Anal Metastasis Originating from Colorectal Cancer: Report of Two Cases

Anal metastasis from colorectal cancer rarely occurs, but it severely impairs the patient’s quality of life, often requiring wide resection including the anal sphincter with permanent colostomy. This lesion can be misdiagnosed as a perianal fistula or an abscess, and it can be overlooked at the time of surgery because it is not included in the routine surgical extent of low anterior resection. We report two rare cases of anal metastasis from colorectal cancer. In both cases, perianal nodules with an internal solid portion were detected on preoperative rectal magnetic resonance imaging and additional local excisions of the anal lesions were performed during the process of treatment. Anal metastasis was pathologically confirmed by histology and immunohistochemical staining.ope

The value of phosphohistone H3 as a proliferation marker for evaluating invasive breast cancers: A comparative study with Ki67

BACKGROUND: Established measurements of proliferation in breast cancer are Ki67 and mitotic-activity-index (MAI), with problems in reproducibility and prognostic accuracy. Phosphohistone H3 (PHH3), a relatively novel IHC marker is specific for mitosis with good reproducibility. We hypothesized that PHH3 would be more reproducible and better represent proliferation than Ki67. RESULTS: PHH3 identified easily-missed mitosis by MAI, as demonstrated by upgrading M grade at diagnosis (n = 29/218, evenly distributed). PHH3 accurately found hot-spots, supported by mitotic count agreement between low-power and 10HPFs (R2 = 0.999; P = 0.001). PHH3 was more reproducible than Ki67, measured by five-rater inter-class correlation coefficient (0.904 > 0.712; P = 0.008). Finally, despite a relatively short follow-up (median 46 months; 7 recurrences) PHH3 was the only variable correlated with disease-free survival (P = 0.043), while all other conventional clinicopathologic variables, including Ki67 (P = 0.356), did not. MATERIALS AND METHODS: We compared Ki67 and PHH3 for 218 breast cancer surgical cases diagnosed from 2012 to 2013 at Severance hospital. The most representative invasive breast cancer surgical slides were immunohistochemically stained for Ki67 and PHH3. CONCLUSIONS: Poor reproducibility and inadequate representation of proliferation of Ki67 and MAI may be improved by PHH3, allowing better accuracy in breast cancer diagnostics.ope

Extraosseous Ewing’s Sarcoma Presented as a Rectal Subepithelial Tumor: Radiological and Pathological Features

Purpose: Extraosseous Ewing’s sarcoma (EOE) of the rectum is extremely rare: only three cases have been reported in the literature and none of these reports described their imaging findings in detail. Herein, we describe the tumor imaging and pathological features in detail. Materials and Methods: We report a case of rectal EOE in a 72-year-old female who received local excision and was provisionally diagnosed with a rectal submucosal spindle cell tumor. We used immunohistochemistry, histopathology, and fluorescence in situ hybridization to characterize the tumor and provide a definitive diagnosis of EOE. Results: MRI revealed a well-demarcated submucosal tumor with heterogeneous enhancement and hemorrhagic foci in rectum. EOE was diagnosed by positive staining of tumor cells for CD99 and Fli-1 by immunohistochemistry and the presence of the EWSR1 gene translocation by fluorescence in situ hybridization. Although the patient underwent radiation treatment and surgery, the tumor recurred after 4 months as revealed by computed tomography and magnetic resonance imaging. Conclusion: Rectal EOE may present as a rectal submucosal tumor. The understanding of imaging and histological characteristics of this tumor are critical for accurate diagnosis and appropriate aggressive treatment.ope

Genetic, Clinicopathological, and Radiological Features of Intrahepatic Cholangiocarcinoma with Ductal Plate Malformation Pattern

Background/aims: Intrahepatic cholangiocarcinoma (iCCA) with a ductal plate malformation (DPM) pattern is a recently recognized rare variant. The genomic profile of iCCA with DPM pattern needs to be elucidated. Methods: Cases of iCCA with DPM pattern were retrospectively reviewed based on the medical records, pathology slides, and magnetic resonance imaging (MRI) reports collected between 2010 to 2019 at a single center. Massive parallel sequencing was performed for >500 cancer-related genes. Results: From a total of 175 iCCAs, five (2.9%) cases of iCCA with DPM pattern were identified. All cases were of the small duct type, and background liver revealed chronic B viral or alcoholic hepatitis. Three iCCAs with DPM pattern harbored MRI features favoring the diagnosis of hepatocellular carcinoma, whereas nonspecific imaging features were observed in two cases. All patients were alive without recurrence during an average follow-up period of 57 months. Sequencing data revealed 64 mutated genes in the five cases, among which FGFR and PTPRT were most frequently mutated (three cases each) including an FGFR-TNC fusion in one case. Mutations in ARID1A and CDKN2A were found in two cases, and mutations in TP53, BAP1, ATM, NF1, and STK11 were observed in one case each. No IDH1, KRAS, or PBRM1 mutations were found. Conclusions: iCCAs with DPM pattern have different clinico-radio-pathologic and genetic characteristics compared to conventional iCCAs. Moreover, FGFR and ARID1A variants were identified. Altogether, these findings further suggest that iCCA with DPM pattern represents a specific subtype of small duct type iCCA.ope

Erlotinib monotherapy for stage IIIB/IV non-small cell lung cancer: a multicenter trial by the Korean Cancer Study Group

BACKGROUND: Erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) is an oral, epidermal growth factor receptor tyrosine kinase inhibitor that has antitumor activity and good tolerability in non-small cell lung cancer (NSCLC). In particular, higher response rates have been reported in Asian patients than in Western patients. The aim of this study conducted by the Korean Cancer Study Group was to evaluate the efficacy and tolerability of erlotinib monotherapy as a palliative treatment for advanced NSCLC patients in Korea. PATIENTS AND METHODS: Patients with histologically or cytologically confirmed stage IIIB or IV NSCLC including recurrent or metastatic disease, with performance status from 0 to 3, were eligible either if they had received any anticancer treatment except epidermal growth factor receptor inhibitors or if they were unsuitable for chemotherapy because of poor performance status. Enrolled patients were treated with oral erlotinib at a dose of 150 mg daily until disease progression or development of intolerable toxicity. RESULTS: A total of 120 patients were enrolled between January 2005 and May 2006. Forty-four patients (36.7%) were female and 72 patients were current or former smoker. Fifty percent of patients had received one prior palliative chemotherapy regimens and 34.2% had two or more prior palliative regimens. The overall tumor response rate was 24.2% (95% confidence interval [CI], 16.8-32.8%) with 4 complete responses and 25 partial responses, and the disease control rate was 56.7%. The favorable clinical variables for tumor response were female (P = 0.001), never smokers (P = 0.041), and adenocarcinoma (P = 0.001). The most common adverse event was skin rash (78% of which grade 3 or 4 skin rash occurred in 13.3% of the patients). With a median follow-up of 23.6 months, the median time to progression was 2.7 months (95% CI, 2.2-3.2), and the median overall survival was 12.9 months (95% CI, 6.9-18.8). By multivariate analysis, female and development of skin rash were significantly associated with longer time to progression and overall survival. CONCLUSION: Erlotinib monotherapy showed significant antitumor activity and an acceptable tolerability profile as a palliative treatment in advanced NSCLC patients in Korea, especially in females, never smokers, and patients with adenocarcinoma histology.ope

Multimodality imaging studies of intraductal tubulopapillary neoplasms of the pancreas

PURPOSE: We aimed to investigate multimodality imaging findings of intraductal tubulopapillary neoplasms (ITPN) of the pancreas. METHODS: This study was approved by the institutional review board with waived informed consent. A total of eight patients were histopathologically diagnosed with pancreatic ITPN in a single institution over a 6-year period. The imaging findings of dynamic contrast-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), and positron emission tomography-computed tomography (PET-CT) were reviewed and correlated with clinicopathologic findings. RESULTS: Histopathologically, an invasive carcinoma component was found in 5 of 8 patients (62.5%). The median diameter of the lesions and the main pancreatic ducts were larger in ITPN with invasive carcinoma (19 mm, 13.3-98.0 mm and 13 mm, 5.9-16.3 mm, respectively) than in ITPN without invasive carcinoma (13 mm, 12.7-18.5 mm and 6 mm, 5.6-6.1 mm, respectively), but not significantly (lesions, P = 0.229 and main pancreatic ducts, P = 0.143). Pancreatolithiasis accompanied invasive carcinoma in 3 of 5 patients (60%). Intraductal solid tumors were demonstrated on CT (5/8, 62.5%), MRCP (5/7, 71.4%), and EUS (7/7, 100%). In addition, various imaging findings mimicking chronic autoimmune pancreatitis or pancreatic ductal adenocarcinoma were found in 3 patients (37.5%) on multimodality imaging. The lesion multiplicity and synchronous or metachronous biliary cancer occurred in 3 patients (37.5%), respectively. CONCLUSION: Patients with associated invasive carcinoma from pancreatic ITPN may have presented a trend toward larger tumor size and dilated pancreatic duct with pancreatoliths, but the difference was not statistically significant. Further studies with a larger number of patients are needed to provide better insight into these findings. Pancreatic ITPN can show various atypical imaging findings as well as typical intraductal solid tumor on multimodality imaging. The presence of lesion multiplicity and synchronous or metachronous biliary cancer can be helpful for assisting with the diagnosis of pancreatic ITPN.ope

SEPT9 Expression in Hepatic Nodules: An Immunohistochemical Study of Hepatocellular Neoplasm and Metastasis

The methylated SEPT9 DNA ( mSEPT9 ) in plasma is a US Food and Drug Administration (FDA)-approved screening biomarker in colorectal cancer and is emerging as a promising diagnostic and prognostic biomarker in hepatocellular carcinoma (HCC). We evaluated the SEPT9 protein expression by immunohistochemistry (IHC) in various hepatic tumors from 164 hepatectomies and explants. Cases diagnosed as HCC (n=68), hepatocellular adenoma (n=31), dysplastic nodule (n=24), and metastasis (n=41) were retrieved. SEPT9 stain was performed on representative tissue blocks showing tumor/liver interface. For HCC, archived IHC (SATB2, CK19, CDX2, CK20, and CDH17) slides were also reviewed. The findings were correlated with demographics, risk factors, tumor size, alpha fetoprotein levels at diagnosis, T stage and oncologic outcomes, with significance defined as P <0.05. Percentage of SEPT9 positivity differed significantly among hepatocellular adenoma (3%), dysplastic nodule (0%), HCC (32%), and metastasis (83%, P <0.001). Compared with patients with SEPT9- HCC, those with SEPT9+ HCC were older (70 vs. 63 y, P =0.01). The extent of SEPT9 staining correlated with age ( rs =0.31, P =0.01), tumor grade ( rs =0.30, P =0.01), and extent of SATB2 staining ( rs =0.28, P =0.02). No associations were found between SEPT9 staining and tumor size, T stage, risk factors, CK19, CDX2, CK20, or CDH17 expression, alpha fetoprotein levels at diagnosis, METAVIR fibrosis stage, and oncologic outcome in the HCC cohort. SEPT9 is likely implicated in liver carcinogenesis in a HCC subset. Similar to mSEPT9 DNA measurement in liquid biopsies, SEPT9 staining by IHC may prove helpful as an adjunct diagnostic biomarker with potential prognostic ramifications.restrictio

Stromal p16 Overexpression in Gastric-type Mucinous Carcinoma of the Uterine Cervix

BACKGROUND/AIM: Gastric-type mucinous carcinoma (MC-G) of the uterine cervix displays distinct morphological features and an aggressive clinical course. The expression status of p16 in the stroma has not been investigated in adenocarcinoma of the uterine cervix. Stromal p16 expression was evaluated in endocervical adenocarcinomas, including usual-type endocervical adenocarcinoma (UEA), intestinal-type mucinous carcinoma (MC-I), and MC-G. Whether stromal p16 expression varied significantly according to the histological subtype and whether the expression status is associated with clinicopathological characteristics of MC-G was also investigated. MATERIALS AND METHODS: Immunostaining of p16 was performed for 24, 19, and 18 cases of UEA, MC-I, and MC-G, respectively. RESULTS: UEA and MC-I subtypes exhibited horizontally continuous, strong nuclear p16 immunoreactivity in the tumor cells, whereas none of the MC-G cases showed diffuse and strong nuclear immunoreactivity for p16 in the tumor cells. Instead, 10 (55.6%) cases of MC-G displayed moderately to strongly positive p16 expression in the stroma. Stromal p16 expression of MC-G was significantly higher than that of normal cervix, UEA, and MC-I. Metastatic MC-G had significantly higher stromal p16 expression than primary MC-G. Further, stromal p16 overexpression in MC-G was associated with advanced stage, parametrial invasion, and lymphovascular invasion. CONCLUSION: Stromal p16 expression of MC-G was significantly higher than that of normal cervix and other histological subtypes of adenocarcinoma and was associated with advanced stage, parametrial invasion, and lymphovascular invasion, reflecting the aggressive behavior of MC-G. Our observations suggest that stromal p16 expression is involved in the development and progression of MC-G.restrictio

Increased Expression of the Matrix-Modifying Enzyme Lysyl Oxidase-Like 2 in Aggressive Hepatocellular Carcinoma with Poor Prognosis

Background/Aims: Lysyl oxidase-like 2 (LOXL2), a collagen-modifying enzyme, has been implicated in cancer invasiveness and metastasis. Methods: We evaluated the expression of LOXL2 protein, in addition to carbonic anhydrase IX (CAIX), keratin 19, epithelial cell adhesion molecule, and interleukin 6, in 105 resected hepatocellular carcinomas (HCCs) by immunohistochemistry. Results: LOXL2 positivity was found in 14.3% (15/105) of HCCs, and it was significantly associated with high serum α-fetoprotein levels, poor differentiation, fibrous stroma, portal vein invasion, and advanced TNM stage (p＜0.05 for all). Additionally, LOXL2 positivity was significantly associated with CAIX (p=0.005) and stromal interleukin 6 expression (p=0.001). Survival analysis of 99 HCC patients revealed LOXL2 positivity to be a poor prognostic factor; its prognostic impact appeared in progressed HCCs. Furthermore, LOXL2 positivity was shown to be an independent predictor of overall survival and disease-specific survival (p＜0.05 for all). Interestingly, co-expression of LOXL2 and CAIX was also an independent predictor for overall survival, disease-specific survival, disease-free survival, and extrahepatic recurrence-free survival (p＜0.05 for all). Conclusions: LOXL2 expression represents a subgroup of HCCs with more aggressive behavior and is suggested to be a poor prognostic marker in HCC patients.ope