A novel low-power pure-cut hot snare polypectomy for 10-14 mm colorectal adenomas: An ex vivo and a clinical prospective feasibility study (SHARP trial).

BACKGROUND AND AIM: Hot snare polypectomy using blend or coagulation current is widely used; however, it causes deeper tissue heat injury, leading to adverse events. We hypothesized that hot polypectomy using low-power pure cut current (PureCut, effect 1 10 W) could reduce deeper tissue heat injury. We conducted animal experiments to evaluate the deeper tissue heat injury and conducted a prospective clinical study to examine its cutting ability. METHODS: In a porcine rectum, hot polypectomy using Blend current (EndoCut, effect 3 40 W) and low-power pure cut current was performed. The deepest part of heat destruction and thickness of the non-burned submucosal layer were evaluated histologically. Based on the results, we performed low-power pure cut current hot polypectomy for 10-14 mm adenoma. The primary endpoint was complete resection defined as one-piece resection with negative for adenoma in quadrant biopsies from the defect margin. RESULTS: In experiments, all low-power pure-cut resections were limited within the submucosal layer whereas blend current resections coagulated the muscular layer in 13% (3/23). The remaining submucosal layer was thicker in low-power pure cut current than in blend current resections. In the clinical study, low-power pure-cut hot polypectomy removed all 100 enrolled polyps. For 98 pathologically neoplastic polyps, complete resection was achieved in 84 (85.7%, 95% confidence interval, 77-92%). The lower limit of the 95% confidence interval was not more than 15% below the pre-defined threshold of 86.6%. No severe adverse events occurred. CONCLUSIONS: A novel low-power pure-cut hot polypectomy may be feasible for adenoma measuring 10-14 mm. (UMIN000037678).

Loss of p16 Immunoexpression and Deletions of CDKN2A in the Progression of Extramammary Paget Disease: An Immunohistochemical and Genetic Study of 24 Invasive/Metastatic Cases.

ABSTRACT: Information regarding the genetic alterations in extramammary Paget disease (EMPD) is scarce. This study investigated the significance of CDKN2A and MTAP alterations in EMPD progression using immunohistochemistry and panel DNA sequencing. In total, 24 invasive/metastatic EMPD cases were included in this study. The immunoexpression of p16 and MTAP in the primary in situ, primary invasive, and metastatic tumor components was evaluated. Panel DNA sequencing was performed for metastatic tumor components in 5 of the 24 cases. Immunoexpression of p16 in the in situ tumor component was at least partially preserved in all 19 tested cases (100%). By contrast, the invasive tumor component was diffusely or partially lost in 18 (81.8%) of 22 tested cases. Regarding the foci of lymph node metastasis, 13 (81.2%) of the 16 patients showed a significant loss of p16 expression. Loss of MTAP immunoexpression was observed less frequently compared with the loss of p16 expression. CDKN2A homozygous deletions were confirmed in all 5 tested cases by sequencing, whereas MTAP deletions were detected in only 2 cases. In conclusion, p16 expression loss and CDKN2A deletions can be frequently seen in invasive/metastatic cases of EMPD.

A Japanese case of ovarian mucinous adenocarcinoma with germline double variants of MSH2 and BRCA2.

Germline double heterozygosity (GDH) is rarely reported in cases of inherited cancer syndromes, and GDH of a mismatch repair gene and BRCA has never been reported in Japan. Nonetheless, the current report demonstrates a case of ovarian mucinous adenocarcinoma with initiated Lynch syndrome (LS)-related surveillance because of a known germline MSH2 variant. Six and a half years after oophorectomy, multiple tumors developed in the patient's lungs, bones, and lymph nodes, and histology results confirmed mucinous adenocarcinoma. Systemic chemotherapy including an anti-PD-L1 antibody was effective for >1 year, but brain metastases developed. Pathology of the brain tumors showed mucinous adenocarcinoma without expression of MSH2 and MSH6, while multi-gene panel testing demonstrated not only high microsatellite instability and a high tumor mutation burden, but also germline BRCA2 variants. Further, germline testing in relatives confirmed both variants were from the paternal line, from which many LS-related cancers develop, but not BRCA-related cancer.

Clinicopathologic and genetic characterization of invasive melanoma with BRAF V600K mutation: A study of 16 cases.

BACKGROUND: The clinicopathologic and genetic features of cutaneous melanoma with a BRAF V600K mutation are not well-known. We aimed to evaluate these characteristics in comparison with those associated with BRAF V600E. METHODS: Real-time polymerase chain reaction (PCR) and/or the MassARRAY® system were used to detect BRAF V600K in 16 invasive melanomas and confirm BRAF V600E in another 60 cases. Immunohistochemistry and panel next-generation sequencing were used to evaluate protein expression and tumor mutation burden, respectively. RESULTS: The median age of melanoma patients harboring the BRAF V600K mutation (72.5 years) was higher than those with the BRAF V600E (58.5 years). The two groups also differed in sex (13/16 [81.3%] male in the V600K group vs. 23/60 [38.3%] in V600E) and in the frequency of scalp involvement (8/16 [50.0%] in V600K vs. 1/60 [1.6%] in V600E). The clinical appearance was similar to a superficial spreading melanoma. Histopathologically, non-nested lentiginous intraepidermal spread and subtle solar elastosis were observed. One patient (1/13, 7.7%) had a pre-existing intradermal nevus. Diffuse PRAME immunoexpression was seen in only one (14.3%) of seven tested cases. Loss of p16 expression was observed in all 12 cases (100%) analyzed. The tumor mutation burden was 8 and 6 mutations/Mb in the two tested cases. CONCLUSIONS: Melanoma carrying the BRAF V600K mutation showed the predominance on the scalp of elderly men, lentiginous intraepidermal growth, subtle solar elastosis, possible existence of intradermal nevus component, frequent loss of p16 immunoexpression, limited immunoreactivity for PRAME, and intermediate tumor mutation burden.

A case of extensively spreading acinic cell carcinoma of the breast with microglandular features.

Acinic cell carcinoma (ACC) is an exceptionally rare type of breast carcinoma with a low-grade morphology and a favorable prognosis. It is postulated to be a type of invasive carcinoma arising in microglandular adenosis (MGA). We report a case of extensively spreading ACC of the breast with MGA-like features. Macroscopically, yellowish nodules were widely distributed throughout the right breast, up to the axilla, without mass formation. Microscopically, the tumor consisted of two distinct carcinoma components: one was multiple nodular lesions showing invasive carcinoma with fused solid nests, and the other was a widely spreading lesion exhibiting MGA-like features with uniform small single glands. Immunohistochemically, both components were negative for ER, PR, and HER2, and expressed EMA, S100 and lysozyme. The distinct morphology and molecular expression indicated ACC. The single glands in the MGA-like area lacked myoepithelial cells but were linearly surrounded by type IV collagen, a basement membrane component. This case supports the hypothesis that ACC and MGA have the same lineage and indicates that ACC is not necessarily a low-grade malignancy and can be aggressive.

Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis.

Low-grade neuroendocrine carcinoma of the skin (LGNECS) was proposed in 2017 as a new primary cutaneous neoplasm with neuroendocrine differentiation; however, it is not yet well known due to its rarity. Herein, we perform a detailed clinicopathologic analysis of 13 cases as well as panel DNA sequencing in three cases. The study included 12 males and 1 female with a median age of 71 (43-85) years. All lesions occurred on the ventral trunk. The mean tumor size was 2.2 (0.8-11.0) cm. The histopathology resembled that of well-differentiated neuroendocrine tumors (NETs) in other organs, but intraepidermal pagetoid spreading was seen in 8 (61.5%) cases and stromal mucin deposits in 4 (30.8%). Immunoreactivity for CK7, CK19, EMA, BerEP4, CEA, chromogranin A, synaptophysin, INSM1, GCDFP15, GATA3, ER, and bcl-2 were present in varying degrees in all tested cases. PTEN c.165-1G>A splice site mutation was detected by panel sequencing in one case, and GATA3 P409fs*99 and SETD2 R1708fs*4 in another case. Lymph node metastasis was seen significantly in cases with tumor size >2.0 cm [8/8 (100%) vs. 1/5 (20%)]. All three cases with size >3.0 cm were in unresectable advanced-stage [3/3 (100%) vs. 1/10 (10%)], and two of the three patients succumbed to the disease. The two cases of death revealed mild nuclear atypia (mitosis: 1/10 HPFs) and moderate nuclear atypia (2/10 HPFs). Thus, tumor size would be a better prognostic factor than nuclear atypia, mitotic count, and Ki67 index, unlike in NETs. These clinicopathologic and immunohistochemical features would represent the characteristics as skin adnexal tumors with apocrine/eccrine differentiation rather than NETs; therefore, we rename it as sweat-gland carcinoma with neuroendocrine differentiation (SCAND).

Microsatellite instability is biased in Amsterdam II-defined Lynch-related cancer cases with family history but is rare in other cancers: a summary of 1000 analyses.

BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.

Co-existence of BRAF V600E-mutated malignant melanoma and BRAF V600E-mutated Langerhans cell histiocytosis: A case report.

Langerhans cell histiocytosis (LCH) is a neoplastic condition of Langerhans cells, and can be associated with other neoplasms, especially BRAF-mutant hematological tumors and papillary thyroid carcinoma. Here we present the first case of co-existing LCH and low cumulative sun damage (low-CSD) melanoma, both of which had a BRAF V600E mutation. A 49-year-old man had a 45 × 43 × 15 mm semi-pedunculated, pigmented tumor in his back but had no other systemic symptoms. Histopathology revealed a 2-mm-sized incidental focus of LCH within a large lesion of low-CSD melanoma. Diffuse immunoexpression of CD1a, langerin/CD207, S100 protein, and BRAF (VE1) was observed in the focus of LCH. Sanger sequencing with microdissection confirmed BRAF V600E mutation in the component of LCH. Interestingly, the advanced melanoma also harbored the same BRAF V600E mutation, although the significance of this tumor combination is still unknown.

Present status of germline findings in precision medicine for Japanese cancer patients: issues in the current system.

OBJECTIVE: Since 2019, precision cancer medicine has been covered by national insurance in Japan; however, to date, germline findings have not been fully reported. The aim of this study was to evaluate the current status and raise a problem of germline finding analysis and disclosure in Japanese precision cancer medicine. METHODS: Germline findings of 52 genes were examined in 296 cases with advanced cancer by a case series study. RESULTS: Six (2.0%) cases were examined by the Oncoguide™ NCC Oncopanel with germline testing, but no germline findings were reported. The remaining 290 (98.0%) cases were analyzed by FoundationOne® CDx (tumor-only testing), which recognized 404 pathogenic variants; those of BRCA1/2 were recognized in 16 (5.5%) tumors. Our institutional algorithm suggested 39 candidate germline findings in 34 cases, while the public algorithm listed at least 91 candidate germline findings. Four germline findings had been previously identified (BRCA1: 3 and ATM: 1). Nine of 30 cases with candidate germline findings excluding these known germline findings refused or deferred germline testing. Only 4 of 16 cases that received counseling underwent germline testing, and those 4 revealed 3 germline findings (BRCA2, CDK4 and RAD51C); in total, 8 (2.7%) germline findings were revealed. Reasons for refusing genetic counseling and/or germline testing included extra hospital visits, added expense for germline testing due to limited national insurance coverage, poor patient physical condition and no known family members associated with the possible germline finding. CONCLUSIONS: In current Japanese precision cancer medicine, only a small fraction of the patients undergoes germline testing and demonstrated germline finding. The current results suggested a need for earlier indications for precision cancer medicine, broader insurance coverage and more efficient germline finding prediction algorithms, to increase the number of germline testings and to improve the following managements.

Sweat Gland Carcinoma With Neuroendocrine Differentiation of the Areola as a Potential Clinicopathologic Mimicker of Male Breast Carcinoma and Syringocystadenocarcinoma Papilliferum.

ABSTRACT: Sweat gland carcinoma with neuroendocrine differentiation (SCAND) is a newly proposed tumor entity of primary cutaneous apocrine/eccrine adnexal tumor with neuroendocrine differentiation. The histopathologic variations are not yet well known. In this article, we present a case of SCAND mimicking male breast cancer and syringocystadenocarcinoma papilliferum. A 68-year-old man presented with a reddish 12-mm nodule on his left areola. No lymph node or distant metastases were observed. The patient was disease free 1 year and 9 months after the tumor was surgically resected but died of cerebral hemorrhage. Histopathological examination revealed a predominantly intradermal tumor with marked syringotropism, mimicking a component of mammary ductal carcinoma in situ. In addition, another tissue section displayed a cup-shaped papillated tumor with syringocystadenocarcinoma papilliferum-like features, which were also seen because of marked syringotropism. Diffuse immunoexpression of cytokeratin 7, cytokeratin 19, chromogranin A, synaptophysin, INSM1, estrogen receptor, carcinoembryonic antigen, epithelial membrane antigen, and GATA3 was observed in the tumor, but no BRAF immunoexpression was seen. The present case would help us to understand the histopathological variation and differential diagnosis of SCAND. The histopathological diagnosis of male breast cancer or syringocystadenocarcinoma papilliferum should be made by ruling out SCAND.

Large Cell Neuroendocrine Carcinoma of the Skin/Conjunctiva: A Series of 6 Cases including 1 Combined Case With Squamous Cell Carcinoma.

ABSTRACT: This study sought to reveal the clinicopathologic characteristics of large cell neuroendocrine carcinoma (LCNEC) of the skin/conjunctiva. The retrieved patients included 3 men and 3 women with a median age of 85 (63-95) years. All lesions occurred on the face, including the ears, with a median tumor size of 11.5 (7-65) mm. Lymph node metastasis was observed in 5 (83%) of 6 cases, and distant metastasis was noted in 2 (33%). One patient (17%) who had a 13-mm-sized tumor died of the tumor 13 months after excision. All tumors were mainly located in the dermis, and one of them also exhibited intraepithelial spreading. The cytology resembled that of an LCNEC in other organs. No adnexal differentiation was observed. Five cases were of the pure type, but one had a component of squamous cell carcinoma. Immunoreactivities for CAM5.2, CK7, CK19, BerEP4, epithelial membrane antigen, neuron-specific enolase, synaptophysin, c-KIT, GATA3, and bcl-2 were frequently present, but CK20, neurofilament, Merkel cell polyomavirus large T antigen, mammaglobin, estrogen receptor, HER2, and TTF1 were completely negative in all cases. Mutant-pattern immunostaining of p53, PTEN, and Rb was frequently observed. The Ki67 rate exceeded 70% in all cases. LCNEC of the skin/conjunctiva is a morphologically-defined group of primary cutaneous/conjunctival neuroendocrine neoplasm, although it may be heterogeneous similar to other-site LCNEC or Merkel cell carcinoma. This study highlighted the predominant location for the face, high metastatic and lethal potential, possible combination with other tumor components, and frequent mutant-type immunoexpressions of p53, PTEN, and Rb in this tumor group.

Tip-in Endoscopic Mucosal Resection for 15- to 25-mm Colorectal Adenomas: A Single-Center, Randomized Controlled Trial (STAR Trial).

INTRODUCTION: One-piece endoscopic mucosal resection (EMR) for lesions >15 mm is still unsatisfactory, and attempted 1-piece EMR for lesions >25 mm can increase perforation risk. Therefore, modifications to ensure 1-piece EMR of 15- to 25-mm lesions would be beneficial. The aim of this study was to investigate whether Tip-in EMR, which anchors the snare tip within the submucosal layer, increases en bloc resection for 15- to 25-mm colorectal lesions compared with EMR. METHODS: In this prospective randomized controlled trial, patients with nonpolypoid colorectal neoplasms of 15-25 mm in size were recruited and randomly assigned in a 1:1 ratio to undergo Tip-in EMR or standard EMR, stratified by age, sex, tumor size category, and tumor location. The primary endpoint was the odds ratio of en bloc resection adjusted by location and size category. Adverse events and procedure time were also evaluated. RESULTS: We analyzed 41 lesions in the Tip-in EMR group and 41 lesions in the EMR group. En bloc resection was achieved in 37 (90.2%) patients undergoing Tip-in EMR and 30 (73.1%) who had EMR. The adjusted odds ratio of en bloc resection in Tip-in EMR vs EMR was 3.46 (95% confidence interval: 1.06-13.6, P = 0.040). The Tip-in EMR and EMR groups did not differ significantly in adverse event rates (0% vs 4.8%) or median procedure times (7 vs 5 minutes). DISCUSSION: In this single-center randomized controlled trial, we found that Tip-in EMR significantly improved the en bloc resection rate for nonpolypoid lesions 15-25 mm in size, with no increase in adverse events or procedure time.

Signet-ring cell/histiocytoid carcinoma of the axilla: a clinicopathological and genetic analysis of 11 cases, review of the literature, and comparison with potentially related tumours.

AIMS: The aim of this study was to determine the clinicopathological and genetic characteristics of axillary signet-ring cell/histiocytoid carcinoma (SRCHC) and the relationship between axillary SRCHC, eyelid SRCHC, and conventional apocrine carcinoma (AC). METHODS AND RESULTS: Eleven cases of axillary SRCHC, four cases of eyelid SRCHC, eight cases of axillary AC and five cases of invasive lobular carcinoma (ILC) were retrieved. Additionally, 14 axillary and 43 eyelid SRCHC cases from the literature were reviewed. Male predominance was prominent for axillary SRCHC (24:1) and eyelid SRCHC (42:5). Axillary SRCHC formed a circumscribed plaque or nodule, unlike eyelid SRCHC. Lymph node metastasis was predominantly seen in axillary SRCHC cases (72%, 18/25), but not in eyelid SRCHC cases (19%, 9/47). Axillary SRCHC and eyelid SRCHC were histopathologically similar and showed rare tubular formations. Immunoexpression of cytokeratin 7, cytokeratin 19, mucin 1, mucin 5AC, BerEP4 and androgen receptor was seen in all tested cases of the four diseases. Oestrogen and progesterone receptors were negative in both types of SRCHC and AC, but were strongly positive in ILCs. Complete loss of E-cadherin expression was seen in approximately one-quarter of both types of SRCHC and in all ILCs. PIK3CA mutations were detected in all three sequenced cases (two axillary SRCHCs and one eyelid SRCHC). CONCLUSION: The histopathological, immunohistochemical and genetic findings suggest that both types of SRCHC are phenotypic variants of AC, although there are differences in sex, macroscopic findings and the frequency of lymph node metastasis among the three. In contrast, ILC differs from the other three tumour types.

Retrospective analysis of salvage surgery for local progression of brain metastasis previously treated with stereotactic irradiation: diagnostic contribution, functional outcome, and prognostic factors.

BACKGROUND: Stereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. So far, just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. Based on these results, we reconsidered surgical indication for patients with local progression after STI. METHODS: We evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Kaplan-Meier curves were used for the assessment of overall survival. Prognostic factors for survival were analyzed. RESULTS: Fifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 63.5 years (range 36-79). The median interval from STI to surgery was 12 months. The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1-2 (RPA 1 vs. 3, HR:0.13), (RPA 2 vs 3, HR:0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. The peripheral neutrophil-to-lymphocyte ratio (NLR) of ≤3.65 predicted significantly longer OS (median 25.5 months) than an NLR > 3.65 (median 8 months). CONCLUSION: We insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.

Efficacy and safety of cold-snare endoscopic mucosal resection for colorectal adenomas 10 to 14 mm in size: a prospective observational study.

BACKGROUND AND AIMS: Cold-snare endoscopic mucosal resection (CS-EMR) has been adapted in a piecemeal fashion as a safe and effective procedure for resection of colorectal polyps ≥10 mm. However, few data are available on en bloc CS-EMR for adenomas of 10 to 14 mm. Thus, this study evaluated the efficacy and safety of CS-EMR for these colorectal adenomas. METHODS: In this single-arm, prospective, observational study, patients with at least 1 slightly elevated and sessile colorectal adenoma measuring 10 to 14 mm were recruited to undergo CS-EMR. The primary outcome was histological complete resection rate by CS-EMR, which was defined as en bloc resection, with a pathologically negative vertical margin and no neoplastic tissue obtained from 4 quadrants of the mucosal defect margin. Secondary outcomes were en bloc resection rate by CS-EMR, failure rate of CS-EMR, and the incidence of adverse events. RESULTS: A total of 80 polyps from 72 patients were included. CS-EMR failed in 11 lesions (13.7%), all of which were resected using a high-frequency electric current. The rates of en bloc resection and histologic complete resection by CS-EMR were 82.5% (66 of 80) and 63.8% (51 of 80), respectively. No bleeding occurred during the CS-EMR procedure, and there was no delayed bleeding or perforation at the site where CS-EMR was performed. CONCLUSIONS: CS-EMR can be safely performed in an en bloc fashion for some colorectal adenomas measuring 10 to 14 mm. However, there is room for improvement regarding the resectability and evaluation of the vertical margin after CS-EMR. (Clinical trial registration number: UMIN000031248.).

Mixed pleomorphic lobular and apocrine carcinoma of the breast: A case report suggesting pathogenesis.

Pleomorphic lobular carcinoma (PLC) of the breast is a variant of lobular carcinoma, characterized by loss of E-cadherin expression and high-grade morphologies. Whether the pathogenesis of PLC is in the ductal or the lobular lineage has been discussed. In this report, a case of PLC combined with apocrine carcinoma is presented. Histologically, the tumor showed two distinct carcinoma components: one was a typical apocrine carcinoma, and the other was a pleomorphic invasive lobular carcinoma. The former showed complete membranous expression of E-cadherin, whereas the latter aberrantly expressed it not on the cell membrane, but in the cytoplasm. Both components were triple-negative and strongly positive for GCDFP-15, suggesting apocrine differentiation. The intraductal component showed only a feature of apocrine ductal carcinoma in situ. This case suggests that apocrine carcinoma could be an origin of PLC.

Can positron emission tomography detect colorectal adenomas and cancers?

BACKGROUND AND AIM: Fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography (PET) is effective and less invasive than other modalities used to diagnose tumors, including colorectal cancer (CRC). However, the detectability of adenomas and CRCs, especially in the early stages, is unclear. METHODS: We evaluated the records of 2323 consecutive eligible patients who underwent both a total colonoscopy (TCS) and PET between October 2002 and September 2012 at a tertiary cancer center. The PET findings were verified by TCS performed independently within 1 year. Target lesions were defined as CRCs and adenomas that were 6 mm or larger in size. RESULTS: Total colonoscopy detected 532 target lesions ≥ 6 mm in size: 56 T2-T4 CRCs, 39 T1 CRCs, 223 advanced adenomas, and 214 low-grade adenomas. Of the 532 lesions, 216 (40.6%) were PET positive. Of the 369 cases with positive uptakes, PET detected target lesions in the matched segments for 58.5% (216/369). Sensitivity of PET to T2-T4 CRCs, T1 CRCs, advanced adenomas, and low-grade adenomas was 92.9%, 79.5%, 50.7%, and 9.3%, respectively. PET could detect 76.5% (13/17) of T1 CRCs whose size is 10 to 19 mm and 85.0% (17/20) of T1 CRCs equal or larger than 20 mm. The multivariate analysis excluding T2-T4 CRCs showed malignant histology, larger size, protruded lesions, villous histology, and lesions in distal colon were significant factors. CONCLUSIONS: Sensitivity of PET for detecting T2-T4 and even T1 cancers are promising. However, sensitivity of PET to adenomas, even advanced adenomas, is limited.

Real-time virtual sonography examination and biopsy for suspicious breast lesions identified on MRI alone.

OBJECTIVES: The purpose of our study was to assess whether there is a potential additional value of real-time virtual sonography (RVS) to second-look ultrasound (US) examination and biopsy for breast lesions identified on MRI alone. METHODS: A retrospective review of the records of 70 consecutive patients (78 lesions) with breast abnormalities identified on MRI alone was performed. All suspicious enhancing lesions were subsequently evaluated with second-look US. Lesions not observed on second-look US underwent RVS. Pathological findings were confirmed by subsequent percutaneous biopsy or excision. RESULTS: Of the 78 MRI-detected lesions, second-look US correlation was made in 50 (64 %), including 22 malignant and 28 benign lesions. The remaining 28 lesions (36 %) were scheduled to undergo RVS. Four lesions were not visible on the second breast MRI. The remaining 24 lesions were RVS correlated and underwent RVS-guided biopsy; these included seven malignant and 17 benign lesions. Overall, 74 of 74 (100 %) true MRI-detected lesions were confirmed by histological results without using MRI-guided breast biopsy. The cancer rate was 29 %. CONCLUSIONS: RVS can increase the sonographic detection and biopsy rate of lesions identified on breast MRI alone. KEY POINTS: • All 74 MRI-detected lesions were confirmed without using MRI-guided biopsy. • Four lesions were not visible on second breast MRI. • RVS can increase sonographic detection of lesions identified on breast MRI alone. • RVS-guided breast biopsy can be an alternative to MRI-guided biopsy.

The Ki-67 labeling index and lymphatic/venous permeation predict the metastatic potential of rectal neuroendocrine tumors.

BACKGROUND: Endoscopic resection has been used to treat small rectal neuroendocrine tumors (NETs). However, the indication for additional surgery after endoscopic resection is unclear. The aim of this study was to identify risk factors for rectal NET metastasis and to determine the indication for additional surgery. METHODS: Fifty-five patients with a total of 57 rectal NETs, treated between October 2003 and January 2013, were retrospectively divided into metastatic (11 lesions) and non-metastatic (46 lesions) groups. Tumor size, central depression, invasion depth, lymphatic and venous permeation, mitotic activity, nuclear abnormality, Ki-67 labeling index, and World Health Organization grading classification (G1 or G2) were compared between the groups. Patients underwent endoscopic submucosal resection with a ligation device, transanal full-thickness surgical resection, or radical surgery. RESULTS: By univariate analysis, the odds ratios (OR) for a Ki-67 labeling index >3.0 %, positive lymphatic or venous permeation, World Health Organization grading classification G2, tumor size >10 mm, submucosal invasion >4000 µm, and central depression were 120 (P < 0.001), 67.6 (P < 0.001), 58.7 (P < 0.001), 9.8 (P = 0.0037), 6.8 (P = 0.012), and 5.7 (P = 0.018), respectively. Multivariate logistic regression analyses showed that vascular permeation (OR 111; P = 0.006) and a Ki-67 labeling index >3.0 % (OR 88; P = 0.012) were independent risk factors for metastasis. CONCLUSIONS: The Ki-67 labeling index and lymphatic/venous permeation were reliable predictors of rectal NET metastases.