[Updates on tumours of the salivary glands : 2017 WHO classification]. / Neues zu Tumoren der Speicheldrüsen : WHO-Klassifikation 2017.

In the new 2017 WHO classification, a reduction of the high number of entities of salivary carcinomas was implemented. There is only one new carcinoma entity: secretory carcinoma. There is a slight increase of reactive and benign entities by the inclusion of rare and well-established, but so far not included, lesions. Furthermore, there are some conceptual changes and pure changes in terminology. The impact of molecular findings is increasing and is so far restricted to diagnostic aspects.

[Morphology of non cutaneous head and neck squamous cell carcinoma]. / Morphologie des nicht-kutanen Plattenepithelkarzinoms im Kopf-Hals-Bereich.

Head and neck squamous cell carcinoma (HNSCC) is by far the most frequent malignant tumor in this anatomic region. Today, HNSCC is divided into two morphologically, molecularly and clinically fundamentally different entities: conventional and virus-associated (HPV/EBV) neoplasms. Premalignant lesions of nonvirus-associated HNSCC include conventional leukoplakia, dysplasia and proliferative verrucous hyperplasia with an increasing risk for malignant transformation. The morphology of HNSCC comprises a spectrum of growth patterns. In addition, special types of HNSCC must be delineated. Recently, for virus-associated HNSCC, some important clinicopathological specifics have become relevant including a separate staging system for these neoplasms. For non-virus associated HNSCC, new grading procedures have been proposed, which significantly impact on prognosis. These issues will be discussed in this review.

[Immunoglobulin G4 (IgG4)-related disease. A review of head and neck manifestations]. / Immunglobulin-G4(IgG4)-assoziierte Erkrankung. Gesichertes und Kontroverses der häufigsten Kopf-Hals-Manifestationen.

Immunoglobulin G4 (IgG4)-related disease (also known as hyper-IgG4 disease) is a recently defined emerging condition with highly heterogeneous clinicopathological features and variable disease manifestations. This disorder is characterized by unifocal or multifocal (multiorgan) involvement by tumefactive plasma cell-rich inflammatory infiltrates associated with prominent fibrosclerosis. This not uncommonly interferes with organ function resulting in diverse clinical symptoms. The autoimmune pancreatitis represents the prototype of this disease; however, to date almost all organs have been reported to be involved in this disorder. In the head and neck area several presentations of this disease may be encountered in salivary glands, lacrimal glands, thyroid gland, lymph nodes, soft tissue of the neck, ear and sinonasal tract. However, IgG4 positive plasma cells are occasionally prominent in non-specific chronic inflammatory conditions of the head and neck and the oral cavity unrelated to autoimmune diseases or systemic disorders, thus representing diagnostic pitfalls. The diagnosis of IgG4-related disease should be based on a combination of typical histological, clinical and serological findings.

[Patterns of xanthogranulomatous reaction in salivary glands. Histomorphological spectrum and differential diagnosis]. / Xanthogranulomatöses Reaktionsmuster in Speicheldrüsen. Histomorphologisches Spektrum und Differenzialdiagnose.

Xanthogranulomatous inflammation is an uncommon subtype of chronic inflammatory processes that has been mainly reported in the kidneys, gallbladder and other less common sites. Due to the presence of tumefactive mixed inflammatory infiltrates with variable involvement of surrounding soft tissues, this benign condition is often mistaken for a malignancy on clinical examination. In the salivary glands xanthogranulomatous inflammation is rare and mainly represents reactive changes secondary to a preexisting lesion, in particular infarcted Warthin tumors as well as ruptured ductal cysts and other sialectatic ductal changes. A special type of xanthogranulomatous salivary gland disease is represented by the rare primary (idiopathic) xanthogranulomatous sialadenitis without identifiable predisposing parenchymal or ductal lesions. The histological differential diagnosis is mainly based on the dominant histological pattern and encompasses among others inflammatory pseudotumors of various etiologies (e.g. inflammatory myofibroblastic tumor, IgG4-related disease and sarcoidosis), neoplastic and paraneoplastic xanthogranulomatosis, malignant lymphoma and carcinoma with secondary xanthogranulomatous reactions. Thus, identification of the underlying lesion is necessary for correct classification and to avoid overlooking more serious neoplastic or autoimmune diseases.

[The visionary concept of "lymphoepithelioma" by A. Schmincke in 1921. Subsequent confusion over terminology and current approach to a solution]. / Das visionäre Konzept des "Lymphoepithelioms" 1921 und A. Schmincke. Nachfolgende terminologische Verwirrung und aktuelle Lösungsansätze.

In 1921 Alexander Schmincke established the visionary concept of a clinically and histomorphologically defined carcinoma entity of different lymphoepithelial organs that he named "lymphoepithelioma". This nowadays mainly comprises non-keratinizing oropharyngeal carcinomas frequently associated with human papillomavirus (HPV) and non-keratinizing nasopharyngeal carcinomas mostly associated with Epstein-Barr virus (EBV). The term lymphoepithelioma was originally defined by A. Schmincke and J. Ewing as a combined clinical and histological tumor entity of lymphoepithelial organs. The main reason for the longstanding terminological confusion regarding the term lymphoepithelioma is based on the fact that lateron a pure histological interpretation (lymphoepithelial differentiation) caused an artificial and nonreproducible exclusion of tumors with transitional and basaloid differentiation. For the forthcoming new WHO classification it has been suggested that squamous cell carcinoma of the head and neck should no longer be classified according to the heterogeneous histological differentiation but according to etiopathogenetic criteria (e.g. HPV-related, EBV-related, nicotine and alcohol-related). This proposed classification corresponds much better to the prognosis and therapy and would represent a late acknowledgement of Schmincke's visionary concept of a clinically and histomorphologically defined tumor entity. In addition, the ongoing terminological confusion over the heterogeneous and prognostically weak spectrum of histological differentiation would subside.

[Cutaneous adnexal and salivary gland tumours. Similarities and differences]. / Hautadnex- vs. Speicheldrüsentumoren. Analoges und Divergentes.

Despite major discrepancies in basic microscopic anatomy, remarkable similarities are manifest within the wide spectrum of cutaneous adnexal and salivary gland tumors. In this study salivary gland and adnexal tumors were identified and investigated with respect to similarities in histology, terminology and pathogenesis. Histological similarities of certain types of salivary gland tumors relate to eccrine, apocrine and rarely sebaceous (but not trichofollicular) types of adnexal tumors. The most striking similarity was found with salivary gland pleomorphic adenoma and cutaneous mixed tumor. Multistep carcinogenesis starting with intraductal carcinoma, identified in carcinoma ex pleomorphic adenoma is identical to that found in cutaneous carcinoma ex spiradenoma. Further histological and terminological similarities are shown for mucinous and mucoepidermoid carcinoma, for lymphadenoma and lymphoepithelial carcinoma, for sebaceous adenoma and carcinoma, for adenoid-cystic carcinoma, as well as for salivary gland basal cell adenoma versus cutaneous spiradenoma. Manifest diagnostic problems related to histologically similar salivary gland and adnexal tumors are rare and are topographically limited to the parotid and oral areas.

[HPV-associated oropharyngeal carcinoma. Status quo and relationship with cancer of unknown primary]. / HPV-assoziierte oropharyngeale Karzinome. Aktueller Stand und Verhältnis zum Karzinom unbekannter Herkunft.

Carcinomas of the oropharynx with association to high-risk types of human papillomavirus (HPV) have been identified as a new tumour entity with favourable prognosis, distinct from classical nicotine- and alcohol-associated carcinoma. They develop through oncogenic transformation of the basal cells of reticulated cryptal epithelium of the palatinal tonsils and the base of the tongue. Positivity for HPV strongly correlates with an atypical, non-keratinizing histological differentiation and cystic transformation of lymph node metastases. Strong immunohistological positivity for p16 reliably detects transcriptionally active infection with high-risk HPV. Hence, p16 staining has been regarded as an effectual diagnostic tool in the appropriate setting. Frequent nodal metastasation as well as considerable size of (cystic) metastases, and frequent small size as well as submucosal location of primary tumours all contribute to frequent initial manifestation of cervical cancer of unknown primary (CUP). In a situation of CUP diagnostic testing for HPV (in negative cases in addition to EBV) is recommended in lymph node metastases, due to the high predictive value for the localization of occult primary carcinomas. Intense clinicopathological cooperation is mandatory for improved detection of small, occult primary carcinomas. The relevance of this new carcinoma entity will increase, as the incidence continues to increase worldwide.

[Case report of granulomatous necrotizing sialadenitis. Rarity of first manifestation in submandibular gland]. / Fallbericht einer granulomatös-nekrotisierenden Sialadenitis. Rarität einer Erstmanifestation in der Glandula submandibularis.

This article presents the case of a 43-year-old male patient with recurrent painful swelling of the right submandibular gland. Submandibulectomy was performed. Histological investigations showed an intense granulomatous inflammation with severe destruction of the parenchyma. The inflammatory infiltrate consisted of abscesses with neutrophilic and eosinophilic granulocytes and ill-defined granulomas with multinucleated giant cells. Some of the blood vessels showed evidence of vasculitis. After further clinical and serological investigations with highly elevated levels of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) and antiproteinase-3 antibodies, a rare limited disease of granulomatous polyangiitis (Wegener granulomatosis) was finally diagnosed. Such a manifestation of the disease is exceedingly rare; therefore, only single case reports have so far been described. The certain establishment of the diagnosis seems to be challenging because of the lack of involvement of the respiratory tract and the kidneys. In this case a histological assessment and clinical findings are mandatory for the correct diagnosis.

[Cystic lesion with a displaced tooth in the maxillary sinus]. / Zystischer Kieferhöhlenprozess mit verlagertem Zahn.

Ameloblastomas are epithelial odontogenic tumors in the mandibula or maxilla with potential local infiltrating growth; therefore, relapses can occur after incomplete resection. Among the different histological subtypes, the following are of clinical importance: The so-called unicystic ameloblastoma, radiologically presenting as a common dentigerous cyst, and the so-called extraosseous ameloblastoma. This case report describes the rare combination of a unicystic ameloblastoma with extraosseous localization in the maxillary sinus and association with a displaced tooth. This unusual constellation can cause major diagnostic problems.

Oesophageal ulceration after selective internal radiation therapy in a patient with carcinoma of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) is defined as histologically confirmed metastases in the absence of an identifiable primary tumor. Patients with solely liver metastases from adenocarinomas represent the most frequent subgroup with an unfavourable prognosis. The medium survival averages 6 to 9 months. No chemotherapheutic standard has been established. CASE: We present a patient with hepatic CUP. After cycles of chemotherapy and hemihepatectomy the tumor returned and showed hepatic progression. The patient was evaluated for selective internal radiation therapy (SIRT). Three years after diagnosis she is still alive and tumorfree. Despite a good result and disease control our patient suffered radiation-induced ulceration in the oesophagus, stomach, and duodenum. This side effect appears in up to 12 % of patients, often very late after treatment, is refractory to pharmacotherapy and persistent over a long time. CONCLUSIONS: SIRT is a new, effective treatment in patients with hepatic CUP. Because of the anticipated increase of this therapy, adverse side effects such as ulcerations in the upper-GI tract secondary to ectopic implantation of microspheres may be seen more commonly. Awareness of this and the recognition of microspheres in biopsies is cardinal for appropriate management and maintenance of the patient's quality of life.

[Autoimmune sialadenitis]. / Autoimmunsialadenitis.

Using the European-American classification criteria the diagnosis of autoimmune sialadenitis in Sjögren's syndrome can generally be easily established or excluded. In addition, sonography performed by the ENT physician is helpful in diagnosing and especially in follow-up screening for MALT lymphomas, which 5%-10% of patients develop. Therapy of sicca symptoms is primarily symptomatic using substitution with fluids and stimulation with oral cholinergic drugs. Corticosteroids and/or antibiotics may play a role in patients with severe inflammatory episodes of autoimmune sialadenitis. Systemic therapy with immunomodulatory drugs such as azathioprine or cyclophosphamide is reserved for patients with extraglandular manifestations. However, the efficacy of this therapy is not proven by clinical studies. Rituximab, a new monoclonal CD20 antibody, seems to offer the first possibility of a causal therapy, under which the lymphoepithelial lesions in the salivary glands can disappear and saliva production improves. However, larger clinical studies are needed to evaluate the efficacy of this new therapy. Optimal treatment of autoimmune sialadenitis requires interdisciplinary collaboration between ENT physician, oral and maxillofacial surgeon, rheumatologist, ophthalmologist, dentist, and pathologist.

[Sarcoidosis of lymph nodes in the submandibular compartment]. / Lymphknotensarkoidose der Submandibularisloge.

Sarcoidosis is a granulomatous systemic disease of unknown etiology. Besides the landmark pulmonary lesions, extrathoracic manifestations of the disease can also occur. We report the case of a 53-year-old woman with an obscure swelling of both submandibular compartments. The radiological and pathohistological evaluations confirmed the uncommon diagnosis of sarcoidosis of the submandibular compartment. The tumor in each compartment consisted of a huge lymph node conglomerate respectively displacing the submandibular gland. The major salivary glands and the thorax were not involved.

[Sjögren-associated MALT-type lymphoma of labial salivary glands: rare constellation with amyloidosis and IgM-paraproteinemia]. / Sjögren-assoziiertes MALT-Lymphom der Lippenspeicheldrüsen: Seltene Konstellation mit Amyloidbildung und IgM-Paraproteinämie.

We report a complex and rare combination of clinical and histological findings in a 59-year-old female patient: severe sicca-syndrome due to M. Sjögren, marginal zone B-cell lymphoma (MALT-type) in labial salivary glands with localized amyloid deposition, IgM-paraproteinemia, and Bence-Jones proteinuria. The causal association of these findings could only be elucidated by intense interdisciplinary correlation of all findings.

[Secondary high-malignant transformation of a low-malignant epithelial-myoepithelial carcinoma]. / Sekundäre hochmaligne Transformation eines niedrigmalignen epithelial-myoepithelialen Karzinoms.

The rare entity of epithelial-myoepithelial carcinoma (EMC) belongs to a group of tumors with a biphasic ductular growth pattern, mostly with a dominating myoepithelial component and low-grade malignancy. We report on the rare constellation of a primary low-malignant EMC with high malignant transformation (so-called dedifferentiation) into a highly malignant myoepithelial carcinoma. In the eight published cases so far, the high-malignant component was reported to be either adenocarcinoma or undifferentiated carcinoma or was otherwise not specified. To the best of our knowledge, this is the first case report of a high-grade myoepithelial carcinoma transforming from a low-grade EMC. We discuss interesting parallels to the pathogenesis of secondary transformation of carcinoma ex pleomorphic adenoma.

[Pleomorphic adenoma: pitfalls and clinicopathological forms of progression]. / Das pleomorphe Adenom: Pitfalls in der Diagnostik und klinisch-pathologische Progressionsformen.

In the majority of cases the diagnosis of pleomorphic adenoma (PA) is straightforward. In "monomorphic" types of PA problems may result: Epithelial-rich PA need to be distinguished from basal cell adenoma or canalicular adenoma. PA dominated by mesenchymal, spindle-shaped differentiation need to be distinguished from myoepithelioma or soft tissue tumours like schwannoma. Focal biphasic-tubular differentiation with CK7/18-positive ductal cells is good evidence for a tumour within the wide spectrum of PA. Focal peripheral pseudoinfiltration can represent physiological growth pattern of PA; this may render a difficult distinction from low-malignant carcinomas like adenoid-cystic or epithelial-myoepithelial carcinoma, harbouring also tubular structures. The different progression steps of carcinoma ex pleomorphic adenoma (CEPA), starting with intraductal carcinoma, are highly relevant with respect to prognosis and therapy. Early stages including CEPA with minor extracapsular invasion show favourable prognosis, while cases with extensive extracapsular invasion carry a dismal prognosis.

[Pattern recognition in the differential diagnosis of salivary lymphoepithelial lesions]. / Mustererkennung zur Differenzialdiagnose lymphoepithelialer Läsionen der Speicheldrüsen.

The prototype of a salivary lymphoepithelial lesion is the autoimmune disease Sjögren's syndrome with the characteristic lymphoepithelial duct lesions (LEL). The distinction of Sjögren's syndrome from cases with initial transformation into associated marginal zone B-cell lymphoma (MALT type) can be very challenging, whereby the presence of small "halos" can lead to over-diagnosis. The HIV-associated cystic lymphoepithelial lesion can be histologically almost identical to Sjögren's syndrome and often needs clinical correlation. The sporadic lymphoepithelial cyst of the parotid gland is a frequent finding and has no clinical consequence; however, this entity needs to be identified and distinguished from the above-mentioned entities. The most frequent diagnosis in resected submandibular glands is chronic-fibrosing sialadenitis, so-called Küttner's tumour. Altogether, there is a wide spectrum of lymphoepithelial interaction in the area of salivary glands, including biphasic lymphoepithelial tumours with an obligate lymphoid component, epithelial tumours with facultative tumour-associated lymphoid proliferation, and different processes of intraparotid lymph nodes. The immunohistological reaction for pan-keratin can be very helpful for a thorough pattern analysis of the different lymphoepithelial lesions. The relative frequency of the lesions in different salivary glands can also be diagnostically helpful.

Carcinoma of the collecting ducts of Bellini of the kidney: adjuvant chemotherapy followed by multikinase-inhibition with sunitinib.

INTRODUCTION: Carcinoma of the collecting ducts of Bellini of the kidney (CDC) is very rare but among the most aggressive urological entities. Standard therapy is not well defined with questionable efficacy. METHODS: We present two cases of male patients (49 and 66 years old) with pT3a pN2 CDC treated with a combination of cisplatin plus gemcitabine in an adjuvant setting. Following recurrence the multi-kinase inhibitor sunitinib was administered. RESULTS: Radical nephrectomy with lymphadenectomy revealed CDC in stage pT3a pN2 M0 G3 R0 in both patients. 4 courses of adjuvant chemotherapy with cisplatin 70 mg/m superset2 and gemcitabine 1,500 mg/m superset2 were given. Side effects according to the NCI 3.0 common toxicity criteria were limited to grade 2 asthenia and grade 2 thrombozytopenia/leucopenia. Restaging revealed local recurrence and lymph node metastases. Both patients were re-operated and metastatic CDC was found. Second line therapy with sunitinb malatat (Sutent superset, Pfizer Inc. U.S.) at 50mg p.o. was given. Grade 3 leucopenia and thrombocytopenia and grade 2 asthenia and mucositis were not dose-limiting. After two cycles multiple liver, lung and bone metastases and mediastinal lymphopathy occured. 8 weeks later the patients died with a survival of 8 months from initial diagnosis. CONCLUSIONS: Adjuvant gemcitabine plus cisplatin did not delay recurrence of CDC after surgery. Metastasectomy either had no influence on the course of disease. Anti-angiogenetic therapy with sunitinib treatment was not effective, possibly related to a low vascular density (CD31 expression) in CDC.

[Eosinophilic esophagitis : a cause of dysphagia]. / Die eosinophile Osophagitis : Eine Differenzialdiagnose bei Dysphagie.

BACKGROUND: Eosinophilic esophagitis (EE) is a chronic, interleukin-5-driven inflammatory disease of the esophagus, causing dysphagia and esophageal food impactions. We analyzed the diagnostic results of patients with suspected or proven EE and in this article discuss the relevant aspects of this disease. PATIENTS AND METHODS: Sixteen patients suffering from dysphagia or recurrent esophageal food impactions underwent rigid esophagoscopy to exclude EE. In six patients, 24-h pH monitoring was performed to exclude laryngopharyngeal reflux (LPR). RESULTS: EE was diagnosed in only one patient, a boy with a history of peanut allergy and recurrent esophageal food impactions. In six patients, histological examination of biopsies revealed reflux esophagitis indicating gastroesophageal reflux disease (GERD). Using 24-h pH monitoring, LPR was diagnosed in four of six patients. CONCLUSIONS: Even in patients presenting with typical symptoms of EE, this disease is rarely found. However, in male patients with asthma, allergies, or a history of recurrent esophageal food impactions, EE must be excluded. The most important differential diagnoses of EE are GERD and LPR.

Natural history and surgical treatment of brown tumor lesions at various sites in refractory primary hyperparathyroidism.

OBJECTIVE: Nowadays, the occurrence of brown tumor lesions or osteitis fibrosa cystica caused by long-lasting primary hyperparathyroidism are very rare, since measuring serum calcium became available routinely in the mid-1970s. It is a tumor-like lesion that may affect the entire skeleton, often presenting with diffuse focal bone pain or by pathological fracture. METHODS: We describe our experience of brown tumor lesions at different skeletal sites that were treated at our trauma centre within the last two years. This included surgical therapy for the indications (i) pain at the pelvis, (ii) increased risk for pathological fracture at the tibia and (iii) acute radicular symptoms at the lumbar spine. The literature was reviewed for the current understanding of the pathophysiology as well as therapy of brown tumor lesions in primary hyperparathyroidism. RESULTS: Curettage of a left-sided iliac crest brown tumor terminated focal pain. A less invasive stabilisation system and bone cement decreased both patient pain and the fracture risk of brown tumor lesion sites of the shinbone; and internal fixator including laminectomy at the lumbar spine ended radicular symptoms. CONCLUSION: Patients with refractory primary hyperparathyroidism should be monitored closely by endocrinologists and the patient's serum calcium level should be adjusted as far as possible. Radiography is required only if focal bone pain or pathological fractures or radicular symptoms occur. Surgery should be considered if large bone defects with spontaneous fracture risk or increasing pain are present. Tumor curettage, Palacos plombage and less invasive stabilisation systems have proved to be acceptable surgical options.