Table of contents :

degenerations intracellular extracellular cell senescence cell death apoptosis oncosis necrosis gangrene

• degenerations
• intracellular or plasmatic degenerations
• atrophic degeneration
• albuminoideal degenerations / cloudy swelling : a term formerly applied to an early stage of toxic degenerative changes, especially in the protein constituents of organs in infectious diseases. The tissues appear swollen, parboiled, and opaque, but revert to normal when the cause is removed. At the cellular level, it is characterized by slight swelling of the cell and granularity and cloudiness of the cytoplasm.
• mucous degeneration : a form in which mucus accumulates in epithelial tissues.
• mucinoid, mucinous or myelinic degeneration : a term used to include both mucoid and colloid degeneration
• mucoid degeneration : degeneration accompanied by deposition of myelin and lecithin in the cells
• colloid or gelatiniform degeneration : the assumption by the tissues of a gumlike or gelatinous character
• cylindrical confronting cisternae : cytoplasmic structures often associated with tuboreticular structures in cells in a variety of pathological conditions including immunologic and neoplastic disorders, neurodegenerative diseases, and viral infections.
• vacuolar degeneration : the formation of vacuoles in the cells of a tissue
• hyaline or vitreous degeneration / hyalinosis : a regressive cellular change in which the cytoplasm takes on a homogeneous glassy eosinophilic appearance.


Also used loosely to describe the histologic appearance of tissues (in kidney tubules), e.g. in hyaline droplet degeneration of glomeruli :

• sclerotic degeneration : a variety of hyaline degeneration affecting connective tissue, especially the intima of arteries.
• hydropic or ballooning degeneration : the swelling of cells caused by the accumulation of intracellular water in response to cell injury


• lipoidal degeneration : a condition somewhat resembling fatty change but in which the extraneous material is lipoid
• foamy degeneration : foamy, swollen hepatocytes containing bile
• fatty degenerations / steatoses / lipidoses :
• triglyceridoses :
• hereditary triglyceridoses
• microvesicular steatosis / microsteatosis : fatty change in which numerous small lipid droplets are present in the cytoplasm


• foamy cells, histiocytes, or macrophages look foamy because of loss of lipid droplets during tissue fixation


• macrovesicular steatosis / macrosteatosis : fatty change in which a single large droplet occupies most of the cell, displacing the cytoplasm and nucleus to a ring around the droplet


• phospholipidoses :
• hereditary phospholipidoses
• sphingolipidoses :
• hereditary sphingolipidoses
• mucopolysaccharidoses :
• hereditary mucopolysaccharidoses
• cholesterinoses
• aspecific lysosomal thesaurismoses :
• hereditary lysosomal thesaurismoses
• zebra bodies : concentric, laminated, cytoplasmic inclusions of Schwann cells, occurring singly or in clusters as a result of degeneration phenomena in lysosomes of patients with Fabry disease


• glycogenoses :
• hereditary glycogenoses
• corneal degeneration of the epithelium / keratoses :
• hyperkeratoses
• parakeratoses
• dyskeratoses
• corneal metaplasia
• demyelination / demyelinization / myelinolysis / myelolysis : destruction, removal, or loss of the myelin sheath of a nerve or nerves
• axon or axonal reaction / axonal, Nissl, or retrograde degeneration : the series of changes in a neuron following the severing of its axon, including central chromatolysis with displacement of the nucleus => axonopathies
• distal axonopathy : the more common kind of axonopathy, in which the disease process starts centrally and proceeds towards the periphery
• secondary or wallerian degeneration : fatty degeneration of a segment of nerve fiber distal to a site of axonal transection beginning 4 to 10 days after severing from its nutritive centers, occurring in small axons before large axons. Before degeneration the distal axon segment may remain electrically excitable. Accumulation of organelles & mitochondria in paranodal regions near injury within hours => loss of structure of ER => degradation of neurofilaments associated with influx of calcium and activation of calpain, swelling of mitochondria, fragmented axon is phagocytosed; widening of Schmidt-Lantermann incisura in myelin => paranodal myelin retraction => myelin collapse and forms myelin ovoids.


Schwann cells proliferate and form Büngner's bands / Ledbänder (> 3 mm; bands of syncytium formed by the union of Schwann cells and processes within irregular basement membrane, which provides substrate for axonal regeneration)

If axonal regeneration does not occur Schwann cells atrophy and disappear. Blood-derived macrophages invade transected nerve 3 to 4 days after transection, appear as foamy cells after phagocytosis of sudanophilic (lipid) debris, and persist for 3 to 7 months. Fibroblasts proliferate during first week, migrate adjacent to degenerating fibers and produce some collagen. Integrity of blood-nerve barrier is reestablished over months. Adhesion proteins ninjurin1  and 2 are upregulated in nerve distal to transection
• ascending degeneration : wallerian degeneration affecting centripetal nerve fibers and progressing toward the brain or spinal cord
• apparatus of Perroncito / Perroncito's spirals : a mass of fibrils in the form of spirals and networks with newly formed axons which develop in the cut stump of a nerve during regeneration
• proximal axonopathy : axonopathy in which the disease process starts at the periphery and proceeds towards the center
• dying-back : degeneration of an axon beginning distally and progressing to more proximal areas
• abnormal mitochondria
• selective damage of the mitochondria (i.e., extreme swelling seen on electron microscopy) is the essential lesion of true Reye's syndrome
• parking-lot crystals inside mitochondria are a hallmark of the genetic diseases of mitochondria, in which a portion of their genetic code is faulty. Abnormal creatine kinase is being synthesized and accumulating. Most of these diseases show up primarily in muscle, and the sick mitochondria proliferating around the edges of the worse-involved fibers create a ragged red fiber : muscle fibers characterized by large collections of structurally abnormal mitochondria below the sarcolemmal surface and within the fiber itself that stain red with Gomori trichrome stain; seen in mitochondrial encephalopathy, mitochondrial myopathy and occasionally in other myopathic disorders.


Progression : mild to moderate mitochondrial proliferation (red rim & speckled sarcoplasm) => marked mitochondrial proliferation. Mitochondria have replaced most other structures in one of the muscle fibers. Muscle fibers with mitochondrial proliferation stain darkly for succinic dehydrogenase (SDH) (the most sensitive stain for detecting mitochondrial proliferation), have a clear external rim on H & E stain, increased lipid. Muscle fibers with excessive SDH staining have reduced or absent cytochrome oxidase (COX) staining
• Hürthle cells (oncocytes, Ashkenazy cells, oxyphil cells) have their cytoplasm so packed with mitochondria that there is little room for anything else. Seen in diseases of parathyroid, salivary glands, apocrine glands, ...


• giant mitochondria / megamitochondria of the alcoholic's liver


• elementary or inclusion bodies / inclusions : round, oval, or irregular-shaped bodies occurring in the cytoplasm and nuclei of cells of the body, as in disease caused by filtrable virus infection such as rabies, smallpox, herpes, etc.. Normal inclusions are described in the physiology section, e.g. :
• Birbeck granules (also in histiocytosis X)
• Weibel-Palade bodies (also in blood vessel cancers)
• Herring bodies
• Reinke crystals (in Leydig's cells of testis and ovarian hilus) : pseudotubular hexagonal structures (30 nm) with electrondense component (with longitundinal striae) and electrontransparent component
• Charcot-Bottcher crystalloid body : a body seen near the nuclei of the cells of the seminiferous tubules.
• aggresome : a distinct pericentriolar structure consisting of stable, high molecular weight, detergent-insoluble, multiubiquitinated molecules formed when the capacity of the proteasome is exceeded by the production of aggregation-prone misfolded proteins^ref : e.g. inhibition of proteasome function prevents the degradation of unassembled presenilin-1 molecules leading to their aggregation and deposition in aggresomes. Intact microtubules are required for their formation, accompanied by redistribution of the intermediate filament protein vimentin to form a cage surrounding a pericentriolar core of aggregated, ubiquitinated protein. A frameshift mutation of ubiquitin (UBB(+1)), proteasomal subunits b₅ (a catalytic subunit of the 20S proteasome) and Tbp7 (an ATPase subunit of the 26S proteasome), transglutaminase, tubulin, heat shock proteins 90 HSP70 and HSP90B are found in Mallory bodies. Ubiquitin-binding protein p62 / sequestosome 1 is encoded by an immediate-early response gene that rapidly responds to a variety of extracellular signals involved in cell proliferation, differentiation, and particularly oxidative stress : it acts as an adapter in signal transduction and binds noncovalently to ubiquitin, possibly being involved in the regulation of the fate of ubiquitinated proteins by segregation (i.e., sequestosome or aggresome formation). The general role of p62 in the cellular response to misfolded proteins is substantiated by detection of p62 in other cytoplasmic inclusions, such as neurofibrillary tangles, Lewy bodies, Rosenthal fibers, intracytoplasmic hyaline bodies in hepatocellular carcinoma, and a₁-antitrypsin aggregates. The presence of p62 along with other stress proteins and ubiquitin in cytoplasmic inclusions indicates deposition as aggregates as a third line of defense against misfolded proteins in addition to refolding and degradation.
• Mallory bodies
• mutant huntingtin acts within the nucleus to induce neurodegeneration of striatal neurons, but intranuclear inclusions may reflect a cellular mechanism to protect against huntingtin-induced cell death^ref. Neurons die in a time-independent fashion but one that is dependent on mutant huntingtin dose and polyglutamine expansion; many neurons die without forming an inclusion body. Rather, the amount of diffuse intracellular huntingtin predicts whether and when inclusion body formation or death will occur. Surprisingly, inclusion body formation predicts improved survival and leads to decreased levels of mutant huntingtin elsewhere in a neuron. Thus, inclusion body formation can function as a coping response to toxic mutant huntingtin^ref.
• apoptotic bodies : membrane bound spherical structures in apoptosis


• Councilman's bodies or lesions : apoptotic bodies of hepatocellular origin seen in viral hepatitis, YFV, and other hepatic diseases


• apoptotic or necrobiotic neutrophil
• Michaelis-Gutmann (M-G) bodies : lamellated bull's-eye (targetoid ) basophilic (by means of von Kossa stain) extracytoplasmic or intracytoplasmic membrane-bound calcospherites of variable size and density containing a central crystalline core surrounded by less dense peripheral concentric alternating rings containing undigested bacterial fragments; seen in degenerated foamy histiocytes (von Hansemann cells) with ample cytoplasm containing abundant PAS⁺ granules. As the infection progresses, the central cores increase content of calcium, iron, and mucopolysaccharides. M-G bodies are sometimes difficult to identify by light microscopy underlying the rule of the immunohistochemical and the ultrastructural studies to perform the diagnosis. The principal disorder is probably a monocytic-macrophagic bactericidal defect in immunocompromised hosts


Seen in malacoplakia / malakoplakia (MKP) : a rare, granulomatous, inflammatory disease leading to the formation of soft patches on the mucous membrane of a hollow organ.
• pulmonary malacoplakia in Rhodococcus equi pneumonia
• cutaneous malacoplakia. It occurs mainly in visceral or orificial areas (perineal localization); the condition is rarely purely cutaneous, and appears to be extremely rare in childhood
• Escherichia coli^ref
• tuberculous cervical lymphadenopathy^ref
• streptococcus (group B)^ref
• gastrointestinal malacoplakia
• focal malakoplakia in chronic periapical periodontitis^ref
• malakoplakia of the stomach
• malakoplakia of the pancreas
• colonic malacoplakia
• malakoplakia of the mesocolon
• malakoplakia of the cecum^ref
• in association with ulcerative colitis^ref or rectal adenocarcinoma^ref
• urogenital tract
• genital malacoplakia
• ovarian malacoplakia
• malacoplakia of the endometrium
• malocoplakia of the prostate
• malacoplakia of the epididymis
• malakoplakia of the testis
• urinary malacoplakia^ref
• renal malacoplakia in a transplanted kidney^ref
• ureteral malacoplakia
• malacoplakia vesicae
• retroperitoneal malacoplakia^ref
• malakoplakia of bone
Therapy : if possible, immunosuppressive drugs should be stopped. Quinolone antibiotic treatment and surgical excision or incision and drainage lead to the highest cure rates (90% and 81%, respectively). Specific intracellular penetration of quinolone antibiotics is a possible reason for the higher cure rate achieved with these antibiotics. Bethanechol has been suggested to correct the supposed fundamental disturbance by increasing the intrecellular cyclic guanosine monophosphate concentration, but there is still no convincing evidence of its clinical efficacy. Immunosuppressive regime of prednisolone and azathioprine in infant^ref
• Curschmann's spirals : coiled spiral shaped mucinous fibrils sometimes found in the sputum of patients with (tracheo)bronchial asthma or other COPD


• Charcot-Leyden crystals / asthma crystals (in eosinophils) : elongated needle-shaped birefringent crystals in the form of 2 hexagonal pyramids joined base to base, derived from eosinophil lysophospholipase released from the plasma membranes of disintegrating eosinophils; seen in serous fluids such as the bronchial secretions in (tracheo)bronchial asthma or eosinophilic pneumonia and in stools in some cases of intestinal parasitism


• hepatocyte inclusions
• Mallory bodies (MBs) are hyaline aggresomes that form in hepatocytes in many different chronic liver diseases. Toxic bile acids have a key role in the regulation of hepatocytic CK expression and MB formation.


• ground-glass cells : hepatocytes stained for [HBsAg]


• Councilman's bodies or lesions
• Russell bodies
• Dutcher-Fahey body (DB)
• Rosenthal fibers : eosinophilic masses seen throughout the CNS, particularly just under the pia mater and near blood vessels, in Alexander's disease; they may be the remains of degenerated neuroglial cells.


• neuronal inclusions
• paired helical filaments (PHF) : insoluble aggregates of microtubule-associated protein (MAP) tau which are the constituent of neurofibrillary tangles (NFT) (Alzheimer's neurofibrillary degeneration) in neurons in Alzheimer disease (AD)


• diffuse neurofibrillary tangles with calcification (DNTC) is associated with accumulation of both tau and a-synuclein
• Hirano bodies are eosinophilic, rod-like, highly-refractile (paracrystalline) actin filament-containing inclusions found predominantly adjacent to pyramidal neurons which are often affected by cytoplasmic granulovacoular degeneration (CGD) in the hippocampal CA1 sector with increasing age and are particularly numerous in Alzheimer disease (AD), Pick's disease (PiD), Parkinson-dementia complex and tropical spastic paraparesis (TSP). The shapes of the Hirano bodies vary from small ovoid structures to longer, narrow bodies (5-10 mm in width; 10-30 mm in length). They contain a variety of cytoskeletal proteins :
• F-actin : recently it has been reported that a proportion of the actin in Hirano bodies at least exists as a fragmented form called "fractin" after it has been attacked by the apoptosis protease caspase which cleaves actin at to form two peptides and revealing a peptide (YELPD) against which antibodies were made.  Hirano bodies are different from many other actin structures in that they bind both ADF/cofilin and phalloidin, normally mutually exclusive actin-binding agents. Depending on the section at the E.M. level, Hirano bodies appear to be sets of parallel filaments with equally distanced nodes or associated with feathery projections.
• a-actinin (an actin-filament bundling protein)
• ADF/cofilin (actin-binding severing proteins)
• b-APP (C-terminal : the principle component of Alzheimer's plaques)
• FAC1 (normally a  nuclear protein)
• HCNP (a brain signalling molecule)
• Hsp27 (a chaperonin that also binds actin)
• iNOS
• MAP1
• MAP2
• neurofilament proteins (an intermediate filament protein)
• microtubule-associated protein (MAP) tau
• Tropomyosin (an actin binding protein that regulates interactions with myosin)
• vinculin A (component of the focal adhesion complex that also binds actin)
They have been found in different tissues of experimental animals and, on rare occasions, in glial cells, peripheral nerve axons, extraocular muscles of elderly individuals and in muscle fibers of patients with type II glycogenosis / Pompe's disease. On the contrary of Lewy bodies, Hirano bodies do not contain ubiquitin.

• granulovacuolar bodies of Simchowicz / cytoplasmic granulovacoular degeneration (GVD) (CGD) : are small vacuoles in hippocampal pyramidal neurons. Each vacuole measures about 4 mm in diameter and contains a dense hematoxylinophilic central granule (composed of tubulin and neurofilament proteins) measuring about 1 mm in diameter surrounded by a negatively stained halo. Neurons may contain one or many of these bodies.


• multilamellar bodies (MLB) in tropical spastic paraparesis (TSP)
• Papp-Lantos filaments in oligodendroglia and neurons in multiple system atrophy (MSA)
• perikaryal threads : fine thread-like structures in the neuronal perikarya in the hypothalamus and brainstem nuclei
• axonal spheroids containing abnormally accumulated neurofilaments (normal axons are thin and brown stained elongated structures in the rest of the picture illustrating how tremendously swollen the axon containing the spheroid is) in Hallervorden-Spatz disease and amyotrophic lateral sclerosis (ALS), and neuroaxonal leucoencephalopathy with spheroids (NALS)


• pale bodies (PBs) / colloid (hyaline) inclusion bodies seen in the substantia nigra in idiopathic Parkinson's disease (PD)

‡
• Lewy bodies (LB) : concentrically laminated, eosinophilic round inclusions found in vacuoles in the neuronal perikaryon, around 10 mm in size. Its dense core is surrounded by a clear halo of radiating filaments that can be seen in electron micrographs, which is lacking in the so-called "cortical Lewy bodies". Numerous proteins have been identified in LBs, among which the 3 neurofilament isoforms, ubiquitin and proteasome subunits. More recently, a-synuclein --a pre-synaptic protein--has been found to be the essential constituent of the LB. LBs and Lewy-related dystrophic neurite (accumulation of a-synuclein in neuronal processes) are indeed to be found in many extra-nigral areas of the CNS and PNS : stellate ganglia, cardiac and enteric plexus, pigmented nuclei of the brainstem, basal nucleus of Meynert, amygdala, limbic nuclei of the thalamus, parahippocampal and cingulate gyri, insula and isocortex. Lewy body diseases (LBD) is a progressive neurological disorder with parkinsonism, having many LBs and degenerative changes. LBD is classified into the 3 types according to the distribution of LBs :
• Lewy body disease of brain-stem type is identical to classical idiopathic Parkinson's disease (PD)
• Lewy body disease of transitional type is named Parkinson disease dementia in which Lewy lesions are found in the brainstem and are also abundant in the isocortex. A large number of senile plaques is frequently associated
• Lewy body disease of diffuse type is nominated as diffuse Lewy body disease (DLBD)
• Lewy body variant of Alzheimer's disease (AD) (LBV) : Lewy bodies (LBs) and Lewy-related dystrophic neurites, neuritic plaques (NP) and sometimes neurofibrillary tangles (NFT)
=> dementia with Lewy bodies (DLB), the same lesions are observed but the cognitive deficit occurs first or shortly (< 1 year) after the motor symptoms.
• pure autonomic failure
• neuroaxonal dystrophies
• various amyloidoses and tauopathies
10-30% of necropsies have LBs.

• Pick bodies (PiB) in degenerating cortical neurons of patients with Pick's disease (PiD). They are homogeneous, smooth-edged, and intensely argyrophilic intracytoplasmic inclusions consisting of microtubule-associated protein (MAP) tau and paired helical filaments (PHF). Several PBs are flame shaped, however the large majority are round or ovoid. NFT are more often flame-shaped, have distinct filamentous substructure with irregular edges and lucencies within them, and exhibit variable argyrophilia.


• glial cytoplasmic inclusions (GCI) : within the cytoplasm, but not the meylinated extensions, of oligodendrocytes; argyrophilic granule-associated filaments of about 25 nm in diameter are the predominant constituents, and a-synuclein is selectively present in these filaments. Seen in  multiple system atrophy (MSA).


• neuronal cytoplasmic inclusions (NCI) : rare a-synuclein⁺ in multiple system atrophy
• amyotrophic lateral sclerosis (ALS)
• Lewy body-like hyaline inclusion (LBHI) / hyaline conglomerate (HC) inclusion is a large multifocal accumulation of neurofilaments, a characteristic neuropathological marker of mutant SOD1-linked FALS with posterior column involvement : they also occur as astrocytic hyaline inclusions (Ast-HIs)
• ALS-type inclusions are skeins or small dense filamentous aggregates which can only be demonstrated by ubiquitin immunocytochemistry (ICC)
• proteinopathies
• serpinopathies : accumulation of specifically mutant alleles of serine proteinase inhibitor or serpin superfamily member due to an aberrant conformational transition within the protein and the formation of chains of polymers that tangle within the secretory pathway within hepatocytes
• a₁-antitrypsin severe deficiency variant is the Z allele, which results in the accumulation of mutant protein within hepatocytes. This 'protein overload' causes neonatal hepatitis, cirrhosis and hepatocellular carcinoma. The lack of circulating plasma a₁-antitrypsin results in early-onset panlobular emphysema.
• antithrombin deficiency results in thrombosis
• C1-inhibitor deficiency results in angio-oedema
• a₁-antichymotrypsin deficiency results in emphysema
• neuroserpin results in the retention of polymers within neurones to cause the inclusion body dementia, familial encephalopathy with neuroserpin inclusion bodies (FENIB)
• alpha-synucleinopathies : a group of disorders having in common the abnormal deposition of a-synuclein
• in the cytoplasm of neurons or glial cells :
• in idiopathic Parkinson's disease (PD) and dementia with Lewy bodies (DLB), a-synuclein is the main component of Lewy bodies and dystrophic neurites; a-synuclein also accumulates in the cytoplasm of glial cells
• in multiple system atrophy (MSA), a-synuclein conforms the cytoplasmic oligodendroglial inclusions and the neuronal inclusions which are the hallmark of this disease
• in Hallervorden-Spatz disease
• in extracellular deposits of amyloid : the amyloidogenic fragment 61-95 amino acids of alpha-synuclein is the non-Ab component of senile plaque amyloid in Alzheimer disease (AD)
3-nitrotyrosine  is not a prerequisite for alpha-synuclein deposition^ref. Accumulations of a-synuclein in all these disorders have in common a fibrillar configuration, but they differ in the binding of a-synuclein to distinct proteins with the exception of ubiquitin whose binding to a-synuclein is common to all a-synuclein inclusions. The mechanisms leading to a-synuclein fragmentation and aggegation into extracellular amyloid are not known, although a-synuclein fragment and bA4 aggregates are the result of abnormal cleavage of large precursors. On the other hand, several studies have shown that a-synuclein may adopt a fibrillar conformation and give rise to insoluble forms and high molecular weight aggregates in vitro. Similar complexes have also been observed in a-synucleinopathies. Although studies in vitro and in vivo have shown toxic effects of a-synuclein, the consequence of a-synuclein deposition on cell survival in a-synucleinopathies is not known.
• tauopathies / taupathies (accumulation of microtubule-associated protein (MAP) tau in neurons)

tau isoform / disease	Alzheimer disease (AD)	progressive sopranuclear palsy (PSP) and corticobasal degeneration (CBD)	Pick's disease (PiD)	Dic1
74
69	x	x
64	x	x	x	x
60	x		x	x

• infectious inclusions (in infected cells)
• viral inclusions
• intracytoplasmic viral inclusions
• Negri bodies : oval or round inclusion bodies, seen in the cytoplasm and sometimes in the processes of nerve cells of rabid animals or patients with rabies after death; their presence is considered conclusive proof of rabies virus. Best viewed with Seller's stain.
• lyssa bodies : red staining masses somewhat resembling Negri bodies but less sharply defined and with less internal structure.

• orthopoxviruses : seen in the cells of the affected tissues and in ectodermal cells of the chorioallantoic membrane after hematoxylin-eosin stain
• A-type inclusion bodies : numerous large, homogenous, acidophilic (eosinophilic) inclusios with halo, consisting of the 3’ end of late mRNAs of the ati gene, generated by endoribonucleolytic cleavage at a specific site in the primary transcript.
• Borrell bodies : particles of fowlpox virus; aggregates of Borrel body's in infected cells result in the formation of Bollinger's bodies or granules : relatively large, spheroid or ovoid, usually somewhat granular, acidophilic, intracytoplasmic inclusion body's observed in the infected tissues of birds with fowlpox virus; when body's are ruptured large numbers of fowlpox virus particles are released


• Henderson-Paterson's bodies / molluscum bodies : ellipsoidal, large homogeneous intracytoplasmic inclusion containing numerous virions in the cells of the stratum spinosum (granulosum) and stratum corneum infected with molluscum contagiosum virus, which contain replicating virions and cellular debris. With H+E, the molluscum body is eosinophilic in the stratum spinosum and pale blue in the stratum corneum


• B-type inclusion bodies / Guarnieri's bodies or corpuscles : pale-red, irregular, hematoxylinophilic, stain reddish purple with Giemsa stain, and contain Feulgen-positive material. Another rapid but relatively insensitive test for Guarnieri bodies in vesicular scrapings is Gispen's modified silver stain, in which cytoplasmic inclusions appear black.
• Paschen bodies, corpuscles or granules : inclusion bodies in the cells of the tissues in variola and vaccinia; they are infective but whether they are the infective agents or mechanical carriers of the invisible virus is not known
• Prowazek's bodies : extremely small inclusion bodies found in the material from smallpox pustules and in cowpox vaccine and regarded by Prowazek as the cause of the disease.
• Torres-Teixeira bodies : inclusion bodies found in the cells in variola minor

A number of nucleated erythrocytes are in the ectoderm and free in the mesoderm, and the surface of the pock is ulcerated
• intranuclear viral inclusions
• Cowdry type A or type I inclusion bodies : intranuclear eosinophilic amorphous inclusions surrounded by a clear halo beneath the nuclear membrane; they are composed of nucleic acid and protein seen in cells infected with HHV-1 / HSV-1 (Lipschütz bodies or inclusions, both in the epithelial cells of the primary skin lesion (skin or cornea) and in the affected nerve cells), HHV-2 / HSV-2, HHV-3 / VZV, HHV-5 / CMV, or SSPE virus


• Cowdry type B inclusion bodies :
• basophilic : adenovirus
• acidophilic : in anterior horn cells in poliomyelitis
• Joest-Degen inclusion bodies : single or multiple eosinophilic intranuclear bodies in neurons, sometimes in glia cells, in Borna disease virus


• basophilic inclusions : from papillomaviruses
• JC virus => intranuclear inclusions in the oligodendrocytes (large, different Cowdry inclusions).
• SV40
• both intranuclear and intracytoplasmic
• measles virus
• owl-eye inclusions : HHV-5 / CMV, HHV-1 / HSV-1, HHV-2 / HSV-2
• Councilman bodies and Torres bodies : YFV
• bacterial  inclusions (in infected cells)
Halberstädter or Halberstaedter-Prowazek-Greeff or trachoma bodies : paranuclear semilunar inclusion bodies found in clusters in the cytoplasm of the epithelial cells from the conjunctiva of a trachomatous eye (Chlamydiophila trachomatis) or in RES cells infected with Chlamydiophila pneumoniae
Lindner's initial bodies : cytoplasmic elementary bodies, resembling those in trachomatous epithelia, found in inclusion conjunctivitis of newborns
Tygeson bodies : irregular bodies in RES cells infected with Chlamydiophila pneumoniae
Miyagawa’s bodies or granulocorpuscles : buboes from LGV
Lygranum antigen : LGV
Gamna-Favre bodies : small intracytoplasmic inclusion bodies found in LGV
Babes-Ernst metachromatic granules : poly-P_i granules in Corynebacterium diptheriae
Mooser bodies : bodies resembling rickettsiae, seen in the epithelial cells of the tunica vaginalis exudate in some forms of typhus
Neill-Mooser bodies : large mononuclear cells filled with rickettsiae, seen in the inflammatory exudate of the scrotal swelling of laboratory animals infected with Rickettsia typhi (Neill-Mooser reaction).
Ross's bodies : spherical copper-colored bodies showing dark granulations and sometimes having ameboid movements; seen in the blood and tissue fluids in syphilis.
Winkler's bodies : spherical bodies seen in the lesions of syphilis
Donovan bodies : Klebsiella granulomatis


protozoal inclusions
• cytorrhyctes : cell inclusions, found in various diseases, which may be specific protozoan pathogens, or they may be manifestations of cell reactions to the parasite causing the disease, or they may be degenerations caused by the disease
• Leishman-Donovan bodies / amastigote : kala–azar


• Mott cell / mulberry, berry, grape, or morular cell
asteroid bodies : sporotrichosis
inclusions in granulomas
asteroid bodies (eosinophilic inclusions) : irregulary stellate (star-shaped) inclusion body with numerous rays radiating from a central core. May be seen in cytoplasm of giant cells in granulomas of various entities but are most frequently encountered in the giant cells of foreign body granulomas and sarcoidosis. Structure strongly resembling asteroid bodies may be seen rarely in the cytoplasm of tumor giant cells and in fibrin-rich exudates.


crystalline inclusions : colorless refractile crystals composed predominantly of calcium oxalate are frequently found in the giant cells of granulomas of sarcoidosis and other diseases. E.g. calcium oxalate crystals :


In some cases they may serve as the nidus for deposition of calcium leading to formation of ...
Schaumann's (conchoid) bodies : iron- and calcium-containing, red to brown, laminated inclusion bodies found in the cytoplasm of giant cells in sarcoidosis and other granulomatoses (berylliosis), often containing refractile calcium oxalate crystals. Although usually intracytoplasmic they may, if numerous or very large, be extruded into the extracellar space.


slit-like (cholesterol) crystals : these are occasionally seen in granulomas of various types


Hamazaki-Wesenberg (H-W) bodies : although these structures may occasionally occur as inclusions within giant cells, they are usually found extracellulary in the sinusoids of granuloma-containing lymph nodes in sarcoidosis as well as in non-granulomatous lymph nodes from patients with sarcoidosis and other conditions. They are oval or spindle-shaped, range up to several microns in size, and stain yellow-brown with H&E. The pigment appears to be  lipofuscin. Ultrastructural studies have shown that H-W bodies are giant lysosomes and residual bodies. They are acid-fast and stain with silver stains as well as a variety of other stains. When visualized with silver stains H-W bodies can be easily mistaken for budding yeasts due to clustering of individual bodies


Lafora bodies : large intracytoplasmic inclusions occurring in Lafora myoclonus epilepsy. They are seen in neurons of CNS, muscles, myocardium, other viscera but constantly in epatocytes, therefore the liver biopsy is diagnostic. The inclusions are large, consists of aggregates of randomly arranged glycoprotein and acid mucopolysaccharide fibrils 60 Å in diameter, occupy the entire cytoplasm, granular as ground glass cells but surrounded by a halo. They are seen typically in the periportal area. They may be confused with ground glass cells, glycogenosis type IV and drug inclusions (disulfiram and cyanamide). When in doubt, TEM study becomes crucial.



LE or haematoxylin bodies : a dense, homogeneous, cyanophilous particle consisting of the denatured nuclear material of an injured cell together with a small amount of cytoplasm, occurring in systemic lupus erythematosus (SLE); lymphocytes that ingest such particles are known as LE cells
asbestos or asbestosis bodies are golden yellow ferruginous bodies whose central core is asbestos surrounded by precipitated acidic polysaccharides and hemosiderin (visible). They have enlarged endings (dumbell or balance-wheel look) and resist after tissue incineration : they can be stained with Prussian blue.



Bright's granulations : the granulations seen in chronic interstitial nephritis.
pyroninophilic granulations : structures seen in liver and other cells, which stain red with methyl green–pyronine by Pappenheim's stain; they are one of the early effects of carbon tetrachloride poisoning.
Virchow's granulations : granulations containing ependymal and glial fibers, found in the walls of the cerebral ventricles in general paresis.
RBC inclusions
granulocyte inclusions
• extracellular or metaplasmatic degenerations
• fibrosis / fibrous degeneration : the formation of fibrous tissue, as in repair or replacement of parenchymatous elements.
• postfibrinous fibrosis : fibrosis occurring in tissues in which fibrin has been deposited.
• neoplastic or proliferative fibrosis : fibrosis in which the fibrous elements continue to proliferate after the original causative factor has ceased to operate
• replacement fibrosis : the development of fibrous tissues to replace tissue that has been damaged.
• cirrhosis
• fibrinous degeneration : necrosis with deposit of fibrin within the cells of the tissue.
• myxoid change / mucous degeneration : increased ground substance
• throughout much of the body in hypothyroidism (myxedema)
• pretibial myxedema in Graves' disease
If there is associated damage to the connective tissue fibers, we use the term myxomatous degeneration ("myxoid degeneration")
• cystic medial necrosis
• mitral valve prolapse (MVP) / Barlow's disease / floppy mitral valve
• myxoid change of the intima narrows the renal arteries in scleroderma and Balkan endemic nephropathy (BEN)
• fibrinoid degeneration : deposition of fibrin and other plasma proteins in the walls of arterioles, often accompanied by an inflammatory infiltrate within the walls and thrombosis of the vessel lumen


Aetiology :
• hypertension
• afferent renal arterioles in malignant hypertension
• pulmonary arterioles in primary PAH
• type III hypersensitivity reactions
• radiation injury to vessels appears as hyaline-fibrinoid in vessel walls. Early, there may be some inflammation and/or necrosis. Later, the vessels look more subdued, but the lumen continues to narrow throughout the patient's life-span.
• Splendore-Hoeppli phenomenon : little pink-staining club-shaped things around actinomyces colonies, fungus masses, schistosome eggs, and occasionally other organic-based foreign bodies
• spironolactone bodies : found in the mineralocorticoid-producing cells of the adrenal gland in people treated with X-rays. They are hyaline, laminated things, up to 15 microns, derived from S.E.R.
• in kidney disease, entire glomeruli "hyalinize". Depending on the disease, these dead glomeruli are replaced by basement membrane-mesangial matrix, collagen, and/or plasma proteins
• uratic degeneration : degeneration marked by the deposit of urates or uric acid.
• amyloidoses / b-fibrilloses / diseases of abnormal polymerization (DAP) / amyloid degeneration / glassy swelling
• sporadic
• hereditary
• transmissible
• iatrogenic
The main lesion consists of depots of ...
• b-pleated sheet conformation fibrils (undegradable by proteases, can be detected with
• green birifrangence under polarizing light acquired after Congo red staining


• Lugol reactive
• PAS
• methachromasia
Aetiology :
• reactive systemic amyloidosis / secondary amyloidosis / amyloidosis acute phase (AA) : precursor is serum amyloid A component (SAA). GAGs are heparan sulfate proteoglycans (HSPG) : they lose affinity for Congo red after KMnO₄ treatment. It deposits on blood vessels linings, kidney, spleen and liver
• familial Mediterranean fever (FMF)
• familial hibernian fever (FHF)
• APRs
• Mycobacterium tuberculosis
• Mycobacterium leprae
• osteomyelitis
• bronchiectasias
• bed sores
• infected burns
• rheumatoid arthritis (RA)
• juvenile chronic arthritis (JCA)
• amyloidosis chronic hemodyalisis / dialysis-related amyloidosis (DRA) / hemodialysis-associated amyloidosis (Ab₂M) : precursor is b₂-microglobulin which cannot be removed from the blood by dialysis. It deposits in the joints, synovial membranes, and tendon sheaths. Manifestations include carpal tunnel syndromeand arthritis
• hereditary amyloidosis / familial amyloidosis / heredofamilial amyloidosis : a group of amyloidoses, usually found in limited geographic areas, and characterized by widespread tissue involvement indistinguishable from the reactive systemic form and by the presence of fibrillar proteins of the AA type. Most have autosomal dominant inheritance, the exception being familial Mediterranean fever, which is autosomal recessive. Based on the principal sites of amyloid deposition, it is classified in the following 4 major subtypes :
• familial amyloid polyneuropathies (FAP) / hereditary neuropathic amyloidosis
• AApoAI : precursor is apoA-I
• familial AApoAI : G26R, W50R, L60R, L90P, D61-7 with VT insertion AApoAI
• aortic
• ACys : precursor is cystatin C (familial (Icelandic))
• AFib : a chain of fibrinogen (familial : R254L, E526V, or R554L)
• AGel : precursor is gelsolin
• familial AGel (Finnish) : 187
• ALys : precursor is lysozyme (familial : I56T, D67H)
• nephropathies
• cardiopathies
• amyloidosis transthyretin (ATTR) : precursor is transthyretin  / thyroxin-binding prealbumin (TBPA)
• familial ATTR
• Portuguese-Swedish : V30M
• Japanese : L30P
• Danish : L111M
• systemic senile ATTR
• tenosynovitis
• light chain (AL) amyloidosis (ALA) / immunocyte-derived amyloidosis : k chain (25-33%) or l chain (66-75%). It is a plasma cell disorder in which the deposition of L chain causes progressive organ failure. It occurs in 10-15% of multiple myelomas (micromolecular myeloma, soft tissue myeloma, plasma cell leukemia) and 20-25% of light chain diseases. Sometimes precipitated light chains don't form b-fibrils (k chains more common than l chains). The median survival of patients with AL amyloidosis is only 13 mo from diagnosis. Because this aggressive disease is characterized by the deposition of Ig L chains produced by clonal plasma cells, therapeutic approaches have been based on the use of alkylating agents active against multiple myeloma (MM). However, the median survival is still only 17-18 mo, in contrast to 3 years in MM without AL amyloidosis. The pathogenesis of fibril formation from Ig L chains in AL amyloidosis is unknown. Because the majority of AL amyloid fibrils contain N termini of V region with only small amounts of C region, it is thought that the variable domains plays an important role in the formation of pathological fibrils. In most of the trials with alkylating agents, patients who experienced reductions in their serum or urine monoclonal proteins had significantly prolonged survival compared with nonresponders. Therefore, treatment suppressing the production of amyloid fibrils precursor protein could improve the prognosis of AL amyloidosis.
• amyloid beta (AB), precursor is b-amyloid precursor protein (APP / AbPP)
• amyloid plaques (AP) / argyrophil, neuritic, or senile plaques : microscopic argyrophilic masses composed of fragmented axon terminals and dendrites surrounding a core of amyloid, microtubule-associated protein (MAP) tau and a-synuclein; seen in small amounts in the cerebral cortex of normal elderly people and in larger amounts in those with Alzheimer's disease (AD). Alzheimer neuritic plaques are often adjacent to capillaries or larger blood vessels that have accumulated beta/A4-amyloid in the both subarachnoid and parenchymal vessel walls (cerebral amyloid angiopathy).


Amyloid fibrils commonly exhibit multiple distinct morphologies in electron (EM) microscope and atomic force microscope (AFM) images, often within a single image field. By using EM and solid-state NMR measurements on fibrils formed by the 40-residue ß-amyloid peptide of Alzheimer's disease (Aß_1–40), it has been shown that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Aß_1–40 fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials^ref.
• punch-drunk encephalopathy / boxer's dementia
• senile amyloidosis / amyloidosis of aging (Dutch) : that seen in the elderly and usually involving the heart, brain, pancreas, or spleen.
• amyloidosis endocrine (AE)
• AANF : precursor is ANP
• ACal : precursor is precalcitonin (medullary thyroid carcinoma)
• AIAPP : precursor is amylin / IAPP (insulinomas and type II diabetes mellitus)
• AIns : precursor is exogenous insulin
• APro : precursor is prolactin (prolactinoma or aging)
• ALac : precursor is lactoferrin (cornea)
• APrP^Sc : transmissible spongiform encephalopathies (TSE) : precursor is p27-30^{CD230 / prion protein / PrPc}
• medin is the main constituent of aortic medial amyloid that occurs in virtually all individuals > 60. It is derived from a proteolytic fragment of lactadherin, a mammary epithelial cell expressed glyco-protein that is secreted as part of the milk fat globule membrane. It was previously demonstrated that an octapeptide fragment of medin (NH₂-NFGSVQFV-COOH) forms typical well-ordered amyloid fibrils^ref.
• amyloid P (AP), whose precursor is serum amyloid P component (SAP) (a globular protein in basal membranes)
Laboratory examinations :
• fine-needle aspiration of abdominal fat pad (FNAFP)
• Congo red test : Congo red is injected intravenously; if > 60% of the dye disappears after 1 hour, amyloidosis is indicated.
• paramyloidosis : accumulation of an atypical form of amyloid in tissues
Experimental animal models : casein IV injection in mice for systemic amyloidosis.
• heavy-chain deposition disease (HCDD) :
• light-chain deposition disease (LCDD) : k chain (85%) or l chain (15%)

Aetiology :
• multiple myeloma or lymphoproliferative disease
• no evidence of neoplastic plasma cell proliferation (50%)
Symptoms & signs : renal insufficiency, proteinuria, and nephrotic syndrome
Laboratory examinations : deposition in multiple organs of monoclonal, amorphous, noncongophilic light chains that do not exhibit a fibrillar structure when examined ultrastructurally; a monoclonal protein of the same light-chain type is usually demonstrated in serum or urine, but approximately 25% of patients have no demonstrable light chain in serum or urine by immunoelectrophoresis or immunofixation. Even in the absence of a monoclonal light chain in serum or urine, immunofluorescence usually demonstrates a monoclonal population of plasma cells in the bone marrow of these patients. Serum amyloid P component (SAP), present in all amyloids, is absent from LCDD
• rare cases of combined LCDD and amyloid L have been reported
• light and heavy chain deposition disease (LHCDD)
• dyschromatosis / pathological pigmentations / pigmental degeneration : pigmentary degeneration,   that in which cells of affected tissue become abnormally pigmented
• endogenous pigmentations
• exogenous pigmentations
• calcifications
• dystrophic calcification
• psammoma bodies : spherical, concentrically laminated mass of calcareous material, usually of microscopic size due to necrosis followed by dystrophic calcification. They are found in ...
• benign and malignant epithelial and connective-tissue tumors
• serous cystadenocarcinoma. Nanobacteria promote crystallization of psammoma bodies in ovarian cancer^ref. Archebacteria such as nanobacteria are, for example, involved in kidney stone formation. Nanobacteria deserve close scrutiny as their cytotoxicity and ability to cross the placenta present a potential clinical risk.
• serous endometrial papillary carcinoma
• diffusely sclerosing variant of papillary thyroid carcinoma
• transitional meningioma
• chronic inflammation

• metastatic calcification / calcareous metastasis : the deposit of calcareous material in remote tissues in the event of extensive resorption of osseous tissue in caries, malignant neoplasms, and so on.
• corpora amylacea / amylaceous or amyloid bodies or corpuscles / colloid corpuscles / corpora versicolorata / polyglucosan bodies : small basophilic, PAS⁺, hyaline masses, 5–50 mm in diameter, derived from degenerate cells or inspissated secretions and consisting of a central nidus surrounded by concentric lamellae. They occur in
• prostate (and semen)
• neuroglia
• pulmonary alveoli
... and become more numerous with advancing age - in particular past 50. They may undergo calcification; their significance is not known.

• Valentin's corpuscles : small amyloid bodies sometimes found in nerve tissue.
• supracellular degenerations
• paraphysiological
• Hassall's corpuscles
• pathological
• multinucleate giant cells
• Warthin-Finkeldey giant cells : lymphoreticular origin, intranuclear inclusions, seen in various organs, including lymph nodes, tonsil, appendix, and thymus, just prior to or during the prodromal phase of measles virus infection


• Tzanck cells : a degenerated epithelial cell caused by acantholysis, and found especially in pemphigus, HHV-1 / HSV-1, HHV-2 / HSV-2, HHV-3 / VZV with Tzanck smear or test.


• Rindfleisch cell : macrophages with abundant eosinophilic cytoplasm and erythrophagy, seen in typhoid granulomas (typhoma) and listeriosis granulomas (listerioma)


• Aschoff's bodies or nodules / rheumatic fever nodules are pea sized, painless granulomas found throughout the body, most typically in the heart, in rheumatic fever
• Masson bodies : the cellular components that fill the pulmonary alveoli and alveolar ducts in rheumatic pneumonia and organizing pneumonia, thought to be modified Aschoff bodies.

The fully mature nodule is composed of a central focus of fibrinoid necrosis surrounded by Anichkov's (Anitschkow's) cell or "myocyte" / cardiac histiocyte / caterpillar cell : a plump modified macrophage that contains round to ovoid nuclei with a central, slender, caterpillar-like ribbon of chromatin in longitudinal section and owl eye-like in transverse sections (due to clear perichromatic halo)

• Aschoff cell : Anichkov's cell, particularly in the larger, multinucleate giant cell form with large basophilic cytoplasm
• fibroblast foci : in addition to emerging evidence that inflammation is not more prominent in early stages of usual interstitial pneumonia (UIP)^ref, it is becoming clear that the primary sites of ongoing injury and repair are the regions of fibroblastic proliferation^{ref1, ref2}. These small aggregates of actively proliferating myofibroblasts and fibroblasts constitute many microscopic sites of ongoing alveolar epithelial injury and activation associated with evolving fibrosis^ref.


Morphologic differences between Masson bodies (organizing pneumonia) and fibroblast foci (usual interstitial pneumonia) :
 

process	Masson bodies	fibroblast foci
inflammationref1, ref2	mixed inflammatory cell population seen in the central region	minimal or no inflammation seen
fibroblasts cytoskeletonref	fibroblasts undergo specific changes (i.e. express desmin)	myofibroblast do not express desmin
myofibroblastsref1, ref2, ref3	early apoptosis and disappearance occur; predominant localization of MMP occurs	survival is prolonged; predominant localization of TIMP-2 occurs
ECMref1, ref2, ref3, ref4	loose mode of organization causes susceptibility to degradation; myofibroblasts phagocytose collagen fibrils	imbalance occurs between MMP and TIMPs; dense collagen is progressively deposited
reepithelizationref1, ref2, ref3	occurs rapidly, basement membrane is not severely impaired; regenerated type I alveolar epithelial cells surround the residual collagen nodule	is delayed or absent because of apoptosis and disruption of basement membrane
neovascularizationref	newly formed vessels with well-developed basement membranes are seen	new vessels are usually not found

• Antoni areas and Verocay bodies : small groups of fibrils surrounded by rows of palisaded nuclei, seen in schwannoma


• Luse bodies
• Call-Exner bodies : spherical globules (gland-like spaces) surrounded by granulosa cells in granulosa cell tumour of ovary


• Schiller-Duval bodies : a structure resembling a glomerulus seen in yolk sac tuymor (YST), composed of germ cells surrounding a central blood vessel and occurring within a space lined by germ cells


• cell death

type of cell death	morphological changes			biochemical features	common detection methods
	nucleus	cell membrane	cytoplasm
apoptosis or active (programmed) cell death (ACD / PCD)	chromatin condensation; nuclear fragmentation; DNA laddering	blebbing	fragmentation (formation of apoptotic bodies)	Caspase-dependent	electron microscopy; TUNEL staining; annexin staining; caspase-activity assays; DNA-fragmentation assays; detection of increased number of cells in subG1/G0; detection of changes in mitochondrial membrane potential
Autophagy	partial chromatin condensation; no DNA laddering	blebbing	increased number of autophagic vesicles	caspase-independent; increased lysosomal activity	electron microscopy; protein-degradation assays; assays for marker-protein translocation to autophagic membranes; monodansylcadaverine (MDC) staining
mitotic catastrophe	multiple micronuclei; nuclear fragmentation	-	-	caspase-independent (at early stage) abnormal CDK1/cyclin B activation	electron microscopy; assays for mitotic markers (mitotic phosphoprotein 2 (MPM2)); TUNEL staining
necrosis	clumping and random degradation of nuclear DNA	swelling; rupture	increased vacuolation; organelle degeneration; mitochondrial swelling	-	electron microscopy; nuclear staining (usually negative); detection of inflammation and damage in surrounding tissues
cell senescence	distinct heterochromatic structure (senescence-associated heterochromatic foci)	-	flattening and increased granularity	senescence-associated b-galactosidase (SA-b-gal) activity	electron microscopy; SA-b-gal staining; growth-arrest assays; assays for increased p53, INK4A and ARF levels (usually increased); assays for RB phosphorylation (usually hypophosphorylated); assays for MMP activity (usually upregulated)

• cell senescence :
• the mitochondrial theory of aging suggests that DNA damage in the mitochondrial genome leads to dysfunction and production of ROSs implicated in the aging process. This DNA damage partly results from mutagenic base lesions in the form of 7,8-dihydro-8-oxoguanine (8-oxoG) and uracil. Cells normally utilize DNA glycosylases, such an 8-oxoguanine-DNA glycosylase (OGG1) and uracil-DNA glycosylase (UDG), in the first step of repairing such DNA damage. Aging produces high levels of 8-oxoG damage in mitochondrial DNA : the levels and activity of OGG1 are higher in mitochondrial extracts from older rodents just as a large fraction of OGG1 is caught in the mitochondrial membrane. Mitochondrial OGG1 exists in a precursor (47 kDa) and mature (45 kDa) form, and aged mitochondria contain more of the precursor form as the mature form of OGG1 is released after import into the mitochondria, suggesting that this import is malfunctioning in aged livers. The precursor is much more sensitive to proteolytic  cleavage than the mature form
• oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. In tumours initiated by an endogenous oncogene, ras, senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer^ref. Acute induction of oncogenic Ras provokes cellular senescence involving the retinoblastoma (Rb) pathway, but the tumour suppressive potential of senescence in vivo remains elusive. Recently, Rb-mediated silencing of growth-promoting genes by heterochromatin formation associated with methylation of histone H3 lysine 9 (H3K9me) was identified as a critical feature of cellular senescence, which may depend on the histone methyltransferase Suv39h1. Here we show that Eµ-N-Ras transgenic mice harbouring targeted heterozygous lesions at the Suv39h1, or the p53 locus for comparison, succumb to invasive T-cell lymphomas that lack expression of Suv39h1 or p53, respectively. By contrast, most N-Ras-transgenic wild-type ('control') animals develop a non-lymphoid neoplasia significantly later. Proliferation of primary lymphocytes is directly stalled by a Suv39h1-dependent, H3K9me-related senescent growth arrest in response to oncogenic Ras, thereby cancelling lymphomagenesis at an initial step. Suv39h1-deficient lymphoma cells grow rapidly but, unlike p53-deficient cells, remain highly susceptible to adriamycin-induced apoptosis. In contrast, only control, but not Suv39h1-deficient or p53-deficient, lymphomas senesce after drug therapy when apoptosis is blocked. These results identify H3K9me-mediated senescence as a novel Suv39h1-dependent tumour suppressor mechanism whose inactivation permits the formation of aggressive but apoptosis-competent lymphomas in response to oncogenic Ras^ref.
• immunological senescence
• oncosis (derived from the Greek word "swelling") : cell death due to ischemia characterized by depletion of intracellular ATP stores, cytoplasmic blebbing, dilatation of the endoplasmic reticulum (ER), swelling of the cytosol, normal or condensed mitochondria, and chromatin clumping in the nucleus with disruption of organelles and rupture of the plasma membrane. Pro-oncosis receptor inducing membrane injury (PORIMIN), a member of the cell membrane-associated mucin family, mediates oncosis-like cell death.

in the liver, at gross inspection, the peliotic lesions give the cut sections a "swiss cheese" appearance. Microscopically, 2 different types of peliosis can be distinguished in the liver :

parenchymal peliosis consisting of irregular cavities that are neither lined by sinusoidal cells nor by fibrous tissue

phlebectatic peliosis characterized by regular, spherical cavities lined by endothelium and/or fibrosis.

One of the differential diagnoses that most closely resembles peliosis hepatis is secondary hepatic congestion due to veno-occlusive disease or the Budd-Chiari syndrome.

in the spleen, the peliotic lesions may be arranged sporadically, disseminated, or in clusters in an uneven distribution pattern. Histologically, the cavities show frequently well-demarcated margins that may appear focally lined by sinusoidal endothelium, or totally lack a clear cell lining. Differential diagnoses are hemangiomas and involvement of the spleen in hairy-cell leukaemia. Since the disease may culminate in spontaneous rupture of the affected organ and thus may mimic a violent death at autopsy, peliosis is far more than just another morphological curiosity. Awareness of peliosis at autopsy as well as an appreciation for the histopathological changes in less characteristic or advanced cases may become an important issue for both the forensic and clinical pathologist^ref

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