Wide Local Excision Specimens Research Articles

Histopathological discrepancy of biopsy specimens compared to subsequent Mohs surgery or wide local excision specimens

Histopathological discrepancy of biopsy specimens compared to subsequent Mohs surgery or wide local excision specimens

Residual melanoma in wide local excision specimens after 'complete' excision of primary cutaneous in situ and invasive melanomas.

Wide local excision (WLE) to achieve adequate clearance margins is the standard initial definitive treatment for patients with biopsy-proven primary cutaneous melanoma. Residual melanoma in WLE specimens after prior complete excision-biopsy (CEB) is reported in 0-6.3% of cases. However, studies evaluating the prevalence, clinicopathological features and relevance of persistent disease in WLE specimens are limited. This study sought to determine the frequency of and clinicopathological characteristics associated with residual melanoma in WLE specimens performed after a CEB of primary cutaneous or acral melanoma (in situ or invasive) with clinically and histologically tumour-free margins, and assess its relevance. A review of the research database and pathology archives of a large Australian tertiary referral melanoma treatment centre was performed. Eligible patients were those for whom a definitive WLE was performed after CEB of a primary melanoma (in situ or invasive) with negative clinical and histological margins, between May 2013 and May 2015. All partial biopsies were excluded. Of 640 eligible patients, 510 (79.7%) had invasive melanoma and 130 (20.3%) had melanoma in situ. Residual disease was identified in 20 cases (20/640, 3.1%), of which three (15%) were melanoma in situ on CEB and 17 (85%) were invasive melanoma. On univariate analysis, the presence of residual disease in WLE specimens was associated with lentigo maligna (LM)/LM melanoma (LMM) subtype [odds ratio (OR) 10.33; 95% confidence interval (CI) 2.84-37.54; p=0.004], nodular melanoma (NM) subtype (OR 4.92; 95% CI 1.53-15.85; p=0.0076) and, for invasive tumours, higher tumour mitotic rate (mean 7.7, SD 7.51 vs 3.4, SD 4.83; OR 1.11; 95% CI 1.04-1.18; p=0.0014). Breslow thickness >4 mm was associated with a higher risk of residual disease (OR 7.30; 95% CI 1.88, 28.26; p=0.004). Cases with residual disease had primary tumours with a significantly larger diameter (median 14 mm, range 4-25) than those without residual disease (median 9 mm, range 2-60), (OR 1.07; 95% CI 1.03-1.11; p≤0.001) and were also more likely to be amelanotic (38% vs 14%), (OR 3.69; 95% CI 1.17, 11.60; p=0.026). Residual disease was associated with assessment of >3 slides of tissue (OR 6.98; 95% CI 1.54-31.62; p=0.0118) and complete blocking of the scar (OR 31.69; 95% CI 3.98-252.21; p=0.0011). Residual melanoma in WLE specimens is an infrequent occurrence. Risk factors for residual disease are LM/LMM and NM melanoma subtypes, higher mitotic rate, larger lesion diameter and amelanosis. Tumours with these features warrant more extensive pathological sampling. WLE after CEB for melanoma remains an important procedure to reduce local recurrence; however, limited pathological sampling of the WLE scar is probably appropriate for cases lacking high risk features.

Differences Between Recommended Surgical Margins and Measured Histological Margins in Malignant Melanoma In Situ and Malignant Melanomas.

Wide local excision (WLE) using appropriate surgical margins is the standard surgical management for malignant melanoma in situ (MMIS) and primary cutaneous malignant melanoma (MM). The actual width of the histologic margins is frequently not assessed, whereas narrow histologic margins are associated with an increase in local melanoma recurrence. Our objective was to analyze the actual measured histological margins of WLE specimens of MMIS and MM cases and compare them with their recommended surgical margins. A retrospective study of formalin fixed specimens of MMIS and invasive MM treated with WLE from a large university-affiliated dermatopathology laboratory was conducted. Among a total of 164 MMIS and 128 MM cases, 14 MMIS (8.5%) and 7 MM (5.9%) had positive lateral margins. The median histologic margin for MMIS, after a 15% tissue shrinkage adjusted, was 2.7 mm [1.3-3.9] for LM type and 3.9 mm [2.3-5.6] for non-LM type, in contrast to the recommended 5-mm margin. In 96 MM of T1 type (≤1.0 mm), the median adjusted histologic margin was 6.7 mm [3.5-9.1] in contrast to the recommended 10-mm margin. These results show that measured and adjusted median histologic margins in WLE specimens in both MMIS and MM of T1 type were significantly narrower than the recommended surgical margins, regardless of anatomic location. These differences are concerning, whether they reflect clinicians' intentional or unintentional deviation from recommended guidelines.

Learning from the wastage: histomorphology of columnar cell lesions and other changes in surgical pathology breast specimens

Introduction: In recent few decades, widespread use of mammography has resulted in increased detection of precursor and preinvasive breast lesions such as atypical ductal hyperplasia, ductal carcinoma in situ and, a type of breast lesion termed, ‘Flat epithelial atypia” which belongs to the group of columnar cell lesions with atypia. Although in India, invasive breast cancer is still most common presentation than early preinvasive lesions, with advanced diagnostic set up and increased awareness, early detection of preinvasive lesions is bound to be increased in future. For their accurate diagnosis, it is very necessary to be aware and alert about the morphology of these lesions. Objectives: Present study was undertaken to study the morphology of Columnar Cell Lesion and other changes in Surgical Biopsy specimens received in Histopathology laboratory of a tertiary health care centre. Materials and Methods: Excessive sections were taken from breast tissue surrounding the primary lesion in mastectomy or wide local excision specimens received over two-year duration and were examined for various changes in the epithelium and in the stroma especially columnar cell lesions and other precursor lesions. Results: A spectrum of precursor lesions including columnar cell lesions could be commonly seen in most of the specimens. Their morphology and differential diagnosis could be studied in details in these sections which otherwise are wasted usually. Conclusion: The tissue surrounding primary lesion in surgical pathology breast specimens is a good source to study the detailed morphology of columnar cell lesions and other lesions to get familiar with them for their accurate detection and early diagnosis in future. Keywords: Precursor breast lesions, Columnar cell lesions, Flat epithelial atypia, Ductal hyperplasia.

Considerations for Timing of Defect Reconstruction in Cutaneous Melanoma of the Head and Neck.

The objective of this study is to identify the incidence and characteristics of cases with positive margins on wide local excision for cutaneous melanoma of the head and neck (CMHN) and therefore provide a potential basis for selectively delaying reconstruction pending final histological clearance of melanoma. A systematic review of English language articles was performed on studies retrieved from PubMed and Web of Science. Original investigations published between July 1999 and June 2018 reporting on margin status of CMHN wide local excision specimens were included in the review. The incidence of positive margins after definitive resection for cutaneous melanoma in the literature ranges from 6 to 20.9%. The incidence is higher in cases of advanced patient age, diagnosis by shave biopsy, lentigo maligna melanoma subtype, desmoplastic subtype, tumor thickness, and ulceration. Delayed reconstruction remains the most oncologically sound decision, allowing for interpretation of margin status on paraffin-embedded tissue sections. However, resection and the resultant defect closure in a single stage is more expedient and potentially a more efficient use of resources. The risk-benefit ratio of immediate versus delayed reconstruction must be considered for each case. The incidence of positive margins is higher in cases of advanced patient age, diagnosis by shave biopsy, lentigo maligna melanoma subtype, desmoplastic subtype, increasing tumor thickness, and the presence of ulceration; delayed reconstruction should be strongly considered in these cases.

Clinical feasibility of optical coherence micro-elastography for imaging tumor margins in breast-conserving surgery.

It has been demonstrated that optical coherence micro-elastography (OCME) provides additional contrast of tumor compared to optical coherence tomography (OCT) alone. Previous studies, however, have predominantly been performed on mastectomy specimens. Such specimens typically differ substantially in composition and geometry from the more clinically relevant wide-local excision (WLE) specimens excised during breast-conserving surgery. As a result, it remains unclear if the mechanical contrast observed is maintained in WLE specimens. In this manuscript, we begin to address this issue by performing a feasibility study of OCME on 17 freshly excised, intact WLE specimens. In addition, we present two developments required to sustain the progression of OCME towards intraoperative deployment. First, to enable the rapid visualization of en face images required for intraoperative assessment, we describe an automated segmentation algorithm to fuse en face micro-elastograms with OCT images to provide dual contrast images. Secondly, to validate contrast in micro-elastograms, we present a method that enables co-registration of en face images with histology of WLE specimens, sectioned in the orthogonal plane, without any modification to the standard clinical workflow. We present a summary of the observations across the 17 specimens imaged in addition to representative micro-elastograms and OCT images demonstrating contrast in a number of tumor margins, including those involved by invasive ductal carcinoma, mucinous carcinoma, and solid-papillary carcinoma. The results presented here demonstrate the potential of OCME for imaging tumor margins.

Sampling of wide local excision specimens in cutaneous malignant melanoma.

Wide local excisions (WLEs) are frequently undertaken in the management of cutaneous melanoma; however, there is a considerable variability in their macroscopic sampling. The aim of our study was to establish evidence-based guidelines for the macroscopic handling of these specimens with a subsequent review of the impact on our service. The study group of 128 cases with initial biopsy and subsequent WLE in our institution in 2010 were identified by a computer-generated search. From analysis of this group, guidelines for macroscopic sampling were derived with a repeat search performed in 2012. Residual melanoma was detected only in those cases in which the original specimen had clear margins of ≤1 mm or with a pigmented lesion. A 32% increase in case numbers was noted over this period with a reduction of 6.2% in block numbers. Average block numbers per case were reduced by 2.3 (30.7%). We have shown that for WLE specimens with no evidence of a macroscopic lesion and clear margins on original biopsy, little is to be gained from extensive sampling. In these cases we recommend a maximum of 3 blocks per case. Reduction in sampling based on this evidence would result in saving valuable laboratory resources.

Frequency of Residual Melanoma in Wide Local Excision Specimens After Complete Excisional Biopsy

Wide local excision (WLE) is the standard of care for histologically confirmed, primary cutaneous melanoma. However, there is little available evidence

Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy

We sought to better understand the role of wide local excision (WLE) in the treatment of cutaneous melanoma by analyzing residual or locally metastatic disease in WLE specimens of melanomas initially diagnosed with a complete excisional biopsy. This was a retrospective review of 807 consecutive WLEs of melanomas diagnosed after complete excisional biopsy. All specimens were reviewed by a single dermatopathologist. Risk of residual or locally metastatic disease was analyzed using univariate and multivariate logistic regression models. In the 807 WLE specimens, further melanoma was found in 34 cases (4.2%; 95% confidence interval [CI] 2.9-5.8). Residual primary melanoma was found in 33 of these. On univariate analysis, features associated with residual or locally metastatic disease were histologic subtype (odds ratio 3.0; 95% CI 1.3-7.1, P=.01) and tumor location (odds ratio 7.3; 95% CI 2.0-26.6, P<.01). On multivariate analysis, lentigo maligna was independently associated with melanoma remaining in WLE specimens (odds ratio 2.7; 95% CI 1.0-7.3, P=.04). Residual melanoma in WLE specimens after histologically assessed complete excisional biopsy is not uncommon. Patients with lentigo maligna subtype melanomas are most at risk. Our findings indicate that the procedure of WLE is most important therapeutically for its role in controlling the primary tumor, rather than in preventing local metastatic recurrence.

215. Colour inking of breast wide local excision specimens in theatre: Time economy for the surgeon looking to improve departmental pathology diagnostics

Background: Nipple discharge has a known association with breast cancer, determing which cases to identify as being at high risk is a complex task for the clinician. The current policy at West Herfordshire hospital NHS Trust is to offer microdochectomy to all women who present with unilateral single duct nipple discharge, dominant duct discharge, or persistent duct discharge. The aim of this study was to determine if on basis of the pattern of nipple discharge, patients could be subselected for microdochectomies, and to create a base line to allow future subselection of patients for surveillance only Methods: All patient with single duct unilateral spontaneous nipple discharge, who underwent microdochectomy, were assessed. Demographics, clinical presentation, radiological assessment, cytology, core biopsy. This group of patients was analysed and correlated with their final histological assessment. Results: 122 patients were analysed in this study. 7 ( 5.74%) were diagnosed with carcinomas. 4 patients had ductal carcinoma in situ, three patients had dutcal carcinoma in situ and invasive ductal carcinoma, of these two patients had blood stained nipple discharge. Two other patients had papillary carcinomas, one patient of these two had blood stained nipple discharge. 47 out of 122 patient presented with history of blood statined discharge, 30 were negative for cytology, two patients had (ductal carcinoma in situ with Invasive ductal carcinoma and papillary ca) at final histololgy. 17 of the 47 showed cellular cytology, and one patient had intermediate grade DCIS confirmed on final histology, whereas in the remaining sixteen patients histological features of papillomas, duct ectasia, and benign breast disease was noted. Of the 122 patient 42 patients had mammary duct ectasia (34%), 52 patients had papillomas (42%) at final histology. Conclusions: The negative predictive value (2/30), appears in this series appears to be more valuable than, the positive predictive value (1/17) in cellular smears to predict ductal carcinoma or invasive ductal carcinoma. Cytological assessment of nipple discharge is equivocal at its best. Microdochectomy perford for nipple discharge results in a low rate of malignancy on excision and is comparable with other series. No conflict of interest.

Positive Tumor Margins in Wide Local Excision of Breast Cancer: A 10-Year Retrospective Study

Background. The safety of wide local excision as a standard surgical option for early stage breast cancer management in Ghana has not been evaluated. The aim of this study was to use retrospective histopathological descriptive study to evaluate the prevalence of positive tumor margins in wide local excision specimens and offer recommendations. Study design. We reviewed 147 breast lumps, following wide local excision, which were received in the Department of Pathology, for positive tumor margins. The data was analyzed using SPSS software (version 16). Results. A total of 2,751 female breast cancers were diagnosed during the study period, of which 147 (5.3%) were from wide local excisions (lumpectomies). Thirty-one (21.0%) had positive tumor margins. The mean age of women with positive margins was 53.4 (SD = 17.1) years. The mean size of primary tumor was 4.0 (SD = 2.1) cm, the majority (53.0%) of which were greater than 2.0 cm, but less than or equal to 5.0 cm (T2). A total of 26 (83.4%) of these tumors were invasive ductal carcinomas (NOS), 24 (92.3%) of the cases had combined Bloom-Richardson grading, and many, 10 (41.7%), were grade 1. Conclusion. Our study shows that 21.0% of all wide local excision biopsies had positive tumor margins, a figure that is comparable to those of other studies. Tumors with positive margins in this study were large, 4.0 cm (T2), and common in relatively young women. Treatment failure is therefore likely to occur in these patients.

Audit on clinical coding of breast surgery clinic outcomes

Audit on clinical coding of breast surgery clinic outcomes

The impact of biopsy technique on upstaging, residual disease, and outcome in cutaneous melanoma

Background After skin biopsy of malignant melanoma, the findings in the subsequent wide local excision (WLE) sometimes result in upgrading of the T-category. Herein, we examine the influence of biopsy technique on residual disease in melanoma WLE specimens and on upstaging. Methods We performed a retrospective review of data from malignant melanoma patients who underwent sentinel lymph node biopsy between 1997 and 2010. Results A total of 609 patients were biopsied by shave (51%), punch (19%), and excision (30%). Residual disease was seen in 240 patients (39%) at WLE, of whom 60% had undergone shave biopsy. Fifty-nine patients had a T-category upgrade after WLE (10% of all patients); 64% were sampled by shave. Seven percent of patients with a T-category upgrade had negative margins initially. Positive biopsy margin and greater thickness predicted T-category upgrade. Conclusions Partial biopsy for melanoma resulted in more residual disease at WLE and a higher rate of T-category upgrade. Moreover, the presence of negative margins at biopsy did not ensure lack of residual disease.

Precise correlation between MRI and histopathology – Exploring treatment margins for MRI-guided localized breast cancer therapy

Background Magnetic resonance imaging (MRI) is more often considered to guide, evaluate or select patients for partial breast irradiation (PBI) or minimally invasive therapy. Safe treatment margins around the MRI-visible lesion (MRI-GTV) are needed to account for surrounding subclinical occult disease. Purpose To precisely compare MRI findings with histopathology, and to obtain detailed knowledge about type, rate, quantity and distance of occult disease around the MRI-GTV. Methods and materials Patients undergoing MRI and breast-conserving therapy were prospectively included. The wide local excision specimens were subjected to detailed microscopic examination. The size of the invasive (index) tumor was compared with the MRI-GTV. The gross tumor volume (GTV) was defined as the pre-treatment visible lesion. Subclinical tumor foci were reconstructed at various distances to the MRI-GTV. Results Sixty-two patients (64 breasts) were included. The mean size difference between MRI-GTV and the index tumor was 1.3 mm. Subclinical disease occurred in 52% and 25% of the specimens at distances ⩾10 mm and ⩾20 mm, respectively, from the MRI-GTV. Conclusions For MRI-guided minimally invasive therapy, typical treatment margins of 10 mm around the MRI-GTV may include occult disease in 52% of patients. When surgery achieves a 10 mm tumor-free margin around the MRI-GTV, radiotherapy to the tumor bed may require clinical target volume margins >10 mm in up to one-fourth of the patients.

Comparison of margin assessment by radial and shave sections in wide local excision specimens for invasive carcinoma of the breast

Standard margin assessment of breast carcinoma surgical specimens uses radial sections perpendicular to the margin. Shave sections assess a larger surface area of margin than radial sections. The aim was to assess the value of additional shave sections of the margin. Both types of section were used to assess 471 wide local excision specimens for invasive carcinoma. One hundred and seventy-nine specimens had positive margins: only radial margins were involved (tumour within 5 mm of margin) in 76, only shave margins in 45, and both shave and radial margins in 58. Residual carcinoma was found in re-excision specimens (immediate or later) in 43% when the closest distance to the radial margin was 0-1 mm, 25% for 2-4 mm, 18% for 5-9 mm and 13% for >9 mm. Residual carcinoma was found in 44% of specimens if any shave section was positive and in 9% if all shaves were negative. Residual carcinoma was found in 32% if either radial or shave sections were positive and in 4% if neither was positive. The combination of radial and shave sections appears to be good at separating patients into two groups with high and low risk of residual carcinoma.

2115 Breast MRI and preoperative factors associated with cancers of limited extent in wide-local excision specimens

2115 Breast MRI and preoperative factors associated with cancers of limited extent in wide-local excision specimens

Using Histopathology Breast Cancer Data to Reduce Clinical Target Volume Margins at Radiotherapy

This study aimed to quantify the incidence and extension of microscopic disease around primary breast tumors in patients undergoing breast-conserving therapy (BCT), focusing on a potential application to reduce radiotherapy boost volumes. An extensive pathology tumor-distribution study was performed using 38 wide local excision specimens of BCT patients. Specimen orientation was recorded and microscopic findings reconstructed to assess the incidence of microscopic disease around the macroscopic tumor. A model of disease spread was built, showing probability of disease extension outside a treated volume (P(out,vol)). The model was applied in 10 new BCT patients. Taking asymmetry of tumor excision into account, new asymmetric margins for the clinical target volume of the boost (CTV(boost)) were evaluated that minimize the volume without increasing P(out,TTV) (TTV being total treated volume: V(surgery) + CTV(boost)). Potential reductions in CTV(boost) and TTV were evaluated. Microscopic disease beyond the tumor boundary occurred isotropically at distances > 1 cm (intended surgical margin) and > 1.5 cm (intended TTV margin) in 53% and 36% of the excision specimens, respectively. In the 10 prospective patients, the average P(out,TTV) was, however, only 16% due to larger surgical margins than intended in some directions. Asymmetric CTV(boost) margins reduced the CTV(boost) and TTV by 27% (20 cc) and 12% (21 cc) on average, without compromising tumor coverage. Microscopic disease extension may occur beyond the current CTV(boost) in approximately one sixth of patients. An asymmetric CTV(boost) that corrects for asymmetry of the surgical excision has the potential to reduce boost volumes while maintaining tumor coverage.

Detection of residual disease following breast-conserving surgery.

Assessment of completeness of tumour excision has become an integral part of breast-conserving surgery, but the accuracy of margin analysis has been questioned. This study compared the results of resection margin analysis with an examination of tumour bed biopsies and of the excised cavity wall. One hundred and forty-four patients underwent breast-conserving surgery for T1-2 N0-1 breast cancer. Following wide local excision, four bed biopsies were taken from the cavity wall which was then completely excised. The presence of invasive and in situ disease at the inked resection margin (IRM) and in the adjacent bed biopsies and cavity wall was recorded. Positive margins and/or residual disease in either the bed biopsies or cavity wall was found in 62 (43 per cent) of 144 cases. Residual disease (invasive or in situ) was present at the IRM in 39 specimens (27 per cent) and was present in 25 bed biopsy (17 per cent) and 39 cavity wall (27 per cent) specimens. These comprised different but overlapping groups of patients. Margin analysis of wide local excision specimens is a poor predictor of completeness of excision. Routine resection and examination of the entire cavity wall increases the detection of residual disease compared with examination of bed biopsies alone and is a useful adjuvant to conventional margin evaluation.

Does preoperative MRI influence the extent of surgical resection in conservative breast cancer surgery?

Abstract We assessed prospectively the impact of preoperative breast magnetic resonance (MRI) on the extent of surgical resection. Of 131 breast cancers treated with breast conservation over 18 months, 41 underwent preoperative MRI. Scans were shown to the operating surgeon to indicate the location of lesions and their local extent. Clinical information and histological assessment of wide local excision specimens were compared between those patients who underwent preoperative MRI and those who did not. There was no significant difference between the MRI group ( n =41) and no-MRI group ( n =90) in average specimen weight ( P = 0.72) or circumferential margin status ( P = 0.17). Logistic regression analysis demonstrated a positive correlation between margin status and patient age ( P = 0.045), younger patients being more likely to have involved margins, and a negative correlation with MRI status ( P = 0.006) these women having an MRI being more likely to have negative margins. Preoperative MRI does not currently influence the extent of surgical resection in breast conservation surgery.

Can magnetic-resonance imaging help elucidate natural history of breast cancer multicentricity?

We evaluated prospectivelywhether small enhancing foci, seen separately from the maintumour on contrast-enhanced MRI, were indeed cancer fociand whether MRI could detect all cancer foci identified byradiological-histological correlation.We studied ten patients and did preoperative contrast-enhanced breast MRI. High resolution transverse T1-weighted 3D FLASH images (TR=18 ms, TE=7 ms,FA=40°, TA=4 m 56 s, FOV=410 mm) before and after anintravenous bolus hand injection of dimegluminegadopentetate (Magnevist, 0·2 mL/kg) were acquired at 1·0T (Siemens Magnetom Scanner 42 SP with dedicated breastcoil). The 3D volume was 64 mm thick with 32 partitionsgiving an effective slice thickness of 2 mm and this wassufficient to cover the entire breast in all cases. After surgicalexcision (four mastectomies, six wide local excisions), thespecimens were fixed and sliced at 5 mm intervals in thesame plane as the MRI. Routine histopathologicalexamination was performed by an experienced breastpathologist and the remaining material was radiographed.Two observers identified radiological abnormalities(calcifications, densities, or spiculations) and all lesions thatwere deemed suspicious by either observer were sampledand examined histologically. MRI images were reviewedindependently and findings were compared withhistopathology results.On MRI, 19 enhancing foci separate from the maintumour were identified in seven out of ten patients (figure).On radiography of specimen slices, 71 suspicious areas weresampled and histological examination revealed 15 areas ofin-situ cancer (nine) or invasive cancer (six) in five patients.All five patients with cancer foci were amongst the sevenpatients who had enhancing foci on MRI. In two of these fivepatients, the tumour was surrounded by widespreadenhancement on MRI and all 11 (four+seven) areas sampledshowed cancer foci. In all wide local excision specimens, theenhancing foci on MRI were within 11 mm of the tumouredge and therefore within the resected specimen.Our data suggest that enhancing foci on MRI representcancer foci and that MRI detected 14 out of 15 cancer foci(sensitivity 93%). Of course, this is based on the assumptionthat the radiological-histological correlational method isindeed the gold standard. If that is so, the specificity of MRIfor tumour detection would be 79% (15/19). However,bearing in mind that the spatial resolution of MRI is of theorder of 1–2 mm, it may yet transpire that MRI could haveeven greater sensitivity and specificity which may becomeapparent with an even more obsessional sampling of thespecimen.