Epidermal Growth Factor Receptor Inhibition With Erlotinib in Liver: Dose De-Escalation Pilot Trial as an Initial Step in a Chemoprevention Strategy.

Background And Aims: Effective approaches for prevention of hepatocellular carcinoma (HCC) will have a significant impact on HCC-related mortality. There are strong preclinical data and rationale to support targeting epidermal growth factor receptor (EGFR) for HCC chemoprevention. Small molecule inhibitors of EGFR have been Food and Drug Administration-approved for cancer therapy, which provides an opportunity to repurpose one of these drugs for chemoprevention of HCC.

Democratizing Artificial Intelligence in Anatomic Pathology.

Context.—: Artificial intelligence is a transforming technology for anatomic pathology. Involvement within the workforce will foster support for algorithm development and implementation.

Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial.

Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab.

Using an anomaly detection approach for the segmentation of colorectal cancer tumors in whole slide images.

Colorectal cancer (CRC) is the second most commonly diagnosed cancer in the United States. Genetic testing is critical in assisting in the early detection of CRC and selection of individualized treatment plans, which have shown to improve the survival rate of CRC patients. The tissue slide review (TSR), a tumor tissue macro-dissection procedure, is a required pre-analytical step to perform genetic testing.

Single-Nucleotide Polymorphism Array for Histologically Ambiguous Melanocytic Tumors.

Genome-wide copy number profiling by single-nucleotide polymorphism (SNP) array is increasingly employed in the clinical diagnostic workup of melanocytic tumors. We present our SNP array results on 675 melanocytic tumors, including 615 histologically ambiguous tumors evaluated by our institution's dermatopathology consultation service and a separate validation cohort of 26 known benign nevi and 34 known malignant melanomas. The total number of somatic copy number abnormalities, sub-chromosomal copy number abnormalities, regions of homozygosity, and abnormalities at disease-associated regions was significantly associated with a diagnosis of malignancy across disease categories.

Color Vision Deficiency Survey in Anatomic Pathology.

Objectives: To learn what color vision-deficient pathologists and cytotechnologists consider their most significant problems and advantages as well as any accommodations.

Methods: An anonymous online survey developed for practicing pathologists and cytotechnologists regarding their experiences with stains was sent to the members of 4 national societies.

Results: We received 377 responses.

Dicom_wsi: A Python Implementation for Converting Whole-Slide Images to Digital Imaging and Communications in Medicine Compliant Files.

Background: Adoption of the Digital Imaging and Communications in Medicine (DICOM) standard for whole slide images (WSIs) has been slow, despite significant time and effort by standards curators. One reason for the lack of adoption is that there are few tools which exist that can meet the requirements of WSIs, given an evolving ecosystem of best practices for implementation. Eventually, vendors will conform to the specification to ensure enterprise interoperability, but what about archived slides? Millions of slides have been scanned in various proprietary formats, many with examples of rare histologies.

Clinical significance of SLN benign capsular nevi in patients with melanoma.

Background: Benign capsular nevi (BCN) are not infrequent in sentinel lymph nodes (SLN) of patients with melanoma. Their prognostic significance is unknown and the literature is limited. This study evaluated the clinical significance of incidentally found BCN in these patients.

Image-to-image translation for automatic ink removal in whole slide images.

Deep learning models are showing promise in digital pathology to aid diagnoses. Training complex models requires a significant amount and diversity of well-annotated data, typically housed in institutional archives. These slides often contain clinically meaningful markings to indicate regions of interest.

Correlation of novel ALK with ALK immunohistochemistry and clinical outcomes in metastatic melanoma.

Aims: Recently, a novel isoform of anaplastic lymphoma kinase, with alternative transcription initiation (ALK ), has been described in melanoma and is susceptible to targeted ALK-inhibitor therapy. Clinical outcomes of patients with ALK mutated melanoma as well as correlation with immunohistochemical (IHC) methods have not yet been described.

Methods And Results: Clinicopathological characteristics were abstracted for 324 patients with metastatic melanoma (MM).

Delta-Like Protein 3 Expression and Targeting in Merkel Cell Carcinoma.

Purpose: Delta-like protein 3 (DLL3) is being developed as a predictive biomarker for DLL3-targeting antibody-drug conjugate and other therapies. Given the neuroendocrine features of Merkel cell carcinoma (MCC), we sought to evaluate DLL3 expression and its role in MCC.

Experimental Design: Formalin-fixed and paraffin-embedded MCC cases were consecutively selected.

Identification of novel, immune-mediating extracellular vesicles in human lymphatic effluent draining primary cutaneous melanoma.

Epithelial tumors including melanoma often first metastasize to regional, sentinel lymph nodes (SLN). Thus, the presence of SLN metastases is a critical prognostic factor of survival. Prior to metastasis, accumulating evidence suggests the SLN is immunologically compromised; however, the process by which pre-metastatic niche formation occurs remains unknown.

Mutational Profile in Vulvar, Vaginal, and Urethral Melanomas: Review of 37 Cases With Focus on Primary Tumor Site.

Melanomas of female genital tract are rare tumors with poor prognosis. While BRAF-V600E is the most common pathogenic mutation seen in cutaneous sun-exposed melanomas, mucosal and anogenital melanomas usually lack BRAF mutations and instead they harbor KIT alterations. The American Joint Committee on Cancer staging guideline (AJCC eighth edition) recommends using cutaneous melanoma guidelines for vulvar melanoma staging and does not provide any recommendations for vaginal melanoma staging.

Robust hierarchical density estimation and regression for re-stained histological whole slide image co-registration.

For many disease conditions, tissue samples are colored with multiple dyes and stains to add contrast and location information for specific proteins to accurately identify and diagnose disease. This presents a computational challenge for digital pathology, as whole-slide images (WSIs) need to be properly overlaid (i.e.

Understanding heterogeneous tumor microenvironment in metastatic melanoma.

A systemic analysis of the tumor-immune interactions within the heterogeneous tumor microenvironment is of particular importance for understanding the antitumor immune response. We used multiplexed immunofluorescence to elucidate cellular spatial interactions and T-cell infiltrations in metastatic melanoma tumor microenvironment. We developed two novel computational approaches that enable infiltration clustering and single cell analysis-cell aggregate algorithm and cell neighborhood analysis algorithm-to reveal and to compare the spatial distribution of various immune cells relative to tumor cell in sub-anatomic tumor microenvironment areas.

Classification of Melanocytic Lesions in Selected and Whole-Slide Images via Convolutional Neural Networks.

Whole-slide images (WSIs) are a rich new source of biomedical imaging data. The use of automated systems to classify and segment WSIs has recently come to forefront of the pathology research community. While digital slides have obvious educational and clinical uses, their most exciting potential lies in the application of quantitative computational tools to automate search tasks, assist in classic diagnostic classification tasks, and improve prognosis and theranostics.

CD206-positive myeloid cells bind galectin-9 and promote a tumor-supportive microenvironment.

In patients with metastatic melanoma, high blood levels of galectin-9 are correlated with worse overall survival and a bias towards a Th2 inflammatory state supportive of tumor growth. Although galectin-9 signaling through TIM3 on T cells has been described, less is known about the interaction of galectin-9 with macrophages. We aimed to determine whether galectin-9 is a binding partner of CD206 on macrophages and whether the result of this interaction is tumor-supportive.

Targeting the cyclin dependent kinase and retinoblastoma axis overcomes standard of care resistance in BRAF -mutant melanoma.

Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies.

Comparison of a Medical-Grade Monitor vs Commercial Off-the-Shelf Display for Mitotic Figure Enumeration and Small Object (Helicobacter pylori) Detection.

Objectives: To examine the performance of a commercial off-the-shelf (COTS) monitor vs a medical-grade (MG) monitor for small object enumeration in standardized digital pathology images.

Methods: Pathologists reviewed 35 melanoma or 35 gastric biopsy images using the MG and COTS displays, with a 2-week washout period. Mitotic figure or Helicobacter pylori burden enumerations were compared with reference values reported by an expert subspecialist pathologist using a light microscope.

Histological features and outcome of inverted type-A melanocytic nevi.

The presence of enlarged epithelioid/spindled nests located deep in the reticular dermis of a biphasic melanocytic neoplasm can mimic melanoma arising in a pre-existing nevus, causing over-interpretation of malignancy. We aimed to define the clinicopathologic significance of epithelioid/spindled nests in melanocytic nevi. Retrospectively using clinical and histologic information, we characterized 121 patients with a single lesion showing epithelioid/spindled melanocytes in the reticular dermis or subcutaneous fat, surrounded by melanophages, sometimes blending in with the adnexa.

Cytotechnologists as coinvestigators in anatomical pathology research.

Background: The amount of time available to pathologists with which to perform research is becoming limited due to an increasing manpower shortage in pathology, decreased reimbursement, and increased workload. This is occurring at the same time as demands escalate for pathologists to develop new companion tests, correlate the molecular findings with traditional methods, and assist in the development of individualized medicine. This study examined whether cytotechnologists may be integrated into a research team that uses their expertise in understanding pathology and clinical disease to provide interpretations of experiments that traditionally were performed by pathologists.