Biopsy Margins Research Articles

ASO Visual Abstract: Are Positive Biopsy Margins in Melanoma Significant? A Cohort Study of Micro- Versus Macroscopic Margin Status and Their Impact on Residual Disease and Survival.

ASO Visual Abstract: Are Positive Biopsy Margins in Melanoma Significant? A Cohort Study of Micro- Versus Macroscopic Margin Status and Their Impact on Residual Disease and Survival.

The Histopathology of Chronic "Radiation Conjunctivitis" Shows Diagnostic Features Similar to Those Seen in Radiation Dermatitis, Including Radiation Fibroblasts.

Radiation therapy is a treatment modality for various ocular and ocular adnexal tumors. The histopathology of chronic radiation dermatitis has been well-described. The authors present two cases demonstrating and characterizing "chronic radiation conjunctivitis" which has not been histopathologically illustrated in detail. Retrospective case review of two patients who received proton beam irradiation for an anterior uveal melanoma and external beam radiation for conjunctival lymphoma, and developed leukoplakia and/or thickening of the eyelid margin and symblepharon. Hematoxylin and eosin-stained sections of eyelid margin and conjunctival biopsies as well as clinical histories were reviewed. Conjunctival biopsies in both cases revealed squamous epithelial metaplasia, chronic inflammation and bizarre-appearing stromal cells with hyperchromatic nuclei in a fibrotic/sclerotic stroma, consistent with chronic radiation conjunctivitis. These stromal cells are believed to be the same "radiation fibroblasts" described in chronic radiation dermatitis. The radiation fibroblast is characteristic for the diagnosis of chronic radiation conjunctivitis, as it is in radiation dermatitis. Features of squamous metaplasia of conjunctival epithelium, keratinization, subepithelial fibrosis/sclerosis and chronic inflammation are frequently found but not specific. A detailed history and other ancillary tests help differentiate cicatrizing conjunctival conditions, and biopsy should be performed in the setting of suspicion for a secondary malignancy.

Are Positive Biopsy Margins in Melanoma Significant?: A Cohort Study of Micro- Versus Macroscopic Margin Status and Their Impact on Residual Disease and Survival.

Presence of positive biopsy margins in melanoma can provoke anxiety over potential disease progression from delays to surgical excision, but their impact on outcomes is unknown. We aimed to compare the presence of residual melanoma in the surgical excision specimen and survival between patients with negative, microscopically positive, and macroscopically positive biopsy margins. Patients with cutaneous melanoma who underwent surgical excision over a 13-year period were included. Biopsy characteristics, residual disease in the surgical specimen, and overall and recurrence-free survival were compared between patients with negative, microscopically positive (only scar visible), and macroscopically positive (visible remaining melanoma) biopsy margins. Of 901 patients, 42.4%, 33.3%, and 24.3% had negative, microscopically positive, and macroscopically positive margins, respectively. The incidence of residual invasive melanoma in the surgical specimen varied (P < 0.001), occurring in 5.5%, 17.0%, and 74.9% of patients, respectively. Both microscopically and macroscopically positive margins were associated with residual disease (P < 0.001) but only the latter predicted worse overall (P = 0.013) and recurrence-free survival (P = 0.009). Kaplan-Meier estimated survival was comparable between those with negative and microscopically positive margins, but overall (P = 0.006) and recurrence-free survival (P = 0.004) were significantly worse in the macroscopically positive margin group. These patients had worse prognosis melanoma, with 33.8% being stage III disease, and 23.2% having positive sentinel lymph nodes. Patients and physicians may be reassured in the presence of microscopically positive biopsy margins which arenot associated with worse survival, However, patients with macroscopically positive margins have poorer prognosis and should be treated within an acceptable time frame.

Evaluation and Surgical Management of Pediatric Cutaneous Melanoma and Atypical Spitz and Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group.

The purpose of this study was to develop recommendations for the diagnostic evaluation and surgical management of cutaneous melanoma (CM) and atypical Spitz tumors (AST) and non-Spitz melanocytic tumors (melanocytomas) in pediatric (age 0-10 years) and adolescent (age 11-18 years) patients. A Children's Oncology Group-led panel with external, multidisciplinary CM specialists convened to develop recommendations on the basis of available data and expertise. Thirty-three experts from multiple specialties (cutaneous/medical/surgical oncology, dermatology, and dermatopathology) established recommendations with supporting data from 87 peer-reviewed publications. (1) Excisional biopsies with 1-3 mm margins should be performed when feasible for clinically suspicious melanocytic neoplasms. (2) Definitive surgical treatment for CM, including wide local excision and sentinel lymph node biopsy (SLNB), should follow National Comprehensive Cancer Network Guidelines in the absence of data from pediatric-specific surgery trials and/or cohort studies. (3) Accurate classification of ASTs as benign or malignant is more likely with immunohistochemistry and next-generation sequencing. (4) It may not be possible to classify some ASTs as likely/definitively benign or malignant after clinicopathologic and/or molecular correlation, and these Spitz tumors of uncertain malignant potential should be excised with 5 mm margins. (5) ASTs favored to be benign should be excised with 1- to 3-mm margins if transected on biopsy. (6) Re-excision is not necessary if the AST does not extend to the biopsy margin(s) when complete/excisional biopsy was performed. (7) SLNB should not be performed for Spitz tumors unless a diagnosis of CM is favored on clinicopathologic evaluation. (8) Non-Spitz melanocytomas have a presumed increased risk for progression to CM and should be excised with 1- to 3-mm margins if transected on biopsy. (9) Re-excision of non-Spitz melanocytomas is not necessary if the lesion is completely excised on biopsy.

Does complete resection of infected bone improve clinical outcomes in patients with diabetic foot osteomyelitis?

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12-month follow-up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0-38.0 vs. RO 37.0, 20.8-50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12-month follow-up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0-66.5 vs. RO 50.5, 35.0-75.0, p = 0.02). During the 12-month follow-up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re-infections (NRO 25.3%, RO 29.3%, p = 0.56), re-infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0-365 vs. RO 106, 42.8-365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12-month follow-up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re-infection, amputation, re-ulceration or hospitalization. Level of evidence: 1.

Safety and efficacy of underwater EMR for 10- to 20-mm colorectal serrated lesions (SEA CLEAR study)

Colorectal serrated lesions (SLs) are precursors of colorectal carcinoma via the serrated neoplasia pathway. However, the success rate of endoscopic resection of large SLs is low. Therefore, this study aimed to determine the safety and efficacy of underwater EMR (UEMR) for SLs sized 10 to 20mm. This 2-center, prospective, observational study included patients with at least 1 SL sized 10 to 20mm. We resected the SLs by UEMR and performed tattooing at the resection site. Surveillance colonoscopy was performed 12 months postoperatively to evaluate local recurrence. The primary outcome was the complete resection rate of UEMR, which was defined as en bloc resection with no serrated tissue in the 4 marginal biopsy samples and histologically negative margins. UEMR was performed for 65 SLs in 58 patients, with a median lesion size of 14mm. The en bloc, R0 resection, and complete resection rates were 87.7% (57 of 65), 61.5% (40 of 65), and 60.0% (39 of 65), respectively. Adverse events included 1 (1.5%) immediate bleeding and 1 (1.5%) delayed perforation. Surveillance colonoscopy was performed in 50 patients with 57 scars, and the rates of identification for tattoos and scars were 94.7% (54 of 57) and 100% (57 of 57), respectively. The recurrence rate was 5.3% (3 of 57), and all 3 recurrent lesions were completely resected endoscopically. This 2-center prospective study demonstrated that UEMR for SLs sized 10 to 20mm was comparable to previous conventional EMR outcomes.

Unveiling the unforeseen: Asymptomatic pigmented villonodular synovitis at popliteal fossa

Pigmented villonodular synovitis (PVNS) are rare, locally aggressive, typically benign neoplasms of joints, bursae, and tendon sheaths. Symptoms include pain, stiffness, swelling, recurrent atraumatic hemarthrosis and limitation in range of motion. Our case study presents an asymptomatic PVNS at the popliteal fossa which was purely an incidental finding in a 32-year-old male with a history of trauma while playing football whose MRI was suggestive of Anterior cruciate ligament (ACL), Medial meniscus tear &amp; a focal nodular hypertrophy at posterior aspect of knee. The patient had no significant past history of trauma, swelling, hemarthrosis or similar pain. ACL Reconstruction, Medial Meniscus balancing and marginal excision and biopsy sent for the same. Biopsy suggestive of PVNS (Localised). This case report emphasizes the importance of considering PNVS in the differential diagnosis of soft tissue swelling without pain, swelling or bleeding, and should be considered as a differential diagnosis of soft tissue swellings in the posterior aspect of the knee.

794 Making the Cut: Assessing the Knowledge of and Compliance to Guidelines for Skin Cancer Excision Biopsy Margins Amongst Junior Doctors in Plastic Surgery

794 Making the Cut: Assessing the Knowledge of and Compliance to Guidelines for Skin Cancer Excision Biopsy Margins Amongst Junior Doctors in Plastic Surgery

Increased rate of upstaging of plantar melanomas may warrant more radical treatment: Study at a single NCI-designated Cancer Center

BackgroundAcral lentiginous melanoma holds the worst prognosis of all cutaneous melanomas. We aim to further detail the incidence of upstaging in plantar melanoma (PM) as well as identify factors associated with upstaging. MethodsA retrospective analysis of medical records was performed of patients who underwent surgical intervention for non-metastatic primary PM at a single NCI-designated Comprehensive Cancer Center (January 2011-August 2023). The primary outcome was rate of upstaging, defined as an increase in the T-stage on final surgical pathology compared to biopsy. Clinical and pathologic staging were determined by the AJCC 8th edition. Statistical analysis included Pearson’s Chi-squared test, Fisher’s exact test, Wilcoxon rank sum test, and Kruskal-Wallis rank sum test. ResultsForty-nine patients were identified, with an average age of 65 years (51 % male). Majority self-identified as Caucasian (55 %). Initial biopsy techniques were shave (49 %), punch (34 %) and excisional (17 %). Twenty-four patients (50 %) demonstrated upstaging. Seventy-seven percent (n = 10) of patients with clinical Tis were upstaged. Eight patients required reoperation due to upstaging, with 6 having melanoma in situ on biopsy. On multivariable logistic regression, patients with clinical Tis-T1 were more likely to be upstaged compared to T2-T3 (OR 8.75, p < 0.041). Type of biopsy, lesion size < 15 mm and positive deep margins on biopsy were not associated with risk of upstaging. ConclusionsOur findings suggest a high incidence of upstaging of PM with no identifiable factors associated with upstaging. Patients with clinical Tis or T1 PM should undergo resection with wider margins and be strongly considered for sentinel lymph node biopsy at time of index operation. SynopsisIn this large cohort of patients with non-metastatic primary plantar melanoma, half of the cohort was upstaged following resection. The risk was higher in patients diagnosed with Tis or T1 on biopsy compared to T2-T3. Biopsy type, lesion size < 15 mm and positive deep biopsy margins were not associated with upstaging. More radical treatment of plantar melanomas may be warranted.

A phase 1/2 study of vusolimogene oderparepvec (RP1) in primary melanoma (mel) to reduce the risk of sentinel lymph node (SLN) metastasis.

TPS9614 Background: The majority of the 80,000 newly diagnosed mel patients in the US have localized early-stage disease and undergo wide local excision (WLE) with or without SLN biopsy. The SLN is a critical prognostic marker and pivotal to immune response initiation, and fosters tumor-mediated immune suppression and pre-metastatic niches. Thus, SLN is a key target for local immune intervention. Vusolimogene oderparepvec (RP1), a locally administered oncolytic immunotherapy, provides a unique opportunity for intervention following mel diagnosis, prior to definitive surgical management. Derived from the HSV1 strain RH018A, RP1 exhibits superior killing on human tumor cell lines, designed with deletions in neurovirulence factors (ICP34.5 and ICP47) and immune-stimulating elements (increased US11 expression, GM-CSF and GALV-GP R-) to maximize oncolytic potency and induce cell death. Preclinical and clinical data demonstrate RP1's robust antitumor efficacy in advanced mel. This trial addresses a crucial gap in understanding RP1's impact on SLN dynamics, holding promise for preventing disease recurrence in this high-risk population. We hypothesize that in mel patients with high risk, clinically node negative disease (pT3b-T4b), administration of RP1 will reduce rates of SLN positivity compared to a historic control by favorably reshaping the immune landscape of the primary tumor, SLN and peripheral blood. Methods: This investigator-initiated, single site, open label, non-randomized phase 1/2 pilot study (NCT06216938) will enroll 25 patients with high-risk, clinically node-negative mel (pT3b-T4b). Major eligibility criteria include diagnosis of pT3b, T4a, or T4b non-uveal mel with visible residual tumor or positive initial biopsy margins, ECOG 0 or 1 and adequate organ function on screening labs. Patients will receive 3 doses (1ml/dose) of RP1, locally injected at the primary tumor site before standard WLE and SLN biopsy (SLNB). The first dose on day 1 will be 10e6 pfu/ml, followed by 10e7 pfu/ml for the next two doses on days 15 and 21, administered over 4-5 weeks before WLE and SLNB. Surgery occurs within 35 days of the 1st RP1 injection to avoid delays in definitive treatment. Biopsies and blood samples are obtained pre- and post-treatment. Patients will be followed for up to 3 years. Safety assessments include physical exams, labs, and adverse events (AE) monitoring. The primary endpoint is the rate of SLN positivity in the overall cohort, calculated by comparing the observed rates to the expected number of positive SLNs for that cohort using the Melanoma Institute of Australia's Prediction Tool. Secondary endpoints include safety and tolerability of RP1, RFS and OS. Exploratory correlative assays will compare the immunophenotype in primary tumor and the SLN (IHC) and in peripheral blood (flow cytometry) between baseline and on treatment. Clinical trial information: NCT06216938 .

Quantitative morphometry of compensated liver cirrhosis can aid to predict the outcomes of surgical treatment

Objective — to define quantitative morphometric characteristics of hepatic parenchyma lesions at compensated liver cirrhosis (CLC), which will allow more accurately to assess its functional reserves and predict the outcomes of surgical treatment. Materials and methods. Intraoperative marginal liver biopsy was performed for 74 patients with CLC, who underwent surgical treatment. Morphological examinations with quantitative morphometry of intraoperative liver biopsies were done with the use of cytological analyzer with software «Integral‑2MT» produced by the association «Kvant» (Kyiv). The connective tissue area (CTA), unchanged hepatocytes area (UHA), stromal‑parenchymatous ratio (SPR), the volume of hepatocytes in the state of necrosis and/or necrobiosis (VHSNN), the volume of hepatocytes in the state of division (VHSD) were determined. The statistical analysis was performed by use of Statistica 12 software package. Results. Three types of morphological pattern of CLC were isolated. Type I (type A) portal cirrhosis with weakly pronounced signs of parenchymatous and stromal reaction (mono‑multilobular type, portal cirrhosis). The CTA was 66.73±1.71 mm2, SPR was 0.285±0.019, UHA was 234.13±11.5 mm2, VHSNN was 11.21±0.74%, VHSD was 10.23±0.57%. Type II cirrhosis (type B) — cirrhosis of mono‑multilobular type with moderately expressed signs of parenchymatous and stromal reaction. The CTA was 126.69±12.5 mm2, SPR was 0.617±0.031, UHA was 205.34±13.8 mm2, VHSNN was 17.32±0.63%, VHSD was 15.43±0.48%. Type III cirrhosis (type C) — cirrhosis with pronounced signs of parenchymatous and stromal reaction, more often of multilobular type. The CTA was 240.16±13.4 mm2, SPR was 1.344±0.089, UHA was 178.69±18.7 mm2, VHSNN was 23.97±0.75%, VHSD was 11.07±0.58%. Analysis of immediate results of surgical treatment demonstrated, that no one patient with A‑type CLC died, while 9.5% of patients with B‑type and 25.0% of patients with C‑type CLC died in the early postoperative period. Conclusions. Quantitative morphometry demonstrated that pathological changes in the liver at CLC are heterogeneous and can be categorized in to 3 types (A, B, C). Three types of morphological pattern at CLC, which were isolated, are characterized by significant differences in CTA, UHA, SPR, VHSNN, VHSD parameters. At transition of A‑type cirrhosis into C‑type, volume of hepatic parenchyma becomes to be decreased, while volume of connective tissue becomes to be increased. This is accompanied by decrease in UHA, increase in CTA, SPR and VHSNN. Surgical intervention in patients with type C morphological pattern of cirrhosis is associated with a high risk (25%) of poor outcome, which indicates the need to limitations for indications to elective surgical operations in this category of patients. Thus, quantitative morphometry of liver biopsies in CLC patients can aid to predict the outcomes of surgical treatment.

Role of routine frozen biopsy of cystic duct margin in resectable gallbladder cancer without jaundice

Role of routine frozen biopsy of cystic duct margin in resectable gallbladder cancer without jaundice

Appropriate Surgical Margins for Excision of Squamous Cell Carcinoma of the Lower Lip.

Background Squamous cell carcinoma (SCC) is the most common malignancy on the lower lip. Surgical excision, the standard treatment for SCC, requires full-thickness excision. However, no consensus exists about the appropriate surgical margin. Therefore, we investigated the appropriate surgical margin and excision technique by analyzing 23 years of surgical experience with lower-lip SCC. Methods We reviewed 44 patients with lower-lip SCC who underwent surgery from November 1997 to October 2020. Frozen biopsy was performed with an appropriate margin on the left and right sides of the lesion, and the margin below the lesion was the skin above the sulcus boundary. If the frozen biopsy result was positive, an additional session was performed to secure a negative margin. Full-thickness excision was performed until the final negative margin. In each patient, the total number of sessions performed, final surgical margin, and recurrence were analyzed. Results Forty-one cases ended in the first session, 2 ended in the second session, and 1 ended in the third session. The final surgical margins (left and right; n = 88) were 5 mm (66%), 7 mm (9%), 8 mm (2.3%), 10 mm (20.4%), and 15 mm (2.3%). During an average follow-up of 67.4 months (range, 12-227 months), recurrence occurred in one patient. Conclusion The final surgical margin was 5 mm in 66% (58/88) of the cases, and 97.7% (86/88) were within 10 mm. Therefore, we set the first frozen biopsy margin to 5 mm, and we suggest that a 5-mm additional excision is appropriate when frozen biopsy results are positive.

Intra-operative desorption-electrospray ionization mass-spectrometry for real-time diagnosis, margin assessment, and maximization of brain cancer resection.

2071 Background: Despite advances in our understanding of brain cancer, the ability to discern between infiltrated and non-infiltrated tissue with current adjuncts, remains elusive. Isocitrate dehydrogenase (IDH) mutation is unique to IDH-mut glioma cells and can be used as a surrogate for tumor infiltration. Further, emerging evidence has shown unique signatures in brain cancer lipidomic profiling, with lipid metabolism playing a key role in brain cancer biology. Here, we aimed to evaluate the impact of desorption electrospray ionization-mass spectrometry (DESI-MS) as a near real-time method to determine infiltration status and the use of DESI-MS to perform intra-operative histological diagnosis. Methods: This is a prospective multi-institution cohort study using intra-operative DESI-MS on freshly obtained tumor samples to evaluate 2-hydroxyglutarate (2HG), with post-hoc validation by review by a board-certified neuropathologist. For tumor cell estimation and tissue diagnosis, high-throughput DESI-MS was used for rapid analysis of high-density arrays using lipidomic profiling. Analysis of the data was performed using a pre-written algorithm employing a combination of Python- and MATLAB-based custom software allowing results in less than a second per sample. Results: A total of 496 tumor biopsies from 72 patients have been analyzed. Earlier iterations focused on absolute quantitation of 2HG in 247 biopsies from 49 patients to determine IDH genotype yielding sensitivity, specificity, and accuracy values of 89, 100, and 94% for core biopsies (71). Improvement in accuracy was obtained with relative measurement of 2HG in comparison to glutamate allowing for detection of IDH-mut infiltration at the margin, resulting in 93% sensitivity, 100% specificity, and 98% accuracy with turnover times averaging 3 minutes in 183 biopsies from 23 patients. Margin assessment beyond the limits of neuro-navigation and surgeon assessment showed tumor infiltration in 88% of margin biopsies from IDH mutant tumors (30 of 34 biopsies) with 100% accuracy. Intra-operative tissue diagnosis was pursued in 66 unique tumor samples using DESI-MS lipidomic profiling, including samples of normal brain parenchyma, gliomas, meningiomas and pituitary adenomas, split into two microarray sets (36 and 40 samples). Using estimated principal components as input features, high accuracy ( &gt; 90%; ROC AUCs ≥ 0.89) was obtained for supervised tissue classification using simple machine learning algorithms. Conclusions: We present a novel system for intra-operative evaluation of tumor infiltration at the margin in gliomas and for intra-operative tissue diagnosis of brain cancer. Our method identified tumor infiltration beyond the surgical margins and serves as a foundation for future uses employing DESI-MS to allow for molecularly guided surgery in IDH-mut gliomas.

Nipple margin assessment at the time of nipple-sparing mastectomy.

Documenting negative margins at the nipple-areolar complex (NAC) during nipple-sparing mastectomy (NSM) remains the standard, but how to achieve this and how to manage a positive margin is debated. We sought to review nipple margin assessments at our institution and to analyze the risk factors of a positive margin and rate of local recurrence. Patients who underwent NSM between 2012 and 2018 were reviewed and divided into 3 groups based on indication - cancer, contralateral prophylactic mastectomy (CPM) and bilateral prophylactic mastectomy (BPM). Nipple-sparing mastectomies were performed on 337 patients; 72% for cancer, 20% for CPMs and 8% for BPMs. Nipple margin assessments were performed in 87.8% of patients; 10 patients (3.4%) had a positive margin, 7 of whom underwent NAC excision and 3 were managed with observation. As indications for NSM increase, assessment of nipple margin provides valuable information to manage the NAC in patients with cancer. The routine use of nipple margin biopsies in patients undergoing CPM and BPM may no longer be required, as rates of occult malignant disease are low with no positive biopsies. Further studies with larger sample sizes are needed.

Incomplete resection rates of 4- to 20-mm non-pedunculated colorectal polyps when using wide-field cold snare resection with routine submucosal injection

Background and study aims Incomplete resection of 4- to 20-mm colorectal polyps occur frequently (> 10 %), putting patients at risk for post-colonoscopy colorectal cancer. We hypothesized that routine use of wide-field cold snare resection with submucosal injection (CSP-SI) might reduce incomplete resection rates (IRRs). Patients and methods Patients aged 45 to 80 years undergoing elective colonoscopies were enrolled in a prospective clinical study. All 4- to 20-mm non-pedunculated polyps were resected using CSP-SI. Post-polypectomy margin biopsies were obtained to determine IRRs through histopathology assessment. The primary outcome was IRR, defined as remnant polyp tissue found on margin biopsies. Secondary outcomes included technical success and complication rates. Results A total of 429 patients (median age 65 years, 47.1 % female, adenoma detection rate 40 %) with 204 non-pedunculated colorectal polyps 4 to 20 mm removed using CSP-SI were included in the final analysis. CSP-SI was technical successful in 97.5 % (199/204) of cases (5 conversion to hot snare polypectomy). IRR for CSP-SI was 3.8 % (7/183) (95 % confidence interval [CI] 2.7 %-5.5 %). IRR was 1.6 % (2/129), 16 % (4/25), and 3.4 % (1/29) for adenomas, serrated lesions, and hyperplastic polyps respectively. IRR was 2.3 % (2/87), 6.3 % (4/64), 4.0 % (6/151), and 3.1 % (1/32) for polyps 4 to 5 mm, 6 to 9 mm, < 10 mm, and 10 to 20 mm, respectively. There were no CSP-SI-related serious adverse events. Conclusions Use of CSP-SI results in lower IRRs compared to what has previously been reported in the literature for hot or cold snare polypectomy when not using wide-field cold snare resection with submucosal injection. CSP-SI showed an excellent safety and efficacy profile, however comparative studies to CSP without SI are required to confirm these results.

An invasive squamous cell carcinoma of the ankle: a case report.

The authors present the case of a male patient, 60 years old, who presented with a progressive mass on his left ankle for 2 years with a history of healed burns in that area. The ISCC was diagnosed using histopathology after which he underwent a marginal excision biopsy and split-thickness skin grafting. Wide-marginal excision and split-thickness skin grafting were done. It was noted that the graft had taken well and that there were clear tumour margins postoperatively. The skin graft was almost completely incorporated. No tumour cells were reported on the margins during the postoperative histopathology. This case highlights a successful outcome of the patient improved at the 12-month follow-up, and he expressed a high degree of satisfaction with the treatment. ISCC of the lower extremities is a rare disease that almost never affects the ankle and is frequently treated inappropriately since it mimics chronic wounds. It is important to have an index of suspicion in patients with a history of chronic irritation to the area of interest. Surgery is the primary option if ICCS is detected. Clear tumour margins are important, and, if done well, excision should be curative.

212 Intra-Operative Near Real-Time Detection of Tumor Infiltration in IDH-Mutant Gliomas Using Desorption Electrospray Ionization-Mass Spectrometry (DESI-MS)

INTRODUCTION: Surgery remains the mainstay of treatment in gliomas. However, distinction between tumor infiltrated and non-infiltrated tissues remains a challenge with current surgical adjuncts, particularly at the margin. Isocitrate dehydrogenase (IDH) mutation is unique to IDH mutant glioma cells and can be used as a potential surrogate for tumor infiltration. METHODS: We conducted a prospective study, using intraoperative DESI-MS analysis on freshly obtained tissue samples to evaluate the presence of 2-hydroxyglutarate (2HG) by relative quantitation in comparison with an internal control (glutamate), with subsequent review of each smear by board-certified neuropathologist. RESULTS: Earlier iterations of our DESI-MS allowed for genotyping of the tumor with a total of 247 biopsies from a 49-patient study yielding sensitivity, specificity, and accuracy values of 89, 100, and 94% for core biopsies (n = 71). Subsequent improvement of DESI-MS, from absolute quantitation to relative measurement in comparison to glutamate (GLU) allowed for detection of IDH-mut infiltration at the margin. We have collected 183 biopsies (116 core and 67 margin) from 23 patients. Preliminary results of IDH mutation assessments of core biopsies indicate 93% sensitivity, 100% specificity, and 98% accuracy and margin biopsies indicate 88% sensitivity, 100% specificity, 94% accuracy, with turnover times averaging 3 minutes per patient. Tumor infiltration at the margin after surgical resection was detected in 88% of margin biopsies from IDH mutant tumors (30 of 34 biopsies). CONCLUSIONS: We present a novel system to allow intraoperative evaluation of tumor infiltration at the margin in IDH-mutant gliomas. Our method and its validation identified tumor infiltration beyond the surgical margins and serves as a foundation for future uses employing DESI-MS to allow for molecularly guided surgery in IDH-mut gliomas.

Clinical Impact and Accuracy of Shave Biopsy for Initial Diagnosis of Cutaneous Melanoma

IntroductionEffective treatment of malignant melanomas is dependent upon accurate histopathological staging of preoperative biopsy specimens. While narrow excision is the gold standard for melanoma diagnosis, superficial shave biopsies have become the preferred method by dermatologists but may transect the lesion and result in inaccurate Breslow thickness assessment. This is a retrospective cohort study evaluating an initial method of biopsy for diagnosis of cutaneous melanoma and indication for reoperation based on inaccurate initial T-staging. MethodsWe retrospectively analyzed consecutive patients referred to the Medical College of Wisconsin, a tertiary cancer center, with a diagnosis of primary cutaneous melanoma. Adult patients seen between 2015 and 2018 were included. Fisher's exact test was used to assess the association between method of initial biopsy and need for unplanned reoperation. ResultsThree hundred twenty three patients with cutaneous melanoma from the head and neck (H&N, n = 101, 31%), trunk (n = 90, 15%), upper extremity (n = 84, 26%), and lower extremity (n = 48, 28%) were analyzed. Median Breslow thickness was 0.54 mm (interquartile range = 0.65). Shave biopsy was the method of initial biopsy in 244 (76%), excision in 23 (7%), and punch biopsy in 56 (17%). Thirty nine (33%) shave biopsies had a positive deep margin, as did seven (23%) punch biopsies and 0 excisional biopsies. Residual melanoma at definitive excision was found in 131 (42.5%) of all surgical specimens: 95 (40.6%) shave biopsy patients, 32 (60.4%) punch biopsy patients, and four (19.0%) excision biopsy patients. Recommendations for excision margin or sentinel lymph node biopsy changed in 15 (6%) shave biopsy patients and five (9%) punch biopsy patients. ConclusionsShave biopsy is the most frequent method of diagnosis of cutaneous melanoma in the modern era. While shave and punch biopsies may underestimate true T-stage, there was no difference in need for reoperation due to T-upstaging based on initial biopsy type, supporting current diagnostic practices. Partial biopsies can thus be used to guide appropriate treatment and definitive wide local excision when adjusting for understaging.

Increasing Dosage of Leucovorin Results in Pharmacokinetic and Gene Expression Differences When Administered as Two-Hour Infusion or Bolus Injection to Patients with Colon Cancer

The combination of 5-fluorouracil (5-FU) and leucovorin (LV) forms the chemotherapy backbone for patients with colorectal cancer. However, the LV administration is often standardized and not based on robust scientific data. To address these issues, a randomized pharmacokinetics study was performed in patients with colon cancer. Thirty patients were enrolled, receiving 60, 200 or 500 mg/m2 LV as a single two-hour infusion. Blood, tumor, mucosa, and resection margin biopsies were collected. Folate concentrations were analyzed with LC-MS/MS and gene expression with qPCR. Data from a previous study where patients received LV as bolus injections were used as comparison. Saturation of methylenetetrahydrofolate (MeTHF) and tetrahydrofolate (THF) levels was seen after two-hour infusion and polyglutamated MeTHF + THF levels in tumors decreased with increasing LV dosage. The decrease was associated with decreased FPGS and increased GGH expression, which was not observed after LV bolus injection. In the bolus group, results indicate activation of a metabolic switch possibly promoting TYMS inhibition in response to 5-FU. Different metabolic mechanisms appear to be induced when LV is administered as infusion and bolus injection. Since maximal inhibition of TYMS by the 5-FU metabolite 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) requires excess polyglutamated MeTHF, the results point in favor of the bolus regimen.