Seminars in Diagnostic Pathology

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. Varying sized cysts and sheets composed of three cell types (epidermoid, intermediate, and mucous cells) with varying degrees of atypia form the characteristic histological appearance of MEC. MEC frequently contains a wide variety of modified tumor cells and can be entirely cystic or completely solid. Under these circumstances, MEC requires critical differentiation from many mimickers, ranging from simple cysts and benign tumors to high-grade carcinomas...

Orbital inflammatory diseases represent a heterogenous group of idiopathic, autoimmune-related, and sometimes neoplastic conditions with overlapping clinical and histopathologic features, as well as variable levels of IgG4-positive plasma cells detected within tissue biopsies. Some histopathologic features, especially in an appropriate clinical context, may point to a specific diagnosis in a given patient. Diagnoses of non-specific orbital inflammation, orbital inflammation related to autoimmune diseases such as granulomatosis with polyangiitis and IgG4-related disease, lymphoma, and xanthogranulomatous diseases are discussed, contrasted and illustrated...

IgG4-related kidney disease (IgG4-RKD) encompasses all forms of kidney disease that are part of IgG4-related disease (IgG4-RD). First recognized as IgG4-related tubulointerstitial nephritis (IgG4-TIN), and then IgG4-related membranous glomerulonephritis (IgG4-MGN), we now recognize additional patterns of interstitial nephritis, glomerular disease, and vascular disease that can be seen as part of IgG4-RKD. The clinical presentation is variable and can include acute or chronic kidney injury, proteinuria or nephrotic syndrome, mass lesion(s), and obstruction...

No abstract text is available yet for this article.

With the growing recognition of IgG4-related hepatobiliary disease, establishing a definitive diagnosis relies mainly on a combination of clinical findings, serological markers, and imaging modalities. However, the role of histopathological evaluation remains indispensable, particularly in cases necessitating differential diagnosis or malignancy exclusion. While diagnosing IgG4-related hepatobiliary disease through surgical resection specimens is often straightforward, pathologists encounter substantial challenges when evaluating biopsies...

IgG4-related disease (IgG4-RD) is an immune-mediated condition affecting nearly any organ. This review focuses on the nuances of diagnosing IgG4-RD affecting the head and neck. Salivary gland involvement, especially of the submandibular glands, often permits a definitive diagnosis on biopsy. However, elevated IgG4+ plasma cells are nonspecific and can be seen in chronic sialadenitis, lymphoma, and other mimics. Careful correlation of clinical and pathological findings is essential. Given the significant overlap with chronic sinusitis, IgG4-RD of the sinonasal region is difficult to diagnose histologically...

Autoimmune pancreatitis (AIP) is classified into type 1 (IgG4-related) and type 2 (IgG4-unrelated) and the interpretation of pancreatic biopsy findings plays a crucial role in their diagnosis. Needle biopsy of type 1 AIP in the acute or subacute phase shows a diffuse lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and the infiltration of many IgG4-positive plasma cells. In a later phase, changes become less inflammatory and more fibrotic, making interpretations more challenging. Confirmation of the lack of 'negative' findings that are unlikely to occur in type 1 AIP (e...

IgG4-related disease (IgG4-RD) is a relatively novel fibroinflammatory condition characterized typically by dense lymphoplasmacytic inflammation, storiform fibrosis and obliterative venulitis, together with prominent IgG4+ plasma cells and an IgG4+/IgG+ plasma cell ratio of >40 %. The diagnosis is usually made on a combination of clinical and serological features together with characteristic radiological and histological appearances. The condition may be limited to a single tissue/organ (e.g., autoimmune pancreatitis) or may be multicentric in nature - four clinical 'patterns' of disease distribution have recently been described...

The recognition of immunoglobulin G4-related disease (IgG4-RD) as an entity in the pancreaticobiliary tract was followed by a slew of papers describing inflammation and fibrosis containing IgG4-positive plasma cells in a variety of sites including the respiratory tract, leading to the hypothesis that these abnormalities were attributable to IgG4-RD. Predictably, pathologists began to see requests from clinicians to perform IgG4 immunohistochemistry in lung biopsies "to rule out IgG4-RD". Several years later, the notion that IgG4-RD would prove to be the underlying cause of a wide array of fibroinflammatory lesions in the lung has not panned out as promised...

Microscopes, more than any other instrument, reflect advances in clinical medicine over the past several hundred years. As the primary tool of the pathologist, they were, and continue to be, a key connector between the bedside and basic sciences. One specific example is the science of clinical dermatology, which relies on clinical-pathologic correlation to make a definitive diagnosis. The microscopes used by pathologists, however, are more than scientific artifacts. Many antique microscopes are hand-crafted works of art...

Mark Wick made a wide range of contributions to the field of mediastinal pathology. Early papers amplified the spectrum of neuroendocrine carcinomas of the thymus and brought attention to the aggressive nature of this tumor, also highlighting the occurrence of coexisting carcinoid tumor and small cell carcinoma of this organ. The controversial issue of thymoma classification was addressed in several papers and editorial comments, while also reporting a case of metastatic thymoma. A series of thymic carcinomas as well a report on the unusual clear cell variant bear his name as one of the authors...

No abstract text is available yet for this article.

Birt-Hogg-Dubé syndrome (BHD) represents a rare autosomal dominant tumor predisposition syndrome characterized by skin lesions, lung cysts, and renal tumors. The predominant histological subtypes of BHD-related renal tumors include hybrid oncocytoma-chromophobe tumors, oncocytomas, and chromophobe renal cell carcinomas, all exhibiting eosinophilic/oncocytic features. Immunohistochemistry staining for KIT (CD117) and CK7 exhibits variability in these tumor types. Germline mutations in FLCN have been consistently identified...

The unenlightened clinician may submit a skin specimen to the lab and expect an "answer." The experienced clinician knows that in performing skin biopsies, it is critical to select the most appropriate: 1) anatomic location for the biopsy1 , 2 ; 2) type of biopsy1 , 2 ; 3) depth and breadth of the biopsy; and 4) medium for hematoxylin and eosin staining (formalin) or direct immunofluorescence (Michel's Transport Medium or normal saline).2 Demographic information, anatomic location, clinical context, and differential diagnosis are all critical components of a properly completed requisition form...

The curriculum vitae of Dr. Mark R. Wick contains 57 peer-reviewed publications, 3 editorials, 6 book chapters and a whole book dedicated to diseases of the lung and pleura. It is remarkable that such productivity should represent only a small portion of the overall output of Dr. Wick, which includes (at last count) 341 original peer-review publications, 119 invited review articles, 93 book chapters, 42 editorials, 3 society-related position papers, 18 books and 2 interactive video disks. Yet, his contributions to the literature in pulmonary and pleural pathology have been significant and influential and have established for him a national and international reputation as one of the leading experts in pulmonary pathology...

IgG4-related lymphadenopathy is a nodal manifestation of IgG4-related disease (IgG4RD) which is characterized by increased polytypic IgG4+ plasma cells and IgG4+/IgG+ plasma cell ratio in lymph nodes and morphologically manifested as various patterns of reactive lymphadenopathy: Castleman disease-like, follicular hyperplasia, interfollicular expansion, progressive transformation of germinal centers and inflammatory pseudotumor-like. It typically presents with solitary or multiple, mild to moderate lymph node enlargement in otherwise asymptomatic patients...

Succinate dehydrogenase (SDH), formed by four subunits SDHA, SDHB, SDHC, SDHD, and an assembly factor SDHAF2, functions as a key respiratory enzyme. Biallelic inactivation of genes encoding any of the components, almost always in the presence of a germline mutation, causes loss of function of the entire enzyme complex (so-called SDH deficiency) and subsequent development of SDH-deficient neoplasms which include pheochromocytoma/paraganglioma, gastrointestinal stromal tumor, and renal cell carcinoma (RCC). These tumors may occur in the same patient or kindred...

Hereditary papillary renal cell carcinoma (HPRCC) is an autosomal dominant syndrome characterized by the occurrence of bilateral and multifocal, classic type papillary renal cell carcinomas. In the recent decades, extensive molecular studies have narrowed the molecular underpinnings of this syndrome to missense mutations in tyrosine kinase domain of MET proto-oncogene. Although MET mutations are specific to HPRCC, it has been found in sporadic papillary renal cell carcinomas and as recently reported, in biphasic squamoid alveolar variant of papillary renal cell carcinoma...

Multiple hereditary syndromes predispose to kidney cancer, including Von Hippel-Lindau syndrome, BAP1-Tumor Predisposition Syndrome, Hereditary Papillary Renal Cell Carcinoma, Tuberous Sclerosis Complex, Birt-Hogg-Dubé syndrome, Hereditary Paraganglioma-Pheochromocytoma Syndrome, Fumarate Hydratase Tumor Predisposition Syndrome, and Cowden syndrome. In some cases, mutations in the genes that cause hereditary kidney cancer are tightly linked to similar histologic features in sporadic RCC. For example, clear cell RCC occurs in the hereditary syndrome VHL, and sporadic ccRCC usually has inactivation of the VHL gene...

von Hippel-Lindau (VHL) disease is characterized by biallelic inactivation of the VHL gene leading to abnormal or absent VHL protein function, and constitutive activation of hypoxia-inducible factors (HIF) that leads to pro-tumorigenic signaling. Individuals with VHL disease develop numerous cysts and tumors involving multiple organs including the kidneys, central nervous system, endolymphatic sac, lungs, pancreatobiliary system, adrenal glands, epididymis, and/or broad ligament. On histologic examination, these lesions show morphologic overlap as they are frequently characterized by cells with clear cytoplasm and prominent vascularity...