[Significance of molecular-cytogenetic findings in mucoepidermoid carcinoma as an example of salivary gland tumors]. / Bedeutung molekular-zytogenetischer Befunde bei Speicheldrüsentumoren am Beispiel des Mukoepidermoidkarzinoms.

Chromosome translocations in tumors frequently give rise to fusion genes encoding proteins with oncogenic activities. Mucoepidermoid carcinomas (MEC) are characterized by a t(11;19)(q21-22;p13) translocation found in approximately 60% of the tumors. This t(11;19) translocation results in a fusion gene consisting of exon 1 of the MECT 1 gene and exons 2-5 of the MAML 2 gene. As a result of the t(11;19) a fusion protein is generated which, independent of NOTCH-ligands, activates the transcription of the NOTCH target gene HES 1. The altered function of MAML 2 causes a disruption of NOTCH signalling which suggests a novel mechanism of tumorigenesis. Pending the elucidation of the t(11;19) at the molecular level of an apparently identical chromosomal translocation in Warthin's tumor, the identification of the translocation in MEC by FISH- and/or RT-PCR-analyses may become important in diagnosis and might have prognostic relevance. Warthin's tumors are benign salivary gland neoplasms with a distinctive histomorphology and histogenesis completely different from MEC.

[Immunohistochemical characterization of salivary gland tumors with tissue micro-arrays]. / Immunphänotypische Charakterisierung von Speicheldrüsentumoren unter Verwendung von Gewebe-Micro-Arrays.

Systematic analysis of gene expression in salivary gland tumors is necessary to identify genes associated with specific tumor types. From the salivary gland register of the University Hospital Hamburg-Eppendorf sufficient samples of various tumors were available to generate Tissue Micro-Arrays (TMA). In light of the considerable heterogeneity of salivary gland tumors, this study was aimed at evaluating the suitability of TMA in salivary gland diagnostics and research. Epithelial antigens are not sufficient for a tumor-type-specific characterization. Myoepithelial markers are suitable for distinguishing biphasic tumor types from purely epithelial tumors. The detection of amylase in acinic cell carcinomas, and the detection of steroid hormone receptors in these and other malignant salivary gland tumors particularly in combination with the expression of transcription factors, oncogenes and proliferation associated antigens result in characteristic expression profiles. These may prove to be valuable for further investigations, especially on the molecular level.

[Calcifying epithelial odontogenic tumor of the maxilla (Pindborg tumor)]. / Verkalkender epithelialer odontogener Tumor des Oberkiefers (Pindborg-Tumor).

A male patient presented with an extraordinarily large calcifying epithelial odontogenic tumor (CEOT or Pindborg-tumor) that affected the maxilla. The disease became evident due to alterations in the facial aspect, in particular of the perioral region, caused by the expanding tumor. CEOT is characterised by the slowly growing mass of part of the jaws. Multilocular or extraosseous manifestations are extremely rare. Malignant transformation with metastases is rare. Radiography depicts characteristic, but not obligatory, areas of calcification inside the tumor. The surgical therapy for CEOT is complete local resection with safe margins. If tooth bearing parts of the jaws are affected, these teeth almost always have to be removed. The prognosis is excellent for overall survival. Local recurrences have rarely been reported but may be found even decades after primary treatment. Three years following surgical therapy there is no evidence of local recurrence. A long-term follow-up control is recommended.

[Salivary gland tumors--tumor typing and grading]. / Speicheldrüsentumoren-Tumortypisierung und Grading.

In addition to staging, histological typing and grading provide important information for prognosis and adequate treatment of salivary gland cancers. Current classification and grading systems for mucoepidermoid carcinoma, adenoid cystic carcinoma, and malignant mixed tumor (carcinoma ex pleomorphic adenoma) are discussed.

[Differential diagnosis of basaloid salivary gland tumors]. / Differenzialdiagnose basaloider Speicheldrüsentumoren.

The diagnosis of basaloid tumors of the salivary glands can be challenging. In most cases, conventional histologic examination, if carried out meticulously, will be sufficient. Yet, immunohistochemistry will be of help for the definition of purely myoepithelial tumors, basaloid squamous cell carcinomas, and canalicular adenomas. The differential diagnosis of canalicular adenoma, basal cell adenoma and basal cell adenocarcinoma, adenoid cystic carcinoma, polymorphous low-grade adenocarcinoma, myoepithelial tumors, epithelial-myoepithelial carcinoma, and basaloid squamous cell carcinoma is discussed.

[Undifferentiated salivary gland carcinomas]. / Undifferenzierte Karzinome der Speicheldrüsen.

Undifferentiated salivary gland carcinomas may be divided into small cell and large cell types. Among large cell undifferentiated carcinomas, lymphoepithelial carcinomas have to be distinguished, the latter of which are endemic in the Arctic regions and southern China where virtually all cases of these tumors are associated with the Epstein-Barr virus (EBV). Association with EBV may also be observed in sporadic cases, and detection of EBV gene products may aid their diagnosis. Immunohistology may be employed to resolve the differential diagnosis of undifferentiated salivary gland carcinomas, comprising malignant lymphomas, amelanotic melanomas, Merkel cell carcinomas, and adenoid cystic carcinomas, in particular in small biopsy materials. Because of the rarity of undifferentiated salivary gland carcinomas, the differential diagnosis should always include metastases of undifferentiated carcinomas arising at other primary sites, particularly when expressing the thyroid transcription factor-1 (TTF-1).

The clinical presentation of non-hodgkin lymphomas of the major salivary glands.

The aim of this study was to examine the clinical presentation of patients with malignant lymphoma of the major salivary glands. In a retrospective study, 26 patients with a non-Hodgkin lymphoma (NHL) of the major salivary glands were examined. The results showed a distinct preference for the female gender. Two groups with clinical differences were observed depending on lymphoma manifestation as either extranodal-parenchymal (extranodal) or with intra- or periglandular (nodal) lymph node disease. Differences between these two groups existed with regard to the length of clinical history, recurrent vs continuously progressing symptoms and presentation on ultrasound examination (multiple masses compared to solitary masses). Patients with an extranodal lymphoma always showed disease limited to the affected gland, whereas those patients with a nodal lymphoma presented with stage II or higher (Ann Arbor Classification). In these patients, local recurrence was also five times higher (5/13; 38.4%) than in patients with an extranodal lymphoma (1/13; 7.7%). In 1 patient (7.7%) with extranodal lymphoma, dissemination was observed, compared to 6/13 patients (46.2%) in the group with nodal disease. Seven out of 13 patients (53.8%) with nodal disease died due to lymphoma spread and 1/13 (7.7%) of the patients with extranodal disease. There seem to be distinct clinical differences in the course of patients with NHL of the major salivary glands, depending on extranodal or nodal disease presentation. The histopathological diagnosis, with special recognition of the particular lymphoma pathogenesis, constitutes an important prognostic factor in these patients.

[About the prognostic value of Her-2 gene-amplification and cell-proliferation in salivary duct carcinoma of the major salivary glands - a pilot-study]. / Pilotstudie zur prognostischen Wertigkeit der Her-2 Genamplifikation und Proliferationsaktivität beim Speichelgangkarzinom der grossen Kopfspeicheldrüsen1.

INTRODUCTION: The salivary duct carcinoma (sdc) represents a rare variant of the group of adeno-carcinomas of the salivary glands. Histopathologically, it is marked by solid and cribriform cell nests with central necrosis, displaying distinct similarity with the ductal carcinoma of the breast, where prognosis can be correlated with Her-2 gene-amplification. Based on this histopathological similarity, the prognostic value of Her-2 gene amplification in SDC was examined in the presented pilot-study. PATIENTS AND METHODS: Four own patients with different clinical courses were examined in regard to their histopathological features, Her-2 gene-amplification and proliferation (Ki67). RESULTS: Three of the four patients died tumor related 2.4, 5.5 and 8.2 years after initial diagnosis. The remaining patient died tumor-free 6 year after diagnosis (myocardial infarct). The two patients with an early recurrent disease and distant metastasis showed a high Her-2 expression and proliferation (Ki67), compared to the other two patients. CONCLUSION: In the presented pilot-study a distinct correlation between Her2-gene-amplification, proliferation (Ki67) and clinical course could be observed. Additional analysis to evaluate this aspect seems rectified, especially under recognition of therapy decisions.

[Clinical presentation, therapy and prognosis of non-Hodgkin lymphomas of the major salivary glands]. / Zur Klinik, Therapie und Prognose der Non-Hodgkin-Lymphome der grossen Kopfspeicheldrüsen1.

INTRODUCTION: About 5 - 10 % of all Non-Hodgkin-Lymphomas (NHL) present within the major salivary glands. Two etio-pathologically different groups, the (extranodal)-parenchymal NHL and NHL of intra- or periglandular lymphnodes (nodal lymphomas) have to be distinguished. It was the aim of this study to evaluate the clinical presentation, therapy and biological behaviour of these etiopathologically different lymphoma-groups. MATERIAL AND METHOD: In a retrospective study, therapy and course of disease of 26 patients with a NHL of the major salivary glands were examined (diagnosis and treatment between 1988 and 1996). RESULTS: Staging results in the group of parenchymal lymphoma always showed the disease limited to the effected gland, whereas nodal NHL presented with a stadium II to IV (Ann-Arbor) at time of diagnosis. Local recurrencies were five times higher in nodal NHL compared to parenchymal NHL. In only one case (7.7 %) of the patients with parenchymal NHL, dissemination was observed. In the group of nodal NHL, a dissemination was observed in 6 patients (46.2 %). 7 of 13 patients (53.8 %) with a nodal NHL died due to lymphoma dissemination, compared to one patient (7.7 %) with a parenchymal NHL. CONCLUSION: Based on the presented data, the histopathological diagnosis, under special recognition of the particular lymphoma-pathogenesis, constitutes an important prognostic factor in patients with NHL of the major salivary glands.

Rejection, herpesvirus infection, and Ki-67 expression in endomyocardial biopsy specimens from heart transplant recipients.

We examined 164 endomyocardial biopsy specimens from 29 patients who received an orthotopic heart transplant since 1984. Rejection was graded according to the Hannover classification. Non-isotopic in situ DNA hybridization was conducted on cryostat sections with biotinylated probes for herpes simplex virus, Epstein-Barr virus, and cytomegalovirus. Serial sections of 126 biopsies were investigated immunohistochemically for the presence of activated T lymphocytes and proliferating cells, with monoclonal antibodies against interleukin 2 receptors (CD 25) and Ki-67 antigen. Relations between rejection grades, presence of proliferating cells, and presence of herpesvirus DNA were determined for the total number of biopsies. For some patients correlation of these parameters was studied over time. Herpesviral nucleic acids were detected in 25% of all biopsies: 37% of biopsies with relevant rejection (grades A 2 or A 3; 39% of all biopsies) compared to 18% of biopsies graded A 0, A 1, or A 5 (61% of all samples) (P less than 0.01). 56% of the biopsies with infection showed relevant rejection as compared with only 33% of the uninfected. Ki-67 expression was found in 41% of all biopsies, mainly in infiltrating cells: 69% of biopsies with relevant rejection compared with 23% of cases of minor/no rejection (P much less than 0.001). Ki-67 expression was also associated with herpesvirus infection: 66% of infected biopsies contained Ki-67 positive cells compared with 33% of uninfected biopsies (P less than 0.001). Herpesvirus infection was usually observed within the interstitial cell population, which, in many cases, displayed a considerable Ki-67 expression, too. In few cases only, hybridization was unequivocally found in vascular wall cells or myocytes. Viral myocarditis does not only mimic graft rejection morphologically, but it may also affect the course of rejection, via induction of antigenic changes or direct injury of cardiac tissues. Virus infections may also elicit or aggravate obliterative coronary artery disease, and thus contribute to accelerated graft atherosclerosis.