Doing More With Less: How to Optimize Small Biopsies in Bone and Soft Tissue Pathology

Faculty: Alessandra Nascimento, MD, Case Western Reserve University/Cleveland Medical Centerand and John Reith, MD, Cleveland Clinic

Professional Practice Gap: The practical use of less invasive diagnostic procedures, namely fine needle aspiration (FNA) and core needle biopsy (CNB), in the diagnosis of bone and soft tissue tumors has grown exponentially in the last decade. Although radiologists have become proficient in the performance of these procedures, the amount of tissue provided is often small and pathologists are expected to provide more information than ever with less tissue. This requires comprehensive knowledge of histopathologic features of bone and soft tissue tumors as well as of clinic-radiologic findings and ancillary studies, such as immunohistochemistry and molecular studies.

Learning Objectives:

1. Analyze radiologic features of bone tumors and correlate with histopathologic features.
2. Understand the use, specificity and sensitivity of immunohistochemical markers in the diagnosis of bone and soft tissue tumors.
3. Describe the utility of molecular studies in bone and soft tissue tumors.
4. Discuss the advantages and limitations of FNA and core biopsies in the diagnosis and classification of bone and soft tissue tumors.

Diagnostic Challenges of Primary Bone Tumors

Faculty: Reena Singh, MD, Vanderbilt University Medical Center and Karen Fritchie, MD, Cleveland Clinic

Professional Practice Gap:Hyaline cartilage neoplasms are one of the most commonly encountered types of bone tumors in clinical practice, ranging in behavior from benign to high grade malignancies. As the morphologic features of these entities overlap, especially on core biopsy material, integration of clinical and radiologic findings is essential. Furthermore, ancillary studies such as immunohistochemistry and molecular testing can be helpful in specific differential diagnoses. This course will address the differential diagnoses, clinical implications, and use of ancillary testing in diagnosing hyaline cartilage tumors.

Learning Objectives:

1. Describe benign and malignant hyaline cartilage tumors as well as their morphologic mimics
2. Understand the importance of radiologic correlation in hyaline bone tumors
3. Recognize the utility of molecular testing in tumor with cartilaginous differentiation.

Making Sense of Fatty Tumors. When is Atypia “Atypia”, What Defines “Dedifferentiation”, and When are Ancillary Tests, Such as MDM2, Necessary to Establish or Exclude a Diagnosis?

Faculty: Nooshin Dashti, MD, MPH, Cedars-Sinai Medical Center and Scott Kilpatrick, MD, Cleveland Clinic

Professional Practice Gap: In recent decades, the field of bone and soft tissue tumors has experienced significant expansion in histological and molecular classification. In our collective experience, mature adipocytic neoplasms have been the most encountered soft tissue lesions in general practice and among consultations. The separation of atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDL) from other similar neoplastic and non-neoplastic mimics remains therapeutically and prognostically significant, as it is the only mature fatty tumor capable of “dedifferentiation”, acquiring the risk for more aggressive behavior and distant metastases. Newly described entities, such as atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) and dysplastic lipoma, and further clarification of the spectrum of more established lesions, such as hibernoma and spindle cell/pleomorphic lipoma with their separation from hibernoma-like ALT/WDL and ASPLT, respectively, have created additional diagnostic challenges.

Adipocytic tumors are often submitted for pathologic examination by surgeons who simply designate these lesions as “lipomas”, without further qualifying information. Clinical and radiological correlation is extremely helpful in establishing a more specific diagnosis, also providing important data needed to determine when additional ancillary studies may be required. However, before proceeding, the pathologist needs to know the necessary pertinent questions to answer and specific data needed, reducing the potential for either “over” or “under” diagnosis of ALT/WDL.

Among experienced pathologists, there also remains controversy regarding the separation of ASPLT from spindle cell/pleomorphic lipoma and defining “dedifferentiation”, in particular its reliable separation from cellular forms of ALT/WDL. Evans’ original description of dedifferentiated liposarcoma (DL) required a minimum of 5 or more mitotic figures/10 high power fields to establish a diagnosis of DL, but most subsequent articles failed to use this mitotic index as a defining criterion for “dedifferentiation”. Some authors have even raised the notion of a “low grade” form of dedifferentiation, a designation that does not exist among other bone and soft tissue tumors associated with dedifferentiation.  The current 5^th edition WHO Soft Tissue and Bone Tumours does not attempt to address this issue at all, simply noting “Low-grade DDLPS (dedifferentiated liposarcoma) is virtually indistinguishable from cellular WDLPS (well-differentiated liposarcoma).” There is no further insights or commentary on this topic, although we can obtain some evidence-based guidance from a careful review of the literature.

Learning Objectives:

1. To discuss recent updates in the classification of adipocytic tumors
2. To recognize the importance of clinical and imaging correlation
3. To explain demographic and morphologic differences between ALT/WDL and neoplastic and non-neoplastic mimics
4. To provide criteria for ancillary testing, especially MDM2 immunohistochemistry and FISH analysis
5. To explain the clinical importance of utilizing evidence-based criteria for defining dedifferentiation in liposarcoma

Reporting of Neoadjuvant Breast Cancer Specimens: Practical Steps and Clinical Impacts

Faculty: Veerle Bossuyt, MD, Massachusetts General Hospital and Elena Provenzano, PhD, MBBS, Addenbrooke’s Hospital

Professional Practice Gap: Neoadjuvant treatment has become standard of care for HER2 positive and triple negative breast carcinoma. Neoadjuvant breast specimens are complex and are now seen in all practice settings. Reporting of neoadjuvant specimens has recently been standardized on a national and international level with a new post-neoadjuvant CAP dataset in development (Expected publication date 2023). Many pathologists are not familiar with the breast cancer reporting elements and prognostic factors specific to the neoadjuvant setting. Many pathology reports do not include a detailed assessment of response and quantification of residual disease.  Pathologic assessment of response and quantitative measures of residual disease determine adjuvant treatment decisions and provide important information about prognosis and should be included in pathology reports in all practice settings.

Learning Objectives:

1. Apply the new guidelines for reporting post neoadjuvant therapy breast cancer resections.
2. Determine and interpret Residual Cancer Burden (RCB).
3. Consider how pathology findings determine further adjuvant treatment decisions after post neoadjuvant breast surgery.

Spindle Cell Lesions of Breast: A High-stakes Differential Diagnosis 

Faculty: Indu Agarwal, MD, Feinberg School of Medicine/Northwestern University and Kalliopi P. Siziopikou, MD, PhD, Northwestern University

Professional Practice Gap: Breast spindle cell lesions encompass a broad range of pathologic entities: benign, locally aggressive, and malignant (PMID: 28629810, PMID: 26838327, PMID: 34322734). Their morphological heterogeneity emerges from the multiple different cell lineages, including mesenchymal, epithelial, and myoepithelial cells (PMID: 26015706). Amongst the true mesenchymal lesions, only a few are specific to breast and the rest include a myriad of skin and soft tissue tumors. Yet, many updates in the recent WHO classification of soft tissue tumors further complicates the diagnosis of spindle cell lesions in the breast. Additionally, the criteria for diagnosis of malignant phyllodes have also been updated. This is crucial since the pathologist may not be aware that well-differentiated liposarcoma is no longer regarded a heterologous element, therefore its presence alone is not sufficient to make a diagnosis of malignant phyllodes tumor (PMID: 27040923).

Diagnosis of spindle cell lesions on core biopsy can be particularly challenging as lesions displaying different lineages associated with variable outcomes share overlapping morphologies (scar vs. fibromatosis-like metaplastic carcinoma), on the other hand, individual entities can exhibit a large variety of appearances such as myofibroblastoma (PMID: 35838633, PMID: 28629810). High grade metaplastic spindle cell carcinoma can be especially challenging to differentiate from lesions of mesenchymal origin, however, making this distinction is imperative as neoadjuvant chemotherapy and sentinel lymph node dissection are an integral part of care for carcinomas but not phyllodes tumor or sarcoma (PMID: 35236635). Immunostains for keratins, p63, CD34 have been variously used for this purpose with only less than desired results. Use of immunohistochemical markers like EGFR, CD44, CD24, SNAIL/TWIST, and E-cadherin has been postulated in identifying metaplastic carcinoma (PMID: 16739104, PMID: 21110878, PMID: 22080057). Mutations in TP53, PIK3CA, and losses of PTEN and CDKN2A have been described (PMID: 25688406, PMID: 15376261, PMID: 19435916). Most of these are scattered studies but no consolidated guidelines are available for practical use of these novel markers.

Rare diagnoses like metastatic sarcoma to the breast, Adenomyoepithelioma, and myoepithelial carcinoma have a high potential to be overlooked and misdiagnosed. Accurate diagnosis of spindle cell lesions is problematic due not only to their rarity and overlapping morphologies but also to expansive evaluation using unfamiliar panels and molecular tests (PMID: 35838633).

Learning Objectives:

1. Learn the subtle nuances in the diagnosis of breast spindle cell lesions through observing actual case-based scenarios. Discover potential pitfalls, and then assess and handle actual/possible adverse patient consequences.
2. Understand the most recent updates in diagnostic criteria of malignant phyllodes tumor and updates in other soft tissue tumors that may occur in breast. Familiarize with the most recent management trends.
3. Learn an algorithmic approach to the use of most appropriate tools for identifying metaplastic carcinoma on core needle biopsy, such as novel immunohistochemical and molecular markers.

Breast Pathology in the Era of Genomics

Faculty: Laura Collins, MD, Beth Israel Deaconess Medical Center, Harvard Medical School and Hannah Wen, MD, PhD, Memorial Sloan Kettering Cancer Center

Professional Practice Gap: The field of breast oncology, and the management of breast cancer patients is evolving rapidly. Practicing pathologists need to be up to date on current indications for ancillary testing for both prognostic and predictive factors. The advent of companion diagnostics for this purpose has created challenges for pathologists (and often treating clinicians) in determining which is the most appropriate test for which patient and tumor type.

Learning Objectives:

1. Understand the increasingly complex landscape of molecular testing in breast pathology
2. Discuss the different types of ancillary tests available to support treatment decision-making in breast cancer care
3. Describe the current, most appropriate, methodologies to apply in different clinical situations

Validating And Implementing Artificial Intelligence Algorithms For Routine Breast Pathology Practice With Case-Based And Data-Driven Discussion 

Faculty: Zaibo Li, MD, PhD, MBA, The Ohio State University Wexner Medical Center and Anil Parwani, MD, PhD, MBA, The Ohio State University Wexner Medical Center

Professional Practice Gap: During past several years, we have seen significant technical advancement in the ability to use whole slide imaging (WSI) to digitize pathology slides automatically, rapidly and at high resolution, allowing pathologists to adapt a full digital workflow for primary diagnosis, consultation, quality assurance, and image analysis. Many artificial intelligence (AI) algorithms have been developed and approved for clinical breast pathology practice, including breast cancer biomarker quantification, lymph node metastasis detection, and breast cancer screening etc. Currently, very few institutions have validated and implemented AI algorithms for routine breast pathology practice and there is a paucity of information for pathologists and lab professionals who want to select a vendor for pathology AI algorithms. There are no established guidelines available and there is a lack of standardization as to what systems to select, what are the use cases, challenges, and barriers in implementation of such AI algorithms. This workshop will address this deficiency.

Learning Objectives:

1. To discuss current AI applications in breast pathology
2. To summarize our experience and data of validating/implementing AI algorithms for clinical breast pathology practice
3. To identify pitfalls and challenges in implementing AI algorithms for clinical breast pathology practice

Reporting Challenging Breast Lesions: Best Practices and Pitfalls

Faculty: Miglena Komforti, DO, Mayo Clinic and Barbara Susnik, MD, Baptist Hospital of Miami

Professional Practice Gap: Much, if not all, of the diagnostic interpretation rendered in any surgical pathology specimen depends largely on the histopathologic findings of the H&E slide. Breast pathology specifically is heavily influenced by the clinical and radiographic findings as it pertains to the lesion investigated. It is the standard of care to involve multiple disciplines when caring for a patient with breast diseases, from oncology, surgery, or pathology, to the breast clinic and nursing staff. As such, most experienced breast pathologists are aware of common pitfalls where the clinical picture does not match the histopathologic presentation, or vice versa. However, general surgical pathologists, fellows and residents are not consistently exposed to the non-pathologic problems of breast pathology and their significance to patient management and outcome. On occasion, even the most experienced breast pathologists fall victims to an imperfect system. A structured breast pathology report with a clear diagnosis including all pertinent findings, is crucial to our clinical colleagues. Furthermore, certain uncommon lesions continue to perplex the practicing pathologist, given their rarity, diverse morphologic characteristics, and constant change or conflicts in management (an example is desmoid fibromatosis). With this course, we aim to close the practice gap by answering the relevant questions: what does a diagnosis mean to the patient and their clinical team?  What would a diagnosis mean to the patient if they were to receive care outside the institution? What is the most effective way to approach this case? What is the most significant finding and how would the patient be affected? What is the most efficient way to convey relevant diagnostic information to the practicing clinician?

Learning Objectives:

1. Become familiar with the spectrum of benign and malignant spindle cell tumors and benign high-risk lesions that are found in the breast, and be able to generate differential diagnosis with a supportive ancillary work-up, where applicable
2. Have a systematic approach and reporting to the final diagnosis both on biopsy and resection specimens, which will incorporate correlation with the clinical history, imaging, and gross findings, where applicable
3. Become familiar with relevant patient management approaches, and any prognostic and predictive tests
4. Learn to report breast diagnoses with confidence and thoroughness with the aid of sample reports.

Diagnostic Standardization of Endomyocardial Biopsy: Heart Transplant and Beyond

Faculty: L. Maximilian Buja, MD, The University of Texas Health Science Center at Houston and He Wang, MD, PhD, Yale University

Professional Practice Gap: Endomyocardial biopsy (EMB) is an invasive procedure developed initially for the early diagnosis of heart transplant rejection before clinical symptoms. Since then, this technique has become an important tool for the diagnosis and evaluation of different cardiac disorders, including cardiomyopathies, myocarditis, infiltrative and storage diseases, and tumors. Despite the development of a series of national and international criteria and consensus statements, significant inter-observer differences exist in real world practice, seriously impacting the confidence of cardiologists in our EMB results.  This applies to interpretation of both transplant and non-transplant biopsies.

Learning Objectives:

1. Master the up-to-date diagnostic criteria ACR and AMR
2. Develop expertise to interpret challenging ACR/AMR, together with results of DSA, dd-cf-DNA and other circulating markers
3. Understand the diagnostic criteria and develop expertise to interpret EMB samples for cardiomyopathy and myocarditis
4. Understand the diagnostic criteria and develop expertise to interpret EMB samples for various types of cardiotoxicity of cancer therapeutic agents, including immune checkpoint inhibitors.
5. Understand the current and potential role of machine learning in future interpretation of EMB

Pulmonary Cytology: Diagnostic Challenges and an Update

Faculty: Zahra Maleki, MD, Johns Hopkins University School of Medicine and Liron Pantanowitz, MD, PhD, MHA, University of Pittsburgh Medical Center

Professional Practice Gap: There is sufficient evidence in the literature to support that lung cytopathology remains as a diagnostic challenge with potential harmful mismanagement. While there are lung FNA cases with classic cytomorphologic features and easy to diagnose, there are a considerable number of lung FNA specimens with unusual cytomorphologic features (e.g. Spindle cell variant of squamous cell carcinomas) or uncommon immunostain expression (TTF-1 negative adenocarcinomas) which posses diagnostic challenges. Although pathologists are familiar with basic cytomorphologic features of main entities in lung FNA, they might not be familiar with precise criteria of each entity and the potential diagnostic pitfalls. Also generating a pathology report using standardized reporting system for lung FNA requires familiarity with the reporting system.

Learning Objectives:

1. Describe key cytomorphologic features of primary lung carcinomas, and neuroendocrine neoplasms and employ proper diagnostic terminology.
2. Apply ancillary studies and how to integrate the results in a standardized report.
3. Discuss main potential diagnostic pitfalls.
4. Recognize unusual and uncommon cytomorphologic features and how to use ancillary studies in
   work up.

FNA 2.0: Value of Cytopathologist-Performed Ultrasound-Guided Core-Needle Biopsy

Faculty: David Lieu, MD, MBA, FNA Medical Group/ UCLA

Professional Practice Gap: Palpation-guided fine-needle aspiration (PG-FNA) has been performed by pathologists in the United States for over 30 years and longer in some European countries.  Some clinicians perform the procedure with variable degrees of success.  As a relatively new procedure to supplement or replace the gold standard of surgical biopsy, it can be informally called FNA 1.0 (what is today).  Since its introduction, PG-FNA has improved.  These improvements include ultrasound-guided FNA (UG-FNA) of both palpable and non-palpable masses, flow cytometry of lymphoid lesions, immunohistochemistry (IHC) on cell blocks, molecular studies, and ultrasound-guided core-needle biopsy (UG-CNB).  These changes could be informally designated FNA 2.0.  There are lesions that cannot be adequately diagnosed by UG-FNA even with advanced laboratory methods.  Some degree of architecture or higher cellularity may be required.  Such lesions include invasion in breast cancer, subclassification of lymphomas, sarcomas, highly vascular lesions yielding mostly blood on FNA, and sclerotic masses.  Many of these masses can be diagnosed by UG-CNB.  Pathologists who perform UG-FNA with rapid onsite evaluation (ROSE) are in the ideal position to determine which masses would benefit from UG-CNB immediately following UG-FNA.  Pathologists who perform FNA do not typically perform CNB.  However, the procedure is not much more difficult than UG-FNA and can reap great benefits in terms of definitive diagnosis without resorting to surgical biopsy in select cases (what should be).  A good example is definitive diagnosis of classical Hodgkin lymphoma with UG-CNB, IHC stains, and consultation with hematopathology.

Learning Objectives:

1. Describe how to perform UG-CNB
2. Identify the types of lesions that might benefit from UG-CNB following UG-FNA with ROSE
3. Discuss the type of cases where UG-FNA alone is usually adequate for diagnosis

Approach to Lymph Node Cytology: How Far Can (or Should) We Go?

Faculty: Min En Nga, MD, FIAC, FRCPA, FRCPath, National University Hospital

Professional Practice Gap: For the general practicing pathologist, handling lymph node cytology specimens is a frequent scenario. The spectrum of pathology involving lymph nodes is broad, with a range of widely differing managements. Hence, a single case may require many clinical decisions e.g. how to conduct optimal specimen triage at FNA, what ancillary tests to perform, whether to recommend excision, how far to go pre-operatively, etc. There will also be an emphasis on safe practice – which begins with the understanding of the inherent limitations of lymph node cytology, which also form the basis of the ASCP/CAP guidelines (1, 2).

When making such practical decisions, the likely next clinical diagnostic or management step is a key consideration, and hence it is crucial to consider both patient and clinician factors that may impact the management. For example, the approach to performing ancillary tests may be different for an intra-abdominal lymph node vs a cervical lymph node which is readily amenable to excision biopsy. Institutional practice also differs, and protocols may differ locally and globally.

Thus, clarity is required, not just on morphological approaches but also on patient aspects and institutional practice, because this helps to inform the pathologist on his or her diagnostic approach. A solid appreciation of this will help to minimize duplication of ancillary tests and maximize use of limited tissue, and also maximize cost-efficiency.

Therefore, this course aims to provide not only an algorithmic, morphology-based approach to diagnosis in lymph node cytology, but also to touch on aspects of systems-based practice, in order to practitioners to be more cognizant of the multifactorial considerations in any given case.

Learning Objectives:

1. Broaden one’s perspective of lymph node cytology – appreciating that there is a clinician and a patient at the opposite end of the needle
2. Apply a solid morphologic approach to lymph node cytology
3. Understand the limitations of lymph node cytology
4. Be familiar with common false positives and negatives in lymph node cytology
5. Rationally apply discriminatory ancillary tests in limited cytology specimens

Salivary Gland Pathology: The Complementary Roles of Cytopathology and Histopathology and the Emergence of Molecular Diagnostics

Faculty: Carmen Gomez-Fernandez, MD, University of Miami Miller School of Medicine and Jaylou Velez Torres, MD, University of Miami Miller School of Medicine

Professional Practice Gap: Salivary gland pathology is challenging due to diversity and overlapping morphologic characteristics of benign and malignant diagnostic entities. Diagnostic accuracy is essential for the appropriate management of patients.  Surgical intervention and extent of surgery is generally determined by the diagnosis obtained through sampling of the targeted lesion with fine needle aspiration cytology (FNAC). The cytologic classification of salivary gland lesions has been standardized with the Milan System for Reporting Salivary Gland Cytopathology.  Each category is associated with an implied risk of malignancy (ROM) and a prescribed algorithm for clinical management. More than 70% of salivary gland lesions will be definitively categorized by FNAC as Non-Neoplastic, Neoplastic-Benign, or Malignant. Nevertheless, several cases will fall into the indeterminate Milan categories of Atypia of Undetermined Significance (AUS), Salivary gland neoplasm of Undetermined Malignant Potential (SUMP), or Suspicious for Malignancy (SFM). SUMP may be further subcategorized as Basaloid, Oncocytic/Oncocytoid, or Not Otherwise Specified.  Subtle nuances that help to distinguish specific entities from their mimickers, within the same subcategories, may be elucidated by careful study and comparison to their histologic counterparts.  Recent discoveries of tumor specific translocations and rearrangements have resulted in advances in ancillary testing using IHC, FISH, and NGS on cytologic material, and have helped to further refine the diagnostic classifications.

Learning Objectives:

1. Apply the Milan System for Reporting Salivary Gland Cytopathology to sample cases of salivary gland pathology.
2. Discuss the key cytomorphologic features of non-neoplastic and neoplastic salivary gland entities as they correlate with their histologic counterparts.
3. Distinguish various non-neoplastic and neoplastic entities from their diagnostic mimickers.
4. Evaluate when and how to use ancillary techniques to assist with the cytomorphologic diagnosis.
5. Define a practical step-wise algorithmic approach to the cytologic diagnosis of salivary gland lesions.

Lymphomas in the Skin: Primary or Systemic? An Integrated Dermatopathology and Hematopathology Approach

Faculty: Carlos Torres-Cabale, MD, The University of Texas MD Anderson Cancer Center and Roberto Miranda, MD,The University of Texas MD Anderson Cancer Center

Professional Practice Gap: Dermatopathologists, hematopathologists, and surgical pathologists encounter biopsies showing cutaneous lymphoid infiltrates, either T, B, or NK, that often pose considerable diagnostic difficulties. An important question to address through histopathological examination and use of ancillary tests is to determine whether the lesion represents a primary cutaneous process, or it is secondary  to a systemic disorder. Solving this issue is critical for therapy and prognosis. Through the application of histopathological criteria, clinical correlation, and ancillary methods, pathologists should be able to guide clinicians to the correct diagnosis and appropriate therapy for most of these patients. Awareness of the current available tools and our limitations should improve our daily clinical practice.

Learning Objectives:

1. Adequately interpret clinical, histopathological, and molecular information to arrive to the correct diagnosis of lymphoid infiltrates involving the skin
2. Apply histopathological and molecular criteria to distinguish primary from systemic lymphoid process in the skin
3. Utilize the knowledge gained in this course to discuss cases with colleagues of the clinical team, in order to educate them and contribute with optimal patient care

Mimickers and Mistakes: Diagnostic Dilemmas and Practical Approaches in Dermatopathology

Faculty: Kristine Cornejo, MD, Massachusetts General Hospital and Rosalynn Nazarian, MD, Harvard Medical School

Professional Practice Gap: Many surgical pathologists review both neoplastic and inflammatory dermatopathology cases but often find it challenging as they are unfamiliar with the evolving diagnostic criteria and the importance of clinicopathologic correlation required for their diagnosis. This course fills a gap among general surgical pathologists in key areas of dermatopathology encompassing reactive and inflammatory disorders of vessels, infections, and cutaneous epithelial and melanocytic neoplasms with discussion of relevant differential diagnoses.

Learning Objectives:

1. Develop a practical approach to effectively utilize clinicopathological correlation and ancillary molecular and immunohistochemical studies in dermatopathology.
2. Raise awareness of mimickers and important clues to avoid diagnostic pitfalls in skin biopsy specimens.
3. Improve diagnostic accuracy in the assessment of cutaneous epithelial and melanocytic neoplasms, infections, and inflammatory dermatoses.

Weaving a Rich Tapestry: Improving Workplace Diversity, Inclusion, and Equity in Pathology

Faculty: Scott Lovitch, MD, PhD, Brigham and Women’s Hospital and Marissa White, MD, Johns Hopkins University School of Medicine

Professional Practice Gap: Having made significant strides to improve gender equality in the physician workforce, the next greatest challenge physicians face is to increase diversity, inclusion, and equity to better serve our diverse patient population through the delivery of culturally competent care and unbiased biomedical research. In contrast to other medical specialties where direct patient contact effectively frames and drives the conversation about diversity, the conversation about diversity in pathology is predominantly driven by our students, trainees, and colleagues. In part due to these factors, pathology has lagged behind other specialties in discussing diversity and inclusion, and in taking concrete steps to recruit and retain a diverse workforce (1, 2, 3, 4, 5, 6). Regardless, the time to prioritize the conversation in pathology is upon us. Accrediting bodies expect routine incorporation of diversity, inclusion, and equity instruction into general undergraduate and graduate medical education curricula (7, 8). The pool of students underrepresented in medicine (UIM) continues to expand, however, the number of UIM students ultimately applying to pathology remains significantly lower than those applying to all Association of American Medical Colleges medical specialties, similar to the trend for non-UIM students (9, 10, 11). Furthermore, our non-pathologist laboratory and clinical colleagues (e.g., clinical laboratory technicians and pathologists’ assistants) are increasingly diverse, and taking on expanded responsibilities and working in close collaboration with pathologists. In these settings, conversation about diversity is both necessary and unavoidable, and all practicing pathologists could benefit from a broader conversation about how to weave a rich tapestry in our workplace to foster the development of an inclusive learning and practice environment, with the long-term expectation of increased diversity and equity.

Learning Objectives:

1. Describe the current state of diversity and inclusion in pathology, including representation of women and of members of groups underrepresented in medicine (UIM), both within the broader pathology workforce and in positions of leadership.
2. Recognize obstacles to improving diversity and inclusion in pathology, including the persistence of biological notions of race and harmful racial stereotypes in curricular materials, and impacts of race-based classification in clinical diagnostic algorithms.
3. Discuss the potential role of “pipeline” programs in recruiting students from diverse groups into pathology, and identify features required for a pipeline program to be successful.
4. Recognize the importance of providing individualized and culturally-sensitive mentorship and feedback to graduate trainees in pathology, and identify strategies to provide effective mentorship and feedback, particularly across socioeconomic and cultural differences.

How to Train your Pathologist: Updating Pathology Education to be Engaging and Relevant in a Post-COVID World

Faculty: Scott Lovitch, MD, PhD, Brigham and Women’s Hospital and Laura Wake, MD, Johns Hopkins Medical Institutions

Professional Practice Gap: According to prominent educational and cognitive psychology theories, learning is a method of information processing and assimilation into long-term memory. Current evidence-based research supports the notion that medical educational strategies that help learners’ actively process information are the most efficacious. However, there is a misalignment between education research and education practice. Despite the revelation that active learning techniques are not only effective, but preferred by today’s learners, the delivery of medical education has not changed in centuries, even as the practice of medicine surges towards precision and personalization.

We aim to help realign this gap between research and practice in our course by exposing participants to current medical pedagogy research and educating them about the efficacy of active learning techniques. For those who are up to date on the research, but still not engaging these theories in practice, we will empower with tools and resources, and support with practice opportunities using several novel techniques that will promote learner engagement.

Learning Objectives:

1. Understand the cognitive science behind active learning and the data supporting its efficacy.
2. Identify and describe recent innovations in remote teaching and learning, educational technology, and multimedia content delivery, and their application to undergraduate, graduate, and post-graduate medical education in pathology.
3. Understand the importance of effective feedback and competency assessment, and describe strategies to give and receive effective feedback to trainees and peers.
4. Effectively apply active-learning approaches and educational/multimedia technology to undergraduate, graduate, and post-graduate medical education in pathology.

Neuroendocrine Neoplasms in the 2022 WHO classification: Practical Diagnostic Roadmap for Common Challenges

Faculty: Ozgur Mete, MD, University Health Network, University of Toronto and Stefano La Rosa, University of Insurbia

Professional Practice Gap: The spectrum of neuroendocrine proliferations ranges from epithelial neuroendocrine neoplasms to non-epithelial neuroendocrine neoplasms and paraganglioma-like neuroendocrine neoplasms as outlined in the 2022 WHO Classification. Most pathologists are not widely familiar with the most recent taxonomy and ancillary tools that can be critical in the correct diagnosis and prognostication of these pathologies, and the subtle differences between these various clinically distinct entities. The genetic predisposition syndromes that underlie many of these lesions are also not generally well-recognized and tested in routine surgical pathology practice. Uniform application of terminology and use relevant diagnostic ancillary tools are important. We propose to provide a diagnostic roadmap for pathologists to tackle common diagnostic challenges in the spectrum of neuroendocrine neoplasia.

Learning Objectives:

1. Recognize the IARC/WHO taxonomy and the spectrum of neuroendocrine neoplasia
2. Accurately distinguish various types of neuroendocrine neoplasms
3. Recognize the role of diagnostic, prognostic and predictive biomarkers of neuroendocrine neoplasia
4. Appropriately apply critical ancillary tools to ensure appropriate differential diagnosis.

Anal Masses and What You Don’t Want to Miss

Faculty: Xuefeng Zhang, MD, PhD, Cleveland Clinic and Rondell Graham, MBBS, Mayo Clinic

Professional Practice Gap: Despite its small size, the anal canal is an anatomical structure with significant embryologic/histologic complexity, and can give rise to multiple types of neoplasm. Besides squamous cell carcinoma, which accounts for 90% of anal carcinomas, a wide variety of benign and malignant lesions can also occur in the anal canal. Overall, anal carcinomas comprise approximately 3% of all gastrointestinal malignancies. Because anal tumors are relatively rare, many pathologists are not familiar with these entities, leading to misdiagnosis in some cases ^(1-3). In the consultation practices at both Mayo Clinic and Cleveland Clinic, anal lesions are commonly referred for expert opinions. The most common case scenarios include an unusual finding in hemorrhoids, the diagnosis of squamous intraepithelial neoplasia, the diagnosis of invasive carcinoma in a background of squamous intraepithelial lesion, and the diagnosis/classification of gland-forming tumors. The challenges lie in the protean, non-specific clinical presentation, subtlety of morphological changes of invasion, handling tangential sectioning, and the rarity of anal Paget’s disease and other less common anal tumors. An added challenge is the emergence of new entities such as HPV-positive neuroendocrine carcinoma and novel HPV-related adenocarcinoma mimicking endocervical adenocarcinoma ⁽⁴⁾. Importantly, anal lesions may affect under-represented diverse patients, including patients who practice anoreceptive intercourse and who frequently experience disparities in healthcare. There is increasing urgency to improve pathology education in this area. The professional practice gaps are apparent according to our experience on extramural consultation services as well as noted in a number of articles ^(1-3).

Learning Objectives:

1. Identify important anatomic landmarks and their clinical implication
2. Describe the pathologic criteria and pitfalls in the diagnosis of squamous intraepithelial lesions and various patterns of invasive squamous cell carcinoma
3. Describe a systematic approach in the diagnosis and classification of gland-forming neoplasms
4. Integrate the key points into an effective method to recognize potential neoplasms in hemorrhoids

Beyond GIST: A Practical Guide to Gastrointestinal Mesenchymal Tumors for the General Surgical Pathologist

Faculty: Laura Lamps, MD, University of Michigan and Andrew Folpe, MD, Mayo Clinic

Professional Practice Gap: Based on our consult practices, there is a large knowledge gap among practicing pathologists when evaluating soft tissue tumors of the tubal gastrointestinal tract. Most pathologists are familiar with some basic types of tumors (gastrointestinal stromal tumor, leiomyoma, etc.), but beyond that the differential diagnoses are challenging. In addition to newly described entities, there are also knowledge gaps regarding new molecular and immunohistochemical markers that have both diagnostic and therapeutic implications.

Learning Objectives:

1. Describe the differential diagnoses of the major categories of mesenchymal tumors encountered in the GI tract.
2. Use pertinent immunohistochemical stains and molecular tests, in addition to histologic features, to correctly diagnose mesenchymal tumors encountered in the GI tract.
3. Discuss the prognostic and therapeutic implications of different types of mesenchymal tumors encountered in the GI tract.

Tumor Boards: Enabling Pathologists to Become Leaders of Evolving Health Care Teams

Faculty: Matthew Cecchini, MD, PhD, London Health Science Centre, Western University and Marcio Gomes, MD, PhD, FRCPC, MHPE, The Ottawa Hospital, University of Ottawa

Professional Practice Gap: Tumor boards have a demonstrated positive impact on patient outcomes and have become the standard of practice (1). The majority of pathologists participate in tumor boards as part of their clinical practice and their input is essential to ensure that patients have the right diagnosis and receive the optimal treatments and therapies. However, evidence shows that pathology participation in rounds is often ineffective and does not support management decisions (2). This suboptimal performance relates to the quality of information presentation to the team and, more importantly, to the quality of pathologists’ contribution to team discussion (2). Pathologists who effectively participate in tumor boards have a pivotal role in patient care: they provide pathology-specific information that is relevant, concise and complete; they are able to integrate clinical, radiological and pathological information; and they contribute valuable information to problem-solving cases that do not easily fit into standard treatment guidelines. There are a number of contributing factors to ineffective participation, including the lack of protected time to prepare for tumor boards, lack of role models, and paucity of training opportunities for pathologists to develop skills and strategies for effective participation during tumor boards. Pathologists have everything that it takes to become leaders of evolving healthcare teams and to be strong patient advocates. We need to foster that.

Learning Objectives:

1. Advocate for patients by ensuring that relevant pathology-specific information is presented by pathologists
2. Contribute to discussion by correlating clinical and pathological information and providing insight into the biologic behavior of diseases
3. Engage in a generative conflict of ideas to explore areas of uncertainty and facilitate multidisciplinary problem solving
4. Elicit participation from every discipline and participant to foster diverse and inclusive perspectives

Is it “Pink”? A Clinically Relevant Diagnostic Approach for Oncocytic Renal Tumors

Faculty: Reza Alaghehbandan, MD, Cleveland Clinic and Christopher Przybycin, MD, Cleveland Clinic

Professional Practice Gap: There has been a remarkable interest and enhanced understating of oncocytic renal neoplasms over the last few years. With the 2022 WHO release and incoming flux of new entities in this area, there is a need for practicing pathologists to be aware, understand the diagnostic criteria, other mimickers, and clinical management of such tumors, such as eosinophilic solid and cystic (ESC)-RCC, low-grade oncocytic tumor (LOT), and eosinophilic vacuolated tumor (EVT).

Learning Objectives:

1. Recognize common benign and malignant oncocytic renal neoplasms and their histologic variants and diversity.
2. Identify histologic features of tumors with overlapping morphologic features between renal oncocytoma and chromophobe renal cell carcinoma.
3. Recognize newly-described entities such as EVT and LOT.
4. Understand the role of pathologists encountering core biopsy of oncocytic renal neoplasms.
5. Develop an integrated diagnostic approach which is clinically relevant to the diagnosis of low grade oncocytic tumors.

Contemporary Challenges in Prostate Pathology

Faculty: Samson Fine, MD, Memorial Sloan Kettering Cancer Center

Professional Practice Gap: The focus on prostate cancer pathology has grown beyond issues of Gleason grading, to include subtypes and patterns of adenocarcinoma, quantitation of high grade disease, the spectrum of intraductal carcinoma, and treatment-related neuroendocrine prostate cancer. Given the ubiquity of prostate biopsies, both general and subspecialty pathologists encounter these problematic areas on a routine basis. While recent consensus statements/white papers, as well as the WHO GU 2022 Blue Book have provided expert opinion on how to assess prostate specimens, there is a need for a systematic approach to these issues to set a framework for accurate diagnosis and reporting. This short course focus on three challenging areas of prostate cancer pathology, watershed areas of prostate cancer grading/quantitation, including the most prevalent benign mimics/deceptively benign-appearing carcinomas, how to assess and report large gland lesions of the prostate, and recognition and work-up for the evolving spectrum of neuroendocrine differentiation in prostate cancer.

Learning Objectives:

1. Assign accurate grades to challenging prostate cancer morphologies & have an approach to tumor quantitation that enables clinical management
2. Categorize the variation in intraductal lesions of the prostate and understand the clinical import and rational work-up for large gland lesions of the prostate
3. Recognize the morphologic diversity of neuroendocrine differentiation in prostate cancer, including post-therapy

Practical Molecular for the Practicing Pathologist: Current and Best Use Cases for Molecular in GU Pathology

Faculty: Steven Smith, MD, PhD, VCU School of Medicine and Sara Wobker, MD, MPH, The University of North Carolina at Chapel Hill

Professional Practice Gap: A panoply of molecular testing is available to surgical pathologists and their collaborating surgeons and oncologists, across subspecialty sites, and of growing saliency to GU tumor pathology. Despite the utility of molecular testing, whether conventional or high complexity comprehensive tumor profiling, the “molecular gateway” is insufficiently integrated into diagnostic and consultation practice. This is especially true for send-out testing, often initiated in the clinic rather than at the scope, which can inform classification, prognosis, and even surgical pathology QA/QC. Providing context for the role of molecular testing will empower the practicing pathologist to make decisions about what tests are standard-of-care versus ancillary in the diagnosis of genitourinary tumors. In the ever expanding classification of genitourinary tumors and recent release of the 5th edition WHO Classification, molecular testing has an increasing role in classification and prognostication. It is essential for today’s pathologist to understand the role of practical molecular testing in the work-up of GU tumors, and how best to approach these cases in practice settings which may lack access to a full menu of molecular tests.  Molecular tests are increasingly integrated into diagnosis; the practice gap is how best to address key diagnostic, prognostic, and management challenges in a practical fashion.

Learning Objectives:

1. Contextualize current state of the science in molecular testing in GU tumors with resource conscious discussion of what is standard versus optional
2. Discuss how appropriate molecular tests can resolve challenging differential diagnoses of specific bladder, kidney, prostate and testis tumors, impacting management
3. Use new molecular knowledge to integrate findings from diverse testing types into assessment of a spectrum of different GU tumors

Biomarkers in Squamous and Glandular Precursor Lesions of the Cervix and Vulva

Faculty: Anne Mills, MD, University of Virginia and Taylor Jenkins, MD, Virginia Commonwealth University Health System

Professional Practice Gap: Recent years have expanded our understanding of the pathobiology of squamous and glandular precursor lesions in the cervix and vulva, and many pathologists remain uncomfortable diagnosing these proliferations. In particular, many would like additional guidance on the proper utilization of immunohistochemical stains and in situ hybridization techniques in this setting.

Pathologists should be familiar with the value and limitations of biomarkers in the following: 1) cervical squamous intraepithelial lesions; 2) HPV-associated and HPV-independent vulvar squamous proliferations; and 3) HPV-associated and HPV-independent cervical glandular precursors.

Learning Objectives:

1. To properly employ immunohistochemistry and in situ hybridization techniques for the diagnostic assessment of HPV-associated cervical squamous intraepithelial lesions, with attention upcoming Lower Anogenital Squamous Terminology guidance.
2. To understand the current state of potential prognostic biomarkers in cervical LSIL, with an appreciation for the absence of a clear clinical role for such testing at this time.
3. To recognize the range of p53 expression patterns in differentiated VIN as well as in its potential mimics (including DEVIL, VAAD, HPV-associated/usual-type VIN, and reactive proliferations), understanding the potential value of concomitant p16 and potentially HPV RNA ISH testing in this setting.
4. To appreciate the value and limitations of biomarkers in cervical glandular proliferations with a differential diagnosis of HPV-associated intraepithelial lesions (such as conventional AIS and SMILE) versus HPV-negative processes (including HPV-independent AIS and atypical lobular endocervical hyperplasia).

Molecular Gynecologic Pathology Tumor Board

Faculty: Robert Soslow, MD, Memorial Sloan Kettering Cancer Center/Weill Medical College of Cornell University and Amir Momeni Boroujeni, MD, Memorial Sloan Kettering Cancer Center

Professional Practice Gap: Many pathologists who have not recently completed gynecologic pathology fellowships are not aware of how to use molecularly-directed immunohistochemistry or formal molecular testing for tumor classification, prognostication or therapeutic prediction.  The presumed cost of the assays and the assumption of limited clinical relevance are barriers to implementation.  With only several exceptions, notably DNA mismatch repair deficiency testing, most of the molecular aberrations and their relevance have only been demonstrated within the past several years.  Furthermore, as many as 1/3 of hysterectomies harboring carcinoma in the US are performed by general gynecologists without oncologic training, a situation that does not encourage informed cross-communication between pathologists and gynecologists.

Learning Objectives:

1. Understand the common molecular alterations in gynecologic tumors.
2. Understanding the genotypic/phenotypic associations in gynecologic tumors with emphasis on histopathologic features.
3. Understand when molecular pathology is helpful/required for proper classification, prognostication and treatment prediction
4. Understand the molecular biology of gynecologic tumors with emphasis on tumorigenesis and the functional significance of molecular alterations.

FIGO, WHO, Silva…OMG – How to Best Navigate Recent Updates in Cervical Pathology

Faculty: Anjelica J Hodgson, Toronto General Hospital, University Health Network; Kay J. Park, Memorial Sloan Kettering Cancer Center

Professional Practice Gap: There has been a plethora of recent updates in cervical pathology including the newly revised 2018 FIGO staging for cervical cancer, as well as the 2020 World Health Organization (WHO) Classification of Tumors of the Female Genital Tract which completely changed how cervical tumors are categorized based on etiologic link with HPV. Consequently, various recommendations and position papers from professional societies have also been published on how best to interpret and report these entities. There have also been developments in targeted therapies for cervical cancer, like anti-PD therapy where correct interpretation of ancillary studies is crucial for patient care. These have made daily practice and reporting of cervical pathology more complicated than ever. This course aims to update practicing pathologists on these important changes and to provide practical tips for how to approach diagnostically challenging cases, with a focus on best reporting practices.

Learning Objectives:

1. At the conclusion of the course, participants will feel confident in the interpretation of glandular neoplasia of the cervix as well as Develop a practical approach to deal with the common challenges in cervical glandular pathology interpretation
2. Integrate clinical, radiologic and pathologic information to render the most accurate and clinically relevant pathology report for cervical cancer
3. Navigate common diagnostic pitfalls in the differential diagnosis of cervical glandular pathology
4. Become familiar with new and updated topics as they relate to the interpretation of cervical pathology specimens

Common Diagnostic Dilemmas and Clinical Implications in Head and Neck Pathology — An Interactive Approach with a Surgeon

Faculty: Qihui (Jim) Zhai, MD, Mayo Clinic College of Medicine and Science, Mayo Clinic Florida and John Casler, MD, Mayo Clinic

Professional Practice Gap:

• There are instances in which there is miscommunication between pathologists and otolaryngologists. Some surgeons may not have an accurate conception of the strengths and weaknesses of General pathologists and pathologists-in-training may not understand the clinical scenarios, indications, and information the surgeon needs to know to determine the subsequent treatment modality, such as surgery, radiation therapy, or chemotherapy. These are best classified as “competence deficiencies” and “medical knowledge.” Each specialty is developing rapidly. Pathologists tend to focus on the classification of tumors, new immuno-markers, and new molecular tests; staying current with new advances in otolaryngology may not be on the top of the priority list. As a result, clinical aspects might not be considered comprehensively. Perspectives from a practicing academic otolaryngologist are valuable. Clinical presentations, images, and reviews of surgical procedures could be eye-opening to our fellow general pathologists.
• General pathologists and pathologists-in-training may not have a systematic approach to the analysis of difficult yet critical diagnostic dilemmas in head and neck This is best classified as “competence deficiencies.” Taking salivary glands tumors as an example, an algorithmic approach integrating the histologic features, immunohistochemical profile, and clinical, demographic information will be used when analyzing this group of tumors with such a wide histologic spectrum.
• General pathologists and pathologists-in-training may not have enough exposure to the common diagnostic pearls and pitfalls in handling challenging cases. This is best classified as “competence deficiencies.” General pathologists in community hospitals may not encounter many head and neck cases to accumulate adequate experience and confidence to handle these challenging cases.
• General pathologists and pathologists-in-training may not be aware of newly described lesions that are of clinical significance. This is best classified as “medical ” Sometimes, general surgical pathologists and pathologists in training may not have the opportunity to stay current with new entities.

Learning Objectives:

1. How to classify the histologic variants of squamous cell carcinoma (SCC) in the head and neck area, emphasizing the HPV-association, HPV/p16 detection method, and the clinical significance. Well-documented and newly described variants of SCC will be compared.
2. To apply an algorithmic approach to the classification of salivary gland tumors, using major diagnostic features such as the low power growth pattern (infiltrating or well-circumscribed /encapsulated), the number of tumor cell types (epithelial only or both epithelial and mesenchymal cells), cytologic atypia, etc. Histologic spectrum of pleomorphic adenoma, oncocytic neoplasm, mucoepidermoid carcinoma, and its variants, polymorphous low-grade adenocarcinoma, and salivary gland carcinoma will be discussed. Newly described entities such as mammary analog secretory carcinoma of salivary glands will be updated. FNA induced artifacts will be illustrated to avoid misdiagnoses.

Incorporating New WHO and ICC Genomic Classifications in the Diagnosis of Challenging Myeloid Neoplasms – A Case-Based Course

Faculty: Alexa Siddon, MD, Yale School of Medicine and Amir Behdad, MD, MBA, Cleveland Clinic

Professional Practice Gap: Recent advances in genomic characterization of myeloid neoplasms and molecular diagnostics have significantly shifted classifications of hematologic malignancies.  The 2022 WHO classification and International Consensus Classification (ICC) of myeloid neoplasms, introduce new and updated genomic categories to incorporate these new discoveries. The genomic biomarkers are important to patient treatment decisions and prognostication. Due to the complex integration of molecular and genetic information, peripheral blood counts, morphology, and immunophenotyping, the precise classification of many neoplasms has become challenging, particularly when a case borders on more than one entity. Additionally, due to updates in the classification systems, criteria for some of these entities has recently been changed. Furthermore, there are difference in WHO and ICC classification of minor subset of cases. Increasingly, pathologists are being asked by our patient-facing clinical colleagues to incorporate molecular and cytogenetic information into the evaluation of diagnostic specimens to provide a comprehensive diagnosis. Many of the molecular testing modalities and options have made advances in recent years, and integrating these findings into classifications has become subtle and complex with numerous competing results. Hematologists/oncologists are working more closely than ever with pathologists to solidify diagnoses of myeloid neoplasms and acute leukemia to offer the most up to date patient care.

This session will be a case-based review of challenging myeloid malignancies that exemplify new genomic categories and their classification may differ by the ICC and WHO classifications.

Learning Objectives:

1. Identify new genomic categories of myeloid neoplasms and the differences in recent updates to classification schemas
2. Recognize the appropriate molecular tests to identify genomic alterations in a various myeloid neoplasms
3. Develop decision-making strategies for incorporating numerous data elements into the a hematopoietic workup

How to Avoid Pitfalls in Diagnosis of T-cell Lymphoma

Faculty: Nidhi Aggarwal, MD, University of Pittsburgh School of Medicine and Nathanael Bailey, MD, University of Pittsburgh, UPMC

Professional Practice Gap: Peripheral T-cell lymphoma is a heterogenous group of neoplasms that are difficult to diagnose. According to one study from 2016 about 13% of the cases of reported T-cell lymphomas when reviewed centrally were diagnosed incorrectly including about 5% that represented disorders other than those arising from T-cells (1).  Common pitfalls involve differential diagnosis between reactive versus neoplastic lesions. Unlike B-cells where kappa and lambda staining can be used as a surrogate for clonality, CD4:CD8 ratio can be altered in reactive conditions as well. More recently, the use of TRBC1 as a flow marker is proving to be useful in the diagnosis of T-cell lymphomas of αβ type (2). Normal T and NK -cell populations exist that lack or show diminished expression of some pan T-cell markers (3), expansion of these populations can be seen in reactive and neoplastic conditions. The knowledge of the pattern of expression of pan T-cell antigens on various normal T and NK -cell populations essential in order to understand aberrant expression.  In addition, molecular studies done to establish clonality such as TCR gene rearrangement studies can be positive in non-neoplastic states and may not lineage specific (4) further adding to the complexity of T-cell neoplasms especially in a background of autoimmune diseases. Furthermore, T-cell lymphomas may mimic other malignancies including Hodgkin lymphomas (5), and sometimes non-hematopoietic neoplasms. Anaplastic large cell lymphoma may express PAX5 (6) and cases of Hodgkin lymphoma that lack PAX5 expression have been described. Small cell variant (7) and ALK negative variants of this disease may be particularly difficult to diagnose. Markers of follicular helper T-cells may be expressed in other conditions (8). Lastly, characterization and classification even when T-cell lymphoma is diagnosed may be challenging. Recent studies focusing on mutational analysis may help in some cases (9).

Learning Objectives:

1. Evaluate a case of T-cell lymphoma with differential diagnosis.
2. Use ancillary studies to refine the differential diagnosis.
3. Be aware of the controversies in the literature about various entities and how best to formulate a report.

Hodgkin Lymphoma Mimics: A Clinically Aligned Diagnostic Approach in the Era of New Classification

Faculty: Mir Alikhan, MD, NorthShore University Health System and Girish Venkataraman, MD, MBBS, University of Chicago Medical Center

Professional Practice Gap: Misclassification of other lymphoma entities and reactive lymphoid proliferations as Hodgkin lymphoma is a significant error that results in inappropriate front-line therapy choices significantly impacting patient care. In one study of T-cell lymphomas, Hodgkin lymphoma was diagnosed 3% of the time (Vose J, et al. 2008). Another study highlights the misdiagnosis of so-called “gray-zone lymphomas”, which is often considered in the differential diagnosis of Hodgkin lymphoma (Evens A, et al. 2017). Additionally, with the novel classification schema of the International Consensus Classification (ICC), additional features of these lymphomas need to be highlighted for proper and more pragmatic diagnoses in clinical practice.

Learning Objectives:

1. Recognize the histologic features of various reactive and lymphoma entities that mimic Hodgkin lymphoma
2. Effectively construct an appropriate panel of ancillary immunostains for distinguishing these entities
3. Integrate morphologic and ancillary (flow, immunohistochemistry and molecular) studies appropriately to arrive the correct diagnosis.
4. Highlight that some ancillary studies (such as PDL1) may be helpful in determination of therapy for these neoplasms.

Diagnostic Workup and Follow-up of Mature Lymphoma and Lymphoblastic Leukemia/Lymphoma in the Era of Advanced Molecular Diagnostics – Mutation Analysis and Beyond

Faculty: Yen-Chun Liu, MD, PhD, St. Jude Children’s Research Hospital and Sarah Gibson, MD, Mayo Clinic Arizona

Professional Practice Gap: Like the integrated classification of myeloid neoplasm that includes a significant amount of genetic information, the recently updated lymphoma classification incorporates an increasing amount of genetic data in addition to the morphologic and immunophenotypic findings [1-3]. With the growing interest and understanding in lymphoma genomics, we have seen an expanding demand from the oncologists to apply the genetic data and knowledge clinically [4, 5]. In the era of personalized medicine, it is essential for pathologists to provide relevant and pertinent genetic information, which has become a critical part of the pathology diagnosis due to its great impact on the diagnosis, prognosis and treatment. The call for joint efforts (American Society for Clinical Pathology, American Society of Hematology and College of American Pathologists) to establish the guidelines for lymphoma workup underscores the difficulty pathologists face in routine practice when incorporating this rapidly growing complexity in advanced molecular diagnostics. In fact, ten years after the surge of adopting next-generation sequencing (NGS) into the clinical laboratories, existing and emerging molecular technologies have revolutionized the workup and follow-up of mature lymphoma and lymphoblastic leukemias/lymphomas [6-10]

Learning Objectives:

1. Evaluate and apply the advanced molecular technologies available for the diagnosis and follow-up of lymphoid malignancies.
2. Identify scenarios in which advanced molecular technologies could refine the classification of lymphoid malignancies or impact therapeutic decision-making.
3. Recognize and communicate the essential genetic information provided by the ancillary studies with clinicians.

Navigating the Cutaneous Manifestations of Myeloid Neoplasms: A Molecular Perspective to Transcend ‘Leukemia Cutis’

Faculty: Sam Sadigh, MD, Brigham and Women’s Hospital, Harvard Medical School and Annette Kim, MD, PhD, Brigham and Women’s Hospital

Professional Practice Gap: Acute and chronic myeloid malignancies, such as acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), and myelodysplastic syndromes (MDS), can show a very broad spectrum of manifestations in the skin, with divergent morphologic and immunophenotypic features and different clinical behavior. The historically used blanket term “leukemia cutis” does not capture the essential features of neither the circulating hematologic neoplasm nor its particular skin manifestation and should be removed or limited in the pathology lexicon. Underrecognized by most pathologists, molecular studies have demonstrated that many mature histiocytic/dendritic proliferations, which traditionally might carry the diagnosis of various reactive or independent neoplastic processes, may be clonally related to marrow-based myeloid malignancies. Thus, characterization of these cutaneous lesions requires careful comparative integration of mutational data from skin lesions as well as PB or BM.  The utilization of a molecular-based framework in assessing these cases can illuminate their relationship with the peripheral blood (PB) or bone marrow (BM), lead to more precise designations and highlight progression events.

Learning Objectives:

1. To enumerate the various morphologies and immunophenotypes of cutaneous presentations of acute and chronic myeloid neoplasms.
2. To identify the most common mutations and cytogenetic aberrancies identified in acute myeloid leukemia involving the skin.
3. To be familiar with less common histiocytic/dendritic cell lesions that are clonally-related to marrow-based myeloid malignancies.

Next-gen Adjunctive Testing and Kidney Allograft Biopsies

Faculty: Evan Farkash, MD, PhD, University of Michigan

Professional Practice Gap: Newer molecular tests such as the Molecular Microscope and cf-ddDNA have recently become available, with more expected in the next few years (B-HOT, urine CRISPR-based tests).  However, renal and transplant pathologists do not routinely integrate the results of these tests with histomorphologic diagnosis.  In addition, there are questions of test stewardship and cost effectiveness regarding these assays.

Learning Objectives:

1. Describe the theory and performance of recently adopted molecular tests in the field of transplantation.
2. Compare the specimen types required for each test and how this affects test performance and interpretation.
3. Integrate the results of these tests with histomorphologic and immunohistochemical diagnosis to provide more accurate diagnostic and prognostic information for clinicians and patients.
4. Identify novel testing techniques that are still in clinical development and how they may shape diagnosis in the future.

Drug Induced Liver Injury: Role of the Surgical Pathologist in Diagnosis

Faculty: Romil Saxena, MD, MBBS, FRCPath, Emory University, Shefali Chopra, MD, Keck School of Medicine of USC

Professional Practice Gap: Drug induced liver injury (DILI) is a major cause of liver dysfunction in contemporary practice due to the accelerated pace of drug development as well as a surge in consumption of nutritional supplements and herbal compounds by an increasingly health conscious society. The constant addition of large numbers of new agents to formularies and wellness markets worldwide ensures that practicing surgical pathologists commonly encounter liver biopsies suspicious for DILI. Diagnosis of DILI is however challenging due to (1) the idiosyncratic nature of DILI, (2) overlap of histological findings of DILI with other acute and chronic liver diseases and (3) lack of sufficient volumes of medical liver biopsies in general surgical pathology practices to offer adequate experience in diagnosis and differential diagnosis.

Learning Objectives:

1. Summarize the principles of diagnosis of drug induced liver disease
2. Identify patterns suspicious of drug induced liver disease
3. Identify patterns virtually specific to certain drugs
4. Formulate differential diagnoses in cases of drug induced liver injury.

Tackling the Complex Landscape of Medical Liver Biopsies: A Practical Guide for Pathologists

Faculty: Vishal Chandan, MD, University of California, Irvine and Taofic Mounajjed, MD, Hospital Pathology Associates

Professional Practice Gap: General surgical pathologists may be required to interpret medical liver biopsies, but they may not have much experience and confidence in this topic. They may rely heavily on a single histologic finding (such as portal inflammation or granulomas) to generate a narrative/descriptive diagnosis, which is usually not that useful to the hepatologist. This course will demonstrate a pattern-based approach for the most common entities a general surgical pathologist would encounter during their daily sign-out of benign liver biopsies. This will help them generate an appropriate differential diagnosis and provide a more clinically meaningful pathology report. This course will also discuss different types of hepatitis and highlight common staging and grading pitfalls, such as parenchymal collapse can sometimes be mistaken for fibrosis on a trichrome stain, resulting in over-staging liver fibrosis. Pathologists may sometimes interpret medical liver biopsies without sufficient clinical and laboratory data. This course will also stress the importance of obtaining, analyzing, and incorporating such data in their pathologic interpretation. Finally, during this course, we will highlight subtle histological conditions such as glycogenic hepatopathy and amyloidosis, which can easily be overlooked on a liver biopsy.

Learning Objectives:

1. Learn to use a pattern-based approach for diagnosing common entities such as hepatitis, fatty liver disease, and chronic biliary disease while evaluating benign liver biopsies.
2. Understand common staging and grading pitfalls while evaluating medical liver biopsies.
3. Generate a meaningful differential diagnosis and pathology report for the clinicians.
4. Recognize the importance and utilization of clinical and laboratory data while evaluating a medical liver biopsy.

Predictive Biomarkers for Precision Therapeutics in Solid Tumors

Faculty: Adrián Mariño Enríquez, MD, PhD, Brigham and Women’s Hospital and Lauren Ritterhouse, MD, PhD Massachusetts General Hospital, Harvard Medical School

Professional Practice Gap: The number of druggable molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies in several cancer types in a tumor-specific or tumor-agnostic manner. Molecular pathology has therefore become fundamental not only to inform on tumor diagnosis and prognosis but also to drive therapeutic decisions in daily practice (PMID: 19809276). Successful implementation of precision oncology requires that pathologists identify which patients are most likely to benefit from systemic therapies – cytotoxic, immune and targeted therapies (PMID: 29494219). Pathologists should identify mutations, mutational signatures, or cellular phenotypes that predict therapy response. The landscape of predictive biomarkers in solid tumors is rapidly evolving and is poorly understood by practicing pathologists. There is a knowledge and skills gap within surgical pathologist that needs to be bridged (PMID: 29113995).

Learning Objectives:

1. Understand the significance of the most important predictive molecular biomarkers in solid tumors
2. Describe the principles underlying molecular testing in tumors with driver mutations involving tyrosine kinases and certain mutational signatures
3. Discuss the importance of predicting response to immune checkpoint blockade and cite the most used biomarkers
4. Recommend the appropriate ancillary test for biomarker identification in the clinicopathological contexts most commonly encountered in clinical practice

Practical Approach to the Diagnosis of 2021 CNS WHO Embryonal and Mesenchymal Entities

Faculty: David Meredith, MD, PhD, Brigham and Women’s Hospital, Harvard Medical School and Sanda Alexandrescu, MD, Boston Children’s Hospital, Harvard Medical School

Professional Practice Gap: The methods for diagnosis in neuropathology vary based on available resources, practice setting, and pathologists’ training. The 5th edition of the WHO Classification of Central Nervous Tumours introduced several new histomolecular entities in the embryonal and mesenchymal tumor categories. Some of the existing entities were modified to include new research findings with prognostic and therapeutic implications, which adds to the variability in the diagnostic approach. Given the novelty and rarity of many of these entities and the methods necessary for confirmation, there exists a gap in recognizing them as well as the appropriate diagnostic workup.

Learning Objectives:

1. Describe the clinicopathologic features of newly included CNS embryonal and mesenchymal neoplasms.
2. Determine the appropriate ancillary tests for the diagnosis of CNS embryonal and mesenchymal neoplasms.
3. Compose integrated pathology reports for the above entities that guide clinical management.

Small Biopsies vs EUS-Guided FNA of Tumors of the Pancreatobiliary Tract: Which is Better?

Faculty: Olca Basturk, MD, Memorial Sloan Kettering Cancer Center and Michelle Reid, MD, MSc, Emory University Hospital

Professional Practice Gap: New advances in imaging and surgical techniques have made pancreatobiliary tract infinitely more accessible to biopsy, brushing and FNA, leading to frequent samples from these sites. Because many pathologists are not routinely exposed to these specimens, their experience and comfort with work-up and diagnosis are sometimes limited. Anatomic complexity and post-inflammatory/instrumentation-related changes at these sites make cyto-histologic diagnosis additionally challenging for practicing surgical pathologists and cytopathologists. There have also been recent changes in terminology, grading and classification guidelines for numerous pancreatobiliary neoplasms, as well as newly described entities in these sites. These include intraductal papillary mucinous (IPMN), oncocytic (IOPN) and tubulopapillary (ITPN) neoplasms, flat (Bil-IN) and tumoral intraepithelial biliary tract neoplasms (IPN-B) as well as neuroendocrine neoplasms.

Learning Objectives:

1. Know the cytologic and histo-morphologic spectrum of cystic and solid lesions of the pancreas
2. Understand new terminology, classification and management guidelines for neoplastic mucinous cysts (IPMN, MCN) and non-mucinous intraductal lesions (IOPN, ITPN); Become familiar with newly updated grading methods for neuroendocrine neoplasms; judiciously use immunohistochemistry to recognize and classify NENs (including classical, grade discordant and ambiguous types).
3. Know the morphologic spectrum of benign, reactive and neoplastic biliary lesions including flat (biliary intraepithelial neoplasia (BiI-IN)) and tumoral intraductal papillary neoplasms (IPN-B) and adenocarcinoma.
4. Recognize morphology of inflammatory changes in the biliary tract specimens (due to stenting and instrumentation) and appropriately work-up and diagnose carcinoma on these limited samples.

Neoplasms of the Ampulla and Biliary Tract: A Practical Approach to Evaluating Surgical Pathology Specimens

Faculty: Yue Xue, MD, PhD, Northwestern University Feinberg School of Medicine and Alyssa Krasinskas, MD, Emory University

Professional Practice Gap: Resections and biopsies of ampullary and bile duct neoplasms are common specimens in routine practice, not only in academic centers, but also in community settings. Examination of these specimens can be an extremely difficult and treacherous area for diagnostic pathologists. In particular, small and often fragmented biopsies, in combination with morphologic benign mimickers of neoplasia, generate potential diagnostic pitfalls. In addition, recently proposed entities and advances in molecular diagnostics must be incorporated into practice. While pancreatic pathology courses are not uncommon and may cover ampullary and/or biliary neoplasia, educational activities dedicated to ampullary/biliary pathology are limited. The course faculty participated in numerous recent data-driven studies focused on diagnostic criteria involved in surgical pathology of ampullary and biliary tract lesions. They will give an overview of the histologic diagnosis of these neoplasms and recent advances in the field.

Learning Objectives:

1. Distinguish ampullary carcinoma from pancreatic ductal adenocarcinoma, distal common bile duct, and non-ampullary duodenal carcinoma.
2. Recognize tumoral intraepithelial neoplasms (IAPNs, IPNBs, ITPNs) and dysplasia of the ampulla and biliary tract.
3. Correctly classify ampullary carcinoma based on specific site (intra-ampullary, peri-ampullary/ampullary duodenal, mixed) and histology (intestinal, pancreatobiliary, mixed).

What is New in Pediatric Solid Tumors: Molecular Genetic Update and Practical Approach for General Pathologists

Faculty: Alyaa Al-Ibraheemi, MD, Boston Children’s Hospital and Alanna Church, MD, Boston Children’s Hospital, Harvard Medical School

Professional Practice Gap: The last ten years have seen an explosion of data about the genetic alterations that drive pediatric cancers.  Cytogenetic and molecular alterations have implications for diagnosis, prognosis, and response to therapy. Our clinical colleagues are increasingly demanding molecular profiling in order to provide the most accurate diagnosis and the best care for their patients.  As pathologists, it is imperative that we direct tissue to the appropriate tests in the context of the patient’s disease. Although pediatric tumors are often restricted to specialized pediatric, in fact a very considerable percentage of these lesions are initially evaluated in an outpatient setting or in general community hospitals. Thus, the initial diagnosis of many pediatric tumors frequently falls to the general surgical pathologist. Such lesions may be extremely challenging for general pathologists. General surgical pathologists would benefit significantly from focused didactic activities aimed at increasing their comfort level and diagnostic facility with pediatric tumors. To the best of our knowledge, there are currently no courses at the USCAP or at other widely attended Pathology meeting that specifically address this knowledge gap in surgical pathology. This course will also provide an overview of emerging technologies in the field to support evidence-based test selection.

Learning Objectives:

1. Review commonly encountered pediatric tumors (rhabdomyosarcomas, neuroblastoma, osteosarcoma, Wilms tumor, tyrosine  kinase-altered tumors).
2. Understand the key histologic features necessary for the differential diagnosis and diagnosis and of pediatric solid tumors.
3. Select the best panel of tests to reach a specific diagnosis, based on available laboratory resources and tissue
4. Review the key diagnostic/prognostic/therapeutic molecular alterations of pediatric tumors.
5. Integrate the histologic, molecular, and cytogenetic findings in an integrated report that will provide the clinicians with necessary data to create a personalized treatment plan

Non-Neoplastic Lung Diseases: You Can Learn to Love Them

Faculty: Kristine Konopka, MD, Michigan Medicine and Jeffrey Myers, MD, Michigan Medicine

Professional Practice Gap: The diagnosis of diffuse, non-neoplastic parenchymal lung diseases is a source of anxiety for general pathologists, in part due to these cases being infrequently encountered.  Additionally, Black-Schaffer WS et al (2021) highlighted a need for more training in all types of pulmonary/mediastinal pathology, an impression shared by practicing pathologists and employers alike.  This relative lack of exposure and knowledge in the approach to the diagnosis of diffuse lung disease prompts pathologists to seek consultation in these problematic cases.  A “snapshot” of cases received at the busy thoracic consultation practice at Michigan Medicine shows that lung biopsies performed for evaluation of diffuse lung disease account for over half of cases received for expert opinion (unpublished).  This data underscores the need for continuing education of pathologists in the field of lung pathology with particular emphasis on the diagnosis of diffuse parenchymal lung disease.

Learning Objectives:

1. Apply a systematic approach to the interpretation of lung wedge biopsies performed for the diagnosis of diffuse parenchymal lung disease,
2. Recognize the histologic spectrum of smoking-related lung pathology and understand how to apply terminology
3. Utilize immunohistochemistry to differentiate LAM from histologic mimics, and
4. Consistently apply histological criteria helpful in distinguishing benign epithelial proliferations occurring in the setting of diffuse lung disease from diffuse pneumonic adenocarcinomas.

The Mediastinal Blues – A Practical Approach to Common and Uncommon Scenarios in Biopsies

Faculty: Anja Roden, MD, Mayo Clinic and Andre Moreira, MD, PhD, NYU Langone Health

Professional Practice Gap: The mediastinum harbors a broad range of lesions of neoplastic and non-neoplastic nature. Given the vicinity to many vital structures such as the heart, lungs, superior vena cava, pulmonary artery, and large airways, mediastinal lesions can quickly become life-threatening leading to an anxious clinician which generally passe the anxiety on to the pathologist. Furthermore, the mediastinum harbors some rather uncommon neoplasms such as NUT carcinoma or SMARCA4-deficient undifferentiated tumor among others which many general pathologists are not comfortable with. However, their diagnosis is important given ongoing clinical trials and the urge for immediate initiation of treatment. In addition, the range of neoplasms and non-neoplastic lesions in the mediastinum is wide and includes thymic epithelial tumors, germ cell tumors, lymphomas, cysts, metastases, mesenchymal tumors, fibrosing mediastinitis, and IgG4-related disease among many others. Many of these lesions have overlapping morphologic and immunophenotypic features. Moreover, pathologists sometimes fail to recognize benign thymic lesions or benign thymic gland in a biopsy of a mediastinal lesion. These include benign cysts and thymic hyperplasia (thymic follicular hyperplasia or true thymic hyperplasia), diagnoses that can only be made on a resection specimen. The distinction of benign thymic lesion from thymoma or carcinoma is important as benign lesions can be managed by observation instead of immediately resected. Additionally, recent updates to the classification and nomenclature in neoplastic diseases of the thorax and the staging of thymic epithelial tumors also generate many diagnostic and prognostic questions, which will be addressed in this short course.

Learning Objectives:

1. To distinguish thymoma from thymic carcinoma and lymphoma in the setting of a small biopsy
2. To evaluate immunohistochemical stains that help in the distinction of thymoma from carcinoma and metastatic disease
3. To discuss molecular tests that are helpful in the diagnosis of a subset of mediastinal lesions
4. To recognize non-neoplastic mediastinal lesions in biopsies
5. To identify uncommon neoplasms in the mediastinum

Autopsy Eye Pathology: What You Need to Know

Faculty: Nora Laver, MD, Tufts Medical Center, NEEC and Anat Stemmer-Rachamimov, MD, Massachusetts General Hospital

Professional Practice Gap: Many pathology residency programs lack training in how to handle and report eye specimens, in particular autopsied specimens. Residency programs might not have high enough volume of autopsied eyes or lack the expertise to be able to teach residents how to handle and report them. This leads to a lack of knowledge of common ocular pathology diagnoses, inadequate competence in diagnosing challenging cases and lack of skills to recognize pathologies that need reporting.  Similar problems are also encountered in some neuropathology fellowship training programs.

Learning Objectives:

1. Review the normal ocular histological features of the cornea, conjunctiva, retina, uvea, optic nerve, sclera and lens.
2. Recall gross dissection techniques used in ocular pathology.
3. Compare and contrast the diagnostic features of common intraocular pathologies encountered in autopsied eyes including glaucoma, retinal detachment, intraocular gliosis, fibrous metaplasia of the RPE and ciliary epithelium, changes found in diabetes, hypertension, macular degeneration, and other potential surprise diagnoses.

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Conjunctival Melanocytic Intraepithelial Lesions (CMIL): WHO Classification System

Faculty: Tatyana Milman, Wills Eye Institute/Thomas Jefferson University; Maya Eiger Moscovich, Wills Eye Institute/Thomas Jefferson University

Professional Practice Gap: Conjunctival melanocytic intraepithelial lesions are notoriously challenging to interpret. Multiple classification systems have been proposed for evaluation of these lesions, including primary acquired melanosis classification system (PAM) and conjunctival melanocytic intraepithelial neoplasia classification system (C-MIN). The most recently proposed WHO classification system (CMIL) attempts to bridge the communication gap between pathologists and clinicians, serving as a Rosetta stone for moving between classification systems.

Learning Objectives:

1. Interpret conjunctival melanocytic intraepithelial lesions with the recently proposed WHO CMIL classification system.
2. Integrate the clinical information into a diagnostic approach for conjunctival melanocytic intraepithelial lesions.
3. Integrate immunohistochemical studies into a diagnostic approach for conjunctival melanocytic intraepithelial lesions.

“A Relay-Race for Physician Well-being.” Advocating for Physician Well-Being is a Team Sport; Everyone in the Healthcare System Must Play a Part.

Faculty: Laura Wake, MD, Johns Hopkins Medical Institutions and Alisha Ware, MD, The University of North Carolina School of Medicine

Professional Practice Gap: In the field of medicine, “quality” means striving for excellent patient outcomes. Quality is recognized by high productivity and ample learning opportunities. Research shows that workers and trainees obtain the highest productivity and satisfaction when they are given autonomy, as well as a sense of belonging; when their work or learning environment is dynamic and/or filled with challenges, and when they are part of a team that embraces and respects diversity, inclusion and collegiality. These are the characteristics of an engaged worker: One who is satisfied and has the dedication and motivation to strive to provide the highest quality care.

There is a delicate balance between the factors that establish engagement and those that lead to burnout, or disengagement. These factors include job demands, job resources, personal stressors and personal resilience.

Unfortunately, many places of work, including healthcare institutions, organizations and hospitals, do not fulfill these needs. For many, the increased job demands, decreased resources (i.e., masks, personal protective equipment, and healthcare personnel), and mounting personal stress during the COVID pandemic put a huge strain on personal resilience. Many institutions and organizations are limited in their ability to relieve or change the job demands, increase resources, or educate and train their workers. Instead, individuals are asked to rely on their own resilience to fulfill their jobs. For trainees, residents, and fellows, inactive learning, performing repetitive tasks, and isolation can lead to boredom and potential disengagement, which results in poorer productivity and translates into poorer patient outcomes.

We aim to close this gap by introducing participants to educational resources that raise awareness of the systemic factors that lead to burnout. We will use interactive training to illustrate techniques to help participants recognize and address burnout in their peers, their trainees, and themselves. We encourage participants to take these training resources back to use in their own institutions.

Learning Objectives:

1. Explain the factors and systems that lead to burnout.
2. Recognize the most common symptoms of burnout.
3. Initiate discussion with peers about feelings associated with burnout.
4. List several appropriate resources to help healthcare workers struggling with depression.