The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see https://doi.org/10.1016/j.acpath.2023.100086.1

Dermatologic lesions with notable eosinophilic infiltration of the head and neck region represent a diverse group of conditions, ranging from benign to malignant proliferations. We performed a comprehensive literature review focusing on head and neck dermatologic conditions that commonly present with a prominent eosinophilic infiltrate. This review provides an overview of common entities showing prominent associated eosinophilic inflammatory infiltrates in this region, including epithelioid hemangioma, eosinophilic cellulitis (Wells syndrome), eosinophilic folliculitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), granuloma faciale, and Langerhans cell histiocytosis (LCH). Eosinophils play a key role in the pathogenesis of these disorders, although the exact mechanisms remain poorly understood. Accurate diagnosis is crucial for differentiating these conditions, as they can share similar histologic features. This review aims to enhance understanding of these eosinophilic dermatologic conditions, improving diagnostic accuracy and treatment strategies.

Eosinophilia is a notable feature in various hematological malignancies, including specific types of leukemias and lymphomas that may occur in the head and neck. In hematologic malignancies, eosinophilia can be primary, driven by genetic abnormalities, or secondary, resulting from cytokine and chemokine production by the neoplastic cells or the tumor microenvironment. This review examines the association between eosinophilia and head and neck hematolymphoid malignancies including Classic Hodgkin lymphoma, T-cell lymphoblastic leukemia, mature T and NK-cell lymphomas, and Langerhans cell histiocytosis. It explores the underlying mechanisms of eosinophilia in these malignancies, highlighting the role of chemokines and cytokines such as IL-5, TARC, and eotaxin. Recognition of eosinophilia may aid in the diagnosis of these conditions and understanding the mechanisms of eosinophilia may provide insights into potential prognostic implications and treatment strategies.

Kimura disease (KD) is a rare, chronic inflammatory disorder that primarily affects the head and neck regions, often mimicking neoplastic conditions. This study aims to provide a comprehensive review of KD, focusing on its clinical presentation, diagnostic challenges, optimal management strategies, and primary histopathologic differential diagnosis. A systematic review of literature was conducted using PubMed, Scopus, and Google Scholar databases. We analyzed case reports, retrospective studies, and clinical trials published in English. We extracted data on epidemiology, clinical presentation, laboratory findings, histologic features, current understanding of the pathogenesis, treatment, and prognosis. KD predominantly affects young Asian males, presenting with painless subcutaneous masses, peripheral eosinophilia, and elevated serum IgE levels. Histopathology reveals lymphoid follicular hyperplasia with eosinophilic infiltration. Biopsy is required for diagnosis. The pathogenesis of KD is poorly understood, but recent studies have elucidated some potentially important mechanisms of the disease. Treatment options include systemic corticosteroids, surgical excision, radiotherapy, and cytotoxic therapies, with recurrence rates varying among modalities. KD remains a diagnostic challenge due to its overlapping features with a variety of neoplastic and non-neoplastic conditions. While corticosteroids offer temporary relief and can be useful in cases with renal involvement, surgical excision remains the most definitive treatment. Future research should focus on targeted therapies to improve long-term disease control and reduce recurrence.

The resurgence of measles, syphilis, and HIV presents a significant threat to global health, especially in the wake of the COVID-19 pandemic. These three infections involve lymph nodes and have unique pathologic findings in lymph nodes. We explore the pathological and clinical characteristics of these infections, focusing on their involvement of lymph nodes and their pathologic diagnosis in lymph node specimens. For HIV, lymph nodes are sites of viral replication and reservoirs, and the disease demonstrates multiple patterns within lymph nodes. The recent increase in measles, due in part to declining vaccination rates, signals the need for pathologists to be able to identify the characteristic Warthin-Finkeldey cells present in lymph node specimens. Syphilis, a reemerging sexually transmitted infection, often presents with lymphadenopathy and can mimic other conditions, complicating clinical diagnosis. By revisiting well-established findings and presenting new insights into the histopathological changes within lymphoid tissues, this review provides essential knowledge for pathologists and clinicians to improve diagnostic accuracy and treatment outcomes.

Context.— Urinary and Male Genital Tumours is the 8th volume of the World Health Organization Classification of Tumours series, 5th edition. Released in hard copy in September 2022, it presents an update to the classification of male genital and urinary tumors in the molecular age. Building upon previous volumes in this series, significant effort has been made to harmonize terminology across organ systems for biologically similar tumors (eg, neuroendocrine tumors). Genomic terminology has been standardized and genetic syndromes covered more comprehensively. This review presents a concise summary of this volume highlighting new entities, notable modifications relative to the 4th edition, and elements of relevance to routine clinical practice. Objective.— To provide a comprehensive update on the World Health Organization classification of urinary and male genital tumors, highlighting updated diagnostic criteria and terminology. Data Sources.— The 4th and 5th editions of the World Health Organization Classification of Tumours: Urinary and Male Genital Tumours. Conclusions.— The World Health Organization has made several changes in the 5th edition of the update on urinary and male genital tumors that pathologists need to be aware of for up-to-date clinical practice.

OBJECTIVES:Present-day pathologists may be unfamiliar with the histopathologic features of measles, which is a reemerging disease. Awareness of these features may enable early diagnosis of measles in unsuspected cases, including those with an atypical presentation. Using archived tissue samples from historic patients, a unique source of histopathologic information about measles and other reemerging infectious diseases, we performed a comprehensive analysis of the histopathologic features of measles seen in commonly infected tissues during prodrome, active, and late phases of the disease.METHODS:Subspecialty pathologists analyzed H&E-stained slides of specimens from 89 patients accessioned from 1919 to 1998 and correlated the histopathologic findings with clinical data.RESULTS:Measles caused acute and chronic histopathologic changes, especially in the respiratory, lymphoid (including appendix and tonsils), and central nervous systems. Bacterial infections in lung and other organs contributed significantly to adverse outcomes, especially in immunocompromised patients.CONCLUSIONS:Certain histopathologic features, especially Warthin-Finkeldey cells and multinucleated giant cells without inclusions, allow pathologists to diagnose or suggest the diagnosis of measles in unsuspected cases.

Histiocytic, dendritic, and stromal cell lesions that occur in the spleen are challenging diagnostically, not well studied due to their rarity, and therefore somewhat controversial. New techniques for obtaining tissue samples also create challenges as splenectomy is no longer common and needle biopsy does not afford the same opportunity for examination of tissue. Characteristic primary splenic histiocytic, dendritic, and stromal cell lesions are presented in this paper with new molecular genetic findings in some entities that help differentiate these lesions from those occurring in non-splenic sites, such as soft tissue, and identify possible molecular markers for diagnosis.

Oral ulcers represent a full thickness loss of the mucosal epithelium leading to exposure of the submucosal connective tissue. These are common and usually self-limited lesions, although they may sometimes result from neoplasms, most commonly squamous cell carcinoma. Lymphoproliferative disorders may be difficult to diagnose in apthous ulcers since they mimic reactive inflammation. This review presents ten rare oral lymphoid proliferations which should not be missed when assessing oral ulcer biopsies. The ten lesions include several with diagnostic cells which look similar to the histiocytes of a reactive inflammatory ulcer, including Rosai–Dorfman disease, reticulohistiocytoma, Langerhans cell histiocytosis, and traumatic ulcerative granuloma. Other lesions, such as EBV-positive mucocutaneous ulcer, extranodal marginal zone lymphoma of mucosal-associated lymphoid tissue, and plasmablastic lymphoma have lymphoid and/or plasma cell differentiation that mimic the reactive lymphocytes and plasma cells found in reactive ulcers. Two dendritic cell lesions, follicular dendritic cell sarcoma and blastic plasmacytoid dendritic cell neoplasm, both have distinct phenotypes which are required to make an accurate diagnosis. Each of these lesions are diagnosed by evaluating their histology, along with their phenotypic profile, which is sometimes enhanced by pertinent molecular findings.

Histiocytic neoplasms in the children are very rare, and histiocytoses can occur in the perinatal period. The presumed origins and presentation of specific histiocytoses in the pediatric age group are described. Common and newly described histiocytoses are presented including Langerhans cell histiocytosis, Rosai-Dorfman disease, histiocytic sarcoma, ALK positive histiocytosis, and hemophagocytic lymphohistiocytosis. Molecular findings common to pediatric histiocytoses are also discussed.

Splenic lesions are commonly discovered incidentally at imaging, without clinical signs or symptoms that may aid in diagnosis. As such, the differential diagnosis and subsequent management are based primarily on imaging characteristics. Much has been written about the myriad pathologic conditions that can occur in the spleen; however, there is little guidance on the approach to an incidental splenic mass. Applying an approach frequently used in imaging to the splenic mass-based on the number and consistency of lesions and refined by supplementary imaging features-allows formulation of a useful differential diagnosis. Solitary cystic masses include true cysts, pseudocysts, and parasitic cysts. When multiple cystic lesions are present, the differential diagnosis expands to include infectious lesions (abscess or microabscesses) and lymphangioma (a benign cystic neoplasm). Hemangioma is the most common solitary solid mass, although other vascular lesions (hamartoma, sclerosing angiomatoid nodular transformation) and nonvascular lesions (inflammatory pseudotumor, lymphoma) manifest as solitary and solid. When multiple solid masses are present, diffuse inflammatory disease (sarcoidosis), littoral cell angioma, and lymphoma should be considered. Malignancies, such as angiosarcoma or metastasis, can manifest as solitary or multiple and solid or cystic masses but are typically associated with symptoms or widespread primary malignancy. Careful assessment of the multimodality imaging characteristics of splenic lesions based on this approach aids the radiologist faced with the incidental splenic lesion. Online supplemental material is available for this article. Work of the U.S. Government published under an exclusive license with the RSNA.

Splenic B-cell lymphoma/leukemia, which is unclassifiable, includes low-grade B-cell lymphoproliferative disorders that do not fit into any other splenic lymphoid neoplasm based on current WHO classification. Presently, two provisional entities, splenic diffuse red pulp small B-cell lymphoma (SDRPL) and hairy-cell leukemia variant (HCL-v), are the most recognizable members of this group. SDRPL is an uncommon malignancy representing less than 1% of all non-Hodgkin lymphomas. Frequent clinical manifestations include splenomegaly and lymphocytosis. SDRPL is currently considered a diagnosis of exclusion and requires clinical and paraclinical correlation, including blood smear, bone marrow and spleen morphology, and the correct immunophenotype (typically positive for CD20, DBA.44, and IgG; and negative for CD5, CD10, CD23, CD43, annexin A1, CD11c, CD25, CD103, and CD123), and cytogenetic findings. Cyclin D3 is expressed in the majority of SDRPL in contrast to other types of small B-cell lymphomas. HCL-v is a less common disease accounting for 0.4% of all chronic lymphoproliferative disorders. It resembles classical HCL and SDRPL by diffusely infiltrating the splenic red pulp but is considered biologically unrelated. Splenomegaly and atypical lymphocytosis without monocytopenia are common. Distinguishing features of HCL-v include morphology, immunophenotype (the absence of CD25, CD200, CD123, annexin A1, and TRAP), genotype (wild-type BRAF), and prognosis.

CONTEXT.— Intravascular large B-cell lymphoma (IVLBCL) is a rare hematopathologic entity, posing both a clinical and histologic challenge for diagnosis. Numerous pitfalls can hinder making the diagnosis. OBJECTIVE.— To summarize recent developments in literature pertaining to IVLBCL and point out key pitfalls pathologists should be prepared to encounter. DATA SOURCES.— Literature review via PubMed search and hospital (Darnall Medical Library) resources. CONCLUSIONS.— The 3 primary pitfalls of IVLBCL include masking of IVLBCL, mimicry by IVLBCL, and mimicry of IVLBCL. These scenarios illustrate the importance of histologic pattern recognition and subsequent usage of immunohistochemistry, especially in context of a clinical history that may be noncharacteristic.

Context.-The World Health Organization Classification of Tumours: Digestive System Tumors, 5th edition, was published in 2019 and shows several impactful changes as compared with the 4th edition published in 2010. Changes include a revised nomenclature of serrated lesions and revamping the classification of neuroendocrine neoplasms. Appendiceal goblet cell adenocarcinoma is heavily revised, and intrahepatic cholangiocarcinoma is split into 2 subtypes. New subtypes of colorectal carcinoma and hepatocellular carcinoma are described. Precursor lesions are emphasized with their own entries, and both dysplastic and invasive lesions are generally recommended to be graded using a 2-tier system. Hematolymphoid tumors, mesenchymal tumors, and genetic tumor syndromes each have their own sections in the 5th edition. New hematolymphoid lesions include monomorphic epitheliotropic intestinal T-cell lymphoma; duodenal-type follicular lymphoma; intestinal T-cell lymphoma, not otherwise specified; and indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. This paper will provide an in-depth look at the changes in the 5th edition as compared with the 4th edition. Objective.-To provide a comprehensive, in-depth update on the World Health Organization classification of digestive tumors, including changes to nomenclature, updated diagnostic criteria, and newly described entities. Data Sources.-The 5th edition of the World Health Organization Classification of Tumours: Digestive System Tumours, as well as the 4th edition. Conclusions.-The World Health Organization has made many key changes in its newest update on tumors of the digestive system. Pathologists should be aware of these changes and incorporate them into their practice as able or necessary.

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.

Note: This article was posted on the Archives Web site as an Early Online Release. Early Online Release articles have been peer reviewed, copyedited, and reviewed by the authors. Additional changes or corrections may appear in these articles when they appear in a future print issue of the Archives. Early Online Release articles are citable by using the Digital Object Identifier (DOI), a unique number given to every article. The DOI will typically appear at the end of the abstract.

Lymphoid and histiocytic lesions of the head and neck in pediatric patients is a fascinating topic as most of these lesions are benign, but that the neoplastic cases are essential to diagnose accurately for appropriate treatment. It is thought that 90% of children will have palpable lymph nodes between the ages of 4 to 8; most, but not all, are non-malignant and some resolve spontaneously without treatment. This paper will look at many of the benign and malignant lesions of both lymphocytic and histiocytic origin that present in the head and neck of children focusing on their diagnostic criteria. There is a very pertinent discussion of nonmalignant lymphoid proliferations, as infections and other reactive conditions dominate the pathology of pediatric lymphohistiocytic head and neck lesions. Discussion of those lymphomas which arise more frequently in the head and neck focuses on those seen in children and young adults such as classic Hodgkin lymphoma and Burkitt lymphoma, as well as new more controversial entities such as pediatric-type follicular lymphoma. Histiocytic lesions, both benign and malignant, are described and may be challenging to diagnose.