Deep Surgical Margins Research Articles

Surgical margins and the risk of local-regional recurrence (LRR) following mastectomy for early-stage breast cancer.

95 Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR. Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in 51 (31%). Results: The median follow-up was 6.3 years (range, 1-12.4). The 5-year LRR rate was 5% (95% CI 2-10%) and the DM rate was 3% (95% CI 1-8%). Twelve patients had a LRR; this included the chest wall in 9 and the axilla in 4. Five of the 12 had positive nodes. Four of 92 (4%) with close margins had a LRR vs. 8/75 (11%) with positive margins (log-rank p=0.15). Of the 45 with pure DCIS, 1 (2%) had a LRR. Of those with invasive disease, LRR occurred in 1/28 (4%) who had invasive disease at (positive) or near (close) the superficial margin, 3/38 (8%) with DCIS at or near the superficial margin, 0/12 with invasive disease at or near the deep margin, and 1/12 (8%) with DCIS at or near the deep margin. Both margins were positive or close in 32/122 patients with invasive disease; 6 of these (19%) had a LRR. Conclusions: The risk of LRR in patients with a positive or close surgical margin after mastectomy is generally low. The benefit of post-mastectomy radiation in this population with otherwise favorable features is likely to be small. While there may be a higher risk of LRR in patients with disease at or close to both margins (likely representing extent of disease), numbers in these categories are small and these results should be interpreted with caution.

Association of histologic tumor characteristics and size of surgical margins with clinical outcome after surgical removal of cutaneous mast cell tumors in dogs

To evaluate the relationship between width and depth of surgical margins, amount of edema within and around the tumor, and degree of demarcation between the tumor and surrounding tissues with the clinical outcome following surgical removal of cutaneous mast cell tumors (cMCTs) in dogs. Retrospective cohort study. 100 dogs with 115 resectable cMCTs. Information about the dogs' clinical outcomes following cMCT removal was obtained from primary care veterinarians. Histologic sections of excised tumors were assessed retrospectively for tumor grade and measurement of the narrowest lateral and deep margins of nonneoplastic tissue excised with the tumors; edema within the tumor and surrounding tissues was assessed as minimal, moderate, or severe. Tumors were classified as poorly, moderately, or well demarcated on the basis of the degree of mast cell infiltration into the adjoining connective tissue. Following tumor excision (with no additional postsurgery treatment), 96 dogs had no local recurrence or metastatic disease for 27 to 31 months; 4 metastatic disease-related deaths (dogs with grade II or III tumors) occurred within 3 to 9 months. Histologically, mean lateral and deep surgical margins around the tumors were 8.9 and 5.3 mm, respectively. No recurrence of tumor or metastatic disease developed following excision with lateral margins ≥ 10 mm and deep margins ≥ 4 mm. Edema and degree of demarcation were not correlated with outcome. Results suggested that most grade I and II cMCTs in dogs can be successfully treated by complete surgical removal with margins smaller than those currently recommended.

Advances in Management of Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue tumor that most commonly presents on the trunk and extremities of adults. It is characterized by low metastatic potential and a favorable prognosis, but extensive subclinical growth can contribute to a high risk of local recurrence. Surgical excision is the first-line treatment, using Mohs micrographic surgery or wide local excision with careful evaluation of the peripheral and deep surgical margins. Adjuvant therapy may be beneficial in patients with unresectable, recurrent, or metastatic DFSP. Historically, adjuvant radiation therapy has been used to reduce the risk of local recurrence when residual disease is present after surgery. The advent of targeted molecular therapies, such as the selective tyrosine kinase inhibitor, imatinib mesylate, has provided new effective and safe options for adjuvant treatment of DFSP.

Surgical Treatments of Non-Melnaoma Skin Cancers: A Review

Surgical Treatments of Non-Melnaoma Skin Cancers: A Review

Ultrasonography for Intraoperative Determination of Tumor Thickness and Resection Margin in Tongue Carcinomas

Exact estimation of tumor thickness and the status of the resection margin in tongue carcinoma are important prognostic factors for local recurrence, subclinical nodal metastasis, and survival. This study aims to evaluate the accuracy of intraoral ultrasonography-guided measurement of tumor thickness and define an adequate intraoperative resection margin in squamous cell carcinomas of the tongue. In this prospective study, 13 patients with presurgical, biopsy-proven, clinical T1N0 or T2N0 tongue squamous cell carcinomas who underwent a partial glossectomy were examined preoperatively with ultrasonography to assess tumor thickness under general anesthesia. Nine cases underwent resection by a conventional method, whereas we introduced elastic needles with a metal core to mark a deep surgical margin of 10 mm from the deepest tumor invasion front under ultrasonographic monitoring as a new technique in the remaining 4 cases. Each resected specimen was immediately immersed in gelatin solution while maintaining its original shape and orientation and was placed under refrigeration to solidify. Ultrasonographic observations of the gelatin-embedded specimens were performed from the superior surface of the gelatin block. Very fine ultrasonographic images of the resected specimen could be easily obtained without any special skills, and surgical clearance could be verified intraoperatively. The ultrasonographic tumor thickness measurements corresponded well with those of histologic sections, with a consistency ratio of 91.4% to 98.2% (Pearson correlation coefficient = 0.981, P < .05). Intraoperative ultrasonography is a reliable method to objectively evaluate tumor thickness and surgical margin clearance.

Transoral CO2 laser treatment for Tis–T3 glottic cancer: The University of Brescia experience on 595 patients

Transoral CO(2) laser surgery has been accepted as a valuable therapeutic option for glottic cancer. This was a retrospective analysis of 595 patients. Five-year overall and disease-specific survivals, local control with laser, locoregional, regional control, and organ preservation rates were calculated. The impact of different variables was calculated by univariate analysis. Overall, disease-specific and disease-free survivals, local control with laser, locoregional, regional control, and organ preservation rates were 87.5%, 99%, 81.3%, 92.7%, 98.9%, 98.2%, and 97.1%, respectively. Univariate analysis showed a significant impact of pT category on local control with laser, organ preservation, locoregional and regional control, of endoscopic re-treatment for positive deep surgical margins on local control with laser and organ preservation, and recurrence after endoscopic re-treatment on local control with laser and organ preservation. This series confirms the good oncologic outcomes of endoscopic laser surgery for T(is), T(1), and selected T(2) and T(3) glottic tumors.

Feline injection-site sarcoma: Recurrence, tumour grading and surgical margin status evaluated using the three-dimensional histological technique

The three-dimensional histology technique is used in human medicine for the evaluation of complete lateral and deep surgical margins. In this study, the technique was applied to 48 excised feline injection-site sarcoma specimens. The predictive value of the histological margin status and tumour grading on local recurrence was investigated. In 32/48 cases, the margins were non-infiltrated, whilst in the remaining 16 cases, they were infiltrated. Overall, 6/32 (19%) tumours with non-infiltrated margins and 11/16 (69%) with infiltrated margins recurred. Tumours with infiltrated margins recurred about 10 times more frequently compared to tumours with non-infiltrated margins (P=0.0011). No statistically significant correlation was observed between grading and recurrence. The assessment of margin status using the 3D histology technique showed a good predictivity for post-surgical tumour recurrence. Extensive application of the 3D histology technique is recommended to standardise the evaluation of histological margins and to allow comparison between results from different laboratories.

Molecular Detection of Minimal Residual Cancer in Surgical Margins of Head and Neck Cancer Patients

A great disappointment in head and neck cancer surgery is that 10–30% of head and neck squamous cell carcinoma (HNSCC) patients develop local recurrences despite histopathologically tumor-free surgical margins. These recurrences result from either minimal residual cancer (MRC) or preneoplastic lesions that remain behind after tumor resection. Distinguishing MRC from preneoplasic lesions is important to tailor postoperative radiotherapy more adequately. Here we investigated the suitability of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using human Ly-6D (hLy-6D) transcripts as molecular marker to detect MRC in surgical margins.Submucosal samples of deep surgical margins were collected from 18 non-cancer control patients and 67 HNSCC patients of whom eight had tumor-positive surgical margins. The samples were analyzed with hLy-6D qRT-PCR, and the data were analyzed in relation to the clinicohistological parameters.A significant difference was shown between the group of patients with histopathological tumor-positive surgical margins and the non-cancer control group (p &lt; 0.001), and the group of patients with histopathological tumor-free surgical margins (p = 0.001).This study shows a novel approach for molecular analysis of deep surgical margins in head and neck cancer surgery. The preliminary data of this approach for detection of MRC in deep margins of HNSCC patients are promising.

Molecular detection of minimal residual cancer in surgical margins of head and neck cancer patients.

A great disappointment in head and neck cancer surgery is that 10–30% of head and neck squamous cell carcinoma (HNSCC) patients develop local recurrences despite histopathologically tumor-free surgical margins. These recurrences result from either minimal residual cancer (MRC) or preneoplastic lesions that remain behind after tumor resection. Distinguishing MRC from preneoplasic lesions is important to tailor postoperative radiotherapy more adequately. Here we investigated the suitability of quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using human Ly-6D (hLy-6D) transcripts as molecular marker to detect MRC in surgical margins.Submucosal samples of deep surgical margins were collected from 18 non-cancer control patients and 67 HNSCC patients of whom eight had tumor-positive surgical margins. The samples were analyzed with hLy-6D qRT-PCR, and the data were analyzed in relation to the clinicohistological parameters.A significant difference was shown between the group of patients with histopathological tumor-positive surgical margins and the non-cancer control group (p < 0.001), and the group of patients with histopathological tumor-free surgical margins (p = 0.001).This study shows a novel approach for molecular analysis of deep surgical margins in head and neck cancer surgery. The preliminary data of this approach for detection of MRC in deep margins of HNSCC patients are promising.

Determination of deep surgical margin based on anatomical architecture for local control of squamous cell carcinoma of the buccal mucosa

Of all oral squamous cell carcinomas, squamous cell carcinomas of the buccal mucosa (BSCC) are most associated with poorest prognosis. In particular, patients treated with surgery alone are reported to experience frequent local failures. This is considered to result from the surgeon's determination of the deep surgical margin for resection based on palpation alone when performing BSCC surgery. Therefore, an objective system for classifying the depth of invasion of a tumor appears to be necessary in order to improve the results of BSCC treatment. While current general practice is to treat based on tumor thickness, we would like to emphasize the importance of how far down the cheek wall layer the tumor has invaded. We performed surgery by classifying the depths of tumor invasion in relation to the buccinator. Depth of tumor invasion was assessed mainly using ultrasonography (US). The tumor was defined as D1 when it extended to the mucosal (m) and submucosal layers (sm). In these cases, the tumor was resected, while the buccinator was spared. The tumor was defined as D2 when it extended to the buccinator, but, based on US, muscle continuity was preserved, and the tumor was resected to include the buccinator and its overlying fascia. When the tumor had spread to the buccinator or invaded subcutaneous or cutaneous tissue it was classified as D3 and resection included the skin. The disease-specific survival rate of BSCC when treated based on our classification was 73.7% and the local control rate was 89.5%. These results are superior to those based on surgery alone and this therapeutic modality was considered to be useful.

What is your diagnosis? Preputial mass in a ferret

: A 7-year-old neutered male polecat-type ferret (Mustela putorius furo) was presented for evaluation of a cutaneous mass close to the preputial orifice. Cytologic examination of a fine-needle aspirate revealed numerous large clumps of amorphous pink mucinous material and numerous large clumps of slightly pleomorphic epithelial cells. The cells were arranged in papillary structures, palisades, and loosely cohesive sheets with a vaguely honeycomb appearance. Occasional acinar formations were also seen. The cells had moderate to large amounts of finely granular gray to gray-blue cytoplasm. The cells were round to wispy and elongated, with indistinct borders. Often, anuclear cytoplasmic clumps were seen free in the background or adjacent to intact cells. Nuclei were round to oval and usually off-center. Chromatin was finely stippled and contained 1-3 indistinct nucleoli. Anisokaryosis and anisocytosis were moderate. Binucleated cells were noted occasionally. The cytologic features were consistent with a carcinoma of probable apocrine origin. Histopathologic examination supported a diagnosis of secretory apocrine adenocarcinoma of the preputial skin. Secretory apocrine adenocarcinomas of the prepuce are seen relatively frequently in ferrets, although their cytologic appearance has not been described widely. These neoplasms carry a poor prognosis although prompt surgical removal with wide and deep surgical margins and adjunctive radiotherapy may improve survival.

Accuracy of intraoperative tissue staining in delineating deep surgical margins in oral carcinoma surgery

The purpose of this study was to assess the accuracy of this tissue staining assessment of surgical specimens in delineating deep surgical margins in oral cancer surgery. Fifteen patients who underwent surgery for oral carcinoma were included in the study. Once the tumor was resected, a vertical section of the surgical specimen was taken from the central part of the tumor. The section was consecutively stained with 0.4% indigo carmine and 0.5% Congo red, and deep surgical margins were assessed using a digital microscope with a magnification power of 25-175x. The results of tissue staining analysis were compared with the corresponding results of conventional histopathological analysis with HE staining, which is considered the gold standard. The extent of carcinoma invasion could be visualized after the application of tissue staining solutions. Tissue staining analysis was accurate in 12 of the 15 patients (80%) in evaluating the closest deep surgical margin. There was no significant difference in the tumor-margin distance between tissue staining and histopathological assessment in these 12 patients (Wilcoxon signed-ranks test, P>0.63). The results of this study showed that intraoperative tissue staining of surgical specimens permitted visual inspection and assessment of tumor spread to surgical margin, although the method has some limitations. The method had a possible ability in controlling the deep surgical margin.

FIT biopsy for conjunctival squamous cell carcinoma with extensive intraocular invasion

Dear Editor, Ocular surface squamous neoplasia (OSSN) [conjunctival intraepithelial neoplasia, carcinoma in situ, and invasive squamous cell carcinoma (SCC)] are the most common conjunctival malignancy in the United States, occurring with the incidence of 0.03 cases per 100,000 persons. While OSSN can be locally aggressive, intraocular involvement is infrequent [1, 2]. Histopathologic confirmation of intraocular invasion can be obtained through various diagnostic techniques. Herein, we present a patient with extensive intraocular involvement by SCC, diagnosed with the aid of biopsy with a 25-gauge aspiration-cutter [Finger iridectomy technique (FIT)]. A 73-year-old woman presented with a white, vascular, dome-shaped, nasal limbal lesion, which extended onto adjacent inferonasal right cornea (Fig. 1a). A high-frequency ultrasound biomicroscopy showed no anterior chamber involvement [3]. Excisional biopsy with cryotherapy was performed. Histopathology showed well-differentiated keratinizing SCC (Fig. 1b), with approximately 40% Ki67 proliferation marker labelling index, extending to lateral, but not to deep surgical margins. The patient underwent a course of topical mitomycin-C (0.02%) and was followed closely. Two months after the surgery the epithelial tumour recurred in the region adjacent to the primary site, and the patient had a second course of mitomycin-C. A month later, she presented complaining of pain in her eye. Marked enlargement of conjunctival tumour was noted, associated with increased intraocular pressure, anterior chamber cells, and a mass in the nasal anterior chamber angle (Fig. 2a). The intraocular lesion was biopsied using the FIT. Briefly, A 25-gauge aspiration-cutter (vitrector) was introduced under sodium hyaluronate 1% and through a 1-mm peripheral clear corneal incision. Aspiration (600 mmHg) cutting (300 cpm) was performed to obtain specimens for cytology and histopathology. The detailed methodology of this technique is described in the referenced text [4]. Cytopathologic evaluation of biopsy material revealed dysplastic keratinizing squamous cells and tissue consistent with intraocular invasion by SCC (Fig. 2b). In the course of the next several weeks, the patient developed increasing right eye pain, vitreous debris, and serous retinal detachment. She was advised to undergo orbital exenteration for local tumour control. Histopathologic evaluation of the orbital exenteration specimen revealed well-differentiated SCC. The tumour cells involved the anterior orbit, entered the eye via anterior emissary canals, and infiltrated the anterior chamber angle, Graefes Arch Clin Exp Ophthalmol (2008) 246:467–469 DOI 10.1007/s00417-007-0712-4

P53 Mutations in Deep Tissues Are More Strongly Associated with Recurrence than Mutation-Positive Mucosal Margins

Application of ultrasensitive diagnostics has shown that small numbers of p53 mutation-positive cells may signify the presence of residual tumor in histologically normal tissues after resection of squamous cell carcinomas arising in the head and neck area. To date, most studies in this area have focused on analysis of tissues at the mucosal aspect of the resection and highlighted the importance of molecular changes in the field with respect to the risk of recurrence. In the present investigation, we analyzed normal tissues from mucosal and deep surgical margins, referred to as "molecular margins," for the presence of the signature p53 mutation identified for each tumor. The p53 mutation status of these carcinomas did not correlate with clinical or histopathologic variables, but these mutations provided an excellent target for ultrasensitive analysis of margin status. We found that 11 of 16 (68%) of cases with histologically tumor-free (including 9 without dysplasia), but with p53 mutation-positive molecular margins, developed recurrence. The probability of developing local recurrence was significantly higher for the group with p53 mutation-positive margins when compared with the group with clear margins (P = 0.048) and more strongly associated with p53 mutation-positive deep molecular margins than mutation-positive mucosal molecular margins or positivity at both sites (P = 0.009). This shows that although persistent mucosal fields may contribute to recurrence, clonal p53 mutations in deep tissues are an important cause of treatment failure, and molecular margins from both sites should be analyzed in future prospective series.

Poster 089: Intraoperative Surgical Clearance Confirmation of Soft Tissue Carcinomas Using Ultrasonography

The optimal surgical clearance, i.e., enough safety clearance for its radicality as well as minimal invasion for functional aspect, is the essential part of tumor surgery. However, there was no method to obtain information about surgical clearance intraoperatively. Therefore we proposed a quick and efficient method to confirm the surgical clearance of the resected fresh specimen with fine ultrasonographic (US) images intraoperatively. We also proposed a rational method to define the deep surgical margin using US. Immediately after the resection of tumor, the resected fresh specimen was immersed into gelatin solution maintaining original shape and orientation, and refrigerated for solidification of the gelatin. US observation of the gelatin embedded specimen was performed from the superior surface of the gelatin. The US image of the fresh specimen could be verified to the subsequently prepared histopathological sections later. If it was necessary to confirm the deep surgical margin before resection, guiding needles were introduced to the deepest point of the resection under US monitoring in the intubated patient. Resection of the tumor was performed using the guiding needle as a landmark. n/a In 11 early stage oral carcinomas (9; tongue, 2; oral floor), this technique was applied. Very fine US images of the resected specimens could be obtained within 30 minutes without any special skills in all cases. The consistency ratio between the US images of the fresh specimen and the histopathological findings were ranged from 90 to 96 %. The method to define the deep surgical margin using guiding needle was also very helpful for the accurate resection. A simple method for surgical clearance confirmation was proposed. The operator could confirm the optimality of the surgical clearance during operation with this method. This single testing might replace frozen section to confirm the optimality of the resection in some kind of carcinomas. Appling a guiding technique of the deep surgical margin under US monitoring, determination of the resection margin would be easier and more accurate. After additional experiences, reduction of the resection clearance could be considered.

Transanal endoscopic microsurgery in the treatment of rectal carcinoid tumor

This study aimed to assess the efficacy of transanal endoscopic microsurgery (TEM) in the treatment of rectal carcinoid tumor. Between May 1994 and April 2006, 27 patients with rectal carcinoid tumor underwent TEM, and their clinical data were reviewed retrospectively. The TEM procedure was performed as a primary excision (n = 14) or as completion surgery after incomplete resection by endoscopic polypectomy (n = 13). The average size of a primary tumor was 9.1 mm (range, 5-13 mm), and the average distance of the tumor from the anal verge was 8.5 cm. The mean duration of the operation was 51.6 min. Minor morbidities, transient soilage, and mild dehiscence occurred in two cases (7.4%). Histopathologically, all tumors were localized within the submucosal layer showing typical histology without lymphatic or vessel infiltration, and both deep and lateral surgical margins were completely free of tumors. Among 13 cases of completion surgery after endoscopic polypectomy, 4 (30.8%) were histologically shown to have a residual tumor in the specimens obtained by TEM. No additional radical surgery was performed. The mean follow-up period was 70.6 months, and no recurrence was noted. The results indicate that TEM is a safe, minimally invasive procedure for the local excision of rectal carcinoid tumors, particularly those in the proximal rectum. Furthermore, for patients with microscopic positive margins after endoscopic polypectomy, TEM can be an effective surgical option for complete removal of residual tumors.

Intraoperative digital microscopic assessment of the deep surgical margins in oral carcinoma surgery: a preliminary report

Background This study assessed the possible ability of intraoperative digital microscopic analysis to control the deep surgical margin in oral carcinoma surgery. Methods A vertical section of a surgical specimen was taken from the central part of the resected tumor. The section was assessed using a digital microscope. The results of digital microscopic analysis were compared with the corresponding results of the conventional histopathologic assessment. Results The method was accurate in 10 of the 12 patients (83%) in evaluating the closest deep surgical margin. There was no significant difference in the tumor-margin distance between the digital microscopic and the histopathologic assessments in these 10 patients (Wilcoxon signed-rank test, P > .13). Conclusions The digital microscopic examination was useful in controlling deep surgical margins and selecting the nearest margin for additional frozen section analysis. Additional methods that could clarify the difference between the tumor and fibrous tissue are necessary.

Observation of tumour thickness and resection margin at surgical excision of primary oral squamous cell carcinoma—assessment by ultrasound

Tumour thickness and the status of resection margins are of prognostic significance in the treatment of oral cancer. In a single blind prospective study, 14 patients with biopsy proven oral squamous cell carcinoma had intraoral ultrasound imaging done preoperatively to measure tumour thickness, and intraoperatively to measure the deep surgical margin half way during resection. The cut surface was demonstrated on ultrasound by placing a metal, ultrasound-reflective, retractor into the surgical cut. The ultrasound measurements were compared to the subsequent histological measurements. Using the threshold of 5 mm as indicator of margin clearance, there was agreement in 10 out of 14 cases between ultrasound and histology. Ultrasound detection of close surgical margins had a sensitivity of 83% and a specificity of 63%. For preoperative tumour thickness measurement, ultrasound imaging showed a high degree of correlation with histology (Pearson correlation coefficient = 0.95, P < 0.01). This original paper demonstrates that high resolution ultrasound imaging applied intraorally is a reliable tool in objectively assessing both the tumour thickness and the surgical margin clearance at the time of surgery.

Oncology; oral surgery: The status of the deep surgical margins in tongue and floor of mouth squamous cell carcinoma and risk of local recurrence; an analysis of 68 patients

Oncology; oral surgery: The status of the deep surgical margins in tongue and floor of mouth squamous cell carcinoma and risk of local recurrence; an analysis of 68 patients

The status of the deep surgical margins in tongue and floor of mouth squamous cell carcinoma and risk of local recurrence; an analysis of 68 patients

The objective of this study is to retrospectively assess the clinical relevance, i.c. the event of a local recurrence, in patients surgically treated for tongue and floor of mouth squamous cell carcinoma when tumour cell are observed histopathologically at a distance of less than 0.5cm. Furthermore, the pattern of invasion and the presence or absence of perineural spread were recorded. A total of 68 patients, surgically treated because of a tongue or floor of mouth squamous cell carcinoma, were examined. Patients in whom any degree of epithelial dysplasia was observed in the mucosal surgical margins had been excluded beforehand.Local recurrence occurred in 2 out of 30 patients with a free surgical margins >0.5cm and in 3 out of 38 patients with a free surgical margin <0.5cm, the difference being not statistically significant. Apparently, the presence of tumour cells within a distance of less than 0.5cm, but not into the deep surgical margin, does not necessarily seem to require additional treatment. The pattern of invasion and the presence or absence of perineural spread were not significantly related with local recurrence either.