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Background: High-grade DCIS with immune infiltrates may represent lesions that are able to be kept in check by the immune system, but still are at risk for progression to invasive disease. We and others have demonstrated that the presence of T cells, and in particular the spatial proximity of CD8+/PD-1+ T cells and PD-L1+ cells predicts response to chemotherapy and PD-1 inhibitors in the setting of invasive triple negative breast cancer. DCIS with high-risk features (e.g. large, palpable, high grade, HR-, or HER2+) often have T cell infiltrates. We hypothesized that it might be possible to potentiate the immune response in high-risk DCIS with immune checkpoint blockade. Since mortality for DCIS is extremely low, we proposed an intralesional pembrolizumab (pembro) treatment approach to avoid systemic adverse effects. In a phase 1 dose escalation study of single agent pembro we found 2 doses of 8 mg, administered intralesionally 2-3 wks apart, was tolerable, induced immunological changes within the DCIS lesions, but had little clinical benefit. Herein, we expanded the number of injections to 4 and also tested a combination with mRNA-2752 (Moderna), an mRNA-based therapeutic encoding a T cell co-stimulator OX40L, and pro-inflammatory cytokines IL-23 and IL-36 gamma, to determine if we could find a dose that was both tolerable and elicited anti-tumor responses. Methods Women eligible for this study had DCIS with at least 2 of the following high-risk features: age< 45; high grade, extensive comedonecrosis; palpable mass; hormone receptor negative [HR-]; HER2+; size >5 cm, or microinvasion. A dose expansion cohort was performed using 4 doses of 8 mg pembro, 2-3 wks apart (n=5). We then combined pembro with mRNA-2752 (n=8 cases), initially at 8 and 4 mg, respectively. Dose reductions were implemented based on AEs. Patients received an MRI before and after 2 injections, spaced 2-3 wks apart. A total of 4 injections were allowed. Core biopsy or surgery was conducted after the last MRI. Results We observed an increase in T cell density in the dose expansion cohort (pembro only), except when there was a paucity of T cells in the pre-treatment biopsy. However, only 1 patient in this cohort demonstrated a reduction in lesion size (clinically and on MRI). As of 22SEP22, 8 patients have received the combination of pembro and mRNA-2752; 7 are evaluable. Two patients with minimal T cell infiltrates at baseline (both HR+) failed to respond, based on imaging or pathology. 4/5 patients with moderate to high T cell infiltrates at baseline had partial (2) or complete responses (2) based on imaging (surgery pending), one of whom had absence of DCIS on post-therapy core biopsy and a clear MRI 4 months later. Correlative studies (immune cell densities, spatial proximities) will be presented at the meeting along with complete data (including post-treatment pathology) on the first 8 patients. Side effects were independent of response and included Gr1/2 fever, myalgias, and fatigue starting within 12 hours of injection (3-4 days), enlargement of regional nodes by day 2, and Gr 1/2 erythema and induration of the breast starting at 4 days and lasting 4-20 days. Earlier onset and persistence of symptoms with subsequent exposure required dose reductions for the majority of patients to maintain tolerability (avoid fevers over 39.4°C, intense erythema and swelling of the breast lasting > 4 days). No AEs were higher than grade 2. Conclusion: The combination of intralesional pembro and mRNA-2752 demonstrated modulation of the tumor immune microenvironment and robust antitumor activity in high-risk DCIS (typically HR- or HER2+) with existing T cell infiltrates. This is an ongoing study; the optimal Phase 2 dose for the combination will be based on the totality of evolving safety and translational data. Citation Format: Laura J. Esserman, Alexa Glencer, Kirithiga Ramalingam, Christopher J. Schwartz, Alexander Borowsky, Gillian L. Hirst, Rachel Woody, Nicole Schindler, Nola M. Hylton, Michael Campbell. Intralesional injection of anti-PD-1 (pembrolizumab) and OX40L/IL-23/IL-36 mRNAs (mRNA-2752) results in regression of DCIS characterized by lymphocytic infiltrates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-20-02.

Under the Affordable Care Act, Medicaid expansion effective 1 January 2014 aimed to increase access to health care. We sought to determine the association of Medicaid expansion with disparities in utilization of breast reconstruction. Non-Hispanic Black (NHB) and White (NHW) breast cancer patients undergoing mastectomy +/− reconstruction between 2010 and 2017 were selected from the National Cancer Database. Annual trends for utilization of breast reconstruction by race, income, and education were evaluated by Medicaid expansion status using difference-in-differences regression analyses. Medicaid expansion was categorized by expansion date as early (2010–2013), 2014 (1/2014), late (after 1/2014), or no expansion. Of 443,607 patients, 36.3% (n = 161,128) underwent reconstruction, 13.1% (n = 58,249) were NHB, 16.8% (n = 74,430) had median income < $40,227, and 17.1% (n = 75,718) were in the lowest education quartile. In non-expansion states, lower proportions of NHB patients underwent reconstruction than NHW patients in all years, with the smallest disparity (NHB% − NHW%) (− 6.4%) in 2017. Decreases in disparities between NHB and NHW patients were seen with the smallest difference observed in 2014 (− 2.5%) in early-expansion states, in 2017 (− 0.7%) in 1/2014 expansion states, and in 2017 (− 4.5%) in late-expansion states. Similar findings for convergence of reconstruction utilization rates for the lowest two education levels and lowest two income quartiles were found with Medicaid expansion, with no convergence seen in non-expansion states over the study period. Some improvement in breast reconstruction disparities followed Medicaid expansion. Failure to improve parity without Medicaid expansion should be a consideration with any modifications to Medicaid access.

The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and III patients from the International Melanoma Database and Discovery Platform. Key changes in the eighth edition are regarding subcategorization of T1, M1, pathologic stage grouping of stage I and III, and refining the definitions and terminologies used in the staging system. As the knowledge of tumor biology improves, the staging of melanoma will continue to evolve to enable betterment of care.

Background In response to the COVID-19 pandemic, the American Society of Breast Surgeons and American College of Radiology released a joint statement recommending that all breast screening studies be postponed effective March 26, 2020. Study Design A retrospective review of all canceled mammograms at a single tertiary care institution from January 1-August 31, 2020 was performed to evaluate the effect of this recommendation by quantifying both the number and reason for mammogram cancellations before and after March 26, 2020. Utilization of the electronic patient portal for appointment cancellation as a surrogate for telehealth uptake was noted. Results During the study period, 5340 mammogram appointments were kept and 2784 mammogram appointments were canceled. From a baseline of 30 (10.8%) canceled mammograms in January, cancellations peaked in March (576, 20.6%) and gradually decreased to a low in August (197, 7%). Reasons for cancellations varied significantly by month ( P < .0001) and included COVID-19 related (236, 8.5%), unspecified patient reasons (1,210, 43.5%), administrative issues (147, 5.3%), provider requests (46, 1.7%), sooner appointments available (31, 1.1%), and reasons not given (486, 17.5%). In addition, compared to a baseline in January (51, 16.5%), electronic patient portal access peaked in August (67, 34.0%). Conclusion Screening mammogram cancellations have gradually recovered after early COVID-19 restrictions were lifted and increasing use of electronic patient access appears to be sustained. Consequences for future staging at the time of diagnosis remain unknown. Understanding to what extent the pandemic affected screening may help surgeons plan for post-pandemic breast cancer care.

Retrorectal cysts are cystic lesions located in the retrorectal space and are a distinct subset of retrorectal tumours, which are often misdiagnosed due to their rarity and mimicry of symptoms caused by common diseases. We have described the presentation and management of four patients who were diagnosed with retrorectal cysts from a 10-year retrospective chart review at our institute, a tertiary care centre. In middle-aged women, the following should raise suspicion of retrorectal cyst: gastrointestinal or urinary obstructive features, mass or fullness palpable on the posterior wall on digital rectal examination, presacral dimple, perianal fistula and/or recurrent disease. Such features should prompt an MRI evaluation of the pelvis for definitive diagnosis.

The melanoma expert panel devised the evidence-based eighth edition American Joint Committee on Cancer staging system by conducting vigorous analyses of stage I, II, and III patients from the International Melanoma Database and Discovery Platform. Key changes in the eighth edition are regarding subcategorization of T1, M1, pathologic stage grouping of stage I and III, and refining the definitions and terminologies used in the staging system. As the knowledge of tumor biology improves, the staging of melanoma will continue to evolve to enable betterment of care.

Malignancies of the retroperitoneum are uncommon; they may either be primary or arise secondarily from contiguous organs. Primary retroperitoneal carcinomas are extremely rare. Squamous cell carcinoma (SCC) of the renal pelvis is a rare upper urinary tract urothelial carcinoma arising in the setting of chronic nephrolithiasis. Due to locally advanced disease or metastases, these aggressive malignancies are often inoperable at presentation. We report a case of a 55-year-old man, a hypertensive and chronic smoker with a history of analgesic abuse, who underwent left nephrectomy for a non-functional kidney (chronic pyonephrosis with stag-horn calculus). Histopathological examination of the specimen was neglected and the patient presented 4 months later with advanced, inoperable retroperitoneal SCC which could only be palliated. This article highlights the prognosis associated with renal SCC and the importance of early detection in improving outcomes; periodic imaging with biopsy of suspicious mass lesions should be advocated in patients with renal calculous disease especially stag-horn calculi. Exclusion of malignancy prior to nephrectomy (when indicated) and HPE of the resected specimen is crucial in management. Radical nephrectomy may merit consideration in patients with non-functional kidneys secondary to long-standing nephrolithiasis when malignancy is suspected.

BACKGROUND There are many studies reported in the literature with respect to the Ductal Carcinoma in Situ (DCIS) progressing into Invasive Ductal Carcinoma (IDC) of the breast. However, there is hardly any study on the coexistence of both and its clinical significance. The aim of the study is to analyse the clinical and pathological parameters of synchronous DCIS and IDC to predict the prognostic factors. MATERIALS AND METHODS 42 patients with a final pathological diagnosis of synchronous DCIS and IDC diagnosed in 2009-11 were included in the study. Statistical analysis was done using SPSS software utilising the appropriate analytical methods. RESULTS Majority of the patients in this study group presented with early breast cancer (64.3%). Forty eight percent were Her2 subtype (ER, PR negative and HER2/neu-positive) and 31% were triple negative. Eighty one percent of the IDC associated histology was Not Otherwise Specified (NOS) type. Grade 3 lesions were more common (57%). Recurrence of the disease occurred in 66% of patients during a mean duration of follow up of 3.6 years with predominance of visceral metastasis (51.5%). Recurrence was more common in node positive disease (59.5%), those with lymphovascular emboli (59.5%) and perinodal spread (76%) on histopathological examination. CONCLUSION Synchronous DCIS and IDC disease entity appears to have an aggressive nature compared to the course of IDC alone entity. Prognostic factors relating to IDC appears to correlate well with recurrence than that of the prognostic factors of DCIS component in such synchronous setting.

Introduction Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. Aim To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). Method Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. Results The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. Conclusions Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study.

There is very little awareness of the general physicians and surgeons about the benign breast conditions such as duct ectasia (DE) and periductal mastitis (PDM) causing nipple discharge. Not only that these benign breast diseases ring a false alarm of cancer, they are also the second most common cause of benign breast diseases. The objective was to study the clinical and microbiological profiles of duct ectasia and periductal mastitis in Indian women for better understanding of the disease process, in order to be able to treat them well. Forty-one consecutive patients presenting to the Surgical Out-Patient Department with non-bloody nipple discharge with clinical and radiological features suggestive of DE or PDM were included. Microbial culture and cytopathological study of the nipple discharge were done. Histopathological studies and culture of the ductal tissue taken intraoperatively were carried out. There is no significant difference in the age distribution among women with DE and PDM. Smoking is not associated with DE and PDM of Indian patients in contrast to the Western literature evidence. Infective etiology was present in nearly 46 % of the patients in the study population more so in the periductal mastitis cases. The most common isolated pathogens were Staphylococcus aureus and Staphylococcus epidermidis, unlike in Western population where nearly 50 % were anaerobes. Since the isolated organisms were resistant to the routinely used antibiotics in high proportion of cases, culture and sensitivity should be done in all possible cases for appropriately treating the subareolar sepsis before proceeding with the definitive treatment in the form of duct excision.