Pathologic assessment of surgical margins on frozen and permanent sections in breast conserving surgery

The diagnostic value of frozen section was evaluated in the histologic assessment of surgical margins obtained by wide excision of breast tumors. There were 87 patients with unilateral breast cancer, and 5 with bilateral breast cancers. The periphery of the excised breast tissue was peeled like an orange and histologically examined by frozen and permanent section. If either in situ or infiltrating microscopic tumor was found at the margin, it was considered positive. Using frozen sections, the margin was judged histologically positive or suspicious in 30 tumors (31%) and negative in 67(69%) tumors. Positive surgical margins were histologically confirmed by permanent section in 20(67%) of the 30 tumors diagnosed as positive or suspicious on frozen section. Another 10 tumors had negative margins. In 4 tumors, however, while the initial or re-excised margin was negative on frozen section, the margins were positive by permanent section. These surgical margins were positive due exclusively to the presence of ductal carcinoma in situ (DCIS). Evaluation of surgical margins in breast cancer by frozen section, thus exhibited a diagnostic accuracy of 86&prtcnt;, a sensitivity of 83%, and a specificity of 86%. It is concluded that frozen sections are useful in the determination of involvement of surgical margins after the wide excision of breast cancer. It must be pointed out that frozen sections will ofter overestimate involvement of the surgical margins.     

Accuracy of ultrasound-guided breast-conserving surgery in the determination of adequate surgical margins

The goal of this study was to assess the size of the ultrasound-measured margin associated with an adequate surgical margin during breast-conserving surgery (BCS). The study was designed as a prospective cohort study. Patients with primary invasive breast cancer undergoing BCS were included. The ultrasound-measured surgical margins were compared with the pathological margins. 147 patients were eligible for analysis. 21 (14.3 %) patients had close or positive resection margins and 13 (8.8 %) underwent a second operation. Small excision volume, multifocality, postmenopausal status, high grade tumor-associated intraductal component, and invasion of lymph vessels and lymph nodes were associated with increased risk of positive excision margins. In the study cohort, 882 Ultrasonography (US) margins were measured and a good correlation to the pathological margins was observed. Overestimation of the US-measured margins relative to the pathological margins was increased with younger age, premenopausal status, and intraductal component. The estimated positive and negative predictive values, sensitivity and specificity were 81.0, 96.2, 48.4, and 99.1 %, respectively. We found that a sonographically estimated margin of ≥4 mm was associated with an adequate pathological margin of ≥1 mm in 100 % of tumors that did not have a high grade intraductal component. However, this was not applicable for tumor-associated high grade intraductal component where a US margin of 14 mm was associated with clear pathological margins in 100 % of cases. Intraoperative ultrasonography is a safe and feasible method to obtain clear surgical margins by BCS.     

浸润性乳腺癌MRI征象与HER-2及Ki-67表达的相关性

目的:探讨浸润性乳腺癌（IBC）核磁共振成像（MRI）征象与人表皮生长因子受体2（HER-2）、肿瘤增殖抗原Ki-67表达的相关性。方法:选择2015年6月至2017年12月在我院进行治疗的IBC患者65例为研究对象,对所有患者进行MRI扫描检查,采用免疫组化检查患者的HER-2、Ki-67阳性表达。分析MRI征象与HER-2、Ki-67阳性表达的相关性。结果:MRI扫描检查结果显示:边缘毛刺征患者占比63.08%（41/65）、分叶征患者占比58.46%（38/65）、钙化患者占比73.85%（48/65）、淋巴结转移患者占比67.69%（44/65）。免疫组化检查结果显示:HER-2阳性患者占比69.23%（45/65）、Ki-67阳性患者占比58.46%（38/65）。存在边缘毛刺征、分叶征、钙化、淋巴结转移的患者HER-2、Ki-67阳性表达高于无边缘毛刺征、无分叶征、无钙化、无淋巴结转移的患者（P＜0.05）。经Spearman相关性分析显示,乳腺癌肿块的边缘毛刺征、分叶征、钙化、淋巴结转移与HER-2、Ki-67阳性表达呈正相关（P＜0.05）。结论:IBC的MRI影像学特征与患者的HER-2、Ki-67阳性表达水平呈正相关,可通过对IBC患者细胞生物学因子指标水平的判断,评估患者疾病的严重程度以及预后情况等。     

Malignant seeding of the lumpectomy cavity upon breast-conserving surgery.

One of the etiologic factors involved in local recurrence after breast-conserving surgery may be malignant seeding of the wound during the lumpectomy procedure. A total of 340 patients with stage I and II breast cancer were entered into the study. Of these, 270 patients received breast-conserving surgery (BCS group), and the other 70 patients underwent mastectomy (control group). After resection, lavage cytology was performed at the surgical wound. There were 55 patients (20.4%) who showed positive lavage cytology in the BCS group. In the control group, there were only 3 patients (4.3%) with positive cytology. Positivity was significantly higher in the former group (p = 0.00064). Patients with evidence of cutting across cancer lesions showed significantly higher positive rates in lavage cytology (p < 0.00001). Positivity in lavage cytology was significantly higher in patients with positive surgical margins evaluated by frozen sections (p = 0.0017), touch cytology (p < 0.0001) and formalin-fixed, paraffin-embedded sections (lateral or medial margin; p = 0.0036, anterior and posterior margin: p = 0.0210). The positivity was also significantly higher in patients with an extensive intraductal component (p < 0.0001), and less than or equal to 50 (p = 0.0061) years of age. Multivariate analysis revealed that the highest relative risk factor for positive cytology was evidence of cutting across cancer lesions (relative risk = 8. 166; p < 0.00001).     

Surgical margin status as a cause of local failure after breast conserving therapy

Background  To elucidate the cause of in-breast recurrence after breast conserving surgery, we analyzed the characteristics of resected specimens histopathologically, especially the surgical margin status. Materials and Methods  1) Pathological surgical margin positivity was reevaluated in terms of the distance from the resected surgical margin by pathologists from seven institutions in 486 cases with complete stepwise pathological examination.2) We reviewed pathological specimens including surgical margins from 30 patients with in-breast recurrence for whom serial sections of resected primary breast cancer specimens were available and made comparisons of the time to in-breast recurrence. Results  Cancer cells at the surgical margin were present at a rate of 4.1 % on the surface and 15.2% within 5 mm on the areolar side of the surgical margin. Histopathologically, the reasons for local recurrence after breast conserving therapy included a positive surgical margin (21/30), lymphatic permeation (4/30), and others (5/30). The last category included cases with an inadequate margin diagnosis because of a biopsy scar. Disease-free intervals for the patients without postoperative radiotherapy decreased as the volume of cancer cell nests in the surgical margin increased (P=0.06). On the other hand, this trend was not observed in the group with postoperative radiotherapy. Conclusion  Adequate materials are essential for accurate evaluation of surgical margin status. Quantitative evaluation of surgical margin status, apart from whether or not radiotherapy was performed, is important for estimating the risk and disease-free period to in-breast recurrence.     

Absence of residual fluorescence in the surgical bed at near-infrared fluorescence imaging predicts negative margins at final pathology in patients treated with breast-conserving surgery for breast cancer

IntroductionPositive margins after breast-conserving surgery (BCS) for breast cancer (BC) remain a major concern. In this study we investigate the feasibility and accuracy of indocyanine green (ICG) fluorescence imaging (FI) for the in vivo assessment of surgical margins during BCS.Materials and methodsPatients with BC admitted for BCS from October 2015 to April 2016 were proposed to be included in the present study (NCT02027818). ICG (0.25 mg/kg) was intravenously injected at induction anesthesia and ICG-FI of the surgical beds was correlated with final pathology results.ResultsFifty patients consented to participate and thirty-five patients were retained for final analysis, 15 patients having been excluded for, respectively, incomplete video records data for signal to background ratio (SBR) calculation (11) and in situ tumors (4). The final pathological assessment of 35 breast specimens identified 5 (14.7%) positive margins. Intraoperative ICG-FI revealed hyperfluorescent signals in 15 (42.9%) patients and an absence of fluorescent signals in 20 (57.1%). Median SBR in patients with involved margins was 1.8 (SD 0.7) and was 1.25 (SD 0.6) in patients with clear margins (p = 0.05). The accuracy, specificity, positive and negative predictive value of ICG-FI for breast surgical margin assessment were 71%, 60%, 29% and 100%, respectively.ConclusionICG-FI of BC surgical beds has a high negative predictive value for surgical margin assessment during BCS. The absence of residual fluorescence in the surgical bed of patients with fluorescent tumors predicts negative margins at final pathology and allows the surgeon to avoid further intraoperative analysis.     

Clinicopathologic factors related to surgical margin involvement,reoperation, and residual cancer in primary operable breast cancer – An analysis of 2050 patients

Background

To evaluate whether clinicopathologic factors are related to surgical margin involvement, reoperation, and residual cancer in primary operable breast cancer.

Rapid intraoperative scrape cytology assessment of surgical margins in breast conservation surgery

Rapid intraoperative scrape cytologic examination for diagnosing surgical margin involvement of specimens obtained by breast conservation surgery was evaluated. Four surgical margins (nipple side, two lateral sides and distal side) of the removed breast tissue were cytologically examined and histologically compared following segmentectomy in 50 breast cancer patients (200 margins). Intraductal carcinoma had a tendency to spread most extensively to the nipple, compared with other margins. The margin positive rate of tumors with ductal spread (DS) of over 20 mm was significantly higher than in tumors with a DS under 20 mm (52.2% vs 7.4%) (P<0.001). Of 50 canditates 10 patients underwent total mastectomy due to positive margins on repeat cytologic examination after re-excision. Four of the 10 patients had an extensive intraductal component on microscopy. The sensitivity, specificity and accuracy of cytology were 96.4%, 90.7% and 91.5%, respectively. Scrape cytology is useful to determine surgical margin involvement after segmentectomy for breast cancer, although overestimation of involvement will tend to result.     

Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ

BACKGROUND: Breast conserving surgery (BCS) is common practice for unifocal ductal carcinoma in situ (DCIS) less than 4 cm in size, but the extent of tumor free margin width around DCIS necessary to minimize recurrence is unclear. METHODS: Clinical and pathologic details were recorded from all patients with pure DCIS < 4 cm in size, treated with BCS between 1978 and 1997. Histologic margins were measured by using an ocular micrometer. Patients with clear margins (> 1 mm) were divided up into 3 groups for analysis based on margin of normal tissue excised: 1.1-5 mm, 5.1-10 mm, and 10.1-40 mm. RESULTS: There were 66 patients with close margins (< or = 1 mm), of which 25 cases (37.9%) recurred. The recurrence rates for the 3 clear margin groups ranged from 4.5-7.1%. Median followup was 47 months (range 12-197 mos). Risk of recurrence in the group with close margins was greater than the subgroups with clear margins (P < 0.001); no differences in recurrence was seen between the individual subgroups with clear margins. Nuclear Grade 3 was predictive of recurrence (P = 0.03). Following excision alone, the recurrence rate was 18.6%, compared with 11.1% when radiotherapy was given as adjuvant therapy. Women with clear margins following excision had a recurrence rate of only 8.1%. CONCLUSION: After BCS for DCIS, close margins were associated with a high risk of local recurrence. Radiotherapy did not compensate for inadequate surgical clearance.     

Clear margins for invasive lobular carcinoma: A surgical challenge

Background

The main goal of breast conservative surgery (BCS) is the complete removal of cancer with clear margins and no deformity of the breast. However, in invasive lobular carcinoma (ILC) this goal is hard to achieve because of the underestimation of tumor size. Our study was the first to show the role of surgical techniques in the achievement of clear margins for ILC.

Methods

We reviewed 73 patients with ILC who underwent BCS at Paris Breast Center between January 2005 and June 2008. Full thickness excision (FTE) was performed in a routine basis and oncoplastic surgery (OPS) upon tumor location, volume ratio and overall density of the breast. Margin status was evaluated as positive, close or clear.

Results

Positive/close margins were found in 39% of cases and were lower than what was described in the literature (49-63%). FTE was performed in 47 (64%) patients and OPS in 26 (36%) patients. No positive/close margins were observed in patients with lesions located in the lower/central quadrants. Multivariate analysis showed multifocality, larger tumor size and FTE to be independent risk factors for positive margins at final surgery.

Conclusions

Our rate of positive/close margins for ILC was lower than what was described in the literature. The determinant key difference was in our surgical procedures with FTE or OPS differing from the standard BCS described in the literature and we suggest that OPS is to be considered for ILC. It allows larger breast conservative surgery with good cosmetic results and lower rate of compromised margins.     

The value of breast lumpectomy margin assessment as a predictor of residual tumor burden in ductal carcinoma in situ of the breast

BACKGROUND: Margin width is considered the most important risk factor for local recurrence in ductal carcinoma in situ (DCIS) of the breast. The purpose of this report is to assess the predictive utility of lumpectomy specimen margin assessment for the presence and extent of residual DCIS. METHODS: Specimens from 253 DCIS cases with lumpectomy and reexcision were studied to determine to the probability of residual DCIS on reexcision. The probability of residual tumor was evaluated with respect to tumor size, margin status, nuclear grade, presence of necrosis, patient age, and the extent of specimen processing (number of sections/volume tissue). Lesions were grouped by size: less than or equal to 2 mm, greater than 2-15 mm, greater than 15-40 mm, or greater than 40 mm. Margin width was recorded as the distance of DCIS to the closest specimen edge or, for positive margins, scored as: extensive (margin involvement in > or =8 sections or >4 low-power fields [LPFs]), moderate (5-7 sections or 2-4 LPFs), minimal (2-4 sections or 1 LPF), or focal (1 section, single focus). The amount of residual tumor was graded by maximum dimension on a semiquantitative basis. RESULTS: Initial excision margin significantly predicted for the presence of residual tumor on reexcision. Residual tumor was found on reexcision in 85% of extensively positive, 68% of moderately positive, 46% of minimally positive, 30% of focally positive, 41% of greater than 0-1 mm, 31% of greater than 1-2 mm, and 0% of greater than 2 mm margins (P < 0.0001). On univariate analysis, margin width and lesion size of initial excision specimens significantly predicted for the presence of residual DCIS on reexcision. Age, grade, necrosis, and extent of specimen processing were not significant prognostic factors. On multivariate analysis, both initial margin width (P < 0.0001) and lesion size (P = 0.02) significantly predicted for residual DCIS. As for amount of residual tumor, margin width and initial lesion dimension both significantly predicted for medium to large residuum, whereas age 45 years or younger was of borderline significance on univariate analysis. On multivariate analysis, margin width and lesion size on initial excision both remained significant predictors of larger volume residual tumor. CONCLUSIONS: The margin status of a DCIS lumpectomy specimen is the most important predictive factor for both the presence and amount of residual disease.     

Impact of Using Intra-Operative Ultrasound Guided Breast- Conserving Surgery on Positive Margin and Re-Excision Rates in Breast Cancer Cases with Current SSO/ASTRO Guidelines

Purpose: To review the impact of using intra-operative ultrasound guided breast conserving surgery with frozen sections on nal pathological margin outcome with the current guidelines set forth by the Society of Surgical Oncology (SSO) and the American Society of Surgical Oncology (ASTRO). Materials and Methods: A retrospective review including all cases of intra-operative ultrasound guided breast conserving surgery was performed at the National Cancer Institute Thailand between 2013 and 2016. Patient demographics, tumor variables, intraoperative frozen section and nal pathological margin outcomes were collected. Factors for positive or close margins were analyzed. Results: A total of 86 patients aged between 27 and 75 years with intra- operative ultrasound guided breast conserving surgery were included. Three cases (3.5%) of positive margin were detected by intra-operative frozen section and 4 cases (4.7%) by final pathology reports. There were 18 cases (20.9%) with a close margin (     

Use of an Intraoperative Ultrasonography-Guided Localization and Tissue Fixation Device Demonstrates Less Margin Positivity During Breast-Conserving Surgery for Invasive Breast Cancer Than Standard Preoperative Needle-Wire Localization: A Retrospective Comparative Analysis in a Consecutively Treated Case Series

PurposeTo retrospectively compare 2 methods of pre-resection, image-guided tumor localization—preoperative needle-wire localization (PNWL) and intraoperative ultrasonography-guided localization and tissue fixation (IUGLTF)—for patients with invasive breast cancer at the time of breast-conserving surgery (BCS).Patients and MethodsWe identified 118 cases in which image-guided localization was required for nonpalpable and questionably palpable tumors from a series of 204 consecutive invasive breast cancers treated by BCS. We defined a positive margin as tumor at the inked surface. We defined a close margin as tumor within 1 mm or less of the inked surface.ResultsOf those 118 cases requiring pre-resection, image-guided localization, 54 patients underwent PNWL and 64 underwent IUGLTF placement. A positive margin was identified in 6 of 54 (11.1%) undergoing PNWL compared with 1 of 64 (1.6%) undergoing IUGLTF (P = .046). A positive or close margin was identified in 9 of 54 (16.7%) undergoing PNWL compared with 3 of 64 (4.7%) undergoing IUGLTF (P = .032). The mean volume and mean weight of the BCS specimens were not different in the 2 groups.ConclusionBased on the finding of less margin positivity associated with the IUGLTF technique than the PNWL technique, we believe that the use of an IUGLTF device by surgeons during BCS could be highly advantageous in the surgical management of nonpalpable and questionably palpable invasive breast cancers.     

Margins in Breast-Conserving Surgery for Early Breast Cancer: How Much is Good Enough?

Breast-conserving therapy (breast-conserving surgery (BCS) and radiation therapy) is an effective treatment for early-stage breast cancer (BC). Whilst there is consensus that risk of local recurrence (LR) following BCS is increased if the surgical margins are positive (‘ink on tumour’), consensus on what constitutes adequate negative margins has been elusive despite studies spanning decades. Recent SSO–ASTRO guidelines have recommended ‘no ink on tumour’ as the standard for negative margins in BCS for invasive BC. These were underpinned by study-level meta-analysis reporting that a minimally defined negative margin width be adopted for BCS in invasive BC and showing that wider (than a minimum >1 mm) negative margins do not significantly reduce LR risk. Recommendations on a minimum margin width for ductal carcinoma in situ (DCIS) vary substantially from >1 to 10 mm or wider; evidence-based guidelines are being developed and are expected to address ‘how much is enough’ for margin width in DCIS.     

Mammographic and sonographic features of tubular breast carcinoma

AIMS AND BACKGROUND: This study aimed to describe the mammographic and sonographic features of tubular carcinoma of the breast. METHODS: A retrospective review of 198 consecutive cases of surgically proven breast cancer revealed ten cases of tubular carcinoma of the breast. Only tumors with a tubular component of at least 75% were included in the study. Mean patient age was 56 +/- 9 years, range 35 to 70 years. RESULTS: The mean size of the tumors was 11 +/- 4 mm. On mammography, all tubular carcinomas appeared as an irregularly shaped mass with a central density in 6/10 cases. Eight tubular carcinomas were described as having spiculated margins. Microcalcifications were present in 4/10 cases. On ultrasound the tumor presented as a hypoechoic mass with irregular margins and posterior acoustic shadowing in 7/10 cases. In three cases the tumor presented as a hypoechoic mass with ill-defined margins and posterior acoustic shadowing. CONCLUSIONS: Although some specific mammographic and sonographic features may suggest the presence of a tubular carcinoma, the final differential diagnosis from other spiculated lesions of the breast should rely on histologic evidence only. Therefore, surgical biopsy should be recommended in all cases of stellate lesions of the breast detected at mammography or ultrasonogram.     

手术切缘对晚期声门型喉癌患者生存预后的影响

目的 探讨手术切缘对晚期声门型喉癌患者生存预后的影响.方法 选择接受手术治疗的140例晚期声门型喉癌患者,根据切缘情况分为阴性切缘与阳性切缘,比较二者局部复发率、区域性转移率;根据切缘范围分为≤3mm、4～5 mm、≥5 mm,比较三者局部复发情况;根据有无局部复发比较3年、5年生存率.结果 140例喉癌患者中28例患者的切缘为阳性,112例切缘阴性.阳性切缘患者中局部复发或淋巴结转移16例(57.14％),阴性切缘患者中局部复发或淋巴结转移19例(16.96％),差异具有统计学意义(P＜0.05).手术切缘≤3 mm的局部复发率为57.14％ (8/14),手术切缘4～5 mm的局部复发率为21.87％ (7/32),手术切缘≥5 mm的局部复发率为l0.64％(10/94),手术切缘≤3 mm的局部复发率显著高于手术切缘4～5 mm与≥≥5 mm的患者,比较差异具有统计学意义(P＜0.05).无局部复发患者3年、5年生存率分别为50.00％、36.61％,显著高于局部复发患者的17.86％、7.14％,比较差异具有统计学意义(P＜0.05).结论 手术切缘与晚期声门型喉癌患者的局部复发率及淋巴结转移率密切相关,切缘阳性患者复发率、转移率较高,预后较差,3年、5年生存率较低.术中可将切缘组织送快速冰冻病理检查,根据检查结果再实施手术,以降低切缘阳性率,减少复发,提高预后生存.     

Positive margins following surgical resection of breast carcinoma: analysis of pathologic correlates

BACKGROUND AND OBJECTIVES: Histologic margin positivity represents a significant source of adverse clinical outcome affecting breast conservation therapy for in situ or invasive malignancy. Elucidation of factors associated with positive margin status might clarify and improve local therapy strategies. In order to define our experience with margin positivity and to identify relevant pathologic criteria, we retrospectively analyzed the cases of 143 patients who underwent resections for carcinoma with intent of breast conservation between 1995 and 1999. METHODS: Histologic features and indices of biologic aggressiveness were compared among tumors resected with positive versus negative margins in order to determine whether such markers could be used to anticipate outcome. RESULTS: Twenty-eight pathologic specimens were identified to possess histologically positive margins. Twenty-six patients underwent additional operative procedures. Of the 26 re-excision specimens, 17 (65%) contained residual malignancy. Statistical analysis demonstrated that margin positivity correlated with in situ histology and with Her 2/neu positivity. CONCLUSIONS: These data suggest certain pathologic factors that may portend difficulty in achieving negative resection margins in patients in whom breast conservation therapy is considered.     

Treatment outcome of breast-conserving therapy in patients with positive or close resection margins: Japanese multi institute survey for radiation dose effect

BACKGROUND: The relationship between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) is controversial. To evaluate the radiation dose and other factors influencing the ipsilateral breast tumor control (IBTC) in patients with positive or close resection margins after breast conserving surgery (BCS), the Japanese Radiation Oncology Study Group (JROSG) S-99-3 study group conducted a multi-institute survey of these patients. METHODS: The patients with less than 5 mm tumor-free margins after BCS were eligible for this study. A total of 971 patients from 18 institutes were enrolled in the analysis. The final pathological margin status was classified into 3 groups. Radiation doses to the tumor bed were less than 60 Gy in 252 patients, 60 Gy in 456 patients and more than 60 Gy in 233 patients. RESULTS: IBTR was observed in 55 patients (5.8%). The IBTC rates at 5 and 10 years by the Kaplan Meier method were 95.6% and 87.3%, respectively. There was no significant difference in 10-year IBTC rates according to marginal status; 85.9% in positive margin patients, 91.0% in equal or less than 2 mm margin patients and 87.0% in 2.1-5 mm margin patients. Radiation dose to the tumor bed was a marginally significantly associated with the 10-year IBTC rate (> or = 60 Gy 90.8% vs < 60 Gy 84.2%, p = 0.057). In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better (p = 0.039). The other factors influencing the IBTC were age (> or = 35 years vs < 35 years: p < 0.0001), menopausal status (p < 0.0001) and tumor size (p = 0.023). CONCLUSIONS: In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better than the others. We recommend that the tumor bed be irradiated with at least 60 Gy in the patients with positive margins. Further follow-up is necessary to draw final conclusions.     

Preclinical evaluation of nuclear morphometry and tissue topology for breast carcinoma detection and margin assessment

Prevention and early detection of breast cancer are the major prophylactic measures taken to reduce the breast cancer related mortality and morbidity. Clinical management of breast cancer largely relies on the efficacy of the breast-conserving surgeries and the subsequent radiation therapy. A key problem that limits the success of these surgeries is the lack of accurate, real-time knowledge about the positive tumor margins in the surgically excised tumors in the operating room. This leads to tumor recurrence and, hence, the need for repeated surgeries. Current intraoperative techniques such as frozen section pathology or touch imprint cytology severely suffer from poor sampling and non-optimal detection sensitivity. Even though histopathology analysis can provide information on positive tumor margins post-operatively (~2–3 days), this information is of no immediate utility in the operating rooms. In this article, we propose a novel image analysis method for tumor margin assessment based on nuclear morphometry and tissue topology and demonstrate its high sensitivity/specificity in preclinical animal model of breast carcinoma. The method relies on imaging nuclear-specific fluorescence in the excised surgical specimen and on extracting nuclear morphometric parameters (size, number, and area fraction) from the spatial distribution of the observed fluorescence in the tissue. We also report the utility of tissue topology in tumor margin assessment by measuring the fractal dimension in the same set of images. By a systematic analysis of multiple breast tissues specimens, we show here that the proposed method is not only accurate (~97% sensitivity and 96% specificity) in thin sections, but also in three-dimensional (3D) thick tissues that mimic the realistic lumpectomy specimens. Our data clearly precludes the utility of nuclear size as a reliable diagnostic criterion for tumor margin assessment. On the other hand, nuclear area fraction addresses this issue very effectively since it is a combination of both nuclear size and count in any given region of the analyzed image, and thus yields high sensitivity and specificity (~97%) in tumor detection. This is further substantiated by an independent parameter, fractal dimension, based on the tissue topology. Although the basic definition of cancer as an uncontrolled cell growth entails a high nuclear density in tumor regions, a simple but systematic exploration of nuclear distribution in thick tissues by nuclear morphometry and tissue topology as performed in this study has never been carried out, to the best of our knowledge. We discuss the practical aspects of implementing this imaging approach in automated tissue sampling scenario where the accuracy of tumor margin assessment can be significantly increased by scanning the entire surgical specimen rather than sampling only a few sections as in current histopathology analysis.     

Utility of teledermatopathology for intraoperative margin assessment of melanoma in situ,lentigo maligna type: A 6 year community practice experience

BackgroundAchieving negative margins for melanoma in situ, lentigo maligna type can be challenging, particularly on cosmetically sensitive areas.ObjectiveTo assess the utility of intraoperative frozen section margin assessment using a teledermatopathology system in the treatment of head and neck lentigo maligna.Methods and materialsOver a 6 year period, 96 patients with lentigo maligna had surgical excisions. The margins were assessed intraoperatively with frozen sections prepared in the manner used in Mohs surgery. The surgeon guided the frozen section slides around the margin while a dermatopathologist assessed the margin remotely.ResultsIn 2/96 (2.1%) cases, the safety margin was positive (frozen sections were false negative). In 1 further case (1%) there was a recurrence of the melanoma 13 months following the excision.ConclusionThe described method is effective in treating melanoma in situ, lentigo maligna type with clearance rates similar to previous studies for Mohs surgery.