A classification scheme for childhood cancer

Int. J. Cancer: 40,620-624 (1987) @ 1987 Alan R. Liss. Inc.

Publicatlon of the International Union Against Cancer Publication de I Union Internationale Contre le Cancer

A CLASSIFICATION SCHEME FOR CHILDHOOD CANCER Jillian M. BIRCH’ and Henry B. MARSDEN University of Manchester, Department of Epidemiology and Social Oncology, Children’s Tumour Registry, Christie Hospital, Withington, Manchester M20 9BX, UK.

The International Agency for Research on Cancer (IARC) is sponsoring a worldwide study of childhood cancer incidence. Cancers in children are highly specific and differ in many ways from cancers found in adults. Data for the international study will be presented according to the classification scheme described below which has been devised specifically for use with paediatric cancers. The features of this scheme are: (I) it is based on the International Classification of Diseases for On- cology (ICD-0); (2) diagnostic groups are defined mainly in terms of morphology; (3) the common types of childhood cancer are individually specified; (4) certain other rare conditions of interest are distinguished; (5) it provides for flexibility of data presentation with respect to amount of detail; (6) all possible combinations of ICD-0 morphology and topography codes are included; and (7) the maximum number of codes has been allocated to specific categories. There is a great need for standardization in the classification of childhood cancers and we propose that the scheme be used for presentation of incidence data for results of aetiological and other related studies of cancer in children.

Cancer is an important cause of mortality and morbidity in children. In England and Wales in 1985, malignant disease was exceeded only by accidents and congenital anomalies as a cause of death in the 1-14 year age range (OPCS, 1986). Little is known about the aetiology of cancer in children although there are indications that genetic factors play a major role in certain tumours (Birch, 1987) and that trans-placental carcinogenesis may be important in some cases (Poskanzer and Herbst, 1977; Allen et al. , 1980; Preston-Martin el a / . , 1982). Prenatal exposure to diagnostic X-rays has also been impli- cated (Monson and MacMahon, 1984).

By comparing the incidence of specific types of cancer among various populations throughout the world, clues to aetiology can emerge (Doll and Peto, 1981). Such comparisons between native and migrant populations can be particularly fruitful in estimating the relative importance of genetic and environmental factors in the aetiology of particular cancers.

International comparisons of cancer rates have in general utilized site-based classifications, mainly ICD. e. g., Cancer Incidence in Five Continents (Waterhouse et a l . , 1982). While this is satisfactory for cancers in adults, the majority of which are carcinomas, it is unsuitable for classifying tumours in children. Childhood tumours form a highly specific group, mainly embryonal in type and arising in the lymphoreticular and central nervous systems, connective tissue and viscera. Epithelial tumours are rare. Many of the more common tumours in children are confined almost entirely to the first few years of life (e .g . , Wilms’ tumour and neuroblastoma) or are much more frequent at this time than at later ages (e .g . , acute lymphocytic leukaemia). Some typical childhood turnours, e .g . , rhabdomyosarcoma, can occur virtually anywhere in the body. Conversely, a malignant retroperitoneal tumour (ICD 158.0) might be a rhabdomyosarcoma or other soft-tissue sarcoma, neuroblastoma, teratoma or yolk-sac tumour, or other more rare entity. Clearly a classification scheme based on morphology would be more suited to cancer in children. The ICD-0 (WHO, 1976) allows for coding of neoplasms by both morphology and site and is satisfactory for use with childhood tumours. However, for the purposes of analysis and tabulation of data it is necessary to define a set of diagnostic categories

by aggregation of groups of codes. It is essential for the definition of these diagnostic categories to be standardized if international comparisons are to be made.

IARC is sponsoring a study of childhood cancer involving data from more than 60 registries throughout the world (Parkin et a l . , 1988). The classification scheme to be used in this study is, with minor modifications, that developed for use with the Manchester (UK) Children’s Tumour Registry data. The pur- pose of this report is to describe the classification scheme and to propose that it should be adopted as the standard form for presentation of data on cancer in children.

MATERIAL AND METHODS

The Manchester Children’s Tumour Registry (MCTR) is population-based and registers cases of all malignant and certain benign tumours in children aged less than 15 years who were resident within the boundaries of the North Western Regional Health Authority of England (Manchester Regional Hospital Board before 1974) at the time of diagnosis. The region has a child population of approximately 1 million. The registry was founded in September 1953 and now contains clinical and histopathological records, including actual histopathological material, on approximately 3,200 cases of childhood malignancy.

In devising a classification scheme for analysis and presentation of data on childhood cancer, several considerations were taken into account.

1 . The classification should be based on an internationally accepted coding system. ICD-0 was chosen as more suitable for childhood tumours than ICD for the reasons described above.

2. The diagnostic groups should be defined mainly in terms of morphology but some site-based groupings should be possible to facilitate comparisons with reports based on ICD and to identify more precisely groups of particular interest.

3. The more common types of childhood cancer should be individually specified.

4. It should also be possible to distinguish certain rare conditions of particular interest, e.g. , hepatoblastoma, adrenal cortical carcinoma and thyroid carcinoma.

5 . There should be a small number of main groups and within each of these a number of sub-divisions. This would provide for flexibility as to the degree of detail with which any particular data set is presented while remaining within a standard framework.

6. The classification should include all possible combinations of ICD-0 morphology and topography codes which can be applied to childhood cancers.

7. The maximum number of codes should be allocated to specific categories so that the number grouped under “other categories” is as small as possible.

‘To whom reprint requests should be sent.

Received: April 1, 1987.

CLASSIFICATION SCHEME FOR CHILDHOOD CANCER 62 1

The classification scheme devised by us for use with the MCTR data has been slightly modified for use in the international study. It is the modified version which is presented here. The ways in which this version differs from the original and the reasons for the modifications are discussed below.

The classification scheme Definitions of the main groups and their sub-categories in

terms of ICD-0 morphology and topography codes are given in the Appendix. Twelve main diagnostic groups have been defined.

Group I : Leukaernias The 2 most common forms of leukaemia seen in children,

acute lymphocytic and acute non-lyrnphocytic, appear as separate categories. Chronic myeloid leukaemia, although rare in children, was thought to be of sufficient interest to merit a separate category. In the original “Manchester” version of the classification “other specified leukaemias” and “undifferenti- ated and unspecified leukaemias” appeared as distinct sub- groups. These have been combined as Group I (e) for the international study since it was felt that no meaningful comparisons between contributing centres could be made by using these “residual” categories. Group II: Lymphomas arid other reticuloeridothelial neoplasms

The main categories in this group are Hodgkin’s disease and non-Hodgkin’s lymphoma (NHL). Burkitt’s lymphoma has been allocated a separate category, being of particular epide- miological interest. It was felt necessary to provide a sub- group for unspecified lymphomas rather than to include these with NHL. We believed that results would be easier to inter- pret if the unspecified lymphomas were kept separate. The precise histogenetic origin of histiocytosis X is a matter of some controversy but, for the purposes of the present study, histiocytosis X (including Letterer-Siwe, Hand-Schiiller- Christian and eosinophilic granuloma) has been classified with the reticuloendothelial neoplasms. We recognise that ascertain- ment of histiocytosis X will be incomplete.

Group 111: Central nervous system and miscellaneous intrucraniul and intruspinal neoplasms

It is the practice of most cancer registries to register benign as well as malignant intracranial neoplasms. Some benign neoplasms and neoplasms of uncertain behaviour have been included in Group 111. “Miscellaneous intracranial and intraspinal neoplasms”, category I11 (e) includes pituitary adeno- mas, craniopharyngioma, pinealoma, ganglioglioma, menin- gioma and unbiopsied intracranial or intraspinal neoplasms, whether benign or malignant. Benign intracranial and intraspinal germ-cell tumours are also included in this category. Since the classification lays emphasis on morphology rather than anatomical site, malignant intracranial germ-cell tumours, soft- tissue tumours, sympathetic nervous system tumours, efc., have been classified with their respective groups.

In the “Manchester” version, juvenile (pilocytic) astrocytoma (ICD-0 M-code = 942113) and other types of astrocytoma have been given separate sub-groups, the behaviour and prognosis of the juvenile type being very much more favour- able than that of other more aggressive types of astrocytoma. For the purposes of the international study a single category for astrocytoma has been used since many registries do not distinguish between juvenile and other types of astrocytoma. Group IV: Sympathetic nervous system tumours

Neuroblastoma (including ganglioneuroblastoma) is the principal tumour type in this group. Other types of sympathetic nervous system tumours, e.g., paragangliomas and phaeo- chromocytoma, are rare in children and have been included as a single sub-category in Group IV.

Group V: Retinoblastomu Retinoblastoma represents a distinct clinical entity and is of

exceptional interest to geneticists, molecular biologists and epidemiologists as well as clinicians. Although rare, we feel this turnour merits a separate group. Group VI: Renal tumours

The majority of childhood renal tumours are Wilms’ tumours but a number of other types of renal tumour do occur. These include mesoblastic nephroma (ICD-0 M- code = 8960/1), a tumour of uncertain behaviour which is usually benign or locally aggressive. Mesoblastic nephroma is not generally regarded as a malignant tumour and therefore not recorded by many cancer registries. For this reason it has not been included in the international study although it has been allocated a separate sub-category in the “Manchester” version of the classification. Recently defined entities, bone metastasizing renal tumour (clear-cell sarcoma) and rhabdoid renal tumour, are not at present distinguished by ICD-0 and for the purposes of the international study will be included with Wilms’ tumour. In the “Manchester” classification each of these tumours has been allocated a specially created M- code. Renal carcinomas are occasionally seen and have been given a separate sub-category. Such rare lesions as primary renal rhabdomyosarcoma or leiomyosarcoma are allocated on the basis of morphology to Group IX. Group VII: Hepatic tumours

Although comprising less than 1% of all childhood malig- nancies, hepatic tumours have been dealt with in some detail. Hepatoblastoma is of interest in genetic and molecular biological studies and hepatic carcinomas may be associated with a viral aetiology. Group VIII: Malignant bone tumours

The most frequent bone tumours in children are osteosarcoma and Ewing’s sarcoma, although ethnic variations are seen (Kramer et al., 1983). Chondrosarcoma is much less frequent but represents a distinct entity and appears as a separate sub-category . Mesenchymal chondrosarcoma of soft tissue and soft-tissue Ewing’s tumour are included in Group IX. Group IX: Soft-tissue sarcomas

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Embryonal sarcomas in children in which no rhabdomyoblastic differentiation is seen are nevertheless probably related to rhabdomyosarcoma. Together with soft- tissue Ewing’s tumour, which resembles alveolar rhabdomyosarcoma, these tumours form the main sub-category of Group IX.

A number of fibromatous neoplasms are seen in children including fibrosarcoma, malignant fibrous histiocytoma and neurofibrosarcoma. These tumours form the second sub- category.

Other soft-tissue sarcomas are very uncommon in children and are grouped to form the third sub-category in Group IX. Group X: Germ-cell, trophoblastic and other gonadal neoplasms

The main feature of this group is that we have distinguished between gonadal and non-gonadal lesions. The gonads repre- sent the most common site of malignant germ-cell turnours in children and this distinction enables gonadal tumours to be examined as a group. Malignant intracranial germ-cell tumours are included with the first sub-category of this group, as discussed above. Group XI: Carcinoma and other malignant epithelial neoplasms

Carcinomas in children, although uncommon, present a group worthy of study. While generic and other prenatal

622 BIRCH AND MARSDEN

factors may predominate in the embryonal tumours, it is likely CONCLUSION that extrinsic factors may be of greater importance in carcinomas. International comparisons of the incidence of childhood carcinomas have not hitherto been possible and it is hoped that There is a paucity of data on the incidence of cancer in the forthcoming study will yield some interesting results. children specified by morphology. Such data as are available

Adrenocortical carcinoma is associated with familial cluster- (e.g. , Young and Miller, 1975; Ericsson, 1978; Birch et al., ing of cancers and with a high risk of subsequent primary 1980; McWhirter and Bacon, 1981; Draper et al., 1982; Kra- neoplasms. For these reasons this rare tumour has been allo- mer ef al . , 19837 and data from USA presented by Bredow cated a separate sub-category. and Langholz, 1983) have not been classified in a standard

way and, with the exception of Draper et al. (1982), do not

melanoma. Carcinomas of these sites are seen more frequently comparisons are difficult to make in these circumstances. in children than carcinomas of sites common in adults, e.g., lung, breast and colon. Separate sub-categories have therefore been allocated to these turnours. carcinomas of kidney, liver mise but we feel that the overriding need is for standardization. and gonads are represented by individual sub-categories in We hope that the classification scheme presented here will be Groups VI, VII and X respectively. acceptable to all those concerned with the study of cancer in

children and will be used not only for data on incidence but Group XU: Other and unspecified malignant neoplasms also for the presentation of results of aetiological and other

We have sought to keep this “residual” group as small as related studies. possible. The group includes embryonal-type carcinosarcoma and occasional examples may be seen in the lung (pneumo- blastoma) or pancreas (pancreaticoblastoma). Malignant gran- ular-cell myoblastoma is also included in this group.

Non-biopsy-proven extra-cranial lesions should only be included in a study if there is convincing clinical evidence that the lesion is a malignant tumour.

factors may be imp1icated in the development define a set of diagnostic groups incorporating all cancers in Of carcinoma Of the thyroid, nasopharyngeal carcinoma and children in terms of an accepted coding system, International

classification scheme must a degree Of

ACKNOWLEDGEMENT

The Manchester Children’s Tumour Registry is supported by the Cancer Research Campaign.

REFERENCES

ALLEN, R.W., JR., OGDEN, B.. BENTLEY, F.L., and YUNG, A.L., Fetal hydantoin syndrome, neuroblastoma and hemorrhagic disease in a neo- nate. J. Amer. med. Ass., 244, 1464-1465 (1980). BIRCH, J.M.. Genetic determinants of cancer in man. In: M.J. Waring and B.A.J. Ponder (eds.), Biology of carcinogenesis, pp. 165-189, M.T.P. Press, London (1987). BIRCH, J.M., MARSDAN, H.B., and SWINDELL, R., Incidence of malignant disease in childhood: A 24-year review of the Manchester Children’s Tumour Registry data. Brit. J . Cancer, 42, 215-223 (1980). BRESLOW, N.E., and LANCHOLZ, B., Childhood cancer incidence: geo- graphical and temporal variations. Ini. J . Cancer, 32, 703-716 (1983). DOLL, R., and PETO, R., The causes ofcancer. Oxford University Press, New York (1981). DRAPER, G.J., BIRCH, J.M., BITHELL, J.F., KINNIER WILSON, L.M., LECK, I., MARSDEN, H.B., MORRIS JONES, P.H., STILLER, C.A., and SWINDELL, R. , Childhood cancer in Britain. Incidence, survival and mortality. Stud- ies on medical and population subjects 37. Office of Population Censuses and Surveys, London (1982). ERICSSON, J.L.E., KARNSTROM, L., and MATTSSON, B., Childhood cancer in Sweden, 1958-1974. I. Incidence and mortality. Acta paediat. Scand.,

KRAMER. S. , MEADOWS, A.T.. JARRETT, P., and EVANS, A.E., lncidence of childhood cancer: experience of a decade in a population-based registry. J. nut. Cancer Inst., 70,49-55 (1983).

67,425-432 (1978).

MCWHIRTER, W.R., and BACON, J.E.. Incidence of childhood tumours in Queensland. Brii. J . Cancer, 44,637-642 (1981). MONSON, R.R., and MACMAHON, B., Prenatal X-ray exposure and cancer in children. In: J.D. Boice, Jr. and J.F. Fraumeni, Jr. (eds.), Radiarion carcinogenesis: epidemiology and biological signi’jcance, pp. 97- 105, Raven Press. New York (1984). OFFICE OF POPULATION CENSUSES AND SURVEYS. Deaths by cause, 1985. Reference DH2 86/2. London (1986).

and YOUNG, J.A. (eds.), International Incidence of Childhood Cancer, IARC Scientific Publications (1988). POSKANZER, D.C., and HEKBST, A.L.. Epidemiology of vaginal adenosis and adenocarcinoma associated with exposure to stilbestrol in utero. Can- cer, 39, 1892-1895 (1977). PRESTON-MARTIN. S., Yu MIMI, C., BENTON, B., and HENDERSON, B.E.. N-nitroso compounds and childhood brain tumours: A case-control study. Cancer Res., 42, 5240-5245 (1982). WORLD HEALTH ORCANISATION. ICD-0. Internaiional Class$cation of Diseases for Oncology, 1st ed., WHO, Geneva (1976). WATERHOUSE, J., MUIR, C . , SHANMUGARATNAM, K., and POWELL, J., (eds.). Cancer incidence in five continents, Vol. IV, IARC Scieniific Publication 42, IARC, Lyon (1982). YOUNG, J.L., and MILLER, R.W., Incidence of malignant tumours in US children. J. Pediai., 86, 254-258 (1975).

PARKIN, D.M., BIEBER. A,, DRAPER, G.J., STILLER, C.A.. TERROCINI, B..

APPENDIX - CLASSIFICATION SCHEME FOR CHILDHOOD CANCER: DEFINITION OF DIAGNOSTIC GROUPS

ICD-0 M-code ICD-0 M-code ICD-0 First 4 digits 5th digits T-code Diagnostic group

I . Leuhemias (a) Acute lymphocytic leukaemia (b) Other lvmohoid leukaemia 9820.9822.9823.

982 1,9824

(c) Acute non-IvmDhocvtic leukaemia

(d) Chronic myeloid leukaemia

9825;9850’ 9840,9841,9861. 9864,9866,9891, 9894 9863 3

APPENDIX - CLASSIFICATION SCHEME FOR CHILDHOOD CANCER: DEFINITION OF DIAGNOSTIC GROUPS (conrinuedJ

ICD-0 M-code ICD-0 M-code First 4 dieits 5th dieits Diagnostic group icd-0

T-code

(e) Other and unspecified leukaemia 9800,9804, 9810,9830,9842, 9860.9862.9865.

3

987019890,9892, 9893,9900-9940

11. Lymphomas and other reticuloendothelial neoplasms (a) Hodgkin’s disease 9650-9662 (b) Non-Hodgkin lymphoma 9591,9602-9642,

9690-9701 (c) Burkitt’s lymphoma (d) Unspecified lymphomas (e) Histiocytosis-X

9750 9590,9600,960 1 9722 (also SNOMED morphology codes 77860,77910,77920) 9710-9721, 9730-9741

(0 Other reticuloendothelial neoplasms

Central nervous system and miscellaneous intracranial and intra-spinal neoplasms

111.

(a) Ependymoma (b) Astrocytoma

(c) Medulloblastoma (d) Other glioma

9383,9390-9394

9381,9400-9441 9470-9480

9380

9380

9382,9384,

9481 9442-9460,

192.0

191 .O- 191.9, 192.1- 192.9

(e) Miscellaneous intracranial and intraspinal neoplasms

8270-8281,8300, 9350-9362.9505. 9530-9539 9060-9 102

8000-8004

9990

19 1 .O- 192.9,

19 1 .O- 192.9,

191 .O-192.9,

194.3,194.4

194.3,194.4

194.3,194.4 IV. Sympathetic nervous system tumours

(a) Neuroblastoma and

(b) Other ganglioneuroblastoma

9490,9500

8680,8693-8710, 9501-9504, 9520-9523 95 10-95 12

8960

8050,8120,8122, 8 130,8 140,8230, 8231,8260,8310 8312 8961,8962

8010-8041,8043,

8000-8004,9990

8970

8140,8230,8231, 8260

8010-8041,8O43,

8160-8180 8000-8004,9990

V . Retinoblastoma VI. Renal tumours

(a) Wilms’ tumour (b) Renal carcinoma 189.0

(c) Other and unspecified malignant renal tumours

189.0

155.0,155.1

VII. Hepatic tumours (a) Hepatoblastoma (b) Hepatic carcinoma

(c) Other and unspecified malignant

(a) Osteosarcoma (b) Chondrosarcoma

hepatic tumours VIII. Malignant bone tumours

155.0.155.1

91 80-9190 9220-9230 9240

9260

88 12,9250, 926 1-9330,9370 8000-8004, 8800,8801, 8803,9990

170.0- 170.9, 199.9 170 .O- 170.9, 199.9

(c) Ewing’s sarcoma

(d) Other and unspecified malignant bone tumours

170 .O- 170.9

(continued)

APPENDIX - CLASSIFICATION SCHEME FOR CHILDHOOD CANCER: DEFINITION OF DIAGNOSTIC GROUPS (continued)

ICD-0 M-code First 4 digits -

Diagnostic group

IX. Soft-tissue sarcomas (a) Rhabdomyosarcoma, embryonal sar- 89oO-8920,899 1

coma and soft-tissue Ewing’s tumour 9260

8810,881 1, other fibromatous neoplasms 8813-8832,9540,

9560 (c) Other soft-tissue sarcoma 8840-8895,8990,

9040-9044, 9 120-9170,925 1,

(b) Fibrosarcoma, neurofibrosarcoma, and

9581 9240

8800-8804

X. Germ-cell, trophoblastic and other gonadal neoplasms (a) Non-gonadal germ-cell and trophoblas- 9060-9 102

tic neoplasms

(b) Gonadal germ-cell and trophoblastic

(c) Gonadal carcinoma 8010-804 1,8043,

9060-9102 neoplasms

8 140,8230,823 1, 8260,83 10,8440, 8480,8481 8381,844-8471 8600-8650,9000 (d) Other and unspecified malignant

gonadal tumours 8ooO-8004,9990

(c) Nasopharyngeal carcinoma

(d) Melanomatous neoplasms (e) Other carcinoma

XI. Carcinoma und other malign an^ epithelial neoplasms (a) Adrenocortical carcinoma 8370 (b) Thyroid carcinoma 8010-8041,8043,

8050,8070,8 140, 8230,8231,8260, 8290,8480,85 10 8330-8350,8511 8010-8041,8043, 8070-8082.8 120,

8720-8780 8010-8 154, 8190-8310, 8320-8323,8380 8390- 8440, 8480-8510, 85 12-8580,

8 140,8480,8560

8940

XII. Other and unspecijied malignant neoplasms 8930,8950,895 I , 8980,8981,9020,

9580 9050-9053,9110,

8000-8004.9990

ICD-0 M-code icd-0 5th digits T-code

3 ,63

3,6,9 140.0-169.9, 171.0-195.8

3,6,9

3,6.9

3,6.9

I40 .O- 169.9, 17 1 .O- 195.8 140.0- 169.9, I7 I .O- 199.9

140.0-182.8,

187.1-199.9 183.2- 185.9,

183 .O, 186.0, 186.9 1 83 .O, 1 86.0, 186.9

183.0,186.0, 186.9

194.0 193.9

147.0- 147.9

140.0-146.9, 148.0- 154.8, 156.0-165.9. 1 73 .O- 1 82.8, 183.2-1 85.9. 187.1- 188.9, 189.1-192.9, 194.1-195.8, 199.9

140.0- 154.8, 156.0-169.9, 17 1 .O- 182.8, 183.2-185.9, 187.1-188.9, 189.1 - 190.9, 193.9-194.1, 194.5- 199.9

Notes 1. In the above classification. we believe that we have included virtually all possible types of carcinoma (M codes 8010-8580) occurring in the kidney, liver, ovary, testis,

adrenal cortex. thyroid and nasophavnx. However, should verified carcinomas of other morphological types be found in any of these sites, we recommend that they be included with the other carcinomas ofthe same site for statistical purposes.

2. The above classification assumes that the usual cancer registry practice of coding only the primary site of metastatic tumours is followed. Data for the international studv of childhood cancer incidence have been coded in this way. For use with data coded according to the ICD-0 rules. so that the site code indicates where the biopsy was kk&, an alternative version of the classification scheme is available on request

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A classification scheme for childhood cancer