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The 21-gene RT-PCR recurrence score (RS) is performed in patients with hormone receptor-positive (ER+, PR+), human epidermal growth factor receptor 2 (HER2)-negative, N0 breast cancer to determine which patients will likely benefit from chemotherapy after breast-conserving surgery (BCS). The purpose of this study was to evaluate whether the RS can predict for patients likely to benefit from radiation therapy (RT) after BCS.The National Cancer Database was queried (2004-2017) for female patients with pT1N0 ER+ PR+ HER2-negative breast cancer treated with BCS who had an available RS. Patients were stratified based on their RS (low risk [LR], 1-10; intermediate risk [IR], 11-25; high risk [HR], 26-100). For each RS cohort, propensity score matching was conducted to create 1:1 matched cohorts of patients who received RT and patients who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable and multivariable (MVA) Cox proportional hazard analysis identified clinical and treatment factors prognostic for OS.A total of 79,040 patients met the selection criteria: 18,823 in the LR cohort, 52,341 in the IR cohort, and 7876 in the HR cohort. A total of 92% of patients received RT: 91% in the LR cohort, 93% in the IR cohort, and 92% in the HR cohort. After propensity score matching, the 5-year OS in the LR cohort was 95% for those who received RT and 93% for those who did not (P = .184). In the IR cohort, the 5-year OS was 95% for those who received RT and 93% for those who did not (P = .001). In the HR cohort, the 5-year OS was 95% for those who received RT and 84% for those who did not (P.001). MVA demonstrated that RT was a positive prognostic factor for OS in both the IR cohort (P = .001) and HR cohort (P.001). On MVA in the LR cohort, RT (P = .186) was not predictive of improved OS.An OS benefit was observed with the use of RT in patients with IR or HR RS but not in patients with LR RS. Future prospective evaluation is warranted.

Based on the results of the Cancer and Leukemia Group B (CALGB) 9343 trial, patients age ≥70 with T1N0 hormone receptor positive (ER/PR+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). Because the CALGB 9343 trial did not stratify based on recurrence score (RS) test (Oncotype Dx), we conducted the present retrospective study to determine whether RS is predictive of who may benefit from RT following BCS in this cohort.The National Cancer Database (NCDB) was queried (2004-2017) for patients age ≥ 70 with pT1N0 ER+/PR + HER2- breast cancer treated with BCS and ET. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). Propensity score matching (PSM) created 1:1 matched cohorts of patients who received radiotherapy and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS.A total of 11,891 patients met the selection criteria: 3364 in the LR cohort, 7305 in the IR cohort, and 1222 in the HR cohort. A total of 79 % received RT: 77 % in the LR cohort, 79 % in the IR cohort, and 85 % in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, the 5-year OS in the LR cohort was 91 % for those who received RT and 89 % for those who did not (p = 0.605). In the IRHR cohort, the 5-year OS was 91 % for those who received RT and 87 % for those who did not (p = 0.003). On MVA in the LR cohort, RT (p = 0.727) was not predictive of improved OS. On MVA in the IRHR cohort, RT (p = 0.010) was a positive prognostic factor for OS.In this older cohort of patients, there is an OS benefit with the use of RT in patients with IRHR RS but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.

BACKGROUND The 21-gene assay (Oncotype DX®) can be used to guide use of chemotherapy in the management of patients with pN1 [1–3 positive lymph nodes (LNs)] breast cancer, specifically with respect to assessing potential benefit of chemotherapy. However, practice patterns based on this assay, as well as associated outcomes, have not been prospectively evaluated for pN2 (4–9 positive LNs) disease.METHODS The National Cancer Database (NCDB) was queried for women with newly-diagnosed, non-metastatic, hormone receptor-positive, Her2-negative, pN2 breast cancer who underwent adjuvant endocrine therapy. Kaplan-Meier analysis evaluated overall survival (OS); Cox proportional hazards modeling determined variables associated with OS.RESULTS Of 1,658 patients, 1,109 (67%) received chemotherapy and 549 (33%) did not. Chemotherapy was administered to 54% of patients with a low-risk recurrence score (RS), 67% for intermediate-risk RS, and 75% for high-risk RS. The median follow-up was 49.9 months (interquartile range, 33.6–71.2 months). Chemotherapy was associated with improved 5-year OS in low-risk RS (95.5% vs. 87.4%), intermediate-risk RS (91.9% vs. 83.5%), and high-risk RS (81.3% vs. 50.2%) (p ≤ 0.001 for all). On Cox multivariable analysis, chemotherapy and the RS risk group significantly associated with OS (p CONCLUSIONS Despite the underutilization of chemotherapy for hormone receptor-positive, Her2-negative, pN2 patients, it was associated with improved OS for all 21-gene panel risk groups. These results support the existing standard of chemotherapy for this population, although its omission could be considered in patients over 70 years of age.

Supplementary Figure from A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer

Purpose:A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC.Patients and Methods:In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers.Results:Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders.Conclusions:The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

Supplementary Table from A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer

Purpose/Objectives Mucinous carcinoma (MC) of the breast is an uncommon variant of breast cancer which has a favorable prognosis. Current guidelines for ER/PR-positive, HER2-negative pure-MC state that endocrine therapy (ET) is only required for tumors ≥3cm and node-positive patients while chemotherapy (CTX) is not required but can be considered for node positive-patients. While radiation therapy (RT) currently remains a part of breast-conserving therapy (BCT) for this histology, the prognostic impact of RT in pure MC remains unclear. Materials/Methods The National Cancer Database (NCDB) was queried (2004-2017) for patients with non-metastatic, histologically confirmed MC who received breast-conserving surgery. Kaplan-Meier analysis was used to evaluate overall survival (OS). Univariate (UVA) and multivariate (MVA) analyses were conducted using Cox proportional hazard models to determine which clinical and treatment factors were prognostic for overall survival. Results A total of 24,837 patients with median age 70 (IQR 61-78) were included in this study. A total of 66% of carcinomas were grade 1 and 34% were grade 2. A total of 79% were pT1, 20% were pT2, and 1% were pT3-4. A total of 96% were pN0 and 4% were pN1-3. A total of 99% were ER+, 92% were PR+, and 96% were HER2-. A total of 61% received RT, 70% received ET, and 8% received CTX. The 10-year OS was 73% for those who received RT and 41% for those who did not. On UVA, RT (HR 0.31, p< 0.0001; CI 0.29-0.33), ET (HR 0.52, p< 0.0001; CI 0.49-0.55), CTX (HR 0.40, p< 0.0001; CI 0.35-0.46), and black race (HR 0.87, p= 0.006; CI 0.79- 0.96) were positive prognostic factors for OS while older age (HR 1.10, p< 0.0001; CI 1.09-1.10), CDCC comorbidity score (HR 1.93, p< 0.0001; CI 1.81- 2.06), and tumor size (HR 1.01, p< 0.0001; CI 1.01-1.02) were negative prognostic factors. On MVA, RT (HR 0.64, p< 0.0001; CI 0.59-0.69) and ET (HR 0.85, p< 0.0001; CI 0.78- 0.91) remained positive prognostic factors while older age (HR 1.08, p< 0.0001; CI 1.08-1.09), CDCC comorbidity score (HR 1.61, p< 0.0001; CI 1.50- 1.73), and tumor size (HR 1.02, p< 0.0001; CI 1.01- 1.02) remained negative prognostic factors; chemotherapy (HR 1.19, p= 0.039; CI 1.01- 1.39) became a negative prognostic factor and black race (HR 0.99, p= 0.92; CI 0.89- 1.12) was no longer prognostic. Conclusion This is the largest study to date on mucinous carcinoma of the breast and the role of RT after breast-conserving surgery. Use of postoperative RT after lumpectomy is associated with improved OS in patients with breast MC, suggesting that post-lumpectomy RT should remain standard of care. Citation Format: Neil Chevli, Kaidi Wang, Waqar Haque, Mary R. Schwartz, Julie Nangia, Jennifer Sasaki, Andrew M. Farach, Sandra S. Hatch, E. Brian Butler, Bin S. Teh. Prognostic impact of radiation therapy in mucinous carcinoma of the breast [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-15.

Highlights • Men show higher rates of facial contact than women. • Rates of facial contact can vary in different social situations. • Fatigue and distraction increase rates of facial contact and subsequent infection risk., Background Decreasing facial contact takes on new urgency as society tries to stem the tide of COVID-19 spread. A better understanding of the pervasiveness of facial contact in social settings is required in order to then take steps to mitigate the action. Methods YouTube videos of random individuals were included in a behavioral observation study to document rates of contact to the eyes, nose, and mouth area. Factors including age, sex, the presence of eyewear or facial hair, distraction and fatigue were analyzed as possible contributing factors that increase likelihood of facial contact. Results The median rate of facial contact was 22 contacts per hour. Men had a significantly higher rate of facial contact compared to women. Age, glasses, and presence of facial hair were not contributing factors. The mouth was the most frequently observed site of contact. Fatigue and distraction may increase rates of facial contact. Conclusions Changing personal behavior is a simple and cost-effective action that can be employed to reduce one's risk of acquiring an infectious disease. This study indicates that there are societal differences that put some individuals at higher risk of contracting infectious disease than others.

Unusual or prominent calcifications found on screening mammography may prompt additional radiologic and clinical work-up given the possible association with pre-malignant lesions, other high-risk lesions, or malignancies. Osseous metaplasia (OM) of the breast, also referred to as metaplastic ossification or heterotopic bone formation, is an uncommon finding that may present as radiographic calcification. There are isolated case reports of OM associated with benign or malignant tumors of the breast, as well as with a variety of non-neoplastic conditions. We report 2 cases of OM in the breast associated with a hemangioma and review the relevant literature. To the best of our knowledge, these are the first reported cases of this association in the breast.

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma usually arising in the abdomen or pelvis of young males under 30 years of age. We present a case of a 32-year-old male with a palpable axillary mass and multiple bilateral lung nodules. Excisional biopsy of the axillary mass showed sheets and nests of small round cells with numerous mitoses, areas of necrosis, and desmoplastic stroma. Initial immunohistochemical stains performed at an outside institution demonstrated immunoreactivity for epithelial markers and focal reactivity for breast markers. The tumor was initially diagnosed as poorly differentiated carcinoma, with consideration of a possible primary breast cancer. Additional workup demonstrated strong, diffuse positivity for desmin in tumor cells, leading to the final diagnosis of DSRCT. Subsequent molecular testing confirmed DSRCT with EWSR1 gene rearrangement. This case illustrates the importance of recognizing the morphologic features of DSRCT in the setting of uncommon location or patient age.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for >100 years. Patients (n = 25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28, 2020, to April 14, 2020. Patients were transfused with convalescent plasma, obtained from donors with confirmed severe acute respiratory syndrome coronavirus 2 infection who had recovered. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 after transfusion. Clinical improvement was assessed on the basis of a modified World Health Organization six-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains. At day 7 after transfusion with convalescent plasma, nine patients had at least a one-point improvement in clinical scale, and seven of those were discharged. By day 14 after transfusion, 19 (76%) patients had at least a one-point improvement in clinical status, and 11 were discharged. No adverse events as a result of plasma transfusion were observed. Whole genome sequencing data did not identify a strain genotype-disease severity correlation. The data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease.

Purpose Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC. Methods The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS. Results Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p, Highlights • Metaplastic breast cancer is associated with poor clinical outcomes. • Metaplastic breast cancer associated with worse survival than patients with triple negative invasive ductal carcinoma. • Radiation therapy and chemotherapy associated with improved survival for patients with metaplastic breast cancer.

Purpose: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC. Patients and Methods: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers. Results: Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders. Conclusions: The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

Pure Mucinous breast carcinoma (PMBC) is an invasive breast cancer with favorable prognosis. While pathology-specific guidelines exist for PMBC regarding adjuvant chemotherapy and endocrine therapy, no recommendations exist regarding locoregional treatment based on tumor histology. Prognostic impact of radiotherapy for patients with PMBC remains unclear.The National Cancer Database was queried (2004-2017) for patients with pN0M0 PMBC who underwent lumpectomy. Chi-square testing compared categorical frequencies between patients who received radiotherapy versus those who did not. Propensity score matching created a 1:1 matched cohort of patients who received radiotherapy and patients who didn't. Kaplan-Meier analysis evaluated overall survival (OS). Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS.17,259 patients met selection criteria; 11,087 (74%) received radiotherapy while 3852 (26%) did not. After PSM, radiotherapy (HR 0.629; 95% CI 0.531-0.746), endocrine therapy (HR 0.676; 95% CI 0.567-0.805), black race (HR 0.703; 95% CI 0.498-0.991), and private insurance (HR 0.184; 95% CI 0.078-0.432) were favorable prognostic factors on multivariate Cox regression analysis while age ≥ 70 years (HR 2.668; 95% CI 1.903-3.740), tumor size20 mm (HR 1.964; 95% CI 1.613-2.391), and CDCC score0 (HR 1.770; 95% CI 1.474-2.126) were unfavorable prognostic factors. After PSM, 5-year OS was 86% for those who received radiotherapy and 81% for those who did not (P.001).This is the largest study to date on PMBC and the prognostic impact of adjuvant radiotherapy. Radiotherapy is associated with a survival advantage, suggesting omission of radiotherapy is not warranted.

The inducible nitric oxide signaling (iNOS) pathway is associated with poor prognosis in triple-negative breast cancer (TNBC). Prior studies using in vivo models showed that inhibition of the iNOS signaling pathway using the pan-NOS inhibitor NG-monomethyl-l-arginine (L-NMMA) reduced tumor growth and enhanced survival in patients with TNBC. Here, we report a first-in-class phase 1/2 trial of L-NMMA combined with taxane for treating patients with chemorefractory, locally advanced breast cancer (LABC) or metastatic TNBC. We also examined immune cell correlates of chemotherapy response. 35 patients with metastatic TNBC were recruited: 15 in the phase 1 trial and 24 in the phase 2 trial (including 4 recommended phase 2 dose patients from the phase 1 trial). The overall response rate was 45.8% (11 of 24): 81.8% (9 of 11) for patients with LABC and 15.4% (2 of 13) for patients with metastatic TNBC. Among the patients with LABC, three patients had a pathological complete response at surgery (27.3%). Grade ≥3 toxicity was noted in 21% of patients; however, no adverse events were attributed to L-NMMA. Immune cells analyzed by CyTOF indicated that chemotherapy nonresponders showed greater expression of markers associated with M2 macrophage polarization and increased concentrations of circulating IL-6 and IL-10 cytokines. In contrast, chemotherapy responders showed an increase in CD15

Colonic diverticulosis is pervasive in Western society, with over half of individuals over the age of 60 carrying the diagnosis. A Giant Colonic Diverticulum (GCD) is a rare presentation of diverticulosis, involving one or more colonic diverticula that measure 4 cm or greater. Less than 200 reports of GCD have been published in the literature. Almost all GCD patients present with symptoms, with abdominal pain being the most common. Diagnosis is usually made with CT imaging and recommended treatment is segmental colectomy. We present an atypical case of GCD with an asymptomatic presentation, initial diagnosis made during endoscopy and a minimally invasive resection of multiple GCD within the same patient.

A 35-year-old female with end-stage renal disease on peritoneal dialysis presented with altered mental status and abdominal discomfort. On admission, she was found to have a distended tympanic abdomen and elevated WBC

A 58-year-old male patient with incessant ventricular tachycardia was referred to cardiac magnetic resonance for scar assessment. He was found to have metastatic amelanotic melanoma of the heart. The cardiac magnetic resonance–based diagnosis of cardiac malignancy critically altered the subsequent clinical management. There was a marked response to immunotherapy as evidenced by follow-up imaging studies. (Level of Difficulty: Intermediate.), Graphical abstract, A 58-year-old male patient with incessant ventricular tachycardia was referred to cardiac magnetic resonance for scar assessment. He was found to have…

BACKGROUND High-risk human papillomavirus (HPV)-Papanicolaou (Pap) cotesting is recommended for cervical cancer screening in women aged ≥30 years. The current study analyzed the effectiveness of cotesting on risk management in different age groups. METHODS A retrospective review of a 5-year cytology database identified 9434 women with HPV-Pap cotesting and follow-up cervical biopsy. The 3-year cumulative risk of developing high-grade cervical lesions (≥high-grade squamous intraepithelial lesion [HSIL]) was analyzed using age stratification. RESULTS The 3-year cumulative risk of developing ≥HSIL was found to be significantly different in women with baseline cotesting HPV-positive and Pap-positive results (HPV+/Pap+; defined as ≥atypical squamous cells of undetermined significance), HPV+ and Pap-negative results, and HPV-negative and Pap+ results at 19.2%, 7.9%, and 3.1%, respectively (P

Background Invasive micropapillary carcinoma (IMPC) is an uncommon subtype of breast cancer. Previous studies of this subtype demonstrated a higher propensity for lymph node metastases as compared with invasive ductal carcinoma (IDC). The purpose of the present study was to determine the clinical characteristics, outcomes, and propensity for lymph node metastasis of patients with IMPC of the breast recorded in the National Cancer Database (NCDB). Methods Records of patients with IMPC diagnosed between 2004 and 2014 were retrieved from the NCDB. Log-rank test was performed to evaluate associations of clinical characteristics with overall survival (OS). Cox proportional hazards model was used to determine variables associated with OS. Results Overall, 2660 patients with IMPC met the selection criteria; the 5-year OS rate was 87.5% and 24.9% of patients had nodal involvement at presentation. Patients with ≥ 4 positive lymph nodes had shorter OS than node-negative patients, whereas patients with 1–3 positive nodes had similar OS to node-negative patients. Age

ObjectiveHuman papilloma virus (HPV) detection and genotyping are increasingly used in clinical risk assessment. We aimed to analyze HPV genotyping performance in risk stratification among cytology diagnosis categories.MethodsBetween January 1, 2015 and December 31, 2016, 4562 cases with cytology–HPV co-testing and biopsy follow-up were identified. HPV tests were performed on Cobas (n=3959) or Aptima (n=603) platforms. Of the biopsies, 669 demonstrated high-grade squamous intraepithelial lesions or worse.ResultsPooled high-risk HPV testing had high overall sensitivity (97%) but low specificity (20%) and positive predictive value (20%) for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. HPV16/18 genotyping had considerably improved specificity (81%) and positive predictve value (35%) in predicting high-grade squamous intraepithelial lesions or worse, especially in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion categories. Significantly more biopsy-confirmed high-grade squamous intraepithelial lesions or worse were detected by Aptima than Cobas testing, as measured by HPV16/18 (48% vs 33%, pConclusionsHPV genotyping was sensitive for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in all cytologic categories, and is particularly valuable in risk evaluation for women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The triaging role was greatly diminished in high-risk lesions (atypical glandular cells, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions) due to low specificity and positive predictive value. Aptima performance in risk management was superior to Cobas, with significantly higher positive predictive value for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. Our results highlight the importance of careful data interpretation from studies using different HPV testing methods and the need to incorporate HPV E6/E7-mRNA testing into management guidelines.

Purpose The utility of post-mastectomy radiotherapy (PMRT) in women with a nodal complete response (CRn) to neoadjuvant chemotherapy (NAC) is unknown. The NSABP B-51 trial is evaluating this question, but has not reported results thus far. Therefore, we sought to answer this question with the National Cancer Database. Methods The National Cancer Database was queried for women with cT1–4N1-3M0 breast cancer who had undergone NAC and were ypN0 upon mastectomy. Statistics included multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis, Cox proportional hazards modeling, and construction of forest plots. Results Of 14,690 women, 10,092 (69%) underwent adjuvant PMRT and 4598 (31%) did not. The median follow-up was 55.6 months. In all patients, the 10-year OS was 76.3% for PMRT and 78.6% without (p = 0.412). There were no notable effects of PMRT on OS based on age or the axillary management (number of nodes removed). Specifically, in the NSABP B-51 population of cT1–3 cN1 patients, the 10-year OS was 82.6% for PMRT and 80.0% without (p = 0.250). PMRT benefitted women with increasing cT stage (i.e. cT3–4), increasing ypT stages (with the exception of ypT4 potentially owing to small sample sizes), and cN3 cases (p Conclusions In the absence of published results from NSABP B-51, this assessment of over 14,000 women from a contemporary US database revealed that PMRT may be most useful for a “moderately-high” risk group – women with more advanced primary and/or nodal disease at diagnosis, yet with tumor biology favorable enough that the disease does not progress or remain stable after NAC. The OS findings notwithstanding, this study cannot exclude potential differences between groups in recurrence-free survival, which is the primary endpoint of NSABP B-51, While the results of the NSABP B-51 will confirm optimal management for patients with limited nodal disease having a CRn following NAC, the present results suggest PMRT should remain the standard of care for more advanced disease than NSABP B-51 eligibility criteria.

BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004–2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS. RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy. CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding.

Background: Cardiac metastasis due to colon cancer is extraordinarily uncommon. Given the rarity of diagnosis, there is paucity of evidence and hence, no established guidelines for evaluation or clinical management strategy. Clinical presentation: We present the case of a 59 year old male with a previously treated colonic carcinoma who presented with new onset exertional dyspnea. He was noted to be having a right atrial mass on an echocardiogram performed at his cardiologist’s office. Further workup with CT angiogram of the chest confirmed a right atrial mass measuring 4.0 cm. Serum CEA was normal. Biopsies of the right atrial mass demonstrated metastatic moderately differentiated colonic adenocarcinoma. Mismatch repair protein expression analysis by immunohistochemistry showed no loss of MLH1, MSH2, MSH6 or PMS2 expression. Next generation sequencing for RAS and BRAF mutations was negative. Patient received treatment with FOLFIRINOX/ bevacizumab with noted reduction in size of mass. Conclusion: To the best of our knowledge, this is the first report of next generation sequencing results available on a biopsy of metastatic colorectal cancer to the heart with the largest literature review of 31 reported cases of metastatic colorectal cancer to the heart. It will help direct clinical management and also adds evidence to the potential efficacy of treatment of this rare aggressive disease with chemotherapy in combination with VEGF inhibitors.

Hemangiomas of the breast are uncommon and, in males, almost always present as a palpable breast mass. Here, we report the case of a male patient who was diagnosed with a breast hemangioma following an incidental injury to his breast, which triggered symptoms that prompted clinical work-up. As this diagnosis likely would have otherwise not been made, it follows that benign breast masses in males may be underreported and underdiagnosed.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare mesenchymal tumor of borderline malignancy. It generally involves superficial soft tissue, with a predilection to the lower extremities. Microscopically this tumor is characterized by a fascicular and storiform growth pattern, spindled to epithelioid cells, nuclear atypia with pleomorphism, and eosinophilic granular, and fibrillar to glassy cytoplasm. Strong diffuse immunoreactivity for CD34 is very characteristic of this entity. Due to under-recognition, this tumor is generally underreported. Additionally, cases of recurrence are rarely reported in the literature. We will comprehensively review the English language literature on all reported cases of SCPFT, with emphasis on recurrence.

Pathology training programs throughout the United States have endured unprecedented challenges dealing with the ongoing coronavirus disease 2019 pandemic. At Houston Methodist Hospital, the Department of Pathology and Genomic Medicine planned and executed a trainee-oriented, stepwise emergency response. The focus was on optimizing workflows among areas of both clinical and anatomic pathology, maintaining an excellent educational experience, and minimizing trainee exposure to coronavirus disease 2019. During the first phase of the response, trainees were divided into 2 groups: one working on-site and the other working remotely. With the progression of the pandemic, all trainees were called back on-site and further redeployed within our department to meet the significantly increased workload demands of our clinical laboratory services. Adjustments to trainee educational activities included, among others, the organization of a daily coronavirus disease 2019 virtual seminar series. This series served to facilitate communication between faculty, laboratory managers, and trainees. Moreover, it became a forum for trainees to provide updates on individual service workflows and volumes, ongoing projects and research, as well as literature reviews on coronavirus disease 2019–related topics. From our program’s experience, redeploying pathology trainees within our department during the coronavirus disease 2019 pandemic resulted in optimization of patient care while ensuring trainee safety, and importantly, helped to maintain continuous high-quality education through active involvement in unique learning opportunities.

BackgroundCOVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years.MethodsPatients (n=25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28 – April 14, 2020. Patients were transfused with convalescent plasma obtained from donors with confirmed SARS-CoV-2 infection and had been symptom free for 14 days. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 post-transfusion. Clinical improvement was assessed based on a modified World Health Organization 6-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains.ResultsAt baseline, all patients were receiving supportive care, including anti-inflammatory and anti-viral treatments, and all patients were on oxygen support. At day 7 post-transfusion with convalescent plasma, nine patients had at least a 1-point improvement in clinical scale, and seven of those were discharged. By day 14 post-transfusion, 19 (76%) patients had at least a 1-point improvement in clinical status and 11 were discharged. No adverse events as a result of plasma transfusion were observed. The whole genome sequencing data did not identify a strain genotype-disease severity correlation.ConclusionsThe data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease. Randomized, controlled trials are needed to determine its efficacy.

Breast cancer is the most common malignancy affecting women. Metastatic involvement of the gastrointestinal (GI) tract secondary to a primary breast malignancy is rare. Here, we describe the case of a 60-year-old woman with a history of right lobular breast cancer (diagnosed and treated five years prior to presentation) who presented with fatigue, generalized abdominal pain, distension, weight loss, and vomiting. Her initial imaging was suspicious for a primary gynecological malignancy; however, subsequent workup showed a colonic mass. Total colonoscopy revealed colon metastases, and an immunohistochemical profile favored invasive lobular carcinoma of breast. Most cases of gastrointestinal metastases from breast cancer have lobular histology; however, colonic involvement is rare.

Micropapillary (MP) carcinoma is an uncommon tumor with a distinct histologic pattern. Although micropapillary carcinoma has been reported in the stomach, the concurrence of mucinous carcinoma and micropapillary carcinoma has not been reported to-date. A 69-year-old gentleman who presented with anemia was found at endoscopy to have a 1.7 cm gastric ulcer which was biopsied and subsequently underwent a partial gastrectomy. There was an ulcerated moderately differentiated adenocarcinoma displaying a micropapillary component within a mucinous adenocarcinoma component and a metastatic MP carcinoma in 1 of 18 lymph nodes. The tumor was immunoreactive for EMA, MUC2, MUC5AC, MUC6, CDX2, and p53 in both mucinous and mucinous-MP carcinoma areas; and negative for CK7, CK20, CA-125, synaptophysin, chromogranin, PD-L1, MMR proteins, and EBV. To the best of our knowledge, this is the first reported case of MP gastric carcinoma in association with mucinous carcinoma. Key words: Gastric carcinoma, Micropapillary carcinoma, Mucinous carcinoma

Invasive papillary breast cancer (IPBCA) represents 0.5% of invasive BCA, and is thought to carry a favorable prognosis. This population-based study reports on prognostic factors, treatment, and outcomes of early-stage IPBCA to explore whether there is any evidence to support less aggressive treatment. IPBCA cases from 1990 to 2009 of the recent Surveillance, Epidemiology, and End Results were analyzed. Inclusion criteria included patients with stage T1-2, N0 IPBCA. Univariate and multivariate analyses were performed using the variables of treatment, stage, race, hormone receptor status, grade (G1-3), and age. Treatment modalities included lumpectomy alone (LA), lumpectomy with radiation treatment (LRT), and mastectomy alone (MA). Among 10,485 patients, median follow-up was 56 months. Five and 10-year overall survival (OS) were 93.1% and 76.8%, respectively. Patients treated with LRT had superior mean OS 16.8 versus 14.9 years for MA (P=0.0004) and 14.2 years for LA (P=0.0003). Improved OS also correlated with lower histologic grade (P

Clear cell hidradenoma (CCH) is an uncommon benign dermal-based tumor that typically presents on the head, neck, and upper extremities as a solitary firm nodule. The clear cytoplasm can resemble benign and malignant clear cell neoplasms from multiple sites; thus, a large differential diagnosis is often considered. When CCH is seen in the breast or axilla, glycogen-rich clear cell carcinoma (GRCCC) of the breast enters the differential diagnosis. Although GRCCC is rare, it is important to recognize as a breast carcinoma variant because most reports have suggested that it has a more aggressive course than typical invasive ductal carcinoma. We report a case of CCH in the upper axilla of a 64-year-old woman who also happened to have a remote history of invasive GRCCC to highlight the potential diagnostic pitfalls when evaluating these two histologically similar clear cell tumors. Although immunohistochemical studies can be helpful, overlapping staining patterns can lead to potential confusion and misclassification. Both of our patient's tumors were negative for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and PAX8. ER and PR are typically negative in hidradenomas and can be negative in up to 50% of GRCCC. Although considered a breast marker, GATA-3 can be negative in GRCCC and positive in skin adnexal tumors. p63 can be especially helpful, as it is expressed in skin adnexal tumors, but lost in most (Thike et al., 2010) invasive breast carcinomas. Finally, periodic acid-Schiff (PAS) with and without diastase highlights intra-cytoplasmic glycogen in GRCCC.

High-risk human papillomavirus (hrHPV) testing is important in cervical cancer screening and management algorithms. Roche (Pleasanton, Calif.) cobas hrHPV testing is commonly performed on both ThinPrep (TP) and SurePath (SP) samples, but performance of these platforms has not been fully investigated in the literature.Roche hrHPV testing was performed on 47,885 (TP = 18,295; SP = 29,590) out of 130,648 consecutive Papanicolaou tests, over 16 months; 1895 of those had interpretable biopsies.The overall hrHPV detection rates were similar in TP (13.5%) and SP (13.1%). The hrHPV positive rate was higher in SP (8.5%) than TP (7.3%, P0.0001) in women with negative cytology; the difference in other cytologic diagnosis categories was insignificant. TP samples had significantly fewer negative cytology diagnoses (7.3% versus 8.5%, P0.0001), more low-grade abnormalities in cytology and biopsies, and higher colposcopy referral rate (4.8% versus 2.7%, P0.0001) than SP. There were no differences between TP and SP in detecting ≥HSIL by hrHPV testing, cytology or biopsy. SP samples had a significantly higher rate of HPV 16/18 but a lower rate of non-16/18 hrHPV genotypes than TP.Roche cobas hrHPV testing was similar in both TP and SP platforms. The significantly lower hrHPV detection rate in cytological negative TP samples is likely related to higher cytology reporting rates for indeterminate and low-grade diagnoses in TP than SP samples. Significant differences were also observed in hrHPV genotyping results between TP and SP. Clinical risk stratification based on hrHPV testing may need to take testing platforms into consideration.