Jungsuk An

Micropapillary Carcinoma of Stomach: A Clinicopathologic and Immunohistochemical Study of 11 Cases

Micropapillary carcinoma (MPC) of the stomach is a rare, newly recognized entity, and only 2 patients with this histology have been reported. We investigated clinicopathologic features, expression of mucin (MUC2, MUC5AC, MUC6, CD10) and cytokeratin profiles (CK7 and CK20), epidermal growth factor receptors (EGFR and HER2), prognostic markers (p53 and Ki-67), and outcomes in 11 MPCs of the stomach. The proportion of MPC component ranged from 5% to 70%. Micropapillary features were often found at the deep advancing edge of the tumor. Endolymphatic tumor emboli were found in 10 cases (91%) and lymph node metastases were found in 4 cases (36%). In MPCs, positive expression was observed for Ki-67 (82%), CK7 (73%), EGFR (64%), p53 (64%), MUC5AC (45%), MUC6 (36%), and CK20 (27%). However, MUC2, CD10, and HER2 expression was negative in all cases. In 9 conventional adenocarcinomas and 11 papillary adenocarcinomas with multiple endolymphatic tumor emboli, used as control, positive expression was observed for Ki-67 (100%), CK7 (90%), EGFR (80%), CK20 (70%), p53 (70%), MUC5AC (70%), MUC6 (60%), MUC2 (40%), CD10 (25%), and HER2 (15%). Expression of MUC2, CK20, and the Ki-67 labeling index was significantly higher in control adenocarcinomas as compared with MPCs (P<0.05). However, there was no significant difference in other clinicopathologic features and overall patient survival. Subclassification of MPCs into 2 subgroups according to the proportion of micropapillary component (cut-off value was 20%) failed to find any significant clinicopathologic differences (P>0.05). Although MPCs in other organs show a poor prognosis, this does not seem to be true for gastric MPCs. Further larger studies are necessary to confirm our initial findings.

Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas

Background Human papillomavirus (HPV) is an oncogenic virus in cervical cancer and most invasive carcinomas (ICs) are caused by HPV16 and 18. However, the roles and contributions of other uncommon and rare genotypes remain uncertain. Methods HPV genotypes were retrospectively assessed using an HPV DNA chip that can specify up to 32 HPV genotypes. We arbitrarily regarded genotypes accounting for less than 6% of the total as uncommon and rare genotypes. Results A total of 3,164 HPV-positive cases were enrolled. In groups 2A, 2B, 3, and unclassified HPV genotypes, 2.4% of cases with uncommon HPV genotypes (68, 26, 34, 53, 66, 69, 70, 73, 40, 42, 43, 44, 54, 55, 61, 62, 6, and 11) showed high grade squamous intraepithelial lesions and ICs. There were no HPV32- and 57-infected cases. Conclusions We found that the uncommon and rare HPV genotypes may provide incremental etiologic contributions in cervical carcinogenesis, especially HPV68, 70, and 53. Further studies on these uncommon and rare HPV genotypes will be of importance in establishing the significance of genotypes in different regions, especially in planning a strategy for further vaccine development as well as follow-up on the effectiveness of the currently used vaccines.

Graft-versus-host disease after kidney transplantation.

Graft-versus-host disease (GVHD) is a rare complication after kidney transplantation. We describe a 62-year-old female with end-stage renal disease due to hypertension. She received a kidney with 4 mismatched human leukocyte antigen (HLA) out of 6 HLA - A, B, DR from a deceased donor. After the procedure, the patient showed watery diarrhea on postoperative day (POD) 45. An endoscopic biopsy of the colon revealed some apoptotic cells consistent with GVHD. Thrombocytopenia was gradually developed on POD 54. She received steroid pulse therapy, and thrombocytopenia did not progress. However, pneumonia, renal failure, and cardiac failure occurred. She died due to multiple organ failure. We must consider GVHD in renal transplant recipients without homozygous or identical HLA, who had only watery diarrhea without other typical GVHD symptoms such as skin rash and fever, although GVHD is rare in renal transplant recipients.

Bilateral Stafne Bone Cavity in the Anterior Mandible with Heterotopic Salivary Gland Tissue: A Case Report

Stafne bone cavity is a well demarcated defect of the mandible, usually asymptomatic and located in the posterior portion of the bone.1 Most cases have been reported in male patients between the age of 50 and 70 years.2 This lesion has been labeled with various terms, including ectopic salivary gland, idiopathic defect, mandibular salivary gland inclusion, Stafne bone cavity and cyst.2 The cavities are often filled with normal salivary gland tissue, but occasional cases showed cavity contents that included skeletal muscle, fibrous connective tissue and adipose tissue.1,2 Bilateral Stafne bone cavity of the anterior mandible is extremely rare and only seven such cases have been reported previously.2 Herein, we report a case of bilateral Stafne bone cavity of the anterior mandible.

Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer

Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions 17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET. Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co-amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue samples, and revealed that high expression (except for PGAP3) was significantly associated with shorter overall survival. Knockdown of these genes using small interfering RNA led to significant suppression of GC cell proliferation and migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was attributable to attenuated cell cycle progression and increased apoptosis. This study identified novel candidate CPGs co-amplified with MET or ERBB2, and suggests that they play a functional role in GC.

Improvement of diagnostic performance of pathologists by reducing the number of pathologists responsible for thyroid fine needle aspiration cytology: An institutional experience

Various efforts have been made to improve the diagnostic accuracy of thyroid fine needle aspiration (FNA) cytology. We changed the diagnostic system by reducing the number of pathologists responsible for the thyroid FNA cytology in the routine work, and analyzed the effect on the pathologists diagnostic performance.

Phenylethanolamine N-methyltransferase downregulation is associated with malignant pheochromocytoma/paraganglioma

Malignant pheochromocytoma/paraganglioma (PCC/PGL) is defined by the presence of metastases at non-chromaffin sites, which makes it difficult to prospectively diagnose malignancy. Here, we performed array CGH (aCGH) and paired gene expression profiling of fresh, frozen PCC/PGL samples (n = 12), including three malignant tumors, to identify genes that distinguish benign from malignant tumors. Most PCC/PGL cases showed few copy number aberrations, regardless of malignancy status, but mRNA analysis revealed that 390 genes were differentially expressed in benign and malignant tumors. Expression of the enzyme, phenylethanolamine N-methyltransferase (PNMT), which catalyzes the methylation of norepinephrine to epinephrine, was significantly lower in malignant PCC/PGL as compared to benign samples. In 62 additional samples, we confirmed that PNMT mRNA and protein levels were decreased in malignant PCC/PGL using quantitative real-time polymerase chain reaction and immunohistochemistry. The present study demonstrates that PNMT downregulation correlates with malignancy in PCC/PGL and identifies PNMT as one of the most differentially expressed genes between malignant and benign tumors.

Morphologic Analysis of Cytomegalovirus Infected Cells in Bronchial Washing Cytology: Comparison of Liquid-Based Preparation and Conventional Smear

Background: The cytopathic effects of cytomegalovirus (CMV) infection have been well described since the virus was first reported; however, the morphology of CMV infection has not been clearly studied. We examined the difference in detailed cytologic findings in bronchial washing cytology between liquid-based and conventionally prepared smears. Methods: Bronchial washing cytology was processed using either the conventional preparation (CP) or liquid-based preparation (LBP). Sixty-nine cells with typical cytopathic effects of CMV infection were detected on CP slides and 18 cells on LBP slides. Using the image analyzer, area, circumference, major axis, and minor axis of the cytoplasm, nucleus, and intranuclear inclusion were measured in singly scattered CMV-infected cells, and histiocytes were used as a control. Results: The mean cytoplasmic area of CMV-infected cells was 1.47 times larger than that of histiocytes in CP and 2.92 times larger in LBP (p<.05). The mean nuclear area of CMV-infected cells was 2.61 times larger than that of histiocytes in CP and 4.25 times larger in LBP (p<.05). The nucleus to cytoplasm ratio and intranuclear inclusion to cytoplasm ratio of the mean area, circumference, major axis, and minor axis in CP were larger than those in LBP (p<.05). Conclusions: The sizes of cytoplasm, nucleus, and intranuclear inclusion were larger in LBP than in CP, indicating that CMV-infected cells are easily detectable in LBP. However, the nucleus-to-cytoplasm ratio was larger in CP, suggesting that differentiation from malignancy or regenerative atypia requires caution in CP.