Expression of pRb, p53, p16 and Cyclin D1 and Their Clinical Implications in Urothelial Carcinoma

The aim of this study was to assess immunohistochemical expression of p53, pRb, p16, and cyclin D1, alone or in combination, as prognostic indicators and to investigate their correlation with clinocopathologic features of urothelial carcinoma. Immunohistochemical staining for p53, pRb, p16, and cyclin D1 was performed on a tissue microarray from 103 patients with urothelial carcinoma who underwent radical cystectomy. Of the patient samples analyzed, 36 (35%), 61 (59%), 47 (46%) and 30 (29%) had altered expression of p53, pRb, p16, and cyclin D1, respectively. Abnormal expression of p53 and pRb correlated with depth of invasion (P=0.040 and P=0.044, respectively). Cyclin D1 expression was associated with tumor stage and recurrence (P=0.017 and P=0.036, respectively). Altered pRb was significantly correlated with overall survival (P=0.040). According to the expression pattern of pRb and p53, p53/pRb (altered/normal) had worse survival than p53/pRb (normal/altered) (P=0.022). Alteration of all markers had worse survival than all normal (P=0.029). As determined by multivariate analysis, tumor stage, lymph node metastasis and the combined expression of p53 and pRb are independent prognostic factors. In conclusion, immunohistochemical evaluation of cell cycle regulators, especially the p53/pRb combination, might be useful in planning appropriate treatment strategies.

Application of Bethesda System for Reporting Thyroid Aspiration Cytology

BACKGROUND: The Bethesda classification system for reporting on thyroid fine-needle aspiration (FNA) cytology was recently proposed by the National Cancer Institute, USA. We aimed to report our experience with applying this system for thyroid FNA, with a focus on comparing it with the four categorical system. METHODS: We retrospectively reviewed the 4,966 thyroid FNAs that were performed at the Seoul St. Mary's Hospital between October 2008 and September 2009. All the FNAs were classified according to the Bethesda system and the four tier system. RESULTS: The cytologic diagnoses of the Bethesda system included 10.0% unsatisfactory, 67.7% benign, 3.1% atypia of undetermined significance, 0.6% follicular neoplasm, 0.5% follicular neoplasm, Hurthle cell type, 5.1% suspicious for malignancy and 13.0% malignancy. Using four tier system, 10.1%, 67.6%, 9.3%, and 13% were diagnosed as unsatisfactory, negative for malignancy, atypical cells and malignancy, respectively. Of the 4,966 nodules, 905 were histologically confirmed. The specificity of the Bethesda system and the four tier system for diagnosing malignancy was 99.6% and 82.6%, respectively. CONCLUSIONS: The Bethesda system can classify indeterminate thyroid nodules into more detailed categories and provide clinicians with useful information for management.

Application of Bethesda System for Reporting Thyroid Aspiration Cytology

BACKGROUND: The Bethesda classification system for reporting on thyroid fine-needle aspiration (FNA) cytology was recently proposed by the National Cancer Institute, USA. We aimed to report our experience with applying this system for thyroid FNA, with a focus on comparing it with the four categorical system. METHODS: We retrospectively reviewed the 4,966 thyroid FNAs that were performed at the Seoul St. Mary's Hospital between October 2008 and September 2009. All the FNAs were classified according to the Bethesda system and the four tier system. RESULTS: The cytologic diagnoses of the Bethesda system included 10.0% unsatisfactory, 67.7% benign, 3.1% atypia of undetermined significance, 0.6% follicular neoplasm, 0.5% follicular neoplasm, Hurthle cell type, 5.1% suspicious for malignancy and 13.0% malignancy. Using four tier system, 10.1%, 67.6%, 9.3%, and 13% were diagnosed as unsatisfactory, negative for malignancy, atypical cells and malignancy, respectively. Of the 4,966 nodules, 905 were histologically confirmed. The specificity of the Bethesda system and the four tier system for diagnosing malignancy was 99.6% and 82.6%, respectively. CONCLUSIONS: The Bethesda system can classify indeterminate thyroid nodules into more detailed categories and provide clinicians with useful information for management.

Loss of Heterozygosity on Chromosome 15q15 Near Thrombospondin-1 Gene in Breast Carcinomas

BACKGROUND: Chromosome 15q15 near the thrombospondin-1 (THBS-1) gene may be associated with tumor progression and metastasis. To clarify the potential role of the15q15 region in progression of breast carcinoma, we investigated the loss of heterozygosity (LOH) and the microsatellite instability (MSI) status of chromosome 15q15. Methods : LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. METHODS: LOH and MSI were detected in 84 breast carcinoma specimens using PCR-based microsatellite analysis with three microsatellite markers. RESULTS: Of 77 breast carcinomas containing the heterozygous alleles, 25 (32%) showed LOH in at least one microsatellite marker. Partial LOH and total LOH were detected in 14 (18.27%) and 11 (14.3%) cases. The total LOH were inversely correlated with node metastasis. A single LOH at D15S514 was inversely correlated with nuclear grade and a single LOH at the D15S129 allele was associated with increased expression of the THBS-1 gene. MSI-positive breast carcinomas detected in 14 (17%) cases showed no correlation with any clinicopathologic feature. CONCLUSIONS: These results indicate that loss of the chromosome 15q15 region delays the progression of breast carcinoma because the magnitude of LOH is large and involves the THBS-1 gene and additional genetic elements. The genes located on chromosome 15q15 probably play a tissue-type-dependent role in malignant growth of the tumor.

Protein Expression and Gene Amplification of Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer: Correlation with the Response to Gefitinib Therapy

BACKGROUND: Gefitinib is an EGFR tyrosine kinase inhibitor that has shown dramatic effectiveness in a subset of non-small cell lung cancer (NSCLC) patients. We evaluated the response rate to gefitinib, and the significance of the EGFR and HER2/neu status as predictive markers of the tumor response. METHODS: The EGFR and HER2/neu protein expressions, as determined by immunohistochemistry (IHC) and gene amplification via chromogenic in situ hybridization (CISH), were analyzed in biopsy specimens from 46 patients with advanced NSCLC. After their failure with the first-line treatment, all the patients had received gefitinib treatment. RESULTS: A partial response (PR) was achieved in 8 patients (17.4%). An EGFR overexpression was detected in 80.4% (37/46) of the tumors, and this was observed exclusively in patients with a PR (100% vs 75.3%, respectively; p=0.076). EGFR gene amplification was present in 47.8% of the tumors (22/46). HER2/neu was overexpressed in 13%(6/46) and it was amplified in 17% (7/46). The overall survival was prolonged in the female patients (p=0.007), and in patients with T1 and T2 disease (p=0.039), adenocarcinoma (p=0.010), a PR (p=0.022), an EGFR IHC+ status (p=0.033), an EGFR IHC+/CISH+ status (p=0.010), or an EGFR+/HER2/neu+ status (p=0.030). On multivariate analysis, gender, T disease and EGFR IHC/CISH remained the significant predictors of survival. CONCLUSIONS: Gefitinib showed a modest effect for the patients with chemotherapy-refractory advanced NSCLC. A combination of EGFR IHC and CISH might be important for identifying those patients who are most likely to benefit from gefitinib therapy.

Evaluation for Cytopreservability of Manual Liquid-Based Cytology Liqui-PREP(TM) and its Application to Cerebrospinal Fluid Cytology: Comparative Study with Cytospin / 대한세포병리학회지

Cerebrospinal fluid (CSF) cytology is an effective tool for evaluating diseases involving the central nervous system, but his technique is usually limited by its low cellularity and poor cellular preservation. Here we compared the manual liquid-base Liqui-PREPTM (LP) to the cytospin (CS) with using a mononuclear cell suspension and we applied both methods to the CSFs of pediatric leukemia patients. The cytopresevability, in terms of cell yield and cell size, and the clinical efficacy were evaluated. When 2000 and 4000 mononuclear cells were applied, LP was superior to CS for the cell yield, 16.8% vs 1.7% (P=0.001) and 26.2% vs 3.5% (P=0.002), respectively. The mean size of the smeared cells was 10.60 micrometer in the CS, 5.01 micrometer in the LP and 6.50 micrometer in the direct smear (DS), and the size ratio was 1.7 (CS to DS), 0.8(LP to DS) and 2.1 (CS to LP), respectively. As compared to the cells in the DS, the cells in the CS were significantly enlarged, but those in the LP were slightly shrunken. Upon application to 109 CSF samples, 4 were diagnosed as positive for leukemia (positive), 4 had atypical cells and 101 were negative by CS; 6 were positive, one had atypical cells and 102 were negative by LP. For six cases, in which 4 were positive for leukemia and 2 of 4 had atypical cells by CS, they were positive by LP and they were also confirmed as positive according to the follow-up study. Three cases diagnosed as atypical cells (two by CS and one by LP), were confirmed as negative. In conclusion, these results suggest that LP is superior to CS for the cytopresevability and for rendering a definite diagnosis of cerebrospinal fluid.

Fine Needle Aspiration Cytology of Inflammatory Myofibroblastic Tumor of Lung: A Case Report / 대한세포병리학회지

Inflammatory myofibroblastic tumor (IMT), normally referred to as inflammatory pseudotumor, is a fairly rare condition. Fine needle aspiration cytology (FNAC) of IMT has only rarely been reported. Here, we describe one such case of pulmonary inflammatory myofibroblastic tumor. A 30-year-old man presented with a 2.8cm-sized mass in his lung. Chest CT revealed a well defined, poorly enhancing mass. FNAC showed some fascicular or swirled clusters of spindle cells, admixed with occasional inflammatory cells and foamy histiocytes. The majority of the tumor cells evidenced bland, elongated nuclei, but infrequent pleomorphic nuclei. Some of the tumor cells evidenced nuclear grooves and intranuclear inclusions. Although the cytological differentiation of IMT from malignant lesions is not immensely problematic, due to the general paucity of cytological and nuclear atypia, a definite cytological diagnosis of IMT cannot be rendered simply by FNAC. Therefore, a diagnosis of IMT may be suggested via exclusive diagnosis.

Clinicopathologic Analysis of the Micropapillary Variant of Urothelial Carcinoma in Urinary

BACKGROUND: Micropapillary urothelial carcinoma of urinary bladder is a rare and aggressive subtype of urothelial carcinoma (UC). METHODS AND RESULTS: Seven UCs with a micropapillary component (MPC) were identified by reviewing 135 cystectomy specimens of UC (5.2% in incidence). MPC was associated with conventional UC in 6 cases and the plasmacytoid variant of UC in 1 case. Lymph node metastasis, that characteristically contained MPC was present in 60% (3 out of 5 cases of regional lymph node dissection). Three patients with extensive MPC showed laminar propria invasion (pT1; 33%) and perivesical fat invasion (pT3; 67%). Two out of 3 patients with extensive MPC showed distant metastasis into the colon after cystectomy. The colonic lesions showed exclusively micropapillary differentiation. Four patients with focal or moderate MPC (pT2, 25%; pT3, 75%) were alive without disease at the time of writing this article. All 3 cases with extensive MPC had surface and/or invasive MPC on the prior TURB specimen. Immunohistochemically, the tumor cells were positive for cytokeratin 7, cytokeratin 20, EMA and E-cadherin and tissue retraction spaces that simulate lymphatic spaces were negative for CD34 in all 7 cases. CONCLUSIONS: This study suggests that the micropapillary growth pattern in UC is a manifestation of aggressive behavior and UC with MPC must be included as part of the differential diagnosis when dealing with a metastatic lesion with a micropaillary structure.

Primary Signet-ring-cell Carcinoma of the Right and the Sigmoid Colon in Crohn's Disease

A 31-year-old woman with a 5-year history of Crohn's disease was admitted to our hospital because of recurrent right lower quadrant pain and diarrhea. Abdominal computed tomography showed multiple fistulas between the terminal ileum, the sigmoid colon, and the cecum, and mucosal wall thickenings due to an active inflammatory process and mucosal enhancements. Colonoscopic examinations showed a finger-like projection of a polypoid mass at the ileocecal valve, long-neck, finger-like pseudopolyps at the cecum, and soft, lumen narrowing and multiple pseudopolyps at the sigmoid colon and the intact rectum. There was healing scarring of the anal fistula. These findings were compatible with those of Crohn's disease. Histologic findings were chronic inflammation with erosion and regenerative crypt epithelium. The patient underwent infliximab therapy. She underwent a right colectomy, a Hartman's procedure, and a small bowel segmental resection due to multiple fistulas. The pathologic diagnosis was a signet-ring-cell carcinoma with non-caseating granuloma in the ascending colon, ileum, and sigmoid colon. We report this case of Crohn's disease associated with a colonic signet-ring cell carcinoma.

Fine Needle Aspiration Cytology of Mucinous Cystic Carcinoma of the Pancreas: A Case Report / 대한세포병리학회지

Mucious cystic neoplasm of pancreas is a cystic neoplasm composed of columnar, mucin-producing epithelium and is supported by ovarian-type stroma. The key to the cytologic evaluation of pancreatic cystic lesions is to recognize the cytologic components as being diagnostic of a mucin-producing cystic neoplasm, as all of these neoplasms need to be resected. We report the use of fine needle aspiration cytology in the diagnosis of an invasive mucinous cystic carcinoma confirmed by partial pancreatectomy. The cytologic specimen showed a abundant mucin background and sheets or papillae of neoplastic cells. There are mucin-containing columnar cells that show a variable degree of cytologic atypia.

Fine Needle Aspiration Cytology of the Warthin's Tumor Misinterpretated as Squamous Cell Carcinoma: A Case Report / 대한세포병리학회지

We report a case of Warthin's tumor of the parotid gland in a 53?year?old man, which is incorrectly diagnosed as squamous cell carcinoma. Fine needle aspiration cytology(FNAC) smear obtained from the right parotid gland revealed scattered epithelial cell clusters or nests in a diffuse inflammatory and necrotic background. Some epithelial cells had squamoid appearance showing variable sized bizarre shaped nuclei. They had abundant of dense eosinophilic keratinized cytoplasm. Occasionally, parakeratotic cells were also present. These cytologic findings with significant atypia and necrotic background made diagnosis as squamous cell carcinoma. But, the resection specimen from this patient showed classic Warthin's tumor in addition to abundant areas of inflammation and squamous metaplasia. Metaplastic or infarcted Warthin's tumor in the salivary gland may be confused with false positive diagnosis of malignancy on FNAC. Therefore, cytopathologist should have adequate awareness of potential of erroneous diagnosis in FNAC of Warthin's tumor.

Ependymoma Arising from the Pelvis: A Case Report

We report here on a case of an ependymoma arising from the pelvis in a 25-year-old woman. She had no evidence of abnormality in her brain and bilateral ovaries. The diagnosis was based on light microscopic, immunohistochemical, and ultrastructural features of a typical ependymoma, including the patterns of pseudorosette or true ependymal rosette, the strong immunopositivity for glial fibrillary acid protein and intermediate filaments, and cilia of tumor cells. The mass was over 20 cm in maximum diameter, and it was located between the uterus and rectum without any connection to bilateral ovaries. There were many metastatic nodules in the pelvis and omentum. In addition, the proliferation index in the most active area was 10% by immunohistochemistry using monoclonal antibody MIB-1. Although the prognosis of the pelvic ependymoma is known to be difficult to evaluate, this case may serve to illustrate the poor prognostic course, according to the size of the tumor, the evidence of metastasis, and the MIB-1 labelling index.