Junhun Cho

Needle-tract implantation in hepatocellular carcinoma: frequency and CT findings after biopsy with a 19.5-gauge automated biopsy gun

AbstractBackground: Needle-tract implantation is an important complication of cutting biopsy of hepatocellular carcinoma (HCC). This study was performed to evaluate the frequency of needle-tract implantation after ultrasound (US)-guided percutaneous biopsy of HCC and to describe triple-phase helical computed tomographic (CT) findings of implanted nodules. Methods: Between April 1994 and December 1997, 205 patients underwent US-guided percutaneous biopsy for HCC. Review of medical records and the pathology database disclosed seven patients who were found to have needle-tract implantation of HCC. Among these patients, five underwent triple-phase helical CT examination. We analyzed the frequency of needle-tract implantation and triple-phase helical CT findings of implanted nodules, with particular attention to the morphology and enhancement pattern. Results: Seven of 205 patients (3.4%) had tumor implantation along the needle tract at histologic examination after surgical resection. Eight implanted nodules in five patients were found on triple-phase helical CT images (one nodule in three patients, two nodules in one patient, and three nodules in one patient). All implanted nodules has well-circumscribed margins and were ovoid or lobulated in contour. On triple-phase helical CT, six (75%) implanted nodules were isodense compared with abdominal wall muscle on all triple-phase CTs, and two (25%) nodules were hyperdense on hepatic arterial and portal venous phases and isodense on equilibrium phase. Conclusions: The frequency of needle-tract implantation of HCC after percutaneous needle biopsy was higher than reported previously, and careful attention should be paid during interpretation of CT images in patients with a history of previous percutaneous biopsy.

Heterogeneity of ERBB2 in gastric carcinomas: a study of tissue microarray and matched primary and metastatic carcinomas

Trastuzumab in association with systemic cytotoxic chemotherapy is a therapeutic option for patients with advanced or metastatic ERBB2+ gastric carcinoma. The status of the ERBB2 overexpression or gene amplification is an important predictive marker in gastric cancer. However, it is controversial whether the primary tumor is representative of distant metastases in terms of ERBB2 status. Quadruplicated tissue microarrays from formalin-fixed paraffin-embedded tissues from 498 advanced primary gastric carcinomas and 97 matched metastatic lymph nodes were investigated by immunohistochemistry with HercepTest and silver in situ hybridization. For further comparison, another set of 41 paired primary and distant metastatic gastric carcinomas were also tested. Intratumoral heterogeneity was defined as different results between tissue microarray cores. ERBB2-positivity was observed in 52 gastric carcinomas (10%) and was not associated with recurrence of disease or survival of patients. In ERBB2-positive primary gastric carcinomas, heterogeneous ERBB2 overexpression was observed in 21/63 (33%) gastric carcinomas and heterogeneous ERBB2 gene amplification in 14/62 (23%) cases. Repeated immunohistochemistry and silver in situ hybridization in representative paraffin tumor blocks confirmed focal ERBB2 overexpression and ERBB2 gene amplification and did not change the final results. Discrepancies in ERBB2 results between primary and paired metastatic lymph nodes were observed in 11% of cases by immunohistochemistry and 7% by silver in situ hybridization. Out of the 41 paired primary and distant metastases, 5 (12%) cases were ERBB2-positive, and discrepancy was observed in one case. Intratumoral heterogeneity and discrepant ERBB2 results in primary and metastatic tumor are not uncommon in gastric carcinoma. Results of silver in situ hybridization showed less frequent heterogeneity compared with immunohistochemistry. Wherever possible, ERBB2 immunohistochemistry testing should be performed in both primary and distant metastatic sites.

Pyloric Gland Adenoma in Lynch Syndrome

The prevalence of gastric cancer associated with Lynch syndrome (LS) is highly variable, and the underlying histologic pathway or molecular mechanisms remain unclear. From 1995 to 2012, 15 patients had been treated for both gastric and colonic adenocarcinomas and diagnosed as LS. In all cases, pathologic review, immunohistochemical analysis for mismatch-repair proteins, and microsatellite instability (MSI) tests were performed. To confirm LS, germline mutation tests and multiplex ligation-dependent probe amplification were performed. All gastric and colonic carcinomas were MSI-high and lost expressions of MLH1/PMS2 in 11 (73%) cases and MSH2/MSH6 in 4 (27%) cases. Remarkably, in a patient with LS and germline mutation of MLH1 gene, pyloric gland adenoma (PGA) transformed to adenocarcinoma during follow-up. In 2 additional cases, PGA was found adjacent to advanced gastric cancers. All PGAs in LS patients were MSI-high and lost expression of mismatch-repair proteins (MLH1/PMS2 in 2 cases and MSH2/MSH6 in 1 case), whereas none of the 14 sporadic PGAs was MSI-high or had lost expression of mismatch-repair proteins. On the basis of these observations, although very rare, we suggest the possibility that PGA may be a precursor lesion to gastric adenocarcinoma in LS and that the mismatch-repair deficient pathway of carcinogenesis is involved early in the gastric carcinogenesis pathway.

Ovarian perivascular epithelioid cell tumor not otherwise specified with transcription factor E3 gene rearrangement: a case report and review of the literature

We report the first case of isolated ovarian perivascular epithelioid cell tumor not otherwise specified in a 33-year-old woman with no history of tuberous sclerosis. A right ovary specimen revealed a well-circumscribed 2.5 × 2 cm solid mass. Microscopically, the mass was composed of nests of tumor cells that were separated by fibrous septa. The tumor cells were composed of pure epithelioid cells with abundant clear cytoplasm and dark brown pigments. Immunohistochemically, the tumor cells showed diffuse and strong cytoplasmic staining of HMB45; however, the tumor cells were not reactive for smooth muscle actin, desmin, inhibin-α, calretinin, and carcinoembryonic antigen. Strong nuclear expression of transcription factor E3 protein was observed in most tumor cells, and transcription factor E3 fluorescence in situ hybridization showed transcription factor E3 rearrangements associated with balanced Xp11 translocations.

Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability

Programmed death-ligand 1 (PD-L1) is expressed in a subgroup of gastric cancers that may benefit from immunotherapy. Microsatellite instability-high (MSI-H) is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1. The relationship between PD-L1 expression and MSI-H status remains poorly understood. In this study, we investigated PD-L1 expression in patients with MSI-H gastric cancer. We analyzed PD-L1 expression in 78 MSI-H gastric cancer tissue samples using immunohistochemistry. PD-L1 expression was classified as expression on tumor cells or on immune cells. We observed PD-L1 expression in 48 gastric cancer samples (61.5%), consisting of 7 (9.0%) cases with tumor PD-L1 expression and 47 (60.3%) cases with immune cell PD-L1 expression. Immune cell PD-L1 expression was frequently associated with intestinal type cancer by the Lauren classification (p = 0.015), with a lower risk of lymph node metastasis (p = 0.027) and lower tumor stages (p = 0.029) compared to MSI-H gastric cancers without PD-L1 expression. Moreover, immune cell PD-L1 expression was an independent favorable prognostic factor for overall survival (versus PD-L1 negative; hazard ratio, 3.451; 95% confidence interval, 1.172–12.745; p = 0.025). In MSI-H gastric cancer, PD-L1 expression was observed to be independently associated with a longer survival.

High level of CDK4 amplification is a poor prognostic factor in well-differentiated and dedifferentiated liposarcoma.

The amplification of MDM2 and CDK4 is the main molecular feature of well-differentiated liposarcomas (WDLS) and dedifferentiated liposarcomas (DDLS). Although the diagnostic usefulness of this molecular characteristic in liposarcomas has been investigated, its prognostic utility of quantitative gene level has not been explored. The aim of this study was to assess the prognostic significance of level of CDK4 amplification in MDM2-amplified WDLS/DDLS. MDM2 amplification in liposarcomas was confirmed by fluorescence in situ hybridization. The copy number of MDM2 and CDK4 was further determined by quantitative PCR (qPCR) and multiplex ligation-dependent probe amplification. Among 56 MDM2-amplified liposarcomas, 30 cases were assigned as WDLS, and 26 as DDLS. When liposarcomas were classified by qPCR-determined CDK4 amplification levels, the high-CDK4 group showed significantly poorer progression free survival (P=0.001) and disease specific survival (P=0.033) than the low-CDK4 group. However, MDM2 amplification level did not show prognostic significance. In WDLS/DDLS, the level of CDK4 amplification was useful for prognosis prediction and precise stratification of patients for targeted therapy.

Congenital Peribronchial Myofibroblastic Tumor: A Case Study and Literature Review

Congenital peribronchial myofibroblastic tumor (CPMT) is a benign pulmonary spindle cell neoplasm of intrauterine and perinatal period, which is thought to arise from primitive peribronchial mesenchyme. We present a case detected incidentally in a one-month-old infant. The solid and partially necrotic tumor involved the right middle and lower lobes of the lung with extension to the diaphragm. Histologically, the tumor was composed of fasciculated monotonous spindle cells, proliferating peribronchiolar cartilage and round cells with rich vasculature, and high mitotic activity was identified in the round cell area. Immunohistochemical and electron microscopic studies showed that the spindle cells were myofibroblastic in phenotype. Although the tumor showed several malignant pathological features, recurrence was not observed in the two-year follow-up period, consistent with the benign clinical behavior of CPMT.

Lung parenchymal invasion in pulmonary carcinoid tumor: An important histologic feature suggesting the diagnosis of atypical carcinoid and poor prognosis

The majority of previous studies on pulmonary carcinoid tumor have usually focused on clinical behavior or outcome, seldom considering histopathologic features. We retrospectively collected 63 cases of resected pulmonary carcinoid tumors from 1995 to 2011 at Samsung Medical Center, Seoul, Korea. The clinical and pathological features were correlated and survival analyses were performed. Forty cases (63.5%) were classified as typical carcinoid (TC) and 23 cases (36.5%) were classified as atypical carcinoid (AC) according to WHO classification criteria. AC patients showed a higher frequency of current smoking status and a higher stage of the tumor by the American Joint Committee on Cancer than TC patients. The disease was associated with death and recurrence in five and seven patients, respectively, with almost all of the associations found in AC patients. The five-year survival rate of TC and AC were 100% and 83.5%, respectively, with AC showing poorer prognosis than TC in overall survival (OS) and disease free survival (DFS) (p=0.005 and p=0.002). Lung parenchymal invasion was observed more commonly in AC than in TC (39.1% vs 12.5%, p=0.01) and was a poor prognostic factor in OS and DFS. Rosette-like arrangements were found only in six cases of AC, while abundant basophilic cytoplasm mimicking paraganglioma and ossification were found only in TC. Through the comprehensive study of pulmonary carcinoid tumor in Korea, we suggest that lung parenchymal invasion could be a useful histologic feature to suspect the diagnosis of AC in daily practice as well as to predict the prognosis of carcinoid tumor.

Diagnostic Value of MDM2 and DDIT3 Fluorescence In Situ Hybridization in Liposarcoma Classification: A Single-Institution Experience.

Background The amplification of murine double minutes (MDM2) is the primary feature of well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS), while DDIT3 rearrangement is the main one of myxoid liposarcomas (MLPS). Our aim was to evaluate the added value of MDM2 amplification and DDIT3 rearrangement in making a diagnosis and classifying lipogenic tumors. Methods Eighty-two cases of liposarcoma and 60 lipomas diagnosed between 1995 and 2010 were analysed for MDM2 amplification and DDIT3 rearrangement using a fluorescence in situ hybridization (FISH). The subtypes of liposarcoma were reclassified according to the molecular results, whose results were reviewed with an analysis of the relevant histologic and immunohistochemical findings. Results One case of lipoma (1.67%) was reclassified as a WDLPS. Of the liposarcomas, 13.4% (16/82) were reclassified after the molecular testing. Five cases of MLPS were reclassified as four cases of DDLPS and one case of myxoid lipoma. Two cases of WDLPS were reclassified as one case of spindle cell lipoma and another case of myxofibrosarcoma. Four cases of DDLPS were reclassified as two cases of leiomyosarcoma, one case of angiomyolipoma and another case of fibroinflammatory lesion. Of the six cases of pleomorphic liposarcoma, five were reclassified as DDLPS. Conclusions In our series, a critical revision of diagnosis was found at a rate of 3.5% (5/142) after a review of the lipomatous lesions. The uses of molecular testing by MDM2 and DDIT3 FISH were valuable to make an accurate subtyping of liposarcomas as well as to differentiate WDLPS from benign lipomatous tumor.

Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.