Non-papillary thyroid carcinoma diagnoses in The Bethesda System for Reporting Thyroid Cytopathology categories V and VI: An institutional experience.

BACKGROUND: The non-papillary thyroid carcinoma (PTC) subgroups of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories V (Suspicious for malignancy) and VI (Malignant) are rare, and specific tumor typing is difficult. We aimed to analyze histologic outcomes and to investigate the points of caution. METHODS: We reviewed the electronic database and identified 12,215 cases of thyroid fine-needle aspiration cytology between 2013 and 2022. In total, 2783 patients were diagnosed with TBSRTC V or VI. Of these, 51 patients with non-PTC diagnosis were identified. Histological outcomes were analyzed with the cytologic findings. RESULTS: The subgroups of non-PTC diagnoses in TBSRTC category V or VI consisted of medullary thyroid carcinoma (MTC) (13/51, 25.5 %), anaplastic thyroid carcinoma (3/51, 5.9 %), lymphoma (2/51, 3.9 %), metastatic tumor (4/51, 7.8 %), and malignant, not otherwise specified (NOS) (29/51, 56.9 %). The concordance rate of the histological outcomes was 30 % (12/40), predominantly comprising MTC cases. The obscuring factors for specific tumor typing in the suspicious for malignancy/malignant NOS cytology diagnosis group was mixed pattern of well differentiated thyroid carcinoma and less differentiated carcinoma cells (9/24, 37.5 %), low cellularity (7/24, 29.2 %) and a history of non-thyroid organ malignancy (6/24, 25 %). The less differentiated carcinoma component in mixed pattern consisted of 2 poorly differentiated thyroid carcinomas, 2 anaplastic thyroid carcinomas, 4 high-grade PTCs and 1 high-grade MTC. CONCLUSION: The high-grade feature of PTC or MTC cytology is a noteworthy obscuring factor in specific tumor typing of non-PTC cytology diagnosis.

TROP-2 and 5hmC expression in follicular-patterned thyroid neoplasm emphasizing tiny well-formed papillae.

BACKGROUND: Follicular-patterned thyroid neoplasms (FPTNs), characterized by predominantly follicular growth pattern, represent diverse pathological entities. We aimed to study the nuclear features and the immunoexpression of trophoblast cell-surface antigen 2 (TROP-2) and 5-hydroxymethylcytosine (5hmC) in FPTNs. DESIGN: FPTNs were divided into 4 groups: I) noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), II) encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) with capsular invasion, III) infiltrative FVPTC, and IV) PTC with a predominantly follicular pattern and well-formed papillae (<1%). Nuclear characteristics were evaluated by image analysis. TROP-2 and 5hmC immunostains were analyzed correlating with histological features using QuPath. RESULTS: From the group I to II, III, and IV, there is a gradual increase in nuclear atypia in terms of the nuclear area, max caliper, perimeter, circularity, and hematoxylin OD means (corresponding to nuclear enlargement, membrane irregularity, and clearing). A similar trend is observed in the TROP-2 expression. 5hmC expression is highly preserved in groups I, II, and III in contrast to a significant loss in group IV. Group IV tumors show more frequent regional lymph node involvement and the highest BRAF V600E mutation rate. CONCLUSION: Among FPTNs, group IV tumors exhibit the most advanced nuclear atypia, highest TROP-2 expression, significant 5HMC expression loss, frequent regional lymph node involvement, and the highest BRAF V600E mutation rate. Our data further support that the presence of any true papillae should be an exclusion criterion for NIFTP. Therefore, well-formed papillae even if very minute (<1% of the tumor) should not be overlooked.

Transcriptomic and histopathological analysis of cholangiolocellular differentiation trait in intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse aetiologies, morphologies and clinical outcomes. Recently, histopathological distinction of cholangiolocellular differentiation (CD) of iCCA has been suggested. However, its genome-wide molecular features and clinical significance remain unclear. METHODS: Based on CD status, we stratified iCCAs into iCCA with CD (n=20) and iCCA without CD (n=102), and performed an integrative analysis using transcriptomic and clinicopathological profiles. RESULTS: iCCA with CD revealed less aggressive histopathological features compared to iCCA without CD, and iCCA with CD showed favourable clinical outcomes of overall survival and time to recurrence than iCCA without CD (P<.05 for all). Transcriptomic profiling revealed that iCCA with CD resembled an inflammation-related subtype, while iCCA without CD resembled a proliferation subtype. In addition, we identified a CD signature that can predict prognostic outcomes of iCCA (CD_UP, n=486 and CD_DOWN, n=308). iCCAs were subgrouped into G1 (positivity for CRP and CDH2, 7%), G3 (positivity for S100P and TFF1, 32%) and G2 (the others, 61%). Prognostic outcomes for overall survival (P=.001) and time to recurrence (P=.017) were the most favourable in G1-iCCAs, intermediate in G2-iCCAs and the worst in G3-iCCAs. Similar result was confirmed in the iCCA set from GSE26566 (n=68). CONCLUSIONS: CD signature was identified to predict the prognosis of iCCA. The combined evaluation of histology of CD and protein expression status of CRP, CDH2, TFF1 and S100P might help subtyping and predicting clinical outcomes of iCCA.

Nuclear features of papillary thyroid carcinoma: Comparison of Core needle biopsy and thyroidectomy specimens.

BACKGROUND: Core needle biopsy (CNB) has been used as an alternative or a complementary method for diagnosis of thyroid nodules. However, morphological analysis of the nuclear features of papillary thyroid carcinoma (PTC) cells obtained via CNB remains unclear. Hence, we examined the differences between the PTC nuclear features in CNB and thyroidectomy specimens. METHODS: Ten PTC patients, who underwent both CNB and thyroidectomy, were selected. Microscopic photographs of three representative areas of the PTC and adjacent parenchyma were taken. Ten cells per photograph were chosen, and 1200 cells were evaluated (300 PTC and 300 follicular cells in the CNB and thyroidectomy specimens, respectively). The area, circumference, major axis, and minor axis were measured using an image analyzer. Detailed nuclear features (size and shape, membrane irregularity, chromatin characteristics) were scored using a 3-point scale. RESULTS: The mean nuclear area, circumference, major axis, and minor axis of PTC cells in the CNB specimen were 1.76, 1.34, 1.34, and 1.29 times larger than those of the follicular cells (p<0.001); similar results were seen in the thyroidectomy specimens (2.04, 1.41, 1.37, and 1.37: p<0.001). Comparative analysis revealed that these parameters were significantly smaller in the CNB specimens than those in the thyroidectomy specimens (p<0.001). Nuclear grades were also lower in the former owing to poor chromatin characteristics (clearing and margination) (p<0.01). CONCLUSION: Considering that the PTC nuclei in CNB specimens are smaller with fewer irregularities and less clear than those in thyroidectomy specimens, we need to emphasize caution when using CNB specimens for diagnosis.

Pediatric intracerebral histiocytic sarcoma with rhabdoid features: Case report and literature review.

A 16-year-old boy presented with marked weight loss, weakness of the left extremities and dizziness of 2 months duration and vomiting for 2 days. Brain MRI showed an approximately 6.5 × 5.3 cm-sized huge heterogeneous enhancing mass located in the corpus callosum, extending into the lateral ventricle. Open biopsy showed that the lesion consisted of lymphoplasmacytes and plump histiocytes with rhabdoid morphology, which were stained with S-100 protein, CD68 (KP1) and negative for CD1a. Histiocytic tumor was initially diagnosed. Chemotherapy using methotrexate, 6-mercaptopurine, vinblastine, interferon-alpha and dexamethasone was performed. After 5 months, partial removal was done. Microscopically, plump and bizarre tumor cells as well as rhabdoid features were found. Occasional spindle cells and necrosis were also found. These cells were positive for CD163, CD68, lysozyme, CD4, INI-1 and BRG1. BRAF V600E mutation was detected. The lesion was finally diagnosed as histiocytic sarcoma. Radiotherapy (6000 cGy in 30 fractions) was done. Both cerebral and extracerebral histiocytic sarcomas have long been diagnosed by unclarified criteria; its rarity as well as previously unclarified criteria can easily lead to a misinterpretation. Histiocytic sarcoma of the CNS is exceptionally rare in children, associated with an exceptionally poor prognosis. To date, only seven cases of pediatric cerebral histiocytic sarcomas have been reported. The present case is the first pediatric case showing BRAF V600E-mutated intracerebral histiocytic sarcoma.

A fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and epithelial-mesenchymal transition.

UNLABELLED: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between HCC and CC has been shown to comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common genomic trait of stem-cell-like properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests that S-HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem-cell-like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of transforming growth factor beta (TGF-ß) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. CONCLUSION: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The expression of stem-cell-like traits and TGF-ß/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC. (HEPATOLOGY 2012;55:1776-1786).

Characterization of the genomic alterations in poorly differentiated thyroid cancer.

Poorly differentiated thyroid carcinoma (PDTC) is a subtype of thyroid cancer that has a high rate of metastasis or recurrence and a relatively poor prognosis. However, there are few studies that have been conducted on PDTC at the whole protein-coding gene scale. Here, we performed genomic profiling of 15 patients with PDTC originated from follicular thyroid carcinoma using whole exome sequencing and also performed gene functional enrichment analysis of differentially expressed genes (DEGs) for three patients. Further, we investigated genetic variants associated with PDTC progression and the characteristics of clinical pathology. We revealed somatic genomic alterations in the RAF1, MAP2K2, and AKT2 genes that were not reported in previous studies. We confirmed frequent occurrences in the RAS gene in patients with PDTC; the genetic alterations were associated with the RAS-RAF-MEK-ERK/JNK, PI3K-AKT-mTOR signaling pathways, and the cell cycle. DEG analysis showed that immune response was lower in cancer tissues than in normal tissues. Through the association analysis of somatic mutations and the characteristics of clinical pathology from patients with PDTC, the somatic mutations of ABCA12, CLIP1, and ATP13A3 were significantly associated with a vascular invasion phenotype. By providing molecular genetic insight on PDTC, this study may contribute to the discovery of novel therapeutic target candidates.

Deep learning-based image enhancement in optical coherence tomography by exploiting interference fringe.

Optical coherence tomography (OCT), an interferometric imaging technique, provides non-invasive, high-speed, high-sensitive volumetric biological imaging in vivo. However, systemic features inherent in the basic operating principle of OCT limit its imaging performance such as spatial resolution and signal-to-noise ratio. Here, we propose a deep learning-based OCT image enhancement framework that exploits raw interference fringes to achieve further enhancement from currently obtainable optimized images. The proposed framework for enhancing spatial resolution and reducing speckle noise in OCT images consists of two separate models: an A-scan-based network (NetA) and a B-scan-based network (NetB). NetA utilizes spectrograms obtained via short-time Fourier transform of raw interference fringes to enhance axial resolution of A-scans. NetB was introduced to enhance lateral resolution and reduce speckle noise in B-scan images. The individually trained networks were applied sequentially. We demonstrate the versatility and capability of the proposed framework by visually and quantitatively validating its robust performance. Comparative studies suggest that deep learning utilizing interference fringes can outperform the existing methods. Furthermore, we demonstrate the advantages of the proposed method by comparing our outcomes with multi-B-scan averaged images and contrast-adjusted images. We expect that the proposed framework will be a versatile technology that can improve functionality of OCT.

Gadoxetate disodium-enhanced hepatobiliary phase MRI of hepatocellular carcinoma: correlation with histological characteristics.

OBJECTIVE: The purpose of this study was to assess whether gadoxetate disodium-enhanced hepatobiliary phase MRI could predict the histologic factors of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Fifty-three HCCs histopathologically proved by surgery in 51 patients were evaluated retrospectively. All patients underwent gadoxetate disodium-enhanced MRI before surgical resection. The differences in contrast enhancement ratio of the lesions and differences in contrast-to-noise ratio (CNR) among the histologic grades of HCC were compared by using the Kruskal-Wallis test. The Spearman method was used to determine the correlations among contrast enhancement ratio, CNR, cell density ratio, and positivity for anti-hepatocyte antibody, keratin 7, and keratin 19. RESULTS: Of 53 HCCs, 50 showed low signal intensity on hepatobiliary phase images, whereas three HCCs were hyperintense on hepatobiliary phase images compared with surrounding hepatic parenchyma. Although well-differentiated HCCs tended to show higher contrast enhancement, there was no statistical significance between contrast enhancement ratio of the tumors and histologic grade (p = 0.414). No significant difference was observed between CNR and histologic grade (p = 0.965). The contrast enhancement ratios of the tumors were significantly lower in the keratin 19-positive group than in the keratin 19-negative group (p = 0.015). There was no significant correlation among contrast enhancement ratio, anti-hepatocyte antibody positivity, cell density ratio, and keratin 7 positivity (p > 0.05). CONCLUSION: The contrast enhancement ratio and CNR of HCCs were not correlated with histologic grades. The contrast enhancement ratio was significantly lower in keratin 19-positive HCCs.

Changes in liver stiffness measurement during antiviral therapy in patients with chronic hepatitis B.

BACKGROUND/AIMS: The usefulness of liver stiffness measurement (LSM) for monitoring changes in fibrosis and inflammation in chronic hepatitis B (CHB) patients receiving antiviral therapy is unknown. The aim of this study was to evaluate changes in liver stiffness and correlate them with changes in serological markers and histology in CHB patients receiving entecavir. METHODOLOGY: The study included 38 patients with CHB and 24 cirrhotic patients with CHB. All patients received entecavir for over 12 months. Liver stiffness was measured by transient elastography at baseline and after 48wks of therapy. Liver biopsy was performed on 15 patients at baseline and during therapy. RESULTS: Among 62 treated patients, 51 (82.2%) achieved HBV DNA <50 copies/mL and 43 (69%) achieved alanine aminotransferase (ALT) normalization at 48wks. The median liver stiffness value at baseline was 15.1 kPa (5.6-75.0) and decreased significantly to 8.8kPa (3.0-33.8) after 48wks. A decrease in liver stiffness value during therapy correlated significantly with decreases in albumin (r=-0.357, p=0.004), bilirubin (r=0.342, p=0.007), ALT (r=0.319, p=0.012), and aspartate aminotransferase (AST) (r=0.353, p=0.005) concentrations. Decreases in liver stiffness values correlated significantly with improvement in necroinflammatory scores. CONCLUSION: We suggest that LSM can reflect the changes of necroinflammation in patients with chronic hepatitis B receiving antiviral therapy.

Diagnostic Utility of INSM1 in Medullary Thyroid Carcinoma.

Insulinoma-associated protein 1 (INSM1) is shown to be an excellent marker for neuroendocrine differentiation. However, the diagnostic utility of INSM1 in medullary thyroid carcinoma (MTC) has not yet been extensively investigated. INSM1 staining was performed on 21 MTCs, 7 MTC mimickers (including 3 papillary carcinomas, 2 poorly differentiated carcinomas, 1 follicular adenoma, and 1 nodular plasma cell hyperplasia), and 3 cases of C-cell hyperplasia. INSM1 staining of these cases was compared with the traditional MTC markers including calcitonin (CT), monoclonal carcinoembryonic antigen (mCEA), chromogranin A (CgA), and synaptophysin (Syn). The H-score was generated using the QuPath program, an open-source image analysis software. All 21 MTC cases and 3 C-cell hyperplasia cases were positive for all markers. The MTC mimickers were entirely negative for INSM1. INSM1 and Syn displayed, more consistently, high expression with minimal variability than CgA that showed a wide range of expression with significant variability. mCEA and CT exhibited mostly a high expression with some variability. Being a nuclear stain, interpretation was easier with INSM1 compared to other cytoplasmic markers. INSM1 is an excellent marker for neuroendocrine differentiation, entirely applicable in the diagnosis of MTC and C-cell hyperplasia with high sensitivity and specificity. In comparison with the traditional MTC markers, INSM1 is unique in the crisp nuclear staining pattern with a consistent, diffuse, and strong expression. INSM1 can be potentially combined with CT or mCEA as a dual stain, especially when the lesional tissue is limited for a panel of immunostains.

A case of nontuberculous mycobacteria-associated thyroiditis mimicking subacute thyroiditis.

We describe a case of nontuberculous mycobacteria infection in the thyroid gland in a 54-year-old woman who had painful thyroid enlargement. Ultrasonography showed ill-defined hypoechoic lesions without increased vascularity in both upper lobes of the thyroid gland. Fine needle aspiration biopsy was performed, and pathology showed granulomatous inflammation with necrotic debris that the pathologist suspected was subacute granulomatous thyroiditis or tuberculosis of the thyroid gland. Nontuberculous mycobacteria infection was confirmed after right hemithyroidectomy. Antimycobacterial therapy was initiated as the treatment of choice. Nontuberculous mycobacteria in the thyroid gland appear to be rare. In clinical practice, however, it should be considered as a differential diagnosis of a painful thyroid mass. For accurate diagnosis, clinical and radiological features plus histological examination are required.

TROP-2, 5hmC, and IDH1 Expression in Anaplastic Thyroid Carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has no effective treatment to date. Trophoblast cell-surface antigen 2 (TROP-2), a transmembrane glycoprotein, has been suggested to be a promising novel target for sacituzumab govitecan, an antibody-drug conjugate. 5-Hydroxymethylcytosine (5hmC) has a role in tumor suppression and promoting modification. Additionally, isocitrate dehydrogenase 1 (IDH1) mutations are strongly associated with increased overall survival in gliomas and worse prognosis in leukemias. This study attempts to evaluate the immunoexpression of TROP-2, 5hmC, and IDH1 in ATCs and to determine their potential impact in targeted therapy. METHODS: Twenty-four ATCs were retrieved, with 9 cases that occurred de novo and 15 cases derived from either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma (FTC). Sections were immunostained with TROP-2, 5hmC, and IDH1 antibodies, and evaluated using the QuPath program. The t tests were performed using SPSS software. RESULTS: TROP-2 was detected in 12 ATCs with 9 cases demonstrating a high expression and in all PTC components, and absent in all FTC components of secondary ATCs. 5hmC expression was moderately reduced in PTC and FTC components and markedly reduced in ATC. The entire cohort showed a total absence of IDH1. CONCLUSIONS: Increased TROP-2 immunoexpression in some ATCs supports that these patients may potentially benefit from an antibody-drug conjugate therapy targeting TROP-2. Markedly reduced 5hmC expression suggests that 5hmC may be used as potential therapeutic targets for ATC. The total lack of IDH1 R132H mutation by immunostain indicates that it has no prognostic and therapeutic value in ATC.

Assessment of liver fibrosis and cirrhosis by aspartate aminotransferase-to-platelet ratio index in children with biliary atresia.

BACKGROUND: In patients with biliary atresia (BA), liver fibrosis and cirrhosis commonly occur even after Kasai hepatoportoenterostomy. Although liver biopsy is the gold standard to evaluate liver fibrosis, it is invasive and may result in life-threatening complications. The aspartate aminotransferase-to-platelet ratio index (APRI) is a safe and simple method to assess liver fibrosis in patients with chronic liver diseases. To use APRI as a postoperative follow-up tool, we validated the diagnostic power of APRI for the degree of liver fibrosis in postoperative patients with BA. PATIENTS AND METHODS: Patients with newly diagnosed BA who underwent the Kasai procedure between March 2006 and May 2009 were analyzed. Several laboratory tests including APRI were performed. Liver wedge biopsy specimens were obtained during the surgical procedure, and histopathologic analyses were performed using the Metavir classification. RESULTS: Thirty-five patients (12 boys, median age of 1.9 months) were enrolled. Metavir scores were F1 in 0, F2 in 11, F3 in 11, and F4 in 13 patients. The areas under the receiver operating characteristics curves for F > or = 3 and F = 4 were 0.92 and 0.91, respectively. Distinct optimal cutoff values of APRI for F > or = 3 and F = 4 were obtained (1.01 and 1.41, respectively). Clinical outcomes of patients were significantly different between 2 groups (noncirrhosis vs cirrhosis) based on APRI before and 3 months after the Kasai procedure. CONCLUSION: APRI may be used as a simple and readily available tool for assessing liver fibrosis without additional risks in patients with BA during postoperative follow-up care.

Contribution of cytologic examination to diagnosis of poorly differentiated thyroid carcinoma.

BACKGROUND: The cytologic diagnosis of poorly differentiated thyroid carcinoma (PDTC) is difficult because it lacks salient cytologic findings and shares cytologic features with more commonly encountered neoplasms. Due to diverse cytologic findings and paucicellularity of PDTC, standardization of cytologic diagnostic criteria is limited. The purpose of this study is to investigate and recognize diverse thyroid findings of fine needle aspiration (FNA) cytology and frozen smear cytology in diagnosis of this rare but aggressive carcinoma. METHODS: The present study included six cases of FNA cytology and frozen smears of histologically diagnosed PDTCs. RESULTS: PDTC showed cytologic overlap with well-differentiated thyroid carcinomas (WDTCs). Five of six cases showed dedifferentiation arising from well differentiated thyroid carcinomas. Only one de novo PDTC showed highly cellular smears composed of discohesive small cells, high nuclear/cytoplasmic (N/C) ratio, prominent micronucleoli, and irregular nuclei. Retrospectively reviewed, these findings are highly suspicious for PDTC. Cytologic findings of nuclear atypia, pleomorphism, and irregularity were frequently found, whereas scattered small cells were seen only in the de novo case. CONCLUSIONS: Heterogeneous cytologic findings of PDTCs are shared with those of WDTCs and contribute to difficult preoperative cytologic diagnoses. Most PDTCs show dedifferentiation from WDTCs. Albeit rare, de novo PDTC should be considered with cytology showing discohesive small cells with high N/C ratio. This will enable precise diagnosis and prompt treatment of this aggressive malignancy.

Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution.

BACKGROUND: The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution. METHODS: Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations. RESULTS: Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively). CONCLUSIONS: Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

The application of markers (HSP70 GPC3 and GS) in liver biopsies is useful for detection of hepatocellular carcinoma.

BACKGROUND/AIMS: Liver biopsy for hepatocellular carcinoma (HCC) detection is largely restricted to small hepatocellular lesions, which are often morphologically challenging, requiring careful distinction between dysplastic nodules (high-grade) and well-differentiated HCC. METHODS: We investigated the diagnostic accuracy of a panel of markers (HSP70 GPC3 and GS), previously tested in resection specimens, in a series of liver biopsies of large regenerative nodules (n=13), low-grade dysplastic nodules (n=21), high-grade dysplastic nodules (n=50), very well-differentiated (VWD) (n=17), well-differentiated (WD-G1) (n=40) and G2-3 (n=35) HCC. RESULTS: Almost all cases of large regenerative and low-grade dysplastic nodules did not stain while high-grade dysplastic nodules showed 1 marker (22%) but never 2 or 3. For HCC detection the overall accuracy of marker combination was 60.8% (3 markers) and 78.4% (2 markers) with 100% specificity. When restricted to VWD+WD-G1 HCC the accuracy was 57% (3 markers) and 72.9% (2 markers) with 100% specificity. CONCLUSIONS: This panel proved useful to detect well-differentiated HCC in biopsy. Two immunoreactive markers (out of 3) are recommended as the most valuable diagnostic combination for HCC detection. The diagnostic accuracy of the panel could be improved using additional markers, as suggested by studies of expression profiling in other human models.

Hepatocellular carcinoma variants: radiologic-pathologic correlation.

OBJECTIVE: The purpose of this article is to show the imaging findings of variant types of hepatocellular carcinoma (HCC) with pathologic correlations. CONCLUSION: The variant types of HCC may not share its typical imaging characteristics. An understanding of the radiologic findings for variant types of HCC can be helpful in the differential diagnosis of hepatic tumors.

Cytologic features of metastatic lymphoepithelial carcinoma in pleural fluid: a case report.

BACKGROUND: Lymphoepithelial carcinoma of the salivary gland is a rare undifferentiated or poorly differentiated squamous cell carcinoma associated with abundant inmphocytes. Only a handful of reports descibe the cytologic features of fine needle aspiration in lymphoepithelial carcinoma of the salivary gland and lymph nodes. CASE: A 29-year-old man presented with a painless mass in his right parotid gland. After the surgical specimen was evaluated, the mass was diagnosed as a lymphoepithelial carcinoma, which extended to the periglandular soft tissue with lymph node metastasis. Despite radiation and chemotherapy, multiple mediastinal lymph node metastases, including in the right hilar lymph nodes, occurred. Pulmonary atelectasis of the right upper lobe and a right pleural effusion developed. Aspiration cytology of metastatic lymph nodes and pleural effusion cytology both demonstrated strongly cohesive clusters of tumor cells. These cells had vesicular nuclei and prominent nucleoli admixed with benign lymphoid cells. CONCLUSION: Pleural effusion cytopathology ofmetastatic lymphoepithelial carcinoma is similar to that of primary tumor fine needle aspiration. Therefore, a specific diagnosis of lymphoepithelial carcinoma is possible on the basis of body fluid with these cytologic features.

Primary Necrobiotic Xanthogranulomatous Sialadenitis with Submandibular Gland Localization without Skin Involvement.

Necrobiotic xanthogranulomatous reaction is a multiorgan, non-Langerhans cell histiocytosis with an unknown etiology. Occurrence in the salivary gland is extremely rare. We recently identified a case of necrobiotic xanthogranulomatous sialadenitis in a 73-year-old Korean woman who presented with a painless palpable lesion in the chin. There was no accompanying cutaneous lesion. Partial resection and subsequent wide excision with neck dissection were performed. Pathological examination showed a severe inflammatory lesion that included foamy macrophages centrally admixed with neutrophils, eosinophils, lymphocytes, plasma cells, and scattered giant cells, as well as necrobiosis. During the 12-month postoperative period, no grossly remarkable change in size was noted. Necrobiotic xanthogranulomatous inflammation may be preceded by or combined with hematologic malignancy. Although rare, clinicians and radiologists should be aware that an adhesive necrobiotic xanthogranuloma in the salivary gland may present with a mass-like lesion. Further evaluation for hematologic disease and close follow-up are needed when a pathologic diagnosis is made.