HNF-1ß as an immunohistochemical marker for distinguishing chromophobe renal cell carcinoma and hybrid oncocytic tumors from renal oncocytoma.

The histologic features of renal oncocytoma (RO) are similar to those for the more aggressive chromophobe renal cell carcinoma (ChRCC). To assess immunohistochemical markers of the two, the sensitivity and specificity of cytokeratin 7 (CK7) and C-kit, as well as hepatocyte nuclear factor-1ß (HNF-1ß), were analyzed. Typical cases of ChRCC and RO at Severance Hospital between July 2014 and July 2018 were selected retrospectively. Among 44 cases, 17 were unanimously compatible with ChRCC, 16 were RO, and 11 cases were indeterminate. Samples from all selected cases were used for immunostaining with antibodies against CK7, C-kit, HNF-1ß, and CD10. Immunostaining demonstrated complete loss of HNF-1ß expression in 11 out of 17 (64.7%) ChRCC cases and a partial, but significant loss in > 50% of tumor cells in the remaining 6 cases (35.3%). In contrast, HNF-1ß expression was preserved in tumor cells of RO cases. Fourteen of 17 ChRCC cases (82.4%) were diffusely positive for CK7, whereas cases of RO were focal positive or negative. C-kit staining did not show a significant difference between ChRCC and RO. Two of five ChRCC cases showing diffuse immunoreactivity for CD10 had poor prognoses of local invasion, distant metastasis, or death. Loss of HNF-1ß expression is a useful marker with which to diagnose ChRCC, especially in cases with confusing histologic findings or equivocal CK7 staining. Additionally, CD10 staining in high-grade ChRCC aids in diagnosis and prediction of the clinical prognosis.

Endometrium-Limited Metastasis of Extragenital Malignancies: A Challenge in the Diagnosis of Endometrial Curettage Specimens.

Malignancies of extragenital origin very rarely metastasize to the uterine body. Endometrium-limited metastases may pose diagnostic challenges in endometrial curettage specimens as they may be misdiagnosed as primary endometrial tumors. We investigated the clinicopathological characteristics of seven cases with endometrial-limited metastases from carcinomas of the nasopharynx (n = 1), breast (n = 2), colon (n = 2), stomach (n = 1), and appendix (n = 1). The patients' ages ranged from 36 to 71 (mean: 55.4) years. None of the patients had a remarkable gynecological history, and the presenting sign in all cases was abnormal uterine bleeding. Although myometrial involvement was absent, multiple metastases were already present in extrauterine locations such as the lung, liver, bone, abdominopelvic peritoneum, and omentum. All patients underwent ultrasonographic examination prior to endometrial curettage. The histologies of the endometrial metastases identified from the curettage specimens were identical to those of the corresponding primary tumors. Ancillary tests including immunostaining and Epstein-Barr virus-encoded RNA in situ hybridization confirmed the extragenital origin. Endometrium-limited metastases from extragenital malignancies are extremely rare. They present with abnormal vaginal bleeding and mimic endometrial carcinomas of endometrioid or poorly differentiated types. Since their clinical presentations and histological features are similar to those of primary endometrial tumors, pathologists should consider the possibility of metastases while evaluating endometrial curettage specimens obtained from patients with a history of extragenital malignancies.

Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes.

In recent years, renal epithelial tumors have been among the fastest reclassifying tumors, requiring updates to the tumor classification system. Nonetheless, immunohistochemistry (IHC) remains the most widely used tool for renal epithelial tumors. In this proposal, we aimed to create the most efficient IHC panel for categorizing the diverse subtypes of renal tumors, and to find out more specific immunohistochemical results in each subtype or each antibody. A total of 214 renal tumors were analyzed using 10 possible IHC markers to differentiate subtypes, including three major renal cell carcinoma (RCC) subtypes, clear-cell type (50 cases), papillary type (50 cases), and chromophobe type (20 cases), and minor subtypes (MiT RCC, 13 cases; collecting duct carcinoma, 5 cases; and oncocytoma, 10 cases). A triple immunomarker (cytokeratin 7 (CK7)-carbonic anhydrase IX (CAIX)- alpha-methylacyl-CoA racemase (AMACR)) panel is useful in particular high-grade clear-cell tumors. If IHC remains ambiguous, the use of an adjunctive panel can be suggested, including CD10, epithelial membrane antigen, cathepsin K, c-kit, hepatocyte nuclear factor 1-ß, and E-cadherin. For an efficient immunohistochemical strategy for subtyping of RCC, we conclude that the CK7-CAIX-AMACR panel is the best primary choice for screening subtyping.

HoxB13 expression in ductal type adenocarcinoma of prostate: clinicopathologic characteristics and its utility as potential diagnostic marker.

The histologic criteria and selective biomarkers of prostate ductal type adenocarcinoma (DAC) are relatively unknown compared to that known about acinar type adenocarcinoma (AAC). It is known that genetic alteration in Hox13 gene is associated with carcinogenesis of prostate cancer. In this study, we investigated clinicopathologic characteristics of HoxB13 expression in prostate cancer and compared clinicopathologic profiles of DAC and AAC of prostate. After slide review, some morphological variants of DAC, equivalent to Gleason pattern 3 and 5 of AAC were identified. High level of HoxB13 expression was identified in 46.5% (46 out of 99 cases) and 39.2% (31 out of 79 cases) of cases that belong to the training set and test set, respectively. In the training set, high level of HoxB13 expression was significantly correlated with DAC (P < 0.001), higher Gleason score (P < 0.001), advanced pathologic T stage (P = 0.010), and occurrence of biochemical recurrence (BCR; P < 0.001). The test set confirmed that high level of HoxB13 expression was associated with DAC (P < 0.001), higher Gleason score (P = 0.001), advanced pathologic T stage (P < 0.001), and occurrence of BCR (P < 0.001). Our findings suggest that HoxB13 may be a useful diagnostic marker for detection of DAC and a prognostic marker for prediction of BCR.

Evidence Based Tailored Parotidectomy in Treating External Auditory Canal Carcinoma.

Carcinoma of the external auditory canal (EAC) is a rare tumor and little information is available regarding parotid gland in surgically treating EAC carcinomas. This study aimed to investigate the mode of parotid involvement in EAC carcinoma through staging and histopathological analysis, and to establish surgical guidelines for the parotid gland management when there is no clinical evidence of parotid involvement. Sixty-five patients with EAC carcinoma who underwent temporal bone resection and any type of parotidectomy simultaneously were retrospectively reviewed. The rate of direct parotid invasion and parotid nodal involvement was analyzed according to the stage and histopathological findings. Among the 65 patients, 39 were confirmed to have squamous cell carcinoma (SCC) and 26 were confirmed to have adenoid cystic carcinoma (ACC). Direct parotid invasion occurred in 7 of 39 patients with SCC, only in the advanced stages, and in 15 of 26 patients with ACC, regardless of stage. Metastasis to the parotid node was noted in 6 patients with advanced-stage SCC, whereas no patient with ACC showed parotid nodal metastasis. For adequate tumor control with low risk of surgical complications, evidence based tailored parotidectomy should be applied. With no evidence of parotid involvement, an elective parotidectomy can be excluded in early SCC, whereas a total parotidectomy is recommended for advanced SCC. In ACC, basal resection of the parotid gland rather than a superficial or total parotidectomy should be performed at all disease stages.

Clinical characteristics of T790M-positive lung adenocarcinoma after resistance to epidermal growth factor receptor-tyrosine kinase inhibitors with an emphasis on brain metastasis and survival.

OBJECTIVES: We aimed to investigate the clinical characteristics of lung adenocarcinomas with acquired EGFR T790M mutation focusing on brain metastasis and survival. MATERIALS AND METHODS: Our study included patients who had lung adenocarcinoma harboring EGFR mutation at 1st biopsy and then underwent 2nd biopsy after resistance to first- or second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Statistical analyses were performed to examine the associations between clinicopathologic features of lung adenocarcinoma and presence of acquired T790M mutation. RESULTS: A total of 111 patients were identified. Of these, 58 patients (52.3%) had acquired T790M mutations. Osimertinib was used in 29 patients (26.1%) after resistance to first- or second-generation TKIs. The T790M mutation was more frequently found in patients with exon 19 deletion than in those with L858R mutations (p = .026) and in patients who had longer treatment duration with EGFR-TKI (p = .0398). Multivariate analysis revealed that exon 19 deletion (p = .003) were independently associated with T790M mutation. Patients with acquired T790M mutation showed a longer progression-free survival. In addition, patients who had T790M mutation or who received osimertinib treatment had a longer overall and post-progression survival than patients who did not. Brain metastasis-free survival was also longer in the T790M-positive group or osimertinib-treated group among patients who had no brain metastasis at the time of diagnosis. Osimertinib treatment was independently associated with longer overall, post-progression, and brain metastasis-free survival. CONCLUSION: The status of acquired T790M mutation was correlated with exon 19 deletion and longer progression-free survival to first- or second-generation EGFR-TKIs. A third-generation EGFR-TKI, osimertinib, was strongly associated with brain metastasis-free survival as well as other survival indicators in patients with EGFR-mutant lung adenocarcinoma.

Expression of Zinc Finger and BTB Domain-containing 7A in Colorectal Carcinoma.

BACKGROUND/AIM: Previous studies have revealed that zinc finger and BTB domain-containing 7A (ZBTB7A), an important proto-oncogene, plays multiple roles in carcinogenesis and is up-regulated in several human malignancies. However, the expression of ZBTB7A in colorectal carcinoma (CRC) has seldom been documented. In this study, we investigated the differential expression of ZBTB7A in CRC cell lines and tissues. MATERIALS AND METHODS: Expression levels of ZBTB7A mRNA and protein were examined in CRC cell lines. ZBTB7A protein expression was also evaluated in tissue samples of normal colonic mucosa, high-grade dysplasia, and CRC using immunohistochemical staining. RESULTS: All CRC cell lines exhibited significantly higher ZBTB7A mRNA expression levels than did normal colonic epithelial cells. The ZBTB7A protein expression levels were clearly higher in the CRC cell lines than in the normal colonic epithelial cells. Consistent with the cell line data, immunostaining revealed that there were significant differences in ZBTB7A protein expression between tissue samples of CRC and normal colonic mucosa (p=0.048) and high-grade dysplasia (p=0.015). In addition, metastatic CRC exhibited significantly higher ZBTB7A protein expression levels than primary CRC (p=0.027). CONCLUSION: We demonstrated that ZBTB7A expression is up-regulated in CRC cell lines and tissues. Our data suggest that ZBTB7A is involved in the development and progression of CRC.

Recurrent Indeterminate Dendritic Cell Tumor of the Skin.

Indeterminate dendritic cell tumor (IDCT) is a dendritic cell tumor that displays histologic features similar to those of Langerhans cells. The origin of the indeterminate cells may represent precursors of Langerhans cells or skin dendritic cells. IDCT is extremely rare, and tumor progression and predictive factors are not well known. Here, we report a case of a 61-year-old man who presented with a papule on his back and was finally diagnosed with IDCT based on histology and immunohistochemistry. The tumor recurred three months after surgical excision.

Potential-controlled current responses from staircase to blip in single Pt nanoparticle collisions on a Ni ultramicroelectrode.

Collisions of electrocatalytic platinum (Pt) single nanoparticles (NPs) with a less electrocatalytic nickel (Ni) ultramicroelectrode (UME) surface were detected by amplification of the current by electrocatalysis of NPs. Two typical types of current responses, a current staircase or blip (or spike), in single NP collision experiments were observed at a time with a new system consisting of Pt NP/Ni UME/hydrazine oxidation. The staircase current response was obtained when the collided NPs were attached to the electrode and continued to produce electrocatalytic current. On the other hand, the blip current response was believed to be obtained when the NP attached but was deactivated. The different current responses depend on the different electrocatalytic reaction mechanism, characteristics of the NP, or the electrode material. How the deactivation of the electrocatalytic process affects on the current response of NP collision was investigated using the Ni UME. The current response of a single Pt NP collision is controllable from staircase to blip by changing the applied potential. The current response of the Pt NP was observed as a staircase response with 0 V (vs Ag/AgCl) and as a blip response with 0.1 V (vs Ag/AgCl) applied to the Ni UME.