Ghil-Suk Yoon

Primary synovial sarcoma of the kidney.

The authors present two cases of primary synovial sarcoma of the kidney. Both patients had a mass in the upper part of the right kidney without any primary extrarenal neoplastic lesions. Grossly, the tumors were soft to rubbery masses measuring 5.5 cm and 5 cm in diameter, respectively. Histologically, both tumors were poorly differentiated synovial sarcoma. The lesions exhibited a hypercellular solid or lobular growth of round, oval, or short spindle cells in variably solid sheets, in intersecting fascicles, or in a haphazard fashion. Areas of solid aggregation or fascicles of the tumor cells alternating with hypocellular myxoid tissues, together with areas displaying a prominent hemangiopericytoma-like pattern, were found. Immunohistochemically, vimentin was diffusely positive and a few tumor cells were positive for cytokeratin, epithelial membrane antigen, and neurofilament. The tumor cells were negative for S- 100 protein, CD34, smooth muscle actin, and desmin, whereas CD56 and CD99 were positive. In both cases, reverse transcription-polymerase chain reaction using ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues detected SYT-SSX2 fusion gene transcripts, which are characteristic molecular findings of synovial sarcoma. One patient died 10 months after diagnosis. These tumors are unique cases of primary synovial sarcoma of the kidney confirmed by molecular study.

Epigenetic inactivation of Homeobox A5 gene in nonsmall cell lung cancer and its relationship with clinicopathological features.

Promoter methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. Homeobox A5 (HOXA5) is a master regulator of the morphogenesis and cell differentiation to be implicated as a tumor suppressor gene in breast cancer, but its role in lung cancer is still unknown. In this study, we have investigated the methylation status of the promoter region of the HOXA5 gene in nonsmall cell lung cancers (NSCLCs) using nested and standard methylation‐specific PCR (MSP) and correlated the methylation status with clinicopathological features. With standard MSP analysis, HOXA5 methylation were found in 113 (81.3%) of 139 NSCLCs and 72 (51.8%) in their corresponding nonmalignant lung tissues. RT‐PCR and immunohistochemical analysis showed that HOXA5 methylation correlates with gene expression. Moreover, in the patients with stage I disease, HOXA5 methylation was more frequent in smokers than in never‐smokes (P = 0.01). There was no influence of HOXA5 methylation on survival in all NSCLCs or at stages II–IV. However, in the patients with stage I disease, HOXA5 methylation was associated with a borderline significantly worse survival (P = 0.09). These findings suggest that downregulation of the HOXA5 gene by aberrant promoter methylation occurs in the vast majority of NSCLCs and that it may play a role in the pathogenesis of NSCLC. Additional studies with larger sample sizes are required to evaluate the prognostic value of HOXA5 methylation in patients with stage I NSCLC.

Comparison of primary and secondary cutaneous CD56+ NK/T cell lymphomas.

CD56+ NK/T cell lymphoma (NKTL) frequently involves skin and subcutaneous tissue. The characteristics of primary cutaneous nasal-type CD56+ NKTLs and secondary cutaneous involvement of nasal CD56+ NKTLs have not been clearly separated. This retrospective study analyzed 15 cases of NKTL (10 primary CD56+ NKTLs and 5 secondary CD56+ NKTLs) for their clinicopathologic and immunophenotypic characteristics using CD3, CD4, CD20, CD45RO, CD56, TIA-1, CD30, and Ki-67 antigens. In situ hybridization for Epstein-Barr virus RNA (EBERISH) and PCR for T cell receptor (TCR) &ggr; gene rearrangement were also performed. Clinically, NKTL-P was seen with equal frequency among male (five cases) and female (five cases) patients and presented with subcutaneous nodules without epidermal changes (nine cases), whereas all cases of NKTL-S occurred in male patients and presented with nodules or plaques with distinct epidermal changes (five cases). Microscopically, initial NKTL-P lesions had the panniculitic patterns of small to medium-sized cells (nine cases). NKTL-S lesions were extensive in both subcutis and dermis, with larger and more pleomorphic tumor cells (four cases) that also showed signs epidermotropism (five cases). In initial biopsies of CD56+ NKTL-P, a minority of tumor cells showed signals for EBERISH and in biopsies of CD56+ NKTL-S, virtually every tumor cell showed signals. While all five patients with secondary CD56+ NKTL died of disease with widespread systemic involvement within 16 months after onset of skin lesions, 7 out of the 10 primary CD56+ NKTL patients survived more than 20 months after onset of skin lesions, with slow progression and episodic recurrences. The primary and secondary cutaneous CD56+ NKTLs showed considerable clinicopathologic differences, suggesting differences in pathogenesis.

Combined Positron Emission Tomography and Cerenkov Luminescence Imaging of Sentinel Lymph Nodes Using PEGylated Radionuclide-Embedded Gold Nanoparticles.

New imaging probes with high sensitivity and stability are urgently needed to accurately detect sentinel lymph nodes (SLNs) for successful cancer diagnosis. Herein, the use of highly sensitive and stable PEGylated radionuclide-embedded gold nanoparticles (PEG-RIe-AuNPs) is reported for the detection of SLNs by combined positron emission tomography and Cerenkov luminescence imaging (PET/CLI). PEG-RIe-AuNPs show high sensitivity and stability both in vitro and in vivo, and are not toxic to normal ovarian and immune cells. In vivo PET/CLI imaging clearly reveals SLNs as early as 1 h post PEG-RIe-AuNP-injection, with peak signals achieved at 6 h postinjection, which is consistent with the biodistribution results. Taken together, the data provide strong evidence that PEG-RIe-AuNPs are promising as potential lymphatic tracers in biomedical imaging for pre and intraoperative surgical guidance.

Engineering of Radioiodine-Labeled Gold Core–Shell Nanoparticles As Efficient Nuclear Medicine Imaging Agents for Trafficking of Dendritic Cells

The development of highly sensitive, stable, and biocompatible imaging agents allowing visualization of dendritic cell (DC) migration is one of the essential factors for effective DC-based immunotherapy. Here, we used a novel and efficient synthesis approach to develop radioiodine-124-labeled tannic acid gold core-shell nanoparticles (124I-TA-Au@AuNPs) for DC labeling and in vivo tracking of their migration using positron emission tomography (PET). 124I-TA-Au@AuNPs were produced within 40 min in high yield via straightforward tannic acid-mediated radiolabeling chemistry and incorporation of Au shell, which resulted in high radio-sensitivity and excellent chemical stability of nanoparticles in DCs and living mice. 124I-TA-Au@AuNPs demonstrated good DC labeling efficiency and did not affect cell biological functions, including proliferation and phenotype marker expression. Importantly, 124I-TA-Au@AuNPs in an extremely low amount (0.1 mg/kg) were successfully applied to track the migration of DCs to lymphoid organs (draining lymph nodes) in mice.

Clinical Significance of Substaging and HER2 Expression in Papillary Nonmuscle Invasive Urothelial Cancers of the Urinary Bladder

The study aimed to verify the prognostic utility, therapeutic application and clinical benefits of tumor substaging and HER2 status in papillary non-muscle invasive bladder cancer (NMIBC). Select NMIBC transurethral resection specimens from 141 patients were used to construct tissue microarrays for assessing the substaging, HER2 protein expression by immunohistochemistry (HER2-IHC) and gene amplification by dual-color silver in situ hybridization (HER2-SISH). Substages were identified by the differing depth of tumor invasion (pTa / pT1a / pT1b / pT1c). HER2 protein expression was semiquantitatively analyzed and grouped into negative (score 0, 1+) and positive (score 2+, 3+). Other clinicopathological variables were also investigated. For NMIBC, HER2-IHC and HER2-SISH showed positive results in 6/141 (4.3%) and 4/141 (2.8%) respectively, which correlated well with tumor substaging. In multivariate analysis, substaging, HER2-IHC, and HER2-SISH were found to be independent predictors of progression-free survival (P < 0.001, P < 0.001, P = 0.031). HER2-IHC was the sole independent predictor of recurrent free survival in NMIBC (P = 0.017). It is suggested that tumor substaging and HER2 status are independent predictive markers for tumor progression or recurrence, and thus could be included in diagnostic and therapeutic management for NMIBC. Graphical Abstract

Incidental detection of increased (18)F-FDG uptake and its follow-up in patients with granulomatous prostatitis after BCG treatment for urinary bladder cancer.

Incidental prostate uptake of fluorine-18-fluorodeoxyglucose in positron emission tomography/computed tomography ((18)F-FDG PET/CT) may represent malignancies like prostate malignancy, inflammation or benign prostatic lesions. We report two cases of bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis that showed (18)F-FDG uptake of the prostate gland on (18)F-FDG PET/CT in patients who had previously received intravesical BCG treatment for bladder cancer. The degree of (18)F-FDG uptake was decreased on the follow-up PET/CT scan after one year, without any specific treatment.

Clinicopathologic and molecular pathology of collecting duct carcinoma and related renal cell carcinomas

Collecting duct carcinoma (CDC) and related tumors [ie, renal medullary carcinoma (RMC)] are rare types of highly aggressive renal cell carcinomas (RCC) with poor prognosis. Because of the rarity and diagnostic uncertainty of them, their molecular pathology and significance have not yet been fully elucidated. CDC, RMC, fumarate hydratase–deficient RCC (including hereditary leiomyomatosis and RCC-associated RCC HLRCC-RCC), and recently reported anaplastic lymphoma kinase (ALK)-rearrangement RCC have significant morphologic overlaps, but they are separately distinct entities having different molecular pathway and clinical settings. CDC is more likely to occur in middle to old age population with immunoreactivity for PAX8 and integrase interactor-1 proteins (INI-1). Various chromosomal and genomic alterations have been reported with inconsistent results. In contrast, RMC is more likely to occur in younger patients with sickle cell trait. In RMC, loss of INI-1 expression and OCT3/4 expression are distinguished compared with other RCCs. Finally, ALK-rearrangement RCC seems to have 2 different clinical settings, one with sickle cell trait (VCL-ALK fusion) and the other without (other fusions such as TPM3-ALK, EML4-ALK, and STRN-ALK fusions). Interestingly, VCL-ALK fusion was found in pediatric patients with sickle cell trait, whereas other fusions were detected in adolescent or adult without sickle cell trait. Taken together, CDC and related tumors such as RMC, fumarate hydratase–deficient RCC (including hereditary leiomyomatosis and RCC-associated RCC), and ALK-rearrangement RCC are the distinct entities and their recognition is important for the development of future personalized therapeutic options. This review updates the clinicopathologic features of these tumors with overlapping morphology and outcome.

Lynch syndrome-related small intestinal adenocarcinomas

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

Signet-Ring Cell Carcinoma of the Distal Common Bile Duct: Report of a Case

Signet-ring cell carcinoma (SRCC) of the extrahepatic bile duct is a histologically distinct entity classified by the World Health Organization, in which cells containing intracytoplasmic mucin displacing the nucleus predominate.1 SRCC of the gastrointestinal tract is most commonly found in the stomach, and the impact of this histology on the prognosis is controversial.2,3 Well to moderately differentiated adenocarcinoma is the most common histologic type and complete resection is the only potentially curative therapy for distal bile duct cancer.4 However SRCC of extrahepatic bile duct is extremely rare, so its clinico-pathological features and impact on the prognosis are not well known. To the best of our knowledge, only three cases of SRCC of the extrahepatic bile duct have been reported in the English literature.5,6,7 Herein, we present a case of SRCC originating from the epithelium of the distal extrahepatic bile duct.