Common Diagnostic Challenges and Pitfalls in Genitourinary Organs, With Emphasis on Immunohistochemical and Molecular Updates

Context.— Lesions in the genitourinary (GU) organs, both benign and malignant, can demonstrate overlapping morphology, and practicing surgical pathologists should be aware of these potential pitfalls and consider a broad differential diagnosis for each specific type of lesion involving the GU organs. The following summary of the contents presented at the 6th Annual Chinese American Pathologists Association (CAPA) Diagnostic Course (October 10–11, 2020), supplemented with relevant literature review, exemplifies the common diagnostic challenges and pitfalls for mass lesions of the GU system of adults, including adrenal gland, with emphasis on immunohistochemical and molecular updates when relevant. Objective.— To describe the common mass lesions in the GU system of adults, including adrenal gland, with emphasis on the diagnostic challenges and pitfalls that may arise in the pathologic assessment, and to highlight immunohistochemical workups and emerging molecular findings when relevant. Data Sources.— The contents presented at the course and literature search comprise our data sources. Conclusions.— The diagnostic challenges and pitfalls that arise in the pathologic assessment of the mass lesions in the GU system of adults, including adrenal gland, are common. We summarize the contents presented at the course, supplemented with relevant literature review, and hope to provide a diagnostic framework to evaluate these lesions in routine clinical practice.

Novel Breast Specimen Orientation Approach through 3D Visualizations for Relocating Inadequate Margins based on the Surgical Clips: Feasibility Study.

Purpose: The current breast specimen orientation method after breast-conserving surgery is potentially inaccurate due to deformability and mobility of the extracted breast tissue. This complicates targeted relocation during re-excision or radiation. Therefore, we propose a new 3D-visualization method to communicate the breast specimen orientation to instantly provide an intuitive overview of the resection margins in relation to the surgical clips on the wound bed.Methods: In 15 female patients undergoing breast-conserving surgery, the surgeon labeled the surgical clips on the specimen and the wound bed. During pathologic assessment, after inking, a 3D scan was made of the specimen. Tumor tissue was annotated on the histological image and transposed to the respective location inside the 3D model. The transposed resection margins with respect to the labeled surgical clips were calculated and visualized. Intuitivity of the visualization was tested (face validity) as well as the quality of displayed resection margins and labeled clips.Results: Average face validity score for 3D-visualization was between ‘++’ and ‘+’ for surgeons and between ‘+’ and ‘+/-’ for pathologists. Average difference between computed resection margins and reported histologic margins was 1 mm. In 8 cases not all clips could be labeled in situ. In 5 cases not all labeled clips could be retrieved by pathology. Conclusion: The visualizations appeared valuable in interdisciplinary communications. The displayed resection margins approximated the reported margins. Consistent accurate surgical clip labelling proved challenging.

Tumor Microenvironment in Breast Cancer—Updates on Therapeutic Implications and Pathologic Assessment

The tumor microenvironment (TME) in breast cancer comprises local factors, cancer cells, immune cells and stromal cells of the local and distant tissues. The interaction between cancer cells and their microenvironment plays important roles in tumor proliferation, propagation and response to therapies. There is increasing research in exploring and manipulating the non-cancerous components of the TME for breast cancer treatment. As the TME is now increasingly recognized as a treatment target, its pathologic assessment has become a critical component of breast cancer management. The latest WHO classification of tumors of the breast listed stromal response pattern/fibrotic focus as a prognostic factor and includes recommendations on the assessment of tumor infiltrating lymphocytes and PD-1/PD-L1 expression, with therapeutic implications. This review dissects the TME of breast cancer, describes pathologic assessment relevant for prognostication and treatment decision, and details therapeutic options that interacts with and/or exploits the TME in breast cancer.

Immune-related histologic phenotype in pretreatment tumor biopsy predicts pathologic response to neoadjuvant anti-PD-1 treatment in squamous lung cancer.

e20540 Background: The neoadjuvant platform affords a rich and valuable resource for understanding the responses to therapy and carrying out reverse translation, including pathologic morphology. We aimed to develop a pretreatment histologic scoring system reflecting the preexisting immune response to predict the efficacy of neoadjuvant immunotherapy based on the morphological changes we mastered in the pathologic assessment after neoadjuvant immunotherapy. Methods: Surgical specimens from the 31 squamous cell lung cancer patients recruited in a phase Ib study of neoadjuvant anti-PD-1 therapy and eligible paired pretreatment biopsies from 15 of them were included in this study. The posttreatment surgical specimens were assessed according to the immune-related pathologic response criteria. Immune-related histologic phenotype assessment criteria (irHPC) were developed based on the pathologic features identified after neoadjuvant anti-PD-1 treatment. Three pathologists trained for irHPC independently scored the HE slides of the 15 pretreatment tumor biopsies according to irHPC. Results: Whether necrosis was included in the calculation of percent of residual viable tumor (%RVT) or not had almost no effect on the consistency of pathologic assessment ( P= 0.811) and the histological response grouping. The inter-pathologist variability of assessing %RVT with immune-activated phenotype was not statistically significant ( P= 0.480). Four immune-related features of pretreatment biopsies were included for calculating the predictive score, including three positive features (tumor-infiltrating lymphocytes, tumor-infiltrating eosinophils and dense plasma cells in stroma) and one negative feature (tumor-infiltrating neutrophils) according to the developed irHPC scoring system. The trained pathologist accurately predicted 6 out of 8 patients in the cPR/MPR group and 5 out of 7 patients in the non-cPR/MPR group according to irHPC. For inter-observer reproducibility using “2 points” as the cut-off point, the overall percent agreement (OPA) was 77.8%. The reliability between pathologists for a binary tumor evaluation showed “moderate” agreement (κ = 0.54). Conclusions: The irHPC scoring system reflecting the preexisting immune response could be used to predict the pathologic response of neoadjuvant immunotherapy, but still needs the larger trails to verify.

Clinical outcome and pathologic correlation of stereotactic body radiation therapy as a bridge to transplantation for advanced hepatocellular carcinoma: a case series

Background Stereotactic body radiotherapy (SBRT) is an emerging modality for hepatocellular carcinoma (HCC). However, there is scant information about its safety and effectiveness in the neoadjuvant setting prior to liver transplantation (LT). We present the clinical outcome and pathologic assessment of SBRT followed by LT for patients with advanced HCC. Methods This retrospective study included HCC patients treated with neoadjuvant SBRT prior to LT between 2009 and 2018. Radiographic response and adverse effects, including radiation-induced liver disease (RILD), were evaluated. Pathologic response was assessed by the percentage of tumor necrosis relative to the total tumor volume. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan–Meier method. Results Fourteen patients underwent SBRT for a total of 25 HCC lesions, followed by LT. The median tumor size was 4.45 cm in diameter, and the median prescribed dose was 45 Gy in 5 fractions. SBRT provided significant AFP reduction, 100% infield control, and a 62.5% response rate. The maximum detected toxicity included grade 3 thrombocytopenia and two grade 3–4 hyperbilirubinemia. One patient developed non-classic RILD. Patients were bridged to LT with a median time of 8.4 months after SBRT, and 23.1% of them achieved a complete pathologic response. The median OS and RFS were 37.8 and 18.3 months from the time of LT, respectively. Conclusions SBRT provides favorable tumor control and acceptable adverse effects for patients awaiting LT. Further prospective studies to test SBRT as a bridging therapy for LT are feasible.