Advancing Artificial Intelligence Integration Into the Pathology Workflow: Exploring Opportunities in Gastrointestinal Tract Biopsies.

This review aims to present a comprehensive overview of the current landscape of artificial intelligence (AI) applications in the analysis of tubular gastrointestinal biopsies. These publications cover a spectrum of conditions, ranging from inflammatory ailments to malignancies. Moving beyond the conventional diagnosis based on hematoxylin and eosin-stained whole-slide images, the review explores additional implications of AI, including its involvement in interpreting immunohistochemical results, molecular subtyping, and the identification of cellular spatial biomarkers. Furthermore, the review examines how AI can contribute to enhancing the quality and control of diagnostic processes, introducing new workflow options, and addressing the limitations and caveats associated with current AI platforms in this context.

Whole slide images as non-fungible tokens: A decentralized approach to secure, scalable data storage and access.

Background: Distributed ledger technology (DLT) enables the creation of tamper-resistant, decentralized, and secure digital ledgers. A non-fungible token (NFT) represents a record on-chain associated with a digital or physical asset, such as a whole-slide image (WSI). The InterPlanetary File System (IPFS) represents an off-chain network, hypermedia, and file sharing peer-to-peer protocol for storing and sharing data in a distributed file system. Today, we need cheaper, more efficient, highly scalable, and transparent solutions for WSI data storage and access of medical records and medical imaging data. Methods: WSIs were created from non-human tissues and H&E-stained sections were scanned on a Philips Ultrafast WSI scanner at 40× magnification objective lens (1 µm/pixel). TIFF images were stored on IPFS, while NFTs were minted on the Ethereum blockchain network in ERC-1155 standard. WSI-NFTs were stored on MetaMask and OpenSea was used to display the WSI-NFT collection. Filebase storage application programing interface (API) were used to create dedicated gateways and content delivery networks (CDN). Results: A total of 10 WSI-NFTs were minted on the Ethereum blockchain network, found on our collection "Whole Slide Images as Non-fungible Tokens Project" on Open Sea: https://opensea.io/collection/untitled-collection-126765644. WSI TIFF files ranged in size from 1.6 to 2.2 GB and were stored on IPFS and pinned on 3 separate nodes. Under optimal conditions, and using a dedicated CDN, WSI reached retrieved at speeds of over 10 mb/s, however, download speeds and WSI retrieval times varied significantly depending on the file and gateway used. Overall, the public IPFS gateway resulted in variably poorer WSI download retrieval performance compared to gateways provided by Filebase storage API. Conclusion: Whole-slide images, as the most complex and substantial data files in healthcare, demand innovative solutions. In this technical report, we identify pitfalls in IPFS, and demonstrate proof-of-concept using a 3-layer architecture for scalable, decentralized storage, and access. Optimized through dedicated gateways and CDNs, which can be effectively applied to all medical data and imaging modalities across the healthcare sector. DLT and off-chain network solutions present numerous opportunities for advancements in clinical care, education, and research. Such approaches uphold the principles of equitable healthcare data ownership, security, and democratization, and are poised to drive significant innovation.

Whole slide image features predict pathologic complete response and poor clinical outcomes in triple-negative breast cancer.

INTRODUCTION: Breast cancers are complex ecosystem like networks of malignant cells and their associated microenvironment. Applications for machine intelligence and the tumoral microenvironment are expanding frontiers in pathology. Previously, computational approaches have been developed to quantify and spatially analyze immune cells, proportionate stroma, and detect tumor budding. Little work has been done to analyze different types of tumor-associated stromata both quantitatively and computationally in relation to clinical endpoints. METHODS: We aimed to quantify stromal features from whole slide images (WSI) including stromata (myxoid, collagenous, immune) and tumoral components and combined them with traditional clinical and pathologic parameters in 120 triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy (NAC) to predict pathologic complete response (pCR) and poor clinical outcomes. RESULTS: High collagenous stroma on WSI was best associated with lower rates of pCR, while combined high proportionated stroma (myxoid, collagenous, and immune) most optimally predicted worse clinical survival outcomes. When combining clinical, pathologic, and WSI features, Receiver Operator Characteristics (ROC) curves for LASSO features was up to 0.67 for pCR and 0.77 for poor outcomes. CONCLUSION: The techniques demonstrated in the present study can be performed with appropriate quality assurance. Future trials are needed to demonstrate whether coupling applications for machine intelligence, inclusive of the tumor mesenchyme, can improve outcomes prediction for patients with breast cancer.

Prostate-Specific Membrane Antigen Expression in Meningioma: A Promising Theranostic Target.

Meningioma is the most common intracranial neoplasm, yet there is no effective therapy for recurrent/refractory meningiomas after surgery and radiation. Prostate-specific membrane antigen (PSMA) is an enzyme upregulated on endothelial cells of multiple neoplasms and is being investigated as a theranostic target. Until now, PSMA has not been studied in meningiomas. We aimed to verify PSMA endothelial expression in meningiomas, detect tumor grade variability, and investigate the relationship of PSMA signal with tumor recurrence. We analyzed 96 archival meningiomas including 58 de novo and 38 recurrent specimens. All specimens were stained routinely and immunostained for CD31 and PSMA. Slides were scanned and analyzed producing raw data for images of PSMA, CD31, PSMA/CD31, and PSMA/vasculature. PSMA expression was seen within 98.9% of meningioma samples. In the total cohort, higher-grade tumors had increased expression of raw PSMA and PSMA/CD31, and PSMA/vasculature ratios compared to grade 1 tumors. PSMA expression and PSMA/vasculature ratios (p = 0.0015) were higher in recurrent versus de novo tumors among paired samples. ROC curves demonstrated PSMA/CD31, PSMA/vasculature, and raw CD31 as indicators of tumor recurrence. Thus, PSMA is expressed within endothelial cells of meningiomas, is increased with tumor grade and recurrence, and persists with prior irradiation.

Stromal computational signatures predict upgrade to invasive carcinoma in mass-forming DCIS: A brief report of 44 cases.

Mass-forming ductal carcinoma in situ (DCIS) detected on core needle biopsy (CNB) is often a radiology-pathology discordance and thought to represent missed invasive carcinoma. This brief report applied supervised machine learning (ML) for image segmentation to investigate a series of 44 mass-forming DCIS cases, with the primary focus being stromal computational signatures. The area under the curve (AUC) for receiver operator curves (ROC) in relation to upgrade to invasive carcinoma from DCIS were as follows: high myxoid stromal ratio (MSR): 0.923, P = <0.001; low collagenous stromal percentage (CSP): 0.875, P = <0.001; and low proportionated stromal area (PSA): 0.682, P = 0.039. The use of ML in mass-forming DCIS could predict upgraded to invasive carcinoma with high sensitivity and specificity. The findings from this brief report are clinically useful and should be further validated by future studies.

Longitudinal K-means approaches to clustering and analyzing EHR opioid use trajectories for clinical subtypes.

Identification of patient subtypes from retrospective Electronic Health Record (EHR) data is fraught with inherent modeling issues, such as missing data and variable length time intervals, and the results obtained are highly dependent on data pre-processing strategies. As we move towards personalized medicine, assessing accurate patient subtypes will be a key factor in creating patient specific treatment plans. Partitioning longitudinal trajectories from irregularly spaced and variable length time intervals is a well-established, but open problem. In this work, we present and compare k-means approaches for subtyping opioid use trajectories from EHR data. We then interpret the resulting subtypes using decision trees, examining how each subtype is influenced by opioid medication features and patient diagnoses, procedures, and demographics. Finally, we discuss how the subtypes can be incorporated in static machine learning models as features in predicting opioid overdose and adverse events. The proposed methods are general, and can be extended to other EHR prescription dosage trajectories.

How the COVID-19 Pandemic Impacted Medical Education during the Last Year of Medical School: A Class Survey.

The novel coronavirus disease 2019 (COVID-19) pandemic has changed the medical education platform for students in the United States of America (USA). In that light, medical schools had to rapidly rearrange the dynamics of their educational curricula from the traditional platforms, to incorporate telemedicine. The telemedicine platform is supported in many specialties, allowing students various options to continue their education without interruption during the COVID-19 pandemic, and beyond. Telemedicine platforms are projected to grow exponentially due to the COVID-19 pandemic, allowing a segue for medical schools to modify their curricula by incorporating telemedicine programs. These distant-, e-learning (tele-education) programs align with the recommendations and guidelines for practicing social distancing. In this article, we surveyed fourth-year medical students to better understand their views on multiple aspects of e-learning, and its impact on their medical education during the COVID-19 pandemic. We assessed the medical students' experiences, satisfaction, insight and knowledge with e-learning, tele-education, telehealth, and their related modalities during COVID-19. We provide an organized overview and analysis of the main factors that influence medical education during the COVID-19 pandemic, while bringing forth the main challenges, limitations, and emerging approaches in the field of telemedicine and its application as it relates to medical education and e-learning across medical specialties. We outline the main themes and ideas that the medical students voiced, as to how their medical education is being impacted by the COVID-19 pandemic and how they will incorporate telemedicine and tele-education in their future career. A cross-sectional, mixed-method survey was developed and distributed via Google Surveys to 181 University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, United States of America, 4th year medical students, in December 2020. Results were compiled and analyzed after a 6-day open period for responses to be submitted. The survey instrument consisted of questions that inquire about the students' perspectives as it relates to their rapid switch from their traditional method of learning to the on-line version of medical education during the COVID-19 pandemic. A total of 65 students responded to the survey, of which 63 completed the survey. More than half of the students (n = 63, 57%) indicated that both their specialty of interest, and (n = 21, 33%) their sub-internships were impacted by the temporary lockdown, due to the COVID-19 pandemic. Students also indicated that the top three specialties that were affected included surgery, internal medicine and obstetrics and gynecology. When the students were asked if they were satisfied with the use of aquifer for their health care e-learning, only 35% of the students were satisfied. The students expressed that the school's administration team did a good job in developing the new tele-education curriculum for those in clinical training. In addition, responses indicated that students were open to case-based video learning and readings, when combined with the abbreviated clinical exposure during the make-up "clinical immersions periods" allowed for adequate learning. Overall, the survey responses show that more than half, approximately 54% of the medical students utilized telemedicine platforms during their clerkships that were impacted by COVID-19. The 4th-year medical students did not find tele-education and e-learning to be as effective as traditional medical education that combines in-person didactic classroom instructions and in-person face-to-face in hospital clerkships. Students felt that the telemedicine program that was rapidly set up due to the COVID-19 'lockdown' was fragmented, since it was not a formal integration of a telemedicine E-learning program. Students would have preferred more 'real' cases to follow, instead of the ready-made, aquifer type of cases. Telemedicine has significant potential to address many of the challenges facing the medical education environment today. We believe now that people have become comfortable with this method of teaching, that even after the pandemic ends, we will continue to see tele-education used as a platform for medical education.

Defining Data Migration Across Multidisciplinary Ambulatory Clinics Using Participatory Design.

OBJECTIVE: This study aimed to develop an institutional approach for defining data migration based on participatory design principles. METHODS: We outline a collaborative approach to define data migration as part of an electronic health record (EHR) transition at an urban hospital with 20 ambulatory clinics, based on participatory design. We developed an institution-specific list of data for migration based on physician end-user feedback. In this paper, we review the project planning phases, multidisciplinary governance, and methods used. RESULTS: Detailed data migration feedback was obtained from 90% of participants. Depending on the specialty, requests for historical laboratory values ranged from 2 to as many as 145 unique laboratory types. Lookback periods requested by physicians varied and were ultimately assigned to provide the most clinical data. This clinical information was then combined to synthesize an overall proposed data migration request on behalf of the institution. CONCLUSION: Institutions undergoing an EHR transition should actively involve physician end-users and key stakeholders. Physician feedback is vital for developing a clinically relevant EHR environment but is often difficult to obtain. Challenges include physician time constraints and overall knowledge about health information technology. This study demonstrates how a participatory design can serve to improve the clinical end-user's understanding of the technical aspects of an EHR implementation, as well as enhance the outcomes of such projects.

Is Regional Lymph Node Metastasis of Head and Neck Paraganglioma a Sign of Aggressive Clinical Behavior: A Clinical/Pathologic Review.

BACKGROUND: Head and neck paraganglioma is a rare neoplasm of the paraganglia. It accounts for <1% of all head and neck tumors. It usually has benign clinical course; however, malignant paraganglioma can only be diagnosed by showing metastatic disease. We undertook a retrospective study to assess the clinical significance of regional lymph nodes metastases in head and neck paragangliomas. DESIGN: From 1993 to 2016, primary head and neck paragangliomas are identified. The patient clinical and histopathologic materials were reviewed. RESULTS: Sixty-five specimens from 62 patients (3 patients with more than 1 specimens) with head and neck paragangliomas were recorded (49 female and 13 males) with mean age of 54 (24-78 years). The locations of the tumors were as follows: carotid body: 30, glomus tympanicum: 11, glomus jugulare: 14, parapharyngeal space: 3, and 1 case each of larynx, skull base, paraglottic area, infratemporal fossa, mastoid, cerebellopontine (CP) angle, and pyriform sinus. On histopathology, we found 5 cases of sclerosing variant. Thirty-two (52%) of the 62 patients had regional lymph node biopsy. Four (12%) of the 32 show metastatic paraganglioma (3 females and 1 male with mean age = 35). Two of the 5 cases of sclerosing variant had positive lymph nodes. No evidence of local recurrence or distant metastasis in the patients with positive lymph nodes with a 6 to 11 years follow-up. One of the 28 patients with negative lymph nodes developed metastatic disease to lumbar spine in 5 years. CONCLUSION: Metastatic paraganglioma to regional lymph nodes may have indolent clinical behavior, with disease-free survival of up to 11 years. The incidence of metastatic disease in lymph nodes was 4 (12%) of 32. Forty percent (2/5) of the cases with sclerosing variant of paraganglioma had lymph node metastases indicating that this tumor may have a more aggressive histological behavior.

Neuroendocrine carcinoma of the colon presenting as acute meningitis.

BACKGROUND: Neuroendocrine tumors represent an expansive group of neoplasms that share an etiology of epithelial origin with neuroendocrine differentiation. Poorly-differentiated neuroendocrine carcinomas behave similarly to their aggressive pulmonary counterpart, small cell lung carcinoma. Most patients with gastroenteropancreatic neuroendocrine tumors present with symptoms of metastasis, most commonly to the liver. There have been no case reports, to our knowledge, until now that demonstrate metastasis to the central nervous system. CASE PRESENTATION: A 72-year-old male with poorly-differentiated stage IIIB neuroendocrine carcinoma of the colon presented with acute altered mental status and right facial droop. Head CT was negative for an acute hemorrhagic process without evidence of suspicious lesions. Several days later, the patient developed fever and neck stiffness suspicious for bacterial meningitis. A lumbar puncture procedure was performed. Cytology of the CSF demonstrated metastatic disease to the central nervous system and the final diagnosis of carcinomatous meningitis secondary to metastatic neuroendocrine carcinoma of the colon was made. CONCLUSIONS: High-grade gastroenteropancreatic neuroendocrine carcinomas most commonly metastasize to the liver, which often corresponds with the patient's initial presentation. When neuroendocrine tumors do metastasize to the central nervous system, the primaries are most commonly of pulmonary origin. When meningeal metastasis does occur, it commonly presents as neurologic deficits or cerebrovascular events, rarely does meningeal metastasis mimic bacterial meningitis with symptoms of fever, photophobia and meningismus. As neuroendocrine carcinomas have been increasing in incidence over the past several decades, it is important to consider varying metastatic presentations when working up a patient with a diagnosis of neuroendocrine tumor.

Effective Use of Sirolimus and Zoledronic Acid for Multiosteotic Pseudomyogenic Hemangioendothelioma of the Bone in a Child: Case Report and Review of Literature.

Pseudomyogenic hemangioendothelioma (PMH) is a rare neoplasm with vascular and sarcomatous elements, unpredictable course, and uncommon metastatic or fatal potential. Although systemic chemotherapy has been reported with variable success, generally accepted treatment is aggressive surgery with wide margins. Evidence-based treatment options are lacking, and lack of clear prognostic features poses a risk of undertreatment or overtreatment with associated morbidity and mortality. We report the use of initial systemic therapy with oral sirolimus (SIR) and IV zoledronic acid (ZA) to induce a sustained clinical response and avoidance of amputation in a 6-year-old boy. At 37 months after diagnosis, our patient remains in sustained clinical remission as documented by x-ray, MRI, and PET-CT with return of normal mobility/activity and resolution of swelling and pain. Literature review identified 20 cases of pediatric and young adult patients with PMH, of which 7 received some form of systemic therapy. To the best of our knowledge, our patient represents the youngest reported case of PMH and the first successful and limb-sparing utilization of systemic chemotherapy as primary treatment for PMH.

Reactive histiocytic proliferation in the pleural fluid mimicking metastatic signet ring adenocarcinoma.

Reactive nodular and diffuse histiocytic proliferations of mesothelial and non-mesothelial lined sites have been sporadically reported in the literature. However, there is no cytologic literature describing this process. We report a case of reactive histiocytic proliferation mimicking a metastatic signet ring adenocarcinoma in pleural fluid from a 33-year-old white male. Ancillary studies such as immunohistochemistry should be used to elucidate the cell of origin and avoid diagnostic errors.

Hematologic Malignancies Discovered on Investigation of Breast Abnormalities.

OBJECTIVES: Hematological malignancies of the breast share a presentation similar to primary breast carcinomas but differ substantially in therapeutic approach and clinical outcomes. In this study, we investigate the frequency of hematological malignancies, their relative primary and secondary occurrences, and further characterize the distinct histopathologies of these malignancies with a special focus on lymphomas. To our knowledge this is one of the largest and most comprehensive studies of breast hematologic malignancies. METHODS: We conducted a retrospective review of our institution's pathology database for hematologic neoplasms diagnosed in breast tissue during a period of 22 years (1992-2014). Clinical characteristics, patient history, histologic subtype, and patient outcomes were analyzed. RESULTS: We identified 52 cases; 46 lymphomas, 4 plasmacytomas, and 2 myeloid sarcomas. The lymphoma cases were 15 diffuse large B-cell lymphomas (DLBCLs), 14 follicular lymphomas (FLs), 8 marginal zone lymphomas (MZLs), 2 anaplastic large T-cell lymphomas, 2 peripheral T-cell lymphomas-not otherwise specified, 1 each of small lymphocytic lymphoma, Burkitt lymphoma, mantle cell lymphoma, B-cell lymphoblastic lymphoma, and T-cell lymphoblastic lymphoma. In total, 30 cases were primary and 22 cases were secondary to the breast. Primary lymphomas accounted for 60% of lymphomas. Most FLs and almost all MZLs were primary. CONCLUSIONS: Primary hematological malignancies of the breast are more common than secondary: 58 % versus 42%. This finding is more evident in lymphomas: 63% versus 37%. The most common hematological malignancy in our study was DLBCL, followed by FL and MZL. Most FLs and almost all MZLs were primary. At the same time, the percentage of primary DLBCLs in our study is lower than the percentage reported in previous studies. We suggest that this could be the result of transformation from low-grade lymphomas. Although rare, hematological malignancies of the breast warrant a higher level of clinical suspicion as they present similarly to breast carcinomas but require a substantially different therapeutic approach.

Cytomorphology, clinicopathologic, and cytogenetics correlation of myelomatous effusion of serous cavities: A retrospective review.

BACKGROUND: Myelomatous effusions (ME) of the serous cavities are rare. Identification of the atypical plasma cells in the body fluids may be critical for prognostic considerations. METHODS: We retrospectively reviewed clinicopathologic findings of 21 serous effusion specimens from 13 cases of ME including 10 pleural, two concurrent pleural and pericardial, and one peritoneal from 1994 to 2014. RESULT: All 13 patients had bone marrow biopsy-proven plasma cell myeloma (PCM), including one plasmablastic-variant, one anaplastic-variant and one plasma cell leukemia. The time between the bone marrow diagnoses to serous cavity involvement ranged from 43 days to 9 years (mean 2.6 years, median 1.8 years). Monoclonal protein types showed predominant IgA subtypes (50%) including IgA-kappa (2), IgA-lambda (3), IgG-kappa (2), IgG-lambda (1) free kappa chain (1) and free lambda chain (1) and three unknown. All 13 patients died of disease (median survival 32 days). Concurrent imaging studies showed evidence of adjacent local disease. Cytology of the serous fluids revealed abundant plasma cells with varying degrees of atypia, including large cells with increased N/Cratios, coarse chromatin, and prominent nucleoli. All were CD138 positive. Of these, Cytology confirmed malignancy in 19/21(90%) cases. Five cases were positive for kappa-light chain and eight cases for lambda-light chain. Cytogenetics of 3/7 cases showed normal karyotype and 4/7 cases showed complex-karyotype. The patients with kappa light-chain had better survival compared to lambda light-chain (p = 0.051, log rank test). CONCLUSION: ME in PCM can present early in the natural history of the disease or very late. The preponderance of IgA-myeloma and complex-cytogenetics abnormalities is a noteworthy finding. Although there are different hypotheses regarding how ME develops in PCM, our finding supports the hypothesis that direct spread of PCM into serous cavities is a likely mechanism. Diagn. Cytopathol. 2016;44:742-747. © 2016 Wiley Periodicals, Inc.

Cytological features of Castleman disease: a review.

INTRODUCTION: Castleman disease (CD) is a benign lymphoproliferative disorder with hyaline vascular (HVCD), plasma cell (PC-CD), and mixed subtypes. Only HVCD lymph node cytomorphology has been described, mainly as case reports. We reviewed all CD subtypes. To the best of our knowledge, our case series is the largest and most comprehensive yet published. MATERIALS AND METHODS: We searched our institution's database for histologically confirmed CD cytology cases (fine needle aspiration, touch preps) for the past 23 years. Two independent pathologists evaluated cytomorphology. We then reviewed touch preps from 6 histologically confirmed, non-CD reactive lymph node excisions. RESULTS: 8 patients (5 women, 3 men) had the following subtypes: HVCD (5 patients), PC-CD (2), and mixed (1). All cases had a heterogenous background population composed predominantly of small lymphocytes with single and clustered follicular dendritic cells (FDCs). The FDCs had delicate pale cytoplasm with indistinct borders showing lymphocyte emperipolesis. They were often binucleated or multinucleated with fine chromatin, regular nuclear borders, large nuclei, and small nucleoli. HVCD cases had traversing, frequently hyalinized capillaries. PC-CD cases had increased plasma cells, including binucleate forms, and tingible body macrophages with fewer FDC clusters. Human herpes virus-8 immunostain was negative in all cases. Non-specific follicular hyperplasia cases had abundant tingible body macrophages, rare hyalinized capillaries, and no lymphocyte emperipolesis. CONCLUSIONS: CD is distinguished by background lymphocytes and cohesive FDC clusters with lymphocyte emperipolesis. HVCD has traversing, hyalinized capillaries and PC-CD has increased plasma cells and tingible body macrophages. Knowledge of these features can prevent a lymphoma misdiagnosis.

Unresectable Middle Mediastinal Biphasic Pulmonary Blastoma.

We report a case of a young male who presented with an unresectable, centrally-located classic biphasic pulmonary blastoma (CBPB) involving his bilateral mainstem bronchi and esophagus and a synchronous right testicular seminoma. CBPB is a rare and aggressive tumor that most commonly presents as a solitary mass in the periphery of the lung. Surgical resection is the preferred treatment for CBPB, as chemotherapy and radiation have demonstrated limited effectiveness. In the current case, four cycles of cisplatin, ifosfamide, and etoposide with concurrent radiotherapy resulted in a favorable response at three months. Currently he optimal treatment for unresectable pulmonary blastomas remains undefined.