Young Jin Jun

Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma.

Jang K‐S, Song Y S, Jang S‐H, Min K‐W, Na W, Jang S M, Jun Y J, Lee K H, Choi D & Paik S S
(2010) Histopathology56, 229–239

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas

Purpose Glucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas. Methods We used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis. Results Membranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively). Conclusion GLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.

Clinicopathologic significance of GLUT1 expression and its correlation with Apaf-1 in colorectal adenocarcinomas

AIM To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expression in colorectal adenocarcinomas. METHODS We used tissue microarrays consisting of 26 normal mucosa, 50 adenomas, 515 adenocarcinomas, and 127 metastatic lesions. Medical records were reviewed and clinicopathological analysis was performed. RESULTS GLUT1 expression was absent in normal mucosa and low or moderately apparent in 19 cases (38.0%) of 50 adenomas. However, GLUT1 expression was detected in 423 (82.1%) of 515 adenocarcinomas and in 96 (75.6%) of 127 metastatic lesions. GLUT1 expression was significantly correlated with female gender (P = 0.009), non-mucinous tumor type (P = 0.045), poorer differentiation (P = 0.001), lymph node metastasis (P < 0.001), higher AJCC and Dukes stage (P < 0.001 and P < 0.001, respectively). There was a significant inverse correlation between GLUT1 expression and Apaf-1 expression (P = 0.001). In univariate survival analysis, patients with GLUT1 expression demonstrated poor overall survival and disease-free survival (P = 0.047 and P = 0.021, respectively, log-rank test). CONCLUSION GLUT1 expression was frequently increased in adenocarcinomas and metastatic lesions. GLUT1 expression was significantly correlated with poorer clinicopathologic phenotypes and survival of patients with colorectal adenocarcinomas.

Clinicopathological significance of CADM4 expression, and its correlation with expression of E-cadherin and Ki-67 in colorectal adenocarcinomas

Aims Cell adhesion molecule 4 (CADM4) is a novel tumour suppressor. The purpose of this study was to investigate the correlation between its expression and the expression of E-cadherin and Ki-67 in colorectal adenocarcinomas, as well as its effect on patient survival. Methods We evaluated CADM4 expression in tissue microarrays of 513 colorectal adenocarcinomas by immunohistochemistry. Results CADM4 was highly expressed in 210 of the 513 colorectal adenocarcinomas; expression was reduced in 185 cases and absent in the remaining cases. Loss of CADM4 expression was correlated with larger tumour size (6.2±2.1 cm vs 5.3±2.0 cm, p<0.001), mucinous tumour type (61.5% vs 20.9%, p<0.001), lymph node metastasis (31.4% vs 20.9%, p=0.022), higher Dukes stage (25.5% vs 19.6%, p=0.044), poorer differentiation (38.5% vs 18.8%, p<0.001), absence of E-cadherin expression (28.5% vs 16.0%, p=0.007) and presence of Ki-67 expression (27.3% vs 12.3%, p<0.001). In univariable Cox regression analysis, absence of CADM4 expression was associated with poorer overall survival (HR 0.712; 95% CI 0.512 to 0.989, p=0.042) and disease-free survival (HR 0.732; 95% CI 0.546 to 0.981, p=0.037). In multivariate analysis with the Cox proportional hazards model, CADM4 expression was not an independent prognostic factor of overall survival (HR 0.726; 95% CI 0.516 to 1.021, p=0.066) and disease-free survival (HR 0.762; 95% CI 0.563 to 1.033, p=0.080). Conclusions Loss of CADM4 expression is relatively frequent in colorectal adenocarcinomas and may play an important role in cancer progression and patient survival.

Primary Vesical Actinomycosis Diagnosed by Routine Urine Cytology

Primary vesical actinomycosis, caused by Actinomyces israelii, is extremely rare, and preoperative diagnosis has been known to be difficult due to the vague and nonspecific clinical symptoms.1-3 In most cases, it was misdiagnosed as a vesical tumor and usually confirmed postoperatively through a pathologic examination. An accurate preoperative diagnosis of vesical actinomycosis is possible by routine urine cytologic examination. Herein, we report a rare case of primary vesical actinomycosis, suspected clinically as malignant vesical tumor, which was diagnosed primarily by routine urine cytology. A 44-year-old woman presented with gradually aggravated dysuria, frequency, pyuria and intermittent lower abdominal pain for 7 months. Routine urinalysis showed hazy-colored urine with increased leukocyte count. Pelvic computed tomography revealed diffuse, irregular wall thickening at the right anterolateral side of the urinary bladder. The lesion was accompanied by perivesical fat infiltration and blurring of the peritoneal surface boundary. Clinically, a malignant bladder tumor with perivesical invasion was highly suspected. A routine urine cytologic examination showed a few dusty islands surrounded by a dense population of neutrophils. The characteristic actinomycotic “sulfur granules” with long, slender filamentous structures were found (Figure 1). Our cytologic diagnosis was actinomycosis. Cystoscopic examination was done, and it revealed a broad-based, mass-forming lesion covered with yellowish, puslike material. The lesion was surgically removed, and the histopathologic examination confirmed vesical actinomycosis with

Clinicopathological significance of CADM4 expression in invasive ductal carcinoma of the breast

Aims Cell adhesion molecule 4 (CADM4) is a novel tumour suppressor involved in cell adhesion. Loss or decreased expression of CADM4 has been associated with the development and progression of some cancers. The purpose of this study was to investigate the clinicopathological significance of CADM4 expression in breast cancer. Methods We constructed tissue microarrays to evaluate the immunohistochemical expression of CADM4 in 256 cases of invasive ductal carcinoma (IDC) and 45 cases of ductal carcinoma in situ (DCIS). Results CADM4 was expressed in 37 (82.2%) DCIS cases, and in 173 (67.6%) IDC cases. CADM4 expression was higher in DCIS than in IDC (p=0.049). Loss or decrease of CADM4 expression was significantly correlated with higher histological grade (p=0.020), absence of oestrogen receptors (p<0.001), absence of progesterone receptors (p=0.024), and overexpression of c-erbB-2 (p=0.018). In univariable and multivariable Cox regression analyses of all 256 IDC cases, CADM4 expression was not significantly associated with overall and disease-free survival. However, it showed a significant positive association with longer disease-free survival in 187 stages I and II IDC cases (p=0.039, log-rank test). Conclusions Loss or decrease of CADM4 expression seems to play an important role in breast cancer invasiveness, and it is associated with poorer biological parameters. CADM4 can be used as a novel marker predicting risk of recurrence and disease outcomes in stages I and II IDC.

Fine needle aspiration cytology of a granular cell tumour arising in the thyroid gland.

Dear Editor, Granular cell tumours (GCTs) were considered to be of myogenic origin by Abrikosoff in 1926 but are now regarded as tumours associated with nerve sheath differentiation. GCTs can occur at any age and the male to female ratio is about 1 : 3. The tumours are mainly subcutaneous, but are occasionally found in muscle and skin, and more rarely in internal organs. Approximately 70% of cases occur in the head and neck region, of which 30% are in the tongue. They also arise in the breast, oesophagus, tracheobronchial tree, gastrointestinal tract and urinary bladder. GCTs are almost always benign; recurrence is infrequent (less than 5%) and results from incomplete excision. To our knowledge, eight primary GCTs of the thyroid gland have been previously reported; only two of the reports described cytological findings obtained by fine needle aspiration (FNA). We describe a case of thyroid GCT together with its radiological [computed tomography (CT) and sonography] and cytopathological characteristics. A 24-year-old woman presented with a painless neck mass that had been growing gradually over the previous 3 years. Multiple nodules without tenderness were noted in both lobes of the thyroid gland. Thyroid function tests were within normal limits. Thyroid sonography revealed a markedly hypoechoic nodule, measuring 1.8 cm diameter, on the medial side of the right mid-zone and multiple isoechoic masses, ranging from 0.5 to 2.1 cm in both thyroid lobes. CT revealed a non-enhancing mass, identical to the hypoechoic nodule of the sonogram, and multiple enhancing lesions (Figure 1a). The haematoxylin and eosinand Papanicolaoustained conventional FNA smears of the right mid-zone showed benign follicular cells and large granular cells, which were present as single cells and in syncytial clusters (Figure 1b). These cells had finely granular abundant cytoplasm with ill-defined cellular borders and small round to oval nuclei (Figure 1c). The chromatin pattern was uniformly regular and the nucleoli were small or inconspicuous. Intranuclear inclusions were not noted. Some naked nuclei were present with granular debris due to disruption of cell membranes. No mitotic figures, inflammation or necrosis were evident. The FNA smears were initially interpreted as Benign, consistent with a benign follicular nodule according to the Bethesda system, and we added a comment for the presence of Hürthle cell change. Total thyroidectomy was performed for a presumed follicular neoplasm. Grossly, the surgical specimen consisted of a thyroid gland measuring 9.8 · 5.3 · 2 cm containing six well-demarcated yellowish white nodules ranging from 0.3 to 2.8 cm. Microscopically, the tumour in the mid-zone of the right lobe contained confluent sheets of uniform polygonal to slightly spindle-shaped cells with central or eccentric nuclei surrounded by abundant uniform granular cytoplasm (Figure 1d). On special staining, there were prominent periodic acid Schiff (PAS)-positive fine granules in their cytoplasm. Immunohistochemical stains were positive for S-100, NSE and CD68 and negative for GFAP and TTF-1. The pathological diagnosis was thus confirmed as GCT. The other five nodules showed nodular hyperplasia. The tumour was encapsulated, but in some places the capsule was incomplete and tumour cells mingled with adjacent thyroid follicles. There are suggested criteria of malignant GCT, such as the presence of necrosis and mitoses, high nuclear to cytoplasmic ratio, nuclear pleomorphism, vesicular nuclei with prominent nucleoli, and high Ki-67 expression. In our case, the tumour cells were benign-looking and uniform in appearance and their nuclei had finely dispersed chromatin with inconspicuous nucleoli and no mitotic figures. The Ki-67 labelling index was less than 1%. The partial incomplete capsulation was noted, but we Correspondence: K.-S. Jang, MD, Department of Pathology, College of Medicine, Hanyang University, 17 Haengdang-Dong, SeongdongGu, Seoul 133-792, Korea Tel.: +82-2-2290-8960; Fax: +82-2-2296-7502; E-mail: medartisan@hanyang.ac.kr

Splenic hamartoma: A case report and review of the literature

Splenic hamartoma is a rare benign malformation, composed of an anomalous mixture of normal splenic elements, often found incidentally while working up other complaints or at autopsy. A splenic mass was incidentally found while evaluating the effects of a traffic accident in a 63-year-old woman. Abdominal computed tomography revealed a well-defined splenic mass with rim enhancement. The patient underwent splenectomy. The resected spleen contained a well-defined mass lesion measuring 3.5 cm × 3.0 cm. Microscopic examination revealed disorganized slit-like vascular channels lined by plump endothelial cells without atypia. The cells lining the vascular channels were positive for CD8, CD31, CD34 and vimentin. Endothelial cells that are positive for CD8 are a key feature that differentiates hamartoma from other vascular lesions of the spleen. Although this tumor is very rare, it must be included in the differential diagnosis of splenic mass-forming lesions.

Parosteal lipoma of the rib.

Parosteal lipoma is a rare benign tumor that is composed mainly of benign mature lipocytes, and it has an intimate association with the underlying periosteum of affected bone. Parosteal lipoma involving the rib is quite rare. We believe that only four cases have been previously reported in the English literature. Here we describe an exceedingly rare case of parosteal lipoma that developed in the right seventh rib, which presented in a 50-year-old man having a previous history of trauma at this site.

Cytomegalovirus enteritis with jejunal perforation in a patient with endometrial adenocarcinoma.

Cytomegalovirus (CMV) infection of the gastrointestinal tract has been reported most frequently in the setting of immunodeficiency. The whole gastrointestinal tract can be affected; however, the small bowel is rarely affected. We report a case of CMV enteritis with jejunal perforation in a 53-year-old woman with a history of chemoradiation therapy for endometrial cancer 8 years previously. At follow-up evaluation, lower abdominal pain, diarrhea and vomiting appeared. Abdominal computed tomography showed intra-abdominal free air in the subphrenic space and porta hepatis. The jejunal segment revealed serosal purulent exudates with a perforation. The resected jejunal segment showed a large geographic ulcerative mucosal lesion. The microscopic findings revealed a diffuse ulcerative mucosal change with a prominent granulation tissue formation and many large atypical vascular endothelial cells and stromal fibroblasts with intranuclear or intracytoplasmic inclusion bodies. These cells were positive for CMV antibody. The final diagnosis was CMV-associated jejunitis with a jejunal perforation.