[Possibilities of the personalized approach to solitary thyroid nodules based on molecular profiling]. / Möglichkeiten des personalisierten Vorgehens bei solitären Schilddrüsenknoten basierend auf molekularem Profiling.

BACKGROUND: Molecular profiling is currently not yet widespread in Germany and its potential for personalized treatment of solitary thyroid nodules is not exhausted. METHOD: Narrative assessment of the available options and their evidence based on the current international literature as well as discussion of the options in the German context from the perspective of a thyroid surgeon and a thyroid pathologist. RESULTS: The commercial tests available, especially in the USA, for molecular profiling of thyroid nodules offer good rule-in and somewhat poorer rule-out options, as many differentiated thyroid carcinomas do not display genetic alterations. The costs of these tests and molecular pathology for nodule assessment are still high and the individual mutations have not yet been clearly characterized. CONCLUSION: It can be assumed that molecular profiling will become more important in the coming years and find its way into the clinical routine. At this point in time, however, there is not yet sufficient evidence of the clinical significance of most mutations in thyroid carcinomas to derive therapeutic consequences from them.

Management of transmodiolar and transmacular cochleovestibular schwannomas with and without cochlear implantation.

INTRODUCTION: Hearing rehabilitation with cochlear implants has attracted increasing interest also for patients with cochleovestibular schwannoma. The authors report their experience with the surgical management of tumors with rare transmodiolar or transmacular extension and outcomes after cochlear implantation (CI). METHODS: This retrospective case series included nine patients with either primary intralabyrinthine tumors or secondary invasion of the inner ear from the internal auditory canal. The primary endpoint with CI, performed in six patients, was word recognition score at 65 dB SPL (sound pressure level). Secondary endpoints were intra- and postoperative electrophysiological parameters, impedance measures, the presence of a wave V in the electrically evoked (via the CI) auditory brainstem responses, the specifics of postoperative CI programming, and adverse events. RESULTS: Hearing rehabilitation with CI in cases of transmodiolar tumor growth could be achieved only with incomplete tumor removal, whereas tumors with transmacular growth could be completely removed. All six patients with CI had good word recognition scores for numbers in quiet conditions (80-100% at 65 dB SPL, not later than 6 to 12 months post CI activation). Four of these six patients achieved good to very good results for monosyllabic words within 1-36 months (65-85% at 65 dB SPL). The two other patients, however, had low scores for monosyllables at 6 months (25 and 15% at 65 dB SPL, respectively) with worsening of results thereafter. CONCLUSIONS: Cochleovestibular schwannomas with transmodiolar and transmacular extension represent a rare entity with specific management requirements. Hearing rehabilitation with CI is a principal option in these patients.

[Resection of a submacular traction membrane due to significant visual impairment : Case report]. / Resektion einer submakulären Traktionsmembran bei ausgeprägter Visusminderung : Fallbericht.

An 89-year-old female presented with acute visual impairment and large cells in the vitreous cavity of the left eye. The patient was treated for a suspected intraocular lymphoma. In the follow-up a retinal detachment was diagnosed and treated via pars plana vitrectomy. A resection of the subretinal traction membrane following retinectomy was performed. The histological findings did not reveal any indications of a lymphoproliferative process. A ruptured choroidal neovascularization (CNV) with peripheral exudative hemorrhagic chorioretinopathy (PEHCR) and subretinal membrane formation was diagnosed. There were no signs of malignancy. The resection of a subretinal traction membrane poses a challenge for the vitreoretinal surgeon but can provide the possibility of visual improvement.

[Management of transmodiolar and transmacular cochleovestibular schwannomas with and without cochlear implantation. German version]. / Management transmodiolärer und transmakulärer Vestibularis- und Cochlearisschwannome mit und ohne Cochleaimplantation.

INTRODUCTION: Hearing rehabilitation with cochlear implants has attracted increasing interest also for patients with cochleovestibular schwannoma. The authors report their experience with the surgical management of tumors with rare transmodiolar or transmacular extension and outcomes after cochlear implantation (CI). METHODS: This retrospective case series included nine patients with either primary intralabyrinthine tumors or secondary invasion of the inner ear from the internal auditory canal. The primary endpoint with CI, performed in six patients, was word recognition score at 65 dB SPL (sound pressure level). Secondary endpoints were intra- and postoperative electrophysiological parameters, impedance measures, the presence of a wave V in the electrically evoked (via the CI) auditory brainstem responses, the specifics of postoperative CI programming, and adverse events. RESULTS: Hearing rehabilitation with CI in cases of transmodiolar tumor growth could be achieved only with incomplete tumor removal, whereas tumors with transmacular growth could be completely removed. All six patients with CI had good word recognition scores for numbers in quiet conditions (80-100% at 65 dB SPL, not later than 6 to 12 months post CI activation). Four of these six patients achieved good to very good results for monosyllabic words within 1-36 months (65-85% at 65 dB SPL). The two other patients, however, had low scores for monosyllables at 6 months (25 and 15% at 65 dB SPL, respectively) with worsening of results thereafter. CONCLUSIONS: Cochleovestibular schwannomas with transmodiolar and transmacular extension represent a rare entity with specific management requirements. Hearing rehabilitation with CI is a principal option in these patients.

[Extent of resection in intrathyroidal medullary thyroid cancer]. / Resektionsausmaß beim intrathyreoidalen medullären Schilddrüsenkarzinom.

Improvements in preoperative diagnostic modalities in conjunction with highly sensitive calcitonin assays, ultrasound and functional imaging modalities and differentiated genetic testing for detection of hereditary forms, have enabled detection and resection of medullary thyroid carcinoma at an increasingly earlier stage. These developments open up possibilities to deescalate primary surgery adapted to these stages and avoid surgical overtreatment in locally limited tumor growth: thus, promoting a shift from routinely recommended total thyroidectomy with bilateral central lymph node dissection in favor of limited unilateral thyroid resection. Prerequisites for limited thyroid resection include clinical evidence that the tumor is sporadic, unifocal and confined to the thyroid. Corresponding calcitonin levels should also indicate that a biochemical cure will be achieved after unilateral resection. A decisive structural prerequisite for such a limited concept is the low threshold availability of intraoperative frozen section analysis that reliably detects and evaluates a medullary thyroid carcinoma and can assess a breach of the thyroid capsule and desmoplasia with certainty.

Case report: A fatal case of cryptococcosis in an immunocompetent patient due to Cryptococcus deuterogattii (AFLP6/VGII).

INTRODUCTION: Cryptococcosis in immunocompetent adults is a rare disease in Europe, mostly induced by members of the Cryptococcus gattii species complex. The diagnosis can be challenging due to its rarity, unspecific symptoms and long symptomless latency. CASE PRESENTATION: A 49-year-old woman with a three weeks history of headache was admitted to the hospital due to discrete ataxia and impaired vision. Cranial magnetic resonance imaging (MRI) showed a contrast-enhancing mass in the cerebellum. Further investigations detected a slight leukocytosis and a single subpleural nodule in the right inferior lung lobe. The cerebral lesion was surgically removed, and a direct frozen section only showed an unspecific inflammation. In the course of her admission she developed non-treatable cerebral edema and died ten days after surgical intervention. Histopathological examination of the surgical specimen and postmortem evaluation of the lung and the cerebrum demonstrated fungal elements. Molecular identification of the fungal elements in formalin-fixed paraffin-embedded tissue lead to the diagnosis of cryptococcosis induced by C. gattii sensu lato. Molecular genetic analysis identified the involved cryptococcal species as genotype AFLP6/VGII, recently described as Cryptococcus deuterogattii, which is known to be endemic to the west-coast of Canada and the USA. Additional heteroanamnestic information revealed that she had spent her holidays on Vancouver Island, Canada, two years before disease onset, indicating that infection during this stay seems to be plausible. CONCLUSION: Cryptococcosis due to C. deuterogattii is a rarely encountered fungal disease in Europe, not particularly associated with immunodeficiency, and infection is likely to be contracted in endemic areas. Due to its rarity, long symptomless latency, unspecific symptoms and misleading radiological features the diagnosis can be challenging. Physicians need to be aware of this differential diagnosis in immunocompetent patients, as early adequate therapy can be lifesaving.

[Ectopic tissue of the thyroid gland and the parathyroid glands]. / Ektopes Gewebe der Schilddrüse und der Nebenschilddrüsen.

Ectopic thyroid tissue results from developmental defects of the early stages of thyroid embryogenesis, in which the median thyroid anlage descends from the floor of the mouth to its final pre-tracheal position. The most common sites of ectopic thyroid tissue are accordingly in the area of the floor of the mouth and in the course of the thyroglossal duct. Rare localizations are intrathoracic (mediastinal, cardiac, pulmonary) and sub-diaphragmatic (including the adrenals, liver, gall bladder, and gastrointestinal tract). The most important differential diagnosis of ectopic thyroid is metastasis of differentiated thyroid carcinoma.By contrast, the term parathyroidectopy is not uniformly defined. Usually, the cervical-central localizations are referred to as "positional variants" (with the exception of the maxillary sinus and high parapharyngeal), whereas the cervical-lateral localizations (carotid sheath, vagus nerve) and those below the brachiocephalic and mediastinal positions (extraligamentary, aortopulmonary window, paravagal) and other rare localizations are classified as "ectopic parathyroid tissue". Parathyroidectomy is very common (in autopsy studies in 28 to 42.8% of all humans). In the context of primary hyperparathyroidism (pHPT), there is a prevalence of 6.3 to 16% of ectopic hyperfunctional parathyroid tissue (predominantly adenomas), which play an important role in the surgical treatment of pHPT.

[Non-Small Cell Lung Cancer - Development of Parallel Mechanisms of Resistance]. / Nicht kleinzelliges Lungenkarzinom ­ doppelte Resistenzentwicklung.

Acquired resistances to tyrosine kinase inhibitors in non-small cell lung cancer develop after 9 - 12 month. In 60 % of the cases these resistances arise because of a secondary EGFR-T790 M resistance mutation. This report is describing the case of a patient who developed parallel two different mechanisms of resistance: A T790 M resistance mutation and a transformation into a small cell neuroendocrine cancer. Under therapy with Osimertinib and chemotherapy with carboplatin and etoposide the tumor responsed partially.

[Dacryoliths and Iatrogenic Foreign Bodies as Classical Triggers for Inflammatory Pseudotumors of the Lacrimal Drainage System]. / Dakryolithen und iatrogene Fremdkörper als klassische Auslöser entzündlicher Pseudotumoren der ableitenden Tränenwege.

BACKGROUND: Tumors of the lacrimal duct are rare. Inflammatory pseudotumors do not represent neoplasias as such. Chronic inflammation may lead to an angiomatous granulation tissue. PATIENTS: The first case presents a 53-year-old male patient suffering a mass of the mediocaudal orbit after an acute dacryocystitis has been cured. Using diagnostic dacryoendoscopy, a large dacryolith was detected. Removing the concrement, via external dacryocystorhinostomy, a polypous tissue appeared which was resected as well. The second case concerns a 29-year-old female patient. She had a lacrimal surgery with stenting seven years prior to surgery. The patient's history revealed recurrent mucous secretion of the tear duct and tenderness of the lacrimal sac. An intrasaccal silicon foreign body could be confirmed by dacryoendoscopy. An external dacryocystorhinostomy was performed and the material was extracted. Hereby, an inflammatory tissue mass filling the whole efferent tear duct was removed. RESULTS: In both patients, external dacryocystorhinostomy was performed complication-free. Surgery enabled the reconstruction of the nasolacrimal duct. Temporary autostable silicon intubation was inserted into the nasolacrimal duct (case 1 and 2), as well into osteotomy (case 2). Histologically, reactive granulation tissue was confirmed. During the follow-up of 9 months (patient 1) and 12 months (patient 2), patients were free of complaints. Lacrimal stentings were removed uneventfully and completely. CONCLUSIONS: Dacryoliths and intrasaccal foreign bodies may cause a chronic dacryocystitis. Due to inflammation, reactive tissue proliferation can be initiated. In these cases, a hypertrophic granulation arose. Endogenous (dacryoliths) and exogenous (iatrogenic foreign bodies) triggers may be underlying reasons. Histological examination is essential for differentiating other inflammatory pathologies or tumors.

[Concretions and iatrogenic foreign bodies in the lacrimal system : Treatment recommendations]. / Konkremente und iatrogene Fremdkörper der ableitenden Tränenwege : Therapeutische Empfehlungen.

BACKGROUND: Deposits (dacryoliths or foreign bodies) inside the lacrimal system can cause chronic inflammation and recurrent lacrimal stenosis. Furthermore, dacryoliths can occur due to chronic inflammation. OBJECTIVE: Considering typical clinical courses, the different localizations and surgical options for removing deposits from the lacrimal system are demonstrated. MATERIALS AND METHODS: A retrospective analysis of 1451 lacrimal surgeries in 1131 patients was performed. Fourteen representative lacrimal surgeries of 11 patients were retrospectively analyzed in terms of current complaints, prior surgery, and the performed surgical intervention. In three cases, histologic findings of removed dacryoliths were assessed. The surgical approaches are described using precise photodocumentation. RESULTS: In 220 lacrimal surgeries (15.2 %), dacryoliths were detected. Iatrogenic foreign bodies were found in 0.8 % (n = 12). All chosen patients suffered painful chronic inflammation of the lacrimal system. Localization was either intrasaccular or intracanalicular. In 10 eyes, surgery was performed using a transcanalicular dacryoendoscope, either alone or in combination with another method. An external approach (transcutaneous/transconjunctival) was performed in 4 patients. Regarding the whole study population, dacryoliths were found in 16.9 % (n = 91) of dacryocystorhinostomies, in 14.6 % (n = 77) of dacryoendoscopies, and in 35.6 % (n = 52) of canaliculotomies. CONCLUSION: Foreign bodies and dacryoliths are important differential diagnoses in the treatment of chronic dacryocystitis. Different surgical approaches are possible and should be available for treatment. Patients' history often reports prior lacrimal surgery.

[Intraoperative frozen sections of the thyroid gland]. / Intraoperativer Gefrierschnitt der Schilddrüse.

The goal of evaluation of intraoperative frozen sections of the thyroid gland is to achieve a definitive diagnosis which determines the subsequent surgical management as fast as possible; however, due to the specific methodological situation of thyroid frozen sections evaluation a conclusive diagnosis can be made in only some of the cases. If no conclusive histological diagnosis is possible during the operation, subsequent privileged processing of the specimen allows a final diagnosis at the latest within 48 h in almost all remaining cases. Applying this strategy, both pathologists and surgeons require a high level of communication and knowledge regarding the specific diagnostic and therapeutic peculiarities of thyroid malignancies because different surgical strategies must be employed depending on the histological tumor subtype.

Impact of different methodologies on the detection of point mutations in routine air-dried fine needle aspiration (FNA) smears.

Currently the best method to select suspicious thyroid nodules for surgery is fine needle aspiration (FNA) cytology. However, FNA cytology has some inherent limitations, which can partly be overcome by molecular analysis. Therefore, molecular testing for somatic mutations has emerged as the most promising approach for molecular FNA diagnostics. The objective of this methodological study was to evaluate the feasibility of detecting BRAF, NRAS, HRAS, and KRAS mutations from routine air-dried thyroid FNA smears, and to find an optimal method for detecting these mutations in FNA samples. DNA was extracted from 110 routine air-dried FNA smears and the corresponding surgically obtained formalin-fixed paraffin-embedded tissues. The presence of BRAF, NRAS, HRAS, and KRAS mutations was assessed by real-time PCRs and high resolution melting analysis, and/or pyrosequencing in comparison to real-time PCRs using hybridization probes and fluorescence melting curve analysis. The high-resolution melting-PCRs revealed a significantly lower number of PCR failures and questionable results, and detected more mutations than the PCRs using hybridization probes. The number of PCR failures ranging from 14-16% by high-resolution melting-PCRs could be further reduced to 5-14% by adding pyrosequencing assays. Moreover, pyrosequencing increased the specificity of the assays, up to 98-100%, while the sensitivity ranged between 32-63%. In summary, the mutation detection, especially in air-dried FNA samples, improves when using PCR assays in combination with high resolution melting analysis. Additional improvement can be obtained by subsequent pyrosequencing in comparison to previously described real-time PCRs using hybridization probes and fluorescence melting curve analysis.