[Morphologic diagnostic criteria of noninvasive follicular neoplasia with papillary-like nuclear features (NIFTP) : A diagnostic challenge for the patient's benefit]. / Morphologische Diagnosekriterien der nichtinvasiven follikulären Neoplasie mit PTC-äquivalenten Kernmerkmalen (NIFTP) : Eine diagnostische Herausforderung zum Nutzen des Patienten.

The major goals of the introduction of the noninvasive follicular neoplasia with papillary-like nuclear features (NIFTP) are to spare patients with a biologically indolent subgroup of the follicular variant of papillary carcinoma (FV-PTC) both overtreatment and the psychologically burden of a cancer/carcinoma diagnosis. However, strict histological and molecular pathological criteria have been introduced for the diagnosis of NIFTP. NIFTP tumors may be a few millimeters in diameter, but may also measure more than 4 cm. Histologically, an encapsulated/clearly demarcated lesion with (>70%) follicular structure and the nuclear characteristics of PTC must be present as a prerequisite; invasion of capsule/vessels must be excluded as well as significant proportions (>30%) showing a solid/trabecular/insular growth pattern, psammoma bodies, tumor necrosis, an increased mitotic rate (>3/10 HPF), and/or a BRAF V600E mutation. The establishment of the NIFTP necessitated a redefinition of the diagnostic criteria of PTC and has implications on the evaluation of fine needle biopsy (FNB) of the thyroid gland. Although a prediction is difficult, the correct diagnosis of NIFTP could lead to a 10-20% reduction in thyroid carcinoma incidence.

[Hemithyroidectomy or total thyroidectomy for low-risk papillary thyroid cancer? : Surgical criteria for primary and secondary choice of treatment in an interdisciplinary treatment concept]. / Hemithyreoidektomie oder totale Thyreoidektomie beim papillären Niedrigrisikokarzinom der Schilddrüse? : Chirurgische Kriterien der primären und sekundären Therapiewahl im interdisziplinären Behandlungskonzept.

The increase in small intrathyroid papillary thyroid cancer (PTC) observed worldwide over the past two decades, with no increase in cancer-specific mortality, has challenged the previous concept of total thyroidectomy as a one-size-fits-all panacea. After exclusion of papillary microcarcinomas, a systematic review of 20 clinical studies published since 2002, which compared hemithyroidectomy (HT) to total thyroidectomy (TT), found comparable long-term oncological outcomes for low-risk papillary thyroid cancer (LRPTC) 1-4 cm in diameter, whereas postoperative complication rates were markedly lower for HT. To refine individual treatment plans, HT should be combined with ipsilateral central lymph node dissection and intraoperative frozen section analysis for staging. Based on recent evidence from studies and in consideration of individual risk factors, patients with LRPTC can be offered the concept of HT as an alternative to the standard TT. A prerequisite for the treatment selection and decision is a comprehensive patient clarification of the possible advantages and disadvantages of both approaches.

DLL3 (delta-like protein 3) expression correlates with stromal desmoplasia and lymph node metastases in medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbor somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been identified as a reliable predictor of aggressive behavior and development of lymph node metastases, a possible correlation of DLL3 expression with the presence of stromal desmoplasia was of particular interest. 59 paraffin-embedded samples of sporadic MTC with (44 cases) and without (15 cases) stromal desmoplasia and known lymph node status were included. DLL3 expression was determined by immunohistochemistry; no expression (0%), low expression (1-49%) and high expression (≥50%) were correlated with clinicopathological data. The proportion of DLL3 positivity was significantly correlated with both stromal desmoplasia (P < 0.0001) and lymph node metastases (P < 0.0001). MTC without stromal desmoplasia consistently lack DLL3 expression. This is the first study to focus on MTC regarding DLL3 expression and the relationship to various factors. Our results demonstrate that expression of DLL3 in MTC represents a reliable surrogate marker for stromal desmoplasia and lymph node metastases and might be an indicator for aggressive clinical behavior. DLL3 expression in ≥50% of tumor cells virtually excludes MTC without stromal desmoplasia. DLL3 was discussed as a potential therapeutic target in malignant tumors of other locations with positive immunohistochemical reaction and might therefore be a new therapeutic option in MTC, as well.

Effect of combined intravenous glucocorticoids and orbital radiotherapy in restoring driving competency in patients with Graves' orbitopathy.

Intravenous glucocorticoids and orbital radiotherapy are effective treatments for moderate-to-severe and active Graves' orbitopathy. We examined the ophthalmological outcome in daily life activities, such as driving competency. In a retrospective case series, 23 patients with moderate-to-severe and active Graves' disease (14 women and 7 men) were consecutively treated with combined orbital radiotherapy (13 Gy) and intravenous methylprednisolone (500 mg weekly for 6 consecutive weeks and 250 mg weekly for consecutive 6 weeks). The pretreatment Clinical Activity Score of 5.2 points (SD+/-0.9) decreased significantly to 2.7 points (SD+/-1.1) in the 12-month follow-up. Inflammatory eye signs, for example, pain and pressure sensation, caruncle inflammation, eyelid swelling, and exophthalmos decreased significantly. However, there was no significant improvement of eye motility. Despite anti-inflammatory treatment, 13 patients (61.9%) were not fit to drive a car under binocular conditions and additional stabismologic therapy including strabismus surgery was required. The combined therapy of intravenous glucocorticoids and orbital radiotherapy reduced inflammatory ophthalmological signs. In most cases strabismologic intervention including eye muscle surgery was necessary to restore driving competency.

[Graves' ophthalmopathy]. / Endokrine Orbitopathie.

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease and the full clinical picture can impair the quality of life of the patients considerably. Active inflammation can often be effectively treated by intravenous steroids/immunosuppression, however does not lead to full remission, since inflammation rather quickly results in irreversible fibrosis and increase of orbital fat. Very important is the control of risk factors (smoking cessation, good control of thyroid function, selenium supplementation) to prevent progression to severe stages. Treatment should rely on a thorough assessment of activity and severity of GO. Rehabilitative surgery (orbital decompression, squint surgery, eyelid surgery) is needed in many patients to restore function and appearance. Anti-thyroid-stimulating hormone (TSH) receptor antibodies do specifically occur in these patients and correlate to the course of thyroid and eye disease. The levels of these antibodies can be used for treatment decisions at certain time points of the disease.