Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.

Tissue-resident immune cells are important for organ homeostasis and defense. The epithelium may contribute to these functions directly or by cross-talk with immune cells. We used single-cell RNA sequencing to resolve the spatiotemporal immune topology of the human kidney. We reveal anatomically defined expression patterns of immune genes within the epithelial compartment, with antimicrobial peptide transcripts evident in pelvic epithelium in the mature, but not fetal, kidney. A network of tissue-resident myeloid and lymphoid immune cells was evident in both fetal and mature kidney, with postnatal acquisition of transcriptional programs that promote infection-defense capabilities. Epithelial-immune cross-talk orchestrated localization of antibacterial macrophages and neutrophils to the regions of the kidney most susceptible to infection. Overall, our study provides a global overview of how the immune landscape of the human kidney is zonated to counter the dominant immunological challenge.

Thyroid nodules are common and occur in up to 50% of the adult population; however, less than 7% of thyroid nodules are malignant. High-resolution ultrasonography (US) is commonly used to evaluate the thyroid gland, but US is frequently misperceived as unhelpful for identifying features that distinguish benign from malignant nodules. Microcalcifications are one of the most specific US findings of a thyroid malignancy. Other useful US features include a marked hypoechogenicity, irregular margins, and the absence of a hypoechoic halo around the nodule. Lymphadenopathy and local invasion of adjacent structures are highly specific features of thyroid malignancy but are less commonly seen. The number, size, and interval growth of nodules are nonspecific characteristics. Suspicious US features may be useful for selecting patients for fine-needle aspiration biopsy when incidental nodules are discovered and when multiple nodules are present. Common interpretative pitfalls that may lead to failure to recognize a malignancy include mistaking cystic or calcified nodal metastases for nodules in a multinodular thyroid, mistaking diffusely infiltrative thyroid carcinomas and multifocal carcinomas for benign disease, and failing to recognize microcalcifications in papillary thyroid cancer.

Thyroid nodules are common. Their importance lies in the need to assess thyroid function, degree of and future risk of mass effect, and exclude thyroid cancer, which occurs in 7-15% of thyroid nodules. There are four key components to thyroid nodule assessment: clinical history and examination, serum thyroid stimulating hormone (TSH) measurement, ultrasound and, if indicated, fine-needle aspiration (FNA). If the serum TSH is suppressed, a thyroid scan with Tc can distinguish between a solitary hot nodule, a toxic multinodular goitre or, less commonly, thyroiditis or Graves' disease within a coexisting nodular thyroid. Scintigraphically cold nodules are evaluated in the same way as in the setting of normal or elevated serum TSH levels. Thyroid ultrasonography should be performed only for palpable goitre and thyroid nodules and by specialists with expertise in thyroid sonography. Routine thyroid cancer screening is not recommended, except in high risk individuals, as the detection of early thyroid cancer has not been shown to improve survival. FNA may be performed for nodules ≥ 1.0 cm depending on clinical and sonographic risk factors for thyroid cancer. FNA specimens should be read by an experienced cytopathologist and be reported according to the Bethesda Classification System. Molecular analysis of indeterminate FNA samples has potential to better discriminate benign from malignant nodules and thus guide management. Surgery is indicated for FNA findings of malignancy or indeterminate cytology when there is a high risk clinical context. Surgery may also be indicated for suspicion of malignancy; larger nodules, especially with symptoms of mass effect; and in some patients with thyrotoxicosis.

Some authors have praised the value of fine needle aspiration (FNA) with measurement of intraparathyroid intact parathyroid hormone (iPTH) for localization of the hypersecreting gland(s) in recurrent or persistent primary hyperparathyroidism (HPT). The aim of the present study was to determinate whether FNA for iPTH assay is an effective procedure to distinguish between normal and hypersecreting parathyroid glands. We performed a prospective study of 170 patients who underwent cervicotomy. They were divided into three groups: group A, 50 patients with thyroid diseases; group B, 100 patients with primary HPT; group C, 20 patients with secondary HPT. We performed intraoperative FNA for iPTH measurement from the thyroid, and from the normal and enlarged parathyroid glands, and we compared the different intraglandular iPTH assays. In group A, the intraparathyroid iPTH level was < 1000 pg/ml in 68% of the patients. In group B, in the pathological parathyroid gland iPTH was > 1000 in 88%; conversely, in the normal adjacent parathyroid glands it was < 1000 in 79%. In group C, intraparathyroid iPTH of enlarged glands was > 1000 in 80%. Intrathyroid iPTH was < 100 pg/ml in 96% for the three groups. We conclude that FNA for intraglandular iPTH measurement is an effective tool for distinguishing between normal and pathological parathyroid glands in the setting of primary HPT (p< 0.05), and between thyroid and parathyroid glands in groups A and B. But the procedure should be carried out in conjunction with the sestamibi scan and ultrasonography before surgical reintervention.