Geunghwan Ahn

Early Osteolysis Following Second-Generation Metal-on-Metal Hip Replacement

BACKGROUND Total hip arthroplasty with use of metal-on-metal bearings has been reintroduced as an alternative to the use of metal-on-polyethylene bearings because of theoretical advantages such as reduced wear and a lower prevalence of osteolysis. However, we observed early osteolysis in a cohort of patients who had been managed with second-generation metal-on-metal hip replacements and investigated the possible etiologic role of metal hypersensitivity. METHODS We retrospectively analyzed 165 patients (169 hips) who had undergone primary cementless total hip replacement with a contemporary metal-on-metal total hip design between 2000 and 2002. After a minimum duration of follow-up of twenty-four months, nine patients (ten hips) had an osteolytic lesion localized to the greater trochanter. Skin-patch tests for hypersensitivity to metals were performed on the nine patients and on nine randomly selected patients with total hip replacements who did not have osteolytic changes and who were matched to the study cohort for age and gender. Microbiological cultures, histopathologic examinations, and immunohistochemical analysis were performed on samples of periprosthetic tissue that were collected during revision arthroplasty on two hips with early osteolysis. RESULTS The patients with early osteolysis had a significantly higher rate of hypersensitivity reaction to cobalt compared with controls (p = 0.031). The retrieved periprosthetic tissues showed no evidence of metallic staining, but histologic analysis revealed a perivascular accumulation of CD3-positive T-cells and CD68-positive macrophages and an absence of both particle-laden macrophages and polymorphonuclear cells. Immunohistochemical analysis demonstrated that bone-resorbing cytokines such as IL-1beta and TNF-alpha were produced mainly by infiltrating lymphocytes and activated macrophages. CONCLUSIONS These findings raise the possibility that early osteolysis in patients with this second-generation metal-on-metal hip replacement is associated with abnormalities consistent with delayed-type hypersensitivity to metal. A prospective study in which a large group of patients is evaluated with multiple diagnostic methods is needed in order to establish whether there is a causal relationship between metal hypersensitivity and osteolysis.

Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms.

To clarify possible roles of adhesion molecules including E‐cadherin, β‐ and γ‐catenin, CD44s, CD44v6, CD56, and CD99 in ovarian serous neoplasms, an immunohistochemical study was undertaken for 23 benign, 40 borderline, and 95 malignant ovarian serous neoplasms using tissue microarray (TMA). Significantly reduced expression of E‐cadherin, and overexpression of CD44s, CD56, and CD99 were more frequently observed in adenocarcinomas than in benign and borderline tumors. Expression of CD44v6 and nuclear β‐ and γ‐catenin were detected only in borderline tumors and adenocarcinomas. Reduced expression of E‐cadherin was also correlated with high tumor grade (P = 0.03), presence of peritoneal seeding (P = 0.03), and low overall survival rate (P = 0.02). Overexpression of CD44s was significantly associated with high tumor grade (P = 0.04), advanced stage (P = 0.03), and low overall survival rate (P = 0.02). CD56 was increasingly expressed in the case of advanced stage (P = 0.005) and peritoneal seeding (P = 0.001). Nuclear staining for γ‐catenin was correlated with tumor progression (P = 0.004) and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.02). Only CD44s expression and stage were correlated with overall survival in multivariate study. These results suggest that although E‐cadherin, CD44s, CD56, and nuclear γ‐catenin immunoexpression seem to be useful prognostic markers for serous neoplasm of the ovary, CD44s expression and FIGO stage are independent prognostic factors.

Schwannomas of the Gastrointestinal Tract: Clinicopathological Features of 12 Cases Including a Case of Esophageal Tumor Compared with Those of Gastrointestinal Stromal Tumors and Leiomyomas of the Gastrointestinal Tract

We analyzed the clinicopathological features of 12 gastrointestinal (GI) schwannomas and compared them with those of 37 GI stromal tumors (GISTs) and 15 leiomyomas. Grossly, the schwannomas showed rubbery to firm, yellow-white to tan, glistening, and often trabeculated cut surfaces, resembling soft tissue schwannomas. The GISTs were firm to soft or fish-flesh tan, gray-pink, or variegated tumors with a degenerative change, and the leimyomas resembled typical uterine leiomyomas. Histologically, GI schwannomas were moderately cellular tumors with focal significant nuclear pleomorphism and rare mitotic figures. A characteristic peripheral lymphoid cuff was observed in all cases, but was indistinct in two cases. The GISTs were highly cellular spindle cell, epithelioid or, occasionally, pleomorphic tumors with basophilic appearance. Leiomyomas were paucicellular tumors with eosinophilic appearance. Immunohistochemically, schwannomas were S-100 protein- and glial fibrillary acidic protein (GFAP)-positive, but were negative for c-kit, CD34, and smooth muscle actin (SMA). GISTs were all c-kit- and/or CD34-positive, but GFAP-negative. Leiomyomas were SMA-positive and were negative for c-kit, CD34, S-100 protein, and GFAP. The mean Ki-67 index of schwannoma was 0.7, and those of GIST and leiomyoma were 5.9 and 0.3, respectively. The patients with schwannomas and leiomyomas had a favorable outcome, whereas 12 patients with GISTs showed progression and died of disease. The separation of GISTs from schwannomas is clinically important because the former group has a high risk of malignant behavior. GI schwannomas differed from the conventional soft tissue schwannomas in that they had peripheral lymphoid cuffs, lacked fibrous capsule and vascular hyalinization, and rarely showed degenerative changes. GI schwannomas, however, resembled soft tissue schwannomas in many aspects, and the clinical, gross, histological, and immunohistochemical features were different from those of GISTs and leiomyomas.

Ovarian sex cord tumor with annular tubules

A pathologic study was done on four cases of ovarian sex cord tumor with annular tubules. All for tumors occurred in young women (11–24 years of age) and were not associated with the Peutz‐Jeghers syndrome. Two patients had evidence of hyperestrinism. One patient who had metastasis to the retroperitoneum, left supraclavicular lymph node, and liver confirmed the malignant potential of this tumor. Gross examination revealed tumors that were solid, yellowish, and unilateral, with varying degrees of cystic degeneration. Microscopic examination showed simple or complex annular tubules with prominent basement membranes. Many tumor cells contained lipid in the cytoplasm. Ultrastructural study showed Charcot‐Botteher filaments in all four cases, indicating Sertoli cell differentiation. True lumens and microvilli were identified in one case. The classification of the sex cord tumor with annular tubules as a Sertoli cell tumor, annnular tubular type was proposed on the basis of ultrastructural findings.

Immunoexpression of Inhibin α Subunit, Inhibin/Activin βA Subunit and CD99 in Ovarian Tumors

Abstract Objective.—Anti–inhibin α and inhibin/activin βA subunit and anti-CD99 monoclonal antibodies (mAbs) have recently been demonstrated to be able to label ovarian granulosa cells; thus, they may be of value in the diagnosis of granulosa cell tumors. The present study aimed to determine what combination of these mAbs may be useful for the differential diagnosis of sex cord–stromal tumors of ovary. Design.—Immunohistochemical analyses with anti–inhibin α and inhibin/activin βA subunit antibody and anti-CD99 mAb were performed on 42 ovarian tumors, including sex cord–stromal tumors (29), ovarian epithelial cancers (10), and Krukenberg tumors (3). Results.—All sex cord–stromal tumors were positive for inhibin α subunit, and 17 cases (58.6%) of sex cord–stromal tumors were immunoreactive for inhibin/activin βA subunit. Epithelial tumors and Krukenberg tumors were all negative for inhibin/activin βA subunit except mucinous carcinoma, which showed strong cytoplasmic immunoreactivity. All sex cord–stromal t...

Biliary parasitic diseases including clonorchiasis, opisthorchiasis and fascioliasis

AbstractParasitic infection of the biliary tree is caused by liver flukes, namely Clonorchis sinensis and Opisthorchis viverrini. These flukes reside in the peripheral small bile ducts of the liver and produce chronic inflammation of the bile duct, bile duct dilatation, mechanical obstruction, and bile duct wall thickening. On imaging, peripheral small intrahepatic bile ducts are dilated, but the large bile ducts and extrahepatic bile ducts are not dilated or slightly dilated. There is no visible caused of obstruction. Sometimes, in heavy infection, adult flukes are demonstrated on sonography, CT or MR cholangiography as small intraluminal lesions. The flukes in the gallbladder may appear as floating, small objects on sonography. Chronic infection may result in cholangiocarcinoma of the liver parenchyma or along the bile ducts. Human infection of Fasciola hepatica, a cattle flukes, may occur inadvertently, and the flukes migrate in the liver (hepatic phase) and reside the bile ducts (biliary phase). Image findings in the hepatic phase present with multiple, small, clustered, necrotic cavities or abscesses in the peripheral parts of the liver, showing “tunnels and caves” sign, reflecting parasite migration in the liver parenchyma. In the biliary phase, the flukes are demonstrated in the intra- and extrahepatic bile ducts and the gallbladder as small intraluminal flat objects, sometimes moving spontaneously. Bile ducts are dilated.

Prognostic Significance of Vascular Endothelial Growth Factor Expression and Microvessel Density in Esophageal Squamous Cell Carcinoma: Comparison With Positron Emission Tomography

BackgroundThis study investigated whether the expression of vascular endothelial growth factor (VEGF) in a primary tumor and the intratumoral microvessel density (MVD) were independent prognostic factors in patients with an esophageal squamous cell carcinoma (SCC) in comparison with positron emission tomography (PET) by using 18F-fluorodeoxyglucose (FDG) and stage.MethodsFifty-one patients with a newly diagnosed esophageal SCC who underwent preoperative FDG-PET and esophagectomy with intent to cure were enrolled in this study. The VEGF expression level, the intratumoral MVD, and the Ki-67 labeling index were evaluated by using immunohistochemical staining. Only significant variables in the univariate survival analysis were examined by multivariate survival analysis with the Cox proportional hazards model.ResultCancer-related deaths occurred in 17 of 51 patients during the follow-up. Univariate survival analysis showed that the pathologic stage, pNM, maximum standardized uptake value of the primary tumor, tumor length on PET, number of PET-positive lymph nodes, PET stage, Ki-67 labeling index, intratumoral MVD, and the presence of VEGF expression were significant prognostic predictors for the overall survival. Multivariate analysis revealed that the pathologic stage, number of PET-positive nodes (0, 1, 2, or ≥3), intratumoral MVD (cutoff, 60/mm2), and presence of VEGF expression were independent significant prognostic predictors for overall survival.ConclusionIn addition to the pathologic stage, the intratumoral MVD, the presence of VEGF expression, and the number of FDG-PET–positive nodes were independent prognostic predictors in patients with an esophageal SCC undergoing curative surgery.

Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia.

Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the SOST gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as “leontiasis ossea”, could also be caused by SOST mutations. We discovered mutations c.61G>A (Val21Met) and c.61G>T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the SOST gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of SOST. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in SOST. Unlike the other SOST-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism.

Sixteen Cases of Sclerosing Hemangioma of the Lung Including Unusual Presentations

Sclerosing hemangiomas (SH) of the lung are uncommon tumors and are thought to be benign. However, the biologic behavior of this tumor has not yet been characterized adequately. The clinicopathologic features were reviewed and analyzed for 16 cases of SH. The age of the patients ranged from 37 to 73 yr (mean 50.6 yr). There were fifteen female and one male patient. The SH located at the intraparenchyme in 14 cases, the interlobar fissure in one case and the visceral pleura in one case. The size of SH ranged from 0.3 cm to 8 cm (mean 2.6 cm). There were five unusual presentations of SH including a case having two SH with multiple nodules of atypical adenomatous hyperplasia in the same lobe, a case showing adenocarcinoma-like area within the SH, a case showing one peribronchial lymph node metastasis (N1 nodal stage) with location of interlobar major fissure, a case showing alveolar adenoma-like area within the SH, and one case with a large visceral pleural-based pedunculated mass presenting as mediastinal mass. All patients were alive and well without recurrence at the last follow up. Here, we reviewed previously published literatures and discussed the histogenesis of SH.

Clear cell carcinoma of the inguinal region arising from endometriosis

The second and third examples of clear cell carcinoma of the inguinal region arising from endometriosis are reported. In one patient a right inguinal mass was excised along with an inguinal lymph node dissection. The tumor recurred in the retroperitoneum and was removed, and postoperative radiation therapy was administered. The patient died of recurrent tumor after 11 years. The other patient was treated by excision of a left inguinal mass and an inguinal lymph node dissection and was alive without recurrence 4 years and 8 months later.