CONTEXT.—: Pathology resident education has a steep learning curve. Specimen sampling (grossing) is a procedural task, and procedural fields add video materials to their curricula to familiarize trainees with procedure(s), reduce errors, and improve patient care. Our team applied this strategy to develop original in-house sampling videos for our program. OBJECTIVES.—: To evaluate the effect of in-house sampling videos on resident sampling confidence. DESIGN.—: Sampling videos covering all major organ systems (AMOS) were created for our postgraduate year 1 (PGY1) trainees. Videos were hosted on a Northwestern cloud server for on-demand access. Trainees completed 3 surveys (0, 6, 12 months) evaluating sampling confidence comparing those who used in-house videos as an educational supplement with those who did not use the videos. RESULTS.—: Sampling confidence significantly improved at 6 and 12 months (P < .001) across AMOS and PGY levels. When compared with those who did not use in-house sampling videos, trainees who supplemented their education with in-house sampling videos had significantly higher confidence ratings across AMOS and PGY levels at the start of the study (P < .001) and at 6 months (P = .004). Sampling confidence significantly improved for PGY1 trainees at 6 and 12 months (P < .001); for PGY2 and PGY3 trainees, confidence significantly improved at 6 months (P < .001). When evaluated by organ-specific analyses, sampling and teaching confidence improved across all organ systems and, except for the gastrointestinal system, reached significance at 12 months for all PGY levels. CONCLUSIONS.—: Sampling videos, when used as a supplement to the existing curriculum, significantly improved trainee confidence.

CONTEXT.—: More people receive a diagnosis of skin cancer each year in the United States than all other cancers combined. Many patients around the globe do not have access to the highly trained dermatopathologists, whereas some biopsy diagnoses of patients who do have access result in disagreements between such specialists. Mechanomind has developed software based on a deep-learning algorithm to classify 40 different diagnostic dermatopathology entities to improve diagnostic accuracy and to enable improvements in turnaround times and effort allocation. OBJECTIVE.—: To assess the value of machine learning for microscopic tissue evaluation in dermatopathology. DESIGN.—: A retrospective study comparing diagnoses of hematoxylin and eosin-stained glass slides rendered by 2 senior board-certified pathologists not involved in algorithm creation with the machine learning algorithm's classification was conducted. A total of 300 glass slides (1 slide per patient's case) from 4 hospitals in the United States and Africa with common variations in tissue preparation, staining, and scanning methods were included in the study. RESULTS.—: The automated algorithm demonstrated sensitivity of 89 of 91 (97.8%), 107 of 107 (100%), and 101 of 102 (99%), as well as specificity of 204 of 209 (97.6%), 189 of 193 (97.9%), and 198 of 198 (100%) while identifying melanoma, nevi, and basal cell carcinoma in whole slide images, respectively. CONCLUSIONS.—: Appropriately trained deep learning image analysis algorithms demonstrate high specificity and high sensitivity sufficient for use in screening, quality assurance, and workload distribution in anatomic pathology.

CONTEXT.—: The COVID-19 pandemic has triggered a worldwide crisis that created unprecedented challenges for the health care system, including diagnostic laboratories that faced an ever-increasing demand for SARS-CoV-2 testing. OBJECTIVE.—: To share our experiences mobilizing a large-scale volunteer operation within a diagnostic laboratory in response to the COVID-19 crisis. In particular, during the early stages of the pandemic, research scientists at Vanderbilt University Medical Center were called upon to address challenges put forth by the rapid increase in testing demands. Volunteer scientists became a valuable resource to the clinical laboratory team after stay-at-home orders were in place and rapid diagnostic capabilities for COVID-19 were not yet widespread, thus necessitating significant manual laboratory analysis to support patient care. However, these volunteer efforts were not without challenges, including considerations around the licensure of clinical laboratory workers. Requirements can differ significantly between states and, in our case, were alleviated by an emergency gubernatorial decree. DATA SOURCES.—: We summarize these experiences here as an operational roadmap for other institutions that wish to leverage biomedical research staff in response to future emergencies. We include recruitment and organizational schemes, as well as results of a survey that details participant experiences and identifies strategies for optimization. Lastly, we present considerations around long-term hosting of clinical laboratory volunteers, beyond just the initial stages of an emergency. CONCLUSIONS.—: Through strategic implementation, scientists can provide diagnostic laboratories with invaluable support in times of need, while maintaining high clinical quality and regulatory compliance.

CONTEXT.—: Therapy targeted at HER2 (also known as ERBB2) was used initially for breast and gastroesophageal carcinoma and has more recently been adopted for endometrial serous carcinoma (ESC) and colorectal carcinoma (CRC). There is evidence that predictive biomarker testing algorithms for HER2 must be tumor type specific and that an algorithm validated for one tumor type cannot be applied to another. OBJECTIVE.—: To describe current laboratory practices for HER2 assessment in ESC and CRC. DESIGN.—: We surveyed laboratories participating in the 2021 College of American Pathologists (CAP) HER2 immunohistochemistry proficiency testing program. RESULTS.—: The survey was distributed to 1548 laboratories and returned by 1195, of which 83.5% (998) were in the United States. For ESC, 24.0% (287) reported performing in-house testing for HER2 by immunohistochemical staining and/or in situ hybridization; of these, 44.3% (127) performed it reflexively on all cases of ESC. The most common criteria for evaluating HER2 were the American Society of Clinical Oncology/CAP 2018 guidelines for breast carcinoma (69.0%; 194 of 281), whereas only 16.0% (45) used guidelines specific to ESC. For CRC, 20.2% (239 of 1185) performed in-house HER2 testing, and 82.0% of these (196) did the test only at the clinician's request. A plurality (49.4%; 115 of 233) used gastroesophageal cancer guidelines when scoring CRC, 30.0% (70) used the CRC scoring from the HERACLES trial, and 16.3% (38) used the American Society for Clinical Oncology/CAP 2018 guidelines for breast carcinoma. CONCLUSIONS.—: Laboratories vary in their approach to HER2 testing in ESC and CRC. Most laboratories did not report using tumor type-specific recommendations for HER2 interpretation. The lack of standardization could present a challenge to evidence-based practice when considering targeted therapy for these diseases.

CONTEXT.—: Prostate cancer diagnosis rests on accurate assessment of tissue by a pathologist. The application of artificial intelligence (AI) to digitized whole slide images (WSIs) can aid pathologists in cancer diagnosis, but robust, diverse evidence in a simulated clinical setting is lacking. OBJECTIVE.—: To compare the diagnostic accuracy of pathologists reading WSIs of prostatic biopsy specimens with and without AI assistance. DESIGN.—: Eighteen pathologists, 2 of whom were genitourinary subspecialists, evaluated 610 prostate needle core biopsy WSIs prepared at 218 institutions, with the option for deferral. Two evaluations were performed sequentially for each WSI: initially without assistance, and immediately thereafter aided by Paige Prostate (PaPr), a deep learning-based system that provides a WSI-level binary classification of suspicious for cancer or benign and pinpoints the location that has the greatest probability of harboring cancer on suspicious WSIs. Pathologists' changes in sensitivity and specificity between the assisted and unassisted modalities were assessed, together with the impact of PaPr output on the assisted reads. RESULTS.—: Using PaPr, pathologists improved their sensitivity and specificity across all histologic grades and tumor sizes. Accuracy gains on both benign and cancerous WSIs could be attributed to PaPr, which correctly classified 100% of the WSIs showing corrected diagnoses in the PaPr-assisted phase. CONCLUSIONS.—: This study demonstrates the effectiveness and safety of an AI tool for pathologists in simulated diagnostic practice, bridging the gap between computational pathology research and its clinical application, and resulted in the first US Food and Drug Administration authorization of an AI system in pathology.

CONTEXT.—: Whether androgen receptor (AR) expression can predict prognosis in breast cancer is under debate. OBJECTIVE.—: To analyze, retrospectively, the prognostic and treatment predictive ability of AR status in breast cancer. DESIGN.—: A total of 5765 patients diagnosed with primary invasive breast cancer without distant metastasis in the adjuvant setting were analyzed. The propensity score matching method was used to develop a new cohort of 3978 patients (1989 patients each) in which important prognostic factors were balanced. RESULTS.—: Positive AR expression is an independent prognostic factor for disease-free survival and overall survival. Estrogen receptor (ER)+ and progesterone receptor (PR)+ AR+ breast cancer patients were associated with the longest survival, whereas ER-PR-AR- breast cancer patients were associated with the shortest survival. The ER/PR/AR combinations could not predict the treatment effects for adjuvant trastuzumab but could be used for adjuvant chemotherapy and endocrine therapy selection. The worst survival was found in ER+PR-AR- patients receiving toremifene, ER+PR-AR+ patients receiving exemestane, ER+PR+AR- patients receiving anthracycline, and ER-PR-AR+ patients receiving taxanes. ER+PR-AR-, ER-PR-AR+, and ER-PR-AR- patients were associated with the worst survival among those who received radiotherapy and anthracycline plus taxanes. CONCLUSIONS.—: AR in combination with ER and PR could predict the prognosis and treatment effects of chemotherapy, endocrine therapy, and radiotherapy in the adjuvant setting.

CONTEXT.—: Neurotrophic receptor tyrosine kinase (NTRK) fusion testing has both diagnostic and therapeutic implications for patient care. With 2 tumor-agnostic US Food and Drug Administration-approved tropomyosin receptor kinase (TRK) inhibitors, testing is increasingly used for therapeutic decision making. However, the testing landscape for NTRK fusions is complex and optimal testing depends on the clinicopathologic scenario. OBJECTIVE.—: To compare different NTRK testing methods to help pathologists understand test features and performance characteristics and make appropriate selections for NTRK fusion detection for their laboratory and individual patient specimens. DATA SOURCES.—: A literature search for NTRK gene fusions and TRK protein was performed, including papers that discussed treatment, testing methodology, and detection or prevalence of fusion-positive cases. CONCLUSIONS.—: As standard of care in some tumor types, next-generation sequencing (NGS) panel testing is a cost effective and reliable way to detect a broad range of NTRK fusions. The design of the panel and use of DNA or RNA will affect performance characteristics. Pan-TRK immunohistochemistry may be used as a rapid, less expensive screen in cases that will not undergo routine NGS testing, or on specimens unsuitable for NGS testing. Fluorescence in situ hybridization may be appropriate for low-tumor-content specimens that are unsuitable for NGS testing. Quantitative reverse transcription polymerase chain reaction is best suited for monitoring low-level disease of a specific, previously identified target. This information should help laboratories develop a laboratory-specific NTRK testing algorithm that best suits their practice setting and patients' needs.

CONTEXT.—: Recent genome-wide sequencing studies have identified a subset of pancreatic ductal adenocarcinomas (PDACs) harboring significant alterations in epigenetic regulation genes, including the COMPASS-like complex genes. Whether this subset of PDACs has specific histologic characteristics or carries prognostic or therapeutic implications is unknown. OBJECTIVE.—: To determine the specific clinicopathologic and molecular features of PDACs carrying mutations in COMPASS-like complex genes. DESIGN.—: We analyzed a series of 103 primary and metastatic PDACs with comprehensive molecular profiling, including 13 PDACs carrying loss-of-function COMPASS-like complex gene alterations (study cohort). Another 45 patients carrying PDACs with wild-type COMPASS-like complex genes were used as the control group. RESULTS.—: PDACs within the study cohort were smaller, harboring frequent areas of poor differentiation and concurrent alterations in KRAS, TP53, SMAD4, and CDKN2A. A subset of metastatic PDACs from the study cohort showed squamous differentiation. There was a trend toward decreased survival in the study group. We further interrogated 2 public data sets and found that PDACs with COMPASS-like complex gene alterations have increased rates of TP53 mutation, body-tail location, poor differentiation or undifferentiated histology, and a higher death rate. CONCLUSIONS.—: COMPASS-like complex gene alterations likely represent a subset of more aggressive PDACs with poor or squamous differentiation histologically and increased concurrent TP53 mutations. These findings may have potential prognostic and therapeutic implications.

CONTEXT.—: Minimal/measurable residual disease (MRD) measured by molecular and multiparametric flow cytometry (MFC) has been proven to be predictive of relapse and survival in patients with B-cell acute lymphoblastic leukemia (B-ALL). A universally applicable antibody panel at a low cost but without compromising sensitivity and power of prognosis prediction in adult B-ALL remains unestablished. OBJECTIVE.—: To report our experience of using a single-tube 8-color MFC panel to measure the MRD status as a prognostic indicator in adult B-ALL patients. DESIGN.—: We retrospectively analyzed the characteristics, MRD status, and prognosis of adult B-ALL based on a large real-world cohort of 486 patients during a 10-year period. RESULTS.—: MRD assessed by MFC and polymerase chain reaction (PCR) assays for BCR-ABL+ patients showed concordant results in 74.2% of cases. MRD- status by our MFC panel could clearly predict a favorable relapse-free survival (RFS) and overall survival (OS) both at the end of induction and at the end of 1 consolidation course. Patients with continuous MRD- and with at least 1 MRD- result showed a favorable RFS and OS compared with those with at least 1 MRD+ result and continuous MRD+, respectively. CONCLUSIONS.—: The single-tube 8-color MFC panel demonstrated a low cost, decent sensitivity, and comparability with polymerase chain reaction-MRD but an excellent performance in predicting RFS and OS, and thus could potentially be taken as a routine indicator in the evaluation of the treatment response for adult patients with B-ALL.

CONTEXT.—: Multiplex stool polymerase chain reaction tests (SPTs) simultaneously test for many enteric pathogens. However, the clinical significance of a positive result, particularly in the context of chronic gastrointestinal disease, remains controversial. OBJECTIVE.—: To determine whether SPT results correlate with findings on colon biopsies obtained within a week of SPT or with clinical features. DESIGN.—: We reviewed 261 colon biopsies during a 15-month period that were obtained within a week of SPT, along with available clinical information, from patients with and without chronic idiopathic inflammatory bowel disease (CIIBD). Statistical analysis was used to test associations between SPT result, histologic features, and clinical variables. RESULTS.—: The most commonly detected pathogens were Clostridium difficile, enteropathogenic Escherichia coli, and norovirus. The presence of underlying CIIBD did not correlate with a positive SPT result or with a specific pathogen. Positive SPT result was significantly associated with neutrophilic activity, pseudomembranes, and increased intraepithelial lymphocytes. In addition, the presence of C difficile on SPT was significantly associated with pseudomembranes and neutrophilic activity. There were no other statistically significant relationships between SPT result and any other histologic abnormality. Only about half of SPT positive results were acted on clinically, and most patients with CIIBD were managed as having a presumed IBD flare. CONCLUSIONS.—: SPTs have many advantages; however, interpretation of results, particularly in the background of chronic gastrointestinal disease, remains a challenge. Therapeutic decisions influenced by a positive SPT result should integrate biopsy findings, clinical data, and other laboratory testing to avoid inappropriate treatment.

Comment on Arch Pathol Lab Med. 2022 Aug 1;146(8):921-923.

CONTEXT.—: High-grade appendiceal mucinous neoplasm (HAMN) is a relatively recently introduced term describing a rare epithelial neoplasm of the appendix that demonstrates pushing-type invasion but high-grade cytologic atypia. It remains understudied. OBJECTIVE.—: To describe clinicopathologic features of HAMNs. DESIGN.—: We identified 35 HAMNs in a multi-institutional retrospective study. Clinical and histologic features were reviewed in all cases, as well as molecular features in 8 cases. RESULTS.—: Patients were 57 years of age on average and most commonly presented with abdominal/pelvic pain. Histologically, 57% of the tumors showed widespread high-grade features. Architectural patterns in high-grade areas included flat, undulating, or villous growth, and occasionally micropapillary, cribriform, or multilayered growth. Thirteen cases had intact serosa, and the remaining 22 perforated the serosa, including 7 with peritoneal acellular mucin beyond appendiceal serosa and 10 with grade 2 pseudomyxoma peritonei. Molecular abnormalities included KRAS mutations in 7 cases and TP53 mutations in 4. No tumor confined to the appendix recurred. Two patients without pseudomyxoma peritonei at initial presentation developed pseudomyxoma on follow-up. Among 11 patients who presented with pseudomyxoma peritonei, 5 died of disease and 3 were alive with disease at last follow-up. CONCLUSIONS.—: HAMNs have a similar presentation to low-grade appendiceal mucinous neoplasm, and similar stage-based prognosis. When they spread to the peritoneum, they typically produce grade 2 pseudomyxoma peritonei, which may be associated with a worse prognosis than classical grade 1 pseudomyxoma peritonei.

CONTEXT.—: The College of American Pathologists (CAP), a laboratory accreditation organization with deemed status under the Clinical Laboratories Improvement Amendments of 1988 administers accreditation checklists. Checklists are used by laboratories to ensure regulatory compliance. Peer-level laboratory professionals audit laboratory records during inspections to assess compliance. OBJECTIVE.—: To identify the most frequently cited deficiencies for molecular oncology laboratories undergoing CAP accreditation inspections and describe laboratory improvement opportunities. DESIGN.—: The CAP Molecular Oncology Committee (MOC), which is involved in maintaining the Molecular Pathology checklist, reviewed data and inspector comments associated with the most frequently observed citations related to molecular oncology testing from laboratories inspected by the CAP during a 2-year period (2018-2020). RESULTS.—: Of 422 molecular oncology laboratories that underwent accreditation inspections, 159 (37.7%) were not cited for any molecular oncology-related deficiencies. For the All Common (COM) and Molecular Pathology checklists, there were 364 and 305 deficiencies, corresponding to compliance rates of 98.8% and 99.6%, respectively. The most frequently cited deficiencies are described. The COM checklist deficiencies were associated most often with the analytic testing phase; the MOL checklist deficiencies were more evenly distributed across the preanalytic, analytic, and postanalytic phases of testing. CONCLUSIONS.—: Molecular oncology laboratories demonstrated excellent compliance with practices that support high-quality results for patients and the health care providers who use those test results in patient management. This review includes a critical assessment of opportunities for laboratories to improve compliance and molecular oncology testing quality.

CONTEXT.—: A wide spectrum of mesenchymal tumors harboring ALK gene rearrangements has been identified outside the archetypal example of ALK-positive inflammatory myofibroblastic tumors. OBJECTIVE.—: To evaluate the molecular pathology of unusual ALK-positive mesenchymal tumors and their response to ALK-targeted treatments. DESIGN.—: Seven patients with ALK-positive mesenchymal tumors, including inflammatory epithelioid cell sarcoma, undifferentiated sarcoma, histiocytic neoplasm, smooth muscle tumor of uncertain malignant potential (STUMP), and atypical fibrohistiocytic tumor, were included on the basis of aberrant ALK immunoexpression. Patients with inflammatory myofibroblastic tumors were excluded from the study. ALK gene rearrangement was investigated either by fluorescence in situ hybridization or next-generation sequencing. RESULTS.—: ALK was immunolabeled in all patients, diffusely (≥50%) in 6 patients and partially (10%-50%) in 1 patient. ALK gene rearrangement was discovered in 5 of the 6 available patients. The 3'-partners of ALK fusion were identified in 3 of 4 investigated patients as follows: PRKAR1A-ALK (ALK-positive histiocytic neoplasm), TNS1-ALK (STUMP), and KIF5B-ALK (ALK-positive atypical fibrohistiocytic tumor). We failed to discover ALK translocation in 1 patient with ALK-positive inflammatory epithelioid cell sarcoma. However, transcriptomic investigation showed that this tumor was significantly enriched with ALK-related pathways, which suggested activation of ALK through a nontranslocation pathway, as a constitutive oncogenic mark in this tumor. ALK-targeted inhibitors, which were administered to 3 patients with metastatic diseases, achieved partial remission in 1 patient with ALK-positive inflammatory epithelioid cell sarcoma and stable disease in patients with ALK-positive undifferentiated sarcoma and STUMP. CONCLUSIONS.—: Molecular investigation of ALK-positive mesenchymal neoplasms could allow for an accurate diagnosis and personalized treatment.

CONTEXT.—: Organ weights are an essential part of autopsy analysis. Deviations from normal organ weights provide important clues to disease processes. The assessment of normal organ weights depends on reliable reference tables, but most widely available reference tables are based on data that are either decades old or derived from relatively small sample sizes. OBJECTIVE.—: To provide an updated reference table of organ weights based on contemporary sources and a large sample size. DESIGN.—: Organ weights from 4197 carefully screened autopsies performed on adults at the Palm Beach County Medical Examiner's Office in West Palm Beach, Florida, and the Mayo Clinic Hospital in Rochester, Minnesota. RESULTS.—: Height and body weight data in this study reflect the well-recognized increases in both variables, but most particularly in body weight, seen during the last decades. The study data show a strong positive association between organ weight and body weight for the heart, liver, and spleen. There is a similar but weaker association between body weight and the weight of the lungs and kidneys. Brain weight is independent of body weight but shows a strong negative association with age. Even when controlling for body weight, men's organs are heavier, except for the weight of the liver, which is comparable in men and women. These associations are in agreement with the findings of previous studies. The current study suggests that, for some of the commonly weighed organs, there has been an increase in median organ weight when compared with existing references. CONCLUSIONS.—: The tables presented here provide an updated reference that should prove useful to autopsy pathologists in the forensic and hospital settings.

CONTEXT.—: There is scant literature describing verrucous squamous hyperplasia of the urinary bladder. OBJECTIVE.—: To investigate the possible association between verrucous squamous hyperplasia and carcinoma. DESIGN.—: The case files of the senior author were searched for cases of verrucous squamous hyperplasia diagnosed between August 2010 and February 2021. Cases with available material were tested for in situ hybridization with human papillomavirus, and cases with available material unassociated with carcinoma underwent immunohistochemistry for p53. RESULTS.—: We gathered a series of 23 cases, the largest to date. Eleven cases were associated with carcinoma at diagnosis. Of the 7 cases unassociated with carcinoma in which follow-up was available, 1 patient (14.3%) was given a clinical diagnosis of carcinoma with recommended cystectomy, 2 (28.6%) had benign diagnoses, and 4 (57.1%) were dead not from disease. Of the 13 cases with available material, 13 (100%) were negative for human papillomavirus by high-risk in situ hybridization. CONCLUSIONS.—: Based on the small number of cases with limited follow-up, it is unclear whether verrucous squamous hyperplasia represents a precursor lesion or simply a high-risk association. Until more evidence is accumulated, patients with verrucous squamous hyperplasia of the urinary bladder should receive close clinical follow-up.

CONTEXT.—: The use of targeted therapy in patients with advanced, BRAF-mutated melanomas has necessitated timely access to BRAF mutational status in order for clinicians to proceed with treatment decisions. OBJECTIVE.—: To assess the impact of pathologist-initiated reflex BRAF testing in patients with advanced melanoma on laboratory turnaround time and time to systemic treatment. DESIGN.—: At our tertiary care center and 3 affiliated community hospitals, we implemented a guideline for pathologist-initiated reflex testing for BRAF mutational status in patients diagnosed with melanoma and positive lymph nodes or new diagnosis of a metastatic site. Retrospective review was performed for 65 cases of advanced melanoma for which BRAF testing was ordered, during a period inclusive of 6 months before and after guideline implementation. RESULTS.—: Implementation of reflex testing guidelines did not significantly affect the overall number of BRAF tests ordered for patients with melanoma. In cases with reflex testing compared to routine testing, total turnaround time was reduced by from 52.5 ± 5.6 to 18.6 ± 1.0 days (P < .001). In patients who received systemic therapy, without intentional delay by interval completion lymph node dissection (CLND), the use of reflex BRAF testing reduced time to systematic treatment from 71.7 ± 11.4 to 37.7 ± 4.6 days (P = .02). Time to systematic treatment was unchanged in those who underwent interval CLND (118.9 ± 10.9 versus 110.5 ± 22.5; P = .75). CONCLUSIONS.—: These data support a recommendation for pathologist-initiated reflex testing of BRAF mutational status in advanced melanoma as a standard practice in pathology laboratories.

CONTEXT.—: Allograft liver biopsy is the gold standard in assessing transplant recipients for graft dysfunction. The impact of biopsy sample size on the diagnosis of acute cellular rejection (ACR) has not been studied. OBJECTIVE.—: To assess the relationship of biopsy sample length with the diagnosis and determine optimal biopsy sample size in the transplant setting. DESIGN.—: We retrospectively reviewed 68 core biopsies from patients with a history of liver transplant. Each biopsy sample was read, on 5 different occasions with differing lengths, to assess for ACR per Banff criteria. Categorical agreement was calculated from rejection severity. RESULTS.—: The length of biopsy sample strongly correlated with the number of portal tracts. ACR rates increased from 73.5% to 79.4% with increase in length from 1 cm to 2 cm, and moderate rejection increased from 27.9% to 33.82%. At 1.0 and 1.5 cm, no cases of severe rejection were detected; at 2.0 cm, 1 case was detected; and at 3.0 cm, 2 cases were detected. The major error rate was reduced to less than 10% with a length of 2.0 cm, at which length the average number of complete and partial portal triads was 10 and 13, respectively. CONCLUSIONS.—: The likelihood of diagnosing ACR and rejection grade increased substantially with increase in biopsy sample length. This study suggests that a minimum length of 2 cm, 10 complete portal triads, or 13 partial/complete portal triads should be obtained for confident exclusion and grading of ACR.

CONTEXT.—: The use of saliva samples for diagnosis of SARS-CoV-2 infection offers several advantages, including ease of sample collection, feasibility of self-collection, and minimization of medical staff exposure to infection. The emergence of new SARS-CoV-2 variants has had an impact on the viral load of specimens and the results of real-time reverse transcription-polymerase chain reaction (rRT-PCR). OBJECTIVE.—: To compare nasopharyngeal swab and saliva samples for the diagnosis of SARS-CoV-2 using rRT-PCR. DESIGN.—: In this study, participants were recruited prospectively, and paired nasopharyngeal swab and saliva samples were collected simultaneously from each participant. After adding universal transport medium, RNA was extracted in an identical manner for both sample types, and samples were tested using rRT-PCR. In addition, samples with positive results were tested for SARS-CoV-2 variants. RESULTS.—: Of the 338 paired samples, 100 nasopharyngeal swab and 101 saliva samples tested positive for SARS-CoV-2. The rRT-PCR results of the saliva and nasopharyngeal swab samples showed a positive percent agreement of 95.0% (95% CI, 88.7%-98.4%), a negative percent agreement of 97.9% (95% CI, 95.2%-99.3%), and an overall percent agreement of 96.8% (95% CI, 94.3%-98.4%). SARS-CoV-2 was detected in the saliva samples of 6 participants with negative nasopharyngeal sample results. In addition, the sensitivity of saliva samples was similar to that of nasopharyngeal samples for detecting various SARS-CoV-2 variants, including the Omicron variant. CONCLUSIONS.—: Saliva samples can be used as an alternative to nasopharyngeal samples for convenient and effective detection of various SARS-CoV-2 variants.

CONTEXT.—: The incidence of human epidermal growth factor receptor 2 (HER2) positivity in gastric cancers differs widely across various populations and is unknown in many low-resource settings. OBJECTIVE.—: To evaluate the rates of HER2 positivity in gastric and gastroesophageal adenocarcinoma at a national referral hospital in East Africa. We also assessed the association between HER2 overexpression and patient clinicopathologic characteristics. DESIGN.—: A retrospective review of cases diagnosed as either gastric or gastroesophageal adenocarcinoma between 2013 and 2017 was performed at Muhimbili National Hospital in Dar es Salaam, Tanzania. Of 1205 specimens meeting inclusion criteria, stratified random sampling was conducted to select 150 cases for HER2 immunohistochemistry and clinicopathologic analysis. RESULTS.—: The median age of patients was 56.5 years, with 65.3% (98 of 150) of the cohort composed of male patients, and 34.7% (52 of 150) of female patients. HER2 overexpression was identified in 6.0% (9 of 150) of cases. Approximately half of the tumors (51.3%; 77 of 150) were intestinal-type gastric adenocarcinoma, and 36.0% (54 of 150) were moderately differentiated. Intestinal-type (P = .01) and well-differentiated tumors (P = .001) were associated with HER2 overexpression. CONCLUSIONS.—: HER2 overexpression was primarily seen in intestinal-type and well-differentiated tumors. Therefore, prioritizing HER2 testing for patients with intestinal-type, well-differentiated, or moderately differentiated gastric and gastroesophageal adenocarcinomas may be appropriate in Tanzania in efforts to allocate testing for patients who are most likely to benefit from trastuzumab therapy.

CONTEXT.—: Alveolar soft part sarcoma is a rare soft tissue tumor involving mainly deep soft tissue of the lower extremities. Primary bone involvement is extremely rare. OBJECTIVE.—: To discuss histopathologic and immunohistochemical features of alveolar soft part sarcoma along with challenges in diagnosis and management in the context of primary bone origin. DESIGN.—: Our study constituted 8 patients. Data were collected from the Tata Memorial Hospital, Mumbai, India, during a 10-year period. RESULTS.—: Five patients in our study were female and 3 were male. Their ages ranged from 13 to 56 years. Primary bone involvement was seen in the humerus, tibia, fibula, radius, calcaneus, and rib. Radiologic impression was that of a primary malignant bone tumor in all patients. Conventional histopathologic features were seen in 7 of 8 patients. Positive immunohistochemical expression for TFE3 was demonstrated in 6 patients. All patients had distant metastasis either at presentation or later in the course of the disease. Surgical excision of the primary tumor and adjuvant chemotherapy formed the basis of treatment. Four patients succumbed to disease and 2 were alive with disease. CONCLUSIONS.—: Rare occurrences of primary bone alveolar soft part sarcoma posed a diagnostic challenge in the form of differential diagnoses of metastatic tumors resembling it either morphologically or immunohistochemically. The combined application of clinical and radiologic features along with characteristic histomorphology and immunohistochemistry helps to arrive at a definite diagnosis of alveolar soft part sarcoma. Aggressive behavior of this tumor and its refractoriness to conventional chemotherapy were evident from our series.

CONTEXT.—: Granulosa cell tumors (GCTs) of both adult (AGCT) and juvenile (JGCT) types can rarely be completely or dominantly cystic, creating diagnostic difficulty because the cyst lining epithelium is often denuded. OBJECTIVE.—: To describe clinical, gross, microscopic, immunohistochemical, and molecular features of cystic GCTs with an emphasis on their differential diagnosis. DESIGN.—: We report 80 cystic GCTs (24 AGCTs and 56 JGCTs) in patients from ages 3 to 83 years (average ages, 35 years for AGCT and 22 years for JGCT). RESULTS.—: Nineteen of 43 patients with known clinical information (3 AGCT and 16 JGCT) had androgenic manifestations. All tumors were greater than 8 cm (average, 17 cm) with minimal to absent gross solid component. Denudation of cells lining the cysts was prominent. Invagination of the epithelium into the cyst walls was a key diagnostic feature, was present as cords, trabeculae, solid nests, and small and large follicles, and was identified in most tumors (17 AGCTs and 45 JGCTs). Cytologic atypia was essentially absent in AGCTs, whereas 14 JGCTs showed moderate to severe atypia of bizarre type. A theca cell component was present in all tumors and was extensive in 54. A FOXL2 hotspot mutation was identified in 1 of 4 AGCTs tested. CONCLUSIONS.—: Despite extensive denudation, the finding of typical architectural patterns and cytologic features as well as, in some cases, androgenic manifestations helps differentiate cystic GCTs from follicle cysts, the most common and challenging differential diagnosis, as well as other cystic neoplasms that may enter the differential diagnosis. FOXL2 sequencing may show a false-negative result in cystic AGCT because of the limited number of cells present within the tumor sample.

CONTEXT.—: Standardized structured reporting (SSR) among pathologists results in more complete diagnoses and, subsequently, improved treatment decisions and patient outcomes. Therefore, SSR templates' usage is advocated in oncology guidelines. However, actual SSR usage varies widely. Previous studies have shown multiple impeding and facilitating factors regarding SSR implementation. OBJECTIVE.—: To select, develop, and test an evidence-based multifaceted strategy, tailored to the impeding and facilitating factors to improve SSR implementation in oncologic pathology. DESIGN.—: Six strategy elements to increase the use of SSR were selected on the basis of a barrier and facilitator analysis, literature review, and consecutive discussions with a nationwide expert panel and project team. In collaboration with a professional organization for developing SSR templates (PALGA), we developed elements and combined them in 1 multifaceted strategy and subsequently tested effectiveness and feasibility. RESULTS.—: The 6 strategy elements were as follows: (1) renewed Web site including SSR information; (2) e-learning including SSR instructions; (3) communication manual describing communication about SSR; (4) improved feedback process, including use of the "Feedback Button" within SSR templates and "Frequently Asked Questions" on the Web site; (5) information sheet on SSR updates within SSR templates; and (6) monthly telephone conversations to discuss audit and feedback information regarding local SSR usage. A significant change (12.4%) in SSR usage among test laboratories was noticed. After the first test, e-learning and the "Feedback Button" were deemed most feasible and effective. However, awareness of all elements could be increased. CONCLUSIONS.—: Next steps will be to optimize the tailored strategy, to distribute it to all Dutch pathology laboratories, and to evaluate effectiveness and feasibility in a nationwide setting.