Surgical Pathology Clinics

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Mesenchymal neoplasms of the liver can be diagnostically challenging, particularly on core needle biopsies. Here, I discuss recent updates in neoplasms that are specific to the liver (mesenchymal hamartoma, undifferentiated embryonal sarcoma, calcifying nested stromal-epithelial tumor), vascular tumors of the liver (anastomosing hemangioma, hepatic small vessel neoplasm, epithelioid hemangioendothelioma, angiosarcoma), and other tumor types that can occur primarily in the liver (PEComa/angiomyolipoma, inflammatory pseudotumor-like follicular dendritic cell sarcoma, EBV-associated smooth muscle tumor, inflammatory myofibroblastic tumor, malignant rhabdoid tumor)...

Intrahepatic cholangiocarcinoma is a challenge to the practicing surgical pathologist for several reasons. It is rare in many parts of the world, and thus practical exposure may be limited. Related to the fact of its rarity is the fact that more common tumors which frequently metastasize to the liver can be morphologically indistinguishable (eg, pancreatic ductal adenocarcinoma). Immunohistochemical testing is generally non-contributory in this context. Other difficulties arise from the protean morphologic manifestations of cholangiocarcinoma (ie, small duct vs...

Needle core biopsies of liver lesions can be challenging, particularly in cases with limited material. The differential diagnosis for well-differentiated hepatocellular lesions includes focal nodular hyperplasia, hepatocellular adenoma, and well-differentiated hepatocellular carcinoma (HCC) in noncirrhotic liver, while dysplastic nodules and well-differentiated HCC are the primary considerations in cirrhotic liver. The first part of this review focuses on histochemical and immunohistochemical stains as well as molecular assays that are useful in the differential diagnosis...

Hepatic inflammatory pseudotumor (IPT) describes a mass lesion composed of fibroblasts or myofibroblasts with a dense inflammatory infiltrate comprising lymphocyte, plasma cells, and histiocytes. These lesions are presumed to be an exuberant response to an infectious organism, although in most cases the causative agent is unknown. In specific circumstances, pathologists should consider ancillary techniques to exclude specific infections, such as mycobacteria, Candida, or syphilis. IgG4-related disease may cause a plasma-cell rich IPT...

Although cirrhosis is one of the most common causes of portal hypertension, noncirrhotic portal hypertension can result from hemodynamic perturbations occurring in the prehepatic, intrahepatic, and posthepatic circulation. Intrahepatic portal hypertension can be further subclassified relative to the hepatic sinusoids as presinusoidal, sinusoidal, and postsinusoidal. For many of these differential diagnoses, the etiology is known but the cause of idiopathic noncirrhotic portal hypertension, recently included in porto-sinusoidal vascular disease (PSVD), remains poorly understood...

Pathologists face many challenges when diagnosing sclerosing biliary lesions on liver biopsy. First, histologic findings tend to be nonspecific with similar to identical features seen in numerous conditions, from benign to outright malignant. In addition, the patchy nature of many of these entities amplifies the inherent limitations of biopsy sampling. The end result often forces pathologists to issue descriptive sign outs that require careful clinical correlation; however, certain clinical, radiologic, and histologic features may be of diagnostic assistance...

Hematopoietic stem cell transplantation is used to treat a variety of hematologic malignancies and autoimmune conditions. The immunosuppressive medications as well as other therapies used both before and after transplantation leave patients susceptible to a wide spectrum of complications, including liver injury. Causes for liver damage associated with stem cell transplantation include sinusoidal obstruction syndrome, graft-versus-host disease, iron overload, and opportunistic infection. Here, the authors review the clinical and pathological findings of these etiologies of liver injury and provide a framework for diagnosis...

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...