Computed Tomography Features of Appendiceal Metastasis in Patients With Underlying Malignancy: Comparison With Pathological Findings.

OBJECTIVE: To evaluate the computed tomography (CT) findings compared with pathologic features and to determine whether CT findings are useful for diagnosis of appendiceal metastasis in patients with underlying malignancy. MATERIALS AND METHODS: Preoperative CT examinations of 59 patients who had underlying malignancy and underwent appendectomy were evaluated. Appendiceal metastasis (n = 21) and nonmetastasis (n = 38) were pathologically confirmed. Computed tomography features (appendiceal morphology and diameter, presence of ascites, rectal shelf, omental cake, lymphadenopathy or organ metastasis) were retrospectively reviewed, and compared with histopathological findings. Fisher exact test and Wilcoxon rank sum test were performed for statistical analysis. RESULTS: Mean diameter of appendiceal metastasis was significantly larger (9.1 mm) than that of nonmetastasis (5.2 mm), (P < 0.0001). The CT morphology of appendiceal metastasis showed broad spectrum, and 3 cases of nodular thickening was only detected in appendiceal metastasis. There was a significant difference between groups (P = 0.0102). Appendiceal metastasis was more frequently associated with peritoneal seeding (ascitis, rectal shelf, omental cake) than nonmetastasis (P < 0.0001). Histopathological invasion of appendiceal metastasis was more frequently seen in serosa-mesoappendix (n = 20, 100%) or muscularis propria (n = 17, 85%), than in submucosa (n = 10, 50%) or mucosa layer (n = 7, 35%). Acute appendicitis was more commonly detected in metastasis (n = 4) than in nonmetastasis (n = 1) (P = 0.0495). CONCLUSIONS: Evaluation of CT features of appendix and peritoneum may be useful for prediction of appendiceal metastasis in patients with underlying malignancy.

Sonographic Differentiation Between Angiolipomas and Superficial Lipomas.

OBJECTIVES: The purpose of this study was to compare the sonographic findings of angio lipomas with those of superficial lipomas. METHODS: Preoperative sonograms of 26 angiolipomas from 18 patients and 47 superficial lipomas from 43 patients that were confirmed by biopsy were reviewed retrospectively. The echo texture, echogenicity, internal echogenic stranding, vascularity, visualization of lateral and superficial-deep tumor capsules, shape, and tumor length, width, and length-to-width ratio were evaluated and compared between angiolipomas and superficial lipomas. RESULTS: Angiolipomas frequently appeared as heterogeneous (19 of 26 [73.1%]), hyperechoic (23 of 26 [88.5%]), and ovoid (17 of 26 [65.4%]) masses with lesser visualized lateral tumor capsules (6 of 26 [23.1%]), whereas superficial lipomas appeared as homogeneous (36 of 47 [76.6%]), isoechoic (35 of 47 [74.5%]), and spindle-shaped (23 of 47 [48.9%]) masses with well-visualized lateral capsules (33 of 47 [70.2%]), and the differences were statistically significant (P < .001). Vascularity was seen in 4 angiolipomas (16.7%) and in no superficial lipomas (0%). The mean length and width ± SD of angiolipomas (2.2 ± 1.02 and 0.6 ± 0.27 cm, respectively) were smaller than those of superficial lipomas (4.2 ± 1.52 and 1.1 ± 0.51 cm), with statistical significance (P< .001). The other sonographic findings did not reveal statistically significant differences between the tumor types. CONCLUSIONS: Sonography might help differentiate angiolipomas from superficial lipomas.

Ectopic Human Fasciola hepatica Infection by an Adult Worm in the Mesocolon.

We report here an ectopic case of Fasciola hepatica infection confirmed by recovery of an adult worm in the mesocolon. A 56-year-old female was admitted to our hospital with discomfort and pain in the left lower quadrant of the abdomen. Abdominal CT showed 3 abscesses in the left upper quadrant, mesentery, and pelvic cavity. On surgical exploration, abscess pockets were found in the mesocolon of the sigmoid colon and transverse colon. A leaf-like worm found in the abscess pocket of the mesocolon of the left colon was diagnosed as an adult fluke of F. hepatica. Histologically, numerous eggs of F. hepatica were noted with acute and chronic granulomatous inflammations in the subserosa and pericolic adipose tissues. Conclusively, a rare case of ectopic fascioliasis has been confirmed in this study by the adult worm recovery of F. hepatica in the mesocolon.

Extended gastritis cystica profunda associated with Epstein-Barr virus-positive dysplasia and carcinoma with lymphoid stroma.

We report a case of gastritis cystica porfunda (GCP) associated with gastric carcinoma with lymphoid stroma (CLS). There was dysplastic change in the transitional area between GCP and CLS. Epstein-Barr virus (EBV) in situ hybridization (ISH) revealed positive reaction at the dysplastic area as well as at the CLS area. Immunohistochemical staining disclosed that dysplastic epithelium was similar to GCP in CK 20, MUC5AC, and E-cadherin expression, but similar to CLS in MUC6, CEA, p53, c-erb-B2, and EBV-ISH expression. Results of the EBV-ISH suggested that EBV infection may play a role in dysplastic change.

Clinicopathologic and molecular characteristics of lung adenocarcinoma arising in young patients.

Lung cancer rarely occurs in young patients. Recent studies have demonstrated that epidemiologic data are closely correlated to some molecular characteristics. We investigated the clinicopathologic characteristics of lung adenocarcinoma in young patients and evaluated immunohistochemically detected epidermal growth factor receptor (EGFR) mutation status and anaplastic lymphoma kinase (ALK) positivity. Among lung adenocarcinoma patients, 31 cases were of the ≤ 40 yr-old group and 261 cases of > 50 yr-old group. Young patients were more likely to be females (67.7% vs 40.2%), and nonsmokers (58.1% vs 45.2%) and more often had high TNM stage (stage IV was 80.6% vs 52.1%) and had a high rate of distant metastasis (51.6% vs 28.0%) compared with older patients. The signet ring cell feature was more common (25.8% vs 11.5%) and lepidic growth pattern was rarely present (3.2% vs 16.5%) in the adenocarcinoma of young patients. There was no significant survival difference between the two age groups. The rate of EGFR mutation status and ALK positivity did not show a statistical difference between two groups. In conclusion, lung adenocarcinoma of young patients demonstrates distinct pathologic features with frequent presence of a signet ring cell feature and rare occurrence of lepidic growth pattern. Further investigation for other genetic abnormalities would be needed.

Reclassifying formerly indeterminate thyroid FNAs using the Bethesda system reduces the number of inconclusive cases.

OBJECTIVE: To evaluate the effectiveness of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses following BSRTC adoption. STUDY DESIGN: According to the BSRTC, we reclassified cytologic samples originally diagnosed as 'indeterminate' with sequential surgical resection. Then, we analyzed the causes of cases, which were recategorized as 'atypia undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)'. RESULTS: According to the BSRTC, 154 'indeterminate' cases were reclassified as follows: unsatisfactory, n = 5 (3.2%); benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular neoplasm, n = 7 (7.1%); suspicious for a Hürthle cell neoplasm, n = 4 (2.6%); suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC. Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In addition, papillary microcarcinoma and coexisting Hashimoto's thyroiditis caused inconclusive diagnoses. CONCLUSION: The BSRTC can be easily applied to thyroid fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules into more detailed categories and thus reduce the number of cases classified as indeterminate. However, suboptimal preparation, papillary microcarcinoma, and coexisting Hashimoto's thyroiditis precluded cytopathologists from making definitive diagnoses.

PPARgamma agonist and angiotensin II receptor antagonist ameliorate renal tubulointerstitial fibrosis.

The peroxisome proliferator activated receptor (PPAR)gamma agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARgamma agonist and interaction with angiotensin receptor antagonist in the unilateral ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT), pioglitazone treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14, CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis. The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of TGF-beta1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the pioglitazone inhibited tubulointerstitial fibrosis, however, the synergism between pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1 and TGF-beta/Smad2 in the treated groups, PAI-1 and TGF-beta are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARgamma agonist might be used in the treatment of renal fibrotic disease.

Cytomorphologic features of small cell carcinoma of lung in effusion fluid using a liquid-based cytology technique.

BACKGROUND: Liquid-based cytology (LBC) testing induces morphologic changes due to the use of specific fixatives and preparation techniques, and the cytologies of effusions determined in this manner differ morphologically from those of conventional cytopreparation (CCP) smear methods. We compared the cytologic features of pulmonary small cell carcinoma in effusion fluid using CCP and LBC preparations. METHODS: Fifty-three malignant effusion specimens from 36 patients with small cell carcinoma were examined, including 41 LBCs from 27 patients and 12 CCPs from 9 patients. RESULTS: LBC and CCP preparations preserved the typical features of small cell carcinoma, that is, nuclear molding, very high nuclear to cytoplasmic ratio and granular chromatin. The architectural patterns involved small cohesive clusters and chains with nuclear molding, tight three-dimensional clusters, or single cell dispersion were preserved in both preparations. Oval nuclei (83.3% vs 26.8%, P < .001) and a discernable rim of cytoplasm (66.7% vs 26.8%, P = .043) were more frequently identified in CCPs, whereas cellular degeneration and dry artifact were more frequent in LBC preparations (73.2% vs 8.3%, P < .001). LBC had a tendency to show frequent nuclear size variation (51.2% vs 25.0%) than CCP. CONCLUSION: LBC tends to show more degeneration and dry artifact with exaggerated irregular nuclear shape and nuclear size variation and scanty cytoplasm than CCP. Cytopathologists should be familiar with the cytomorphologic spectrum of this tumor in CCP and LBC prepared effusions.

Extrapulmonary small cell carcinoma of the liver: clinicopathological and immunohistochemical findings.

Patients with primary small cell carcinoma of the liver have rarely been described in medical literature. Knowledge of clinical, pathological and immunohistochemical properties remains limited. We described an 82-year-old female patient with primary small cell carcinoma of the liver. Histologically, the tumor showed typical morphology of a pulmonary small cell carcinoma. Immunohistochemically, the tumor revealed neuroendocrine differentiation; positive reaction for chromogranin, synaptophysin, CD56, and neuron specific enolase. The tumor was also positive for TTF-1 and c-kit but completely negative for hepatocyte, carcinoembryonic antigen, cytokeratin 7; 19; and 20. Herein, we discussed the clinical, pathological and immunohistochemical findings of extrapulmonary small cell carcinoma of the liver and reviewed the relevant literature.

Ciliated muconodular papillary tumor of the lung harboring BRAF V600E mutation and p16INK4a overexpression without proliferative activity may represent an example of oncogene-induced senescence.

Ciliated muconodular papillary tumor (CMPT) is a rare peripheral lung tumor that shows puzzling histologic features encompassing metaplastic and neoplastic nature. This type of tumor is occasionally misdiagnosed as lung adenocarcinoma clinically and pathologically, and its pathogenic mechanism has not been well characterized. We experienced a case of CMPT in a 73-year-old male and performed targeted deep sequencing to characterize its molecular features. The tumor was an ill-defined, subpleural, and non-endobronchial nodule showing glandular and papillary proliferation of mucous cells, ciliated columnar cells, and basal cells without any cytologic atypia. Abundant intra-alveolar mucin surrounded the main lesion. The patient was well without recurrence throughout 36 months of follow-up. Our case harbored BRAF V600E mutation and strongly expressed p16INK4a without proliferative activity, representing senescence and indolent biologic behavior. Overall, the results of this study indicate that BRAF V600E mutation might be the driver for tumorigenesis of CMPT and eventually leads to oncogene-induced senescence of this tumor.

Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma.

BACKGROUND: Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. METHODS: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. RESULTS: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. CONCLUSIONS: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome.

The effect of neutral-surface iron oxide nanoparticles on cellular uptake and signaling pathways.

In recent years, iron oxide nanoparticles (IONPs) have been applied widely to biomedical fields. However, the relationship between the physicochemical properties of IONPs and their biological behavior is not fully understood yet. We prepared 3-methacryloxypropyltrimethoxysilane (MPS)-coated IONPs, which have a neutral hydrophobic surface, and compared their biological behavior to that of Resovist (ferucarbotran), a commercialized IONP formulation modified with carboxymethyl dextran. The rate of MPS-IONP uptake by human aortic endothelial cells (HAoECs) was higher than ferucarbotran uptake, indicating that the neutral hydrophobic nature of MPS-IONPs allowed them to be absorbed more readily through the plasma membrane. However, the signaling pathways activated by MPS-IONPs and ferucarbotran were comparable, suggesting that surface charge is not a key factor for inducing changes in HAoECs. In vivo fate analysis showed that MPS-IONPs accumulated for longer periods in tissues than hydrophilic ferucarbotran. These findings could enlarge our understanding of NP behavior for advanced applications in the biomedical field.

Aspiration cytology of fibrosarcomatous variant of dermatofibrosarcoma protuberans with osteoclastlike giant cells in the chest wall: a case report.

BACKGROUND: A case of fibrosarcomatous variant of dermatofibrosarcoma protuberans (FS-DFSP) with osteoclastlike giant cells involved the dermis and subcutaneous tissue of the chest wall. This case was misdiagnosed as primary breast tumor clinically and had cytologic features similar to those of the metaplastic breast carcinoma (MRBC). CASE: A 53-year-old female presented with a nodular breast mass enlarging slowly over a long period of time and growing rapidly for about 3 months. The aspirates showed high cellularity with both individually scattered and fascicular arrays of spindle cells. A few multinucleated giant cells without nuclear atypia were intermixed with dissociated spindle cells. There was no epithelial component in the smear. Cytologic evaluation suggested the possibility of a low grade spindle cell sarcoma as well as MBC. Subsequently, the patient underwent modified radical mastectomy, and the diagnosis of FS-DFSP was made. CONCLUSION: Distinguishing FS-DFSP with osteoclastlike giant cells from other spindle cell tumors of the breast, especially MBC showing predominantly spindle cell components, may pose significant challenges to the pathologist. However, clinical and radiologic findings and a meticulous search for other components raised the possibility of FS-DFSP on aspiration cytology.

Multiple visceral artery aneurysms managed by Yasargil aneurysm clips.

Here, we present the case of a 37-year-old woman with multiple visceral artery aneurysms in the pancreaticoduodenal, inferior pancreatic and splenic arteries associated with celiac trunk stenosis. An aneurysmectomy and end-to-end anastomosis was performed for two adjacent aneurysms, while clipping with intracranial aneurysm clips were performed for the other three aneurysms. During 36-month follow-up, no recurrence or newly developed lesions were noted, and the celiac artery had been reconstituted spontaneously. We believe that using intracranial aneurysm clips in the treatment of visceral artery aneurysms is feasible and safe and can be considered when endovascular procedures are unlikely to be successful.

Metastatic follicular thyroid carcinoma to the thymus in a 35-year-old woman.

Clinically detectable metastatic follicular thyroid carcinoma to the thymus is very rare in the literature and sometimes confused with false positive uptake of Iodine(131) (I(131)) in the normal thymus or hilar lymph node. The authors report a 35-year-old woman with metastatic follicular carcinoma to the thymus. She underwent total thyroidectomy and I(131) ablation with 200 mCi. Six months later, a follow-up I(131) whole body scan showed continued radioactive iodine uptake in the retrosternal area and the serum thyroglobulin level remained continuously elevated with levothyroxine suppression therapy (22.3 and 36.4 ng/ml, 6 and 10 months after total thyroidectomy, respectively). CT scan of the chest revealed several aggregated cystic lesions in the retrosternal mediastinum, suspected to represent mediastinal metastasis. The surgically resected retrosternal mass was confirmed as a metastatic follicular carcinoma to the thymus. After surgical excision, the serum thyroglobulin level was below 1.0 ng/ml and I(131) whole body scan showed no radioactive iodine uptake in the mediastinum. The patient showed no evidence of recurrence after excision of thymic metastasis during one year of 0.2 mg levothyroxine suppression therapy. We report a case of metastatic follicular thyroid carcinoma to the thymus without bone or pulmonary involvement.

Primary papillary carcinoma arising in a thyroglossal duct cyst.

We report a case of papillary carcinoma arising in a thyroglossal duct cyst, presenting with an anterior neck mass of a 31-year-old woman. The tumor was judged to be a primary lesion on the basis of intraoperative examination of the thyroid and pathologic findings of the mass. One year later, a small nodular mass in the left thyroid gland and lymph node enlargement of the right cervical lymph node were noted by follow-up imaging studies. Total thyroidectomy, right modified radical neck dissection and central neck dissection were performed. The thyroid gland revealed nodular hyperplasia without evidence of malignancy. On the other hand, the dissected neck lymph nodes revealed metastatic papillary carcinoma. Taken together, these findings suggested the tumor was a primary papillary carcinoma arising in the thyroglossal duct cyst.

Cytologic evaluation of low grade transitional cell carcinoma and instrument artifact in bladder washings.

OBJECTIVE: To identify key cytologic features for the separation of low grade transitional cell carcinomas (TCCs) from nonneoplastic lesions in bladder washings. STUDY DESIGN: The cytomorphologic features of 95 bladder washing specimens showing papillary fragments, which included 50 low grade TCCs and 45 nonneoplastic lesions, were reviewed retrospectively. RESULTS: Bladder washings from low grade TCCs showed papillary and irregular groups of cells with ragged borders, cytoplasmic homogeneity and subtle nuclear changes, such as increased nuclear/cytoplasmic ratio and irregular nuclear border. Bladder washings after instrumentation from nonneoplastic lesions of the bladder showed cellular specimens with cohesive, ball-shaped and papillary clusters with smooth borders lined with a denser-staining cytoplasmic collar. Reactive urothelial cells often displayed loose aggregates with irregular borders but no cytoplasmic collar. CONCLUSION: In bladder washing cytology, nuclear changes and cytoplasmic homogeneity play a major role in the diagnosis of carcinoma.

Preparation of compact agarose cell blocks from the residues of liquid-based cytology samples.

BACKGROUND: Inevitable loss of diagnostic material should be minimized during cell block preparation. We introduce a modified agarose cell block technique that enables the synthesis of compact cell blocks by using the entirety of a cell pellet without the loss of diagnostic material during cell block preparations. The feasibility of this technique is illustrated by high-throughput immunocytochemistry using high-density cell block microarray (CMA). METHODS: The cell pellets of Sure- Path residues were pre-embedded in ultra-low gelling temperature agarose gel and re-embedded in standard agarose gel. They were fixed, processed, and embedded in paraffin using the same method as tissue sample processing. The resulting agarose cell blocks were trimmed and represented on a CMA for high-throughput analysis using immunocytochemical staining. RESULTS: The SurePath residues were effectively and entirely incorporated into compact agarose cell buttons and embedded in paraffin. Sections of the agarose cell blocks revealed cellularities that correlated well with corresponding SurePath smears and had immunocytochemical features that were sufficient for diagnosis of difficult cases. CONCLUSIONS: This agarose-based compact cell block technique enables preparation of high-quality cell blocks by using up the residual SurePath samples without loss of diagnostic material during cell block preparation.

Repeat Fine-Needle Aspiration Biopsy within a Short Interval Does Not Increase the Atypical Cytologic Results for Thyroid Nodules with Previously Nondiagnostic Results.

OBJECTIVE: The purpose of this study was to determine whether the recommended waiting period of 3 months is necessary for repeat fine-needle aspiration biopsy (FNAB). STUDY DESIGN: A retrospective review of 128 nodules from 126 patients with initial nondiagnostic (ND) results was performed for the period between January 2009 and December 2012. Demographic and clinical factors were recorded including age, sex, time interval between FNABs, and ultrasound (US) factors, i.e. nodule size, location, consistency, suspicious malignant findings and thyroiditis. The time interval was subdivided into