Publisher Summary The classification of cell death can be based on morphological or biochemical criteria or on the circumstances of its occurrence. Currently, irreversible structural alteration provides the only unequivocal evidence of death; biochemical indicators of cell death that are universally applicable have to be precisely defined and studies of cell function or of reproductive capacity do not necessarily differentiate between death and dormant states from which recovery may be possible. It has also proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances. One of these patterns is the swelling proceeding to rupture of plasma and organelle membranes and dissolution of organized structure—termed “coagulative necrosis.” It results from injury by agents, such as toxins and ischemia, affects cells in groups rather than singly, and evokes exudative inflammation when it develops in vivo. The other morphological pattern is characterized by condensation of the cell with maintenance of organelle integrity and the formation of surface protuberances that separate as membrane-bounded globules; in tissues, these are phagocytosed and digested by resident cells, there being no associated inflammation.

Cell death : the significance of apoptosis

The historical development of the cell death concept is reviewed, with special attention to the origin of the terms necrosis, coagulation necrosis, autolysis, physiological cell death, programmed cell death, chromatolysis (the first name of apoptosis in 1914), karyorhexis, karyolysis, and cell suicide, of which there are three forms: by lysosomes, by free radicals, and by a genetic mechanism (apoptosis). Some of the typical features of apoptosis are discussed, such as budding (as opposed to blebbing and zeiosis) and the inflammatory response. For cell death not by apoptosis the most satisfactory term is accidental cell death. Necrosis is commonly used but it is not appropriate, because it does not indicate a form of cell death but refers to changes secondary to cell death by any mechanism, including apoptosis. Abundant data are available on one form of accidental cell death, namely ischemic cell death, which can be considered an entity of its own, caused by failure of the ionic pumps of the plasma membrane. Because ischemic cell death (in known models) is accompanied by swelling, the name oncosis is proposed for this condition. The term oncosis (derived from onkos, meaning swelling) was proposed in 1910 by von Reckling-hausen precisely to mean cell death with swelling. Oncosis leads to necrosis with karyolysis and stands in contrast to apoptosis, which leads to necrosis with karyorhexis and cell shrinkage.

Apoptosis, oncosis, and necrosis : an overview of cell death

Apoptosis is a distinct mode of cell death that is responsible for deletion of cells in normal tissues; it also occurs in specific pathologic contexts. Morphologically, it involves rapid condensation and budding of the cell, with the formation of membrane-enclosed apoptotic bodies containing well-preserved organelles, which are phagocytosed and digested by nearby resident cells. There is no associated inflammation. A characteristic biochemical feature of the process is double-strand cleavage of nuclear DNA at the linker regions between nucleosomes leading to the production of oligonucleosomal fragments. In many, although not all of the circumstances in which apoptosis occurs, it is suppressed by inhibitors of messenger RNA and protein synthesis. Apoptosis occurs spontaneously in malignant tumors, often markedly retarding their growth, and it is increased in tumors responding to irradiation, cytotoxic chemotherapy, heating and hormone ablation. However, much of the current interest in the process stems from the discovery that it can be regulated by certain proto-oncogenes and the p53 tumor suppressor gene. Thus, c-myc expression has been shown to be involved in the initiation of apoptosis in some situations, and bcl-2 has emerged as a new type of proto-oncogene that inhibits apoptosis, rather than stimulating mitosis. In p53-negative tumor-derived cell lines transfected with wild-type p53, induction of the gene has, in rare cases, been found to cause extensive apoptosis, instead of growth arrest. Finally, the demonstration that antibodies against a cell-surface protein designated APO-1 or Fas can enhance apoptosis in some human lymphoid cell lines may have therapeutic implications.

Apoptosis. Its significance in cancer and cancer Therapy

The Respiratory System

结节病易误诊,据王洪武等~([1])收集国内18篇关于此病误诊的文献,误诊率高达63.2%,当然有误诊就会有误治,如孙永昌等~([2])报道26例结节病在影像学检查诊断的第一印象中拟诊结核5例,其中就有2例完成规范的抗结核治疗,为此应引起临床对本病诊治的重视。

Sarcoidosis

Thoroughly revised and up-dated, this comprehensive, authoritative reference will help both the experienced and novice practitioner diagnose skin diseases and disorders more accurately and effectively. In this title, a superb full colour art programme illustrates the salient pathological features of both neoplastic and non-neoplastic conditions and will help the reader easily interpret key clinical and diagnostic points. This single-authored text incorporates the wealth of Dr Weedon's own personal observations and experience in his approach to the diagnosis and interpretation of skin biopsies and is full of useful diagnostic clues and pearls. This remarkable book is an indispensable resource for all those involved in the identification and evaluation of skin disorders.

Weedon's Skin Pathology

Apoptosis is a distinctive mode of cell death with characteristic morphologic features which serves as a balance to mitosis in regulating the size of animal tissues. In contrast to coagulative necrosis, the cytologic features of apoptosis suggest active self-destructive rather than progressive disintegration. It typically affects scattered individual cells which condense and bud to produce many membrane-bounded fragments in which organelles appear intact when viewed by the electron microscope. These apoptotic bodies are then phagocytosed and digested by cells resident in the tissue. Apoptosis, unlike coagulative necrosis, does not itself evoke an inflammatory response. Apoptosis is a feature of such diverse processes as deletion of phylogenetic vestiges during normal embryonic development, involution of endocrine-dependent organs after withdrawal of trophic hormones, cell-mediated immune attack on tissues, and therapeutically induced regression of neoplasms. Apoptosis has received scant attention in dermatopathology. However, it is now known to be an important feature of lichen planus, certain drug eruptions, the skin lesions of graft-versus-host reactions, the regression of plane warts, and the effects of ultraviolet damage. It is also involved in the kinetics of cutaneous neoplasms. In some of these situations, apoptotic bodies have, in the past, been given names such as Civatte bodies, colloid bodies, single-cell necrobiosis, sunburn cells, and dyskeratotic cells without their basic nature having been recognized.

Apoptosis. Its nature and implications for dermatopathology.

Atypical fibroxanthoma is a controversial entity with a disputed histogenesis. It has recently been suggested that most atypical fibroxanthoma are actually variants of squamous cell carcinoma. We reviewed 100 purported cases of atypical fibroxanthoma received over 4 years to perform clinical follow up and immunohistochemical markers. In particular, we focused on the detection of any recurrence or metastasis. Ten cases were subsequently excluded on the basis of either incorrect coding, or insufficient or absent paraffin blocks on file. A further case was interpreted as a malignant fibrous histiocytoma. Additional new markers, such as CD10 and CD99, were employed in a proportion of cases. Our cases were typical of the usual clinical presentation of atypical fibroxanthoma on the skin of the sun-damaged elderly. We found no cases of recurrent or metastatic atypical fibroxanthoma. Two patients developed a second primary atypical fibroxanthoma. CD10 proved to be a useful marker for atypical fibroxanthoma when used on 20 cases in the present study, as was CD99 in seven cases. The only case demonstrating positive staining for keratin also stained for CD10. It had dual features of atypical fibroxanthoma and squamous cell carcinoma. However, as the majority of atypical fibroxanthoma had no adjacent solar keratosis, our data suggest it is unlikely that atypical fibroxanthoma is a variant of squamous cell carcinoma.

Atypical fibroxanthoma: a clinicopathological study of 89 cases.

Tumors of the epidermis

Evidence of previous spontaneous regression was found in 6% of 400 randomly selected basal cell carcinomas. A further 14% showed small foci of active regression usually less than 1 high power field in area and characterized by a lymphocytic infiltrate of tumor nests associated with many apoptotic tumor cells. Spontaneous regression of basal cell carcinomas has been paid scant attention in the past.

David Weedon

Papers

Weedon's Skin Pathology

Apoptosis. Its nature and implications for dermatopathology.

Atypical fibroxanthoma: a clinicopathological study of 89 cases.

Tumors of the epidermis

Spontaneous regression in basal cell carcinomas.