Prostate cancer (PCa) is a biologically diverse malignancy with a clinical trajectory that often culminates in treatment resistance and aggressive phenotypes. Among these, neuroendocrine prostate cancer (NEPC) represents a particularly lethal variant that arises either de novo or through transdifferentiation from conventional adenocarcinoma under therapeutic pressure. This review summarizes the recent advances in our understanding of neuroendocrine differentiation in prostate cancer. We review the genetic, epigenetic, and transcriptional drivers of lineage plasticity, including key roles for TP53, RB1, EZH2, MYCN, and REST, and highlight emerging entities such as amphicrine prostate cancers. Furthermore, we discuss the evolving WHO classification, diagnostic challenges, and therapeutic strategies targeting NEPC, including PARP inhibitors (DNA damage repair-deficient subsets), Aurora kinase inhibitors (N-Myc/AURKA activation), and DLL3-directed approaches.

Chondrogenic tumors represent the most common group of primary bone neoplasms and may also occur in soft tissue. They encompass a wide spectrum of benign, locally aggressive, and malignant lesions. Histologically, they share the presence of cartilaginous matrix, which may be present in variable amounts. Chondrogenic tumors often show characteristic features on imaging studies, and correlation with radiologic findings is critical, particularly in lesions arising in bone. The term chondroid is often used to refer to both tumors with "true" cartilage matrix and those with cartilage-like stroma, which can introduce some confusion. A number of recurrent molecular alterations helpful for diagnosis have been identified across a range of benign and malignant cartilaginous and chondroid tumors. This review provides a practical approach to chondrogenic and chondroid neoplasia in the bones and soft tissue, emphasizing key clinical, radiologic, histologic, and molecular features and highlighting recently described entities.

Radiologic-pathologic correlation is essential for diagnostic accuracy, particularly when dealing with primary bone tumors. Basic radiology knowledge is an advantage for the pathologist. While most pathologists understand the value of radiologic correlation, it seems the development of the pathologist's own radiologic skills is less emphasized in pathology residency training than, for instance, most surgical specialties, yet radiology remains a critically important datapoint for the pathologist to integrate. As pathologic diagnoses remain the gold standard for bone and soft tissue tumor classification, it behooves pathologists to leverage the invaluable complementary information that can only be gained from direct radiologic correlation. Moreover, with some practice, we find that integration of the corresponding radiologic features provides a window into the biological timeline / aggressiveness of a particular tumor and therefore increases the pathologist's diagnostic confidence. In addition, other valuable clues come with the identification of matrix mineralization (or lack thereof), zones of transition (narrow or wide) with or without corresponding sclerosis, osseous remodeling, periosteal reaction, and much more. While we certainly encourage close interdepartmental collaboration with our musculoskeletal radiology colleagues, we also stress the value of pathologist direct review of imaging and the development of their own radiology skills which improves diagnostic accuracy and confidence. Finally, while this review provides the reader with a strong foundation in musculoskeletal radiology, we firmly believe the best way to build these invaluable skills is through consistent real-time review of the corresponding imaging and direct correlation with histology.

Vascular disorders of the gastrointestinal tract represent a variety of disease processes that impair blood flow or directly damage vessel walls, resulting in ischemia and its consequences. These conditions include thromboembolic disease, systemic vasculitides, drug-induced vascular injury, and structural vascular abnormalities. Histologic features vary among these conditions, with some demonstrating specific identifying findings and others having nonspecific changes that overlap with other diagnoses. While the result is often nonspecific ischemic-type changes, careful histopathologic examination can provide critical diagnostic clues. Integrating these microscopic findings with clinical, laboratory, and radiologic data is essential for accurate diagnosis. This review provides a framework for recognizing the major categories of gastrointestinal vascular pathology to aid surgical pathologists in refining differential diagnoses, avoiding diagnostic misinterpretation, and improving patient care.

The macroscopic handling of mandibular resection specimens for odontogenic tumors presents a distinct set of challenges and considerations that differentiate it from the examination of mandible specimens resected for oral squamous cell carcinoma, osteoradionecrosis, metastases or primary bone sarcoma. The following outlines the background considerations and operational methodology around mandibular resection specimens performed in the treatment of odontogenic tumors. This manuscript is intended as the initial step in process alignment rather than a disease-specific review. This work highlights the importance of unique considerations within grossing strategies and provides a framework for practice in this area of head and neck pathology.

Bone and soft tissue pathology - perhaps more than in any other surgical pathology subspecialty - has been profoundly shaped by a cadre of trailblazing female pathologists who have seamlessly integrated morphologic expertise, molecular innovation, and educational leadership. While no single review can capture the full breadth of contributions made by women in this field, this article highlights the remarkable achievements of six such leaders - Drs. Sharon W. Weiss, Adrienne M. Flanagan, Julia A. Bridge, Cristina R. Antonescu, Judith V.M.G. Bovée, and Jeanne M. Meis - whose careers collectively mirror the evolution of musculoskeletal pathology from morphology-centered diagnoses to an era of integrative molecular precision. Through their work, we trace a historical journey encompassing seminal tumor descriptions, transformative advances in immunohistochemistry and molecular cytogenetics, and parallel improvements in classification and clinical management.

Papillary ductal proliferations of the salivary glands encompass a spectrum of benign neoplasms and reactive conditions. The present review will focus on the sialadenoma papilliferum (SP) family of tumors and inverted ductal papillomas (IDP). Intraductal papilloma is a rare salivary gland lesion with poorly defined diagnostic criteria, significant overlap with more reproducible entities, and histologic features distinct from SP and IDP, and is therefore excluded from this review. The SP family of tumors comprises conventional SP, SP-like intraductal papillary tumor, and tubulopapillary hidradenoma-like tumor of the mandible, is characterized by a consistent small ductal proliferation and a variable exophytic component, and is often driven by BRAF p.V600E mutations. Inverted ductal papillomas exhibit a distinct endophytic growth pattern reminiscent of their sinonasal counterparts but are restricted to the salivary ducts. While generally indolent, these tumors can mimic malignant entities such as intraductal carcinoma, mucoepidermoid carcinoma, or squamous cell carcinoma. Accurate diagnosis is essential to ensure appropriate conservative management and avoid unnecessary treatment. This review provides an overview of the clinical, histopathological, and molecular features of these papillary ductal proliferations, outlining key diagnostic criteria to distinguish them from their mimics.

Gross examination of surgical pathology specimens is a foundational component of pathology training and remains essential for the accurate evaluation of resection specimens. Bone and soft tissue tumors represent a rare and diagnostically challenging group of neoplasms that often require specialized expertise and subspecialty training for proper classification. Although definitive diagnosis typically relies on the careful integration of clinical, radiologic, histologic, immunophenotypic, and molecular findings; gross (macroscopic) features can provide valuable early diagnostic clues regarding tumor type, surgical adequacy, and biologic behavior. Despite their diagnostic value, the gross features of bone and soft tissue tumors are often underappreciated, in part due to the relative rarity of these neoplasms. In this review, we highlight selected bone and soft tissue tumors to emphasize the practical importance of careful gross examination in the evaluation and diagnosis of musculoskeletal neoplasia.

Odontogenic lesions can present the diagnostic pathologist with uncertainty due to the range of clinical presentations and histological features. Whilst most of the tooth-forming apparatus involutes on completion of tooth formation, small remnants of both the epithelial and mesenchymal components remain in many individuals, both within the jaws and the overlying gingival mucosa. These developmental remnants can give rise to a range of lesions which span from reactive/inflammatory lesions through hamartomata to those which are neoplastic in nature. This varied etio-pathogenesis does not result in discrete diagnostic entities, but rather a range of overlapping clinical presentations and histological features, which makes definitive diagnosis challenging. This spectrum of lesions and their interrelationships have long been the subject of discussion in the oral pathology literature, and because many of the issues raised regarding our understanding of the biological potential of these lesions remain unresolved, this has contributed to persistent ambiguity in their diagnostic features. In this paper, we will outline the literature published relating to two poorly defined and understood epithelial and mesenchymal odontogenic lesions, which commonly arise in the gingiva and in relation to the crown of unerupted teeth, respectively. We aim to provide clearer diagnostic criteria for two poorly described entities, the odontogenic gingival epithelial hamartoma (OGEH) and the odontogenic follicular hamartoma (OFH), whilst acknowledging the spectrum of lesions which exist and where diagnostic certainty cannot be assured. Additionally, we briefly review the recent progress in understanding the inter-relationship of developing odontoma and ameloblastic fibro-odontoma with a view to suggesting helpful features which will allow for greater diagnostic certainty in this area.

The term "adenoid ameloblastoma" (AA) was formally introduced as an aggressive subtype of conventional ameloblastoma, and the name remains today despite controversies surrounding its nomenclature. As additional cases accumulated, the 2022 WHO Classification of odontogenic tumors classified AA as a distinct entity, and not a subtype of ameloblastoma. Although AA shares microscopic features with other odontogenic tumors, including adenomatoid odontogenic tumor (AOT), dentinogenic ghost cell tumor (DGCT), and odontogenic carcinoma with dentinoid (OCD), recent genetic investigations have shed light on the pathogenesis and molecular characterization of AA, confirming CTNNB1 mutations in 25% to 67% of cases. Due to the increasing histopathologic and molecular similarities between AA and DGCT, we recommend that consideration be given to renaming AA as adenoid dentinogenic ghost cell tumor to more closely reflect its biological aggressiveness and pathogenesis.

Gynecologic pathology is undergoing major changes in classification and diagnosis with recent advances in molecular pathology. Not only have advances allowed for refinement of diagnostic algorithms, but they have also translated into more targeted therapies for many patient groups. Molecular pathology is an area which necessitates ongoing review by the practicing pathologist, especially those in a multi-disciplinary setting. While the field of gynecologic pathology has many areas which are showing developments, a comprehensive review would span the length of a textbook. In this review article, the authors focus on two of the most common and therefore most applicable categories, endometrial and ovarian carcinoma. A review of the molecular underpinnings of recent developments is presented alongside new testing which is available to translate these findings into therapies for patients.

Pleomorphic sarcomas represent a heterogenous group of sarcomas characterized by marked nuclear anaplasia and overlapping high-grade morphology, often requiring ancillary studies for accurate subclassification. This category includes undifferentiated pleomorphic sarcoma, myxofibrosarcoma, and pleomorphic variants of rhabdomyosarcoma, leiomyosarcoma, and liposarcoma, as well as dedifferentiated liposarcoma and malignant PEComa, among others. Equally important are several non-sarcoma mimics, including superficial CD34-positive pleomorphic fibroblastic tumor and, perhaps most importantly, non-mesenchymal malignancies, such as undifferentiated / dedifferentiated or transdifferentiated melanoma and sarcomatoid carcinoma, which can closely resemble pleomorphic sarcomas, but require fundamentally different management. In this review, we summarize key diagnostic pearls of these entities and present a practical, algorithmic approach integrating clinical, radiologic, gross, histologic, immunohistochemical, and molecular findings to facilitate accurate classification, minimize diagnostic pitfalls, and reduce clinically significant diagnostic errors.

In the 5th edition World Health Organisation (WHO) classification of head and neck tumours, lesions that are distinctive in the jaws for reasons of presentation, behaviour or molecular changes are separated from the bone tumour classification and listed with head and neck tumours in a section on odontogenic and maxillofacial bone tumours. The molecular characterisation of these lesions has advanced recently and this narrative review discusses critically the genetic alterations in the odontogenic tumours that form bone/cementum (variable findings), giant cell-rich lesions of the jaws (sporadic giant cell granulomas with mutually exclusive TRPV4, KRAS or FGFR1 mutations, brown tumours with KRAS mutations and cherubism with SH3BP2 mutations), and bone cysts (aneurysmal bone cyst with USP6 rearrangements and simple bone cyst lacking NFATC2 rearrangement). Additionally, fibro-osseous lesions are discussed, with fibrous dysplasia harbouring GNAS mutations, familial florid cemento-osseous dysplasia, familial gigantiform cementoma and gnathodiaphyseal dysplasia sharing ANO5 mutations and psammomatoid ossifying fibroma showing SATB2 rearrangements. In most cases the changes support the current classification, but areas of uncertainty are described and differences between jaw lesions and similar lesions elsewhere in the skeleton are highlighted.

Molecular characterisation of odontogenic cysts and tumours has advanced recently and molecular pathogenesis for several tumour types is included in the 5th edition World Health Organisation (WHO) classification of head and neck tumours. This narrative review examines critically the genetic and signalling alterations reported in odontogenic cysts and tumours and groups them by the signalling pathways affected: MAPK/ERK (mostly BRAF and KRAS mutations), Wnt/beta-catenin (mostly CTNNB1 mutations) and HH (PTCH1 mutations). Odontogenic tumours characterized by gene rearrangements are also discussed. Apparent negative results and areas requiring further analysis are included. These genetic signatures illustrate the successes and limitations in interpreting molecular data for classification, diagnosis, pathogenesis, and targeted therapies for odontogenic tumours.