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Differentiated vulvar intraepithelial neoplasia (dVIN) has been well accepted as a precursor lesion of human papillomavirus (HPV)-independent squamous cell carcinoma (SCC) of the vulva. (1,2) Recognition of dVIN and its [...], * Context.--Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with the potential for rapid progression to invasive squamous cell carcinoma (SCC). The histopathologic features of dVIN are diverse, have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC), and may be diagnosed by dermatopathologists or gynecologic pathologists because of the vulva&apos;s anatomic location. Objectives.--To identify the salient histopathologic features of dVIN, particularly those that predict progression to SCC, and to evaluate interobserver agreement in diagnosing dVIN within the same subspecialty and across subspecialties. Design.--One general surgical pathologist, 2 pathology-trained dermatopathologists, and 1 gynecologic pathologist blinded to the final diagnoses were asked to record 20 histopathologic features and to provide their final interpretations on cases of dVIN (n = 65), LS (n = 126), LSC (n = 112), and LS with LSC (n = 6). Results.--Interobserver agreement for the 4 diagnoses and 10 histopathologic features was moderate. Logistic regression analysis indicated that keratin pearls, basal pleomorphism, and basal layer disarray were independent variables for diagnosing dVIN (coefficients 1.95,1.97, and 0.91, respectively; P < .001) and progression to SCC (coefficients 1.96,1.20, and 1.08, respectively; P < .001). Conclusions.--There is no single histopathologic feature pathognomonic for dVIN; however, the presence of keratin pearls, basal pleomorphism, and basal layer disarray should raise high suspicion for dVIN and concurrent SCC. Expertise in both dermatologic and gynecologic pathology is beneficial for diagnosing dVIN. (Arch Pathol Lab Med. 2023;147:1431-1437; doi: 10.5858/arpa.2022-0088-OA)

Biliary tree cancers can be classified as intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PCC), distal cholangiocarcinoma (DCC), and gallbladder carcinoma (GBC) based on their anatomic location. Within the ICC category, there [...], Context.--The Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines propose a classification scheme that differs from the Union for International Cancer Control (UICC) system, in which the anatomic U-P point is the boundary between intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma (PCC). Objective.--To investigate whether this classification system improves clinicopathologic and genomic differentiation. Design.--Fifty-eight PCC cases defined by the UICC system were collected and classified into intrahepatic PCC (IPCC) and extrahepatic PCC (EPCC) categories using U-P point division. They were analyzed by next-generation sequencing using a panel that targeted 425 cancer-related genes. Results.--The IPCC group exhibited a significant larger tumor size compared with the EPCC group (4.67 [+ or -] 2.44 cm versus 2.50 [+ or -] 0.91 cm, P = .002). The mutation frequency of KRAS proto-oncogene, GTPase (KRAS) Q61 was also significantly higher in the IPCC group than in the EPCC group (16.7% versus 0.0%, P = .03). There were no statistically significant differences in other pathologic features or genomic characteristics, including tumor mutation burden and microsatellite instability. Significant differences in gene mutation rates, such as phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PlK3CA; 0.0% versus 15.8%, P = .01) and tumor protein p53 (TP53; 34.5% versus 63.2%, P = .04), were observed between PCC and adjacent biliary tract cancers. Conclusions.--This study offers valuable insight into the clinicopathologic and genomic features of PCC. It is proposed that the U-P point division may have limited potential to refine the characterization of PCC regarding these features, and that the UICC classification system can readily demonstrate the molecular specificity of PCC. doi: 10.5858/arpa.2023-0547OA

The history of notochordal lesions has its origin in 1846, when Virchow observed a small slimy excrescence on the surface of the clivus. He published these findings using the term [...], Context.--Chordomas are uncommon malignant neoplasms with notochordal differentiation encountered by neuropathologists, bone/soft tissue pathologists, and general surgical pathologists. These lesions most commonly arise in the axial skeleton. Optimal therapy typically involves complete surgical resection, which is often technically difficult owing to the anatomic location, leading to a high rate of recurrence. Lesions have been generally resistant to radiation and chemotherapy; however, experimental studies involving targeted therapy and immunotherapy are currently underway. Objective.--To summarize the clinical and pathologic findings of the various types of chordoma (conventional chordoma, dedifferentiated chordoma, and poorly differentiated chordoma), the differential diagnosis, and recent advances in molecular pathogenesis and therapeutic modalities that are reliant on accurate diagnosis. Data Sources.--Literature review based on PubMed searches containing the term "chordoma" that address novel targeted and immunomodulatory therapeutic modalities; ongoing clinical trials involved in treating chordoma with novel therapeutic modalities identified through the Chordoma Foundation and ClinicalTrials.gov; and the authors&apos; practice experience combined with various authoritative texts concerning the subject. Conclusions.--Chordoma is a clinically and histologically unique malignant neoplasm, and numerous diagnostic considerations must be excluded to establish the correct diagnosis. Treatment options have largely been centered on surgical excision with marginal results; however, novel therapeutic options including targeted therapy and immunotherapy are promising means to improve prognosis. (Arch Pathol Lab Med. 2022;146:386-395; doi: 10.5858/arpa.2020-0258-RA)

More than 90% of ovarian malignancies consist of epithelial cancers, (1) which are further classified into 5 major subtypes, namely high-grade serous carcinoma (HGSC), low-grade serous carcinoma (LGSC), clear cell [...], * Context.--Despite several studies focusing on the validation of whole slide imaging (WSI) across organ systems or subspecialties, the use of WSI for specific primary diagnosis tasks has been underexamined. Objective.--To assess pathologist performance for the histologic subtyping of individual sections of ovarian carcinomas using a light microscope and WSI. Design.--A panel of 3 experienced gynecologic pathologists provided reference subtype diagnoses for 212 histologic sections from 109 ovarian carcinomas based on optical microscopy review. Two additional attending pathologists provided diagnoses and also identified the presence of a set of 8 histologic features important for ovarian tumor subtyping. Two experienced gynecologic pathologists and 2 fellows reviewed the corresponding WSI images for subtype classification and feature identification. Results.--Across pathologists specialized in gynecologic pathology, concordance with the reference diagnosis for the 5 major ovarian carcinoma subtypes was significantly higher for a pathologist reading on a microscope than each of 2 pathologists reading on WSI. Differences were primarily due to more frequent classification of mucinous carcinomas as endometrioid with WSI. Pathologists had generally low agreement in identifying histologic features important to ovarian tumor subtype classification with either an optical microscopy or WSI. This result suggests the need for refined histologic criteria for identifying such features. Interobserver agreement was particularly low for identifying intracytoplasmic mucin with WSI. Inconsistencies in evaluating nuclear atypia and mitoses with WSI were also observed. Conclusions.--Further research is needed to specify the reasons for these diagnostic challenges and to inform users and manufacturers of WSI technology.

Dynamic, contrast-enhanced magnetic resonance imaging (MRI) is a highly sensitive imaging modality for the detection of breast cancer. (1-8) Over the past decade, the clinical role of breast MRI has [...], * Context.--Dynamic, contrast-enhanced magnetic resonance imaging (MRI) is a highly sensitive imaging modality used for screening and diagnostic purposes. Nonmass enhancement (NME) is commonly seen on MRI of the breast. However, the pathologic correlates of NME have not been extensively explored. Consequently, concordance between MRI and pathologic findings in such cases may be uncertain and this uncertainty may cause the need for additional procedures. Objective.--To examine the histologic alterations that correspond to NME on MRI. Design.--We performed a retrospective search for women who underwent breast MRI between March 2014 and December 2016 and identified 130 NME lesions resulting in biopsy. The MRI findings and pathology slides for all cases were reviewed. The follow-up findings on any subsequent excisions were also noted. Results.--Among the 130 cases, the core needle biopsy showed 1 or more benign lesions without atypia in 80 cases (62%), atypical lesions in 21 (16%), ductal carcinoma in situ in 22 (17%), and invasive carcinoma in 7 (5%). Review of the imaging features demonstrated some statistically significant differences in lesions that corresponded to malignant lesions as compared with benign alterations, including homogeneous or clumped internal enhancement, type 3 kinetics, and T2 dark signal; however, there was considerable overlap of features between benign and malignant lesions overall. Of 130 cases, 54 (41.5%) underwent subsequent excision with only 6 cases showing a worse lesion on excision. Conclusions.--This study illustrates that NME can be associated with benign, atypical, and/or malignant pathology and biopsy remains indicated given the overlap of radiologic features. doi: 10.5858/arpa.2020-0266-OA

To the Editor.--We read with concern the manuscript by Gill et al (1) that described autopsy findings for 2 adolescents who died after COVID-19 vaccination. The authors correctly stated that [...]

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). (1) Significant infection often manifests as acute respiratory distress syndrome, reflecting the virus's predominant [...], * Context.--Coronavirus disease 2019 (COVID-19) has been shown to have effects outside of the respiratory system. Placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection remains a topic of great interest because earlier studies have shown mixed results. Objective.--To ascertain whether maternal SARS-CoV-2 infection is associated with any specific placental histopathology, and to evaluate the virus&apos;s propensity for direct placental involvement. Design.--Placentas from 65 women with polymerase chain reaction-proven SARS-CoV-2 infection underwent histologic evaluation using Amsterdam consensus group criteria and terminology. Another 85 placentas from women without SARS-CoV-2 constituted the negative control group. A total of 64 of the placentas from the SARS-CoV-2-positive group underwent immunohistochemical staining for SARS-CoV-2 nucleocapsid protein. Results.--Pathologic findings were divided into maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammatory lesions, amniotic fluid infection sequence, increased perivillous fibrin, intervillous thrombi, increased subchorionic fibrin, meconium-laden macrophages (MLMs) within fetal membranes, and chorangiosis. There was no statistically significant difference in prevalence of any specific placental histopathology between the SARS-CoV2-positive and SARS-CoV-2-negative groups. There was no immunohistochemical evidence of SARS-CoV-2 virus in any of the 64 placentas that underwent staining for viral nucleocapsid protein. Conclusions.--Our study results and a literature review suggest that there is no characteristic histopathology in most placentas from women with SARS-CoV-2 infection. Likewise, direct placental involvement by SARS-CoV-2 is a rare event. (Arch Pathol Lab Med. 2021;145:648-656; doi: 10.5858/arpa.2020-0793-SA

In many hospitals, pathologic specimens at the time of primary hip and knee arthroplasty are routinely sent for gross or microscopic examination regardless of the diagnosis. (1-3) The Joint Commission [...], Background: Many practices require tissues from hip and knee arthroplasty procedures to be sent for pathologic examination. These examinations rarely provide information beyond the clinical or radiologic diagnosis and rarely alter clinical management. We aimed to determine the rate at which histologic diagnoses based on gross assessment alone or gross plus microscopic assessment correspond with reported clinical diagnoses in patients undergoing total joint arthroplasties and whether the histologic diagnoses alter patient management. Methods: We retrospectively reviewed arthroplasty cases performed at a high-volume teaching hospital in Manitoba, Canada. The clinical diagnosis was compared with the final pathology report based on gross examination, with or without histologic assessment. The results of the comparison were classified into 3 categories: concordant (same diagnosis), discrepant (different diagnoses without alterations in management) and discordant (different diagnoses resulting in management change). The overall provincial cost for pathologic examination was determined by multiplying the total examination cost by the estimated number of arthroplasty cases. Results: There were 773 patients in our study sample. The concordant rate was 98.3% (95% confidence interval [CI] 97.1%-99.1%), the discrepant rate was 1.7% (95% CI 0.9%-2.9%) and the discordant rate was 0.0% (95% CI 0%-0.5%) for 773 cases. The pathology diagnosis did not alter patient management in any case. A total of 91.5% of specimens did not require full histologic review and received gross descriptions only. The discrepancy rate was higher in cases that included microscopic examination than in those that received only gross descriptions (15.2% v. 0.4%, p < 0.001). The overall provincial cost for pathologic examination was estimated at Can$304 556. Conclusion: Submitting routine tissue from arthroplasty procedures to pathology does not affect patient management and therefore provides no value for the health care resources expended in doing so. Contexte : Beaucoup d&apos;etablissements exigent que des tissus soient envoyes pour un examen anatomopathologique apres une arthroplastie de la hanche et du genou. Ces examens n&apos;apportent generalement pas d&apos;information nouvelle quant au diagnostic clinique ou radiologique et modifient rarement la prise en charge. Notre objectif etait de determiner le pourcentage de correspondance entre les diagnostics histologiques fondes sur l&apos;inspection grossiere uniquement ou sur l&apos;inspection grossiere et l&apos;examen au microscope, et les diagnostics cliniques des patients qui subissent des arthroplasties totales. Nous cherchions egalement a savoir si les diagnostics histologiques modifient la prise en charge. Methodes : Nous avons procede a une analyse retrospective d&apos;arthroplasties effectuees dans un grand h[delta]pital universitaire du Manitoba, au Canada. Le diagnostic clinique etait compare au rapport final de pathologie fonde sur une inspection grossiere, avec ou sans examen histologique. Les resultats de cette comparaison etaient classes en 3 categories : concordance (meme diagnostic), divergence (diagnostics differents, sans modification de la prise en charge) et discordance (diagnostics differents entrainant une modification de la prise en charge). Le cout global pour la province associe aux examens pathologiques a ete etabli en multipliant le cout total d&apos;un examen par le nombre estime de cas d&apos;arthroplastie. Resultats : Notre echantillon comprenait 773 patients. Le taux de concordance etait de 98,3 % (intervalle de confiance [IC] de 95 % 97,1 %-99,1 %), le taux de divergence etait de 1,7 % (IC de 95 % 0,9 %-2,9%) et le taux de discordance de 0,0 % (IC de 95 % 0 %-0,5 %). Dans tous les cas, le diagnostic pathologique n&apos;a pas modifie la prise en charge. Au total, 91,5 % des specimens ne necessitaient pas d&apos;examen histologique complet et n&apos;ont fait l&apos;objet que d&apos;une inspection grossiere. Le pourcentage d&apos;anomalie etait plus eleve pour les specimens analyses au microscope que pour ceux ayant uniquement subi une inspection grossiere (15,2 % c. 0,4 %, p < 0,001). Le cout total des examens pathologiques pour la province a ete estime a 304 556 $ CA. Conclusion : L&apos;analyse pathologique systematique de tissus preleves lors d&apos;arthroplasties n&apos;entraine pas une modification de la prise en charge du patient; il n&apos;y a donc pas de valeur associee aux ressources de sante utilisees pour ces examens.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease (ILD) associated with a histologic and/or radiographic pattern of usual interstitial pneumonia (UIP) and a prognosis similar to [...], * Context.--Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) requires multidisciplinary diagnosis that includes clinical, radiologic, and often pathologic assessment. In 2018, the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and the Latin American Thoracic Society (ATS/ERS/JRS/ALAT) and the Fleischner Society each published guidelines for the diagnosis of IPF, which include criteria for 4 categories of confidence of a histologic usual interstitial pneumonia (UIP) pattern. Objective.--To (1) identify the role of the guidelines in pathologic assessment of UIP; (2) analyze the 4 guideline categories, including potential areas of difficulty; and (3) determine steps the Pulmonary Pathology Society and the greater pulmonary pathology community can take to improve current guideline criteria and histopathologic diagnosis of interstitial lung disease. Data Sources.--Data were derived from the guidelines, published literature, and clinical experience. Conclusions.--Both guidelines provide pathologists with a tool to relay to the clinician the likelihood that a biopsy represents UIP, and serve as an adjunct, not a replacement, for traditional histologic diagnosis. There are multiple challenges with implementing the guidelines, including (1) lack of clarity on the quantity and quality of histologic findings required, (2) lack of recognition that histologic features cannot be assessed independently, and (3) lack of guidance on how pathologists should incorporate clinical and radiographic information. Current criteria for "probable UIP" and "indeterminate for UIP" hinder accurate reflection of the likelihood of IPF. These challenges highlight the need for further morphologic-based investigations in the field of pulmonary pathology. doi: 10.5858/arpa.2020-0052-RA

In 2016, the World Health Organization (WHO) classification of renal epithelial tumors was updated to include 14 adult malignancies (ie, renal cell carcinomas [RCC]). (1) The distinction of these tumor [...], * Context.--Renal malignancies can be divided into cortical- and medullary-based tumors, the latter of which classically infiltrate the renal parenchyma by extending between nonneoplastic structures. Although high-grade cortical tumors can rarely exhibit the same growth pattern, the infiltrative morphology should elicit a differential diagnosis to be considered in each case. However, these diagnoses can be challenging to distinguish, especially on small renal biopsy samples. Objective.--To provide an overview of the clinical, gross, and microscopic findings; genetic and molecular alterations; and immunohistochemical evaluation of medullary-based renal tumors and other tumor types with overlapping morphologies and growth patterns. Data Sources.--Literature review and personal observations were used to compile the information in this review. Conclusions.--Collecting duct carcinoma is a prototypical medullary-based tumor, and although diagnostic criteria exist, it remains a diagnosis of exclusion, especially with ancillary techniques aiding the recognition of established as well as more recently described neoplasms. Other medullary-based malignancies included in the differential diagnosis include renal medullary carcinoma/ renal cell carcinoma unclassified with medullary phenotype, fumarate hydratase-deficient renal cell carcinoma, and upper tract urothelial carcinoma. Moreover, other rare entities should be excluded, including metastatic carcinoma, lymphoma, and melanoma. In addition to potential prognostic differences, accurate diagnoses can have important surgical and clinical management implications. (Arch Pathol Lab Med. 2021;145:1148-1170; doi: 10.5858/arpa.2020-0464-RA

The estimated agreement between consecutive anal cytologic examinations, between concurrent cytologic examinations, histopathology, between highresolution anoscopy (HRA) visual impression and histopathology and the estimation of the prevalence of severe dysplasia by concurrent cytologic category is studied. The candidate interventions to treat or prevent precursor lesions from entering clinical development, standardization and improvement of measurement methods are essential.

Anaplastic large cell lymphoma (ALCL), as defined in the Revised European-American Classification of Lymphoid Neoplasms (REAL) (1) and World Health Organization Classification of Hematopoietic and Lymphoid Neoplasms, (2) is a [...], The sarcomatoid variant of anaplastic large cell lymphoma is one of the rarest histologic variants of this neoplasm. Due to its sarcomatoid features, it is frequently misdiagnosed as a poorly differentiated sarcoma, anaplastic carcinoma, or melanoma. We report the case of a 92-year-old woman with a sarcomatoid anaplastic large cell lymphoma mimicking a primary breast neoplasm. The patient presented with a rapidly enlarging lump in the left breast and nodules in the right axilla. The immunohistochemical profile showed reactivity for leukocyte common antigen, UCHL-1, vimentin, and CD30, but immunoexpression of anaplastic lymphoma kinase was lacking. Anaplastic large cell lymphomas are lymphoid neoplasms of T-cell/null-cell lineage that consistently express the activation marker CD30 and usually carry a gene rearrangement of the anaplastic lymphoma kinase gene. To the best of our knowledge, this is the first reported case of sarcomatoid anaplastic large cell lymphoma presenting as a primary breast neoplasm in which anaplastic lymphoma kinase expression was assessed.

Research was conducted to examine the prevalence and infection by Helicobacter bacteria in pigs using histological and polymerase chain reaction techniques. Results from 60 pigs showed 50 pigs were infected with H. heilmannii type 1 and the rest with type 2.