IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies

Reappraisal of Morphological Differences between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-Deficient Renal Cell Carcinoma

Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the overlapping morphology found among these clinically aggressive infiltrating high-grade adenocarcinomas of the kidney, reproducible differences in morphology emerged between these categories after rigorous characterization. Finally, we recommend that definitive diagnosis of CDC should only be made if RMC and FH-deficient RCC are excluded

IgG4-related Disease of the Genitourinary Tract

IgG4-related disease (IgG4-RD) is a recently established albeit well recognized fibro-inflammatory condition with distinctive features including a characteristic histopathological appearance; a propensity to develop tumefactive lesions in multiple body sites; and oft elevated serum IgG4 levels. The consensus statement on IgG-4 RD equips practicing pathologists with a set of working guidelines for the diagnosis of pathologic lesions identified in a host of different organ system affected with this disease. The diagnosis of IgG4-RD requires the combined presence of the characteristic histopathological appearance and increased numbers of IgG4-positive plasma cells. The essential histopathological features include a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. Tissue IgG4-positive plasma cell counts and IgG4: IgG ratios are significant ancillary aids in establishing the diagnosis. The spectrum of IgG4-RD continues to expand and involve multiple body sites. The genitourinary system comprising of the kidneys, ureters, urinary bladder, urethra, prostate gland, testes and penis is one of the multiple organ systems to be affected by IgG4-RD. This review describes the clinical and histopathologic patterns of involvement of the genitourinary system by IgG4-RD, in association with serologic and radiological features. [J Interdiscipl Histopathol 2014; 2(1.000): 3-18

Dry Nonproductive Cough as the Presenting Symptom of Giant Cell Arteritis

Giant cell arteritis (GCA) is a systemic vasculitis affecting medium-sized and large-sized vessels. The disease most commonly affects the cranial branches of arteries originating from the aortic arch

Comprehensive cardiopulmonary life support (CCLS) for cardiopulmonary resuscitation by trained paramedics and medics inside the hospital

The cardiopulmonary resuscitation (CPR) guideline of comprehensive cardiopulmonary life support (CCLS) for management of the patient with cardiopulmonary arrest in adults provides an algorithmic step-wise approach for optimal outcome of the patient inside the hospital by trained medics and paramedics. This guideline has been developed considering the infrastructure of healthcare delivery system in India. This is based on evidence in the international and national literature. In the absence of data from the Indian population, the extrapolation has been made from international data, discussed with Indian experts and modified accordingly to ensure their applicability in India. The CCLS guideline emphasise the need to recognise patients at risk for cardiac arrest and their timely management before a cardiac arrest occurs. The basic components of CPR include chest compressions for blood circulation; airway maintenance to ensure airway patency; lung ventilation to enable oxygenation and defibrillation to convert a pathologic 'shockable' cardiac rhythm to one capable to maintaining effective blood circulation. CCLS emphasises incorporation of airway management, drugs, and identification of the cause of arrest and its correction, while chest compression and ventilation are ongoing. It also emphasises the value of organised team approach and optimal post-resuscitation care

Compression-only life support (COLS) for cardiopulmonary resuscitation by layperson outside the hospital

The cardiopulmonary resuscitation (CPR) guidelines of compression-only life support (COLS) for management of the victim with cardiopulmonary arrest in adults provide a stepwise algorithmic approach for optimal outcome of the victim outside the hospital by untrained laypersons. These guidelines have been developed to recommend practical, uniform and acceptable resuscitation algorithms across India. As resuscitation data of the Indian population are inadequate, these guidelines have been based on international literature. The guidelines have been recommended after discussion among Indian experts and the recommendations modified to ensure its practical applicability across the country. The COLS emphasises on early recognition of cardiac arrest and activation, early chest compression and early transfer to medical facility. The guidelines emphasise avoidance of any interruption of chest compression, and thus relies primarily on chest compression-only CPR by laypersons

Basic cardiopulmonary life support (BCLS) for cardiopulmonary resuscitation by trained paramedics and medics outside the hospital

The cardiopulmonary resuscitation guideline of Basic Cardiopulmonary Life Support (BCLS) for management of adult victims with cardiopulmonary arrest outside the hospital provides an algorithmic stepwise approach for optimal outcome of the victims by trained medics and paramedics. This guideline has been developed considering the need to have a universally acceptable practice guideline for India and keeping in mind the infrastructural limitations of some areas of the country. This guideline is based on evidence elicited in the international and national literature. In the absence of data from Indian population, the excerpts have been taken from international data, discussed with Indian experts and thereafter modified to make them practically applicable across India. The optimal outcome for a victim with cardiopulmonary arrest would depend on core links of early recognition and activation; early high-quality cardiopulmonary resuscitation, early defibrillation and early transfer to medical facility. These links are elaborated in a stepwise manner in the BCLS algorithm. The BCLS also emphasise on quality check for various steps of resuscitation