Hyalinizing Trabecular Tumor of the Thyroid Gland, a Diagnostic Challenge in Fine-Needle Aspiration Cytology: Case Report

Hyalinizing trabecular tumor (HTT) is a rare thyroid tumor with low to minimal malignant potential. HTT is often misinterpreted as other thyroid tumors, including papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC), on fine-needle aspiration (FNA) cytology, because of its overlapping cytologic features, such as nuclear grooves and intranulcear pseudoinclusions. Although cytopathologists cannot definitely conclude HTT by FNA cytology, suspicion of HTT is necessary to avoid misdiagnosing HTT as PTC or MTC and to avoid unnecessary aggressive treatment. Here, we report a case of HTT with novel cytologic features in CellPrep liquid based cytology that was diagnosed as suspicious for papillary carcinoma by FNA and finally diagnosed as HTT in the surgical specimen.

Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

Localized Gastric Amyloidosis with Kappa and Lambda Light Chain Co-Expression

Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression.

CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway.

Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma

BACKGROUND: A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). METHODS: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). RESULTS: TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054). CONCLUSIONS: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis.

Diagnostic Accuracy of Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology of Pancreatic Lesions

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC) is currently the most commonly used procedure for obtaining cytologic specimens of the pancreas. It is accurate, minimally invasive, safe and cost-effective. However, there is discrepancy between cytological and surgical diagnoses. This study was aimed at evaluating the diagnostic accuracy of EUS-FNAC of the pancreas. METHODS: We performed a retrospective review of 191 cases of pancreatic lesions initially diagnosed by EUS-FNAC with subsequent histological diagnosis between 2010 and 2012 in the Department of Pathology, Seoul National University Hospital. Cytologic and surgical diagnoses were categorized into five groups: negative, benign, atypical, malignant, and insufficient for diagnosis. Subsequently, 167 cases with satisfactory yield in both surgical and cytology specimens were statistically analyzed to determine correlations with diagnosis. RESULTS: In comparison to surgical diagnoses, cytologic diagnoses were true-positive in 103 cases (61.7%), true-negative in 28 cases (16.8%), false-positive in 9 cases (5.4%), and false-negative in 27 cases (16.1%). The diagnostic accuracy was 78.4%, sensitivity was 79.2%, and specificity was 75.7%. The positive predictive value was 92.0%, and negative predictive value was 50.9%. CONCLUSIONS: EUS-FNAC has high accuracy, sensitivity, specificity and positive predictive value. Overcoming the limitations of EUS-FNAC will make it a useful and reliable diagnostic tool for accurate evaluation of pancreatic lesions.

Differential Features of Microsatellite-Unstable Colorectal Carcinomas Depending on EPCAM Expression Status

BACKGROUND: Recent studies have revealed that a small subset of Lynch syndrome-associated colorectal carcinomas (CRCs) is caused by a germline EPCAM deletion-induced MSH2 epimutation. Based on the finding of this genetic alteration, we investigated the implications of EPCAM expression changes in microsatellite instability-high (MSI-H) CRCs. METHODS: Expression of EPCAM and DNA mismatch repair proteins was assessed by immunohistochemistry in 168 MSI-H CRCs. Using DNA samples of these tumors, MLH1 promoter methylation status was also determined by methylation-specific real-time polymerase chain reaction method (MethyLight). RESULTS: Among 168 MSI-H CRCs, complete loss (CL) and focal loss (FL) of EPCAM expression was observed in two (1.2%) and 22 (13.1%) cases, respectively. Both of the EPCAM-CL cases were found in MSH2-negative tumors without MLH1 promoter methylation. However, only nine of the 22 EPCAM-FL tumors had MSH2 deficiency. Of the 22 EPCAM-FL tumors, 13 showed MLH1 loss, and among them, nine cases were determined to have MLH1 methylation. EPCAM-FL was significantly associated with advanced stage (p=.043), distant metastasis (p=.003), poor differentiation (p=.001), and signet ring cell component (p=.004). CONCLUSIONS: Loss of EPCAM expression is differentially associated with clinicopathological and molecular features, depending on the completeness of the loss, in MSI-H CRCs.