Hereditary papillary renal cell carcinoma.

Hereditary papillary renal cell carcinoma (HPRCC) is an autosomal dominant syndrome characterized by the occurrence of bilateral and multifocal, classic type papillary renal cell carcinomas. In the recent decades, extensive molecular studies have narrowed the molecular underpinnings of this syndrome to missense mutations in tyrosine kinase domain of MET proto-oncogene. Although MET mutations are specific to HPRCC, it has been found in sporadic papillary renal cell carcinomas and as recently reported, in biphasic squamoid alveolar variant of papillary renal cell carcinoma. Dual MET/VEGFR2 kinase inhibitor and tyrosine kinase inhibitors have shown promising results in systemic therapy for HPRCC.

Experimental study on strength and failure characteristics of sandstone rock mass with complex cataclastic structure using 3D printing models.

A cataclastic rock mass is a poor type of engineering geological rock mass. The determination of the shear failure characteristics and shear strengths of cataclastic rock masses can provide key basis for the design and construction of infrastructure. Physical model samples of a sandstone cataclastic rock mass were first produced by a combination of three-dimensional (3D) printing technology and manual pouring. Shear tests were conducted with respect to the shear stresses parallel to the trace line plane and perpendicular to the trace line plane of the cataclastic rock mass model. Based on an extensive analysis of the shear failure characteristic, shear stress evolution characteristic curve and shear strength. When the shear stress was parallel to the trace line plane, and when the rock block that was cut and confined by the trace line exhibited a significant tip, the end stress concentration effect of the cataclastic rock mass was more significant during the shear process with the anisotropy of the rock block increased. In addition, the shapes of the rock blocks that were confined and cut by the joints were the main influencing factors of the strength of the cataclastic rock mass. When the shear stress was perpendicular to the trace line plane, the structure of the rock wall was the main influencing factor of the deformation and failure process of the shear failure plane and the shear strength. The physical and mechanical properties of the shear failure plane of the cataclastic rock mass were found to be closely related to the joint-rock wall system characteristics of the cataclastic rock mass. Therefore, when determining the shear strength of cataclastic rock mass, the shape and combination form of the rock block, shear direction, and structural failure characteristics of the rock wall should be comprehensively considered during the shear process.

Shear strength deterioration effect of rock mass joint surface under cyclic shear load.

Understanding the shear strength degradation mechanism of a rock mass joint surface under cyclic shear load and determining a corresponding analytical model is an important foundation for accurately evaluating the safety of rock mass engineering under seismic loads. It is worth noting that, to date, there has been a dearth of studies on the strength characteristics of joint surfaces that consider the number of loading cycles, normal load, and initial undulant angle of the structural plane. In this study, focused on the behaviour of sandstone, the particle flow code (PFC) modelling framework was used to simulate a joint surface cyclic shear test considering first- and second-order undulations. Based on the experimental results, the comprehensive effects of the number of cyclic shear cycles, the normal stress, first- and second-order undulation and the dilatancy angle on shear stress during cyclic shear were analysed. Formulas for the joint surface shear basic friction angle and dilatancy angle under cyclic shear were proposed, and a method for calculating the joint surface peak shear strength under cyclic shear considering the deterioration of the dilatancy angle and basic friction angle was established. The peak shear strength of a sample after five cycles of shearing was calculated using the proposed formula and compared with the results of numerical simulations, the Barton method, and the Homand method. The results showed that the calculated values have good consistency with the results of the numerical simulations, demonstrating the effectiveness and accuracy of the proposed formula. However, under a low normal stress, there could be errors in estimating the cyclic shear strength of the joint surface.

Shear characteristics and shear strength model of rock mass structural planes.

Accurately determining the shear strength of structural planes is crucial for evaluating the stability of rock masses. The shear test using the sawtooth structural plane usually captures the main influencing factors of its shear characteristics. In this study, the two-dimensional particle flow code (PFC2D) numerical simulation method was used to conduct shear tests on the sawtooth structural planes of rock masses with undulant angles of 10°, 20°, and 30°, respectively. With the increase in normal stress and the undulant angle, the shear failure of the structural planes was found to no longer be pure slip failure or shear failure but accompanied by a compression-induced fracture phenomenon. Based on the analysis of the shear test results, a peak shear strength model considering different undulant angles and normal stresses was proposed, and the hyperbolic function post-peak shear strength model was improved. The peak shear strength obtained from the physical direct shear tests was compared with those calculated using the proposed model, Parton model, and Shen model. The calculation error under low and high normal stress of the proposed method was found to be within an acceptable range. Additionally, when calculating the peak shear strength of a structural plane under high normal stress, applying the calculation method proposed in this study is a better option than applying the other models. Furthermore, although the variation trend of the post-peak shear strength was similar to that of the experimental results, the values obtained using the hyperbolic variation model were too large. The variation trend of the post-peak shear strength obtained using the improved function was essentially consistent with the experimental results, and the calculated values were close to the experimental results. The systematic research on the shear strength calculation model of rock mass structural planes contributes to the theoretical research of rock mass mechanics, and this study can act as a guide for landslide prediction and control projects.

Method of calculating shear strength of rock mass joint surface considering cyclic shear degradation.

When a rock mass shears along a joint surface, the shear resistance is affected by joint surface undulations and friction between the contact regions. During an earthquake, the seismic load causes dynamic deterioration of the joint surface mechanical properties, mostly reflected as follows. (1) The peak shear strength of the joint surface decreases with an increase in the shear rate. (2) Under a seismic load cyclic shear, the undulant angle αk decreases. (3) Under a dynamic load, the friction coefficient of the joint surface is reduced. By studying the cyclic shear test of the joint surface, the strength deterioration effect of the joint surface under cyclic shearing is first analysed, and the equations of the dilatation angle and the basic friction angle of the joint surface under the cyclic shearing load are proposed. Then, starting with the effect of cyclic shear deterioration on the joint surface in the rock mass and the reduction in the dynamic friction coefficient between sliding rock blocks caused by relative velocity, an equation for calculating the shear strength of a rock mass joint surface under cyclic shear loading is recommended. Through two case calculations, the shear strength obtained using the proposed method is compared with the experimental results. The results show that the model proposed in this study is in good agreement with the experimental results and can also be used to calculate the structural surface shear strength of the asperity-rich sample. However, when the calculation equation is used to estimate the cyclic shear strength of the joint surface where the sum of the initial undulation angle and the basic friction angle is greater than 70°, there may be some errors in the calculation results.

The role of α-smooth muscle actin in confirming the microinvasion of laryngeal squamous cell carcinoma.

BACKGROUND: The diagnosis of microinvasive laryngeal squamous cell carcinoma (LSCC) is not always straightforward and sometimes can be very challenge in daily clinical practice. The focus lies in the confirmation of microinvasion. Cancer-associated fibroblasts (CAFs), as the major element of reactive tumor stroma, are believed to participate actively in the growth and invasion of tumor cells. OBJECTIVES: To evaluate the diagnostic role of α-smooth muscle actin (α-SMA) labelling CAFs in microinvasive LSCC. METHODS: A total of 81 laryngeal biopsy specimens were retrieved, including 41 cases of microinvasive LSCC with depth of invasion no more than 3 mm, 20 laryngeal squamous intraepithelial lesion (SIL), and 20 benign pseudoepitheliomatous hyperplasia (PEH). All cases were stained for immunohistochemistry, using antibody against the α-SMA antigen. The correlation between the presence of CAFs in microinvasive LSCC and tumor histological characteristics was investigated. RESULTS: Immunoreactivity of α-SMA was detected in twenty-nine microinvasive LSCC (29/41, 71%), while no reactivity was observed in laryngeal SIL (0/20, 0%), and rarely in PEH (2/20, 10%). The α-SMA expression pattern in stroma of microinvasive LSCC was significantly different from that of SIL (χ2 = 26.966, p = 0.000) and PEH (χ2 = 19.838, p = 0.000). In addition, there seemed to be a certain correlation between the histological characteristics of microinvasive LSCC and the presence of interstitial CAFs. CONCLUSIONS: This study highlights the practical role of utilizing α-SMA in the pathological diagnosis of microinvasive LSCC, with emphasis on variable histomorphologic features of microinvasive LSCC.

Clonal evaluation of early onset prostate cancer by expression profiling of ERG, SPINK1, ETV1, and ETV4 on whole-mount radical prostatectomy tissue.

BACKGROUND: Expression profiles of erythroblast transformation-specific (ETS)-related gene fusions and serine protease inhibitor Kazal-type 1 (SPINK1) in early onset prostate cancer have not been thoroughly explored. METHODS: We retrieved 151 radical prostatectomy specimens from young men with prostate cancer (<55 years) and characterized the expression of ETS-related gene (ERG), SPINK1, ETS Variant 1 (ETV1), and ETV4 by dual immunohistochemistry and dual RNA in situ hybridization. Age, race, family history, preoperative prostate-specific antigen, biochemical recurrence, and pathological variables using whole-mount radical prostatectomy tissue were collected. RESULTS: A total of 313 tumor nodules from 151 men including 68 (45%) Caucasians and 61 (40%) African Americans were included in the analysis. Positive family history of prostate cancer was seen in 65 (43%) patients. Preoperative prostate-specific antigen ranged from 0.3 to 52.7 ng/mL (mean = 7.04). The follow-up period ranged from 1 to 123.7 months (mean = 30.3). Biochemical recurrence was encountered in 8 of 151 (5%). ERG overexpression was observed in 85 of 151 (56%) cases, followed by SPINK1 in 61 of 151 (40%), ETV1 in 9 of 149 (6%), and ETV4 in 4 of 141 (3%). There were 25 of 151 (17%) cases showing both ERG and SPINK1 overexpression within different regions of either the same tumor focus or different foci. Higher frequency of ERG overexpression was seen in younger patients (≤45 years old; 76% vs 49%, P = .002), Caucasian men (71% vs 41% P = .0007), organ-confined tumors (64% vs 33%, P = .0008), and tumors of Gleason Grade groups 1 and 2 (62% vs 26%, P = .009). SPINK1 overexpression was more in African American men (68% vs 26%, P = .00008), in tumors with high tumor volume (>20%) and with anterior located tumors. ETV1 and ETV4 demonstrated rare overexpression in these tumors, particularly in the higher-grade tumors. CONCLUSION: This study expands the knowledge of the clonal evolution of multifocal cancer in young patients and support differences in relation to racial background and genetics of prostate cancer.

Immunohistochemical characteristics of renomedullary interstitial cell tumor: a study of 41 tumors with emphasis on differential diagnosis of mesenchymal neoplasms.

Renomedullary interstitial cell tumors (RMICTs) are almost always incidentally identified either at autopsy or upon resection of the kidney for other reasons. However, rare cases that are large, resulting in a clinical mass, have been reported. The immunohistochemical phenotype of usual, incidental RMICT using modern soft tissue tumor markers is largely unknown, however, providing little information to aid in classification of larger or atypical tumors. We retrieved 41 RMICTs from 36 patients and studied pathologic characteristics including morphology, immunohistochemistry (S100, keratin AE1/AE3, smooth muscle actin, desmin, estrogen and progesterone receptors, calponin, CD34, CD35), and histochemical staining. Data collected included age, sex, tumor size, laterality, and indication for kidney examination. RMICTs (n = 41) were identified in 23 men and 13 women, with a mean age of 57 years (range, 24-83 years); tumor sizes ranged from less than 1 to 13 mm (median, 4 mm). Kidneys were resected for 32 tumors, 1 chronic pyelonephritis, 1 trauma, and 2 autopsies. All (41; 100%) had entrapped renal tubules, 5 (12%) of which included cystic or dilated tubules. Most (35; 85%) had collagenous fibers, all of which were negative for Congo red. RMICT demonstrates a largely negative immunohistochemical phenotype with weak-to-moderate labeling for smooth muscle actin and calponin that is substantially less than myofibroblastic lesions. Positive staining for estrogen and progesterone receptors is common (61%), which could overlap with mixed epithelial and stromal tumor and other entities; however, staining is typically weak. CD34 is usually negative, with occasional weak labeling, in contrast to solitary fibrous tumor.

Robotic resection of a mediastinal parathyroid cyst.

Mediastinal parathyroid cysts (PC) are rare, benign lesions, reported in fewer than 150 cases worldwide. Although most are asymptomatic and discovered incidentally on imaging, symptoms of dyspnea, dysphagia, hoarseness, palpitations, hypercalcemia, and innominate or jugular venous thrombosis have been reported. Sternotomy or thoracotomy has traditionally been the approach used to resect mediastinal PCs. We describe the first reported case of a robot-assisted resection of a mediastinal PC.

[Olfactory neuroblastoma with unusual structures: a clinical pathologic study].

OBJECTIVE: To investigate unusual pathological features of olfactory neuroblastoma (ONB) and its correlation with the clinical prognosis. METHODS: Totally 40 cases of ONB were studied using histology and immunohistochemistry techniques. All the cases of ONB were graded according to Hyams Grading system. RESULTS: ONB consisted of small round tumor cells growing in nests or lobules separated by fibrovascular septa. Characteristically, there were neurofibrillary intercellular matrices and Homer-Wright or Flexner-Wintersteiner rosette formation. The unusual structures including epithelial components such as mucous or squamous cell nests which were found in 45.0% (18/40), and 15.0% (6/40) respectively. In addition, 3 cases showed an in-situ form with invasion of tumor into olfactory epithelium, and there was exogenous papillary proliferation seen in 2 cases. Log-rank survival analysis demonstrated that Hyams Grading had no statistical correlation with the prognosis. The presence of necrosis was correlated with a poor prognosis (P = 0.016) while the presence of mucous cells was correlated with a good prognosis (P = 0.011). CONCLUSIONS: Unusual pathological structures including epithelial structures, in-situ invasion of tumor tissue into the involving olfactory epithelium and exogenous papillary proliferation can be found in ONB, suggesting that ONB may originate from the undifferentiated basal cells of olfactory epithelium, through bipotential differentiation. The presence of tumor necrosis in ONB is a poor prognostic indicator while the presence of mucous cells suggests a good prognosis.