The V600E mutation of the B-type Raf kinase (BRAF) gene is a common event in papillary thyroid carcinoma (PTC) and seems to play a key role in the development and progression of this disease. We evaluated the expression of the mutated BRAF V600E protein in 144 cases of PTC using a novel mutation-specific antibody. Seventy-six PTCs (52.8%) showed unequivocal diffuse cytoplasmic expression of the mutated BRAF protein, and the T1799A point mutation was confirmed by sequencing analysis in selected cases. No statistical difference in V600E BRAF protein expression was seen between microcarcinomas and macrocarcinomas. Further, no significant correlation of V600E expression with clinicopathologic parameters of aggressiveness such as lymph node metastasis, peritumoral infiltration, or perithyroidal infiltration was found. BRAF V600E protein expression was significantly more common in tumors with tall cell or oncocytic features but was less common in tumors with follicular growth pattern. Diffuse sclerosing, solid and follicular variants did not show the mutated BRAF protein. Immunohistochemical detection of the mutated V600E BRAF protein in PTC may facilitate mutational analysis in the clinical setting. Our data show that the expression of the mutated BRAF V600 protein and thus the corresponding BRAF mutation seems not to be per se a marker of aggressiveness but is already seen in clinically indolent microcarcinomas. Nevertheless, the investigation of BRAF V600E protein expression might be of clinical interest especially in therapy-resistant disease, as new therapeutics inhibiting the mutated protein are clinically available.

Meningiomas of the ventricle system are extremely rare. We report on a series of 16 intraventricular meningiomas (IVMs) treated at our institution between 1980 and 2004, with a special interest on the surgical outcome of using the intra/inter-parietal and parieto-occipital approach and the benefits of neuro-navigation. A retrospective analysis of the medical files for clinicoradiological findings, surgical interventions and surgical outcome was carried out. In 16 IVM patients with a female/male ratio of 11:5, age ranged from 24 years to 84 years (median 44 years). Duration of symptoms ranged from a few days to several years, and the cardinal symptoms were signs of increased intracranial pressure (86%), followed by corticospinal tract signs (43%), visual field defects (36%), cognitive changes (29%) and seizures (7%). The majority of tumours was located in the trigone (88%), and one was found in each the temporal horn and in the fourth ventricle. Tumour size ranged from 2.5 cm to 8 cm (median 5 cm), and the radiological appearance was uniform. The neuropathological workup revealed most IVMs as meningothelial, transitional (mixed) or lymphoplasmacyte-rich meningiomas (81%). Three tumours were classified as atypical (19%) and the MIB-1 proliferation index ranged from 1% to 40%. Complete resection was possible in all but one case. The trigonal IVMs were resected via an intraparietal/inter-parietal or parieto-occipital approach, and neuro-navigation was used in eight tumours. We encountered one perioperative death and one severely disabled patient. All other patients had a Glasgow outcome scale score of 5, and most of the pre-existing symptoms disappeared or improved after surgery. IVMs are a surgically curable tumour entity in most cases. The intraparietal/inter-parietal and parieto-occipital approach is very safe, and neuro-navigation allows early devascularisation of the tumour.

Incidentally detected PMC, even when multifocal, is a biologically indolent tumor that seldom if ever progresses. In contrast, clinically occult PMC detected due to clinically suspected and histological confirmed lymph node metastases or extrathyroidal growth may show a more aggressive course with disease recurrence and an eventual poorer prognosis.

A European Federation of Cytology Societies (EFCS) working party of 28 members from 14 European countries met at the European Congress of Cytology in Lisbon in September 2009, with two observers from the USA, to discuss the need for standardising thyroid FNA nomenclature in the light of the National Institute of Cancer (NCI) recommendations resulting from the State of the Science conference in Bethesda in 2007. The data were obtained through two questionnaires sent by email and a transcript of the live discussion at the congress, which is presented in full. The surveys and discussion showed that there were currently no national terminologies for reporting thyroid FNA in the different European countries except in Italy and the UK. Personal, 'local', surgical pathology and descriptive terminologies were in use. All but one of the working party members agreed that thyroid FNA reporting should be standardised. Whilst almost a third would adopt the NCI Bethesda terminology, which offers the advantages of a 'risk of cancer' correlation and is linked to clinical recommendations, more than half favoured a translation of local terminology as the first step towards a unified nomenclature, as has been done recently in the UK. There was some disagreement about the use of: a) the six-tiered as opposed to four or five-tiered systems, b) the use of an indeterminate category and c) the 'follicular neoplasm' category, which was felt by some participants not to be different from the 'suspicious of malignancy' category. The conclusions will be passed to the different national societies of cytology for discussion, who will be asked to map their local terminologies to the Bethesda classification, observe its acceptance by clinicians and audit its correlation with outcome.

Our data indicate that a desmoplastic stromal reaction seems to be an indicator of invasive behaviour of papillary thyroid microcarcinomas significantly associated with lymph node metastases. Papillary microtumours without signs of invasion, e.g. desmoplasia, should not be regarded as invasive carcinoma, as they are more likely to be thyroidal intraepithelial neoplasias.

Medullary thyroid carcinomas are aggressive neoplasias that metastasize very early to loco-regional lymph nodes, and tumors with a desmoplastic stromal reaction have a higher incidence of lymph node metastasis. In order to characterize the desmoplastic response in thyroid cancers, we evaluated the expression pattern of three molecular markers of activated fibroblasts/myofibroblasts, namely, fibroblast activation protein α (FAPα), tenascin-C (Tn-C), and α-smooth muscle actin (α-SMA), as well as the endothelial markers endoglyx-1, CD34 and CD31 in a series of 28 metastatic and non-metastatic medullary thyroid cancers. Immunohistochemical studies demonstrated that the three fibroblast activation markers (FAPα, Tn-C, α-SMA) are consistently expressed in the peritumoral and intratumoral stromal compartment of medullary thyroid carcinomas and expression of FAPα and Tn-C correlated with the degree of desmoplasia determined histologically (p=0.001 for FAPα and p<0.001 for Tn-C). Moreover, the extent of desmoplasia as well as the expression of FAPα and Tn-C correlated with the presence of lymph node (LN) metastases (p=0.002, p=0.005 and p=0.002, respectively). No correlation was found between the microvessel density (neoangiogenesis) in the tumor stroma, assessed with the endoglyx-1, CD34 and CD31 markers, and the degree of desmoplasia or incidence of LN metastases. Using a bioinformatics-based search of the BioExpress™ database we found in a series of 48 thyroid cancers a significant correlation between FAPα RNA expression and incidence of LN metastases also in papillary cancers. These findings suggest that the link between specific molecular markers of tumor stromal reaction and locoregional metastasis extends from medullary to other thyroid cancer types.

The preliminary data suggest that the combination of radiation and concomitant docetaxel is highly effective in patients with ATC. However, a formal phase II study is needed to assess the therapeutic potential of this combination.

BACKGROUNDSince the first description of Central neurocytomas (CNs) as a benign tumor entity in 1982, there has been great enthusiasm regarding the benign course and the curative surgical approach to this disease. The current study was performed to investigate the frequency of disease recurrence during long‐term follow‐up.METHODSA retrospective analysis of the medical files with emphasis on clinicoradiologic findings and histologic and immunohistochemical features was performed.RESULTSBetween 1985–2003. surgical resection was performed in 14 patients with CNs ages 16–43 years (7 were female and 7 were male). Two patients (14%) died postoperatively and one patient had a malignant disease course (7%). In the remaining 11 patients, one patient with an incompletely resected CN had disease progression after 37 months but at the time of last follow‐up had had stable disease for 10 years. In addition, the authors reported 5 patients with disease recurrence occurring at a median of 67 months after surgery (range, 51–79 months after surgery), all of which occurred after complete surgical resection was performed. The observation period for the remaining 5 patients was short (median of 34 months [range, 5–44 months]). Extensive histologic and immunohistochemical workup did not identify any significant prognostic parameters. The MIB‐1 proliferation index ranged from 0.8–11% (median of 4.6%), but was reported to be 46.8% in the malignant transformed tumor. All patients with disease recurrence responded well to different forms of focal radiation therapy (gamma knife radiosurgery in three patients and interstitial irradiation in one patient) and for one patient with a recently detected recurrence, gamma knife radiosurgery was planned.CONCLUSIONSCNs appear to have a higher tendency to recur during long‐term follow‐up than previously reported, even after complete resection. Therefore, periodic neuroradiologic follow‐up examinations should be considered mandatory in all patients, even after several years. Cancer 2005. © 2005 American Cancer Society.