Soft tissue tumors are a relatively rare and diagnostically challenging group of neoplasms that can have varying lines of differentiation. Accurate diagnosis is important for appropriate treatment and prognostication. In the 8 years since the publication of the 4th Edition of World Health Organization (WHO) classification of soft tissue tumors, significant advances have been made in our understanding of soft tissue tumor molecular biology and diagnostic criteria. The 5th Edition of the 2020 WHO classification of tumors of soft tissue and bone incorporated these changes. Classification of tumors, in general, but particularly in soft tissue tumors, is increasingly based on the molecular characteristics of tumor types. Understanding tumor molecular genetics improves diagnostic accuracy for tumors that have been difficult to classify on the basis of morphology alone, or that have overlapping morphologic features. In many large hospitals in the United States and Europe, molecular tests on soft tissue tumors are a routine part of diagnosis. Therefore, surgical pathologists should be familiar with newly emerging molecular genetic techniques in clinical settings. In the near future, molecular tests, particularly in soft tissue tumor diagnosis, will become as routine during diagnosis as immunohistochemistry is currently. This new edition provides an updated classification scheme and essential diagnostic criteria for soft tissue tumors. Newly recognized entities and subtypes of existing tumor types, several reclassified tumors, and newly defined molecular and genetic data have been incorporated. Herein, we summarize the updates in the WHO 5th Edition, focusing on major changes in each category of soft tissue tumor, and the newly described tumor entities and subtypes.

Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other mesenchymal and nonmesenchymal bone lesions can complicate diagnosis. Accurate histologic diagnosis is crucial for appropriate management and prognostication. Since the publication of the fourth edition of the World Health Organization (WHO) classification of tumors of soft tissue and bone in 2013, significant advances have been made in our understanding of bone tumor molecular biology, classification, prognostication, and treatment. Detection of tumor-specific molecular alterations can facilitate the accurate diagnosis of histologically challenging cases. The fifth edition of the 2020 WHO classification of tumors of soft tissue and bone tumors provides an updated classification scheme and essential diagnostic criteria for bone tumors. Herein, we summarize these updates, focusing on major changes in each category of bone tumor, the newly described tumor entities and subtypes of existing tumor types, and newly described molecular and genetic data.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that is characterized by a proliferation of myofibroblastic and fibroblastic spindle cells, accompanied by an inflammatory infiltrate that is abundant in plasma cells, lymphocytes, and eosinophils. IMT can arise in various anatomical locations but most commonly occurs in the abdominal cavity, retroperitoneum, and lung, particularly in children and young adults. IMT typically demonstrates local invasion or recurrence, whereas metastasis is rare. IMTs pose a diagnostic challenge because of their overlapping morphological characteristics with a heterogeneous group of nonneoplastic and neoplastic lesions. Precise diagnosis is crucial for optimal management and accurate prognostication. Despite recent advancements in IMT diagnosis and treatment, its biological complexity and clinical management remain challenging due to significant histological heterogeneity and molecular genetic diversity. This review provides comprehensive updates on the clinical, molecular, and pathological characteristics of IMT, highlighting the diagnostic approaches and key differential diagnoses.

Retroperitoneal sarcomas are a heterogenous group of rare tumors arising in the retroperitoneum. Retroperitoneal sarcomas comprise approximately 10% of all soft tissue sarcomas. Though any soft tissue sarcoma histologic types may arise in the retroperitoneal space, liposarcoma (especially well-differentiated and dedifferentiated types) and leiomyosarcoma do so most commonly. Retroperitoneal sarcomas are diagnostically challenging, owing to their diversity and morphological overlap with other tumors arising in the retroperitoneum. An accurate diagnosis is necessary for correct management and prognostication. Herein, we provide an update on the diagnostic approach to retroperitoneal sarcomas and review their key histologic findings and differential diagnoses.

Hepatocellular carcinoma (HCC) is a primary liver cancer characterized by hepatocellular differentiation. HCC is molecularly heterogeneous with a wide spectrum of histopathology. The prognosis of patients with HCC is generally poor, especially in those with advanced stages. HCC remains a diagnostic challenge for pathologists because of its morphological and phenotypic diversity. However, recent advances have enhanced our understanding of the molecular genetics and histological subtypes of HCC. Accurate diagnosis of HCC is important for patient management and prognosis. This review provides an update on HCC pathology, focusing on molecular genetics, histological subtypes, and diagnostic approaches.

Context.—: Spindle cell neoplasms arising in the skin comprise a heterogeneous group of tumors with divergent lineages. Cutaneous spindle cell neoplasms are relatively common and present surgical pathologists with diagnostic challenges. Recognition of their histopathologies is important for correct diagnosis and management. The current review presents a pattern-based diagnostic approach to common cutaneous spindle cell neoplasms that often cause diagnostic difficulties. Objective.—: To provide a useful guide for diagnosis of cutaneous spindle cell neoplasms. Data Sources.—: PubMed (US National Library of Medicine) reports and the authors' personal experiences are reviewed. Conclusions.—: The authors briefly summarize the histologic features and differential diagnoses of common cutaneous spindle cell neoplasms.