Primary Tumor Depth Research Articles

The Effects of Tumor Size, Degree of Differentiation, and Depth of Invasion on the risk of Neck Node Metastasis in Squamous Cell carcinoma of the Oral Cavity

Cervical lymph node metastasis is the most important prognostic factor in patients with head and neck carcinoma. We retrospectively analyzed the effects of three different variables-tumor size, degree of differentiation, and depth of invasion-on the risk of neck node metastasis in 50 adults who had been treated with surgery for primary squamous cell carcinoma of the oral cavity. Primary tumor depth and other pathologic features were determined by reviewing the pathology specimens. Preoperatively, 36 of the 50 patients were clinically N0; however, occult lymph node metastasis was found in 13 of these patients (36.1%). The prevalence of neck node metastasis in patients with T1/T2 and T3/T4 category tumors was 51.5 and 58.8%, respectively. The associations between the prevalence of neck node metastasis and both the degree of differentiation and the depth of invasion were statistically significant, but there was no significant association between neck node metastasis and tumor size. We conclude that the prevalence of neck lymph node metastasis in patients with squamous cell carcinoma of the oral cavity increases as the tumor depth increases and as the degree of tumor differentiation decreases from well to poor, as has been shown in previous studies. It is interesting that tumor size, which is the most important component of the TNM system, was not significantly associated with neck node involvement.

Process of distant lymph node metastasis in colorectal carcinoma: Implication of extracapsular invasion of lymph node metastasis

BackgroundWe previously demonstrated that extracapsular invasion (ECI) at a metastatic sentinel node was significantly associated with the presence of positive non-sentinel nodes in patients with breast cancer. However, the mechanism of metastatic spreading of tumor cells to distant lymph nodes in patients with colorectal carcinoma is not fully understood. In this study, we investigated the factors that may determine the likelihood of additional regional lymph node metastasis when metastasis is found in nodes at the N1 site in colorectal cancer, especially focusing on the presence of ECI.MethodsTwo hundred and twenty-eight consecutive patients who underwent colorectal resection were identified for inclusion in this study, of which 37 (16.2%) had positive lymph nodes at the N1 site. Six of these 37 cases had additional metastasis in N2 site lymph nodes. We reviewed the clinicopathological features of these cases and performed statistical analysis of the data.ResultsIn the univariate analysis ECI at the N1 site was the only factor significantly associated with the presence of cancer cells in the N2 site. Other factors, including number of positive lymph nodes, lymphovascular invasion of the primary tumor, tumor size and tumor depth of invasion, were not associated with metastatic involvement at the N2 site.ConclusionsOur results suggest that the presence of ECI at metastatic lymph nodes at the N1 site is correlated with further metastasis at the N2 site. These findings imply the possibility that ECI might indicate the ability of colorectal tumor cells to disseminate to distant lymph nodes.

Histopathologic findings of HPV and p16 positive HNSCC

Human papilloma virus (HPV) and p16INKa (p16) positivity in head and neck squamous cell carcinomas (HNSCCs) is currently thought to be an encouraging prognostic indicator. However, the histopathologic changes responsible for this behavior are poorly understood. It is our objective to elucidate these histopathologic characteristics to help define the clinical utility of these markers. Retrospective cohort study. 71 HNSCC tumors between July 1, 2008 and August 30, 2009 were examined for HPV, p16, and epidermal growth factor receptor (EGFR). Specified pathologic features were examined: perivascular invasion (PVI), perineural invasion (PNI), grade of squamous differentiation, basaloid classification. HPV and p16 had no direct impact on perineural or perivascular invasion. However, HPV and p16 were strongly predictive of poorly differentiated tumors, as well as basaloid squamous cell carcinoma (SCCA) (P < .001). Additionally, upon multivariate analysis, HPV(+) and p16(+) tumors had an increased risk of nodal metastasis (HPV: odds ratio [OR] = 23.9 (2.2, 265.1) p = .01; p16: OR = 6.5 (1.4, 31.2) p = .02; PVI: OR = 6.0 (1.6, 22.8) p < .01). The area under the curve (AUC) of receiver operating characteristic (ROC) curves demonstrated improved predictive value for lymph node metastasis above standard H&E histopathologic features (76.7%) for both HPV (83.2%) and p16 (81.3%) individually. HPV(+) and p16(+) are highly predictive for poorly differentiated tumors and basaloid SCCA. Additionally, HPV and p16 positivity demonstrate superior predictive value for lymph node metastasis above standard H&E histopathologic features. Although exact recommendations should be tempered by considerations of primary tumor subsite, T-stage, and depth of invasion, head and neck multidisciplinary teams should strongly consider aggressive lymph node treatment for any HPV(+) or p16(+) tumor.

Pretreatment Primary Tumor SUVmax Measured by FDG-PET and Pathologic Tumor Depth Predict for Poor Outcomes in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

The pathologic tumor depth is an independent prognosticator for local control (LC) and survival in patients with oral cavity squamous cell carcinoma (OSCC). We sought to investigate the prognostic value of the preoperative maximal standardized uptake value (SUVmax) at the primary tumor in OSCC patients with pathologically positive lymph nodes. A total of 109 OSCC patients with pathologically positive lymph nodes were investigated. All patients underwent 2-deoxy-2[(18)F]fluoro-d-glucose-positron emission tomography within 2 weeks before surgery and neck dissection. All patients were followed for >or=24 months after surgery or until death. The optimal cutoff value for the primary tumor SUVmax was selected according to the 5-year LC rate. Independent prognosticators were identified by Cox regression analysis. The median follow-up for all patients was 26 months (39 months for surviving patients). A cutoff SUVmax of 19.3 provided the greatest prognostic information for the 5-year LC rate (55% vs. 88%, p = 0.0135). A tumor depth >or=12 mm appeared to be the most appropriate cutoff for predicting the 5-year LC rate (76% vs. 95%, p = 0.0075). A scoring system using the primary tumor SUVmax and tumor depth was formulated to define distinct prognostic groups. Patients with both a SUVmax of >or=19.3 and tumor depth of >or=12 mm (n = 8) had significantly poorer 5-year LC, 5-year disease-free, 5-year disease-specific, and 5-year overall survival rates compared with the other patient groups. The combination of the primary tumor SUVmax (>or=19.3) and pathologic tumor depth (>or=12 mm) identified a subgroup of OSCC patients at greatest risk of poor LC and death.

Importance of Sentinel Lymph Node Biopsy in Patients With Thin Melanoma

The status of the sentinel node (SN) confers important prognostic information for patients with thin melanoma. We queried our melanoma database to identify patients undergoing sentinel lymph node biopsy for thin (< or =1.00-mm) cutaneous melanoma at a tertiary care cancer institute. Slides of tumor-positive SNs were reviewed by a melanoma pathologist to confirm nodal status and intranodal tumor burden, defined as isolated tumor cells, micrometastasis, or macrometastasis (< or =0.20, 0.21-2.00, or >2.00 mm, respectively). Nodal status was correlated with patient age and primary tumor depth (< or = 0.25, 0.26-0.50, 0.51-0.75, or 0.76-1.00 mm). Survival was determined by log-rank test. Disease-free and melanoma-specific survival. Of 1592 patients who underwent sentinel lymph node biopsy from 1991 to 2004, 631 (40%) had thin melanomas; 31 of the 631 patients (5%) had a tumor-positive SN. At a median follow-up of 57 months for the 631 patients, the mean (SD) 10-year rate of disease-free survival was 96% (1%) vs 54% (10%) for patients with tumor-negative vs tumor-positive SNs, respectively (P < .001); the mean (SD) 10-year rate of melanoma-specific survival was 98% (1%) vs 83% (8%), respectively (P < .001). Tumor-positive SNs were more common in patients aged 50 years and younger (P = .04). The SN status maintained importance on multivariate analysis for both disease-free survival (P < .001) and melanoma-specific survival (P < .001). The status of the SN is significantly linked to survival in patients with thin melanoma. Therefore, sentinel lymph node biopsy should be considered to obtain complete prognostic information.

Evaluation of risk factors associated with local recurrence after radical resection of rectal carcinoma

To investigate the risk factors of local recurrence after radical resection of rectal carcinoma. Clinical and follow-up data of 535 patients with rectal carcinoma, received radical resection between August 1994 and July 2004 in our department, were reviewed retrospectively. The association of clinicopathological factors and local recurrence was analyzed using Log-rank test. Cox multiple variate analysis was conducted to determine the independent risk factors. All the 535 rectal carcinoma patients underwent radical resections. Local recurrence occurred in 53 cases (9.9%), and distant metastasis co-occurred in 39 cases (7.3%). The time from the first operation to the recurrence was 4-54 months with a median of 12 months. The Log-rank test showed that the primary tumor site (P<0.01), differentiation(P<0.01), histological type(P=0.038), lymph node metastasis(P=0.023), Dukes staging(P=0.045), blood transfusion(P=0.001), and total mesorectum excision (TME)(P<0.001) were associated with the recurrence, but the operative style(P=0.908), invasive depth of primary tumor(P=0.735), massive pathological type(P=0.562), degree of surgeon(P=0.171) and post-operative chemotherapy (P=0.772) were not associated with the recurrence. Cox multiple variate analysis revealed that blood transfusion, primary tumor site, differentiation, lymph node metastasis, and TME principle were independent prognostic factors affecting local recurrence after radical resection of rectal cancer. Blood transfusion, low position of tumor, poor differentiation, lymph node metastasis are the risk factors associated with local recurrence in rectal cancer. Application of TME principle is the key point to decrease the local recurrence rate.

Salvage therapy in relapsed squamous cell carcinoma of the oral cavity: How and when?

Relapse of tumors in patients with oral cavity squamous cell carcinoma (OSCC) is associated with a poor prognosis. In addition, salvage therapy may be a significant source of morbidity in patients with relapsing OSCC. The objective of the current study was to determine prognostic factors that predict which patients may benefit from such treatment. From 953 patients who underwent primary radical surgery between 1996 and 2005, 272 patients with early-relapsed OSCC (n = 161) or late-relapsed OSCC (n = 111) were identified. The optimum cutoff point for relapse was chosen on the basis of 5-year disease-specific survival (DSS) and overall survival (OS). The optimal cutoff value for relapse was 10 months. Late relapses were associated with a better prognosis than relapses that occurred within the first 10 months (P < .0001 for both 5-year DSS and 5-year OS). Among patients with early-relapsed OSCC, a primary tumor depth <10 mm was associated significantly and independently with a better 5-year DSS (P = .014) and OS (P = .011). Among patients with late-relapsed OSCC, neck recurrence was a significant risk factor for adverse outcomes (P < .001 for both 5-year DSS and 5-year OS). A late relapse was associated with better survival than a relapse that occurred within the first 10 months. Patients with late-relapsed OSCC may benefit from salvage therapy, especially those who have a local recurrence. Among patients with early-relapsed OSCC, salvage therapy should be considered for those who have a primary tumor depth <10 mm.

2-Deoxy-2-[F-18]fluoro-d-glucose Positron Emission Tomography/Computed Tomography in the Management of Melanoma

2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single exam. The role of FDG-PET is proven in a variety of cancers, including melanoma, but the estimates of sensitivity and specificity are based in the majority of the published studies on dedicated PET, not PET/CT. Therefore, we were prompted to review our experience with FDG-PET/CT in the management of melanoma. This is a retrospective study on 106 patients with melanoma (20-87 years old; average: 56.8 +/- 15.9), who had whole-body FDG-PET/CT at our institution from January 2003 to June 2005. Thirty-eight patients (35.9%) were women and 68 patients (64.1%) were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. All patients had the study for disease restaging. The primary tumor depth (Breslow's thickness) at initial diagnosis was available for 76 patients (71.7%) and ranged from 0.4 to 25 mm (average: 3.56 mm). The anatomic level of invasion in the skin (Clark's level) was determined for 70 patients (66%): 3, level II; 13, level III; 43, level IV; 11, level V. The administered dose of (18)F FDG ranged from 9.8 to 21.6 mCi (average: 15.4 +/- 1.8 mCi). FDG-PET/CT had a sensitivity of 89.3% [95% confidence interval (CI): 78.5-95] and a specificity of 88% (95% CI: 76.2-94.4) for melanoma detection. This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk melanoma, prior to selection of the most appropriate therapy.

Prognostic significance of Wilms tumor gene (WT1) mRNA expression in soft tissue sarcoma

There have been several recent reports that Wilms tumor gene (WT1) mRNA is overexpressed in many types of neoplasms, and those results suggested that WT1 has oncogenic properties. The objective of the current study was to evaluate the prognostic significance of WT1 mRNA expression in patients with soft tissue sarcoma. Levels of WT1 mRNA expression were examined by quantitative, real-time reverse transcriptase-polymerase chain reaction analysis in frozen tissue samples from 52 patients with soft tissue sarcoma. Various clinicopathologic factors were analyzed along with the disease-specific survival rate for correlations with WT1 mRNA expression levels. The levels of WT1 mRNA expression in a variety of soft tissue sarcomas were significantly greater compared with the levels in normal soft tissue samples (P = .0212). No significant correlation was observed between the level of WT1 mRNA expression and clinicopathologic factors, including gender, age, primary tumor site, tumor depth, tumor size, histologic grade, and distant metastasis at initial presentation. The disease-specific survival rate for patients with high WT1 mRNA expression levels was found significantly poorer compared with the rate for patients with low WT1 mRNA expression levels (P = .0182). Moreover, multivariate analysis indicated that a high WT1 mRNA expression level was an independent, adverse prognostic factor for disease-specific survival (hazards ratio, 2.6; P = .0488). WT1 mRNA expression level can serve as a potent prognostic indicator in soft tissue sarcoma patients.

Sentinel lymph node biopsy for melanoma and other melanocytic tumors in adolescents

Background/Purpose Melanoma is rare, accounting for only 1% of all pediatric malignancies. The management of pediatric melanoma is controversial but largely parallels that of an adult occurrence. Sentinel lymph node biopsy (SLNBX) has become a standard of care for adults with melanoma, but the role of this procedure in the staging of pediatric patients remains to be established. The goal of this study was to determine outcomes and complications of children and adolescent patients undergoing SLNBX at the authors' institution. Methods A retrospective review of patients younger than 21 years (N = 20) undergoing SLNBX for melanoma or other melanocytic skin lesions at the University of Colorado Health Science Center between 1996 and 2003 was conducted. Results Sentinel lymph node biopsy was successful in all 20 patients, and 8 patients (40%) were found to have metastases within the sentinel node. As in adults, the sentinel node status correlates with primary tumor depth. No complications occurred in patients undergoing SLNBX, but 4 clinically significant complications (57%) occurred in the 7 patients undergoing a completion lymph node dissection. At 33 months median follow-up, all patients were disease free. Conclusions Sentinel lymph node biopsy can be successfully and safely performed in pediatric patients for melanoma and atypical nevi. However, the prognostic information and therapeutic implications of SLNBX results for children and adolescents remain unclear. Completion lymph node dissection for microscopic disease is a morbid procedure with uncertain benefit to pediatric or adult patients with a positive SLNBX result. Long-term follow-up data are needed before SLNBX can become a standard of care in pediatric melanoma or as a diagnostic tool to distinguish the atypical Spitz nevus from melanoma.

Immunomagnetic detection and clinical significance of micrometastatic tumor cells in malignant melanoma patients.

Positive associations between the presence of micrometastatic tumor cells and disease aggressiveness have been reported in several tumor types, but the clinical implications are still not established. We wanted to test a new, sensitive immunomagnetic detection method on bone marrow (BM) and peripheral blood (PB) samples from patients with malignant melanoma and relate the findings to clinical outcome. Samples from 210 patients admitted for relapse of cutaneous melanoma were examined. Mononuclear cell fractions isolated from BM and PB were incubated with superparamagnetic particles coated with antimelanoma antibodies. Live tumor cells with bound beads were isolated with a magnet and identified in a microscope as cell-bead rosettes. Beads without antibody or with an irrelevant antibody were used as controls. The whole procedure was completed within 2-3 h. The identity of the cells was confirmed with a new double labeling procedure with fluorescent microparticles. Rosetted melanoma cells were found in BM aspirates of 35 of 186 (19%) patients, but in only 2 of 208 (1%) PB samples. The controls were all negative. After a median observation time of 1.1 year (range, 0-6.8 years), patients with tumor cells in BM showed a significantly shorter overall survival from time of BM aspiration (P = 0.009). In multiple regression analysis, a positive BM test was a strong indicator of overall survival (P = 0.021), associated with disease stage (American Joint Committee on Cancer) and with the number of metastatic sites, but not with the primary (Breslow) tumor depth and morphology. The results demonstrate the prognostic significance of detecting BM micrometastasis in melanoma patients. The results strengthen the validity of the immunobead technique. In contrast to other techniques, the method identifies intact, live tumor cells that can be further characterized, making the assay attractive for extended use.

Clinicopathological significance of vascular endothelial growth factor-C and cyclooxygenase-2 in esophageal squamous cell carcinoma.

Vascular endothelial growth factor-C (VEGF-C) is a specific growth factor of lymphatics, which is known to play some role in tumor growth and metastasis to lymph nodes and distant organs in various malignancies. The purpose of the present study was to investigate the expression of VEGF-C in human esophageal squamous cell carcinomas (ESCC) to elucidate its role in tumor progression and lymph node metastasis. Another aim of the study was to investigate the relation between VEGF-C and cyclooxygenase-2 (COX-2) in ESCC. The expression of VEGF-C and COX-2 in ESCC was evaluated in 13 endoscopic mucosal resection specimens and in 21 surgical specimens by immunohistochemical staining. Clinical data were obtained from medical records. The degree of VEGF-C expression increased as the depth of primary tumor progressed (r = 0.521, P = 0.002), the stage progressed (r = 0.572, P < 0.001), and the degree of COX-2 expression increased (r = 0.387, P = 0.024). The VEGF-C positive rate was different between early cancers in which regional lymph node metastasis was thought to be absent and advanced cancers in which regional lymph node metastases were confirmed after surgery (20.0% vs 100.0%; P < 0.001). The VEGF-C expression in ESCC is related to COX-2 expression, and VEGF-C is also associated with the depth of primary tumor, the stage, and probably lymph node metastasis. Thus the investigation of VEGF-C expression in ESCC may assist in management planning.

Clinical significance of BRAF mutations in metastatic melanoma

Forty to eighty percent of melanoma tumors have activating mutations in BRAF although the clinical importance of these mutations is not clear. We previously reported an analysis of BRAF mutations in metastatic melanoma samples from 68 patients. In this study, we correlated patient baseline characteristics, prognostic factors, and/or clinical outcomes with the presence of BRAF mutations. No significant differences were observed in age, gender, location of primary melanoma, stage at the diagnosis, and depth of primary tumor between patients with and without BRAF mutations. Melanomas harboring BRAF mutations were more likely to metastasize to liver (P = 0.02) and to metastasize to multiple organs (P = 0.048). Neither time to progression to stage IV nor overall survival were associated with BRAF mutations. In conclusion, we observed no significant differences in clinical characteristics or outcomes between melanomas with or without BRAF mutations. Although there was an increased frequency of liver metastasis and tendency to metastasize to multiple organs in tumors with BRAF mutations, there was no detectable effect on survival. Future prospective studies should include analysis of whether BRAF mutations in melanoma tumors correlate with an increased tendency to metastasize to liver or to multiple organs.

Patterns of recurrence after sentinel lymph node biopsy for cutaneous melanoma

Background Previous sentinel lymph node (SLN) studies for cutaneous melanoma have shown that the SLN accurately reflects the nodal status of the corresponding nodal basin. However, there are few long-term studies that describe recurrence site patterns, predictors for recurrence, and overall survival and disease-free survival after SLN biopsy. Methods A retrospective review of patients over a 6-year period was performed to determine patient outcomes and the patterns of recurrence. In all cases, Tc-99 sulfur colloid along with isosulfan blue dye was injected at the primary melanoma site. After resection, the SLN was serially sectioned and evaluated by hematoxylin and eosin staining and immunohistochemistry. Results One hundred ninety-eight patients were identified who underwent SLN biopsy for cutaneous melanoma including T1 (n = 21), T2 (n = 88), T3 (n = 75), and T4 (n = 14) primary tumors. Of these patients, 38 had a positive SLN. Of the 38 patients with a positive SLN (mean follow-up 38 months), recurrent disease was identified in 10 (26.3%) at a mean interval of 14.2 months. The site of first recurrence was distant (n = 4) and local (n = 6). Regional lymphatic basin recurrence was not identified. Of the 160 patients with a negative SLN (mean follow-up 50 months), recurrent disease was identified in 16 (10.0%) at a mean interval of 31.3 months. The site of first recurrence was systemic (n = 11), local (n = 4), and nodal (n = 1). Overall survival and disease-free survival for patients with a positive SLN at 55 months was 53.3% and 47.7% respectively, while overall survival and disease-free survival for patients with a negative SLN at 53 months was 92.2% and 87.7% respectively ( P <0.01). Univariate and multivariate analysis of the entire cohort (n = 198) identified primary tumor depth and positive SLN status as significant predictors of recurrence. Conclusions The incidence of nodal basin recurrence after SLN biopsy was found to be 0.6%. Primary tumor depth and pathological status of the SLN are significant predictors of local and systemic recurrence. Long-term follow-up indicates that patients with a positive SLN clearly recur sooner and have decreased overall survival than those with a negative SLN.

Malignant melanoma in different ethnic groups in Israel. Incidence and biologic behavior.

The Jewish population of Israel is divided into two ethnic groups: Ashkenazic Jews (AJ) who immigrated from Europe and are fair-skinned, and Sephardic Jews (SJ) who immigrated from the Orient and Africa and who are dark-skinned. The biologic behavior of malignant melanoma (MM) in these two groups has not been investigated. Three hundred forty-eight of 380 patients with MM, who could be accurately grouped ethnically, constitute this study group. The gender, site and depth of primary tumor, metastatic involvement and survival analysis, including univariate analysis for level of invasion, were examined. Of 348 patients with MM, 285 were AJ and 63 were SJ. The female:male ratio was 2:1 and 0.9:1, for AJ and SJ, respectively (P < 0.05). Lesion site distribution was similar. The lesions were more invasive in SJ, 53% Clark level 4-5 versus 41% in AJ (P < 0.05). The 5-year survival was worse in SJ relative to AJ--50% versus 71% for female patients and 30% versus 62% for male patients--but did not reach statistical significance (NS). The actuarial 10-year survival showed poorer survival for female SJ: 27% versus 67% in female AJ (P < 0.05) and male SJ; 32% versus 65% in male AJ (P < 0.01). For all stage I MM, the actuarial 10-year survival was in male patients 32% versus 79% (P < 0.05), and in female patients, 27% versus 72% (P < 0.05) in SJ and AJ, respectively. For the more invasive lesions (Clark levels 4 and 5), the actuarial 10-year survival was for male patients 19% versus 75% (P < 0.05) and for female patients, 65% versus 67% (NS) in SJ and AJ, respectively. The dark-skinned SJ tend to have MM less than the fair-skinned AJ, but once MM occurs in SJ, it appears to have a more virulent nature.