Ok-Ran Shin

Current trends in the epidemiological and pathological characteristics of gastrointestinal stromal tumors in Korea, 2003-2004.

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patients survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patients survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patients survival, but the mechanism still needs to be clarified through future studies.

HER-2/neu Oncogene Amplification by Chromogenic in situ Hybridization in 130 Breast Cancers Using Tissue Microarray and Clinical Follow-up Studies

Determining of HER-2/neu oncogene amplification has become clinically important for managing breast cancer. Fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) are currently regarded as the standard methods. Chromogenic in situ hybridization (CISH) was investigated as a new modification with an accurate, sensitive technique. From 1998 to 2002, using CISH and IHC, the amplification and protein expression of the HER-2/neu oncogene were examined using paraffin sections in 130 breast carcinomas and to determine the prognostic role of HER-2/neu for outcome after a follow-up of 24-64 months. Amplifications by CISH and overexpression by IHC were observed in 28 (22%) and 27 cases (20.8%), respectively. Of the 104 patients, 20 patients (19.2%) with amplification had a shorter disease-free interval (34.9 months vs. 38.0 months in controls) (p=0.372). 15 patients (14.4%) had a disease recurrence, but there is no significant difference between 3 patients amplifying the oncogene and 12 patients without oncogene (20.6 months vs. 19.6 months) (p=0.862). 6 patients (5.8%) of these died. CISH is a useful alternative, particularly for confirming the IHC results. There is no relationship between the early recurrence and the HER-2/neu positive group, but lymph node status was statistically significant.

Arterial Micro-Calcification of Vascular Access is Associated with Aortic Arch Calcification and Arterial Stiffness in Hemodialysis Patients

Vascular calcification of the coronary arteries or aorta is an independent risk factor for cardiovascular outcome, but clinical significance of arterial micro‐calcification (AMC) of vascular access is unclear in hemodialysis (HD) patients. Sixty‐five patients awaiting vascular access operation were enrolled. We compared surrogate markers of cardiovascular morbidity such as aortic arch calcification (AoAC) by chest radiography, arterial stiffness by brachial‐ankle pulse wave velocity (baPWV) and endothelial dysfunction by flow‐mediated dilatation (FMD) between patients with and without AMC of vascular access on von Kossa staining. AMC of vascular access was detected in 36 (55.4%). The AMC‐positive group had significantly higher incidence of AoAC (63.9% vs. 20.7%, p < 0.001) and higher baPWV (26.5 ± 9.4 m/s vs. 19.8 ± 6.6 m/s, p = 0.006) than the AMC‐negative group. There was no significant difference in FMD between the two groups (5.4 ± 2.6% vs. 5.7 ± 3.5%, p = 0.764). The AMC‐positive group had higher incidence of diabetes mellitus, higher systolic blood pressure and wider pulse pressure than the AMC‐negative group. This study suggests that AMC of vascular access may be associated with cardiovascular morbidity via AoAC and arterial stiffness in HD patients.

Inflammatory pseudotumor in the middle ear cavity

Inflammatory pseudotumor includes a diverse group of lesions characterized by inflammatory cell infiltration and variable fibrotic responses. It is extremely rare in the middle ear alone. A 7-year-old girl presented right hearing impairment. Because an otitis media with effusion was first suspected, a myringotomy was performed, but it found a mass that was different from a congenital cholesteatoma. Canal wall-down tympanomastoidectomy removed the mass successfully. The pathologic study of the specimen confirmed an inflammatory pseudotumor. We report an extremely rare case of the inflammatory pseudotumor in the middle ear with a review of the poor literature about this subject.

C-Kit-Negative Gastrointestinal Stromal Tumor in the Stomach.

C-kit-negative gastrointestinal stromal tumors (GISTs) are uncommon, and there have been few reports about the diagnosis and treatment of c-kit-negative GISTs in the stomach. We report the case of a patient who was diagnosed with a huge and atypical GIST in the stomach. The GIST was completely resected and finally diagnosed as c-kit-negative GIST based on immunohistochemical staining of tumor cells, which were negative for CD117 and CD34 and positive for Discovered on GIST-1 (DOG1). C-kit-negative GISTs could be treated by complete resection and/or imatinib, which is the same treatment for c-kit-positive GISTs.

Micropapillary urothelial carcinoma in a renal transplant recipient: a case report on urine cytomorphology emphasizing differentiation from high‐grade urothelial carcinoma

mas show an intimate admixture of carcinomatous and sarcomatous elements. A variety of mesenchymal components and growth patterns have been described in PSC, which include intersecting spindle cell fascicles, storiform pattern, pseudoangiomatous and haemangiopericytomatous patterns, rhabdomyoblastic, and cartilaginous differentiation, an osteosarcomatous component and a variable degree of myxoid change. Similarly, giant cells, variable pleomorphism, mitotic activity, necrosis and lymphovascular invasion have also been documented. The sarcomatoid component is believed to develop from the carcinomatous areas by dedifferentiation. Most PSCs show a minor epithelial component in the form of papillary, verrucous or basaloid SCC. Immunohistochemically, the spindle cell component shows diffuse vimentin expression and focal EMA, AE1/AE3 and S-100 positivity; other mesenchymal markers are usually negative. Most PSCs are highgrade tumours. Of the cases reported by Velazquez et al., 89% had an aggressive clinical course with inguinal node metastasis. The mean age of these patients was 59 years. Sarcomatoid carcinomas, which are rare in the penis, occur more frequently in other sites, such as the head and neck, oesophagus, kidney and prostate. The morphological features of PSC and sarcomatoid carcinoma of other locations are indistinguishable. Inguinal lymph node aspirate in the present case showed a distinct biphasic morphology. Although SCC is the most common malignancy of the penis, it was disregarded because of a lack of essential features, such as keratinization and nuclear pyknosis; immunocytochemically, p63 negativity confirmed the absence of squamous differentiation. The non-haemorrhagic nature of the aspirate, absence of endothelial differentiation and histiocytic cells, and the presence of epithelioid to spindle cell transition excluded the possibilities of angiosarcoma/ haemangioendothelioma, malignant fibrous histiocytoma and fibrosarcoma. CD99 positivity excluded synovial sarcoma. Metastatic amelanotic melanoma was ruled out by the tight clustering of cells (unusual in melanoma), melan-A and HMB-45 negativity and CK positivity. The positive expression of CK and negative expression of SMA and desmin excluded leiomyosarcoma and rhabdomyosarcoma. Although, tumour cells were S-100 positive, a strong immunoexpression of CK excluded a malignant peripheral nerve sheath tumour (MPNST). Thus, a high index of suspicion with an appropriate ICC panel facilitated the precise diagnosis of metastatic PSC. Interestingly, in contrast with the cases recorded in the literature, our case lacked squamous differentiation with the expression of both epithelial and mesenchymal antigens in both spindle and epithelial cell components.

Gastrointestinal: Large mucin pool within the remnant stalk of an adenomatous polyp after resection and its association with colitis cystica profunda

A 65-year-old man underwent a screening colonoscopy, conducted by his primary physician. The colonoscopy showed a large pedunculated polyp in the proximal sigmoid colon. No biopsy was performed. The patient had a medical history of hypertension. He had no family history of colon cancer and was referred to our hospital for management of the colon polyp. We performed a colonoscopy for polyp resection. The colonoscopy showed a 2.0 × 1.5 cm pedunculated polyp with a long, thick stalk in the proximal sigmoid colon (Fig. 1a). An endoscopic polypectomy was performed using the clip-and-cut technique. First, three endoclips were positioned to partially clamp the stalk at its base to prevent bleeding. Second, the polyp was resected at the upper portion of the stalk (Fig. 1b). A VIO300D electrosurgical unit (ERBE, Tübingen, Germany) and snare (SD-9U-1, Olympus, Tokyo, Japan) were used. After resection, we applied additional endoclips to prevent delayed bleeding from the remnant stalk. The remaining part of the stalk in the colonic wall contained a thick, yellowish mucin pool (Fig. 1c). The resected specimen measured 2.0 × 1.5 × 1.5 cm and was composed of a head portion and stalk containing yellowish mucin. The microscopic findings showed that the overlying epithelium was composed of a mixed hyperplastic adenomatous polyp with low-grade dysplasia (Fig. 2a, HE, orig. mag. × 10). There were multiple cystic dilated mucincontaining glands in the submucosa of the stalk, consistent with colitis cystica profunda (Fig. 2b, HE, orig. mag. × 40). Colitis cystica profunda (CCP) is a rare benign lesion of the colon and rectum characterized by submucosal mucin-filled cysts. While a localized form presents as single polypoid mass, a diffuse form involves variable length of the rectal mucosa or colon. CCP has been associated with a variety of disease, including solitary rectal ulcer syndrome, rectal prolapse, inflammatory bowel disease, diverticulitis, radiation, and infectious colitis. In addition, CCPs accompanied by colonic adenoma or adenocarcinoma have been reported. It is possible that the mucin pool within the stalk stump in this case could have resulted from deeper-placed epithelial glands being forced into the submucosa. A possible mechanism is trauma from torsion of pedunculated polyps, resulting in a mechanical disruption at the base of the adenoma. However, the exact etiology of CCP is still unknown. In the present case, there were no complications, such as delayed bleeding or perforation. Follow-up colonoscopy revealed no remarkable findings six months after the polypectomy.

Resistance to Erythropoiesis-Stimulating Agents Is Associated with Arterial Microcalcification in Early Hemodialysis Patients

The aim of this study was to evaluate the relationship between arterial microcalcification (AMiC) and erythropoiesis-stimulating agents (ESA) hyporesponsiveness in hemodialysis patients. The presence of AMiC was confirmed by pathologic examination of von Kossa-stained arterial specimens acquired during vascular access surgery. We assessed the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram body weight divided by the hemoglobin level. AMiC was detected in 33 (40.2%) of 82 patients. Patients with diabetes had a higher incidence of AMiC than patients without diabetes. The serum levels of albumin and cholesterol were higher in patients without AMiC than in patients with AMiC. The serum levels of intact parathyroid hormone were lower in patients with AMiC than in patients without AMiC. The serum levels of phosphate and calcium-phosphorus product did not differ between the two groups. The mean EHRI value was higher in patients with AMiC than in patients without AMiC. In multivariate analyses, ESA hyporesponsiveness and diabetes showed a significant association with AMiC. In conclusion, ESA hyporesponsiveness may be a clinical relevant parameters related to AMiC in hemodialysis patients.

Gastroenterology: Sweet's syndrome in a patient with acutely exacerbated ulcerative colitis

A 67-year-old Korean male presented with a 3-day history of acute fever, 8–10 daily episodes of diarrhea, hematochezia, and painful skin eruptions. In 2010, the patient was diagnosed with active ulcerative proctitis, which was under remission with 5-aminosalicylic acid (5-ASA). Two months before admission, his symptoms recurred. He was administered 5-ASA without prednisone, and the symptoms gradually improved. On admission, a physical examination revealed erythematous papules and plaques of the face, neck, trunk, hands, and legs (Fig. 1a, b). Laboratory examination indicated a 6,880/mm leukocyte count with 76.2% neutrophils, 11.7 g/dL hemoglobin, 44 mm/h erythrocyte sedimentation rate, 13.13 mg/dL C-reactive protein. Skin biopsy histology revealed edema of the derma papillae and papillary dermis, a dense focal neutrophilic infiltrate in the superficial dermis, and the absence of microscopic vasculitis (Fig. 2). These findings were compatible with the diagnosis of Sweet’s syndrome. A colonoscopy revealed massive mucosal ulcers, hemorrhage, necrosis, and circumscriptus pseudopolyps in the rectum, sigmoid, and descending colon (Fig. 3). Treatment with intravenous methylprednisolone was initiated, resulting in rapid improvement of the skin manifestations. The patient continued to receive oral prednisone (40 mg/ day) due to active ulcerative colitis (UC), and azathioprine was administered. Currently, his symptoms are being controlled with oral steroids and azathioprine. Sweet’s syndrome is characterized by an acute fever, neutrophilia, and tender erythematous skin lesions with an upper dermal infiltrate of mature neutrophils on histology. Classical or idiopathic Sweet’s syndrome is associated with conditions including infections, autoimmune diseases, inflammatory bowel disease (IBD), pregnancy, or malignancy (particularly hematologic malignancies). Sweet’s syndrome is more common in patients with Crohn’s disease than in those with UC, with association rates of ∼70% and 30%, respectively. In addition, all patients with IBD and Sweet’s syndrome exhibit colonic involvement, and only 20% of patients with Crohn’s disease had ileal involvement in addition to colonic disease, suggesting that the presence of colonic bacteria might be responsible for this syndrome. Neutrophilic dermatoses, including pyoderma gangrenosum and Sweet’s syndrome, potentially share one or more pathological mechanisms with IBD. Sweet’s syndrome almost always affects females between 30 and 50 years old unlike other skin manifestations of IBD, which have no gender predilection. The characteristic skin lesions are suddenly erupting, tender, red or reddish papules or nodules or less frequently vesicles, pustules, or bullae. Frequently affected sites include the face and neck, trunk, and extremities, notably the backs of hands. The mainstay of treatment for Sweet’s syndrome is systemic corticosteroid therapy. Symptoms promptly improve, and skin manifestations may resolve after a 6-week course of steroid treatment.

Clinicopathological Characteristics of Serrated Polyposis Syndrome in Korea: Single Center Experience

Background/Aim. Serrated polyposis syndrome (SPS) is a rare condition characterized by multiple serrated polyps throughout the colon and rectum. The aim of this study was to evaluate the clinicopathological characteristics of SPS in Koreans. Methods. This retrospective analysis of prospectively collected data was performed using information from the endoscopy, clinical records, and pathology database system of Uijeongbu St. Marys Hospital. Consecutive patients satisfying the updated 2010 World Health Organization criteria for SPS between June 2011 and May 2014 were enrolled. Results. Of the 17,552 patients who underwent colonoscopies during the study period, 11 (0.06%) met the criteria for SPS. The mean age of these patients was 55.6 years. Ten patients (91%) were males. None had a family history of CRC or a first-degree relative with SPS. Seven patients (64%) had synchronous advanced adenoma. One patient had coexistence of SPS with CRC that was diagnosed at the initial colonoscopy. Five patients (45%) had more than 30 serrated polyps. One of the patients underwent surgery and 10 underwent endoscopic resection. Conclusion. The prevalence of SPS in this study cohort was comparable to that in Western populations. Considering the high risk of CRC, correct diagnosis and careful follow-up for SPS are necessary.