Small Vessel Invasion Research Articles

Prognostic performance of microscopic size measurements in small invasive carcinomas arising in intraductal papillary mucinous neoplasms of the pancreas.

Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication. In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes. The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis. For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis.

The Prognostic Reliability of Lymphovascular Invasion for Patients with T3N0 Colorectal Cancer in Adjuvant Chemotherapy Decision Making

Simple SummaryThis retrospective analysis evaluated the prognostic implications of lymphovascular invasion (LVI) associated with adjuvant chemotherapy in 1634 patients with pT3N0 colorectal cancer. Extensive pathologic review and dual immunohistochemical (IHC) staining with CD31 and D2-40 were undertaken in a subset of 242 patients to determine the reliability of LVI as a prognostic factor. The diagnosis of LVI and PNI changed in 82 (33.9%) and 61 (25.2%) patients, respectively, after central pathologic review (mean follow up duration, 50 (1–114) months). Five-year recurrence-free survival (RFS) and overall survival (OS) rates were 92% and 94.8%, respectively. Before and after pathologic review, LVI was not associated with OS but was associated with RFS after reviewing patients with pT3N0 colorectal cancer. In this patient cohort, the prognostic implications of LVI may have been underrecognized when using hematoxylin and eosin staining slides only for pathologic diagnoses, possibly leading to low recurrence prediction rates.Lymphovascular invasion (LVI) is a high-risk feature guiding decision making for adjuvant chemotherapy. We evaluated the prognostic importance and reliability of LVI as an adjuvant chemotherapy indicator in 1634 patients with pT3N0 colorectal cancer treated with curative radical resection between 2012 and 2016. LVI and perineural invasion (PNI) were identified in 382 (23.5%) and 269 (16.5%) patients, respectively. In total, 772 patients received adjuvant chemotherapy. The five-year recurrence-free survival (RFS) and OS rates were 92% and 94.8%, respectively. Preoperative obstruction, PNI, and positive margins were significantly associated with RFS and OS; however, adjuvant chemotherapy and LVI were not. Pathologic slide central reviews of 242 patients using dual D2-40 and CD31 immunohistochemical staining was performed. In the review cohort, the diagnosis of LVI and PNI was changed in 82 (33.9%) and 61 (25.2%) patients, respectively. Reviewed LVI, encompassing small vessel invasion, lymphatic invasion, and large vessel invasion, was not an independent risk factor associated with OS but was related to RFS. The prognostic importance of LVI and adjuvant chemotherapy was not defined because LVI may be underrecognized in pathologic diagnoses using hematoxylin and eosin staining slides only, leading to low recurrence rate predictions. Using LVI as a guiding factor for adjuvant chemotherapy requires further consideration.

Ampullary Neuroendocrine Neoplasms: Identification of Prognostic Factors in a Multicentric Series of 119 Cases

Neuroendocrine neoplasms (NENs) of the major and minor ampulla are rare diseases with clinico-pathologic features distinct from non-ampullary-duodenal NENs. However, they have been often combined and the knowledge on prognostic factors specific to ampullary NENs (Amp-NENs) is limited. The aim of this study was to identify factors associated with metastatic potential and patient prognosis in Amp-NENs. We clinically and histologically investigated an international series of 119 Amp-NENs, comprising 93 ampullary neuroendocrine tumors (Amp-NETs) and 26 neuroendocrine carcinomas (Amp-NECs). Somatostatin-producing tubulo-acinar NET represented the predominant Amp-NET histologic subtype (58 cases, 62%, 12 associated with type 1 neurofibromatosis). Compared to Amp-NETs, Amp-NECs arose in significantly older patients and showed a larger tumor size, a more frequent small vessel invasion, a deeper level of invasion and a higher rate of distant metastasis, and, importantly, a tremendously worse disease-specific patient survival. In Amp-NETs, the WHO grade proved to be a strong predictor of disease-specific survival (hazard ratio: 12.61, p < 0.001 for G2 vs G1), as well as patient age at diagnosis > 60 years, small vessel invasion, pancreatic invasion, and distant metastasis at diagnosis. Although nodal metastatic disease was not associated with survival by itself, patients with > 3 metastatic lymph nodes showed a worse outcome in comparison with the remaining Amp-NET cases with lymphadenectomy. Tumor epicenter in the major ampulla, small vessel invasion, and tumor size > 16 mm were independent predictors of nodal metastases in Amp-NETs. In conclusion, we identified prognostic factors, which may eventually help guide treatment decisions in Amp-NENs.

Tumor Size, Not Small Vessel Invasion, Predicts Survival in Patients With Hepatocellular Carcinoma.

The 8th edition American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been criticized for failing to stratify patients. We aimed to reassess and modify the tumor staging criteria for HCC. Three independent study cohorts were collected and analyzed. The initial cohort consists of 103 patients with HCC. By Kaplan-Meier survival analysis, the 8th edition failed to distinguish between T1b and T2. Only tumor size and large vessel invasion, but not small vessel invasion or other histopathologic parameters, predicted HCC survival. We modified the T staging criteria by eliminating small vessel invasion while emphasizing tumor size in the middle categories (T2 and T3), which achieved more even distribution of cases and significantly improved risk stratifications (P < .001). This modification was then validated in a cohort of 250 consecutive patients from Mount Sinai Hospital and an online Surveillance, Epidemiology, and End Results data set comprising 9,685 patients, which showed similar results. Small vessel invasion was not an independent prognostic factor in either validation cohort. Our study showed that tumor size, but not small vessel invasion, predicts survival in patients with HCC. We suggest incorporating our modified T staging criteria in future AJCC revisions.

Overexpression of Forkhead Box O3a and Its Association With Aggressive Phenotypes and Poor Prognosis in Human Hepatocellular Carcinoma.

Recent research has demonstrated that forkhead box O3a (FoxO3a) may function as an oncogenic transcription factor. We sought to validate the clinicopathologic significance of FoxO3a expression in hepatocellular carcinoma (HCC). Western blotting and immunohistochemistry were used to determine FoxO3a expression. In vitro cell proliferation and migration assays were performed in a HepG2 cell line. FoxO3a was overexpressed in 121 (64.71%) cases of HCC. FoxO3a overexpression was associated with aggressive phenotypes of HCC, such as histologic grade (P < .001), stage (P = .031), and small vessel invasion (P < .001). FoxO3a overexpression was also correlated with poor disease-free survival in both univariate and multivariate survival analyses (P = .001 and P = .018, respectively). Downregulation of FoxO3a in a HepG2 cell line inhibited cell proliferation and migration. These results suggest a role for FoxO3a in HCC progression and support the potential use as a prognostic biomarker.

Diagnostic and prognostic relevance of CP2c and YY1 expression in hepatocellular carcinoma.

Recent studies have demonstrated an oncogenic role of the transcription factor (TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c directly interacts with another TF, YY1, which is also overexpressed in multiple cancers, including HCC. To evaluate if these proteins are co-regulated in carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136) tissues and examined the correlation between their expression and clinicopathological characteristics of HCC. Receiver operating characteristic analysis exhibited the validity of CP2c and nuclear YY1 expression as a diagnostic factor in HCC tissues. High expression of CP2c was significantly correlated with patient age, and higher histological grade, American Joint Committee on Cancer (AJCC) stage, and small and large vessel invasion in HCC tissues, whereas high expression of nuclear YY1 was significantly associated with higher AJCC stage and small vessel invasion. In univariate and multivariate analyses, high expression of CP2c was significantly correlated with disease free survival (DFS), indicating that CP2c expression is an independent prognostic factor for DFS in HCC patients. Patients with high expression of both CP2c and nuclear YY1 usually had a shorter median survival time and worse DFS prognosis than other patients, suggesting that combined detection of CP2c and nuclear YY1 is a useful prognostic marker in HCC patients.

Features Associated With Metastases Among Well-Differentiated Neuroendocrine (Carcinoid) Tumors of the Appendix: The Significance of Small Vessel Invasion in Addition to Size.

The risk of metastatic disease among carcinoid tumors of the appendix increases with tumor size. However, it is unclear if any features other than size are also associated with an increased risk of metastatic disease. The aim of this study was to review the characteristics of appendiceal carcinoid tumors and determine if other histologic features besides size should guide surgical decision making. This study involved a retrospective case series. This study was conducted at a single tertiary acute care hospital. Patients diagnosed with an appendiceal carcinoid tumor between 2000 and 2014 were identified. Goblet cell carcinoids, adenocarcinomas with neuroendocrine features, and tumors from other primary locations were excluded. Simple appendectomy or segmental/total colectomy with lymphadenectomy was performed. The primary outcomes measured were metastases, recurrence, and overall survival. Seventy-nine patients were included. The overall incidence of metastatic disease was 10%. Patients with metastatic disease were more likely to be male (75% vs 28%, p = 0.008), have small-vessel invasion (43% vs 5%, p = 0.001), and have larger tumors (median 2.0 cm vs 0.5 cm, p < 0.001). Among tumors <2 cm, the incidence of metastases among tumors with small-vessel invasion was 60% compared with 0% among those without small-vessel invasion (p < 0.001). Among tumors ≥2 cm, the incidence of metastases was 50% irrespective of small-vessel invasion. If small-vessel invasion was used as a second indication for performing a right hemicolectomy along with size ≥2 cm, both the sensitivity and negative predictive value would have been 100% compared with 63% and 96% if size was used alone. Patients with metastatic disease had a higher incidence of recurrence (13% vs 0%, p = 0.003), but overall survival was 100% in both groups. Small sample size, retrospective design, and limited long-term follow-up were the limitations of this study. Carcinoid tumors of the appendix <2 cm with small-vessel invasion have similar metastatic potential as tumors ≥2 cm. Therefore, a recommendation for a right hemicolectomy should be considered for tumors <2 cm with small-vessel invasion. Additional prospective multicenter studies are warranted.

Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance.

A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1–10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ≥3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making.

Grading of Well-differentiated Pancreatic Neuroendocrine Tumors Is Improved by the Inclusion of Both Ki67 Proliferative Index and Mitotic Rate

The grading system for pancreatic neuroendocrine tumors (PanNETs) adopted in 2010 by the World Health Organization (WHO) mandates the use of both mitotic rate and Ki67/MIB-1 index in defining the proliferative rate and assigning the grade. In cases when these measures are not concordant for grade, it is recommended to assign the higher grade, but specific data justifying this approach do not exist. Thus, we counted mitotic figures and immunolabeled, using the Ki67 antibody, 297 WHO mitotic grade 1 and 2 PanNETs surgically resected at a single institution. We quantified the Ki67 proliferative index by marking at least 500 cells in "hot spots" and by using digital image analysis software to count each marked positive/negative cell and then compared the results with histologic features and overall survival. Of 264 WHO mitotic grade 1 PanNETs, 33% were WHO grade 2 by Ki67 proliferative index. Compared with concordant grade 1 tumors, grade-discordant tumors were more likely to have metastases to lymph node (56% vs. 34%) (P<0.01) and to distant sites (46% vs. 12%) (P<0.01). Discordant mitotic grade 1 PanNETs also showed statistically significantly more infiltrative growth patterns, perineural invasion, and small vessel invasion. Overall survival was significantly different (P<0.01), with discordant mitotic grade 1 tumors showing a median survival of 12 years compared with 16.7 years for concordant grade 1 tumors. Conversely, mitotic grade 1/Ki67 grade 2 PanNETs showed few significant differences from tumors that were mitotic grade 2 and either Ki67 grade 1 or 2. Our data demonstrate that mitotic rate and Ki67-based grades of PanNETs are often discordant, and when the Ki67 grade is greater than the mitotic grade, clinical outcomes and histopathologic features are significantly worse than concordant grade 1 tumors. Patients with discordant mitotic grade 1/Ki67 grade 2 tumors have shorter overall survival and larger tumors with more metastases and more aggressive histologic features. These data strongly suggest that Ki67 labeling be performed on all PanNETs in addition to mitotic rate determination to define more accurately tumor grade and prognosis.

Differences in the prognostic implications of vascular invasion between lung adenocarcinoma and squamous cell carcinoma

ObjectivesVascular invasion (VI) has been accepted as a universally important prognostic factor for patients with lung carcinoma. However, the clinical significance of VI in each of the histological subtypes has been unclear. The aim of the present study was to investigate differences in the clinicopathological implications of VI between adenocarcinoma and squamous cell carcinoma. MethodA total of 336 patients were evaluated, of whom 81 were diagnosed as having peripheral-type squamous cell carcinoma, and 255 as having adenocarcinoma. ResultAmong the 336 patients, the five-year survival rates for those who were VI-positive and VI-negative were 38.4% and 76.3%, respectively, the difference being significant (p<0.0001). Multivariate analysis identified VI as an independent prognostic factor (hazard ratio: 1.86). Although the difference in cancer-free survival between VI-positive and -negative patients was statistically significant for adenocarcinoma (p<0.0001), it was not significant for squamous cell carcinoma (p=0.086). For adenocarcinoma, the difference between the survival curves for VI-positive and -negative patients was significant for the subtypes with a predominant lepidic (p<0.0001), papillary (p=0.0026), and acinar (p=0.0060) component, whereas that for the predominantly solid subtype was not significant (p=0.58). Squamous cell carcinomas were then divided into two groups on the basis of the diameter of vessels that had been invaded by the cancer cells: large-vessel invasion (LVI; 1000μm or more) and small-vessel invasion (SVI; less than 1000μm). Although there was no difference in the survival curves between the LVI and SVI groups, the LVI group showed a significantly higher incidence of cavity formation and distant metastasis. ConclusionWe conclude that VI is a useful prognostic indicator in lung carcinoma, although the clinical implications of VI differ between adenocarcinoma and squamous cell carcinoma.

A Rare Case of Hepatocellular Carcinoma in Addition to Diffused Cirrhosis-like HCC

Purpose: Hepatocellular carcinoma (HCC) usually arises from underlying chronic liver disease and cirrhosis. Diffused cirrhosis like HCC is a rare variant of carcinoma, especially when diagnosed after liver transplant in the explanted liver. Only one case in a series of 10 patients studied has been reported. We presented the case of a 62-year-old Caucasian male who came to our clinic for a liver transplant evaluation. He was diagnosed with Hepatitis C 17 years ago and treated with interferon/ribavirin for 6 months, but was a poor responder. He used to be a heavy drinker but quit 30 years ago and has a past medical history of IV heroin abuse. His physical exam showed no ascites, hepatomegaly or splenomegaly. His laboratory findings included a normal basic metabolic panel with an AST of 115, ALT 227, alkaline phosphatase of 63, GGT of 81, bilirubin of 0.5, and INR of 1.1. His MELD score on his initial visit was 7 with an AFP level of 4.7. Two and a half years later, he was diagnosed with a single 5 × 5.3 cm lesion HCC. A liver biopsy confirmed the diagnosis of both HCC and cirrhosis. He then had a Radio Frequency Ablation (RFA) of the lesion followed by Transcatheter Arterial Chemoembolization (TACE) with LC Beads loaded with Doxorubicin. The lesion decreased to 3.4 × 3 cm, meeting the Milan criteria for liver transplant. His AFP pre- and post- RFA/TACE were 3.9 and 4.7, respectively. He then went for an orthotopic liver transplant. The gross examination of the explanted liver showed multiple yellow and green nodules, as seen in the picture attached, as well as a necrotic mass in the right lobe consistent with the previously treated HCC. The pathology showed well differentiated HCC with multiple nodules consistent with diffused cirrhosis-like variant of HCC. At least 70 viable tumor nodules were seen on the pathology slides, correlating with several hundred seen on the gross specimen. Small or large vessel invasion of the tumor was not identified. This is the first case reported of a single HCC lesion after transplant with underlying diffused cirrhosis-like HCC diagnosed in the explant. Liver transplant seems to be the definite treatment for these cases.Figure: No Caption available.

Chromophobe Renal Cell Carcinoma

Despite multiple studies, many clinicopathologic issues about chromophobe renal cell carcinoma (RCC) remain contentious; for example, its biological behavior-whether better or similar to papillary RCC, the incidence of sarcomatoid features, and whether pathologic features such as necrosis, nuclear grade, and tumor stage predict worse outcome. We studied 203 consecutive primary chromophobe RCCs resected at our institution in an attempt to answer these and other questions. The tumors showed significant progressive decrease in size and stage (P=0.047 and 0.001) from 1980 to 2000. Five patients had metastasis at presentation, and further disease-specific events (recurrence/metastasis/death due to disease) occurred in 8 more. Only 4 of 203 tumors had sarcomatoid features. Over median follow-up of 6.1 years (range, 0.1 to 18 y), 5-year and 10-year disease-specific events occurred in 3.7% (95% CI, 1.5%, 7.4%) and 6.4% (95% CI, 2.7%, 12.2%) patients. Outcomes showed significant association with tumor size, small-vessel invasion, sarcomatoid features, and microscopic necrosis (P≤0.05 each). pT stage or nodal metastasis tended to show some association, without reaching statistical significance (P=0.05 and 0.06, respectively). A modified tumor grading scheme, somewhat similar to that proposed recently, mitotic index, cytologic eosinophilia, and architecture, were not significantly associated with outcome. In conclusion, sarcomatoid differentiation is quite uncommon in chromophobe RCC. Tumor size, small-vessel invasion, sarcomatoid differentiation, and microscopic necrosis are the only features that are significantly associated with adverse outcome. On the basis of this long follow-up on a large number of cases, chromophobes seem to have better clinical outcomes than those reported for clear cell and papillary RCCs.

Determining the Need for Radical Surgery in Patients With T1 Rectal Cancer

In the era of modern preoperative staging of patients with rectal cancer, lymph node metastases can be reliably predicted by the histological features of the tumor and preoperative imaging. Local resection can then be safely offered to the patients who are at low risk of having malignant lymph nodes. We reviewed the records of 109 consecutive patients with preoperative imaging results suggestive of T1N0 or T2N0 disease who underwent total mesorectal excision. All patients underwent preoperative endorectal ultrasonography or magnetic resonance imaging and computed tomography, with or without positron emission tomography. Final pathologic investigation identified T3 disease in 27 patients. History, physical examination results, and radiologic and pathologic data were evaluated for predictors of positive nodes in the remaining 82 patients. Tertiary care referral center. Patients with preoperative imaging suggestive of T1N0 or T2N0 rectal cancer. To evaluate different clinical and pathologic tumor features as predictors of positive lymph nodes in T1 and T2 rectal cancers with negative radiographic nodes. Local resection of T1 and T2 rectal cancer results in lower morbidity compared with radical resection. However, recurrence rates after local resection are higher, likely owing to unresected nodal metastasis. Reports on predictors of lymph node metastasis remain inconsistent in the literature. Although local resection may be appropriate for some rectal cancers, selection criteria remain unclear. Despite indications of negative nodes on radiographic examination, 4 of 35 patients with T1 disease (11%) and 13 of 47 with T2 disease (28%) had positive nodes. On univariate analysis, the only significant predictor was depth of invasion: 24 of 65 patients with negative nodes (37%) vs 13 of 17 patients with positive nodes (76%) had tumors invading the lower third of the submucosa and beyond (P = .02). On logistic regression analysis accounting for depth of invasion (lower third of the submucosa and beyond), size, distance from anal verge, differentiation, and lymphovascular and small-vessel invasion, only depth of invasion remained a significant predictor. In all, 89% of patients with T1 disease (31 of 35) and 72% of those with T2 disease (34 of 47) underwent unnecessary radical resection. Endorectal ultrasonography or magnetic resonance imaging and computed tomography, with or without positron emission tomography, for preoperative staging could not identify these patients reliably. In addition, histologic markers of aggressive disease were not helpful. Thus, local resection for T2 rectal cancer is not justified. Local resection should be offered only to patients with superficial T1 tumors who will adhere to aggressive postoperative surveillance.

Diffuse Cirrhosis-like Hepatocellular Carcinoma

A rare variant of hepatocellular carcinoma (HCC) is encountered that produces small cirrhosis-like nodules diffusely throughout the liver (CL-HCC), instead of a larger evident mass. This pattern remains undetected as carcinoma clinically and radiographically and is unexpectedly discovered after liver transplantation in the explanted native liver. We studied 10 such cases (9 males and 1 female, age 35 to 80 y) from 4 medical centers. The pretransplant clinical, laboratory, and radiographical studies were reviewed to determine the cause and stage of liver disease, alpha-fetoprotein (AFP) levels, and detectability of a mass on imaging. All 10 cases had underlying cirrhosis of varying etiology [3 hepatitis C virus (HCV), 3 alcoholic hepatitis, 1 hepatitis B virus, 1 autoimmune, and 2 mixed HCV/alcoholic hepatitis and hemochromatosis/HCV] and underwent orthotopic liver transplantation with no preoperative clinical suspicion of HCC. Ultrasound and/or dynamic imaging showed cirrhosis and no definite HCC. AFP levels were only mildly elevated in only 3 of 10 cases (144, 150, and 252 ng/mL). Grossly, there were innumerable (from about 20 to >1000) small CL-HCC nodules (0.2 to 0.6 cm) scattered among cirrhotic nodules. Histologically, these were well or moderately differentiated HCC, often with pseudoglandular pattern, perinodular sclerotic rims, cholestasis, frequent Mallory bodies, and small vessel invasion. In addition to the usual HCC immunophenotype, CL-HCC showed frequent ubiquitin and cytoplasmic and membranous CD10 positivity, relatively low Ki-67 proliferative index and absence of AFP immunohistochemically. CL-HCC warrants recognition as a unique HCC variant that evades pretransplant detection despite massive tumor burden, mimics cirrhotic nodules, and shows some uncommon pathologic and immunophenotypical characteristics.

Prognostic factors for relapse in stage I seminoma managed with surveillance: A validation study.

4535 Background: A prognostic model for stage I seminoma managed by orchiectomy alone has limited predictive value since the high risk group has only a 30% relapse rate. Although the model has not been validated in an independent data set, it has been applied widely in treatment policies. We tested the value of the model in a consecutive series of patients managed by surveillance in the past decade. Methods: Individual data on 687 stage I seminoma patients managed by surveillance between 1998 and 2005 at the Copenhagen National Hospital, Princess Margaret Hospital and British Columbia Cancer Agency was retrospectively analyzed. Impact of age at diagnosis, original pathology [tumor size, histologic subtype, rete testis invasion, epidydimis, extratesticular soft tissue, spermatic cord, tunica albuginea, and small vessel invasion (SVI)] were analyzed for prognostic importance for relapse. The analysis was limited by missing data in significant proportion of reports [rete testis (33%), SVI (25%), tumor size 2...

4. A comparison of synoptic and free-text reporting in oesophageal carcinoma

Background Synoptic reporting of specimens of resected oesophageal carcinoma was introduced by the department of anatomical pathology at Royal North Shore Hospital (RNSH) in August 2007. Although synoptic reporting is widely regarded as resulting in better reporting quality, there is little hard evidence for this widespread belief. Aim The purpose of this study was to ascertain whether synoptic reporting of resected oesophageal carcinoma specimens resulted in better reporting of pertinent data for a single institution via the introduction of a minimum data set, compared with traditional free-text reporting. Methods 27 synoptic reports and 42 free-text reports from RNSH were compared. Results Tumour size was reported microscopically or macro-scopically in all synoptic reports and 38 (90.5%) free-text reports. Invasion depth was reported in all free-text reports and in 26 (96.3%) synoptic reports. Pathological stage was reported in only 4 (9.5%) free-text reports, compared to all synoptic reports. However, stage could be determined from all reports. Grade was reported in all synoptic reports, but not in 3 (7.1%) free text-reports. Surgical resection margins were reported at higher rates in the synoptic reports (in particular radial/circumferential margin), as were measurements of tumour to resection margins. Small vessel and perineural invasion were reported in all synoptic reports, but only 36 (85.7%) and 31 (73.8%) free-text reports, respectively. Degree of regression post-preoperative chemoradiation was reported in 25 (92.6%) synoptic reports, but only 8 (19%) free-text reports. Conclusion The introduction of synoptic reporting at RNSH has resulted in increased information being contained in surgical pathology reports.

Lymphovascular Invasion in Colorectal Cancer

Lymphovascular invasion (LVI) in colorectal cancer (CRC) is considered a strong stage-independent prognostic factor and influences decisions regarding adjuvant chemotherapy in patients with stage II tumors. However, the degree of interobserver agreement among pathologists for LVI in CRC is largely unknown. This study was undertaken to examine such interobserver variability, and we hypothesized that the use of immunohistochemical markers for vascular and lymphatic channels could improve interobserver agreement. Fifty cases of American Joint Committee on Cancer stage II moderately differentiated CRC from 1990 to 2005 from the pathology archives were selected; mucinous, medullary, and other recognized special subtypes were excluded. Fifty hematoxylin and eosin (H&E) slides (1 from each case) were circulated to 6 gastrointestinal pathologists, who independently assessed small and large vessel invasion. No diagnostic guidelines were given to the participating pathologists; each was instructed to apply the criteria for LVI that he or she used in daily practice. Immunohistochemistry (IHC) for D2-40 and CD31 was performed on corresponding paraffin blocks. The IHC slides were randomized, recirculated, and rescored for LVI. Results were analyzed by kappa (kappa) statistics, which correct for agreement by chance, and for percentage agreement. The average kappa values were determined for the H&E slides (large and small vessel), CD31 (small vessel), and D2-40 (small vessel) (Fig. 1). Agreement was fair for H&E small vessel invasion [kappa=0.28; 95% confidence interval (CI): 0.22-0.34]. The least agreement was seen in interpretation of H&E large vessel invasion (kappa=0.18; 95%CI: 0.11-0.26). Agreement was not improved by use of immunohistochemical stains: CD31 (large vessel, kappa=0.42, 95%CI: 0.20-0.63, small vessel, kappa=0.26, 95%CI: 0.10-0.42) and D2-40 (kappa=0.32, 95%CI: 0.21-0.42). Interobserver variability in diagnosis of LVI was substantial on H&E slides and did not improve upon use of IHC. Agreement in evaluation of large vessel invasion was only slightly higher than would be seen by chance alone. This study highlights the need for criteria in evaluation of LVI, as this assessment may impact patient prognosis and thus change the course of clinical treatment.

Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas.

The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.

Prognostic Factors for Relapse in Stage I Testicular Seminoma Treated With Surveillance

Purpose We sought to identify prognostic factors predictive of disease progression in patients with clinical stage I seminoma on surveillance following orchiectomy. Materials and Methods Between January 1981 and December 1993, 201 patients 20 to 86 years old (median age 34) with clinical stage I seminoma were placed on surveillance following orchiectomy. The potential prognostic factors studied included age, tumor size, mitotic count, S phase fraction, ploidy, presence of small vessel invasion, syncytiotrophoblasts and tumor infiltrating lymphocytes, expression of beta-human chorionic gonadotropin and low molecular weight keratin on immunohistochemistry. Results With a median followup of 6.1 years (range 1.3 to 12.3) 31 patients had relapse for an actuarial 5-year relapse-free rate of 84.9%. The 5-year actuarial survival rate was 97.1% and the cause specific survival rate was 99.5%. On univariate analysis factors predictive of relapse were tumor size (5-year relapse-free rate 88 and 67% for tumors 6 cm. or less and greater than 6 cm., respectively, p = 0.004), age (5-year relapse-free rate 79 and 91% for age 34 years or younger versus older than 34 years, respectively, p = 0.009) and presence of small vessel invasion (5-year relapse-free rate 86 versus 69%, p = 0.01). On multivariate analysis age and tumor size were predictive of relapse, while small vessel invasion approached statistical significance. The risk of relapse in 57 patients with none of the 3 adverse prognostic factors (age greater than 34 years, tumor 6 cm. or smaller and no small vessel invasion) was 6%. Conclusions We identified age, size of the primary tumor and small vessel invasion as important prognostic factors for relapse in patients with stage I seminoma treated with surveillance. Further followup and assessment of biological factors are needed to optimize selection of patients at a high risk for relapse who should receive immediate postoperative therapy.

Cytogenetic abnormalities and clinical stage in testicular nonseminomatous germ cell tumors

To study the impact of chromosomal abnormalities on the clinical behavior of testicular nonseminomatous germ cell tumors (TNSGCTs), we compared the chromosomal constitution of primary tumors of patients who initially presented and remained without metastases to those with metastatic disease. Furthermore, the chromosomal pattern of primary TNSGCTs was compared to ploidy and the clinicopathologic risk factors histology and small-vessel invasion. The modal chromosome number and the ploidy were in agreement. No correlation was found between the modal chromosome number and histology, presence of vascular invasion, or clinical stage. No correlation was found between structural chromosome abnormalities, like the number of copies of the i(12p) chromosome, and clinical stage. No obvious differences were found in chromosomal constitution of metastatic and non-metastatic tumors. The results of the present study suggest that in TNSGCTs differences in clinical behavior are not associated with gross chromosomal differences.