Modified oncoplastic lift, lymphatic excision, and reconstruction: Introduction of a novel technique in oncoplastic breast surgery with simple surgical principles.

INTRODUCTION: Oncoplastic surgery is an important component of the management of breast cancer. As prognosis has improved, the need for proficient techniques to achieve disease eradication while maintaining cosmesis for naturally appearing breasts has gained importance. This study describes an easy-to-learn modified oncoplastic technique for patients undergoing breast-conserving treatment. DESCRIPTION OF THE TECHNIQUE: Tumor resection is performed through different peri-areolar, inframammary, or radial incisions. To reduce the size of the surgical defect created after tissue resection, an internal purse-string is performed parallel to the chest wall or base of the wound with subsequent staggering in three or more layers as needed, while maintaining the parallel orientation of the needle. This is followed by the creation and overlapping of internal breast tissue flaps that are rearranged to decrease the dead space with the aim of improving cosmesis. The redundant skin is removed for the skin envelope to maintain shape. The wound is closed in layers. We also describe steps in performing sentinel lymph node and tumor extraction through the same periareolar, inframammary, or radial incisions for tumors located in outer quadrants. Following closure, contour and projection of the breast were maintained without indentation or loss of projection, with a symmetrical appearance to the contralateral side. CONCLUSION: This simplified oncoplastic (MOLLER) technique can be easily learned and used by surgeons who treat cancer patients and have limited oncoplastic training. It uses basic known surgical principles to decrease the size of the defect created while minimizing the need for larger incisions/pedicles.

Stalled at the intersection: insurance status and disparities in post-mastectomy breast reconstruction.

PURPOSE: Post-mastectomy breast reconstruction (PMBR) is an important component of breast cancer treatment, but disparities relative to insurance status persist despite legislation targeting the issue. We aimed to study this relationship in a large health system combining a safety-net hospital and a private academic center. METHODS: Data were collected on all patients who underwent mastectomy for breast cancer from 2011 to 2019 in a private academic center and an adjacent public safety-net hospital served by the same surgical teams. Multivariable logistic regression was used to assess the effect of insurance status on PMBR, controlling for covariates that included socioeconomic, demographic, and clinical factors. RESULTS: Of 1554 patients undergoing mastectomy for breast cancer, 753 (48.5%) underwent PMBR, of which 592 (79.9%) were privately insured, 50 (6.7%) Medicare, 68 (9.2%) Medicaid, and 31 (4.2%) uninsured. Multivariable logistic regression showed a significantly higher likelihood of not undergoing PMBR for uninsured (OR 6.0, 95% CI 3.7-9.8; p < 0.0001), Medicare (OR 1.9, (95% CI 1.2-3.0; p = 0.006), and Medicaid (OR 1.5, 95% CI 1.0-2.3; p = 0.04) patients compared with privately insured patients. Age, stage, race and ethnicity, and hospital type confounded this relationship. CONCLUSION: Patients without health insurance have dramatically reduced access to PMBR compared to those with private insurance. Expanding access to this important procedure is essential to achieve greater health equity for breast cancer patients.

Axillary Response to Neoadjuvant Therapy in Node-Positive, Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients: Predictors and Oncologic Outcomes.

BACKGROUND: One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) patients is axillary downstaging to avoid axillary dissection. OBJECTIVE: The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response. METHODS: A prospectively collected database was queried for node-positive, ER+, HER2- breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model. RESULTS: A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p = 0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p = 0.03). NET patients with ypN0 were younger and were treated for a longer period of time (>6 months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR. CONCLUSIONS: For patients with node-positive, ER+, HER2- breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response.

Overcoming disparities: Multidisciplinary breast cancer care at a public safety net hospital.

PURPOSE: Public safety net hospitals (SNH) serve a disparate patient population; however, little is known about long-term oncologic outcomes of patients receiving care at these facilities. This study is the first to examine overall survival (OS) and the initiation of treatment in breast cancer patients treated at a SNH. METHODS: Patients presenting to a SNH with stage I-IV breast cancer from 2005 to 2017 were identified from the local tumor registry. The hospital has a weekly breast tumor board and a multidisciplinary approach to breast cancer care. Kaplan-Meier survival analysis was performed to identify patient, tumor, and treatment characteristics associated with OS. Factors with a p < 0.1 were included in the Cox proportional hazards model. RESULTS: 2709 breast cancer patients were evaluated from 2005 to 2017. The patient demographics, tumor characteristics, and treatments received were analyzed. Five-year OS was 78.4% (93.9%, 87.4%, 70.9%, and 23.5% for stages I, II, III, and IV, respectively). On multivariable analysis, higher stage, age > 70 years, higher grade, and non-Hispanic ethnicity were associated with worse OS. Patients receiving surgery (HR = 0.33, p < 0.0001), chemotherapy (HR = 0.71, p = 0.006), and endocrine therapy (HR = 0.61, p < 0.0001) had better OS compared to those who did not receive these treatments. CONCLUSION: Despite serving a vulnerable minority population that is largely poor, uninsured, and presenting with more advanced disease, OS at our SNH approaches national averages. This novel finding indicates that in the setting of multidisciplinary cancer care and with appropriate initiation of treatment, SNHs can overcome socioeconomic barriers to achieve equitable outcomes in breast cancer care.

Axillary response rates to neoadjuvant chemotherapy in breast cancer patients with advanced nodal disease.

PURPOSE: Utilization of sentinel lymph node biopsy (SLNB) in breast cancer patients with positive nodes after neoadjuvant chemotherapy (NAC) has increased. We examine axillary response rates after NAC in patients with clinical N2-3 disease to determine whether SLNB should be considered. METHODS: Breast cancer patients with clinical N2-3 (AJCC 7th Edition) disease who received NAC followed by surgery were selected from our institutional tumor registry (2009-2018). Axillary response rates were assessed. RESULTS: Ninety-nine patients with 100 breast cancers were identified: 59 N2 (59.0%) and 41 (41.0%) N3 disease; 82 (82.0%) treated with axillary lymph node dissection (ALND) and 18 (18.0%) SLNB. The majority (99.0%) received multiagent NAC. In patients undergoing ALND, cCR was observed in 20/82 patients (24.4%), pathologic complete response (pCR) in 15 patients (18.3%), and axillary pCR in 17 patients (20.7%). In patients with a cCR, pCR was identified in 60.0% and was most common in HER2+ patients (34.6%). CONCLUSION: In this analysis of patients with clinical N2-3 disease receiving NAC, 79.3% of patients had residual nodal disease at surgery. However, 60.0% of patients with a cCR also had a pCR. This provides the foundation to consider evaluating SLNB and less extensive axillary surgery in this select group.

Diagnostic application of cyclin D1 fluorescent in situ hybridization for histologically undetermined early lesions of acral melanoma in situ: A case series.

Histologically undetermined early acral melanoma in situ (HUAMIS) is rare but a diagnostic challenge, being clinically and dermoscopically MIS (late onset, a large size (>7 mm), parallel ridges pattern) but microscopically without recognizable cytological atypia. Cyclin D1 (CCND1) gene amplification is a genetic aberration occurring in the early radial growth phase of AMs and could thus help determine malignancy for this disease. We determine the value of CCND1 amplification by FISH as a diagnostic marker for HUAMIS. CCND1 amplification was examined in paraffin-embedded skin biopsies and excisions using a dual-probes fluorescence in situ hybridization (FISH) (11q13 and CEP11). One FISH-negative case 6 was additionally examined by Mypath Melanoma (qRT-PCR). Seventeen cases (12 dysplastic nevi, 3 AMIS, and 2 invasive AM) were served as negative controls for FISH. All six patients (4 females and 2 males) were Hispanic. Pigment lesions were on the left plantar foot (4), right third finger palm (1), and right thumb subungual (1). All cases showed similar clinical and dermoscopical characteristics, including late onset (50 to 74 years old), long duration (from 2 to 15 years), large-sized pigments (from 16 to 40 mm), and a parallel ridge pattern. Junctional melanocytes with no or minimal atypia from five cases showed CCND1 amplifications. Four of 5 cases were received 1st or/and 2nd wide excisions, which demonstrated foci of histologically overt MIS. One FISH-negative case 6 demonstrated "likely malignancy" scores (>2) by Mypath Melanoma (qRT-PCR). None of negative controls showed the amplification. We propose here a simple CCND1 FISH is a practical diagnostic test to determine the malignancy of the very early progression phase of AM preceding histopathologically defined MIS. Cases presented here could be an indolent subtype of AMIS characterized by carrying a long latent radial growth phase without vertical growth, mimicking lentigo maligna.

Surgical Management of the Axilla in Patients with Occult Breast Cancer (cT0 N+) After Neoadjuvant Chemotherapy.

BACKGROUND: Occult breast cancer (OBC) is a rare clinical entity. Current surgical management includes axillary lymphadenectomy (ALND) with or without mastectomy. We sought to investigate the role of sentinel lymph node biopsy (SLNB) in patients with OBC treated with neoadjuvant chemotherapy (NAC). METHODS: Patients with clinical T0N+ breast cancer were selected from the National Cancer Data Base (NCDB, 2004-2014) and compared according to axillary surgical approach, SLNB (≤ 4 LNs) or ALND (> 4 LNs). Primary outcome was overall survival (OS), calculated using Kaplan-Meier methods. Secondary outcome was complete pathological response (pCR). RESULTS: A total of 684 patients with OBC were identified: 470 (68.7%) underwent surgery upfront and 214 (31.3%) received NAC. Of the NAC patients, 34 (15.9%) underwent SLNB and 180 (84.1%) ALND. One hundred and fifty-three (72%) patients received radiotherapy (RT). There was no difference in pCR rates between the ALND and SLNB (34.3% vs 24.5%, respectively p = 0.245). In patients undergoing surgery first, improved OS was observed with ALND compared to SLNB (106.9 vs 85.5 months, p = 0.013); however, no difference in OS was found in patients who received NAC (105.6 vs 111.3 months, p = 0.640). RT improved OS in patients who underwent NAC followed by SLNB (RT, 123 months vs no RT, 64 months, p = 0.034). Of NAC patients who did not undergo RT, ALND had superior survival compared to SLNB (113 vs 64 months, p = 0.013). CONCLUSION: This is the first comparative analysis assessing the surgical management of the axilla in patients with OBC who underwent NAC. In this population, there was a decrease in survival in patients who underwent SLNB alone; however, with the addition of RT, there was no difference in OS between SLNB and ALND. SLNB plus RT may be considered as an alternative to ALND in patients with OBC who have a good response to NAC.

Breast fibromatosis: Making the case for primary vs secondary subtypes.

Fibromatosis of the breast is a rare condition that can be locally aggressive. The mainstay of treatment remains wide local excision, with varied adjuvant therapy as needed. The authors describe their experience in the treatment of a series of patients and propose the classification of primary and secondary breast fibromatosis. A single-institution retrospective analysis of patients treated for breast fibromatosis from 2003 to 2017 was completed. Demographic data, pertinent past medical history, and treatment modalities were reviewed. Primary breast fibromatosis was defined as arising in the absence of previous surgery or radiation therapy to the ipsilateral breast. Secondary breast fibromatosis was defined as arising in the setting of previous surgery or radiation therapy to the ipsilateral breast. A total of 16 patients were included with the median age 40 (28-64) years. The average size of the lesion was 6.37 cm (range of 1.5-15 cm). Mean follow-up time was 65 months. Surgical excision was completed in 14 patients, with two recurrences. There were no recurrences in patients with surgical margins >1 cm. Two patients were treated nonsurgically. There were seven patients with primary fibromatosis of the breast and nine patients with secondary fibromatosis of the breast. Fibromatosis of the breast is difficult to diagnose prior to surgical excision. We advocate for the multi-disciplinary treatment of this disease process with an aggressive surgical approach to achieve margins >1 cm.

Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) for the Prevention of Breast Cancer-Related Clinical Lymphedema After Axillary Lymph Node Dissection.

OBJECTIVE: To assess the efficiency of Simplified Lymphatic Microsurgical Preventing Healing Approach (S-LYMPHA) in preventing lymphedema (LE) in a prospective cohort of patients. BACKGROUND: LE is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 25%. LYMPHA has been proposed as an effective adjunct to ALND for the prevention of LE. This procedure, however, requires microsurgical techniques and significant coordination between services. METHODS: All patients, undergoing ALND with or without S-LYMPHA between January 2014 and December 2016 were included in the study. During follow-up visits, tape-measuring limb circumference method was used to detect LE. The incidence of LE was compared between ALND with and without S-LYMPHA. RESULTS: A total of 380 patients were included in the analysis. Median follow-up time was 15 (1-32) months. Patients, who underwent S-LYMPHA, had a significantly lower rate of LE both in univariate and multivariate analysis [3% vs 19%; P = 0.001; odds ratio 0.12 (0.03-0.5)]. Excising more than 22 lymph nodes and a co-diagnosis of diabetes mellitus were also correlated with higher clinical LE rates on univariate analysis, but only excising more than 22 lymph nodes remained to be significant on multivariate analysis. CONCLUSIONS: S-LYMPHA is a simple method, which decreases incidence of LE dramatically. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.

Extent of regional lymph node surgery and impact on outcomes in patients with early-stage breast cancer and limited axillary disease undergoing mastectomy.

PURPOSE: Management of the axilla in patients with early-stage breast cancer (ESBC) has evolved. Recent trials support less extensive axillary surgery in patients undergoing mastectomy. We examine factors affecting regional lymph node (RLN) surgery and outcomes in patients with ESBC undergoing mastectomy. METHODS: Women with clinical T1/2 N0 M0 invasive BC who underwent mastectomy with 1-2 positive nodes were selected from the National Cancer Database (2004-2015). Axillary surgery was defined by number of RLNs examined: 1-5 sentinel LN dissection (SLND), and ≥ 10 axillary LND (ALND). Binary logistic regression and survival analyses were performed to assess the association between axillary surgery and clinical characteristics, and overall survival (OS), respectively. RESULTS: 34,243 patients were included: 13,821 SLND (40%) and 20,422 ALND (60%). SLND significantly increased from 21% (2004) to 45% (2015) (p < .001). Independent factors associated with SLND were treatment year, non-Academic centers, geographic region, tumor histology, and postmastectomy radiotherapy (PMRT). Multivariable survival analysis showed that ALND was associated with better OS (HR 0.78, 95% CI 0.72-0.83, p < .001) relative to SLND; however, there was no difference in patients with LN micrometastases treated without RT (HR 0.87, 95% CI 0.73-1.05, p = .153) or patients receiving PMRT (HR 0.92, 95% CI 0.76-1.13, p = .433). CONCLUSIONS: SLND has significantly increased in patients undergoing mastectomy with limited axillary disease and is influenced by patient, tumor, and treatment factors. Survival outcomes did not differ by axillary treatment for patients with LN micrometastases treated without RT or patients who received PMRT. SLND may be considered in select patients with ESBC and limited axillary disease undergoing mastectomy.

The role of matricellular proteins and tissue stiffness in breast cancer: a systematic review.

Malignancies consist not only of cancerous and nonmalignant cells, but also of additional elements, as extracellular matrix. The aim of this review is to summarize meta-analyses, describing breast tissue stiffness and risk of breast carcinoma (BC) assessing the potential relationship between matricellular proteins (MPs) and survival. A systematic computer-based search of published articles, according to PRISMA statement, was conducted through Ovid interface. Mammographic density and tissue stiffness are associated with the risk of BC development, suggesting that MPs may influence BC prognosis. No definitive conclusions are available and additional researches are required to definitively clarify the role of each MP, mammographic density and stiffness in BC development and the mechanisms involved in the onset of this malignancy.

A tailored approach to regional nodal irradiation.

Regional nodal irradiation for breast cancer has recently been shown to improve disease-free survival, distant disease-free survival, and breast-related mortality but is associated with morbidity. A tailored approach adding regional nodal irradiation only to patients with involvement of the internal mammary nodes is improving prognosis while minimizing morbidity.

Metastatic gastric cancer (MGC) patients: Can we improve survival by metastasectomy? A systematic review and meta-analysis.

BACKGROUND: Prognosis with current management strategies continues to be dismal in metastatic gastric cancer (MGC) patients. We aimed to evaluate the role of metastasectomy in improving survival. METHODS: A comprehensive search of MEDLINE, EMBASE, SCOPUS, and Cochrane central databases (1965 to present) was performed. All comparative studies measuring survival in MGC patients undergoing metastasectomy versus other therapies were included. Pooled risk ratios with corresponding 95% confidence intervals (CI) were calculated for survival at 1, 3, and 5 years. RESULTS: Sixteen studies with 1712 patients (378 patients in metastasectomy, 1334 patients in other therapies) were eligible for the final meta-analysis. Median age was 63 years. For patients undergoing metastasectomy, a significant survival advantage was observed at 1 year (RR 0.52, CI 0.43-0.62), 3 year (RR 0.75 CI 0.67-0.83), and 5 year (RR 0.82, CI 0.74-0.91); mean increased difference in survival conferred by metastasectomy averaged between 9.3 and 15.7 months; P < 0.001 for all results. Age, ECOG status, and STROBE score did not contribute to differences in survival. CONCLUSION: Metastasectomy is associated with increased survival at 1, 3, and 5 years in MGC patients. Large prospective randomized controlled trials are critically needed to evaluate the role of metastasectomy in MGC.

Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

BACKGROUND: Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance. METHODS: A total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept. RESULTS: A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept. CONCLUSION: [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.

Surgical and Oncologic Outcomes With Intraoperative Radiation Therapy for Early Breast Cancer.

BACKGROUND: For selected patients with early-stage breast cancer (BC), intraoperative radiation therapy (IORT) has emerged as a convenient alternative to standard whole breast irradiation (WBI). We report a single institution experience with IORT in terms of oncologic outcomes, toxicities, and cosmesis. METHODS: Clinicopathological and perioperative outcomes of patients who underwent IORT for early-stage BC at a public hospital from 2017 to 2020 were retrospectively retrieved. Toxicity was categorized to acute or chronic based on 6 months post-IORT cutoff. RESULTS: 85 patients underwent IORT and had complete data, aged 49-85 years (mean 62). Intraoperative radiation therapy added 23 minutes on average to the total operative time. Final stage was 0, I, and II in 40%, 58.9%, and 1.1% of patients, respectively. Mean tumor size was 0.8 cm (range .1-2.1), with ductal histology comprising 94% of cases. Surgical margins were positive in 2 patients, and adjuvant WBI was required in 5 patients. After a median follow-up of 17 months (range 3-41), none of the patients had local recurrence and no mortality was recorded. Early wound complications included wound dehiscence (n = 1), seroma/hematoma (n = 15), and re-operation with loss of nipple-areola complex (n = 1). Chronic skin toxicities were reported in 10 (12%) patients and good or excellent cosmetic outcome was reported in 93% of patients. CONCLUSIONS: Utilizing IORT among low-risk early BC patients may be a safe and more convenient alternative to traditional WBI, with low toxicity rate, acceptable cosmetic results, and good oncologic outcomes at 17 months. Longer follow-up and further prospective controlled studies are needed to confirm these findings.

TP53 genomics predict higher clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine ± trastuzumab.

To determine rates of pathologic complete response (pCR) and near-complete response (npCR) in operable early-stage breast cancer using neoadjuvant capecitabine plus docetaxel, with or without trastuzumab, and investigate biomarkers of pathologic response. Women with operable early-stage breast cancer were enrolled in a multicenter study of neoadjuvant therapy for four 21-day cycles with capecitabine 825 mg/m(2) plus docetaxel 75 mg/m(2) if human epidermal growth factor receptor 2 (HER2)-negative, and additionally, a standard trastuzumab dose if HER2-positive. Primary endpoint was rate of pCR and npCR. Secondary endpoints were potential associations between response and TP53 mutational analysis using the AmpliChip TP53 assay or immunohistochemical (IHC) staining, and genomic subtyping using the PAM50 assay. In patients who completed treatment and surgery, pCR and npCR rates were 15.8% in patients with HER2-negative and 50% in patients with HER2-positive tumors. Stratified by genomic subtype, patients of HER2-enriched subtype had the best response (72.2%), and luminal A (9.1%) and B (4.8%) subtypes, the poorest. Of 147 patients tested for TP53 mutations using the AmpliChip assay, 78 variants were detected; 55 were missense. Response rate among TP53-mutated patients was 30%, significantly higher than TP53 wild-type patients (10%; P = 0.0032). Concordance between AmpliChip mutation status versus TP53 IHC staining was 65%, with AmpliChip status predictive of response and IHC status not predictive. Capecitabine plus docetaxel in HER2-negative, and with trastuzumab in HER2-positive patients, provided a good response rate with four cycles of non-anthracycline-containing therapy. TP53 mutational analysis and genomic subtyping were predictive.

Novel IL-21 signaling pathway up-regulates c-Myc and induces apoptosis of diffuse large B-cell lymphomas.

Interleukin-21 (IL-21), a member of the IL-2 cytokine family, has diverse regulatory effects on natural killer (NK), T, and B cells. In contrast to other cytokines that are usually immunostimulatory, IL-21 can induce apoptosis of murine B cells at specific activation-differentiation stages. This effect may be used for treatment of B-cell malignancies. Herein we report that diffuse large B-cell lymphoma (DLBCL) cell lines exhibit widespread expression of the IL-21 receptor (IL-21R) and that IL-21 stimulation leads to cell-cycle arrest and caspase-dependent apoptosis. IL-21 also induces apoptosis in de novo DLBCL primary tumors but does not affect viability of human healthy B cells. Furthermore, IL-21 promotes tumor regression and prolongs survival of mice harboring xenograft DLBCL tumors. The antilymphoma effects of this cytokine are dependent on a mechanism involving IL-21-activated signal transducer and activator of transcription 3 (STAT3) up-regulating expression of c-Myc. This up-regulation promotes a decrease in expression of antiapoptotic Bcl-2 and Bcl-X(L) proteins triggering cell death. Our results represent one of the first examples in which the STAT3-c-Myc signaling pathway, which can promote survival and oncogenesis, can induce apoptosis in neoplastic cells. Moreover, based on IL-21's potency in vitro and in animal models, our findings indicate that this cytokine should be examined in clinical studies of DLBCL.

Axillary Reverse Lymphatic Mapping in the Treatment of Axillary Accessory Breast Cancer: A Case Report and Review of Management.

Accessory breast tissue is a rare aberration of normal breast development, that presents most commonly in the axilla. Similar to normal breast tissue, it can undergo physiologic and pathologic changes, including malignant transformation. We report a rare case of accessory breast cancer, treated with surgical resection and axillary reverse mapping (ARM), and review current literature focusing on management. We report a 68-year-old female with a history of left breast cancer treated with lumpectomy and axillary dissection, who later developed in-breast recurrence treated with re-lumpectomy and sentinel node biopsy which mapped at the contralateral (right) axilla, but was negative. Two years later screening imaging revealed right axillary tail focal asymmetry with two spiculated masses. Core biopsy showed invasive ductal carcinoma (IDC), and histologic examination of the biopsy could not determine whether this represents a new primary breast cancer or axillary metastasis from the contralateral site. She underwent lumpectomy of the two masses and sentinel node biopsy. During surgery, the masses were identified in the axilla itself, rather than the axillary tail. Final pathology revealed IDC, pT1N0(sn), and extensive ductal carcinoma in situ (DCIS). Due to positive margins, she underwent re-lumpectomy with ARM. Final pathology revealed residual DCIS with negative new margins. The patient was referred for adjuvant radiotherapy. Accessory axillary breast tissue can be confused with axillary tail tissue. It is necessary for the surgeon to distinguish between them by meticulous physical examination and radiologic evaluation, as resection of axillary breast tissue may warrant reverse lymphatic mapping for lymphedema prevention.