Woon Sup Han

Diagnostic algorithm for papillary urothelial tumors in the urinary bladder

Papillary urothelial neoplasms with deceptively bland cytology cannot be easily classified. We aimed to design a new algorithm that could differentiate between these neoplasms based on a scoring system. We proposed a new scoring system that enables to reproducibly diagnose non-invasive papillary urothelial tumors. In this system, each lesion was given individual scores from 0 to 3 for mitosis and cellular thickness, from 0 to 2 for cellular atypia, and an additional score for papillary fusion. These scores were combined to form a summed score allowing the tumors to be ranked as follows: 0–1 = UP, 2–4 = low malignant potential (LMP), 5–7 = low-grade transitional cell carcinoma (TCC), and 8–9 = high-grade TCC. In addition to the scoring system, ancillary studies of MIB and p53 indexes with CK20 expression pattern analyses were compared together with clinical parameters. The MIB index was strongly correlated with disease progression. Four of the 22 LMP patients (18.2%) had late recurrences, two of these four (9.1%) had progression to low-grade carcinoma. The MIB index for LMP patients was strongly associated with recurrence (recurrence vs. non-recurrence, 16.5 vs. 8.1, p < 0.001). The proposed scoring system could enhance the reproducibility to distinguish papillary urothelial neoplasms.

Sarcomatoid hepatocellular carcinoma with hepatoblastoma-like features in an adult

A mixed epithelial and mesenchymal tumor of the liver arising in an adult is rare and is mostly classified as sarcomatoid hepatocellular carcinoma (HCC). In this study, a case of sarcomatoid HCC in an adult with hepatoblastoma (HB)‐like features, which produced difficulty in the differential diagnosis between sarcomatoid HCC and mixed HB, is presented. The epithelial component of the tumor composed of poorly differentiated HCC, Edmondsons grade III, and more primitive components, which were embryonal and small cell undifferentiated components of HB‐like areas. The small undifferentiated cells surrounded HCC and the embryonal component of HB‐like area, and revealed transition partly to areas of rhabdomyosarcoma. A small portion of chondrosarcoma was also noted. Immunohistochemical analysis showed that HCC and the embryonal component of HB‐like areas expressed alpha‐fetoprotein (AFP) and cytokeratin 8. The small undifferentiated cells were negative for AFP but stained with cytokeratin 8 as well as CD56, which is a marker of primitive cells in many sarcoma and HB. It is not certain whether small undifferentiated cells belong to hepatic progenitor cells or primitive mesenchymal cells. Polymerase chain reaction–single‐strand conformation polymorphism analysis for beta‐catenin mutation using microdissection revealed no mutation of any components. A review was undertaken of the cases previously reported as adult hepatoblastoma without detailed immunohistochemical study and consider many of them may be sarcomatoid HCC. These primitive and sarcomatoid components would be arising from the dedifferentiation process of HCC.

Pericarditis due to Tsutsugamushi Disease

Tsutsugamushi Disease is an acute febrile illness caused by Rickettsia tsutsugamushi, which enters into the human bloodstream through the bite of leptotrombidium. It is characterized by eschar, fever and cutaneous rash. Pericardial effusion in Tsutsugamushi Disease is not a common manifestation, although a high rate of effusion was reported in autopsy in those who had died of the disease. Here, we report a case of Tsutsugamushi pericarditis documented by indirect immunofluorescent test of pericardial fluid, and give a brief review of the literature.Tsutsugamushi Disease is an acute febrile illness caused by Rickettsia tsutsugamushi, which enters into the human bloodstream through the bite of leptotrombidium. It is characterized by eschar, fever and cutaneous rash. Pericardial effusion in Tsutsugamushi Disease is not a common manifestation, although a high rate of effusion was reported in autopsy in those who had died of the disease. Here, we report a case of Tsutsugamushi pericarditis documented by indirect immunofluorescent test of pericardial fluid, and give a brief review of the literature.

Questionable role of human herpesviruses in the pathogenesis of Kikuchi disease

CONTEXT Kikuchi disease is a self-limiting febrile lymphadenopathy characterized by a patchy area of apoptosis. Kikuchi disease is thought to be caused by a virus, but this has not been clearly demonstrated. Human herpesviruses 6 and 7 (HHV-6 and HHV-7) are lymphotropic viruses that can induce apoptosis in infected lymphocytes. Recently, HHV-8 was reported to be a possible etiologic agent of Kikuchi disease. OBJECTIVE To investigate the incidence of HHV-6, HHV-7, and HHV-8 infection in patients with Kikuchi disease. DESIGN Seventy archival tissue specimens (from 50 Kikuchi disease cases and 20 control cases) were tested for the presence of HHV-6 and HHV-7 using a nested polymerase chain reaction, and for the presence of HHV-8 using single-step polymerase chain reaction. Immunohistochemistry for HHV-8 expression was carried out in those cases in which HHV-8 was detected using polymerase chain reaction. RESULTS Of the 50 cases with Kikuchi disease, 21 (42%) were HHV-6 positive and 32 (64%) were HHV-7 positive. Eight (40%) of the 20 control cases were HHV-6 positive and 9 (45%) were HHV-7 positive. Both HHV-6 and HHV-7 were detected in 15 (30%) of the cases with Kikuchi disease and in 3 (15%) of the control cases. Three (6%) of the 50 cases of Kikuchi disease were HHV-8 positive but revealed no positive cells on immunohistochemical analysis for HHV-8. Human herpesvirus 8 was not expressed in any of the control cases. CONCLUSIONS There was no association between the presence of HHV-6 or HHV-7 and Kikuchi disease. Because the HHV-8 genome but not protein was detected in a small proportion of the cases of Kikuchi disease, its potential causative role in this disease should be determined by further studies.

A case of pyothorax-associated lymphoma simulating empyema necessitatis

We describe a case of a diabetic man with a 40-year history of chronic tuberculous empyema presented with fever, chest pain and bulging soft tissue of the right chest wall. CT scan revealed a huge chest wall mass showing extensive necrosis with air-bubbles and destruction of the ribs. Decortication and extirpation of the chest wall mass were performed, and histopathologic examination confirmed diffused large cell type non-Hodgkins lymphoma.

Detection of Transforming Growth Factor-α in the Serum of Gastric Carcinoma Patients

Transforming growth factor-α (TGF-α) is a ligand for epidermal growth factor receptor (EGFR) and it is overexpressed in various malignancies including lung, esophageal, colorectal, ovarian and gastric carcinomas. In patients with gastric carcinoma, its overexpression may be associated with advanced stage or poor prognosis. We have recently demonstrated that the mean serum level for EGFR in gastric carcinoma patients was significantly elevated compared with that of healthy controls. Using the enzyme-linked immunosorbent assay, the levels of TGF-α were determined in serum from 40 patients with gastric carcinoma (5 patients with stage I, 2 stage II, 4 stage III, and 29 stage IV patients) and 33 healthy controls. The mean serum level for TGF-α in the gastric carcinoma patients was significantly elevated as compared with that of healthy controls (104 ± 235 vs. 22 ± 16 pg/ml; p = 0.03). Eleven patients with gastric carcinoma (27.5%) showed elevated serum TGF-α levels above the cutoff value of 54 pg/ml (defined as 2 standard deviations above the mean of the control group). No significant association was noted between the positivity of TGF-α and clinicopathologic characteristics including gender, age and stage. However, poorly differentiated adenocarcinoma showed a higher positivity of serum TGF-α (43.8%) compared with other histologic types, which was marginally significant (p = 0.06). These results suggest that serum TGF-α could be useful as a tumor marker of gastric carcinoma for predicting prognosis and follow-up after surgery in patients whose initial serum TGF-α levels are elevated.

Leiomyoma of the bronchus treated by endoscopic resection

Leiomyoma of the bronchus is a rare benign tumor. The type of surgical resection depends on the location of the tumor and secondary lung destruction, although most surgical treatment has required thoracotomy. Two Korean women who had pedunculated masses in the left main bronchus and in the right lower lobe bronchus were successfully treated by endoscopic resection. Their postoperative courses were uneventful. They are well 19 months and 10 months, respectively, after resection.

Cancer of unknown primary finally revealed to be a metastatic prostate cancer: a case report.

The vast majority of patients with metastatic prostate cancer present with bone metastases and high prostate specific antigen (PSA) level. Rarely, prostate cancer can develop in patients with normal PSA level. Here, we report a patient who presented with a periureteral tumor of unknown primary site that was confirmed as prostate adenocarcinoma after three years with using specific immunohistochemical examination. A 64-year old man was admitted to our hospital with left flank pain associated with masses on the left pelvic cavity with left hydronephrosis. All tumor markers including CEA, CA19-9, and PSA were within the normal range. After an exploratory mass excision and left nephrectomy, the pelvic mass was diagnosed as poorly differentiated carcinoma without specific positive immunohistochemical markers. At that time, we treated him as having a cancer of unknown primary site. After approximately three years later, he revisited the hospital with a complaint of right shoulder pain. A right scapular mass was newly detected with a high serum PSA level (101.7 ng/ml). Tissues from the scapular mass and prostate revealed prostate cancer with positive immunoreactivity for P504S, a new prostate cancer-specific gene. The histological findings were the same as the previous pelvic mass; however, positive staining for PSA was observed only in the prostate mass. This case demonstrates a patient with prostate cancer and negative serological test and tissue staining that turned out to be positive during progression. We suggest the usefulness of newly developed immunohistochemical markers such as P504S to determine the specific primary site of metastatic poorly differentiated adenocarcinoma in men.

Sporadic lymphangioleiomyomatosis with multiple atypical adenomatoid hyperplasia: differentiation from multifocal micronodular pneumocyte hyperplasia

Sporadic lymphangioleiomyomatosis with multiple atypical adenomatoid hyperplasia: differentiation from multifocal micronodular pneumocyte hyperplasia H.-H. Cho , S.S. Shim *, Y. Kim , W.S. Han b Department of Radiology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea Department of Pathology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea

Chemotherapy-induced amennorrhea: Predictive markers of response to neoadjuvant chemotherapy in breast cancer.

281 Background: There is controversy about the benefit of chemotherapy-induced amenorrhea (CIA) in breast cancer. We investigated significance of CIA after neoadjuvant chemotherapy for predicting response to neoadjuvant chemotherapy in breast cancer patients. METHODS We reviewed the records of 198 premenopausal patients with breast cancer treated with neoadjuvant chemotherapy between January 2005 and December 2010. Chemotherapy-induced amenorrhea (CIA) was defined as serum FSH level ≥40 IU/L after completion of all scheduled neoadjuvant chemotherapy and prior to definitive surgery. RESULTS Among 198 breast cancer patients, 132 pts (66.7%) developed CIA after neoadjuvant chemotherapy. 156 pts (78%) underwent DA chemotherapy. The age of CIA patients was older than non-CIA patients (41.55±5.55 vs. 38.27± 6.86 years, p=0.001). The incidence of CIA after neoadjuvant chemotherapy was significantly higher in responder group (responder vs. nonresponder: 87 pts (74.4%) vs. 45 pts (55.6%); p=0.006). Additionally, FSH level after all scheduled neoadjuvant chemotherapy was significantly higher in responder group (FSH 56.41±32.41 mIU/ml vs. 45.76±30.31 mIU/ml; p=0.021). In univariate analysis, CIA (p=0.006) and total number of chemotherapy cycle regardless of chemotherapy regimen (p=0.04) were significantly predictive of tumor response. CIA was only significant predictive factor for tumor response after neoadjuvant chemotherapy on multivariate analysis (p=0.012). CONCLUSIONS CIA is independent predictive markers of response to neoadjuvant chemotherapy in locally advanced breast cancer.