Active surveillance (AS) has been recommended as the first-line treatment strategy for low-risk (LR) papillary thyroid microcarcinoma (PTMC) according to the guidelines. However, preoperative imaging and fine-needle aspiration could not rule out a small group of patients with aggressive PTMC with large-volume lymph node micro-metastasis, extrathryoidal invasion to surrounding soft tissue, or high-grade malignancy from the AS candidates.
Among 2,809 PTMC patients, 2,473 patients were enrolled in this study according to the inclusion criteria. Backward stepwise multivariate logistic regression analysis was used to filter clinical characteristics and ultrasound features to identify independent predictors of high-risk (HR) patients. A nomogram was developed and validated according to selected risk factors for the identification of an HR subgroup among \"LR\" PTMC patients before operation.
For identifying independent risk factors, multivariable logistic regression analysis was performed using the backward stepwise method and revealed that male sex [3.91 (2.58-5.92)], older age [0.94 (0.92-0.96)], largest tumor diameter [26.7 (10.57-69.22)], bilaterality [1.44 (1.01-2.3)], and multifocality [1.14 (1.01-2.26)] were independent predictors of the HR group. Based on these independent risk factors, a nomogram model was developed for predicting the probability of HR. The C index was 0.806 (95% CI, 0.765-0.847), which indicated satisfactory accuracy of the nomogram in predicting the probability of HR.
Taken together, we developed and validated a nomogram model to predict HR of PTMC, which could be useful for patient counseling and facilitating treatment-related decision-making.

Bipolar androgen therapy (BAT) relies on oscillating levels of serum testosterone as a way to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Aggressive-variant prostate cancers typically require combination chemotherapy and are frequently associated with loss-of-function mutations in tumor suppressor genes. Here we report clinical outcomes after BAT among patients with mCRPC harboring pathogenic alterations in at least two of three genes: TP53, PTEN, and RB1. In this setting, BAT induced a meaningful PSA50 response rate, progression-free survival and overall survival, particularly in patients without prior chemotherapy.
UNASSIGNED: Bipolar androgen therapy, in which drugs are used to raise testosterone levels and then allow them to decrease again in a cycle, may be a safe and effective treatment for prostate cancer that is resistant to testosterone suppression and has mutations in tumor suppressor genes. A randomized study comparing this approach to chemotherapy is needed to confirm the findings.

This review will discuss micropapillary urothelial carcinoma with respect to biology, histopathologic characteristics, genetic and molecular features, diagnosis, clinical management, and future directions of research.
Recent consensus opinion study showed only moderate interobserver reproducibility in the diagnostic criteria. The most reproducible criteria with the highest consensus were multiple nests in the same lacunar spaces. There are recent reports of high rates of intratumoral heterogeneity of ERBB2 amplification within tumor containing both micropapillary and classic urothelial components. Micropapillary urothelial carcinoma is a well-documented highly aggressive variant of urothelial carcinoma with proven worse outcomes. Accurate recognition and reporting of this pattern is critical for optimal management. Newer therapeutic strategies related to the molecular and genetic findings seen in MPUC remain to be explored further.

The term aggressive variant prostate cancer (AVPCa) refers to androgen receptor (AR)-independent anaplastic forms of prostate cancer (PCa), clinically characterized by a rapidly progressive disease course. This involves hormone refractoriness and metastasis in visceral sites. Morphologically, AVPCa is made up of solid sheets of cells devoid of pleomorphism, with round and enlarged nuclei with prominent nucleoli and slightly basophilic cytoplasm. The cells do not show the typical architectural features of prostatic adenocarcinoma and mimic the undifferentiated carcinoma of other organs and locations. The final diagnosis is based on the immunohistochemical expression of markers usually seen in the prostate, such as prostate-specific membrane antigen (PSMA). A subset of AVPCa can also express neuroendocrine (NE) markers such as chromogranin A, synaptophysin and CD56. This letter subset represents an intermediate part of the spectrum of NE tumors which ranges from small cell to large cell carcinoma. All such tumors can develop following potent androgen receptor pathway inhibition. This means that castration-resistant prostate cancer (CRPCa) transdifferentiates and becomes a treatment-related NE PCa in a clonally divergent manner. The tumors that do not show NE differentiation might harbor somatic and/or germline alterations in the DNA repair pathway. The identification of these subtypes has direct clinical relevance with regard to the potential benefit of platinum-based chemotherapy, poly (ADP-ribose) polymerase inhibitors and likely further therapies.

Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. Despite being important to recognise, the clinical features of NEPC are poorly defined and could help guide when to perform a biopsy to look for NEPC histologic transformation.
We reviewed baseline, treatment and outcome data of 87 patients with metastatic prostate cancer and tumour biopsy confirming NEPC histology. Forty-seven (54.0%) NEPC cases presented de novo, and 40 (46.0%) were therapy-related (t-NEPC). Thirty-six (41.4%) were classified as pure small-cell carcinoma, and 51 (58.6%) demonstrated mixed features with both small-cell carcinoma and adenocarcinoma present. Genomic data were available for 47 patients.
The median age at time of NEPC was 68.1 years, median prostate-specific antigen (PSA) was 1.20 ng/ml (0.14 ng/mL small-cell carcinoma, 1.55 ng/mL mixed carcinoma) and sites of metastases included bone (72.6%), lymph node (47.0%), and viscera (65.5%). Median time from adenocarcinoma to t-NEPC diagnosis was 39.7 months (range, 24.5-93.8) with a median of two lines of prior systemic therapy. Platinum chemotherapy was used to treat 57.5% of patients, with a median progression-free survival of 3.9 months. Small-cell carcinoma was associated with worse overall survival (OS) than mixed histology (8.9 months from NEPC diagnosis versus 26.1 months, P < 0.001). Median OS of de novo NEPC was shorter than that of t-NEPC (16.8 months from prostate cancer diagnosis versus 53.5 months, P = 0.043). An average PSA rise per month of ≤0.7 ng/ml before t-NEPC; elevated lactate dehydrogenase levels, RB1 and TP53 loss and liver metastases were poor prognostic features.
We describe the clinical features of a cohort of patients with NEPC. These characteristics may inform future diagnostic strategies.

Solid variant papillary thyroid carcinoma (SVPTC) is a rare variant of papillary thyroid cancer (PTC) and its prognostic value is still unclear. The purpose of this systematic clinical review and meta-analysis is to investigate the prognostic value of SVPTC in comparison with classical PTC (cPTC).
Four electronic databases, including PubMed, Scopus, Web of Science, and Virtual Health Library, were searched in June 2017. Extracted data were pooled into odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence interval (CI) using the random-effect model.
From 1439 articles, we finally included 11 studies with 205 SVPTCs for meta-analysis. Overall, SVPTC manifested a significantly higher risk for vascular invasion, tumor recurrence, and cancer mortality as compared to cPTC. The genetic profile of SVPTC was also distinct from that of cPTC.
A case of SVPTC should be regarded as an aggressive variant of PTC because of a higher risk for tumor recurrence and mortality.

Prostate cancer initiation, development and progression is driven by androgen receptor (AR) signaling. Androgen deprivation therapy is the primary treatment for patients that present with locally advanced or metastatic disease. However, androgen deprivation therapy is not curative, and patients will progress to castrate-resistant disease (CRPC). Although most patient\'s progress to CRPC via restoration of AR signaling (CRPC-Ad), approximately a quarter of patients will progress via mechanisms independent of AR signaling. This highly lethal phenotype is termed aggressive variant prostate cancer (AVPC). Data from clinical and preclinical studies demonstrate that AVPC involves combinatorial loss-of-function mutations in key tumor suppressor genes, low to absent AR levels, and re-expression of reprogramming, stem, and neuroendocrine related gene signatures. Further, AVPC is shown to evolve from a CRPC-Ad phenotype. Overall, lineage plasticity underlying progression to AVPC is thought to be provoked by genome-wide chromatin remodeling. Here, we will discuss an emerging focus on key drivers of chromatin remodeling in AVPC, and how their identification could provide noninvasive biomarkers to predict or detect AVPC emergence, and therapeutic targets to prevent or reverse progression to AVPC.

Pituitary adenomas with high proliferation rate and rapid growth are well known, but the clinical characteristics, prognosis, and treatment algorithm remain unclear. The clinical characteristics and mid-term prognosis of patients with non-functioning pituitary adenomas with high proliferative potential were retrospectively investigated. This study identified 53 patients with Ki-67 labeling index of > 3% among 845 patients with non-functioning pituitary adenoma (6.3%) initially treated by surgery. Prophylactic treatment was not applied for patients with residual tumor, but salvage treatment was performed if tumor progression was identified within the follow-up period. Twenty-two patients remained progression-free, whereas 31 patients suffered tumor progression. Comparison of gross total removal (n = 22) and non-total removal (n = 31) groups showed significantly longer progression-free period in the former group (P < 0.001). As salvage treatment gamma knife radiosurgery was applied for 11 patients resulting in 10 patients remaining progression-free and regrowth in 1 patient. Fractionated irradiation was applied for 10 patients, resulting in 2 patients remaining progression-free, deaths in 5 patients including 3 of transformation to pituitary carcinoma, dementia in 1 patient caused by frontal lobe dysfunction, and progression in 2 patients requiring additional surgery and gamma knife radiosurgery. Temozolomide was administered in 2 patients, resulting in deaths in both patients including 1 transformation to pituitary carcinoma. Total removal and gamma knife radiosurgery can result in good outcome. However, the prognosis is extremely poor for patients inadequate for gamma knife radiosurgery. Development of new salvage treatments is essential.

Papillary thyroid carcinoma is the most common thyroid malignancy and it is usually associated with a good prognosis. However, recurrence, metastases, and cancer death may occur in 10 to 15% of patients with more aggressive types of papillary thyroid carcinoma, such as tall cell, columnar cell, solid variant, or the more recently described hobnail variant of papillary thyroid carcinoma. Papillary thyroid carcinoma with a prominent hobnail pattern is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. The hobnail variant of papillary thyroid carcinoma shows prominent hobnail features, which have also been referred to as micropapillary. The typical hobnail/micropapillary morphological features show loss of cellular polarity/cohesiveness and support an epithelial-mesenchymal transition as a possible mechanism of metastasis. BRAF p.V600E is the most common mutation in papillary thyroid carcinoma, including the hobnail variant; recent and continuing studies are focused on defining other molecular anomalies that may be useful for prognostic stratification and may provide therapeutic targets.

Metastatic castration-resistant prostate cancer (CRPC) is associated with substantial clinical, pathologic, and molecular heterogeneity. Most tumors remain driven by androgen receptor (AR) signaling, which has clinical implications for patient selection for AR-directed approaches. However, histologic and clinical resistance phenotypes can emerge after AR inhibition, in which the tumors become less dependent on the AR. In this review, we discuss prostate cancer variants including neuroendocrine (NEPC) and aggressive variant (AVPC) prostate cancers and their clinical implications. Improvements in the understanding of the biologic mechanisms and molecular features underlying prostate cancer variants may help prognostication and facilitate the development of novel therapeutic approaches for subclasses of patient with CRPC.