Nerves are emerging regulators of cancer progression and in several malignancies innervation of the tumour microenvironment is associated with tumour aggressiveness. However, the innervation of thyroid cancer is unclear. Here, we investigated the presence of nerves in thyroid cancers and the potential associations with clinicopathological parameters. Nerves were detected by immunohistochemistry using the pan-neuronal marker PGP9.5 in whole-slide sections of papillary thyroid cancer (ptc) (n = 75), compared to follicular thyroid cancer (FTC) (n = 13), and benign thyroid tissues (n = 26). Nerves were detected in most normal thyroid tissues and thyroid cancers, but nerve density was increased in PTC (12 nerves/cm 2 [IQR 7-21]) compared to benign thyroid (6 nerves/cm 2 [IQR: 3-10]) (p = 0.001). In contrast, no increase in nerve density was observed in FTC. In multivariate analysis, nerve density correlated positively with extrathyroidal invasion (p < 0.001), and inversely with tumour size (p < 0.001). The majority of nerves were adrenergic, although cholinergic and peptidergic innervation was detected. Perineural invasion was present in 35% of PTC, and was independently associated with extrathyroidal invasion (p = 0.008). This is the first report of infiltration of nerves into the tumour microenvironment of thyroid cancer and its association with tumour aggressiveness. The role of nerves in thyroid cancer pathogenesis should be further investigated.

Metastases in thyroid cancer are associated with aggressive disease and increased patient morbidity, but the factors driving metastatic progression are unclear. The precursor for nerve growth factor (proNGF) is increased in primary thyroid cancers, but its expression or significance in metastases is not known. In this study, we analysed the expression of proNGF in a retrospective cohort of thyroid cancer lymph node metastases (n = 56), linked with corresponding primary tumours, by automated immunohistochemistry and digital quantification. Potential associations of proNGF immunostaining with clinical and pathological parameters were investigated. ProNGF staining intensity (defined by the median h-score) was significantly higher in lymph node metastases (h-score 94, interquartile range (IQR) 50–147) than in corresponding primary tumours (57, IQR 42–84) (p = 0.002). There was a correlation between proNGF expression in primary tumours and corresponding metastases, where there was a 0.68 (95% CI 0 to 1.2) increase in metastatic tumour h-score for each unit increase in the primary tumour h-score. However, larger tumours (both primary and metastatic) had lower proNGF expression. In a multivariate model, proNGF expression in nodal metastases was negatively correlated with lateral neck disease and being male. In conclusion, ProNGF is expressed in locoregional metastases of thyroid cancer and is higher in lymph node metastases than in primary tumours, but is not associated with high-risk clinical features.

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Nevus lipomatosus cutaneous superficialis (NLCS) is a rare, benign hamartomatous lesion characterized histologically by the presence of ectopic adipocytes in the dermis. This condition was first reported in 1921 in a German journal for dermatologic and venereal diseases. 1 Such lesions are often reported classically as Hoffman-Zurhelle lesions-the namesake of its founders. They are described as multiple, pedunculated lesions presenting en masse. The other, rarer clinical variant, is characterized by a singular rounded papule with no stalk. 2 Hoffman-Zurhelle NLCS can present at birth or in the first 3 decades of life, whereas the solitary variant appears typically after the second decade of adult life. 2 They are uncommonly seen with a necrotic or ulcerating appearance. In this report, we describe a unique case of a torted and infarcted NLCS found in the intergluteal cleft of an 18-hour-old female neonate. | CASE PRESENTATIONA Gravida 4 Para 2 Caucasian lady was referred to the Maternal Fetal Medicine service at our center-a tertiary children's hospital-for an abnormal "soft tissue mass" discovered in her third-trimester antenatal ultrasound. Geographically, she lived >4 hours away and was receiving