"Thanatosomes": a unifying morphogenetic concept for tumor hyaline globules related to apoptosis.

Abstract:

:Hyaline globules (HG) have been observed in a large variety of unrelated categories of tumors and benign tissues. Different explanations for their formation have been proposed, varying according to tumor type and anatomic location. We have studied 80 tumor cases containing HG, by light microscopy, electron microscopy, immunohistochemical stains for various plasma proteins, and in situ DNA-end labeling for apoptosis. On light microscopy, HG were invariably related to areas of increased apoptosis and often contained apoptotic nuclear fragments. The HG stained as expected, with variable intensity with acidic stains. Most cells containing HG stained with immunohistochemical stains for all plasma proteins examined (alpha-1-antitrypsin, ferritin, C3, kappa and lambda light chains, and IgG), indicating an increased plasma membrane permeability. A morphologic change associated with the increased permeability was cytoplasmic blebbing. In the HG themselves, immunohistochemical stains for the plasma proteins were either diffusely positive or stained only the periphery of the larger HG. Double stains for apoptosis and plasma proteins confirmed the increased plasma membrane permeability to proteins of apoptotic cells in general and cells containing HG in particular. Free hyaline globules were often linked to the extracellular matrix by fibrin fibrils. Ultrastructurally, the HG appeared as phagosomes/secondary lysosomes or areas of cytoplasmic condensation surrounded by rough endoplasmic reticulum whorls. These were always associated with intense cytoplasmic blebbing. We conclude that HG reflect stages of cell injury, which in most instances relate to apoptotic cell death. They are specifically associated with the cytoplasmic blebbing and condensation typically seen in this form of cell death. These phenomena are accompanied by plasma protein influx (insudated plasma) and formation of distinct intracellular "hyalinized" cellular fragments. With cell fragmentation, the HG become extracellular and are likely to be ultimately disposed of by a process of "remodeling" and incorporation into the extracellular matrix, followed by collagenization. The latter process partly occurs by the initial linking of all components (HG, collagen fibers, cellular fragments, etc.) by a network of fibrin. The process of formation of HG follows a stereotypical pathway independent of cell type. Because it results mostly from apoptotic cell death, it is more pronounced in rapidly growing tumors or posttreatment. We propose the term thanatosomes for the entire spectrum of HG to emphasize their relationship to cell death. HUM PATHOL 31:1455-1465.

journal_name

Hum Pathol

journal_title

Human pathology

authors

Papadimitriou JC,Drachenberg CB,Brenner DS,Newkirk C,Trump BF,Silverberg SG

doi

10.1053/hupa.2000.20376

subject

Has Abstract

pub_date

2000-12-01 00:00:00

pages

1455-65

issue

12

eissn

0046-8177

issn

1532-8392

pii

S0046-8177(00)17478-7

journal_volume

31

pub_type

杂志文章
  • Potential risks in retrovenous revascularization of the myocardium.

    abstract::Retrovenous perfusion of the myocardium via the coronary sinus and cardiac veins was one of the earliest attempted forms of myocardial revascularization. Although coronary artery revascularization has almost completely replaced venous revascularization as the procedure of choice, the latter approach is still occasiona...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/0046-8177(89)90073-7

    authors: Tickman RJ,Gravanis MB,Hunter SB

    更新日期:1989-08-01 00:00:00

  • Nup88 (karyoporin) in human malignant neoplasms and dysplasias: correlations of immunostaining of tissue sections, cytologic smears, and immunoblot analysis.

    abstract::Nuclear pore complexes (NPCs) are elaborate macromolecular structures that regulate the bidirectional nucleocytoplasmic traffic system. In vertebrate cells, NPCs include a family of 50 to 100 proteins termed nucleoporins (Nups). The 88-kD Nup has been found to be linked in a dynamic subcomplex with the oncogenic CAN/N...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1053/hupa.2002.124785

    authors: Gould VE,Orucevic A,Zentgraf H,Gattuso P,Martinez N,Alonso A

    更新日期:2002-05-01 00:00:00

  • Immunohistochemical characteristics of renomedullary interstitial cell tumor: a study of 41 tumors with emphasis on differential diagnosis of mesenchymal neoplasms.

    abstract::Renomedullary interstitial cell tumors (RMICTs) are almost always incidentally identified either at autopsy or upon resection of the kidney for other reasons. However, rare cases that are large, resulting in a clinical mass, have been reported. The immunohistochemical phenotype of usual, incidental RMICT using modern ...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2018.07.010

    authors: Lu Z,Al-Obaidy K,Cheng L,Perry KD,Grignon DJ,Williamson SR

    更新日期:2018-12-01 00:00:00

  • Expression of Epstein-Barr virus in carcinomas of major salivary glands: a strong association with lymphoepithelioma-like carcinoma.

    abstract::To elucidate the role of Epstein-Barr virus (EBV) in salivary gland carcinomas, 56 cases of carcinomas of major salivary glands were investigated. These included 14 mucoepidermoid carcinomas, 13 adenoid cystic carcinomas, seven malignant mixed tumors, four adenocarcinomas, four salivary duct carcinomas, two acinic cel...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(96)90066-0

    authors: Tsai CC,Chen CL,Hsu HC

    更新日期:1996-03-01 00:00:00

  • SCL/Tal-1 expression in T-acute lymphoblastic leukemia: an immunohistochemical and genotypic study.

    abstract::A comparative study of the immunohistochemical (Stem cell leukemia/T-cell acute leukemia [SCL/TAL-1] protein expression) and genotypic (deletions in the SCL/tal-1 gene) findings in T-acute lymphoblastic leukemia (T-ALL) is presented. Formalin-fixed tissue from 50 cases of T-ALL were stained with a novel monoclonal ant...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/0046-8177(95)90089-6

    authors: Chetty R,Pulford K,Jones M,Mathieu-Mahul D,Close P,Hussein S,Pallesen G,Ralfkiaer E,Stein H,Gatter K

    更新日期:1995-09-01 00:00:00

  • Mutation of von Hippel-Lindau tumor suppressor gene in a sporadic endolymphatic sac tumor.

    abstract::Endolymphatic sac tumor (ELST) is a low-grade adenocarcinoma of the temporal bone that is presumed to originate from the endolymphatic system. Although ELSTs are extremely rare in the general population, a significant number of studies have documented the occurrence of ELST among patients with von Hippel-Lindau (VHL) ...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1053/hupa.2001.28961

    authors: Hamazaki S,Yoshida M,Yao M,Nagashima Y,Taguchi K,Nakashima H,Okada S

    更新日期:2001-11-01 00:00:00

  • Pure versus combined Merkel cell carcinomas: immunohistochemical evaluation of cellular proteins (p53, Bcl-2, and c-kit) reveals significant overexpression of p53 in combined tumors.

    abstract::Merkel cell polyomavirus is of oncogenic significance in approximately 80% of Merkel cell carcinomas. Morphological subcategories of the tumor differ in regard to viral status, the rare combined type being uniformly virus negative and the predominant pure type being mainly virus positive. Indications that different bi...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2015.05.008

    authors: Lai JH,Fleming KE,Ly TY,Pasternak S,Godlewski M,Doucette S,Walsh NM

    更新日期:2015-09-01 00:00:00

  • Primary multipotential malignant neoplasm of bone: chondrosarcoma associated with squamous cell carcinoma.

    abstract::A primary neoplasm of the proximal humerus in a 68-year-old woman was unique histologically in that it contained both malignant cartilaginous and squamous cell components. The epithelial differentiation was confirmed by the demonstration of keratin by immunohistochemical techniques and of basement membrane, tonofilame...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(83)80227-5

    authors: Ling LL,Steiner GC

    更新日期:1986-03-01 00:00:00

  • Systemic mastocytosis associated with generalized osteopenia. Histopathological characterization of the skeletal lesion using undecalcified bone from two patients.

    abstract::Although mast cell proliferation in the bone marrow frequently occurs in systemic mastocytosis and is often associated with radiographically detectable bone lesions, the pathologic correlates of the skeletal abnormalities are poorly characterized. We therefore examined three nondecalcified transiliac crest biopsy spec...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(81)80084-6

    authors: Fallon MD,Whyte MP,Teitelbaum SL

    更新日期:1981-09-01 00:00:00

  • Exploration of BRAFV600E as a diagnostic adjuvant in the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

    abstract::The non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) are distinguished from classical papillary thyroid carcinoma with predominantly follicular architecture (CPTCPFA) by distinct histomorphologic and molecu...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2018.06.033

    authors: Johnson DN,Sadow PM

    更新日期:2018-12-01 00:00:00

  • Giant cell pneumonia associated with parainfluenza virus type 3 infection.

    abstract::Giant cell pneumonia associated with parainfluenza virus type 3 infection and chronic poliovirus type 2 meningoencephalomyelitis are documented in an infant with combined immunologic deficiency (Swiss type). Caution should be exercised in attributing cases of giant cell pneumonia to measles virus without serologic or ...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(81)80032-9

    authors: Little BW,Tihen WS,Dickerman JD,Craighead JE

    更新日期:1981-05-01 00:00:00

  • Urethral caruncle: clinicopathologic features of 41 cases.

    abstract::Urethral caruncle is a benign polypoid mass of the urethral meatus in primarily postmenopausal women. Although a conclusive association with malignancy, urologic disorder, or systemic disease has not been established, often the lesion carries a challenging clinical differential diagnosis that includes malignancy. Conv...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2011.10.015

    authors: Conces MR,Williamson SR,Montironi R,Lopez-Beltran A,Scarpelli M,Cheng L

    更新日期:2012-09-01 00:00:00

  • Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse prognosis in ovarian clear cell carcinoma.

    abstract::Recent studies demonstrated that protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative str...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2017.04.008

    authors: Aman M,Ohishi Y,Imamura H,Shinozaki T,Yasutake N,Kato K,Oda Y

    更新日期:2017-06-01 00:00:00

  • Lymph node metastasis in early gastric cancer: evaluation of a novel method for measuring submucosal invasion and development of a nodal predicting index.

    abstract::After endoscopic resection of early gastric cancer (EGC), it is imperative to accurately determine whether follow-up surgery is indicated, since this technique is used as a first line of treatment. Herein, we developed a scoring system to indicate the risk of lymph node metastasis in submucosal EGC (smEGC), and presen...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2013.07.037

    authors: Kim JY,Kim WG,Jeon TY,Kim GH,Jeong EH,Kim DH,Park DY,Lauwers GY

    更新日期:2013-12-01 00:00:00

  • Chronic myelogenous leukemia: molecular diagnostic considerations.

    abstract::Chronic myelogenous leukemia (CML) is associated in 95% of cases with the Philadelphia chromosome (Ph1) by cytogenetic analysis. This acquired karyotypic abnormality is the product of a balanced translocation between the c-abl oncogene on chromosome 9 and the breakpoint cluster region (BCR) gene on chromosome 22. The ...

    journal_title:Human pathology

    pub_type: 杂志文章,评审

    doi:10.1016/0046-8177(94)90225-9

    authors: McClure JS,Litz CE

    更新日期:1994-06-01 00:00:00

  • Reactive vascular lesion of nasal septum simulating angiosarcoma in a cocaine abuser.

    abstract::We report the case of an exuberant ulcerative angiomatoid nasal lesion in a cocaine abuser. The lesion was made up of polymorphous endothelial cells with occasional mitoses, arranged in a lobular pattern with infiltrative-looking areas. There were extensive areas of thrombosis with focal recanalization. Intravascular ...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(00)80226-9

    authors: Alameda F,Fontane J,Corominas JM,Lloreta J,Serrano S

    更新日期:2000-02-01 00:00:00

  • Staging of colorectal cancers based on elastic lamina invasion.

    abstract::Peritoneal involvement in colorectal cancer (CRC) has prognostic significance and is an important parameter in pathologic tumor staging. Restaging of tumors based on peritoneal elastic lamina invasion (ELI) has prognostic significance in CRCs classified as pathologic stage 3 tumors without regional lymph node metastas...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2018.10.019

    authors: Liang WY,Wang YC,Hsu CY,Yang SH

    更新日期:2019-03-01 00:00:00

  • Endocardial fibroelastosis and myocardial calcification secondary to an anomalous right coronary artery arising from the pulmonary trunk.

    abstract::The case of an infant with endocardial fibroelastosis and a coexistent anomalous right coronary artery that originated from the pulmonary trunk is presented. The causal relation between the two conditions is discussed. ...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(85)80138-6

    authors: Huang TY,Hsueh Y,Tsung SH

    更新日期:1985-09-01 00:00:00

  • Human cytomegalovirus infection of the gastrointestinal tract in apparently immunocompetent patients.

    abstract::Human cytomegalovirus (HCMV) infection is usually reported in immunocompromised patients. This study reports 11 cases of HCMV infection of the gastrointestinal (GI) tract diagnosed in apparently immunocompetent hosts. The median age of the patients studied was 76 years, and the major presenting symptoms were diarrhea,...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2003.08.005

    authors: Maiorana A,Baccarini P,Foroni M,Bellini N,Giusti F

    更新日期:2003-12-01 00:00:00

  • Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    abstract::Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2015.09.031

    authors: Sandhu R,Chollet-Hinton L,Kirk EL,Midkiff B,Troester MA

    更新日期:2016-02-01 00:00:00

  • The role of liver biopsy in evaluating acute allograft dysfunction following liver transplantation: a clinical histologic correlation of 34 liver transplants.

    abstract::One hundred six liver biopsy specimens from 34 orthotopic liver transplant (OLT) patients were examined and the histologic findings correlated with the clinical course of the patients to determine if specific morphologic patterns were associated with specific causes of acute allograft dysfunction. The principle causes...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(88)80268-5

    authors: Ray RA,Lewin KJ,Colonna J,Goldstein LI,Busuttil RW

    更新日期:1988-07-01 00:00:00

  • Polymerase chain reaction-based methods for the detection of mutations in oncogenes and tumor suppressor genes.

    abstract::Altered expression of oncogenes and tumor suppressor genes, the normal function of which is to regulate cell growth and differentiation, represents a central event in the pathogenesis of human cancer. Aberrant expression of these genes is often a result of a mutational event. In vitro amplification of DNA with the pol...

    journal_title:Human pathology

    pub_type: 杂志文章,评审

    doi:10.1016/0046-8177(94)90220-8

    authors: Loda M

    更新日期:1994-06-01 00:00:00

  • Expression of human telomerase reverse transcriptase in gastrointestinal stromal tumors occurs preferentially in malignant neoplasms.

    abstract::Telomerase is expressed in many human cancers and cell lines and is thought to contribute to their immortality. To date, little is known about the expression of telomerase in nonepithelial tumors. The objective of this study was to evaluate the expression of human telomerase reverse transcriptase (hTERT) in gastrointe...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2004.07.010

    authors: Sabah M,Cummins R,Leader M,Kay E

    更新日期:2004-10-01 00:00:00

  • Primitive neuroectodermal tumors of the central nervous system.

    abstract::Primitive neuroectodermal tumors are morphologically similar malignant tumors arising in intracranial and peripheral sites of the nervous system, showing varying degrees of cellular differentiation with a tendency to disseminate along cerebrospinal fluid pathways. They occur primarily in children and young adults. Und...

    journal_title:Human pathology

    pub_type: 杂志文章,评审

    doi:10.1016/s0046-8177(83)80006-9

    authors: Becker LE,Hinton D

    更新日期:1983-06-01 00:00:00

  • Spatial resolution requirements for acquisition of the virtual screening slide for digital whole-specimen breast histopathology.

    abstract::We examined the effect of lateral spatial resolution and reader specialty on the accuracy of detection of breast cancer. The motivation for this pilot study was the need to acquire and display very large data sets in whole-specimen 3D digital breast histopathology imaging. The ultimate goal is to determine the minimum...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2007.04.006

    authors: Clarke GM,Zubovits JT,Katic M,Peressotti C,Yaffe MJ

    更新日期:2007-12-01 00:00:00

  • An ultrastructural and light microscopic study of the synovium in ochronotic arthropathy.

    abstract::The synovium in two well-documented cases of alkaptonuric ochronosis was studied by transmission electron and light microscopy. A feature of alkaptonuria previously unreported in the English-language literature was the presence of phagocytosis of large collagen fibrils by synovial macrophages in both cases. The origin...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(87)80385-4

    authors: Gaines JJ Jr,Tom GD,Khankhanian N

    更新日期:1987-11-01 00:00:00

  • Erythroleukemic infiltration of a lymph node: use of hemoglobin immunohistochemical techniques in diagnosis.

    abstract::Isolated submandibular adenopathy developed in a patient who had subacute erythroleukemia. Lymph node biopsy revealed a proliferation of immature cells and scattered foci of dyserythropoietic normoblasts. Since a review of the literature revealed no detailed description of an erythroleukemic lymph node infiltrate, a h...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(84)80254-3

    authors: Keifer J,Zaino R,Ballard JO

    更新日期:1984-11-01 00:00:00

  • Immunohistochemical analysis of retroperitoneal Müllerian cyst.

    abstract::Retroperitoneal cysts are uncommon diseases, and benign nonneoplastic Müllerian cysts are extremely rare among the known cases. We report a case of a 35-year-old woman with a retroperitoneal Müllerian cyst with the tubal type of epithelium. The patient presented with a large (20 cm in diameter), palpable abdominal mas...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1053/hupa.2003.12

    authors: Konishi E,Nakashima Y,Iwasaki T

    更新日期:2003-02-01 00:00:00

  • Aberrant crypt foci in human colons: distribution and histomorphologic characteristics.

    abstract::Aberrant crypt foci (ACF) are one of the earliest putative preneoplastic, and in some cases, neoplastic lesions in human colons. These microscopic lesions, identified on methylene blue-stained mucosa with a low-power-magnification microscope, are thought to be closely related to the earliest steps in multistage coloni...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/s0046-8177(98)90062-4

    authors: Shpitz B,Bomstein Y,Mekori Y,Cohen R,Kaufman Z,Neufeld D,Galkin M,Bernheim J

    更新日期:1998-05-01 00:00:00

  • A validation study of quantum dot multispectral imaging to evaluate hormone receptor status in ductal carcinoma in situ of the breast.

    abstract::The assessment of hormone receptors, including estrogen receptor and progesterone receptor, has become a standard practice in breast cancer management. However, the need for multiple sections to evaluate each receptor individually by conventional immunohistochemistry may preclude the analysis on some core biopsies wit...

    journal_title:Human pathology

    pub_type: 杂志文章

    doi:10.1016/j.humpath.2012.06.002

    authors: Yu J,Monaco SE,Onisko A,Bhargava R,Dabbs DJ,Cieply KM,Fine JL

    更新日期:2013-03-01 00:00:00