Positive Final Margins Research Articles

Benign and borderline phyllodes tumors of the breast: Clinicopathologic analysis of 205 cases with emphasis on the surgical margin status and local recurrence rate

BackgroundThe management of benign and borderline phyllodes tumors of the breast with a positive surgical margin is still controversial. Our aim in this study was to evaluate the impact of surgical margin status on the local recurrence rate of benign and borderline phyllodes tumors. MethodsWe reviewed 205 phyllodes tumors (191 benign, 14 borderline) that were surgically excised at our hospital between 2005 and 2019. Follow-up information extending to at least 6 months after surgery was retrieved from the clinical, radiology, and pathology records. ResultsThe initial surgical margin was negative in 54 (26%) cases, close (≤ 1 mm) in 29 (14%) cases, and positive in 122 (60%) cases. Approximately half of the cases with a close margin and two-third of the cases with a positive margin underwent re-excision to obtain negative margins. Three (2.3%) local recurrences were observed among 131 cases with follow-up information, all three with benign phyllodes tumor. Of these three patients, one had a positive final margin, and two had negative final margins. There was no significant difference in the rate of local recurrence between PT with a positive surgical margin versus a close and negative margin. ConclusionThe study results suggest that close clinical and radiologic follow-up may provide a better course of management rather than re-excision when managing positive margins in benign and borderline phyllodes tumors.

Cytopathologic assessment of gloves and instruments after major head and neck surgery

PurposeTo investigate the potential for cancer cells to be transferred between anatomic sites via instruments and other materials. Materials and methodsPilot prospective study from April 2018–January 2019 at Rush University Medical Center. Glove and instrument washings were collected from 18 high-risk head and neck cancer resection cases (36 samples total). Each case maintained at least one of the following features in addition to a diagnosis of squamous cell carcinoma or sarcoma: palliative/salvage surgery, positive margins, extensive tumor burden, and/or extra capsular extension (ECE). Surgical gloves and four main instruments were placed through washings for blind cytological assessment (2 samples/case). Results18 patients undergoing surgical tumor resection for biopsy-proven squamous cell carcinoma with at least one of the aforementioned characteristics were included. 26.7% of cases had ECE, 40.0% had positive final margins and 46.7% had close final margins. Tumor locations included: oral cavity (10), neck (4), parotid gland (2), and skin (2). Malignant cells were isolated on glove washings in 1 case (5.5%). No malignant cells were isolated from instrument washings. The single case of malignant cells on glove washings occurred in a recurrent, invasive squamous cell carcinoma of the scalp with intracranial extension. Anucleated squamous cells likely from surgeon skin were isolated from 94.4% of washings. Squamous cells were differentiated from mature cells by the absence of nuclei. ConclusionsMalignant squamous cells can be isolated from surgical glove washings, supporting the practice of changing of gloves after gross tumor resection during major head and neck cancer resections.

Specimen oriented intraoperative margin assessment in oral cavity and oropharyngeal squamous cell carcinoma

ObjectiveEvaluate the oncologic outcomes and cost analysis of transitioning to a specimen oriented intraoperative margin assessment protocol from a tumour bed sampling protocol in oral cavity (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC).Study designRetrospective case series and subsequent prospective cohort studySettingTertiary care academic teaching hospitalSubjects and methodsRetrospective case series of all institutional T1-T2 OCSCC or OPSCC treated with primary surgery between January 1st 2009 – December 31st 2014. Kaplan-Meier survival estimates with log rank tests were used to compare patients based on final margin status. Cost analysis was performed for escalation of therapy due to positive final margins. Following introduction of a specimen derived margin protocol, successive prospective cohort study of T1-T4 OCSCC or OPSCC treated with primary surgery from January 1st 2017 – December 31st 2018. Analysis and comparison of both protocols included review of intraoperative margins, final pathology and treatment cost.ResultsAnalysis of our intra-operative tumour bed frozen section protocol revealed 15 of 116 (12.9%) patients had positive final pathology margins, resulting in post-operative escalation of therapy for 14/15 patients in the form of re-resection (7/14), radiation therapy (6/14) and chemoradiotherapy (1/14). One other patient with positive final margins received escalated therapy for additional negative prognostic factors. Recurrence free survival at 3 years was 88.4 and 50.7% for negative and positive final margins respectively (p = 0.048). Implementation of a specimen oriented frozen section protocol resulted in 1 of 111 patients (0.9%) having positive final pathology margins, a statistically significant decrease (p < 0.001). Utilizing our specimen oriented protocol, there was an absolute risk reduction for having a final positive margin of 12.0% and relative risk reduction of 93.0%. Estimated cost avoidance applying the specimen oriented protocol to our previous cohort was $412,052.812017 CAD.ConclusionImplementation of a specimen oriented intraoperative margin protocol provides a statistically significant decrease in final positive margins. This change in protocol leads to decreased patient morbidity by avoiding therapy escalation attributable only to positive margins, and avoids the economic costs of these treatments.Graphical abstract

Differences in Re-excision Rates for Breast-Conserving Surgery Using Intraoperative 2D Versus 3D Tomosynthesis Specimen Radiograph

Intraoperative specimen radiographs performed during breast conservation surgery for cancer reduces the need for re-excision for positive margins. We studied 2D versus 3D image-guided cavity margin excision and compared it to final pathology and need for additional surgery. We conducted a retrospective review of 657 breast-conserving operations performed for cancer from 2013 to 2018. Procedures were performed by four surgeons at a single tertiary institution with access intraoperatively to 2D and 3D radiographs. Data collected included demographics, intraoperative margin assessment, final pathology, and re-excision rates. A total of 466 patients had 2D and 191 had 3D specimen imaging. The 2D group had a lower mean age and a higher body mass index and proportion of minority patients than the 3D group (P < 0.01). In the 3D group, there was a higher percentage of patients with mammographically denser breasts (P < 0.06); 58% of patients in the 3D group had additional imaging-directed cavity margins excised versus 32% of patients in the 2D group (P < 0.01). In the 2D group, 44 patients (9%) had positive final margins versus 8 patients (4%) in the 3D group (P = 0.02). No difference was found on total volume of excision (P = 0.56). The re-excision rate for the 2D group was 11% versus 5% for the 3D group (P = 0.02; adjusted odds ratio = 0.41, 95% confidence interval 0.19-0.86). Re-excision rates using both modalities are low. A lower re-excision rate is independently associated with 3D tomosynthesis. This allows surgeons to excise additional margins at the index operation, decreasing reoperations and anxiety/costs for patients.

Incidence and impact of dysplasia at final resection margins in cancers of the oral cavity

Background The literature often cites margin status as being free, close or involved by tumor but there is very sparse evidence of the relevance of dysplasia at resection margin. Aims/Objectives: To compare the impact of dysplasia at final resection margin (D-FRM) and other margin statuses on overall survival (OS) and disease free survival (DFS). Methods This is a retrospective review of 1700 treatment naïve oral squamous carcinoma patients who underwent surgery between January 2012 and December 2015. The study arm consisted of patients with dysplasia at final resection margin (D-FRM). Each of these patients were double propensity matched to obtain positive (P-FRM), close (C-FRM) and free final resection margins (F-FRM). Results There was no hazard discrimination in survival among the D-FRM and C-FRM (vs F-FRM; p-0.597, HR-1.207 (0.621–2.346) and p-0.075, HR-1.594 (0.947–2.684), respectively). A decreasing survival trend was observed as the grade and number of D-FRM margins increased. Although not significant, the addition of adjuvant therapy for D-FRM showed a trend towards improved survival outcomes compared to C-FRM, especially with chemotherapy. Conclusion and relevance: The presence of D-FRM, irrespective of grade, had a similar impact on survival as C-FRM and underscores the possible need for treatment intensification.

Abstract B37: Cytopathologic assessment of gloves and instruments after major head and neck surgery: Implications for intraoperative practices

Abstract Introduction: The purpose of the present study was to investigate the potential for cancer cells to be transferred between anatomic sites via instruments and other materials, promoting the dissemination of cancerous cells from existing tumors to previously unaffected regions of the body. Methods: Pilot prospective study over a 6-month period (April-August 2018) at Rush University Medical Center of glove and instrument washings from 15 high-risk head and neck cancer resection cases (30 samples total). Each case maintained at least one of the following features in addition to a biopsy-proven diagnosis of squamous cell carcinoma or sarcoma of the head and neck: palliative surgery or salvage surgery, positive initial or final margins, extensive tumor burden, and/or extracapsular extension (ECE). After completion of each ablative procedure, surgical gloves of the primary surgeon and the four main surgical instruments in direct contact with the tumor were placed through washings for cytologic assessment (2 samples per case). Tumor and case characteristics were recorded. Samples were blindly evaluated by a board-certified cytopathologist for cytologic assessment. Results: 15 patients (11 males, 4 females, average age 65.13 years) undergoing surgical tumor resection for biopsy-proven squamous cell carcinoma with at least one of the aforementioned additional characteristics were included in the study. 26.7% of cases had ECE, 40.0% of cases had positive final margins, and 46.7% of cases had close final margins. Resected tumor locations included the oral cavity (7 cases), neck (4 cases), parotid gland (2 cases), and skin (2 cases). Malignant cells were isolated on glove washings in 1 case (6.7% of cases). No malignant cells were isolated from instrument washings. The single case of malignant cells on glove washings occurred in a recurrent, invasive squamous cell carcinoma of the scalp with intracranial extension. Anucleated squamous cells likely from surgeon skin contamination were isolated from 93.3% of instrument washings and 93.3% of glove washings. These squamous cells were differentiated from mature cells of the oral cavity by the absence of nuclei. Conclusions: Malignant squamous cells can be isolated from surgical glove washings. This supports the common practice of changing gloves during major head and neck cancer resections and may have important implications for intraoperative practices. Additional investigation is needed to assess for viability of detected malignant cells. Citation Format: Hannah N. Kuhar, Aryan Shay, Peter C. Revenaugh, Kerstin Stenson, Bobby Tajudeen, Paolo Gattuso, Samer Al-Khudari. Cytopathologic assessment of gloves and instruments after major head and neck surgery: Implications for intraoperative practices [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B37.

Survival Outcomes for Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck.

Survival outcomes for advanced non-melanoma skin cancers of the head and neck treated with surgical resection are not well described in the literature. We aimed to describe outcomes for T3 and T4 cutaneoous squamous cell carcinoma of the head or neck treated with surgical resection at 1 tertiary academic medical center. We analyzed a retrospective cohort of patients diagnosed with T3 or T4 cutaneous squamous cell carcinoma (SCC) of the head or neck from 2005 to 2016 treated with definitive surgical resection. Survival outcomes were examined using Kaplan-Meier analysis, and multivariate analysis was completed with Cox proportional hazard model. Forty-three patients met inclusion criteria. The mean age at diagnosis was 74.7 years (SD = 10.2), and 34 (79.1%) patients were male. Twelve (27.9%) patients were immunosuppressed. Radical resection, defined as temporal bone resection, orbital exenteration, calvarial resection, mandibulectomy, or maxillectomy, was performed in 25 (58.1%) cases. Final surgical margins were positive in 19 (44.2%) cases. Patients with tumors of the scalp/neck had a 1-year survival probability of 85.7%, and the probability of survival 1 year after a neck dissection was greater than 93%. Anatomical subsites, specifically scalp/neck tumors, tended to have worse overall survival. Positive final margins tended to indicate a worse prognosis, and overall survival and recurrence were not significantly different among patients who underwent radical surgical resection compared to soft tissue resection.

Soft tissue sarcoma of the hand: Is unplanned excision a problem?

BackgroundSoft tissue sarcoma (STS) of the hand are prone to unplanned excisions, altering oncologic outcomes. The aim of this study is to compare STS of the hand with initial treatment at an oncology center versus those initially treated at a non-oncology center. Additionally, we evaluated what factors were associated with oncologic outcomes. MethodsWe retrospectively identified patients with a STS of the hand using ICD-9 codes along with an institutional oncologic database. We included all adult patients with a non-metastatic STS of the hand (n = 64) with a median follow up of 4.0 years (IQR:1.7–10.0). ResultsEight-three percent (n = 53) of tumors had an unplanned excision, of which one was treated at the oncology center. Patients treated primarily at an oncology center were older (57.6 vs. 43.6 years), had fewer operations and tended to have a larger tumors (median 4.7 cm vs. 3.0 cm) compared to those initially treated at a non-oncology center. The 5-year survival for patients treated at an oncology center was 60% compared to 89% in those initially treated at a non-oncology center. Worse disease-free survival was associated with positive final margins and subfascial tumors. ConclusionTumors with primary treatment at an oncology center were larger and presented in older patients, having worse overall survival compared to those initially treated at a non-oncology center. Initial treatment at a non-oncology center did not influence the oncologic outcomes, but lead to more re-excisions and amputations. Final tumor margins and tumor depth determined oncologic outcomes.

The Relationship of Breast Density and Positive Lumpectomy Margins.

A positive lumpectomy margin after breast-conserving surgery (BCS) is a significant predictor for ipsilateral cancer recurrence. The MarginProbe, a Food and Drug Administration (FDA)-approved device for intraoperative assessment of lumpectomy margins, is associated with a reduction in re-excision surgery. This study aimed to evaluate the relationship of mammographic breast density (MBD) and clinicopathologic characteristics with margin status in women undergoing BCS with the MarginProbe. The institutional database was queried for patients with breast cancer who had BCS with the MarginProbe from 2013 to 2017. Clinicopathologic characteristics were collected. The study defined MBD as less dense (Breast Imaging Reporting and Data System [BI-RADS] A and B) and more dense (BI-RADS C and D). A positive margin was defined as smaller than 1mm. Pearson Chi square and uni- and multivariate logistic regression were performed. Of 1734 patients, 341 met the study criteria. The median patient age was 63years. The patients with higher mammographic density were younger (p < 0.0001) and had a lower body mass index (BMI) (p < 0.0001). The patients with higher MBD were more likely to present with a palpable mass (p = 0.0360). Of the 341 patients, 135 (39.6%) had one or more positive margins on the main specimen, and 101 (74.8%) were converted to final negative margins after the MarginProbe directed re-excisions. Positive final margins were associated with larger tumor size (p = 0.0242) and more advanced stage of disease at diagnosis (p = 0.0255). In this study of patients undergoing BCS, breast density was not correlated with the likelihood of a positive margin. The presence of positive final lumpectomy margins was associated with older age and more extensive disease.

Digital Breast Tomosynthesis for Intraoperative Margin Assessment during Breast-Conserving Surgery.

Intraoperative margin assessment for breast cancer patients undergoing segmental mastectomy (SM) enables identification of positive margins, with immediate excision of additional tissue to obtain negative margins. The aim of this study was to determine the ability of digital breast tomosynthesis (DBT) to detect positive margins compared with an institution's standard extensive processing (SEP). SM specimens underwent intraoperative SEP with two-dimensional (2D) imaging of the intact and sliced specimen, with review by a breast radiologist and gross assessment by a breast pathologist. Findings guided the surgeon to excise additional tissue. DBT images of intact specimens were prospectively obtained and retrospectively reviewed by a breast radiologist. A positive margin was defined as tumor at ink. Ninety-eight patients underwent 99 SMs. With SEP, 14 (14%) SM specimens had 19 positive margins. SEP did not detect 3 of the 19 positive margins, for a sensitivity of 84%, specificity of 78%, positive predictive value (PPV) of 11%, and negative predictive value (NPV) of 99%. Moreover, DBT did not detect 5 of the 19 positive margins, for a sensitivity of 74% (p > 0.05), specificity of 91% (p < 0.05), PPV of 21.5%, and NPV of 99%. With SEP guidance to excise additional tissue, six cases had final positive margins, with SEP not identifying three of these cases and DBT not identifying two. Pathology from the second surgery of these patients showed either no additional malignancy or only focal ductal carcinoma in situ. DBT is an accurate method for detecting positive margins in breast cancer patients undergoing SM, performing similar to institutional labor-intensive, intraoperative standard processing.

The Influence of Smoking and Age on Pathologic Features and Outcomes in Oral Cavity Squamous Cell Cancer: A Multi-institutional Collaborative Study

To evaluate the impact of smoking and age on the frequency of pathological risk factors and outcomes for surgically staged oral cavity squamous cell carcinoma (OCSCC) in a multi-institutional analysis. A collaborative database of patients with primary OCSCC among 6 academic medical centers encompassing non-metastatic cases diagnosed between 2005 and 2015 was constructed. All cases were treated with surgery +/- adjuvant radiation therapy (RT) +/- concomitant chemotherapy (CRT) according to risk factors. Patients were categorized based on smoking history and age and the resultant groups were compared for demographic data, pathologic features and treatment modalities using t-test and Chi-squared tests. Kaplan-Meier curves and Log-rank p-values as well as multivariate analysis (MVA) for recurrence free survival (RFS). We identified 1055 cases that met our inclusion criteria after excluding 227 patients with unknown smoking history and incomplete records. Median age was 61 years, 60% of cases were men, 88% were White; and oral tongue (22%) followed by floor of mouth (18%) were the most common sub-sites. The median follow up time was 40 months (15-195 months). Surgery alone, surgery + RT and surgery + CRT were utilized in 32%, 37% & 31% of cases respectively. Smokers either during or at any point before diagnosis (“Ever Smoked”) were 730 cases (69%), whereas “Never Smoked” constituted the remaining 31% (n=325). Smoking was significantly associated with male sex, heavy alcohol use (38% vs 3%) and floor of mouth location (28% vs 6%) (p<0.001 for all). Adverse pathologic features were similar in both groups including grade, AJCC stage, lymphovascular (LVI) and extracapsular space invasion (ECE); except for perineural invasion (PNI) that was detected more in smokers (48% vs 37%; p=0.003). Three and 5 years RFS were not influenced by smoking (62.8% & 57.7% for Ever Smoked vs. 62% & 56.2% for Never Smoked; p=0.553). Even when we further categorized our study population into current (36%), former (33%) and never smokers (31%) similar results were attained both for risk features and RFS and the same occurred within different AJCC stages. RFS for patients younger than 50 years (n=193; 18%) was also not significantly different when compared to older ones 50-70 (n=584; 56%) and > 70 years (n=278; 26%) with 3-year RFS of (67%, 74% & 51%) and 5-year RFS of (64%, 73% & 51%) for the three groups respectively (p=0.74). On MVA, classical factors namely higher AJCC stage, PNI, LVSI, ECE and positive final margins were independently associated with worse RFS (p<0.05 for all). Both smoking and young age were not associated with any detrimental effect. In our multi-institutional analysis that included one of the largest cohorts to date for oral cavity squamous cell carcinoma treated with modern modalities with adequate follow up, smoking history and young age did not skew outcomes. Smoking was not correlated with any adverse risk feature except for perineural invasion.

Fibroepithelial lesions of the breast: a comprehensive morphological and outcome analysis of a large series

AbstractMammary fibroepithelial lesions encompass a wide spectrum of tumors ranging from an indolent fibroadenoma to potentially fatal malignant phyllodes tumor. The criteria used for their classification based on morphological assessment are often challenging to apply and there is no consensus as to what constitutes an adequate resection margin. We studied a retrospective cohort of 213 fibroepithelial lesions in 178 patients (80 fibroadenomas with unusual features and 133 phyllodes tumors: 63 benign, 41 borderline, and 29 malignant) in order to describe the spectrum of changes within each group, with special emphasis on margin evaluation. Outcome data were available for 153 fibroepithelial lesions in 139 patients (median 56 months, range 3–249 months). Positive final margin (tumor transected), age < 50 years and a predominantly myxoid stroma were statistically significant predictors of local recurrence, while age > 50, stromal overgrowth, diffuse marked atypia, necrosis and mitotic index of ≥ 10 per 10 HPF were predictive of distant metastases. Tumors with satellite/bulging nodules were at a significantly higher risk to have a final positive resection margin. Our findings highlight important aspects of the interpretation and reporting of fibroepithelial lesions: the amount of myxoid stroma and the presence of satellite nodules are clinically relevant and should be routinely assessed and reported; infiltrative border might not be a prerequisite for the diagnosis of malignant phyllodes tumor, while the presence of tumor necrosis, massive stromal overgrowth or mitotic index of ≥ 25 per 10 HPF is diagnostic of malignant phyllodes tumor. On the other hand, increased mitotic index outside of the range of the World Health Organization guidelines in the absence of other worrisome features should be treated with caution, as it can be found in benign tumors.

Sporadic Abdominal Wall Desmoid type Fibromatosis: treatment paradigm after thirty two years

BackgroundDesmoid-type fibromatosis is a benign mesenchymal neoplastic process. It exhibits an uncertain growth pattern and high recurrence rate. Previously radical surgical resection was the mainstay of treatment, but recently more surgeons are opting for conservative management with observation (“wait and see” policy). The authors intend to evaluate different therapeutic modalities and oncological outcomes for abdominal wall desmoid tumors.MethodsWe performed a retrospective study of patients who underwent surgical, hormonal or chemotherapy treatment for abdominal wall desmoid tumors between 1982 to 2014 at two institutions affiliated with the University of São Paulo, Brazil.ResultsIn the study period, 32 patients were included. Twenty-seven patients had surgery upfront. Of those, 89% were women with a median age of 33 years. Mean tumor size was 10 cm. Pathology confirmed free margins in 92% of resections. Tumor recurrence rate was 11%, with median relapse-free survival being 24 months. Multivariate analysis showed that positive final margins (p < 0.001) and positive frozen section (p = 0.001) were independent predictors of recurrence. For the 5 patients who underwent pharmacological therapy, median age was 33 years and median tumor diameter before treatment was 13 cm. Four patients exhibited partial response by Response Evaluation Criteria in Solid Tumors (RECIST). The single patient who did not respond to RECIST underwent radiotherapy.ConclusionDesmoid tumor treatment has been evolving over the past decade towards a more conservative approach. Pharmacological treatment may result in tumor size regression. When surgical excision is indicated, positive margins represent an important prognostic factor for local tumor recurrence.

The impact of caudate lobe resection on margin status and outcomes in patients with hilar cholangiocarcinoma: a multi-institutional analysis from the US Extrahepatic Biliary Malignancy Consortium

BackgroundThe objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma. MethodsA database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes. ResultsA total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival. ConclusionCaudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation.

Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2 Squamous Cell Carcinoma.

Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.

Phyllodes Tumors

Phyllodes tumors are rare primary breast neoplasms graded as benign, borderline, or malignant based on pathology characterization of the stromal component. Core-needle biopsy is recommended as the first diagnostic step for breast lesions suspicious for phyllodes. Surgical excisional biopsy is recommended for a core-needle biopsy showing cellular fibroepithelial lesion or a mass suspicious for phyllodes tumor as pathology diagnosis is challenging, especially on limited tissue specimens. Surgical treatment parallels that for soft tissue sarcoma rather than breast adenocarcinoma. Wide local excision and mastectomy, with 1 cm tumor-free margins, provide equivalent oncologic outcomes. Tumor enucleation, subtotal resection, and positive final margins should be avoided. Axillary surgery is not recommended as lymph node metastases are rare. Adjuvant radiation is not recommended as routine, nor is adjuvant chemotherapy, although either or both may be considered for primary or recurrent high-risk malignant phyllodes tumors on a case-by-case basis. Local recurrence rates are influenced by margin status and tumor grade. Distant metastases occur in up to 25% of patients with borderline/malignant tumors and bestow a poor prognosis. Recent molecular genetic analyses of phyllodes tumors have identified potentially targetable mutations that may guide future therapy for high-risk, recurrent, or metastatic phyllodes tumors. This review contains 5 figures, 5 tables, and 53 references. Key words: biomarkers, breast sarcoma, diagnosis, outcomes, pathology, phyllodes tumor, surgery, treatment

Phyllodes Tumors

Phyllodes tumors are rare primary breast neoplasms graded as benign, borderline, or malignant based on pathology characterization of the stromal component. Core-needle biopsy is recommended as the first diagnostic step for breast lesions suspicious for phyllodes. Surgical excisional biopsy is recommended for a core-needle biopsy showing cellular fibroepithelial lesion or a mass suspicious for phyllodes tumor as pathology diagnosis is challenging, especially on limited tissue specimens. Surgical treatment parallels that for soft tissue sarcoma rather than breast adenocarcinoma. Wide local excision and mastectomy, with 1 cm tumor-free margins, provide equivalent oncologic outcomes. Tumor enucleation, subtotal resection, and positive final margins should be avoided. Axillary surgery is not recommended as lymph node metastases are rare. Adjuvant radiation is not recommended as routine, nor is adjuvant chemotherapy, although either or both may be considered for primary or recurrent high-risk malignant phyllodes tumors on a case-by-case basis. Local recurrence rates are influenced by margin status and tumor grade. Distant metastases occur in up to 25% of patients with borderline/malignant tumors and bestow a poor prognosis. Recent molecular genetic analyses of phyllodes tumors have identified potentially targetable mutations that may guide future therapy for high-risk, recurrent, or metastatic phyllodes tumors. This review contains 5 figures, 5 tables, and 53 references. Key words: biomarkers, breast sarcoma, diagnosis, outcomes, pathology, phyllodes tumor, surgery, treatment

Effect of Margin Status on 10-Year Local Recurrence and Survival Outcomes in a Large Population-Based Analysis of Women Treated With Breast-Conserving Therapy

A 2014 SS0/ASTRO consensus statement suggests “no ink on tumor” is a sufficient surgical margin for invasive breast cancer treated with breast conserving surgery (BCS). Whether long-term outcomes in cases with close margin <2mm are inferior to cases with clear margins >2mm remains controversial. This study evaluates 10-year outcomes by margin status in a population-based cohort of women treated with BCS and adjuvant radiotherapy (RT). Subjects were 10,863 women with pT1-T3, any N, M0 invasive breast cancer referred from July 1, 2001 to Dec. 31, 2011, an era in which re-excision was generally used for close or positive margins. Data on margin location was available in a subset of 2381 cases referred from Jan. 1, 2010 to Dec. 31, 2011. All women underwent BCS and adjuvant whole breast ± boost RT (boost RT generally used for close or positive final margins or age < 50). Ten-year local recurrence (LR), and breast cancer-specific survival (BCSS) were examined using Kaplan-Meier (KM) and competing risk analysis in cohorts with negative (>2mm; n=9241, 85%), close (≤2mm; n=1310, 12%), or positive (tumor touching ink; n=312, 3%) margins. Competing risk multivariable analysis (MVA) was performed using Fine and Gray modeling. Matched-pair analysis compared LR and BCSS between close/positive cases matched to negative margin controls. Median follow-up was 8 years. Systemic therapy was used in 87% of patients. Boost RT was used in 34.1%, 76.9% and 79.5% of patients with negative, close, and positive margins, respectively. In the negative, close, and positive margin cohorts, 10-year KM outcomes were: LR 2.8%, 4.3%, and 4.0% and BCSS 93.7%, 91.5%, and 87.4%, respectively. On competing risk MVA, close margins were not significantly associated with either increased LR (HR 1.25, 95% CI 0.79-1.97, p=0.35) or reduced BCSS (HR 1.25, 95% CI 0.98-1.58, p=0.07) relative to negative margins. Age <45, grade 3, ≥4 positive nodes, and no systemic therapy were factors associated with both increased LR and reduced BCSS. On MVA, use of boost RT was not associated with LR (p=0.92) or BCSS (p=0.30). On matched-pair analysis, close margin cases had similar LR (p=0.11) and BCSS (p=0.10) compared to negative margin controls. Among the 554 cases with close or positive margins from 2010-2011 in whom data on margin location were available, 57% were anterior or posterior, so these findings may not be broadly generalizable to cohorts in which the majority of close margins are potentially re-resectable. In patients treated with breast-conserving therapy for invasive breast cancer, close margins were not associated with increased LR or reduced BCSS compared to negative margins. This population-based analysis corroborates the SSO/ASTRO consensus statement.

Frozen section during partial nephrectomy: Does it predict positive margins? Gordetsky J, Gorin MA, Canner J, Ball MW, Pierorazio PM, Allaf ME, Epstein JI. BJU Int. 2015 Dec; 116(6):868-72. [Epub 2015 Mar 23]. doi: 10.1111/bju.13011.

To investigate the clinical utility of frozen section (FS) analysis performed during partial nephrectomy (PN) and its influence on intra-operative management. We performed a retrospective analysis of consecutive PN cases from 2010 to 2013. We evaluated the concordance between the intra-operative FS diagnosis and the FS control diagnosis, a postoperative quality assurance measure performed on all FS diagnoses after formalin fixation of the tissue. We also evaluated the concordance between the intra-operative FS diagnosis and the final specimen margin. Operating reports were reviewed for change in intra-operative management for cases with a positive or atypia FS diagnosis, or if the mass was sent for FS. A total of 576 intra-operative FSs were performed in 351 cases to assess the PN tumor bed margin, 19 (5.4%) of which also had a mass sent for FS to assess the tumor type. The concordance rate between the FS diagnosis and the FS control diagnosis was 98.3%. There were 30 (8.5%) final positive specimen margins, of which four (13.3%) were classified as atypia, 17 (56.7%) as negative and nine (30%) as positive on FS diagnosis. Intra-operative management was influenced in six of nine cases with a positive FS diagnosis and in one of nine cases with an FS diagnosis of atypia. The relatively high false-negative rate, controversy over the prognosis of a positive margin, and inconsistency in influencing intra-operative management are arguments against the routine use of FS in PN cases.

Surgeon performed continuous intraoperative ultrasound guidance decreases re-excisions and mastectomy rates in breast cancer

BackgroundIntraoperative ultrasound guided (IUG) breast conserving surgery (BCS) is being increasingly embraced by breast surgeons worldwide. We aimed to compare the efficacy of IUG-BCS for palpable and nonpalpable breast cancer with respect to margin status, re-excision rate, tissue sacrifice and cost-time analysis. MethodsIntraoperative localization protocol includes intraoperative ultrasound prior to excision to localize the lesion and guide the initial resection. The excised specimen was then examined visually and by palpation and the specimen and cavity was examined with ultrasound. Frozen sections were obtained routinely from a portion of all six faces of the resected specimen, and shaved cavity margins were sent for permanent histology. ResultsOf the 208 patients, 57.2% had nonpalpable tumors. The sensitivity of ultrasound localization was 100%. Negative margins were achieved in 92.43% of nonpalpable and 91.01% of palpable lesions at initial procedure. The involved margins were correctly identified by the surgeon via specimen sonography in 95.4% of cases. Final positive margin rate was 2.4%. Calculated resection ratio and time analysis revealed nothing significant. ConclusionIUG-BCS is an invaluable and effective modality for obtaining clear surgical margins with optimum resection volumes and reducing re-operations. Furthermore, by means of this algorithm, in case of shaving cavity margins of the tumor bed for permanent analysis, frozen section evaluation might be omitted.