Post-COVID-19 Cholangiopathy: A Novel Entity.

INTRODUCTION: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution. METHODS: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19. RESULTS: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19. DISCUSSION: We believe that these cases constitute a novel severe post-COVID-19 cholangiopathy with potential for long-term hepatic morbidity.

Structural and functional cardiac changes in endomyocardial fibrosis treated with endomyocardial resection: Disease progression captured by multimodality imaging.

Eosinophilic myocarditis, a rare and under-recognized disease process, occurs due to cytotoxic inflammation of the endomyocardium that over time may lead to a restrictive cardiomyopathy. We report clinical, multimodality imaging, and pathologic findings in a 45-year-old woman over a 17-month period as she progressed from suspected acute eosinophilic myocarditis to phenotypic endomyocardial fibrosis resulting in recurrent ascites. Interval echocardiograms demonstrate definitive pathologic structural changes that reflect the hemodynamic consequences of the underlying cardiomyopathy. Despite a negative myocardial biopsy, characteristic findings on cardiovascular magnetic resonance imaging clarified the diagnosis which led to successful treatment with endomyocardial resection and valve replacements.

Evaluation of ChatGPT pathology knowledge using board-style questions.

OBJECTIVES: ChatGPT is an artificial intelligence chatbot developed by OpenAI. Its extensive knowledge and unique interactive capabilities enable its use in various innovative ways in the medical field, such as writing clinical notes and simplifying radiology reports. Through this study, we aimed to analyze the pathology knowledge of ChatGPT to advocate its role in transforming pathology education. METHODS: The American Society for Clinical Pathology Resident Question Bank 2022 was used to test ChatGPT, version 4. Practice tests were created in each subcategory and answered based on the input that ChatGPT provided. Questions that required interpretation of images were excluded. We analyzed ChatGPT performance and compared it with average peer performance. RESULTS: The overall performance of ChatGPT was 56.98%, lower than that of the average peer performance of 62.81%. ChatGPT performed better on clinical pathology (60.42%) than on anatomic pathology (54.94%). Furthermore, its performance was better on easy questions (68.47%) than on intermediate (52.88%) and difficult questions (37.21%). CONCLUSIONS: ChatGPT has the potential to be a valuable resource in pathology education if trained on a larger, specialized medical data set. Those relying on it (in its current form) solely for the purpose of pathology training should be cautious.

National pilot of entrustable professional activities in pathology residency training.

Entrustable professional activities (EPAs) are observable clinical skills and/or procedures that have been introduced into medical education at the student and resident levels in most specialties to determine readiness to advance into residency or independent practice, respectively. This publication describes the process and outcomes of a pilot study looking at the feasibility of using two anatomic pathology and two clinical pathology EPAs in pathology residency in 6 pathology residency programs that volunteered for the study. Faculty development on EPAs and their assessment was provided to pilot program faculty, and EPA assessment tools were developed and used by the pilot programs. Pre- and post-study surveys were given to participating residents, faculty, and program directors to gauge baseline practices and to gather feedback on the EPA implementation experience. Results demonstrated overall good feasibility in implementing EPAs. Faculty acceptance of EPAs varied and was less than that of program directors. Residents reported a significant increase in the frequency with which faculty provided formative assessments that included specific examples of performance and specific ways to improve, as well as increased frequency with which faculty provided summative assessments that included specific ways to improve. EPAs offered the most benefit in setting clear expectations for performance of each task, for providing more specific feedback to residents, and in increasing Program director's understanding of resident strengths abilities and weaknesses.

Meningothelial Hamartoma Overlying a Prior Craniotomy: A Case Report and Review of Literature.

Meningothelial hamartomas are benign lesions of the scalp with a handful of case reports published. Usually thought to be congenital lesions, they have, on occasion, been seen in older adults. In this report, we describe the first ever reported case of a patient diagnosed with a meningothelial hamartoma overlying a prior craniotomy performed two decades prior. We also briefly describe the literature surrounding these rare lesions, as well as their management and differential diagnosis.

Nature and Significance of Stromal Differentiation, PD-L1, and VISTA in GIST.

The role of stromal differentiation (SD), program death-ligand 1 (PD-L1), and v-domain Ig suppressor of T cell activation (VISTA) in gastrointestinal stromal tumor (GIST) is largely unknown. Looking forward, the assessment of SD and immune check point inhibition will become more ubiquitous in surgical pathology. Immature, myxoid stroma has been found to be a poor prognostic signature in many cancer subtypes (colon, breast, cervix, esophagus, stomach); although little is known regarding its significance in GIST. For immune check-point inhibition, studies have demonstrated expression to be associated with patient outcomes in numerous cancer subtypes. The present body of work aims to evaluate SD, PD-L1 and VISTA; both in terms of its nature and significance in a clinical setting. Here we found PD-L1 expression in immune cells (IC) and immature SD to be associated with worse cancer free survival, while positive VISTA expression was found to be associated with improved outcomes. High-grade, immature SD had the highest propensity for death/recurrence and was the only variable found to have prognostic significance on multivariate analysis. Our findings support the evaluation of SD, PD-L1 and VISTA in GIST, with clinical practice implications for pathologists. Ultimately, we hope our findings lead to improved prognostication, further optimization of therapeutics, and improved outcomes in a true clinical environment. For GIST, PD-L1 and VISTA could be both clinically relevant and targetable, while SD may be the answer to clinical heterogeneity.

Superpixel image segmentation of VISTA expression in colorectal cancer and its relationship to the tumoral microenvironment.

Colorectal cancer (CRC) is the third most common cause of cancer related death in the United States (Jasperson et al. in Gastroenterology 138:2044-2058, https://doi.org/10.1053/j.gastro.2010.01.054 , 2010). Many studies have explored prognostic factors in CRC. Today, much focus has been placed on the tumor microenvironment, including different immune cells and the extracellular matrix (ECM). The present study aims to evaluate the role of V-domain immunoglobulin suppressor of T cell activation (VISTA). We utilized QuPath for whole slides image analysis, performing superpixel image segmentation (SIS) on a 226 patient-cohort. High VISTA expression correlated with better disease-free survival (DFS), high tumor infiltrative lymphocyte, microsatellite instability, BRAF mutational status as well as lower tumor stage. High VISTA expression was also associated with mature stromal differentiation (SD). When cohorts were separated based on SD and MMR, only patients with immature SD and microsatellite stability were found to correlate VISTA expression with DFS. Considering raised VISTA expression is associated with improved survival, TILs, mature SD, and MMR in CRC; careful, well-designed clinical trials should be pursued which incorporate the underlying tumoral microenvironment.

A Holistic Appraisal of Stromal Differentiation in Colorectal Cancer: Biology, Histopathology, Computation, and Genomics.

Cancer comprises epithelial tumor cells and associated stroma, often times referred to as the "tumoral microenvironment". Cancer-associated fibroblasts (CAFs) are the most notable components of the tumor mesenchyme. CAFs promote the initiation of cancer through angiogenesis, invasion and metastasis. Histologically, the differentiation of stroma has been reported to correlate with prognostic outcomes in patients with colorectal cancer. This review summarizes our current understanding of the extracellular matrix (ECM) in colorectal carcinoma (CRC), showcasing the functions of CAFs and its role in stromal differentiation (SD). We also review current state-of-the-art biology, histopathology, computation, and genomics in the setting of the stroma. SD is distinctive morphologically, and is easily recognized by a surgical pathologist; we offer a lexicon and guide for discovering the essence of stroma, as well as an incipient vision of the future for computation and molecular genomics. We propose that the mesenchymal phenotype, which encompasses a cancer migratory/metastatic capacity, could occur through the process of SD. Looking forward, pathologists will need to invest time and energy into SD, embracing the concept and propagating its use. For patients with colorectal cancer, stroma is a brave new frontier, one not only rich in biologic diversity, but also potentially critical for therapeutic decision making.

Clinical Significance of Program Death Ligand-1 and Indoleamine-2,3-Dioxygenase Expression in Colorectal Carcinoma.

Colorectal cancer is a heterogenous disease with striking biological diversity. Colorectal carcinoma (CRC) is one of the most common malignancies, accounting for over 9% of all cancers worldwide. To put it in perspective, 5% of people will develop CRC in their lifetime. Biomarkers specific to a particular cancer type can assist in the evaluation of survival probability and help clinicians assess treatment modalities, an example being programmed death ligand-1 (PD-L1). With regards to PD-L1, this is the first study to evaluate the SP-142 antibody clone in CRC. The Ventana PD-L1 (SP-142) assay for PD-L1 expression identifies patients who may benefit from treatment with atezolizumab. SP-142 was chosen as large stage 3 clinical trials are being undertaken with atezolizumab in CRC. Indoleamine 2,3-dioxygenase (IDO-1) was also chosen as there are several ongoing trials for Epacadostat, the best-in-class oral IDO-1 enzyme inhibitor, in many solid tumors. For solid tumors, IDO-1-based immune escape has the potential to inhibit monotherapeutic efficacy of PD-L1-based therapeutics. In this study, a total of 223 cases of CRC were retrospectively reviewed and clinicopathologic data were analyzed in relation to PD-L1 and IDO-1 protein expression. Moreover, tumor-infiltrating lymphocytes, mismatch repair deficiency, high mitotic index, and worse survival outcomes were found in cohorts with significant PD-L1 and IDO-1 expression. Both PD-L1 and IDO-1 are actionable biomarkers, with potential therapeutic implications in CRC. Our findings support the theoretical foundation for targeting PD-L1 and IDO-1 in CRC, which now needs verification in well-designed robust clinical trials.

Whole slide imaging and colorectal carcinoma: A validation study for tumor budding and stromal differentiation.

Whole slide imaging (WSI) has recently received FDA approval for sign out in surgical pathology and some anticipate this to mature into the gold standard. During this transition, it will be important to validate WSI for its intended use. And many studies have validated whole slide imaging by comparing diagnostic accuracy with that of conventual light microscopy (CLM); however, the assessment of histopathologic markers is prone to much more discrepancy. One of the best examples being tumor-bud scoring in colorectal carcinoma. Other signatures, including stromal differentiation or desmoplastic reaction; could better represent the epithelial-mesenchymal transition. The findings in our study suggest stromal differentiation on both digital and glass slides to be much more reproducible (0.3585-0.9368) when compared to tumor budding (0.0968-0.7871). When comparing interobserver variation between glass and digital slides for three observers; stromal differentiation was more reliable on glass slides (0.4492), when compared to its digital counterpart (0.3016). On the other hand, interobserver variation for tumor bud scoring was more reliable on digital (0.1661), than glass slides (0.1026). Overall, there is significant variation between different observers and reproducibility issues present on conventual light microscopy transfer to digital slides. Although it is possible that too much emphasis is being placed on the concordance of WSI with CLM. In future, applications in artificial intelligence may be key to diagnostic precision and improved patient outcomes.

Myocardial hypoattenuation in cardiac sarcoidosis: CT correlation with CMR, PET and SPECT.

We report a marked abnormality in myocardial attenuation on non-gated contrast-enhanced CT in a patient with multiorgan sarcoidosis and correlate our findings with CMR, PET and SPECT. The noteworthy observation of myocardial hypoattenuation, in correspondence with the multimodality cardiovascular imaging findings, suggests that standard contrast-enhanced CT may provide information regarding tissue characterization. This report also demonstrates the independent clinical utility of CMR and PET in the evaluation and management of cardiac sarcoidosis.

Immature Stroma and Prognostic Profiling in Colorectal Carcinoma: Development and Validation of Novel Classification Systems.

Many pathological characteristics have utility for predicting prognosis in colorectal carcinoma (CRC). Some of the most important include tumor stage (TS), lymph node status (LNS) and tumor budding (TB). Tumor budding is a phenomenon originally described in 1949 as sprouting. TB assessment is not always reliable however, as it is subject to high inter-observer variation. This finding persists despite the current trends for sub-specialty training in surgical pathology. In light of this, new and reproducible histological prognostic markers could change the way we diagnose and manage patients with colorectal carcinoma. Studies have shown that desmoplastic reaction (DR) categorization can actually outperform other conventional prognostic factors, including tumor budding and tumor stage in predicting disease-free survival (DFS). Our study aimed to evaluate and assess the prognostic value of desmoplastic reaction in an American cohort with colorectal cancer using 3 different stromal classification scoring systems. In all three stromal grading systems, immature stroma was the most significant independent prognostic factor in CRC. Currently, none of the reporting protocols for the College of American Pathologists, the Royal College of Pathologists of the United Kingdom, and the Japanese Society for Cancer report on the presence of immature stroma. Importantly, regarding the ability to predict survival outcomes, our novel classification system has the potential to outperform other scoring methodologies.

IgG4-Related Sclerosing Disease of the Breast in a Male Patient.

IgG4-related sclerosing disease of the breast is a rare entity with 10 reports in the literature. We report the first case in a male patient. A 48-year-old male presented with 4-week history of palpable right upper outer quadrant breast mass associated with skin puckering. He reported a family history of breast cancer in his aunt. Ultrasound and mammography showed a spiculated 2.5-cm mass associated with skin retraction with extension to the pectoralis muscle. Ultrasound-guided core biopsy was performed. The findings were interpreted as acute and chronic inflammatory process. The patient subsequently denied improvement of the mass, and an excisional biopsy was performed. Histologic examination showed fibrosis and dense lymphoplasmacytic inflammation in the breast mass and muscle biopsy. Focal obliterative phlebitis was noted. IgG4-positive plasma cells were increased with counts of over 50 per high-power field. The diagnosis was confirmed as sclerosing IgG4-related disease of breast.

Fine-needle aspiration biopsy of lytic bone lesions: An institution's experience.

OBJECTIVES: Fine needle aspiration (FNAB) is an effective, minimally-invasive, inexpensive, diagnostic technique. The objective of this study was to evaluate the accuracy of FNAB in the diagnosis of bone lesions. METHODS: FNABs of bone lesions diagnosed at our institution over a 2-year period were retrospectively analyzed. RESULTS: 241 samples were reviewed. Patients included 121 males and 120 females, with ages ranging from 4-95 years (mean = 66 years). Of these 241 cases, 43.2% had FNAB and 56.8% had FNAB with core needle biopsy (CNB). The cytologic diagnoses were categorized as nondiagnostic, benign, atypical, suspicious, and positive for malignant cells. Total of 84.3% of FNABs were diagnostic. Of the malignant cases, 78.5% were metastases from nonosseous primary sites, 17.1% were lymphoproliferative lesions, and 4.4% were primary bone tumors. The most common site of metastasis was the pelvic bones (43.5%) followed by the vertebral column (38.7%). Breast (21%), lung (12.7%), and prostate (11.3%) were the most common identifiable primary site in metastatic cases. FNA smears and cell blocks allowed identification of metastatic lesions in 94.3% cases with immunohistochemistry (IHC). Obtaining a concomitant CNB did not result in a statistically significant increase in overall diagnostic yields (P = .20), ascertaining presence of metastatic lesion (P = .96) or ability to identify site of primary tumor in cases of metastasis (P = .53) compared to FNAB alone. Diagnostic accuracy was improved by reviewing clinical history, performing cell block, and IHC. CONCLUSIONS: FNAB is a reliable tool for diagnosis of bone lesions with comparable diagnostic sensitivity to CNB.

Aberrant Expression of Napsin A in Breast Carcinoma With Apocrine Features.

An incidental finding of napsin A-positive breast carcinoma with apocrine features during workup for metastatic cancer in an axillary lymph node led to our investigation of the incidence of napsin A expression in breast carcinomas, focusing on those with apocrine features. We included 97 cases of breast carcinomas and performed immunohistochemistry with napsin A, GATA-3, thyroid transcription factor-1, and GCDFP-15. There was a statistically significant difference between apocrine and nonapocrine cases with respect to polyclonal napsin A H-scores (P < .00152), monoclonal napsin A H-scores (P < .00631), GATA-3 H-scores (P < .00029), and GCDFP-15 H-scores (P < .00251). Of the 49 cases of apocrine carcinoma, monoclonal napsin A antibody was positive in 66.7% of cases, including in 7 (14.6%) that showed 3+ staining. The majority of nonapocrine cases were negative (62.5%) or weakly (1+) positive (29.2%), with none exhibiting 3+ strength. It is important for pathologists to be aware that breast carcinomas with apocrine features can express napsin A.

Utility of telepathology as a consultation tool between an off-site surgical pathology suite and affiliated hospitals in the frozen section diagnosis of lung neoplasms.

BACKGROUND: Increasingly, as in our institution, operating rooms are located in hospitals and the pathology suite is located at a distant location because of off-site consolidation of pathology services. Telepathology is a technology which bridges the gap between pathologists and offers a means to obtain a consultation remotely. We aimed to evaluate the utility of telepathology as a means to assist the pathologist at the time of intraoperative consultation of lung nodules when a subspecialty pathologist is not available to directly review the slide. METHODS: Cases of lung nodules suspicious for a neoplasm were included. Frozen sections were prepared in the usual manner. The pathologists on the intraoperative consultation service at two of our system hospitals notified the thoracic pathologist of each case after rendering a preliminary diagnosis. The consultation was performed utilizing a Nikon™ Digital Sight camera and web-based Remote Medical Technologies™ software with live video streaming directed by the host pathologist. The thoracic pathologist rendered a diagnosis without knowledge of the preliminary interpretation then discussed the interpretation with the frozen section pathologist. The interpretations were compared with the final diagnosis rendered after sign-out. RESULTS: One hundred and three consecutive cases were included. The frozen section pathologist and a thoracic pathologist had concordant diagnoses in 93 cases (90.2%), discordant diagnoses in nine cases (8.7%), and one case in which both deferred. There was an agreement between the thoracic pathologist's diagnosis and the final diagnosis in 98% of total cases including 8/9 (88.9%) of the total discordant cases. In two cases, if the thoracic pathologist had not been consulted, the patient would have been undertreated. CONCLUSIONS: We have shown that telepathology is an excellent consultation tool in the frozen section diagnosis of lung nodules.

Malakoplakia of the thyroid gland: a case report and review of literature.

Malakoplakia is a rare granulomatous disease that most commonly occurs in the urinary tract. It is characterized by sheets of histiocytes with granular basophilic inclusions and Michaelis-Gutmann bodies. We present an exceedingly rare case of malakoplakia of the thyroid in a 54-year-old Caucasian woman on immunosuppressive therapy for renal transplant performed in 1994.

Pulmonary adenofibroma: cytologic and clinicopathologic features of a rare benign primary lung lesion.

We report a case of pulmonary adenofibroma in a 29-year-old female found by CT scan during work-up for midline chest pain. To our knowledge, the cytological features of this entity have not been previously reported. Cytology demonstrated bland epithelial and stromal cells of varying size without karyorrhexis, pyknosis, or necrosis and with very rare mitoses. Stromal cells were present as either naked bipolar nuclei, as spindle cells with fragile eosinophilic cytoplasm, or as rare larger carrot shaped nuclei. Epithelial cells were present as small loosely cohesive groups with smooth round nuclei and moderate amounts of cytoplasm. Histologically, this lesion consisted of a leaf-like fibroepithelial pattern in which the clefts were lined by a single layer of cuboidal epithelium reminiscent of adenofibroma occurring in the female genital tract. Immunohistochemical analysis demonstrated epithelium that stained positively for pan-cytokeratin and TTF-1. The stroma stained positively for vimentin and desmin, and was weakly positive for SMA-1. The lesion was confirmed to be pulmonary adenofibroma with a smooth muscle component. The differential diagnosis for this lesion includes, but is not limited to, pulmonary hamartoma, pulmonary blastoma, adenomyofibroma, synovial sarcoma, and visceral metastases. It is important for cytopathologists to be aware of this benign entity because it can be encountered on lung FNA specimens. Considering this benign lesion in the differential diagnosis may help plan for minimal lung resection. Confirmatory intraoperative frozen section is a reasonable option.

Osteological associations with unique tooth development in manatees (Trichechidae, Sirenia): a detailed look at modern Trichechus and a review of the fossil record.

Modern manatees have a unique type of tooth development, continually forming identical new molars in the posterior end of each quadrant of their mouths, and then progressively moving teeth anteriorly, only to reabsorb roots and spit out worn crowns. This process is not only developmentally complex, but requires space in the oral cavity that imposes its own limitations on other uses of that space. To gain a clearer understanding of the anatomical constraints on the evolution of this unique developmental process, we identified the specialized craniodental features in modern Trichechus that permit this specialization using visual observation and CT. Furthermore, to better understand the evolution of these traits, we review the fossil record of trichechids for these traits, including CT analysis of the skull of Miosiren kocki, a possible early member of the family from the Early Miocene of Belgium.