The Prognostic Implications of Cystic Change in Clear Cell Renal Cell Carcinoma

Background : Cystic renal cell carcinoma has been reported to have a good prognosis. However, previous studies included cases of multilocular cystic renal cell carcinoma, which has an excellent prognosis, and renal cell carcinoma with cystic necrosis, which has an adverse prognosis. Therefore, we analyzed the prognostic influence of cystic change in clear cell renal cell carcinoma after excluding those morphological features. Methods : We identified 225 patients with clear cell renal cell carcinoma who underwent nephrectomy between 2001 and 2003. The clinicopathologic features were compared with clinical outcomes. Results : Cystic change in clear cell renal cell carcinoma (n = 66) was significantly associated with younger patient age (< 55), smaller tumor size (<= 4 cm), lower pT stage (pT1, T2), M0 stage at initial diagnosis, lower tumor, node, and metastasis stage (I, II), and lower nuclear grade (1, 2). Patients with cystic change in clear cell renal cell carcinoma had significantly longer cancer-specific (p = 0.015) and progression-free survival (p = 0.004) than those without cystic change, by univariate analysis. Multivariate analysis revealed that cystic change significantly decreased the risk of cancer progression (risk ratio, 0.27; 95% confidence interval, 0.11 to 0.69). Conclusions : In patients with clear cell renal cell carcinoma, cystic change is a good independent predictor for survival.This work was supported by grant No. 04-2009-007 from the SNUH Research Fund.Jemal A, 2009, CA-CANCER J CLIN, V59, P225, DOI 10.3322/caac.20006Lopez-Beltran A, 2009, INT J UROL, V16, P432, DOI 10.1111/j.1442-2042.2009.02302.xGobbo S, 2008, AM J SURG PATHOL, V32, P1239Gong K, 2008, J CANCER RES CLIN, V134, P433, DOI 10.1007/s00432-007-0302-1Webster WS, 2007, UROLOGY, V70, P900, DOI 10.1016/j.urology.2007.05.029Lopez-Beltran A, 2006, EUR UROL, V49, P798, DOI 10.1016/j.eururo.2005.11.035Suzigan S, 2006, AM J CLIN PATHOL, V125, P217, DOI 10.1039/AH6FC77PYR2V6YAYFrank I, 2005, J UROLOGY, V173, P1889, DOI 10.1097/01.ju.0000158043.94525.d6Patard JJ, 2005, J CLIN ONCOL, V23, P2763, DOI 10.1200/JCO.2005.07.055Kim H, 2004, HUM PATHOL, V35, P1556, DOI 10.1016/j.humpath.2004.06.011Ficarra V, 2004, EUR UROL, V46, P559, DOI 10.1016/j.eururo.2004.07.002Han KR, 2004, UROL ONCOL-SEMIN ORI, V22, P410, DOI 10.1016/S1078-1439(03)00173-XImura J, 2004, APMIS, V112, P183Cheville JC, 2003, AM J SURG PATHOL, V27, P612Frank I, 2002, J UROLOGY, V168, P2395, DOI 10.1097/01.ju.0000035885.91935.d5Nassir A, 2002, UROLOGY, V60, P421GREENE FL, 2002, AJCC CANC STAGING MACorica FA, 1999, J UROLOGY, V161, P408Bielsa O, 1998, BRIT J UROL, V82, P16USUBUTUN A, 1998, INT UROL NEPHROL, V30, P391LYNCH CF, 1995, CANCER, V75, P316HARTMAN DS, 1986, UROLOGY, V28, P145

Treatment Response and Long Term Follow-up Results of Nonspecific Interstitial Pneumonia

The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse

Clinicopathological parameters for circulating tumor DNA shedding in surgically resected non-small cell lung cancer with EGFR or KRAS mutation.

BACKGROUND:Circulating tumor DNA (ctDNA) is cell-free DNA that is released into peripheral blood by tumor cells. ctDNA harbors somatic mutations and mutant ctDNA obtained from blood can be used as a biomarker in advanced non-small cell lung cancer (NSCLC). In this study, we investigated the clinicopathological properties of tumors that shed ctDNA in surgically resected NSCLC patients. METHODS:Consecutive cases of NSCLC with matching surgically resected tissue specimens and peripheral or specimen blood samples were eligible for this study. EGFR and KRAS mutations in plasma ctDNA and formalin-fixed paraffin-embedded tissue were analyzed using peptide nucleic acid clamping-assisted method. The plasma and tissue results were compared according to clinicopathological features. RESULTS:Mutation analyses were available for 36 cases. EGFR and KRAS mutations were present in 41.7% (15/36) and 16.7% (6/36) of tissue samples, respectively. Among EGFR and KRAS-mutant tumors, plasma mutation detection sensitivity was 13.3% (2/15) for EGFR and 33.3% (2/6) for KRAS. The presence of ctDNA in plasma was significantly associated with higher pathological tumor stage (p = 0.028), nodal metastasis (p = 0.016), solid adenocarcinoma pattern (p = 0.003), tumor necrosis (p = 0.012), larger primary tumor diameter (p = 0.002) or volume (p = 0.002), and frequent mitosis (p = 0.018) in tissue specimens. All tumors larger than 4 cm in maximal diameter or 25 cm3 in volume shed ctDNA in plasma. In subgroup analysis among EGFR mutated adenocarcinoma, ctDNA was significantly associated with nodal metastasis (p = 0.029), vascular invasion (p = 0.029), solid adenocarcinoma pattern (p = 0.010), and tumor necrosis (p = 0.010), high mitotic rate (p = 0.009), large pathological tumor size (p = 0.027), and large tumor volume on CT (p = 0.027). CONCLUSION:We suggest that primary or total tumor burden, solid adenocarcinoma morphology, tumor necrosis, and frequent mitosis could predict ctDNA shedding in pulmonary adenocarcinoma

Correlation between maximal tumor diameter of fresh pathology specimens and computed tomography images in lung adenocarcinoma.

The authors compared maximal tumor diameters between fresh lung tissue and axial and multiplanar reformatted chest computed-tomography (CT) images in lung adenocarcinoma and investigated the factors affecting tumor-size discrepancies. This study included 135 surgically resected lung adenocarcinomas. An experienced pulmonary pathologist aimed to cut the largest tumor section and measured pathological tumor size (PTS) in fresh specimens. Radiological maximal tumor sizes (RTS) were retrospectively measured on axial (RTSax) and multiplanar reformatted (RTSre) chest CT images. Mean PTS, RTSax, and RTSre were 19.13 mm, 18.63 mm, and 20.80 mm, respectively. RTSre was significantly larger than PTS (mean difference, 1.68 mm; p<0.001). RTSax was also greater than PTS for 6-10-mm and 11-20-mm tumors. PTS and RTS were strongly positively correlated (RTSax, r2 = 0.719, p<0.001; RTSre, r2 = 0.833, p<0.001). The intraclass correlation coefficient was 0.915 between PTS and RTSax and 0.954 between PTS and RTSre. Postoperative down-staging occurred in 11.0% and 27.4% of tumors on performing radiological staging using RTSax and RTSre, respectively. Postoperative up-staging occurred in 12.3% and 1.4% of tumors on performing radiological staging using RTSax and RTSre, respectively. Multiple linear regression revealed that pleural dimpling (p = 0.024) was an independent factor affecting differences between PTS and RTSax. Specimen type (p = 0.012) and tumor location (p = 0.020) were independent factors affecting differences between PTS and RTSre. In conclusion, RTSre was significantly larger than PTS and caused postoperative down-staging in 27.4% of the tumors. Reliability analysis revealed that RTSre was more strongly correlated with PTS than RTSax. Specimen type and anatomical tumor location influenced the measured size differences between PTS and RTSre

A novel FLCN gene mutation causing Birt–Hogg–Dubé syndrome in a Korean family

Spontaneous pneumothorax is a common manifestation of Birt–Hogg–Dubé (BHD) syndrome, an inherited disorder caused by mutation of the folliculin (FLCN) gene. A 44-year-old female with a history of breast cancer was diagnosed with recurrent pneumothorax. Chest CT showed multiple cysts with left lung pneumothorax, and she received surgery for the diagnosis. Because the patient also had a family history of spontaneous pneumothorax, a FLCN genetic examination was conducted. A novel heterozygous, likely pathogenic variant (NM_144997.5:c.779+2T > C) was detected in the proband, her mother, and aunt. This is the first report of a new mutation of FLCN gene in a BHD syndrome patient

Tufting Enteropathy with EpCAM Mutations in Two Siblings

Tufting enteropathy is a rare autosomal recessive disorder presenting with early-onset severe intractable diarrhea. The epithelial cell adhesion molecule gene (EpCAM) has recently been identified as the gene responsible for tufting enteropathy. Based on histology, a diagnosis of tufting enteropathy was made in two Korean siblings. They developed chronic diarrhea and failure to thrive. They had a broad nasal bridge and micrognathia. Duodenal and colonic biopsies showed villous atrophy, disorganization of surface enterocytes, and focal crowding resembling tufts. Protracted diarrhea continued and so cyclic parenteral nutrition was supplied. The sister had juvenile rheumatoid arthritis. Mutation analysis of EpCAM identified two compound heterozygous mutations in these siblings: 1) a donor splicing site mutation in intron 5 (c.491+1G>A) and 2) a novel nonsense mutation in exon 3 (c.316A>T, Lys106X). Analysis of EpCAM will be useful for genetic counseling and prenatal diagnosis of tufting enteropathy

Correlation between the Size of the Solid Component on Thin-Section CT and the Invasive Component on Pathology in Small Lung Adenocarcinomas Manifesting as Ground-Glass Nodules

Introduction: We aimed to evaluate the correlation between the size of the solid component on thin-section computed tomography (CT) and invasive component on pathology in small lung adenocarcinomas manifesting as subsolid nodules. Methods: Fifty-nine subsolid nodules in 58 patients were evaluated. The maximum diameters of subsolid nodules and the solid component on CT were measured by two radiologists in three-dimensional (3D) and two-dimensional (2D) planes using in-house software. In addition, the maximum diameters of the tumor and invasive component were measured on pathology by two pathologists. CT measurements were compared with pathologic measurements. Results: There was a strong correlation between the size of the solid component on CT and invasive component on pathology, as well as the size of subsolid nodules and the tumor size (r = 0.82-0.87 for 3D measurement, 0.72-0.88 for 2D measurement; p &lt; 0.0001). The size of subsolid nodules in 3D and 2D measurements was significantly larger than tumor size (p &lt; 0.0001). In regard to measurement of the solid component, 3D measurements tended to be larger than the size of the invasive component whereas 2D measurement tended to be similar to the size of the invasive component. By applying a size criteria of solid component that was 3 mm or lesser in maximum diameter, preinvasive and minimally invasive adenocarcinoma was predicted with a specificity of 100% (28 of 28). Conclusion: We found a significant correlation between the size of the solid component on thin-section CT and the invasive component on pathology.N

18F-FDG PET/CT features of pulmonary sclerosing hemangioma

Background: Pulmonary sclerosing hemangioma (PSH) has been reported to show increased FDG uptake and be potential false-positives on 18F-FDG PET/CT examination. However, it is still unclear whether the previously-reported high FDG uptake is a universal characteristic of PSH, and furthermore, there have been no investigations on what kind of radiologic or histologic features may have been related with its FDG uptake values. Purpose: To investigate the 18F-FDG PET/CT features of pulmonary sclerosing hemangiomas (PSHs), and to evaluate the relating factors with their FDG uptake values. Material and Methods: We identified 10 PSHs in eight patients who had a pathologic diagnosis and available antecedent 18F-FDG PET/CT images. 18F-FDG PET/CT images were investigated both qualitatively and quantitatively, along with their histopathologic features. Correlation between 18F-FDG PET features and radiologic as well as histopathologic features were also evaluated. Results: Mean diameter of the 10 PSHs in our study was 16.9 mm +/- 6.26 (range 5-25 mm). Four tumors showed intense uptake, and four tumors showed moderate uptake on 18F-FDG PET/CT scans. In the remaining two tumors, there were no significant FDG uptakes. The SUVmax of tumors ranged from 0.60-4.7 (median 2.30; 2.51 +/- 1.42), and was significantly correlated with the tumor size (r = 0.754, P = 0.012) and three out of four tumors &gt;= 2 cm (75%) showed intense FDG uptake and their SUVmax values were greater than 2.5. Immunohistochemical results for GLUT-1, GLUT-4, and Ki-67 and other pathologic features were not correlated with the tumors&apos; FDG uptake. Conclusion: The majority of PSHs show increased FDG uptakes, and their SUVmax values are significantly correlated with their tumor size. PSH &gt;= 2 cm can frequently be falsely interpreted as malignancy in FDG-PET/CT. Further studies with large study population are warranted to confirm our observations.N