Angular restriction fluorescence optical projection tomography to localize micrometastases in lymph nodes.

Lymph node biopsy is a primary means of staging breast cancer, yet standard pathological techniques are time-consuming and typically sample less than 1% of the total node volume. A low-cost fluorescence optical projection tomography (OPT) protocol is demonstrated for rapid imaging of whole lymph nodes in three dimensions. The relatively low scattering properties of lymph node tissue can be leveraged to significantly improve spatial resolution of lymph node OPT by employing angular restriction of photon detection. It is demonstrated through porcine lymph node metastases models that simple filtered-backprojection reconstruction is sufficient to detect and localize 200-µm-diameter metastases (the smallest clinically significant) in 1-cm-diameter lymph nodes.

Paired-Agent Fluorescence Molecular Imaging of Sentinel Lymph Nodes Using Indocyanine Green as a Control Agent for Antibody-Based Targeted Agents.

Purpose: Paired-agent molecular imaging methods, which employ coadministration of an untargeted, "control" imaging agent with a targeted agent to correct for nonspecific uptake, have been demonstrated to detect 200 cancer cells in a mouse model of metastatic breast cancer. This study demonstrates that indocyanine green (ICG), which is approved for human use, is an ideal control agent for future paired-agent studies to facilitate eventual clinical translation. Methods: The kinetics of ICG were compared with a known ideal control imaging agent, IRDye-700DX-labeled antibody in both healthy and metastatic rat popliteal lymph nodes after coadministration, intradermally in the footpad. Results: The kinetics of ICG and antibody-based imaging agent in tumor-free rat lymph nodes demonstrated a strong correlation with each other (r = 0.98, p < 0.001) with a measured binding potential of -0.102 ± 0.03 at 20 min postagent injection, while the kinetics of ICG and targeted imaging agent shows significant separation in the metastatic lymph nodes. Conclusion: This study indicated a potential for microscopic sensitivity to cancer spread in sentinel lymph nodes using ICG as a control agent for antibody-based molecular imaging assays.

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.].

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.

The presence of a CD21+ follicular dendritic cell network distinguishes invasive Quilty lesions from cardiac acute cellular rejection.

BACKGROUND: Quilty lesions are a significant source of interobserver variability and overdiagnosis of rejection. These lesions, characterized by a central aggregate of B-cells with a rim of T-cells admixed with capillary-sized blood vessels, exhibit an organization similar to lymphoid tissue. We postulated that this organization is dependent on a follicular dendritic cell (FDC) network and that the presence of such a network would be useful in distinguishing invasive Quilty lesions from acute cellular rejection. METHODS: Thirty-nine lesions of acute cellular rejection [International Society for Heart and Lung Transplantation (ISHLT) grade 1A/1B, n = 7; grade 2, n = 13; grade 3A/3B, n = 18; grade 4, n = 1] and 32 invasive Quilty lesions were collected from our pathology archives. Immunohistochemical staining for CD21 was used to determine the presence of a FDC network. RESULTS: A compact CD21 FDC network was present in 24 of 32 invasive Quilty lesions, and, more significantly, in 23 of 24 invasive Quilty lesions measuring larger than 0.3 mm in greatest dimension. When present, the FDCs were in the center of the lesion and the number of positive cells was proportional to the size of the lesion. A FDC network was completely absent in all but one of the 39 lesions of acute cellular rejection. Review of the H&E material from this single case showed features more consistent with a diagnosis of an invasive Quilty lesion. CONCLUSIONS: The presence of a CD21 FDC network is a reliable diagnostic tool to differentiate invasive Quilty lesions from acute cellular rejection, especially in those lesions (> 0.3 mm) that are most likely to be overdiagnosed as moderate or severe acute cellular rejection (sensitivity 96%, specificity 100%, positive predictive value 100%).

Multiple paragangliomata of the lungs and temporal bone.

We report the case of a 71-year-old woman with multiple benign lung paragangliomata and a benign glomus jugulare paraganglioma in one temporal bone that mimicked a malignancy. The patient's lung lesions did not regress with chemotherapy. Subsequent histologic markers suggested several very slowly dividing tumors. We review the patient's medical course and pathology from both sites. A finding of multiple lung paragangliomata should raise the suspicion of a multicentric rather than malignant tumor. Before any chemotherapeutic regimen is initiated, a thorough physical examination of the head and neck should be performed, and biopsy material should be tested for markers of cell division.

CD95 signaling deficient mice with a wild-type hematopoietic system are prone to hepatic neoplasia.

Patients with mutations in the death receptor CD95 (Fas/APO-1) frequently develop B-cell lymphoma. However, solid tumors have not been found in the context of defective CD95. This could be due to the fatal autoimmune proliferative disease that develops in the absence of functional CD95 or to a difference in CD95 signaling in lymphoid versus nonlymphoid tissues. To test this we reconstituted mice that harbor a point mutation in the death domain of CD95 (lpr(cg) mice), either in one or in both alleles, with bone marrow from wild-type (wt) mice. After a year one third of the lpr(cg)/lpr(cg) mice developed spontaneous hepatic neoplasms. In contrast only one of the wt/lpr(cg) mice and none of the wt mice developed liver cancer. The agonistic anti-CD95 antibody Jo2 induced massive apoptosis in the liver of wt mice but not in the livers of either wt/lpr(cg) or lpr(cg)/lpr(cg) mice. The susceptibility of lpr(cg)/lpr(cg) mice to liver cancer cannot solely be due to impaired CD95 mediated apoptosis because there was no clear correlation between apoptosis resistance and tumor formation. A gene chip analysis identified genes selectively upregulated in the liver of wt and wt/lpr(cg) mice which may protect these mice from developing liver cancer. Our data represent the first case of CD95 protecting from developing a solid cancer.