Surgical Pathology Clinics

Oncotherapeutic agents can cause a wide range of liver injuries from elevated liver functions tests to fulminant liver failure. In this review, we emphasize a newer generation of drugs including immune checkpoint inhibitors, protein kinase inhibitors, monoclonal antibodies, and hormonal therapy. A few conventional chemotherapy agents are also discussed.

The liver is involved in many multisystem diseases and commonly may manifest with abnormal liver chemistry tests. The liver test perturbations may be multifactorial in nature, however, as patients are receiving many different medications and can also have intrinsic liver disease that may be exacerbated by the systemic disorder. Some disorders have typical histologic findings that can be diagnosed on liver biopsy, whereas others will show a more nonspecific histology. Clinicians should be aware of these conditions so as to consider the performance of a liver biopsy at the most opportune time and setting to help establish the diagnosis of acute or chronic liver disease...

The development of liver dysfunction in patients having various systemic diseases is common and has a broad differential diagnosis, at times being the initial manifestation of the disorder. Liver injury associated with systemic lupus erythematosus is heterogeneous and may present with nonspecific histology. Differentiating autoimmune hepatitis from lupus hepatitis is challenging on histologic grounds alone. Other systemic diseases that may present mostly with nonspecific findings are rheumatoid arthritis and celiac disease...

Liver fibrosis staging has many challenges, including the large number of proposed staging systems, the heterogeneity of the histopathologic changes of many primary liver diseases, and the potential for slight differences in histologic interpretation to significantly affect clinical management. This review focuses first on fibrosis regression. Following this, each of the major categories of liver disease is discussed in regard to (1) appropriate fibrosis staging systems, (2) emerging concepts, (3) current clinical indications for liver biopsy, (4) clinical decisions determined by fibrosis stage, and (5) histologic challenges and pitfalls related to staging...

This article focuses on how hepatologists view the role of liver biopsy in diagnosis, assessment, and management of chronic and acute liver disease, and its variable use among different etiologies of liver disease and in the evaluation of liver fibrosis.

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Lymphoma is a clinically and biologically heterogeneous disease. Next-generation sequencing (NGS) has expanded our understanding of this heterogeneity at the genetic level, refining disease classification, defining new entities, and providing additional information that can be used in diagnosis and management. This review highlights some of the NGS findings in lymphoma and how they can be used as genetic biomarkers to aid diagnosis and prognosis and guide therapy.

Therapeutic monoclonal antibodies (therapeutic mAb) and adoptive immunotherapy have become increasingly more common in the treatment of hematolymphoid neoplasms, with practical implications for diagnostic flow cytometry. Their use can reduce the sensitivity of flow cytometry for populations of interest owing to downregulation/loss of the target antigen, competition for the target antigen, or lineage switch. Expanded flow panels, marker redundancy, and exhaustive gating strategies can overcome this limitation...

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and is a heterogeneous disease with variable patient outcomes. A multidisciplinary technical evaluation, including flow cytometry, immunohistochemistry, molecular and cytogenetic analyses, can comprehensively characterize a patient's leukemia at diagnosis, identify important prognostic biomarkers, and track measurable residual disease; all of which can impact patient management. This review highlights the key concepts, clinical significance, and main biomarkers detectable with each of these technical approaches; the contents are a helpful resource for medical practitioners involved in the workup and management of patients with CLL...

Genetic characterization of myeloma at diagnosis by interphase fluorescence in situ hybridization and next-generation sequencing (NGS) can assist with risk stratification and treatment planning. Measurable residual disease (MRD) status after treatment, as evaluated by next-generation flow cytometry or NGS on bone marrow aspirate material, is one of the most important predictors of prognosis. Less-invasive tools for MRD assessment such as liquid biopsy approaches have also recently emerged as potential alternatives...

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...

Cutaneous lymphomas encompass a heterogeneous group of neoplasms with a wide spectrum of clinical presentations, histopathologic features, and prognosis. Because there are overlapping pathologic features among indolent and aggressive forms and with systemic lymphomas that involve the skin, clinicopathologic correlation is essential. Herein, the clinical and histopathologic features of aggressive cutaneous B- and T-cell lymphomas are reviewed. Indolent cutaneous lymphomas/lymphoproliferative disorders, systemic lymphomas, and reactive processes that may mimic these entities are also discussed...

Pathologic staging including assessment of margins is essential for the proper management of patients with breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). As most patients present with effusion, cytologic examination with immunohistochemistry and/or flow cytometry immunophenotyping are essential for diagnosis. Upon a diagnosis of BIA-ALCL, en bloc resection is recommended. When a tumor mass is not identified, a systematic approach to fixation and sampling of the capsule, followed by pathologic staging and assessment of margins, is essential...

Hodgkin lymphoma is a B-cell neoplasm that typically presents with localized, nodal disease. Tissues are characterized by few large neoplastic cells, usually comprising less than 10% of tissue cellularity, present in a background of abundant nonneoplastic inflammatory cells. This inflammatory microenvironment, although key to the pathogenesis, can make diagnosis a challenge because reactive conditions, lymphoproliferative diseases, and other lymphoid neoplasms may mimic Hodgkin lymphoma and vice versa. This review provides an overview of the classification of Hodgkin lymphoma, its differential diagnosis, including emerging and recently recognized entities, and strategies to resolve challenging dilemmas and avoid diagnostic pitfalls...

This review summarizes the current understanding of mature T-cell neoplasms predominantly involving lymph nodes, including ALK-positive and ALK-negative anaplastic large cell lymphomas, nodal T-follicular helper cell lymphoma, Epstein-Barr virus-positive nodal T/NK-cell lymphoma, and peripheral T-cell lymphoma (PTCL), not otherwise specified. These PTCLs are clinically, pathologically, and genetically heterogeneous, and the diagnosis is made by a combination of clinical information, morphology, immunophenotype, viral positivity, and genetic abnormalities...

Although pediatric hematopathology overlaps with that of adults, certain forms of leukemia and lymphoma, and many types of reactive conditions affecting the bone marrow and lymph nodes, are unique to children. As part of this series focused on lymphomas, this article (1) details the novel subtypes of lymphoblastic leukemia seen primarily in children and described since the 2017 World Health Organization classification and (2) discusses unique concepts in pediatric hematopathology, including nomenclature changes and evaluation of surgical margins in selected lymphomas...

Follicular lymphoma (FL) is a lymphoid neoplasm composed of follicle center (germinal center) B cells, with varying proportions of centrocytes and centroblasts, that usually has a predominantly follicular architectural pattern. Over the past decade, our understanding of FL has evolved significantly, with new recognition of several recently defined FL variants characterized by distinct clinical presentations, behaviors, genetic alterations, and biology. This manuscript aims to review the heterogeneity of FL and its variants, to provide an updated guide on their diagnosis and classification, and to describe how approaches to the histologic subclassification of classic FL have evolved in current classification schemes...

Sources of immune deficiency and dysregulation (IDD) are being increasingly recognized and defined, as are IDD-related B-cell lymphoproliferative lesions and lymphomas occurring in these patients. In this review, basic biology of Epstein-Barr virus (EBV) as it relates to classification of EBV-positive B-cell lymphoproliferative disorders (LPDs) is reviewed. Also discussed is the new paradigm of classification of IDD-related LPDs adopted by the fifth edition World Health Organization classification. IDD-related EBV-positive B-cell hyperplasias, LPDs, and lymphomas are discussed with particular attention to unifying and unique features that assist with recognition of these IDD-related lesions and their classification scheme...

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 and is associated with pronounced hematopathologic findings. Peripheral blood features are heterogeneous and very often include neutrophilia, lymphopenia, myeloid left shift, abnormally segmented neutrophils, atypical lymphocytes/plasmacytoid lymphocytes, and atypical monocytes. Bone marrow biopsies and aspirates are often notable for histiocytosis and hemophagocytosis, whereas secondary lymphoid organs may exhibit lymphocyte depletion, pronounced plasmacytoid infiltrates, and hemophagocytosis...

Lymphadenopathy occurring in patients with immunoglobulin G4 (IgG4)-related disease, termed IgG4-related lymphadenopathy, shows morphologic heterogeneity and overlap with other nonspecific causes of lymphadenopathy including infections, immune-related disorders, and neoplasms. This review describes the characteristic histopathologic features and diagnostic approach to IgG4-related disease and IgG4-related lymphadenopathy, with comparison to nonspecific causes of increased IgG4-positive plasma cells in lymph nodes, and with emphasis on distinction from IgG4-expressing lymphoproliferative disorders...