The clinical characteristics and prognostic factors of combined Hepatocellular Carcinoma and Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma after Surgical Resection: A propensity score matching analysis.

Background: Clinical characteristics and prognosis among combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (cHCC-CC) with HCC and intrahepatic cholangiocarcinoma (ICC) were inconsistent in previous studies. The aim of this study was to compare postoperative prognosis among cHCC-CC, HCC and ICC, and investigated the prognostic risk factor of cHCC-CC after surgical resection. Methods: A total of 1041 eligible patients with pathological diagnosis of cHCC-CC (n=135), HCC (n=698) and ICC (n=208) were enrolled in this study. Univariate and multivariate Cox analysis were applied for assessing important risk factors. cHCC-CC were further 1:1 matched with HCC and ICC on important clinical risk factors. Survival curves of matched and unmatched cohorts were depicted by Kaplan-Meier method with log-rank test. Results: Patients with cHCC-CC had similar rate of sex, age and cirrhosis with HCC (p<0.05) and comparable incidence of hepatitis B or C with ICC (p=0.197). Patients of cHCC-CC had intermediate prognosis between HCC and ICC, with median overall survival (OS) time of cHCC-CC, HCC and ICC of 20.5 months, 35.7 months and 11.6 months (p<0.001). In matched cohorts, the OS of cHCC-CC were worse than HCC (p<0.001) but comparable with ICC (p=0.06), while the disease-free survival (DFS) of cHCC-CC was worse than HCC but better than ICC (p<0.05). And lymph node infiltration and postoperative transarterial chemoembolization (TACE) were independent risk factors of cHCC-CC associated with prognosis. Conclusion: The long term survival of cHCC-CC was worse than HCC but comparable with ICC when matched on albumin level, tumor size, lymph node infiltration, tumor stage and margin. Presence of lymph node infiltration and no postoperative TACE were associated with poor prognosis of cHCC-CC.

Outcomes of Yttrium-90 Radioembolization for Unresectable Combined Biphenotypic Hepatocellular-Cholangiocarcinoma.

PURPOSE: To evaluate outcomes of yttrium-90 radioembolization in patients with combined biphenotypic hepatocellular-cholangiocarcinoma (cHCC-CC). MATERIALS AND METHODS: A retrospective review of patients with biopsy-confirmed cHCC-CC treated with yttrium-90 radioembolization between 2012 and 2018 was performed. Twenty-two patients with cHCC-CC (mean age 65.6 y, 17 men, 5 women) underwent 29 radioembolization treatments (5 resin, 24 glass microspheres). Survival data were available in 21 patients, and hepatic imaging response data were available in 20 patients. Hepatic imaging response to radioembolization was assessed on follow-up CT or MR imaging using modified Response Evaluation Criteria In Solid Tumours criteria. Univariate stepwise Cox regression analysis was used to evaluate the association between demographic and clinical factors and survival. Logistic regression evaluated associations between clinical factors and response to treatment, overall response, and disease control. RESULTS: Hepatic imaging response was as follows: 15% complete response, 40% partial response, 10% stable disease, and 35% progressive disease (55% response rate, 65% disease control rate). Two patients were downstaged or bridged to transplant, and 1 patient was downstaged to resection. Median overall survival was 9.3 mo (range, 2.5-31.0 mo) from time of radioembolization. Nonreponse to treatment, bilobar disease, presence of multiple tumors, and elevated carbohydrate antigen 19-9 before treatment were associated with reduced survival after radioembolization. CONCLUSIONS: Radioembolization is a viable option for locoregional control of cHCC-CC with good response and disease control rates.

Goblet Cell Carcinoid/Carcinoma: An Update.

Goblet cell carcinoid (GCC) or goblet cell carcinoma is a unique mixed endocrine-exocrine neoplasm that is almost exclusively seen in the appendix. The hallmark of GCC is the concentric infiltration of the appendiceal wall by small tight clusters, nests or cords of tumor cells that exhibit a goblet cell morphology with a small compressed nucleus and conspicuous intracytoplasmic mucin. The coexistence of high-grade adenocarcinoma with GCC has been increasingly recognized as a common finding, which has been called adenocarcinoma ex GCC or mixed GCC-adenocarcinoma. A number of studies have shown that it is the high-grade adenocarcinomatous component that dictates the prognosis. Several histologic classification/grading systems have been proposed, which correlate with overall patient survival. Treatment options are primarily based on tumor stage and the presence or absence of a high-grade adenocarcinomatous component.

Biallelic tumour suppressor loss and DNA repair defects in de novo small-cell prostate carcinoma.

Small-cell prostate carcinoma (SCPC) is an aggressive malignancy that is managed similarly to small-cell lung cancer. SCPC can evolve from prostate adenocarcinoma in response to androgen deprivation therapy, but, in rare cases, is present at initial cancer diagnosis. The molecular aetiology of de novo SCPC is incompletely understood, owing to the scarcity of tumour tissue and the short life-expectancy of patients. Through a retrospective search of our regional oncology pharmacy database, we identified 18 patients diagnosed with de novo SCPC between 2004 and 2017. Ten patients had pure SCPC pathology, and the remainder had some admixed adenocarcinoma foci, but all were treated with first-line platinum-based chemotherapy. The median overall survival was 28 months. We performed targeted DNA sequencing, whole exome sequencing and mRNA profiling on formalin-fixed paraffin-embedded archival tumour tissue. We observed frequent biallelic deletion and/or mutation of the tumour suppressor genes TP53, RB1, and PTEN, similarly to what was found in treatment-related SCPC. Indeed, at the RNA level, pure de novo SCPC closely resembled treatment-related SCPC. However, five patients had biallelic loss of DNA repair genes, including BRCA1, BRCA2, ATM, and MSH2/6, potentially underlying the high genomic instability of this rare disease variant. Two patients with pure de novo SCPC harboured ETS gene rearrangements involving androgen-driven promoters, consistent with the evolution of de novo SCPC from an androgen-driven ancestor. Overall, our results reveal a highly aggressive molecular landscape that underlies this unusual pathological variant, and suggest opportunities for targeted therapy strategies in a disease with few treatment options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Long-term outcomes of combined hepatocellular-cholangiocarcinoma after hepatectomy or liver transplantation: A systematic review and meta-analysis.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy. We conducted a systematic review and meta-analysis to assess the evidence available on the long-term outcomes of cHCC-CC patients after either hepatectomy or liver transplantation (LT). DATA SOURCES: Relevant studies published between January 2000 and January 2018 were identified by searching PubMed and Embase and reviewed systematically. Data were pooled using a random-effects model. RESULTS: A total of 42 observational studies involving 1691 patients (1390 for partial hepatectomy and 301 for LT) were included in the analysis. The median tumor recurrence and 5-year overall survival (OS) rates were 65% (range 38%-100%) and 29% (range 0-63%) after hepatectomy versus 54% (range 14%-93%) and 41% (range 16%-73%) after LT, respectively. Meta-analysis found no significant difference in OS and tumor recurrence between LT and hepatectomy groups. CONCLUSION: Hepatectomy rather than LT should be considered as the prior treatment option for cHCC-CC.

Response to Loco-Regional Therapy Predicts Outcomes After Liver Transplantation for Combined Hepatocellular-Cholangiocarcinoma.

INTRODUCTION AND AIM: Combined hepatocellular-cholangiocarcinoma (HCC-CCA) is a rare liver malignancy distinct from either hepatocellular carcinoma (HCC) or cholangiocarcinoma. Liver transplantation (LT) is not recommended for HCC-CCA because of suboptimal outcomes. Non-invasive diagnosis of HCC-CCA is extremely challenging; thus, some HCC-CCAs are presumed as HCC on imaging and listed for LT with the correct diagnosis ultimately made on explant pathology. We compared HCC-CCA with HCC to determine the utility of response to pre-transplant loco-regional therapy (LRT) in predicting outcomes for HCC-CCA after LT as a potential means of identifying appropriate HCC-CCA patients for LT. MATERIAL AND METHODS: Retrospective review of 19 patients with pathologically confirmed HCC-CCA were individually matched to 38 HCC patients (1:2) based on age, sex, and Milan criteria at listing was performed. The modified response evaluation criteria in solid tumors was used to categorize patients as responders or non-responders to pre-transplant LRT based on imaging performed before and after LRT. Overall survival (OS) and recurrence-free survival (RFS) were examined. RESULTS: OS at 3 years post-transplant was 74% for HCC-CCA and 87% for HCC. RFS at 3 years was 74% for HCC-CCA, and 87% for HCC. Among responders to LRT, the 3-year OS was 92% for HCC-CCA and 88% for HCC; among non-responders, 3-year OS was 43% for HCC-CCA and 83% for HCC. Higher 3-year OS was observed among HCC-CCA responders (77%) compared with HCC-CCA non-responders (23%). CONCLUSIONS: OS was similarly high among.

Liver transplantation in patients with incidental hepatocellular carcinoma/cholangiocarcinoma and intrahepatic cholangiocarcinoma: a single-center experience.

BACKGROUND: Reports of liver transplantation (LT) in patients with mixed hepatocellular carcinoma/cholangiocarcinoma (HCC/CC) and intrahepatic cholangiocarcinoma (ICC) are modest and have been mostly retrospective after pathological categorization in the setting of presumed HCC. Some studies suggest that patients undergoing LT with small and unifocal ICC or mixed HCC/CC can achieve about 40%-60% 5-year post-transplant survival. The study aimed to report our experience in patients undergoing LT with explant pathology revealing HCC/CC and ICC. METHODS: From a prospectively maintained database, we performed cohort analysis. We identified 13 patients who underwent LT with explant pathology revealing HCC/CC or ICC. RESULTS: The observed recurrence rate post-LT was 31% (4/13) and overall survival was 85%, 51%, and 51% at 1, 3 and 5 years, respectively. Disease-free survival was 68%, 51%, and 41% at 1, 3 and 5 years, respectively. In our cohort, four patients would have qualified for exception points based on updated HCC Organ Procurement and Transplantation Network imaging guidelines. CONCLUSIONS: Lesions which lack complete imaging characteristics of HCC may warrant pre-LT biopsy to fully elucidate their pathology. Identified patients with early HCC/CC or ICC may benefit from LT if unresectable. Additionally, incorporating adjunctive perioperative therapies such as in the case of patients undergoing LT with hilar cholangiocarcinoma may improve outcomes but this warrants further investigation.

Mixed hepatocellular and cholangiocarcinoma: a rare tumor with a mix of parent phenotypic characteristics.

BACKGROUND: Intrahepatic lesions of mixed hepatocellular (HCC) and intrahepatic cholangiocellular carcinoma (ICC) histology are rare. The aim was to describe the natural history of these tumors relative to monomorphic ICC or HCC utilizing the National Cancer Data Base (NCDB). METHODS: Patients with ICC, HCC, and mixed histology (cHCC-CCA) were identified in the NCDB (2004-2012). Inter-group comparisons were made. Kaplan-Meier and multivariable Cox Proportional Hazards analyzed overall survival. RESULTS: The query identified 90,499 patients with HCC; 14,463 with ICC; and 1141 with cHCC-CCA histology. Patients with cHCC-CCA histology were relatively young (61 vs. 62 (HCC, p = 0.877) and 67 (ICC, p < 0.001) years) and more likely to have poorly differentiated tumor (29.2% vs. 10.3% (HCC) and 17.2% (ICC) p < 0.001). Median overall survival for cHCC-CCA was 7.9 months vs. 10.8 (HCC) and 8.2 (ICC, all p < 0.001). Stage-specific survival for mixed histology tumors was most similar to that of HCC for all stages. cHCC-CCA were transplanted at a relatively high rate, and transplant outcomes for mixed tumors were substantially worse than for HCC lesions. DISCUSSION: cHCC-CCA demonstrate stage-specific survival similar to HCC, but post-surgical survival more consistent with ICC. Patients with a pre-operative diagnosis of cHCC-CCA should undergo resection when appropriate.

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database.

BACKGROUND: Mixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC). METHODS: Retrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994-2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared. RESULTS: We identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002). DISCUSSION: Patients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively.

Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma.

BACKGROUND AND OBJECTIVES: Although transplantation has demonstrated survival benefit for patients with hepatocellular carcinoma (HCC), there is limited data to support or refute transplantation for combined hepatocellular-cholangiocarcinoma (cHCC-CC). We hypothesized that cHCC-CC patients had poorer overall survival (OS) than HCC patients after liver transplantation. METHODS: Patients with localized HCC and cHCC-CC treated with surgical resection or transplant were identified using the Surveillance, Epidemiology, and End Results (SEER) Database (1973-2007). Cox proportional hazards models were used to examine survival. RESULTS: We identified 3,378 (1,447 [43%] transplant, 1,931 [57%] resection) patients with HCC, and 54 (19 [35%] transplant, 35 [65%] resection) patients with cHCC-CC. Patients undergoing resection of HCC and cHCC-CC had similar 3-year OS (55% vs. 46%, P = 0.4). Three-year OS of patients undergoing transplant was significantly greater for HCC (78%) than for cHCC-CC (48%, P = 0.01). In adjusted models, patients transplanted for cHCC-CC had higher hazard of death compared to HCC patients (HR 2.5, 95% CI: 1.2-5.1, P = 0.01). CONCLUSIONS: Transplantation for localized cHCC-CC confers a survival benefit similar to liver resection for cHCC-CC, but inferior to transplantation for HCC. With survival data that mimics historic reports of transplant for intrahepatic cholangiocarcinoma, this study questions the benefit of transplantation for patients with cHCC-CC.

Varying malignant potential of appendiceal neuroendocrine tumors: importance of histologic subtype.

BACKGROUND: Neuroendocrine tumors (NETs) of the appendix include malignant carcinoid tumor (MCT), goblet cell carcinoid (GCT), and composite goblet cell carcinoid-adenocarcinoma (CGCC-A). METHODS: We compared characteristics and outcomes of these histologic subtypes. Patients with appendiceal NETs were identified from the National Cancer Database (1998-2007). Descriptive statistics were used to compare cohorts and associations between clinicopathologic factors and overall survival (OS) were examined using Cox proportional hazards models. RESULTS: A total of 2,812 patients with appendiceal NETs were identified. The most common histologic subtype was GCT (59.6%), followed by MCT (32.1%), CGCC-A (6.9%), and others (1.4%). CGCC-A had a significantly higher incidence of lymph node metastases (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.1-4.8) and distant metastases (OR, 6.0; 95% CI = 3.8-9.3) than GCT. The 5-year OS was 86.3% (95% CI, 81.4-89.9) for MCT, 77.6% (95% CI, 74.0-80.8) for GCT, and 56.3% (95% CI, 42.1-68.4) for CGCC-A (P < 0.0001). CONCLUSION: Appendiceal NETs represent a spectrum of disease with varying malignant potential: MCT (low), GCT (intermediate), and CGCC-A (high). GCTs represent the most common subtype, whereas CGCC-As place the patient at highest risk for regional and distant metastases and have the worst prognosis.

Signet ring cell mixed histology may show more aggressive behavior than other histologies in early gastric cancer.

BACKGROUND: Signet ring cell carcinoma (SRC) of the stomach is known to have different microscopic and biologic characteristics compared to non-SRC. The pathologic report has documented partly SRC component with main histologies. However, the clinical significance of SRC mixture has not been reported. Aim was to investigate clinicopathologic features of mixed-SRC histology in early gastric cancer (EGC). METHODS: Two thousand two hundred eight patients were diagnosed with EGC and underwent surgery. The patients were divided into three groups such as adenocarcinoma with partly SRC (mixed-SRC group), only adenocarcinoma (adenocarcinoma group), and SRC (SRC group). Clinicopathologic characteristics were compared. RESULTS: The SRC group was more associated with younger age, female, mid-body, mucosa-confined, depressed type, lower lymph node metastasis (LNM), lower lymphovascular invasion, and better survival rate than adenocarcinoma group. The mixed-SRC group was more associated with younger age, female, upper-body, and depressed type than adenocarcinoma group, similar to SRC group. However, the mixed-SRC group showed more submucosal invasion, larger size, and higher LNM than other groups. The mixed-SRC component was one of the independent risk factors of LNM. CONCLUSIONS: Mixed-SRC histology in EGC showed more aggressive behavior than other histologies. Clinical considerations of mixed-SRC histology may be helpful to decide on a specific cancer treatment.

Solid-pseudopapillary neoplasms of the pancreas: clinical and pathological features of 33 cases.

PURPOSE: Solid-pseudopapillary neoplasms (SPNs) are rare pancreatic tumors, with a low potential for malignancy. The clinical and pathological features of 33 SPNs were reviewed. METHODS: This study conducted a retrospective analysis of 33 patients who underwent surgery for a pathologically confirmed SPN from 2000 to 2011. RESULTS: Thirty of the 33 patients (91 %) were female, and the median age at diagnosis was 29.2 years (range 12-59). The most common symptom was abdominal discomfort with dull pain (58 %). Others included asymptomatic lesions that were only detected incidentally during imaging (21 %), a palpable abdominal mass (15 %) and indigestion (6 %). All 33 patients underwent surgery with a curative intent and 3 (9 %) underwent laparoscopic surgery. The mean diameter of the tumors was 4.9 cm (range 2-15 cm), and they occurred in the head (9, 27 %), neck (5, 15 %), body or tail (19, 58 %) of the pancreas. One patient had lymph node metastases, one patient had portal venous invasion and 8 patients had perineural invasion. The patient follow-up ranged from 4 to 118 months, and 32 patients were alive and well without recurrence. One patient relapsed 10 months after distal pancreatectomy with splenectomy and underwent a second surgery via laparotomy. Unfortunately, the patient died of multiple organ failure 12 days after the second surgery. CONCLUSION: SPNs are rare neoplasms with malignant potential but excellent prognosis. Adequate surgical resection, including laparoscopic surgery, may therefore be performed safely and is associated with a long-term survival, even in invasive cases.

Multi-Center Analysis of Liver Transplantation for Combined Hepatocellular Carcinoma-Cholangiocarcinoma Liver Tumors.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma liver tumors (cHCC-CCA) with pathologic differentiation of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma within the same tumor are not traditionally considered for liver transplantation due to perceived poor outcomes. Published results are from small cohorts and single centers. Through a multicenter collaboration, we performed the largest analysis to date of the utility of liver transplantation for cHCC-CCA. STUDY DESIGN: Liver transplant and resection outcomes for HCC (n = 2,998) and cHCC-CCA (n = 208) were compared in a 12-center retrospective review (2009 to 2017). Pathology defined tumor type. Tumor burden was based on radiologic Milan criteria at time of diagnosis and applied to cHCC-CCA for uniform analysis. Kaplan-Meier survival curves and log-rank test were used to determine overall survival and disease-free survival. Cox regression was used for multivariate survival analysis. RESULTS: Liver transplantation for cHCC-CCA (n = 67) and HCC (n = 1,814) within Milan had no significant difference in overall survival (5-year cHCC-CCA 70.1%, HCC 73.4%, p = 0.806), despite higher cHCC-CCA recurrence rates (23.1% vs 11.5% 5 years, p < 0.001). Irrespective of tumor burden, cHCC-CCA tumor patient undergoing liver transplant had significantly superior overall survival (p = 0.047) and disease-free survival (p < 0.001) than those having resection. For cHCC-CCA within Milan, liver transplant was associated with improved disease-free survival over resection (70.3% vs 33.6% 5 years, p < 0.001). CONCLUSIONS: Regardless of tumor burden, outcomes after liver transplantation are superior to resection for patients with cHCC-CCA. Within Milan criteria, liver transplant for cHCC-CCA and HCC result in similar overall survival, justifying consideration of transplantation due to the higher chance of cure with liver transplantation in this traditionally excluded population.

The prognosis of invasive ductal carcinoma, lobular carcinoma and mixed ductal and lobular carcinoma according to molecular subtypes of the breast.

BACKGROUND: To investigate the prognosis of females with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) according to hormone receptor (HR) and HER2 status. METHODS: Data of 171,881 patients from the SEER database were analyzed. Propensity score matching was used to balance the covariates. Breast cancer-specific survival (BCSS) and overall survival (OS) of IDC, ILC, and IDLC were investigated. RESULTS: Patients with ILC were older, had lower tumor grade, higher tumor stage, larger tumor size, more nodal metastasis, higher estrogen receptor(+), lower HER2(-), and less likely to receive partial mastectomy and chemotherapy compared with IDC and IDLC. ILC and IDLC showed better prognosis than IDC after matching by Kaplan-Meier curves. Multivariate Cox regression showed better OS of ILC and IDLC compared with IDC with hazard ratio and a 95% confidence interval of 0.84 (0.77-0.90) and 0.91 (0.83-1.00), respectively. For HR(+)HER2(-) subgroup, ILC showed better OS than IDC; IDC showed worse BCSS and OS than IDLC. For HR(+)HER2(+); ILC showed better OS compared with IDLC; there were no survival differences of IDC, ILC, and IDLC for HER2(+). For HR(-)HER2(-), ILC and IDC showed better BCSS and OS compared with IDLC by multivariate analysis. CONCLUSIONS: The prognoses of female patients with IDC, ILC or IDLC were associated with the molecular subtypes of breast carcinoma. Management decisions should be based on pathological types and molecular subtypes.

Combination of Pembrolizumab With Platinum-containing Chemotherapy for Pleomorphic Carcinoma of the Lung.

BACKGROUND/AIM: Pleomorphic carcinoma of the lung is a rare, highly malignant subtype of lung cancer, with a more aggressive clinical course compared with other types of non-small-cell lung cancer (NSCLC). Platinum-containing chemotherapy has been the standard therapy for patients with NSCLC and pembrolizumab is one of the novel and reliable agents for these patients. CASE REPORT: We herein report the case of a 60-year-old man with advanced chemo-naïve pleomorphic carcinoma of the lung who was successfully treated with a combination of pembrolizumab with platinum-containing chemotherapy. CONCLUSION: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of this tumor, our case demonstrates the potential utility of the combination of pembrolizumab with platinum-containing chemotherapy. Our result also suggest that this combination of therapy may be key to the treatment of pleomorphic carcinoma of the lung.

Predictors of Lymph Node Metastasis and Differences Between Pure and Mixed Histologic Types of Early Gastric Signet-ring Cell Carcinomas.

The aim of this study was to investigate predictors of lymph node metastasis (LNM) in early gastric signet-ring cell carcinoma (SRCC) and determine clinicopathologic and prognostic differences of different histologic subtypes. We retrospectively analyzed 13,661 gastric cancer patients; 231 were eligible for inclusion. Data for clinical, endoscopic, and histopathologic characteristics and prognoses were collected. Patients were followed up regarding postresection survival; overall and disease-specific survival rates were estimated by the Kaplan-Meier method with a log-rank test, and prognostic factors were evaluated by Cox regression. LNM incidence in early SRCC was 16.0% (37/231) overall: 6.9% (8/116) and 25.2% (29/115) in patients with pure and mixed SRCC, respectively. Univariate and multivariate analyses revealed SM2 invasion (odds ratio [OR]=5.070, P=0.003), lymphovascular invasion (LVI) (OR=14.876, P<0.001), pathologic pattern of mixed SRCC (OR=3.226, P=0.026), ulcer presence (OR=3.340, P=0.019) and lesion size over 20 mm (OR=2.823, P=0.015) as independent risk factors for LNM. Compared with pure SRCC, the mixed subtype was associated with older age, larger lesion size, higher LVI frequency, more frequent perineural invasion, and most importantly, higher LNM incidence. Patients with pure SRCC showed significantly longer overall survival (P=0.004) and disease-specific survival (P=0.002) than mixed SRCC patients. Pathologic subtype (hazard ratio [HR]=3.682; P=0.047), age (HR=5.246; P=0.001), SM1 invasion (HR=6.192; P=0.023), SM2 invasion (HR=7.529; P=0.021) and LNM (HR=5.352; P<0.001) were independent prognostic factors. Independent risk factors for LNM in early gastric SRCC were SM2 invasion, LVI, pathologic pattern, ulcer presence and lesion size over 20 mm. Early SRCC should be further classified by the purity of the SRC component.

Gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC): An immunohistochemistry study of 13 microsatellite stable cases.

BACKGROUND: Mixed adenoneuroendocrine carcinoma (MANEC) is currently included in the category of neuroendocrine carcinomas but the therapeutically management is not yet defined. AIMS: To present the immunohistochemical (IHC) features of the epithelial mesenchymal transition (EMT) of MANEC. MATERIALS AND METHODS: The clinicopathological features of 13 consecutive cases of MANEC (6 gastric and 7 colorectal) were correlated with the IHC expression of the biomarkers E-cadherin, ß-catenin, N-cadherin, vimentin, maspin, CD44 and S100. In all of the cases open surgery was performed. RESULTS: All of the cases showed microsatellite stable status, expressed E-cadherin and membrane ß-catenin in both components (neuroendocrine and adenocarcinoma) and were negative for N-cadherin, vimentin and S-100. The colorectal MANECs were negative for maspin. In gastric MANECs, maspin showed cytoplasm positivity in the neuroendocrine component and nuclear translocation in the adenocarcinoma cells. CD44 was positive in all of the cases, in both components. No tumor buddings were identified. Three of the 13 patients survived for at least 32 months, all of them showing lymphatic emboli but not lymph node metastases. Pure neuroendocrine lymph node metastases were seen in only four of the cases: one from stomach, two of the ascending colon and two cases of the upper rectum. CONCLUSIONS: Gastrointestinal MANEC is a microsatellite stable tumor with nodular growth, which components might originate from a CD44-positive stem-like precursor cell. Lymph node status remains the most reliable prognostic parameter and agressivity seems to not be influenced by tumor budding degree or EMT-related features. The histologic aspect of metastatic component (neuroendocrine versus adenocarcinoma) should be included in the histopathological reports and might be used for establishing the proper-targeted therapy of MANEC.

Sarcomatoid carcinomas of the gallbladder: clinicopathologic characteristics.

Sarcomatoid carcinomas recently came into the spotlight through genetic profiling studies and also as a distinct model of epithelial-mesenchymal transition. The literature on sarcomatoid carcinomas of gallbladder is limited. In this study, 656 gallbladder carcinomas (GBC) were reviewed. Eleven (1.7%) with a sarcomatoid component were identified and analyzed in comparison with ordinary GBC (O-GBC). Patients included 9 females and 2 males (F/M = 4.5 vs. 3.9) with a mean age-at-diagnosis of 71 (vs. 64). The median tumor size was 4.6 cm (vs. 2.5; P = 0.01). Nine patients (84%) presented with advanced stage (pT3/4) tumor (vs. 48%). An adenocarcinoma component constituting 1-75% of the tumor was present in nine, and eight had surface dysplasia/CIS; either in situ or invasive carcinoma was present in all cases. An intracholecystic papillary-tubular neoplasm was identified in one. Seven showed pleomorphic-sarcomatoid pattern, and four showed subtle/bland elongated spindle cells. Three had an angiosarcomatoid pattern. Two had heterologous elements. One showed few osteoclast-like giant cells, only adjacent to osteoid. Immunohistochemically, vimentin, was positive in six of six; P53 expression was > 60% in six of six, keratins in six of seven, and p63 in two of six. Actin, desmin, and S100 were negative. The median Ki67 index was 40%. In the follow-up, one died peri-operatively, eight died of disease within 3 to 8 months (vs. 26 months median survival for O-GBC), and two were alive at 9 and 15 months. The behavior overall was worse than ordinary adenocarcinomas in general but was not different when grade and stage were matched. In summary, sarcomatoid component is identified in < 2% of GBC. Unlike sarcomatoid carcinomas in the remainder of pancreatobiliary tract, these are seldom of the "osteoclastic" type and patients present with large/advanced stage tumors. Limited data suggests that these tumors are aggressive with rapid mortality unlike pancreatic osteoclastic ones which often have indolent behavior.

Efficacy of mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) in patients with advanced pulmonary pleomorphic carcinoma.

OBJECTIVES: Pulmonary pleomorphic carcinoma (PC) is a rare type of lung tumor with a dismal prognosis. There is no consensus on a chemotherapy regimen for PC, and conventional platinum-based chemotherapy has been associated with disappointing response rates and PFS. In searches for a new regimen, the sarcomatoid (spindle or giant cell) component has been assumed to be susceptible to chemotherapy used for soft tissue sarcoma. MATERIALS AND METHODS: The medical records of 17 patients who received mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for advanced PC between January 2010 and February 2017 were retrospectively analyzed for clinicopathological features and outcomes. RESULTS AND CONCLUSION: The median age was 59 years. Sixteen patients were male, and only one patient had never smoked. Six patients achieved partial response to MAID, leading to an objective response rate of 35%. The median PFS was 2.8 months, and the median OS was 8.7 months. Hematologic toxicity-related adverse events were the most frequent, which comprised grade 3-4 anemia in 35% of patients, neutropenia in 47%, thrombocytopenia in 24%, and febrile neutropenia in 29%. No febrile neutropenia was reported in patients who received 5-day granulocyte-colony stimulating factor (G-CSF) prophylaxis. Most adverse events resolved without complications, except for one death due to sepsis. MAID is an effective, and possibly important, regimen for PC. MAID could be more safely used in clinical practice with appropriate dose modifications and G-CSF primary prophylaxis according to patients' status.