Imaging Characteristics of and Multidisciplinary Management Considerations for Atypical Ductal Hyperplasia and Flat Epithelial Atypia: Review of Current Literature.

High-risk lesions of the breast are frequently encountered in percutaneous biopsy specimens. While benign, these lesions have historically undergone surgical excision due to their potential to be upgraded to malignancy. However, there is emerging evidence that a tailored management approach should be considered to reduce overtreatment of these lesions. Flat epithelial atypia (FEA) and atypical ductal hyperplasia (ADH) are two of the most commonly encountered high-risk lesions. FEA has been shown to have a relatively low rate of progression to malignancy, and some guidelines are now recommending observation over routine excision in select cases. Selective observation may be reasonable in cases where the target lesion is small and completely removed at biopsy and when there are no underlying risk factors, such as a history of breast cancer or genetic mutation or concurrent ADH. ADH has the highest potential upgrade rate to malignancy of all the high-risk lesions. Most society guidelines continue to recommend surgical excision of this lesion. More recently, some literature suggests that ADH lesions that appear completely removed at biopsy, involve limited foci (less than two or three) with no necrosis or significant atypia, manifest as a small group of mammographic calcifications, or demonstrate no enhancement at MRI may be reasonable for observation. Ultimately, management of all high-risk lesions must be based on a multidisciplinary approach that considers all patient, radiologic, clinical, and histopathologic factors. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Patient Perspectives and Quality of Life after Breast Reconstruction and the Impact of Subsequent Revisions.

There is limited research on the impact of revisional surgery after breast reconstruction on patient experience and postoperative quality of life (QoL). Methods: Patients undergoing mastectomy with immediate implant-based or autologous free-flap breast reconstruction from 2008 to 2020 were reviewed. These patients were categorized by revisions (0-1, 2-3, and 4+) and surveyed on QoL metrics using BREAST-Q and Was It Worth It? (WIWI) questionnaires. BREAST-Q QoL, satisfaction, and WIWI metrics between revision groups were evaluated. Results: Among 252 patients, a total of 150 patients (60%) underwent zero to one revisions, 72 patients (28%) underwent two to three revisions, and 30 patients (12%) underwent four or more revisions. Median follow-up was 6 years (range, 1-11 years). BREAST-Q satisfaction among patients with four or more revisions was significantly lower (P = 0.03), while core QoL domains (chest physical, psychosocial, and sexual well-being) did not significantly differ. Analysis of unplanned reoperations due to complications and breast satisfaction showed no significant difference in QoL scores between groups (P = 0.08). Regarding WIWI QoL metrics, four or more revisions were associated with a higher rate of worse QoL (P = 0.035) and worse overall experience (P = 0.001). Most patients in all revision groups felt it was worthwhile to undergo breast reconstruction (86%), would choose breast reconstruction again (83%), and would recommend breast reconstruction to others (79%). Conclusions: Overall, a majority of patients undergoing revisions after breast reconstruction still have a worthwhile experience. Although reoperations after breast reconstruction do not significantly impact long-term BREAST-Q QoL domains, patients undergoing four or more revisions have significantly lower breast satisfaction, worse QoL, and a postoperative experience worse than expected.

Postoperative Complication Impact on Quality of Life after Postmastectomy Breast Reconstruction.

BACKGROUND: Although the overall psychosocial benefits and body image gains of postmastectomy breast reconstruction are well-established, there is limited information on how postoperative complications affect patient quality of life (QOL). STUDY DESIGN: A single-institution cross-sectional survey analysis was performed on patients who underwent postmastectomy breast reconstruction between 2008 and 2020. QOL was assessed using the BREAST-Q and the Was It Worth It questionnaires. The results were compared among patients who had major complications, minor complications, and no complications. Responses were compared using 1-way ANOVA and chi-square tests as appropriate. RESULTS: A total of 568 patients met inclusion criteria, and 244 patients responded (43% response rate). Most patients did not have any complications (n = 128; 52%), 41 had minor complications (17%), and 75 had major complications (31%). There were no differences in any of the BREAST-Q well-being metrics based on degree of complication. Across all 3 groups, patients reported that surgery was worthwhile (n = 212; 88%), they would choose reconstruction again (n = 203; 85%), and they would recommend it to a friend (n = 196; 82%). Overall, 77% reported that their overall experience either met or exceeded expectations, and 88% of patients had unchanged or improved overall QOL. CONCLUSIONS: Our study demonstrates that QOL and well-being are not negatively impacted by postoperative complications. Although patients who had no complications had an overall more positive experience, nearly two-thirds of all patients, no matter the degree of complication, stated that their overall experience either met or exceeded their expectations.

PDJ amplicon in triple negative breast cancer.

Amplification of chromosome 9p24.1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes. However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in TNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non-metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.1 PDJ amplicon, 9q24.3, and 9q34.1. Samples with mean PDJ signal of > 4.5 copies, and ratios of PDJ/9q24 ≥ 2 and/or PDJ/9q34.1 ≥ 2 were called amplified (PDJ+). Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons in TNBCs. In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ- TNBCs. Matched pre- and post-neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status. Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon in TNBC.

Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer.

Genome-wide fragmentation patterns in cell-free DNA (cfDNA) in plasma are strongly influenced by cellular origin due to variation in chromatin accessibility across cell types. Such differences between healthy and cancer cells provide the opportunity for development of novel cancer diagnostics. Here, we investigated whether analysis of cfDNA fragment end positions and their surrounding DNA sequences reveals the presence of tumor-derived DNA in blood. We performed genome-wide analysis of cfDNA from 521 samples and analyzed sequencing data from an additional 2147 samples, including healthy individuals and patients with 11 different cancer types. We developed a metric based on genome-wide differences in fragment positioning, weighted by fragment length and GC content [information-weighted fraction of aberrant fragments (iwFAF)]. We observed that iwFAF strongly correlated with tumor fraction, was higher for DNA fragments carrying somatic mutations, and was higher within genomic regions affected by copy number amplifications. We also calculated sample-level means of nucleotide frequencies observed at genomic positions spanning fragment ends. Using a combination of iwFAF and nine nucleotide frequencies from three positions surrounding fragment ends, we developed a machine learning model to differentiate healthy individuals from patients with cancer. We observed an area under the receiver operative characteristic curve (AUC) of 0.91 for detection of cancer at any stage and an AUC of 0.87 for detection of stage I cancer. Our findings remained robust with as few as 1 million fragments analyzed per sample, demonstrating that analysis of fragment ends can become a cost-effective and accessible approach for cancer detection and monitoring.

Pilot/Phase II Trial of Hypofractionated Radiation Therapy to the Whole Breast Alone Before Breast Conserving Surgery.

Purpose: Our purpose was to report the results of a phase II trial of patients with breast cancer treated with hypofractionated whole breast radiation therapy (RT) before breast-conserving surgery (BCS). Methods and materials: Between 2019 and 2020, patients with cT0-T2, N0, M0 breast cancer were enrolled. Patients were treated with hypofractionated whole breast RT, 25 Gy in 5 fractions, 4 to 8 weeks before BCS. Pathologic assessment was performed using the residual cancer burden (RCB). Toxicities were assessed according to Common Terminology Criteria for Adverse Events (version 4). Quality of life was assessed with Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, The Breast Cancer Treatment Outcome Scale, Linear Analogue Self-Assessment, and Patient-Reported Outcomes Measurement Information System. Results: Twenty-two patients were enrolled. Median follow-up was 7.6 months (range, 0.2-16.8). Seven (32%) and 2 (9%) patients experienced grade 2+ or 3 toxicities, respectively. Overall quality of life Linear Analogue Self-Assessment and Patient-Reported Outcomes Measurement Information System did not change significantly from baseline (P = .21 and P = .72, respectively). There was no clinically significant change (≥1 point) in any of The Breast Cancer Treatment Outcome Scale domains. Only 1 (5%) patient experienced a clinical deterioration that corresponded to a "fair" outcome on the Harvard Cosmesis Scale. At pathologic evaluation, 14 (64%) patients had RCB-0 or RCB-I, including 3 (14%) patients with a pathologic complete response (RCB-0). Eight patients (36%) had RCB-II. No local or distant recurrences have been observed. Conclusions: Extremely hypofractionated whole breast RT before BCS is a feasible approach. There were low rates of toxicities and good cosmesis. Further investigation into this approach with RT before BCS is warranted.

The impact of mastectomy and reconstruction technique on patient perceived quality of Life.

BACKGROUND: We sought to evaluate the impact of mastectomy type, post-mastectomy reconstruction choice, and procedure bilaterality, on patient perceived postoperative quality of life (QoL). METHODS: Patients who underwent post-mastectomy reconstruction between 2008 and 2020 were identified in a prospective database. QoL was assessed with the BREAST-Q and the Was It Worth It (WIWI) questionnaires. The results were compared between reconstruction type, reconstruction laterality, and type of mastectomy. Responses were compared using one-way analysis of variance (ANOVA) and chi-square tests. RESULTS: 568 patients met inclusion criteria, and 244 patients responded (43%). QoL did not significantly vary between different reconstructions selected, procedure laterality, or mastectomy type. Patients who underwent DIEP flap were significantly more satisfied with their reconstructed breasts than implant-based reconstruction. Overall, over 85% of patients experienced improved or unchanged QoL no matter what reconstruction choices were made. CONCLUSION: Most domains of QOL are not impacted by mastectomy type, post-mastectomy reconstruction, or laterality.

Long-term breast and nipple sensation after nipple-sparing mastectomy with implant reconstruction: Relevance to physical, psychosocial, and sexual well-being.

BACKGROUND: The effect of postoperative sensation on quality-of-life (QoL) following nipple-sparing mastectomy (NSM) with implant-based reconstruction is not well described. We evaluated the impact of breast and nipple sensation on patient QoL by using BREAST-Q. METHODS: Patients undergoing NSM with implant reconstruction from 2008 to 2020 were mailed a survey to characterize their postoperative breast and nipple sensation. BREAST-Q metrics were compared between totally numb patients and those with sensation. RESULTS: A total of 349 patients were included. Overall, 131 (38%) responded; response rates regarding breast and nipple sensation were 36% (N = 124/349) and 34% (N = 117/349). Median time from surgery to survey completion was 6 years. The majority had bilateral procedures (101, 77%), including direct-to-implant (99, 76%) and tissue expander (32, 24%) reconstruction. Regarding breast sensation, the majority of patients reported their reconstructed breasts as totally numb (47, 38%) or much less sensation than before surgery (59, 48%). Regarding nipple sensation, the majority of patients reported their nipples were totally numb (67, 57%) or had much less sensation than before surgery (37, 32%). Total numbness of reconstructed breasts resulted in a significantly lower chest physical well-being (mean score: 73.5 vs. 81.2, respectively, P = 0.048). Total numbness of postoperative nipple(s) resulted in significantly lower chest physical (mean score: 74.8 vs. 85.2, respectively, P = 0.007), psychosocial (mean score 77.4 vs. 84.4, respectively, P = 0.041), and sexual well-being (mean score: 55.7 vs. 68.3, respectively, P = 0.002). CONCLUSIONS: Long-term breast and nipple sensation are significantly diminished after NSM with implant reconstruction. Patients with preserved sensation experience better physical, psychosocial, and sexual well-being.

Merkel cell carcinoma of unknown primary: Clinical presentation and outcomes.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion. METHODS: We reviewed 415 patients with biopsy-proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease-free survival, and overall survival. RESULTS: Patients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence-free survival was 59.3% at 5 years. Disease-specific survival was 63.3% at 5 years. CONCLUSION: Patients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

Postoperative Hematomas in the Era of Outpatient Mastectomy: Is Ketorolac Really to Blame?

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols following mastectomy with or without implant-based breast reconstruction (IBBR) include ketorolac for multimodal perioperative analgesia. There are concerns that ketorolac could be associated with increased risk of postoperative hematoma formation. METHODS: Retrospective review of patients undergoing mastectomy with or without IBBR between January 2013 and December 2019 at a single institution. Patients received 15 mg, 30 mg, or no ketorolac depending on ERAS protocol adherence, patient characteristics, and surgeon preference. Clinically significant hematoma was defined as requiring surgical intervention on day of surgery or postoperative day 1. Patients were compared by demographics, surgical characteristics, ketorolac dose, and hematoma prevalence. Univariable and multivariable logistic regression evaluated hematoma formation odds. RESULTS: Eight hundred patients met inclusion criteria: 477 received ketorolac. Those who received ketorolac were younger, had lower ASA scores, were more likely to have bilateral procedures and undergo concomitant IBBR, had longer operative times, were less likely to take antiplatelet or anticoagulation medications, had higher PACU pain scores, and had higher incidence of hematomas requiring surgical intervention. Of the cohort, 4.4% had clinically significant hematomas. The 15 mg and 30 mg ketorolac groups had similar prevalence (6.0% vs 5.8%, p = 0.95). On univariable regression, there were increased odds of hematoma formation in patients who were younger, had bilateral procedures, had longer OR times, and who received ketorolac. On multivariable regression, none of the prior variables remained significant. CONCLUSION: After accounting for associations with longer operative times, concomitant IBBR, and bilateral procedures, ketorolac administration did not remain an independent risk factor for hematoma formation.

Accuracy of Posttreatment Imaging for Evaluation of Residual in Breast Disease After Neoadjuvant Endocrine Therapy.

BACKGROUND: Neoadjuvant endocrine therapy (NET) can help downstage certain breast cancers prior to surgical resection. This study measured the accuracy of conventional mammography (MMG), ultrasound (US), magnetic resonance imaging (MRI), and contrast-enhanced mammography (CEM) for assessing breast tumor size in response to NET. PATIENTS AND METHODS: Patients who underwent surgery after NET from 2013 to 2021 were identified. The maximal dimension of residual tumor on imaging was compared with the maximal dimension on final pathology. Lin's concordance correlation coefficient (rc) and Spearman's rank correlation coefficient (r) were used to assess agreement. RESULTS: In total, 119 patients with invasive breast cancer underwent NET, posttreatment imaging, and surgery. Tumor size reported on posttreatment CEM correlated with size on final pathology to within 1 cm in n = 42 (58%) of patients, equivalent to the accuracy of MRI (n = 35, 58%). Size was accurately predicted by US in 54% and in 48% of MMG. Posttreatment imaging tumor size was moderately correlated with final tumor size on pathology CEM (r = 0.49; rc = 0.38), MRI (r = 0.52; rc = 0.45), and US (r = 0.41; rc = 0.28). MMG was weakly correlated (r = 0.21; rc = 0.16). Similar findings were shown in subgroup analysis; in those who received all four post-NET imaging, CEM and MRI again performed comparably, with r = 0.36 and 0.41, respectively, US (r = 0.43) and MMG (r = 0.28). CONCLUSIONS: Compared with mammography and US, CEM and MRI had higher accuracy in estimating final tumor size for breast cancers treated with NET. Contrast-enhanced imaging is a helpful adjunct when response to preoperative therapy will impact clinical management.

Chest wall resection for breast cancer: 21st century Mayo clinic experience.

BACKGROUND: We hypothesized full-thickness chest wall resection (FTCWR) with advanced surgical techniques and modern systemic therapy is safe, provides local control, and good overall survival. METHODS: Retrospective review of FTCWR (including rib or part of sternum) for breast cancer between 2000 and 2020. Primary endpoints included 90-day morbidities and all-cause mortality. Secondary endpoints were loco-regional and distant recurrence, DFS and overall survival (OS). RESULTS: A total of 35 patients met the criteria. 34 FTCWR were for recurrence and the median time to chest wall recurrence was 6 years. Tumor subtype was triple-negative in 51% and the remainder HR+ Her2-. 58% were palliative resections. FTCWR included rib(s) in 89% and portion of sternum in 57%; 94% required reconstruction and 80% were R0 resections. There were no 90-day mortalities. Overall morbidity was 10/35(28%). 17(49%) patients received neoadjuvant systemic therapy for their recurrence and three received neoadjuvant radiation. Adjuvant treatment included chemotherapy (8), endocrine therapy (3), and both (8). Ten patients (28%) received adjuvant radiation. The Median follow-up was 31 months and there were 6 (17%) loco-regional and 7 (20%) distant recurrences. OS was 86% and 67% at 1 and 3 years, respectively. CONCLUSION: FTCWR was associated with low morbidity, mortality, recurrence rates, and good OS. Selective FTCWR is safe and has acceptable short-term survival rates.

Association of breast cancer risk, density, and stiffness: global tissue stiffness on breast MR elastography (MRE).

PURPOSE: Quantify in vivo biomechanical tissue properties in various breast densities and in average risk and high-risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk based on patient demographics and clinical data. METHODS: Patients with average risk or high-risk of breast cancer underwent 3.0 T breast MR imaging and elastography. Breast parenchymal enhancement (BPE), density (from most recent mammogram), stiffness, elasticity, and viscosity were recorded. Within each breast density group (non-dense versus dense), stiffness, elasticity, and viscosity were compared across risk groups (average versus high). Separately for stiffness, elasticity, and viscosity, a multivariable logistic regression model was used to evaluate whether the MRE parameter predicted risk status after controlling for clinical factors. RESULTS: 50 average risk and 86 high-risk patients were included. Risk groups were similar in age, density, and menopausal status. Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high-risk patients (N = 55) compared to average risk patients (N = 34; all p < 0.001). Stiffness remained a significant predictor of risk status (OR = 4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, BPE, age, and menopausal status. Similar results were seen for elasticity and viscosity. CONCLUSION: A structurally based, quantitative biomarker of tissue stiffness obtained from MRE is associated with differences in breast cancer risk in dense breasts. Tissue stiffness could provide a novel prognostic marker to help identify high-risk women with dense breasts who would benefit from increased surveillance and/or risk reduction measures.

Seldom one and done: Characterizing rates of reoperation with direct-to-implant breast reconstruction after mastectomy.

BACKGROUND: Limited data exist outlining reoperations after direct-to-implant (DTI), tissue expander (TE) and autologous free-flap breast reconstruction. METHODS: Patients undergoing mastectomy with reconstruction from 2008 to 18 were reviewed. Patient factors, surgical techniques, planned, unplanned, and total reoperations were analyzed. RESULTS: Among 544 total patients, the majority underwent DTI (294, 54%) or TE (176, 32%); 74 (14%) received autologous free-flaps. Majority of DTI patients (55%) underwent subsequent reoperations. Compared to autologous tissue, DTI had less patients undergo additional surgery (76% vs. 55%, P = 0.001). Incidence of total unplanned reoperations did not significantly differ between reconstructive groups. The rate of unplanned reoperations due to complications was lowest for DTI (39%) when compared to TE (48%) and autologous (55%, P = 0.015). Compared to TE, DTI carried a lower risk for ≥2 total reoperations (OR = 0.21, 95% CI 0.13-0.33, P < 0.001). CONCLUSIONS: Seldom "one and done," additional surgery after DTI remains significant.

Finite Element Modeling of Quantitative Ultrasound Analysis of the Surgical Margin of Breast Tumor.

Ultrasound is commonly used as an imaging tool in the medical sector. Compared to standard ultrasound imaging, quantitative ultrasound analysis can provide more details about a material microstructure. In this study, quantitative ultrasound analysis was conducted through computational modeling to detect various breast duct pathologies in the surgical margin tissue. Both pulse-echo and pitch-catch methods were evaluated for a high-frequency (22-41 MHz) ultrasound analysis. The computational surgical margin modeling was based on various conditions of breast ducts, such as normal duct, ductal hyperplasia, DCIS, and calcification. In each model, ultrasound pressure magnitude variation in the frequency spectrum was analyzed through peak density and mean-peak-to-valley distance (MPVD) values. Furthermore, the spectral patterns of all the margin models were compared to extract more pathology-based information. For the pitch-catch mode, only peak density provided a trend in relation to different duct pathologies. For the pulse-echo mode, only the MPVD was able to do that. From the spectral comparison, it was found that overall pressure magnitude, spectral variation, peak pressure magnitude, and corresponding frequency level provided helpful information to differentiate various pathologies in the surgical margin.

Preoperative Nutritional Optimization of the Oncology Patient: A Scoping Review.

BACKGROUND: Malnutrition is common among patients with cancer and is a known risk factor for poor postoperative outcomes; however, preoperative nutritional optimization guidelines are lacking in this high-risk population. The objective of this study was to review the evidence regarding preoperative nutritional optimization of patients undergoing general surgical operations for the treatment of cancer. METHODS: A literature search was performed across the Ovid (MEDLINE), Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCOhost), and Web of Science (Clarivate) databases. Eligible studies included randomized clinical trials, observational studies, reviews, and meta-analyses published between 2010 and 2020. Included studies evaluated clinical outcomes after preoperative nutritional interventions among adult patients undergoing surgery for gastrointestinal cancer. Data extraction was performed using a template developed and tested by the study team. RESULTS: A total of 5,505 publications were identified, of which 69 studies were included for data synthesis after screening and full text review. These studies evaluated preoperative nutritional counseling, protein-calorie supplementation, immunonutrition supplementation, and probiotic or symbiotic supplementation. CONCLUSIONS: Preoperative nutritional counseling and immunonutrition supplementation should be considered for patients undergoing surgical treatment of gastrointestinal malignancy. For malnourished patients, protein-calorie supplementation should be considered, and for patients undergoing colorectal cancer surgery, probiotics or symbiotic supplementation should be considered.

Is the presence of tumor-infiltrating lymphocytes predictive of outcomes in patients with melanoma?

BACKGROUND: The significance of tumor-infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs. METHODS: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma-specific survival (MSS). RESULTS: Overall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P < .05). The median follow-up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P < .001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values < .05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.95; P = .0154). CONCLUSIONS: TILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered.