A diagnosis of recurrent lesion was made as new or progressive lesions confirmed by histologic and radiologic examination. Cases were further categorized into two groups according to the region of recurrent lesion: pelvic and extrapelvic recurrence. Depth of stromal invasion was evaluated after a microscopic examination by an experienced pathologist and was defined as more than 1 mm in depth of stromal, which is routinely accessed in our center.
According to the fractions of cervical wall thickness, depth of stromal invasion was expressed as inner third, middle third, outer third, full-thickness and outer full-thickness, which was routinely performed by the histopathologist in our center.
If the tumor was middle third infiltration, a specific description of either more than half infiltration or not was used. Full-thickness infiltration was defined as only the whole cervical invasion but no involvement of cervical-parametrial transition zone. Outer full-thickness invasion was used as the microscopic involvement of the cervical-parametrial transition zone without parametrial involvement was found. Thus, outer full-thickness invasion without positive parametrial margin is not regarded as the high-risk factor but only the intermediate risk predictors.
Patients in the cohort were categorized into three groups according to the specific depth of stromal invasion: inner full-thickness IF, middle third depth to full-thickness , full-thickness FT and outer full-thickness invasion OF. The probabilities of DFS, OS were calculated using the Kaplan-Meier method, and the log-rank test was further used to compare survival curves.
COX proportional hazards models were developed by forward, stepwise regression to identify independent predictors related to recurrence and survival. All analyses were carried out using SPSS software release Table 1 revealed the clinicopathological features of the patients. A total of 3, patients with postoperative deep stromal invasion were included. The median age of all patients was The majority of histological subtype was squamous cell carcinoma 2,, Approximately Overall, positive LVSI, lymph node metastasis, parametrial involvement, and vaginal margin invasion accounted for Among the whole cohort, 2, The association between the DSI and clinicopathological characteristics was shown in Table 1.
These results indicate that different depth of stromal invasion might present different biological behaviors. The median follow-up time range of all the patients was For the entire cohort, The patients with recurrent diseases had a median survival time of Statistically significant difference was observed when different depth of stromal invasion was compared.
On univariate analysis, histologic types, FIGO stage, depth of stromal invasion, tumor diameter, DSI, LVSI, lymph node metastasis, parametrial involvement, vaginal margin invasion, recurrence region, adjuvant radiotherapy and chemotherapy were significant predictors for both DFS and OS. View in new window. Univariate and multivariate analysis of the predictors for disease-free survival DFS and overall survival OS among the whole patients. Subgroup analysis was then performed in separate histologic type patients for both recurrence and survival Supplementary Tables 1 In patients with adenocarcinoma, only preoperative serum cancer antigen CA and lymph node metastasis were found to be independent prognostic factors for both DFS and OS Fig.
However, only preoperative serum cancer antigen CA and outer full-thickness invasion were found to be independently significant to OS in adenosquamous carcinoma Fig. In order to avoid the negative effect of high-risk factors on recurrence and survival, subgroup analysis was conducted among patients with isolated inter-mediate risk factors for recurrence and survival.
A total of 2, patients with one or more inter-mediate risk factors were included Table 3. The records of patients with isolated full-thickness invasion without any other unfavorable high and inter-mediate pathological findings were further analyzed. The majority of histological subtype was squamous cell carcinoma , A Disease-free survival, B overall survival among patients with squamous cell carcinoma for recurrence and survival. Multivariate analysis of the predictors for DFS and OS among patients with isolated full-thickness invasion without any other unfavorable pathological findings.
With a median follow-up of In addition, most majority of patients with early stage tumor present one or more intermediate-risk factors, including great tumor volume, LVSI, or DSI, which are closely related to recurrence.
These patients are often advised to receive adjuvant pelvic radiotherapy. Deep stromal invasion, defined as the fractions of cervical wall thickness, is one of the intermediate risk factors often encountered in clinical settings.
However, the criteria of depth of invasion is only expressed as inner third, middle third, and outer third of cervical wall thickness according to the Sedlis criteria [ 12 ]. Moreover, full-thickness or outer full-thickness invasion is one frequently encountered situation at clinical practice. Unlike obvious parametrial involvement, tumors with full-thickness infiltration only invade the whole cervical wall but not reaching the cervical-parametrial transition zone.
Besides, situations with outer full-thickness invasion were observed as the microscopic involvement of the cervical-parametrial transition zone without parametrial involvement. It brings the question if full-thickness and outer full-thickness invasion without positive parametrial margins should be treated the same as DSI.
Little evidence has been presented on the difference of clinical and prognostic characteristics between full-thickness invasion and DSI, or whether full-thickness should be regarded as a major or minor risk factor. In this study we compared the relationship with clinicopathological characteristics of patients with different DSI.
In the present study, patients were analyzed according to the depth of deep stromal invasion, tumors with OF and FT differs from those with IF in those were associated with high prevalence of great tumor burden, positive LVSI, lymph nodes, parametrium and surgical margin.
Full-thickness invasion seemed to be more aggressive than inner full-thickness invasive tumors. It has been reported that deep cervical invasion was strongly associated with a parametrial disease [ 13 , 14 ]. Our findings in conjunction with the studies above clearly support the hypothesis that the tumor is getting close to spread to parametrium with the depth of invasion increases.
Such a recurrence has not yet been documented in multiple studies. After analyzing the literature mentioned above, we are convinced that pathologists ought to start reporting whether destructive stromal invasion is present in endocervical adenocarcinoma cases to give clinicians a valuable piece of supplemental information for treatment decisions.
Perhaps one day clinical trials will also support an improved staging system incorporating pattern of invasion. Lab Best Practice. Enter search words Subscribe to Lab Best Practice Subscribe to our blog and receive notifications of new stories by email. Please retry. Pattern B with foci of destructive invasion with desmoplastic reaction The Silva system seems intuitive, and results were compelling when this system was applied to their study population.
Figure 2: Pattern C with diffuse destructive stromal invasion The average depth of cervical stromal invasion was lower with Pattern A, but there were exceptions.
Table 1: Outcome table from the paper by De Vivar et al, A group in the Netherlands applied the system to their 82 cases Spaans et al Best Practices The evidence is promising that the Silva system is helpful in identifying cases that may warrant a different treatment approach than depth of invasion alone suggests.
Sources: Adegoke et al. Bhatla N et al. De Vivar A et al. Park K and Roma A. Roma et al. Spaans V et al. Stolnicu S et al. Accepted 10 Apr Published 08 Jun Abstract Stromal invasion invasive growth of tumor tissue into portal tracts and fibrous septa is now recognized as the most important finding in the diagnosis of the well-differentiated type of early hepatocellular carcinomas HCCs. Introduction Recently, international consensus for the histological diagnosis of hepatocellular carcinoma, especially of well-differentiated type of early stage early HCC , was published by the International Consensus Group for Hepatocellular Neoplasia ICGHN [ 1 ].
Figure 1. Various features of stromal invasion of hepatocellular carcinoma HCC and pseudo-invasion A Crossing type. Cancer tissue HCC invades across fibrous septa f of tumor nodule. B Longitudinal type. Tumor cells grow longitudinally within fibrous septa arrowheads. C Irregular type. Portal areas are irregularly invaded by tumor cells Masson trichrome stain. D A non-cancerous area without invasion, and a portal area and fibrous septa are clearly seen.
E Pseudo-invasion. Benign non-cancerous cells are found in the fibrous stroma Masson trichrome stain. F Macroscopic view of stromal invasion. In the non-cancerous area without invasion area of a , fibrous septa are clearly seen. In the area of tumor spread area of b , septa are indistinct. G A panoramic view of stromal invasion. In the same way as in F , the non-cancerous area without invasion area of a shows distinct fibrous septa.
The area of tumor spread area of b shows indistinct septa because stromal invasion of longitudinal type and irregular type B , C reduced the amount of fibrous component.
H Continuity of fibrous invasion and vascular invasion. The arrows show portal vein p invasion. I Masson trichrome staining of pseudoinvasion. J Silver staining of the same specimen as I.
Liver cells are clearly surrounded by reticulin fibers. K Masson trichrome staining of true invasion. L Silver staining of the same specimen as K. Carcinoma cells are not surrounded by reticulin fibers. M Ductular reaction, confirmed by CK 7 staining, is clearly seen in a non-cancerous, non-invasive area. N Ductular reaction is not found in the invasive area. N Adapted from Y. Kondo et al. Kondo [ 11 ]. Figure 2. Histological features which make the assessment of stromal invasion difficult a True stromal invasion of very mild grade.
This pattern was formed by dissection of liver parenchyma by very thin fibrous tissue. Reticulin fibers circumscribing cancer tissue are seen even in the area of true invasion yellow arrow. However, noncircumscribed tumor cells are also seen in the same fibrous septum green arrows. Red arrows show ordinary tumor tissue with reticulin fibers surrounding the fibrous tissue. Figure 3. Relationship between cancer development, vascularity, histological feature fatty change , and stromal invasion.
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