- Email: [email protected]
Thin cutaneous malignant melanoma and the MIN terminology
THE LANCET
COMMENTARY treatment planning of patients at risk of disorders such as osteoporosis4,6 and heterotopic ossification following jointreplacement surgery.3
Edward M Greenfield, Victor M Goldberg Department of Orthopaedics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-5000, USA 1
2
3 4 5 6 7
8
9
Rogers J, Shepstone L, Dieppe P. Bone formers: osteophyte and enthesophyte formation are positively associated. Ann Rheum Dis 1997; 56: 85–90. Vezyroglou G, Mitropoulos A, Kyriazis N, Antoniadis C. A metabolic syndrome in difuse idiopathic skeletal hyperostosis. A controlled study. J Rheum 1996; 23: 672–76. Lewallen DG. Heterotopic ossification following total hip arthroplasty. Instr Course Lect 1995; 44: 287–92. Eisman JA. Vitamin D receptor gene alleles and osteoporosis: an affirmative view. J Bone Miner Res 1995; 10: 1289–93. Peacock M. Vitamin D receptor alleles and osteoporosis: a constrasting view. J Bone Miner Res 1995; 10: 1294–97. Ralston SH. Genetic markers of bone metabolism and bone disease. Scand J Clin Lab Invest 1997; 57 (S227): 114–21. Beamer W, Shultz K, Frankel W, Donahue L, Baylink D, Rosen CJ. Genetic loci for cortical bone density in inbred mice. J Bone Miner Res 1997; 12 (S1): 174. Gong Y, Vikkula M, Boon L, et al. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13. Am J Hum Genet 1996; 59: 146–51. Johnson ML, Gong G, Kimberling W, Recker SM, Kimmel DB, Recker RR. Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13). Am J Hum Genet 1997; 60: 1326–32.
Thin cutaneous malignant melanoma and the MIN terminology The incidence of cutaneous malignant melanoma is rising worldwide, mainly because of an increased number of thin tumours. The percentage of thin malignant melanoma (<0·76 mm) has been reported as rising from 9·4% in 1960–64 to 31·5% in 1980–84.1 It is generally accepted that such a change is a result of early diagnosis, which probably reflects increased public awareness about melanoma. The clinical distinction between small thin melanomas and their possible precursors is often subtle. The diagnosis of a thin melanoma relies on histological interpretation. Unfortunately, the histological distinction between thin malignant melanoma and borderline lesions can be difficult.2–4 To address this problem, in 1991 the Cancer Research Campaign (CRC) Melanoma Pathology Panel started an investigation of observer variation in the diagnosis of melanoma.5 There was strong agreement in the broad categories of benign and malignant diagnoses but not in the separation of benign lesions with severe atypia from thin melanoma, despite standardisation of the diagnostic criteria. Since the clinical management is largely the same for the two disorders, the panel suggested that these two diagnoses should not be separated. Instead it introduced the term melanocytic intraepidermal neoplasia (MIN) to cover thin malignant melanoma and benign lesions with atypia. The most obvious analogy would be cervical intraepidermal neoplasia (CIN). The CRC panel also introduced the term microinvasion for invasive melanoma that was still in the radial growth phase and thereby not expected to have metastatic potential. The panel put these terms to the test in a nationwide study of the observer variation in the diagnosis of thin cutaneous malignant melanoma. Histological slides were circulated twice among 148 pathologists. In the first round when they had to classify slides as benign naevus, benign 1264
naevus with atypia, or melanoma, there was little agreement among the pathologists. In the second round, after the pathologists were introduced to standardised diagnostic criteria and the MIN definition, there was a higher level of agreement in classifying slides as benign naevi, MIN with or without microinvasion, or melanoma.6 What is the clinical consequence of using the MIN terminology? Clinicians require a diagnosis accurate enough for definitive treatment in the short term, for prognostic information for the patient, and for long-term follow-up. To fulfil these requirements, the histological diagnosis must reflect the biology of the melanocytic lesion. This relation has been established for the spectrum of invasive melanomas, where index cases have metastasised either at the time of excision or following incomplete excision. Such is not the case for intraepidermal melanocytic lesions. Clinicians are comfortable with the term melanoma in situ (MIS), knowing that if left alone this lesion may well never become an invasive/metastasising melanoma. They can easily convey this message to patients. However, patients and physicians in non-dermatological specialties may find it difficult to understand descriptive terms such as atypical melanocytic hyperplasia, pagetoid melanocytic proliferation, and naevus with slight, moderate, or severe dysplasia, and to explain the need for re-excision when there is severe, but not when there is slight, dysplasia, and why MIS is diagnosed by one pathologist and not by the other. Consistent and understandable criteria should be available to enable a trained pathologist to make a diagnosis and use these descriptive terms repeatedly, with confidence, and without significant interindividual or intraindividual variation. However, the CRC panel has shown that, even after re-evaluation of criteria, some melanocytic lesions are not identified consistently.5 Hence the suggestion that the intraepidermal melanocytic lesions, MIS, and naevi with severe intraepidermal dysplasia be lumped descriptively under the collective term MIN. The suggestions leave us with three categories—a large group of benign melanocytic naevi, a group of definite melanomas, and an intermediate group of subtle and curious melanocytic lesions of unknown biological potential, but which should be managed like MIS. The risk of such lumping, apart from skewing the epidemiology and increasing morbidity, will be a low threshold for the diagnosis and treatment (or overtreatment) of these MINs. Since the alternative seems to be “melanocytic confusion”, this risk seems acceptable for the time being, but should not curb efforts to identify with greater precision those lesions with a true invasive/metastatic potential.
Lone Skov, Ole Clemmensen, Ole Baadsgaard Departments of Dermatology, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark, and Department of Dermatology, Odense University Hospital 1
2
3
Thorn M, Ponten F, Bergstrom R, Sparen P, Adami HO.Trends in tumour characteristics and survival of malignant melanoma 1960–84: a population-based study in Sweden. Br J Cancer 1994; 70: 743–48. Hastrup N, Clemmensen OJ, Spaun E, Sondergaard K. Dysplastic naevus: histological criteria and their inter-observer reproducibility. Histopathology 1994; 24: 503–09. de Wit PE, van’t Hof Grootenboer B, Ruiter DJ, et al.Validity of the histopathological criteria used for diagnosing dysplastic naevi: an interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group. Eur J Cancer 1993; 29A: 831–39.
Vol 350 • November 1, 1997
THE LANCET
COMMENTARY 4
5
6
Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 1996; 27: 528–31. Cook MG, Clarke TJ, Humphreys S, et al.The evaluation of diagnostic and prognostic criteria and the terminology of thin cutaneous malignant melanoma by the CRC Melanoma Pathology Panel. Histopathology 1996; 28: 497–512. CRC Melanoma Pathology Panel. A nationwide survey of observer variation in the diagnosis of thin cutaneous malignant melanoma including the MIN terminology. J Clin Pathol 1997; 50: 202–05.
Coronary artery calcification on computed tomography Several reports, notably from Tel Aviv1 and Bristol,2 have shown that coronary-artery calcification can be nearly as well demonstrated by modern computed tomography (CT) as by ultrafast electron beam computed tomography (EBCT). EBCT is capable of acquiring images in around 50 ms and can therefore show static images of the beating heart. By capturing images at different phases of systole and diastole through electrocardiographic triggering, a cine loop showing the axial anatomy of the beating heart can be created. Thus EBCT was hailed as a breakthrough for many aspects of cardiac imaging. However, the machines are expensive and their asymmetrical gantry geometry makes them less useful for routine CT work. So they have not been widely adopted outside major cardiothoracic centres. Furthermore, rapid improvement in magnetic resonance imaging (MRI) is making techniques available for evaluating myocardial perfusion and coronary anatomy. But MRI does not show calcification, let alone coronary calcification, all that well. Hence EBCT has been regarded as the state-of-the-art investigation for detecting and quantifying coronary artery calcification.3–5 Now EBCT is being challenged by the newer CT systems, which are capable of obtaining an entire set of thoracic images in a single comfortable breath-hold. On the spiral system used by J Shemesh and colleagues,1 20 3·2 mm thick contiguous sections through the proximal 6 cm of the coronary arteries can be obtained in about 20 s. Previous necropsy studies6 have shown that calcification of the more distal arteries does not occur without proximal involvement. Numerous methods have been developed for quantifying the extent of coronary artery calcification. Perhaps the best known is that proposed by Agatston7 which summates the area of calcification on each image and the severity (as judged by the Hounsfield attenuation). This yields a coronary-artery calcification score, which can be used to compare various groups of patients with age and sex matched controls. Such a scoring method, with a minor thresholding adaptation, was used by Shemesh et al on a spiral CT system to confirm the EBCT findings that coronary artery calcification was significantly more prevalent in symptomatic patients aged 45–62 with angiographic obstructive coronary artery disease (>83%) than in those without (27%) and in healthy age-matched controls (34%).1 Sensitivity in detecting obstructive coronary artery disease was high (91%) but specificity was low (52%) because of calcification seen at CT in lesions that were not causing obstruction on angiography. Overall spiral CT was 84% accurate in determining obstructive coronary artery calcification as judged by angiography. The Bristol group2 used a somewhat less advanced CT system—on a par with that in most district general
Vol 350 • November 1, 1997
hospitals in the UK. Furthermore, they reviewed CT examinations performed along a standard thoracic CT protocol (8 mm thick contiguous sections) for routine clinical problems (eg, staging lung cancer). Nevertheless, their findings are not far behind those of EBCT. Certainly the trend for the prevalence of calcification at different age and sex was similar, with men showing calcification earlier but being overtaken by women in the long run (age over 80). This pattern has also been shown in the abdominal aorta, both by plain radiography8 and CT.9 The high prevalence of coronary calcification in elderly women prompted firther work by the Tel-Aviv group, which showed that all women aged 60–76 free from coronary calcification on CT had normal coronary arteriograms.10 So where does all this lead? The latest comment from the American Heart Association11 states that “EBCT has been shown to be sufficiently accurate for predicting angiographic stenosis somewhere in the coronary arteries and for predicting likely endpoints in symptomatic patients”. The Bristol conclusions are more dogmatic. They suggest2 that the detection of coronary artery calcification on routine thoracic CT should prompt a cardiological referral. Such a practice would create a massive extra cardiological workload with, as yet, no known benefit. One could argue that individuals aged under 50 with coronary artery calcification might constitute a special case. The Bristol group’s more sanguine recommendation, that those patients with coronary calcification scheduled for surgery should be seen by a cardiologist, may prove to be beneficial. Such a policy might warn of unexpected intra-operative events.12
Adrian K Dixon, Richard A Coulden Department of Radiology, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 2QQ, UK 1
Shemesh J, Apter S, Rozenman J, et al. Calcification of coronary arteries; detection with double-helix CT. Radiology 1995; 197: 779–83. 2 Callaway MP, Richards P, Goddard P, Rees M. The incidence of coronary artery calcification on standard thoracic CT scans. Br J Radiol 1997; 70: 572–74. 3 Reinmuller R, Lipton MJ. Detection of coronary artery calcification by computed tomography. Dynamic Cardiovasc Imaging 1987; 1: 139–45. 4 Breen JF, Sheedy PF, Schwartz RS, et al. Coronary artery calcification detected with ultrafast CT as a predictor of coronary artery disease. Radiology 1992; 185: 435–39. 5 Kaufmann RB, Sheedy PF, Breen JF, et al. Detection of heart calcification with electron beam CT: interobserver and intraobserver reliability for scoring quantification. Radiology 1994; 190: 347–52. 6 McCarthy JH, Palmer FJ. Incidence and significance of coronary artery calcification. Br Heart J 1974; 36: 499–506. 7 Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography, J Am Coll Cardiol 1990; 15: 827–32. 8 Elkeles A. A comparative study of calcified atheroma in males and females over 50 years of age. Lancet 1957; ii: 714–15. 9 Dixon AK, Lawrence JP, Mitchell JRA. Age related changes in the abdominal aorta shown by computed tomography. Clin Radiol 1984; 35: 33–37. 10 Shemesh J, Tenebaum A, Fisman EZ, et al. Absence of coronary calcification on double-helical CT scans: predictor of angiographically normal coronary arteries in elderly women. Radiology 1996; 199: 665–68. 11 Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: Pathophysiology, epidemiology, imaging methods and clinical implications. A statement for health care professionals from the American Heart Asociation. Circulation 1996; 94: 1175–92. 12 Moore EH, Greenberg RW, Merrick SH, Miller SW, McCloud TC, Shepard J-AO. Coronary artery calcifications: significance of incidental detection on CT scans. Radiology 1989; 172: 711–16.
1265
COMMENTARY treatment planning of patients at risk of disorders such as osteoporosis4,6 and heterotopic ossification following jointreplacement surgery.3
Edward M Greenfield, Victor M Goldberg Department of Orthopaedics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-5000, USA 1
2
3 4 5 6 7
8
9
Rogers J, Shepstone L, Dieppe P. Bone formers: osteophyte and enthesophyte formation are positively associated. Ann Rheum Dis 1997; 56: 85–90. Vezyroglou G, Mitropoulos A, Kyriazis N, Antoniadis C. A metabolic syndrome in difuse idiopathic skeletal hyperostosis. A controlled study. J Rheum 1996; 23: 672–76. Lewallen DG. Heterotopic ossification following total hip arthroplasty. Instr Course Lect 1995; 44: 287–92. Eisman JA. Vitamin D receptor gene alleles and osteoporosis: an affirmative view. J Bone Miner Res 1995; 10: 1289–93. Peacock M. Vitamin D receptor alleles and osteoporosis: a constrasting view. J Bone Miner Res 1995; 10: 1294–97. Ralston SH. Genetic markers of bone metabolism and bone disease. Scand J Clin Lab Invest 1997; 57 (S227): 114–21. Beamer W, Shultz K, Frankel W, Donahue L, Baylink D, Rosen CJ. Genetic loci for cortical bone density in inbred mice. J Bone Miner Res 1997; 12 (S1): 174. Gong Y, Vikkula M, Boon L, et al. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13. Am J Hum Genet 1996; 59: 146–51. Johnson ML, Gong G, Kimberling W, Recker SM, Kimmel DB, Recker RR. Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13). Am J Hum Genet 1997; 60: 1326–32.
Thin cutaneous malignant melanoma and the MIN terminology The incidence of cutaneous malignant melanoma is rising worldwide, mainly because of an increased number of thin tumours. The percentage of thin malignant melanoma (<0·76 mm) has been reported as rising from 9·4% in 1960–64 to 31·5% in 1980–84.1 It is generally accepted that such a change is a result of early diagnosis, which probably reflects increased public awareness about melanoma. The clinical distinction between small thin melanomas and their possible precursors is often subtle. The diagnosis of a thin melanoma relies on histological interpretation. Unfortunately, the histological distinction between thin malignant melanoma and borderline lesions can be difficult.2–4 To address this problem, in 1991 the Cancer Research Campaign (CRC) Melanoma Pathology Panel started an investigation of observer variation in the diagnosis of melanoma.5 There was strong agreement in the broad categories of benign and malignant diagnoses but not in the separation of benign lesions with severe atypia from thin melanoma, despite standardisation of the diagnostic criteria. Since the clinical management is largely the same for the two disorders, the panel suggested that these two diagnoses should not be separated. Instead it introduced the term melanocytic intraepidermal neoplasia (MIN) to cover thin malignant melanoma and benign lesions with atypia. The most obvious analogy would be cervical intraepidermal neoplasia (CIN). The CRC panel also introduced the term microinvasion for invasive melanoma that was still in the radial growth phase and thereby not expected to have metastatic potential. The panel put these terms to the test in a nationwide study of the observer variation in the diagnosis of thin cutaneous malignant melanoma. Histological slides were circulated twice among 148 pathologists. In the first round when they had to classify slides as benign naevus, benign 1264
naevus with atypia, or melanoma, there was little agreement among the pathologists. In the second round, after the pathologists were introduced to standardised diagnostic criteria and the MIN definition, there was a higher level of agreement in classifying slides as benign naevi, MIN with or without microinvasion, or melanoma.6 What is the clinical consequence of using the MIN terminology? Clinicians require a diagnosis accurate enough for definitive treatment in the short term, for prognostic information for the patient, and for long-term follow-up. To fulfil these requirements, the histological diagnosis must reflect the biology of the melanocytic lesion. This relation has been established for the spectrum of invasive melanomas, where index cases have metastasised either at the time of excision or following incomplete excision. Such is not the case for intraepidermal melanocytic lesions. Clinicians are comfortable with the term melanoma in situ (MIS), knowing that if left alone this lesion may well never become an invasive/metastasising melanoma. They can easily convey this message to patients. However, patients and physicians in non-dermatological specialties may find it difficult to understand descriptive terms such as atypical melanocytic hyperplasia, pagetoid melanocytic proliferation, and naevus with slight, moderate, or severe dysplasia, and to explain the need for re-excision when there is severe, but not when there is slight, dysplasia, and why MIS is diagnosed by one pathologist and not by the other. Consistent and understandable criteria should be available to enable a trained pathologist to make a diagnosis and use these descriptive terms repeatedly, with confidence, and without significant interindividual or intraindividual variation. However, the CRC panel has shown that, even after re-evaluation of criteria, some melanocytic lesions are not identified consistently.5 Hence the suggestion that the intraepidermal melanocytic lesions, MIS, and naevi with severe intraepidermal dysplasia be lumped descriptively under the collective term MIN. The suggestions leave us with three categories—a large group of benign melanocytic naevi, a group of definite melanomas, and an intermediate group of subtle and curious melanocytic lesions of unknown biological potential, but which should be managed like MIS. The risk of such lumping, apart from skewing the epidemiology and increasing morbidity, will be a low threshold for the diagnosis and treatment (or overtreatment) of these MINs. Since the alternative seems to be “melanocytic confusion”, this risk seems acceptable for the time being, but should not curb efforts to identify with greater precision those lesions with a true invasive/metastatic potential.
Lone Skov, Ole Clemmensen, Ole Baadsgaard Departments of Dermatology, Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark, and Department of Dermatology, Odense University Hospital 1
2
3
Thorn M, Ponten F, Bergstrom R, Sparen P, Adami HO.Trends in tumour characteristics and survival of malignant melanoma 1960–84: a population-based study in Sweden. Br J Cancer 1994; 70: 743–48. Hastrup N, Clemmensen OJ, Spaun E, Sondergaard K. Dysplastic naevus: histological criteria and their inter-observer reproducibility. Histopathology 1994; 24: 503–09. de Wit PE, van’t Hof Grootenboer B, Ruiter DJ, et al.Validity of the histopathological criteria used for diagnosing dysplastic naevi: an interobserver study by the pathology subgroup of the EORTC Malignant Melanoma Cooperative Group. Eur J Cancer 1993; 29A: 831–39.
Vol 350 • November 1, 1997
THE LANCET
COMMENTARY 4
5
6
Farmer ER, Gonin R, Hanna MP. Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 1996; 27: 528–31. Cook MG, Clarke TJ, Humphreys S, et al.The evaluation of diagnostic and prognostic criteria and the terminology of thin cutaneous malignant melanoma by the CRC Melanoma Pathology Panel. Histopathology 1996; 28: 497–512. CRC Melanoma Pathology Panel. A nationwide survey of observer variation in the diagnosis of thin cutaneous malignant melanoma including the MIN terminology. J Clin Pathol 1997; 50: 202–05.
Coronary artery calcification on computed tomography Several reports, notably from Tel Aviv1 and Bristol,2 have shown that coronary-artery calcification can be nearly as well demonstrated by modern computed tomography (CT) as by ultrafast electron beam computed tomography (EBCT). EBCT is capable of acquiring images in around 50 ms and can therefore show static images of the beating heart. By capturing images at different phases of systole and diastole through electrocardiographic triggering, a cine loop showing the axial anatomy of the beating heart can be created. Thus EBCT was hailed as a breakthrough for many aspects of cardiac imaging. However, the machines are expensive and their asymmetrical gantry geometry makes them less useful for routine CT work. So they have not been widely adopted outside major cardiothoracic centres. Furthermore, rapid improvement in magnetic resonance imaging (MRI) is making techniques available for evaluating myocardial perfusion and coronary anatomy. But MRI does not show calcification, let alone coronary calcification, all that well. Hence EBCT has been regarded as the state-of-the-art investigation for detecting and quantifying coronary artery calcification.3–5 Now EBCT is being challenged by the newer CT systems, which are capable of obtaining an entire set of thoracic images in a single comfortable breath-hold. On the spiral system used by J Shemesh and colleagues,1 20 3·2 mm thick contiguous sections through the proximal 6 cm of the coronary arteries can be obtained in about 20 s. Previous necropsy studies6 have shown that calcification of the more distal arteries does not occur without proximal involvement. Numerous methods have been developed for quantifying the extent of coronary artery calcification. Perhaps the best known is that proposed by Agatston7 which summates the area of calcification on each image and the severity (as judged by the Hounsfield attenuation). This yields a coronary-artery calcification score, which can be used to compare various groups of patients with age and sex matched controls. Such a scoring method, with a minor thresholding adaptation, was used by Shemesh et al on a spiral CT system to confirm the EBCT findings that coronary artery calcification was significantly more prevalent in symptomatic patients aged 45–62 with angiographic obstructive coronary artery disease (>83%) than in those without (27%) and in healthy age-matched controls (34%).1 Sensitivity in detecting obstructive coronary artery disease was high (91%) but specificity was low (52%) because of calcification seen at CT in lesions that were not causing obstruction on angiography. Overall spiral CT was 84% accurate in determining obstructive coronary artery calcification as judged by angiography. The Bristol group2 used a somewhat less advanced CT system—on a par with that in most district general
Vol 350 • November 1, 1997
hospitals in the UK. Furthermore, they reviewed CT examinations performed along a standard thoracic CT protocol (8 mm thick contiguous sections) for routine clinical problems (eg, staging lung cancer). Nevertheless, their findings are not far behind those of EBCT. Certainly the trend for the prevalence of calcification at different age and sex was similar, with men showing calcification earlier but being overtaken by women in the long run (age over 80). This pattern has also been shown in the abdominal aorta, both by plain radiography8 and CT.9 The high prevalence of coronary calcification in elderly women prompted firther work by the Tel-Aviv group, which showed that all women aged 60–76 free from coronary calcification on CT had normal coronary arteriograms.10 So where does all this lead? The latest comment from the American Heart Association11 states that “EBCT has been shown to be sufficiently accurate for predicting angiographic stenosis somewhere in the coronary arteries and for predicting likely endpoints in symptomatic patients”. The Bristol conclusions are more dogmatic. They suggest2 that the detection of coronary artery calcification on routine thoracic CT should prompt a cardiological referral. Such a practice would create a massive extra cardiological workload with, as yet, no known benefit. One could argue that individuals aged under 50 with coronary artery calcification might constitute a special case. The Bristol group’s more sanguine recommendation, that those patients with coronary calcification scheduled for surgery should be seen by a cardiologist, may prove to be beneficial. Such a policy might warn of unexpected intra-operative events.12
Adrian K Dixon, Richard A Coulden Department of Radiology, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 2QQ, UK 1
Shemesh J, Apter S, Rozenman J, et al. Calcification of coronary arteries; detection with double-helix CT. Radiology 1995; 197: 779–83. 2 Callaway MP, Richards P, Goddard P, Rees M. The incidence of coronary artery calcification on standard thoracic CT scans. Br J Radiol 1997; 70: 572–74. 3 Reinmuller R, Lipton MJ. Detection of coronary artery calcification by computed tomography. Dynamic Cardiovasc Imaging 1987; 1: 139–45. 4 Breen JF, Sheedy PF, Schwartz RS, et al. Coronary artery calcification detected with ultrafast CT as a predictor of coronary artery disease. Radiology 1992; 185: 435–39. 5 Kaufmann RB, Sheedy PF, Breen JF, et al. Detection of heart calcification with electron beam CT: interobserver and intraobserver reliability for scoring quantification. Radiology 1994; 190: 347–52. 6 McCarthy JH, Palmer FJ. Incidence and significance of coronary artery calcification. Br Heart J 1974; 36: 499–506. 7 Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography, J Am Coll Cardiol 1990; 15: 827–32. 8 Elkeles A. A comparative study of calcified atheroma in males and females over 50 years of age. Lancet 1957; ii: 714–15. 9 Dixon AK, Lawrence JP, Mitchell JRA. Age related changes in the abdominal aorta shown by computed tomography. Clin Radiol 1984; 35: 33–37. 10 Shemesh J, Tenebaum A, Fisman EZ, et al. Absence of coronary calcification on double-helical CT scans: predictor of angiographically normal coronary arteries in elderly women. Radiology 1996; 199: 665–68. 11 Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: Pathophysiology, epidemiology, imaging methods and clinical implications. A statement for health care professionals from the American Heart Asociation. Circulation 1996; 94: 1175–92. 12 Moore EH, Greenberg RW, Merrick SH, Miller SW, McCloud TC, Shepard J-AO. Coronary artery calcifications: significance of incidental detection on CT scans. Radiology 1989; 172: 711–16.
1265