Subcutaneous Leiomyosarcoma: An Aggressive Malignancy Portending a Significant Risk of Metastasis and Death.

Subcutaneous leiomyosarcoma (LMS) is a rare, poorly understood variant. The current literature on the subject is sparse, consisting of isolated case reports and small clinicopathologic studies compromised by the inclusion of both its more common and indolent counterpart, cutaneous LMS (atypical intradermal smooth muscle neoplasm), as well as highly aggressive deep-seated tumors. Thus, precise clinicopathologic characterization is limited.

The Role of Surgery in Oligometastatic Retroperitoneal Sarcoma.

Retroperitoneal sarcomas are extremely rare, comprising <15% of primary sarcomas. Distant metastasis occurs in about 20% of cases, with pulmonary and hepatic metastasis as the most common sites of hematogenous spread. Although surgical resection is well established as the main treatment of localized primary disease, there are limited guidelines for the surgical treatment of intra-abdominal and distant metastases.

Patient Preferences and Satisfaction With Decisions in Stage-III Melanoma: A Mixed Methods Study.

Introduction: Rapid accumulation of data in surgical and medical oncology has changed the treatment landscape for patients with stage-III melanoma, introducing options for active surveillance and adjuvant systemic therapy; however, these options have increased the complexity of decision making.

Methods: We conducted an explanatory sequential mixed-methods study consisting of surveys and semistructured interviews among patients diagnosed with stage-III melanoma at a single institution from August 2019 to December 2021. The survey included the validated 30-point satisfaction with decision scale (SWD).

A pilot multi-institutional study to evaluate the accuracy of a supine MRI based guidance system, the Breast Cancer Locator™, in patients with palpable breast cancer.

Background: Evaluate whether the Breast Cancer Locator™ (BCL), a novel guidance system based on supine MRI images, can be safely and effectively deployed by several surgeons at multiple sites.

Methods: Patients with palpable breast cancer underwent supine MRI at their local institution. A three dimensional (3D) digital image of the tumor in the breast was derived from supine MRI images and used to generate 1) an interactive 3D virtual image of the tumor in the breast (Visualizer) and 2) a plastic bra-like form that allowed the surgeon to place a central wire and bracketing wires in the breast (BCL).

A High-Content Screen for C/EBPα Expression Identifies Novel Therapeutic Agents in Dedifferentiated Liposarcoma.

Purpose: Dedifferentiated liposarcoma (DDLS), one of the most common and aggressive sarcomas, infrequently responds to chemotherapy. DDLS survival and growth depend on underexpression of C/EBPα, a tumor suppressor and transcriptional regulator controlling adipogenesis. We sought to screen and prioritize candidate drugs that increase C/EBPα expression and may therefore serve as differentiation-based therapies for DDLS.

Resident memory CD8 T cells in regional lymph nodes mediate immunity to metastatic melanoma.

The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8 T cells were defined by the tissue of occupancy.

Dendritic cells maintain anti-tumor immunity by positioning CD8 skin-resident memory T cells.

Tissue-resident memory (T) T cells are emerging as critical components of the immune response to cancer; yet, requirements for their ongoing function and maintenance remain unclear. APCs promote T cell differentiation and re-activation but have not been implicated in sustaining T cell responses. Here, we identified a novel role for dendritic cells in supporting T to melanoma.

Resident and circulating memory T cells persist for years in melanoma patients with durable responses to immunotherapy.

While T-cell responses to cancer immunotherapy have been avidly studied, long-lived memory has been poorly characterized. In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8 T-cell responses across tissues, and across several years. Single-cell RNA sequencing revealed three subsets of resident memory T (T) cells shared between tumors and distant vitiligo-affected skin.

Large intraperitoneal lipoleiomyoma in a pre-menopausal woman: a case report.

Background: Lipoleiomyoma is a rare, benign variant of the commonplace uterine leiomyoma. Unlike leiomyoma, these tumors are composed of smooth muscle cells admixed with mature adipose tissue. While rare, they are most frequently identified in the uterus, but even more infrequently have been described in extrauterine locations.

Immunotherapy for Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive form of skin cancer which, while chemosensitive, has high rates of relapse and chemoresistance, limiting the impact of chemotherapy. An immunogenic tumor, the management of advanced MCC has changed dramatically with the introduction of checkpoint inhibitors. This review will focus on the impact of immunotherapy in unresectable and metastatic MCC, ongoing research in the adjuvant and neoadjuvant settings, and future directions of immune-based strategies for this challenging cancer.

Memory CD8 T cell responses to cancer.

Long-lived memory CD8 T cells play important roles in tumor immunity. Studies over the past two decades have identified four subsets of memory CD8 T cells - central, effector, stem-like, and tissue resident memory - that either circulate through blood, lymphoid and peripheral organs, or reside in tissues where cancers develop. In this article, we will review studies from both pre-clinical mouse models and human patients to summarize the phenotype, distribution and unique features of each memory subset, and highlight specific roles of each subset in anti-tumor immunity.

What matters most: Randomized controlled trial of breast cancer surgery conversation aids across socioeconomic strata.

Background: Women of lower socioeconomic status (SES) with early-stage breast cancer are more likely to report poorer physician-patient communication, lower satisfaction with surgery, lower involvement in decision making, and higher decision regret compared to women of higher SES. The objective of this study was to understand how to support women across socioeconomic strata in making breast cancer surgery choices.

Methods: We conducted a 3-arm (Option Grid, Picture Option Grid, and usual care), multisite, randomized controlled superiority trial with surgeon-level randomization.

Management of Regional Nodal Melanoma.

Regional nodal melanoma management has changed substantially over the past 2 decades alongside advances in systemic therapy. Significant data from retrospective studies and from 2 randomized controlled trials show no survival benefit to completion lymph node dissection compared with observation in sentinel lymph node-positive melanoma patients. Observation is becoming the standard recommendation in these patients, whereas patients with clinically detected lymph nodes are still recommended to undergo lymph node dissection.

A Randomized Prospective Trial of Supine MRI-Guided Versus Wire-Localized Lumpectomy for Breast Cancer.

Background: Wire-localized excision of non-palpable breast cancer is imprecise, resulting in positive margins 15-35% of the time.

Methods: Women with a confirmed diagnosis of non-palpable invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) were randomized to a new technique using preoperative supine magnetic resonance imaging (MRI) with intraoperative optical scanning and tracking (MRI group) or wire-localized (WL group) partial mastectomy. The main outcome measure was the positive margin rate.

Small and Isolated Immunohistochemistry-positive Cells in Melanoma Sentinel Lymph Nodes Are Associated With Disease-specific and Recurrence-free Survival Comparable to that of Sentinel Lymph Nodes Negative for Melanoma.

Although immunohistochemistry (IHC) has improved our ability to detect melanoma metastases in sentinel lymph nodes (SLN), the American Joint Committee on Cancer (AJCC) does not provide a lower threshold for determining if a SLN is positive for metastasis. Existing literature suggests that even a small aggregate or an enlarged, abnormal cell detectable by IHC can be associated with an adverse outcome. In our experience, however, some SLNs contain small solitary cells the size of neighboring lymphocytes demonstrable only by IHC.

Oncogenic BRAF Governs Regulatory T-cell Recruitment during Melanoma Tumorigenesis.

Regulatory T cells (Treg) are critical mediators of immunosuppression in established tumors, although little is known about their role in restraining immunosurveillance during tumorigenesis. Here, we employ an inducible autochthonous model of melanoma to investigate the earliest Treg and CD8 effector T-cell responses during oncogene-driven tumorigenesis. Induction of oncogenic BRAF and loss of Pten in melanocytes led to localized accumulation of FoxP3 Tregs, but not CD8 T cells, within 1 week of detectable increases in melanocyte differentiation antigen expression.

VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival.

Adaptive immune responses contribute to the pathogenesis of melanoma by facilitating immune evasion. V-domain Ig suppressor of T-cell activation (VISTA) is a potent negative regulator of T-cell function and is expressed at high levels on monocytes, granulocytes, and macrophages, and at lower densities on T-cell populations within the tumor microenvironment. In this study, 85 primary melanoma specimens were selected from pathology tissue archives and immunohistochemically stained for CD3, PD-1, PD-L1, and VISTA.

Collagen quantification in breast tissue using a 12-wavelength near infrared spectral tomography (NIRST) system.

A portable near infrared spectral tomography (NIRST) system was adapted for breast cancer detection and treatment monitoring with improved speed of acquisition for parallel 12 wavelengths of parallel frequency-domain (FD) and continuous-wavelength (CW) measurement. Using a novel gain adjustment scheme in the Photomultiplier Tube detectors (PMTs), the data acquisition time for simultaneous acquisition involving three FD and three CW wavelengths, has been reduced from 90 to 55 seconds, while signal variation was also reduced from 2.1% to 1.

A Patient-Specific 3D-Printed Form Accurately Transfers Supine MRI-Derived Tumor Localization Information to Guide Breast-Conserving Surgery.

Background: Wire-localized excision of nonpalpable breast cancer is imprecise, resulting in positive margins 25-30% of the time.

Methods: Patients underwent preoperative supine magnetic resonance imaging (MRI). A radiologist outlined the tumor edges on consecutive images, creating a three-dimensional (3D) view of its location.

Resident memory T cells in the skin mediate durable immunity to melanoma.

Tissue-resident memory T (T) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific T cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment.

Myeloid Cells That Impair Immunotherapy Are Restored in Melanomas with Acquired Resistance to BRAF Inhibitors.

Acquired resistance to BRAF inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. Although there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment, initially reduced by BRAFi treatment.