors as superficial tumors, deep tumors, or lower pole tumors. We also investigated the same parameters after dividing the lower pole tumors into superficial and deep types. RESULTS: Lower pole tumors had distinct characteristics from superficial and deep tumors. The incidence of facial nerve paresis was significantly higher and the operating time was significantly longer for deep tumors than for either superficial or lower pole tumors, while there were no significant differences between superficial and lower pole tumors. In addition, there were no significant differences in any of the parameters between the superficial and deep types of lower pole tumor.

Two-phase computed tomography study of warthin tumor of parotid gland: differentiation from other parotid gland tumors and its pathologic explanation.

OBJECTIVE: The objective of this study was to define the radiological characteristics of 2-phase computed tomography (CT) of parotid gland Warthin tumors (WTs) with a pathologic basis for these findings. METHODS: We prospectively enrolled 116 patients with parotid gland tumor who underwent preoperative 2-phase CT scans(scanning delays of 30 and 120 seconds). The attenuation changes and enhancement patterns were analyzed according to pathology. We also evaluated size-matched samples of WTs and pleomorphic adenoma by staining CD31, vascular endothelial growth factor-receptor 2, collagen IV, and smooth muscle actin. RESULTS: Computed tomography numbers in WTs were significantly higher than those in other tumors in early-phase scans and lower in delayed scans. Pathologically, CD31(+) blood vessel area was significantly higher in WTs than in pleomorphic adenomas. In addition, WTs had an extensive capillary network and many leaky blood vessels. CONCLUSIONS: The enhancement pattern of early fill-in and early washout is the typical finding of WTs on 2-phase CT scans, which may be attributed pathologically to abundant blood vessel and extensive capillary network.

The metaplastic variant of Warthin tumor of the parotid gland: dynamic multislice computerized tomography and magnetic resonance imaging findings with histopathologic correlation in a case.

Metaplastic Warthin tumor is a rarely seen subtype of Warthin tumor. It can resemble squamous carcinomas histopathologically, because it contains atypical squamous cells on the necrotic surface. Making a diagnosis can become easier by knowing this entity of Warthin tumor well and by correlating the radiologic findings with pathology. In this case presentation, imaging features of a metaplastic Warthin tumor are presented together with its histopathologic findings. When a solid mass with peripheral enhancing cystic-necrotic component and well defined contour and capsule that shows early enhancement and washout is identified with imaging methods in parotid gland, metaplastic Warthin tumor should be indicated in the differential diagnosis before the histopathologic evaluation.

Lymphadenoma of parotid gland: Two additional cases and a literature review.

For classification purposes, proper identification of infrequent and unique salivary gland tumors requires the gradual accumulation of a sufficient number of cases. Lymphadenoma (i.e., an adenomatous, generally parotid-based lesion with an exaggerated lymphocytic infiltrate, but a lack of sebaceous differentiation) has approximately 9 reported cases. This report adds 2 additional cases occurring as a discrete, at least partially encapsulated nodule in the parotid gland. Embedded within the extensive lymphocytic component were isolated nests of solid or glandular epithelium, with 1 case displaying a few foci of chondrocytic differentiation. Immunohistochemical investigation of the latter case revealed the presence of both luminal and myoepithelial cells.

A trial for histopathological subclassification of papillary cystadenoma lymphomatosum by 99Tcm-pertechnetate in a patient with multiple bilateral lesions of the parotid glands.

OBJECTIVES: The purpose of this report was to evaluate the possibility of subclassification of papillary cystadenoma lymphomatosum (PCL) with 99Tc(m)-pertechnetate. METHODS: A patient with multiple bilateral PCLs in the parotid glands was examined by using 99Tc(m)-pertechnetate. RESULTS: All PCLs of the present case, which were diagnosed as the subtype-II histopathologically, showed similar radioactive indexes in scintigraphy (the mean radioactive index = 3.62), although tumours were different in size. The mean radioactive index corresponded well with that from four cases of subtype-II of our previous report (the mean radioactive index = 3.84). CONCLUSIONS: The results of the present report suggest a possibility of histopathological subclassification of PCLs into subtypes by 99Tc(m)-pertechnetate scintigraphy.

Warthin's tumor of parotid gland on Tc-99m pertechnetate scintigraphy with lemon juice stimulation: Tc-99m uptake, size, and pathologic correlation.

The aim of this study was to evaluate the usefulness of technetium-99m (Tc-99m) pertechnetate scintigraphy with lemon juice stimulation in the diagnosis of Warthin's tumor and its correlation with Tc-99m uptake, tumor size, and histologic subtype. Tc-99m pertechnetate scintigraphy before and after lemon juice stimulation and pathologic specimens of 34 Warthin's tumors and 47 non-Warthin's lesions were retrospectively evaluated. Tc-99m uptake of Warthin's tumors before and after stimulation was visually graded as follows: absent; indeterminate; low grade; definite; and strong. Tumor size was defined as maximum diameter of the tumor measured from the surgical specimen. Warthin's tumors were classified into three histologic subtypes according to the ratio of epithelial and lymphoid stromal components: predominant epithelial; intermediate; and low-grade epithelial types. Eighteen of 34 (53%) Warthin's tumors and one benign lymphoepithelial cyst showed higher uptake than that of the normal parotid gland on Tc-99m scintigraphy before lemon juice stimulation. Thirty-two of the 34 (94%) Warthin's tumors, one benign lymphoepithelial cyst, one pleomorphic adenoma, and one oncocytoma revealed higher uptake than that of the normal parotid gland on Tc-99m scintigraphy after lemon juice stimulation. The mean size was 37 mm in strong uptake Warthin's tumors, 24 mm in definite uptake tumors, 19 mm in low-grade uptake tumors, and 12 mm in low-grade uptake tumors excluding those tumors with large cystic component. There was a significant correlation between tumor size and degree of Tc-99m uptake after lemon juice stimulation. However, there was no correlation between histologic subtype and Tc-99m uptake, and histologic subtype and tumor size in Warthin's tumors. Our study concludes that Tc-99m pertechnetate scintigraphy with lemon juice stimulation is useful for the detection and diagnosis of Warthin's tumor. The degree of uptake in Warthin's tumor on Tc-99m scintigraphy with lemon juice stimulation depends mainly on tumor size and the presence of large cystic component in it.

Immunohistochemical comparison of cutaneous lymphadenoma, trichoblastoma, and basal cell carcinoma: support for classification of lymphadenoma as a variant of trichoblastoma.

Cutaneous lymphadenoma is an uncommon basaloid epithelial tumor of uncertain histogenesis, most recently classified as a variant of trichoblastoma. Because characteristic immunohistochemical findings have been reported in trichoblastomas, we evaluated the staining patterns of five cutaneous lymphadenomas and compared the results to those of ten trichoblastomas and ten nodular basal cell carcinomas (BCCs), using antibodies to cytokeratin 20 (CK20), bcl-2, and CD34. In addition, because lymphadenomas contain intraepithelial S100-positive putative Langerhans cells, we compared staining of all tumor groups for S100 protein and CD1a. We also attempted to corroborate recent reports of CD30-positive activated lymphocytes in lymphadenomas. We identified CK20-positive Merkel cells in 3/5 lymphadenomas, 7/10 trichoblastomas, and none of the BCCs. Staining for bcl-2 accentuated the peripheral epithelial layer in all lymphadenomas and in 3/10 trichoblastomas, while the remaining trichoblastomas and all BCCs stained diffusely. There was stromal staining with CD34 in two lymphadenoma, 4 trichoblastomas, and 3 BCCs. All lymphadenomas featured numerous intraepithelial S100-positive cells which were also positive for CD1a in three cases tested. In addition, 8/10 trichoblastomas and 2/10 BCCs contained modest numbers of cells labelling for S100 and CD1a. Two of three lymphadenomas contained rare single cells resembling histiocytes faintly positive for CD30, and similar cells labelled for CD68. We conclude that the similar staining patterns of lymphadenomas and trichoblastomas support the classification of lymphadenoma as a variant of trichoblastoma. Staining with CD34 does not reliably distinguish between these tumors and BCCs. Lymphadenomas, trichoblastomas, and BCCs may all contain Langerhans' cells. The relationship between these cells and the striking lymphoid infiltrates seen in lymphadenomas is not clear. In our cases, the CD30-positive cells in lymphadenomas appear to represent histiocytes rather than activated lymphocytes.

Image cytophotometric DNA analysis of cystadenolymphomas.

Warthin's tumour of the parotid gland is generally a benign lesion, consisting of an epithelial and a lymphoid component with unclear histogenetic relationship, 17 cases of Warthin's tumour were investigated for ploidy related parameters by the image analysis system CAS200. All cases investigated were euploid. A diploid DNA pattern (Auer type I) was detected in 7/17 (41%) cases both in the epithelial and lymphoid component of the same tumour. In addition to a diploid cell fraction a tetraploid cell component was found in 7/17 (41%) cases, coincidentally, in the epithelial and lymphoid component (Auer type II). Euploidy in all investigated cases is in agreement with the generally benign nature of Warthin's tumours. The similarity of the DNA pattern (Auer type) in the genetically unrelated epithelial and lymphoid components in most cases (84%) is suggested to be related to a similar functional state of these two components and is discussed in relation to the histogenesis of cystadenolymphomas.

[Carcinoma in pre-existing Warthin tumors (cystadenolymphoma) of the parotid gland. Classification, pathogenesis and differential diagnosis]. / Karzinome in vorbestehenden Warthin-Tumoren (Zystadenolymphomen) der Parotis. Klassifikation, Pathogenese und Differentialdiagnose.

Malignant transformation of pre-existing Warthin tumours of the parotid gland in carcinomas is very rare compared with the development of carcinomas in pre-existing pleomorphic adenomas. Five cases examined in the Salivary Gland Register of Hamburg 1965-1996 were classified in 2 cases as mucoepidermoid carcinoma and in each of one case as oncocytic carcinoma, squamous cell carcinoma and acinic cell carcinoma. In the pathogenesis the benign oncocytic epithelial formations at the surface of the cystic spaces are restricted by malignant neoplastic epithelial cells in the course of which transitions of squamous cell metaplasia or goblet cell metaplasia can be observed. In the further course an infiltrating spread of the carcinoma takes place into the lymphoid stromal component of the Warthin tumour, sometimes also an infiltration of the surrounding tissue und rarely to cervical lymph node metastases. The own findings are analysed concerning the classification of the carcinomas and the differential diagnosis under consideration of the until now reported cases of the literature.

Multiple tumours of the salivary glands--terminology and nomenclature.

Multiple tumours of the salivary glands are very rare and their combinations according to histological classification of the tumours, localisation and origin (origin in independent topographical areas or in the same tissue) are diverse. The following two categories can be distinguished: common occurrence of multiple salivary gland tumours with identical histology, or with different histology. In either group the tumours can be unilateral or bilateral, synchronous or metachronous. The most common multiple tumours with an identical histology are Warthin tumours and pleomorphic adenomas. Bilateral occurrence has been observed especially in oncocytomas, acinic cell carcinomas and basal cell adenomas. In the group of multiple tumours with differing histology, Warthin tumours and pleomorphic adenomas show a number of combinations with other adenomas or carcinomas of the salivary glands. Notable also is the simultaneous occurrence of salivary gland tumours with other oral tumours or extraglandular tumours, especially thyroid carcinomas and breast carcinomas. Multiple salivary gland tumours must be distinguished by nomenclature from tumours with biphasic differentiation and hybrid tumours. Tumours with biphasic differentiation are defined as regular, recurring mixtures of two cellular components in the same tumour and have a corresponding term in the tumour classification. Hybrid tumours are very rare and are composed of two different tumour entities within the same topographical area. Each of the tumour entities conforms with an exactly defined tumour category.

Morphometrical analysis of cystadenolymphoma (Warthin's tumor). Subclassification and characterization of the lymphoid stroma in comparison with gastric lymphoid follicles.

Morphometrical analysis was applied to cystadenolymphoma (Warthin's tumor, adenolymphoma: CAL). By quantitative analysis of tissue sections, the examined cases were divided into three subtypes according to the ratio of the lymphoid stroma (LS) to the whole tissue: type I "stroma-rich type", the LS of this type was more than 57% of the whole tissue; type II "typical type", the LS of this type was 37% to 56% of the whole tissue; and type III "stroma-poor type", the LS of this type was less than 36% of the whole tissue. The average age of the patients in subtypes I, II and III was 57.7, 68.0, and 62.4 years, respectively. The age of the patients with type I CAL was significantly lower than that of those with type II CAL. In many type II cases, a reticular distribution of IgE in the germinal centers was frequently observed. From an analysis of the sections immunohistochemically stained with monoclonal antibodies to B and T cells, there appeared to be a trend that the greater the percentage of the LS to the whole tissue, the lower the ratio of B cell region to the LS. In contrast to CAL, an analysis of the change of the ratio of B cell region to the lymphoid follicles (LF) seen in the gastric mucosa of patients with chronic gastritis showed that the larger the volume of LF, the higher the ratio of the B cell region to the entire LF.(ABSTRACT TRUNCATED AT 250 WORDS)

[Benign tumors of epithelial origin of the salivary glands. The authors' own experience and cases]. / Tumori benigni di origine epiteliale delle ghiandole salivari. Esperienza e casistica personale.

Following a review of the most recent literature on benign tumours of the salivary glands of epithelial origin, the paper illustrates an up-to-date classification of these tumours in anatomical and pathological terms. The author's personal clinical experience in 50 cases of major and minor salivary glands operated during the period between 1985 and 1991.

Warthin's tumor (cystadenolymphoma) of salivary glands. A clinicopathologic investigation of 278 cases.

This article reviews the detailed clinical and pathologic features of 278 cases of Warthin's tumor (cystadenolymphoma) from the files of the British Salivary Gland Tumor Panel. The tumor was found exclusively in the parotid gland, where it accounted for 14% of the total primary epithelial parotid tumors. The male predominance (1.6:1) was lower than in many earlier reports, and this observation is discussed. Some histopathologic features of both epithelium and stroma were semiquantified, and the presence of ciliated epithelium in a few tumors was confirmed. The Warthin's tumors were subclassified according to the scheme proposed by Seifert and colleagues. No examples of metaplastic Warthin's tumor were seen, but a few tumors were extensively necrotic and probably infarcted. The age distribution of patients with stroma-poor Warthin's tumor supported the concept that this variant develops by progressive adenomatous growth of typical Warthin's tumor. The histogenesis of Warthin's tumor is discussed briefly.

Histologic subclassification of the cystadenolymphoma of the parotid gland. Analysis of 275 cases.

Cystadenolymphomas (CAL) of the parotid gland are variable in their epithelial differentiation and the ratio of the epithelial tumor component to lymphoid stroma. Two hundred and seventy five cases of CAL from the files of the Salivary Glands Register of the Institute of Pathology, University of Hamburg (1965-1979) were analysed. Their pathogenesis from parenchyma included in regional lymph nodes is discussed. The following subclassification was established. 1. Depending on to the ratio of epithelial tumor component to lymphoid stroma, three subtypes were distinguished. Subtype 1, "typical CAL" with an epithelial tumor component of 50%, amounted to 77% of all cases of CAL studied. Oncocytic differentiation and focal metaplasia to goblet cells or squamous epithelium was also found. 13.5% of CAL were classified as subtype 2, "stroma-poor CAL" with an epithelial tumor component of 70 to 80%. The tumor structure was similar to that of an oncocytoma in places. Two per cent of the CAL were in subtype 3, "stroma-rich CAL" with an epithelial tumor component of only 20 to 30%. Subtype 3 was found solely in men. The average age at presentation (61 years) was slightly lower than that of all the cases studied (65 years). 2. In 7.5% of the cases large areas of squamous cell metaplasia and regressive changes was found within a CAL. These cases were classified as subtype 4 ("metaplastic CAL"). The average age was 67 years. The case histories showed that 20% of these metaplastic CAL had previously been irradiated. 3. Bilateral CAL was found in 7.5% of the cases. In 4% multifocal CAL occurred in the parotid gland unilaterally. Recurrences were observed in 2% of all CAL. 4. Carcinoma in CAL is rare (we found two cases in our own material). In 50% of all cases reported radiotherapy was mentioned in the case histories. 5. Malignant tumors coincident with CAL were recorded in 3% of the cases. 6. The lymphoid stroma showed reaction patterns similar to those of the regional lymph nodes. These included granulomatous changes (foreign body granuloma with cholesterol deposits, tuberculosis) and tumor metastases. In the neighborhood of oncocytic tumor epithelium focal accumulations plasma cells forming IgA and IgG were found. Metaplasia to squamous epithelium is believed to be caused by circulatory disturbances, irradiation, and other noxae. In the differential diagnosis of the stroma-poor subtype 2, oncocytoma and cystic sialadenoma must be excluded, and in the differential diagnosis of subtype 4 (the metaplastic CAL), sebaceous adenoma, mucepidermoid tumor, squamous cell carcinoma, lymphoepithelioma, and other non-tumorous lesions of the parotid gland (lymphoepithelial cysts, myoepithelial parotitis) must be ruled out. Our findings suggest that CAL develops from parenchyma included in parotid lymph nodes with the oncocytic ductal epithelium representing the neoplastic component.