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INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS No.25

Histological Typing of Kidney Tumours

WORLD HEALTH ORGANIZATION ISBN 9241760257 ©World Health Organization 1981

Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. For rights of reproduction or translation of WHO publications, in part or in toto, application should be made to the Office of Publications, World Health Organization, Geneva, Switzerland. The World Health Organization welcomes such applications. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Director-General of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. Authors alone are responsible for views expressed in this publication.

PRINTED IN THE UNITED STATES OF AMERICA 79/4368-Waverly-5750 INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS No. 25

HISTOLOGICAL TYPING OF KIDNEY TUMOURS

F. K. MOSTOFI Head, WHO Collaborating Centre for the Histological Classification of Male Urogenital Tract Tumours, Armed Forces Institute of Pathology, Washington, DC, USA

in collaboration with

I. A. SESTERHENN L. H. SOBIN Armed Forces Institute Pathologist, of Pathology, World Health Organization, Washington, DC, USA Geneva, Switzerland

and pathologists in seven countries

WORLD HEALTH ORGANIZATION GENEVA 1981 PARTICIPANTS

WHO Collaborating Centre for the Histological Classification of Male Urogenital Tract Tumours/ Armed Forces Institute of Pathology, Wash­ ington, DC, USA

Head of Centre Dr. F. K. Mostofi

Participants Dr E. CHAVES, Department of Pathology, Hospital of Paraiba, Joao Pessoa, Paraiba, Brazil Dr L. GALINDO, Department of Pathology, Hospital Santa Cruz y San Pablo, Fundaci6n Puigvert, Universidad Aut6noma, Barcelona, Spain Dr C. GouYGOu, 2 Service central d'Anatomie pathologique, Centre hospi­ talo-universitaire Henri Mondor, Creteil, France Dr N. A. KRAYEVSKY, Department of Pathology, Cancer Research Centre of the USSR Academy of Medical Sciences, Moscow, USSR Dr V. J. McGovERN, Fairfax Institute of Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia Dr M.S. RAGBEER, Department of Pathology, University ofthe West Indies, Mona, Kingston, Jamaica, West Indies Dr L. H. SoBIN, Cancer Unit, WHO, Geneva, Switzerland Dr A. C. THACKRAY, Bland-Sutton Institute of Pathology, Middlesex Hos­ pital Medical School, London, England

1 This centre deals with tumours of the urinary bladder, testis, kidney, and prostate. The participants listed here have dealt only with kidney tumours. 2 Deceased. ALREADY PUBLISHED IN THIS SERIES:

No. 1. Histological typing of tumours (1967) No. 2. Histological typing of breast tumours (1968) No. 3. Histological typing of tumours (1969) No. 4. Histological typing of oral and oropharyngeal tumours (1971) No. 5. Histological typing of odontogenic tumours, jaw , and allied lesions (1971) No. 6. Histological typing of bone tumours (1972) No. 7. Histological typing of salivary gland tumours (1972) No. 8. Nomenclature of cytology of the female genital tract (1973) No. 9. Histological typing of ovarian tumours ( 1973) No. 10. Histological typing of urinary bladder tumours (1973) No. 11. Histological typing of thyroid tumours (1974) No. 12. Histological typing of tumours (1974) No. 13. Histological typing offemale genital tract tumours (1975) No. 14. Histological and cytological typing of neoplastic diseases of hae- matopoietic and lymphoid tissues (1976) No. 15. Histological typing of intestinal tumours (1976) No. 16. Histological typing of testis tumours (1977) No. 17. Cytology of non-gynaecological sites (1977) No. 18. Histological typing of gastric and oesophageal tumours (1977) No. 19. Histological typing of upper respiratory tract tumours (1978) No. 20. Histological typing of tumours of the liver, biliary tract and (1978) No. 21. Histological typing of tumours of the central nervous system ( 1979) No. 22. Histological typing of prostate tumours (1980) No. 23. Histological typing of endocrine tumours (1980) No. 24. Histological typing of tumours of the eye and its adnexa (1980) CONTENTS

Page General preface to the series 9

Preface to Histological typing of kidney tumours . 11

Introduction . 13

Histological classification of kidney tumours 15

Definitions and explanatory notes 17

Index. 25

Colour photomicrographs

The photomicrographs reproduced in this volume were taken by Mr B. B. Allen, Jr, and Mr L. Duckett, Armed Forces Institute of Pathology, Washington, DC, USA. -7-

GENERAL PREFACE TO THE SERIES

Among the prerequisites for comparative studies of cancer are international agreement on histological criteria for the classification of cancer types and a standardized nomenclature. At present, pathologists use different terms for the same pathological entity, and furthermore the same term is sometimes applied to lesions of different types. An internationally agreed classification of tumours, acceptable alike to physicians, surgeons, radiologists, pathologists and statisti­ cians, would enable cancer workers in all parts of the world to compare their findings and would facilitate collaboration among them. In a report published in 1952, 1 a subcommittee of the WHO Expert Committee on Health Statistics discussed the general principles that should govern the statistical classification of tumours and agreed that, to ensure the necessary flexibility and ease in coding, three separate classifications were needed according to (1) anatomical site, (2) histological type, and (3) degree of malignancy. A classification according to anatomical site is available in the International Classification of Diseases. 2 The question of establishing a universally accepted classification by histolog­ ical type has received much attention during the last 20 years and a particularly valuable Atlas of Tumor Pathology-already numbering more than 40 vol­ umes-is being published in the USA by the Armed Forces Institute of Pathology under the auspices of the National Research Council. An Illustrated Tumour Nomenclature in English, French, German, Latin, Russian and Spanish has also been published by the International Union Against Cancer (UICC). In 1956 the WHO Executive Board passed a resolution3 requesting the Director-General to explore the possibility that WHO might organize centres in various parts of the world and arrange for the collection of human tissues and their histological classification. The main purpose of such centres would be to develop histological definitions of cancer types and to facilitate the wide adoption of a uniform nomenclature. This resolution was endorsed by the Tenth World Health Assembly in May 19574 and the following month a Study Group on Histological Classification of Cancer Types met in Oslo to advise WHO on its implementation. The Group recommended criteria for selecting tumour sites

1 , WHO Technical Report Series, No. 53, 1952, p. 45. 2 WoRLD HEALTH ORGANIZATION. Manual of the international statistical classification of diseases, injuries, and causes of death, 1975 revision. Geneva, 1977. 3 WHO Official Records, No. 6R, 1956, p. 14 (resolution EB 17.R40). 4 WHO Official Records, No. 79, 1957, p. 467 (resolution WHAIO.lS). -9- lO INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS for study and suggested a procedure for the drafting of histological classifica­ tions and testing their validity. Briefly, the procedure is as follows: For each tumour site, a tentative histopathological typing and classification is drawn up by a group of experts, consisting of up to ten pathologists working in the field in question. A centre and a number of collaborating laboratories are then designated by WHO to evaluate the proposed classification. These labo­ ratories exchange histological preparations, accompanied by clinical informa­ tion. The histological typing is then made in accordance with the proposed classification. Subsequently, one or more technical meetings are called by WHO to facilitate an exchange of opinions and the classification is amended to take account of criticisms. In addition to preparing the publication and the photomicrographs for it, the centre produces up to 100 sets of microscope slides showing the major histolog­ ical types for distribution to national societies ofpathology. Since 1958, WHO has established 23 centres covering tumours of the lung; breast; soft tissues; oropharynx; bone; ; salivary glands; thyroid; skin; male urogenital tract; jaws; female genital tract; stomach and oesophagus; intestines; central nervous system; liver, biliary tract and pancreas; upper respiratory tract; eye; and endocrine glands; as well as oral precancerous conditions; the leukaemias and lymphomas; comparative ; and exfol­ iative cytology. This work has involved more than 300 pathologists from over 50 countries. Most of these centres have completed their work, and their classifications have already been published (see page 6). The World Health Organization is indebted to the many pathologists who have participated in this large undertaking. The pioneer work of many other international and national organizations in the field ofhistological classification of tumours has greatly facilitated the task undertaken by WHO. Particular gratitude is expressed to the National Cancer Institute, USA, which, through the National Research Council and the USA National Committee for the International Council of Societies of Pathology, is providing financial support to accelerate this work. Finally, WH 0 wishes to record its appreciation of the valuable help it has received from the International Council of Societies of Pathology (ICSP) in proposing participants and in undertaking to distribute copies of the classifications to national societies ofpathology all over the world. PREFACE TO HISTOLOGICAL TYPING OF KIDNEY TUMOURS

The WHO Collaborating Centre for the Histological Classification of Male Urogenital Tract Tumours was established at the Armed Forces Institute of Pathology, Washington, DC, USA.

The Centre prepared and distributed microscope specimens from selected cases of kidney tumours to the participants for histological typing according to a tentative classification. This was subsequently reviewed and modified in the light of the study.

It will, of course, be appreciated that the classification reflects the present state of knowledge, and modifications are almost certain to be needed as experience accumulates. Although the present classification has been adopted by the members of the group, it necessarily represents a view from which some pathologists may wish to dissent. It is nevertheless hoped that, in the interests of international cooperation, all pathologists will try to use the classification as put forward. Criticism and suggestions for its improvement will be welcomed; these should be sent to the World Health Organization, Geneva.

The publications in the series International Histological Classification of Tumours are not intended to serve as textbooks but rather to promote the adoption of a uniform terminology of tumours that will facilitate and improve communication among cancer workers. For this reason the literature references have intentionally been kept to a minimum and readers should refer to standard works on the subject for extensive bibliographies.

-11-

INTRODUCTION

This classification is based primarily on the microscope characteristics of tumours and therefore is concerned with morphologically identifiable cell types and histological patterns as seen with conventional light microscopy. The term tumour is used synonymously with . The phrase tumour­ like is applied to lesions which clinically or morphologically resemble , but do not behave biologically in a neoplastic manner. They are included in this classification because they give rise to problems in differ­ ential diagnosis and because of the unclear borderline between neoplasms and certain non-neoplastic lesions. Synonyms are listed only if they have been widely used, or if they are considered to be helpful for the understand­ ing of the lesion. In such cases, the preferred term is given first, followed by the synonym in brackets. Although the emphasis of this classification is on histological typing, in the examination of kidney tumours consideration should be given to the degree of cellular anaplasia, extent of local spread, vascular and lymphatic invasion and the occurrence of metastasis. The scheme of histological grading suggested here is as follows: Grade I applies to the tumours that have the least degree of cellular anaplasia compatible with a diagnosis of malignancy; Grade III applies to tumours with the most severe degrees of cellular anaplasia; and Grade II lies in between. This scheme is applicable to the of the renal paren­ chyma and pelvis. In addition to histological assessment, the clinical and histopathological staging of the extent of the tumour should be taken into account for the purposes of treatment and prognosis. Such a system of staging has been developed by the International Union Against Cancer.1 The main histopath­ ological categories for renal cell regarding local spread are as follows: pTl A small tumour without enlargement of the kidney. There is limited calyceal distortion or deformity and the tumour is surrounded by renal parenchyma. pT2 A large tumour with deformity and/or enlargement of the kidney or calyceal or pelvic involvement. The continuity of the cortex is pre­ served. pT3 Evidence of spread into perinephric fat, peripelvic fat or hilar renal vessels.

1 HARMER, M. H. (ED.) TNM classification of malignant tumours, 3rd ed. Geneva, Interna­ tional Union Against Cancer, 1978. -13- 14 INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS pT4 Evidence of extension into neighbouring organs or abdominal wall. The histological classification which appears on pages 15 and 16 contains the corresponding morphology code numbers of the International Classifi­ cation of Diseases for Oncology (ICD-0)1 for tumours, and of the Systema­ tized Nomenclature of Medicine (SNOMED)2 for tumour-like lesions.

1 WoRLD HEALTH ORGANIZATION. International classification of diseases for oncology (ICD- 0). Geneva, 1976. 2 COLLEGE OF AMERICAN PATHOLOGISTS. Systematized nomenclature of medicine (SNOMED). Chicago, IL, 1976. HISTOLOGICAL CLASSIFICATION OF KIDNEY TUMOURS

I. EPITHELIAL TUMOURS OF RENAL PARENCHYMA A. ADENOMA 8140/0* B. CARCINOMA I. 8312/3 2. Others

II. EPITHELIAL TUMOURS OF RENAL PEL VIS A. TRANSITIONAL CELL PAPILLOMA 8120/0 B. TRANSITIONAL CELL CARCINOMA 8120/3 c. 8070/3 D. OF RENAL PELVIS 8140/3 E. UNDIFFERENTIATED CARCINOMA OF RENAL PELVIS 8020/3

III. NEPHROBLASTIC TUMOURS A. NEPHROBLASTOMA (WILMS' TUMOUR] 8960/3 B. 8960/1 c. MULTILOCULAR CYSTIC NEPHROMA a

IV. NON-EPITHELIAL TUMOURS A. BENIGN I. 8860/0 2. 8810/0 3. Haemangioma 9120/0 4. Others B. MALIGNANT

V. MISCELLANEOUS TUMOURS A. JUXTAGLOMERULAR CELL TUMOUR 8361/1 B. OTHERS

• These numbers refer to the morphology coding of the ICD-0 and SNOMED. "No code available.

-15- 16 INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS

VI. SECONDARY TUMOURS ____ j6b

VII. UNCLASSIFIED TUMOURS 8000/-c

VIII. TUMOUR-LIKE LESIONS A. PERSISTENT RENAL BLASTEMA 21400 B. MASSIVE RENAL BLASTEMA a c. RENAL DYSGENESIS 20000 D. VASCULAR MALFORMATIONS 24600 E. CYSTS 33400 F. RENAL TUBULAR HYPERPLASIA 72000 G. XANTHOGRANULOMATOUS PYELONEPHRITIS 44070 H. MALAKOPLAKIA 43180 I. OTHERS

"No code available. b Code specific type. ' /0 for benign; /3 for malignant tumours. DEFINITIONS AND EXPLANATORY NOTES

I. EPITHELIAL TUMOURS OF RENAL PARENCHYMA

A. ADENOMA (Fig. 1-7): A benign epithelial tumour of the renal paren­ chyma. A renal adenoma is composed of uniform cells with regular nuclei seldom exhibiting mitotic activity. The cytoplasm is scant and may be clear or granular, or a mixture. The tumour is circumscribed but has no capsule. Adenomas may be compact, or to a varying extent cystic, and the tumour cells may either line tubular structures or be arranged in papillary formations. These descriptive terms may be applied to appropriate tumours but as the arrangement and proportions of the cells may vary in different areas of any one tumour, and as there seems to be no practical value in further subdivi­ sions, the tumours are best classified simply as "adenoma". Rarely, some or all of the cells have finely granular strikingly eosinophilic cytoplasm, rich in mitochondria, the so-called oncocytic appearance. Tu­ mours entirely composed of such cells may reach a large size, with a characteristic brownish cut surface. Although the distinction between adenomas and small grade I carcinomas may not be possible on a histological basis, single layers of cells with little cytoplasm and small regular nuclei and the presence of prominent fibrovas­ cular stalks in papillary tumours (Fig. 1) favour the diagnosis of a benign tumour. Adenomas rarely cause symptoms and are usually found incidentally during surgical procedures or radiographic examinations, or at autopsy. B. CARCINOMA l. Renal cell carcinoma (Fig. 8-29): A malignant epithelial tumour of the renal parenchyma. These tumours often show a glandular pattern with cuboidal and columnar cells arranged in acinar, tubular, cystic, and papillary formations of varied size and shape. Some tumours, however, contain large areas where the cells are in cords or pavemented masses, and a few are entirely solid. The tumour cells may have a fmely granular cytoplasm, but most often the cells are large and contain abundant lipid and glycogen in their cyto­ plasm, which appears vacuolated or even quite clear in paraffin sections. These clear cells are the commonest cell type and may be the only component. Cell membranes are distinct. Nuclei are usually small, dense and regular with little mitotic activity. These cytoplasmic and nuclear characteristics often result in a deceptively bland appearance. A few tumours are entirely made up of granular cells. Mixtures of these two main cell types are often seen. Rarely, cells of oncocytic type may be found in malignant tumours. In -17- 18 INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS anaplastic tumours, there is pleomorphism, with or without giant cells, and increased mitotic activity. One variety has spindle-shaped cells and this spindle cell carcinoma may give rise to confusion with or invading pelvic carcinomas. The stroma of renal cell carcinomas varies in its density and extent, but is usually scant and very vascular with large thin-walled blood spaces which give a characteristic angiographic appearance. The papillary-cystic and spindle cell varieties are very much less vascular. Collections of foamy histiocytes, haemorrhages, necrosis, and calcification are frequent in these tumours. Cartilaginous and osseous have been described. Around the expanding tumour, there is often dense capsule­ like fibrosis. Blood vessel and lymphatic invasion, renal capsular penetration and involvement of renal pelvis and hilar structures are common. These structural variables account for the typically variegated macroscop­ ical appearance. Cysts may form within tumours and carcinomas may arise in the lining of a pre-existing . The occurrence of multiple renal tumours, i.e., carcinomas and adenomas, and cysts is a feature of von Hippel-Lindau disease. Renal cell carcinoma has been known as renal adenocarcinoma, hyper­ nephroma, and Grawitz tumour. 2. Others Most renal cell carcinomas arise in the cortex, probably from convoluted tubules. Rarely, carcinomas originate in the medulla and some of these may mimic the of the collecting tubules, i.e., ducts of Bellini, with appearances ranging from columnar to stratified. Tubular, papillary, trabe­ cular and solid patterns occur, frequently mixed (Fig. 30-33).

II. EPITHELIAL TUMOURS OF RENAL PEL VIS

The classification, definitions and terminology of tumours of the renal pelvis correspond to the scheme devised for tumours of the urinary bladder.' A. TRANSITIONAL CELL PAPILLOMA: A papillary tumour with a delicate fibrovascular stroma covered by regular transitional epithelium indistin­ guishable from that of the normal renal pelvis and not more than six layers thick. The individual cells are slender and lie parallel to each other, at right angles to the basement membrane. Mitotic figures are either extremely rare or entirely absent. If present, they are located in the basal region. The nuclei are of uniform size and show finely distributed chromatin. Anaplasia is absent. Transitional cell papilloma as defined is very rare, and most papillary tumours of the renal pelvis are carcinomas.

1 MOSTOFI, F. K., SOBIN, L. H. & TORLONI, H. Histological typing of urinary bladder tumours. Geneva, World Health Organization, 1973 (International Histological Classification of Tumours, No. 10). HISTOLOGICAL TYPING OF KIDNEY TUMOURS 19 B. TRANSITIONAL CELL CARCINOMA (Fig. 34-36): A tumour of transitional epithelium showing anaplasia or invasion. The criteria for anaplasia are: increased cellularity, nuclear crowding, disturbances of cellular polarity, failure of differentiation from the base to the surface, irregularity in size and shape of cells, variations of shape and chromatin pattern of the nuclei, displaced or abnormal mitotic figures, and giant cells. It must be emphasized that some of these features may be present in certain inflammatory, reactive or regenerative conditions, without signi­ fying malignancy. A papillary lesion showing any degree of anaplasia as defined above should be diagnosed as carcinoma. This diagnosis can and should be made on the basis of such anaplastic changes, even in the absence of any evidence of invasion. The degree of cellular anaplasia forms the basis of histological grading of these tumours (see Introduction). The growth patterns of transitional cell carcinomas of the renal pelvis are similar to those of the bladder, namely, papillary; papillary and infiltrating; infiltrating; and nonpapillary-noninfiltrating (carcinoma in situ). As in the bladder, transitional cell carcinoma may contain foci of squa­ mous and/or glandular elements. C. SQUAMOUS CELL CARCINOMA (Fig. 37): A malignant epithelial tumour with cells forming keratin or having intercellular bridges. The tumour must be of one cell type. 0. ADENOCARCINOMA OF RENAL PELVIS (Fig. 38): A malignant epithelial tumour with cells forming glands, with varying amounts of mucus production. This rare tumour must be distinguished from pyelitis glandularis and pyelitis cystica, which are more common conditions. E. UNDIFFERENTIATED CARCINOMA OF RENAL PELVIS: A malignant tumour of epithelial structure that is too poorly differentiated to be placed in any of the other groups of pelvic carcinoma. The term "undifferentiated" is used in a histological sense and is not employed here as a synonym for cellular anaplasia. When an undifferentiated pelvic tumour invades the kidney substance, there may be difficulty in distinguishing it from a primary tumour of the parenchyma or secondary tumour from elsewhere.

III. NEPHROBLASTIC TUMOURS

The entities described in this section and some of those considered to be tumour-like lesions, namely, persistent renal blastema, massive renal blas­ tema and renal dysgenesis (VIlLA, Band C below) occur mainly in infants and children and rarely in adults. Occasionally, and particularly in infants and children, a renal tumour may contain elements of more than one of the above entities, indicating that a distinct interrelationship exists. 20 INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS A. NEPHROBLASTOMA (WILMS' TUMOUR] (Fig. 39-55): A malignant tumour of primitive nephroblastic tissue which forms structures resembling those of embryonic kidney. It occurs primarily in children.

This process may result in the formation of recognizable structures or may halt at less mature stages. A typical nephroblastoma is one in which there is a mixture of primitive nephroblastic tissue, epithelial cells forming tubules, glomerulus-like structures, and mesenchymal, often oedematous, tissue, sometimes with smooth and , cartilage and bone. While most nephroblastomas show this mixed pattern, the tumour may consist predom­ inantly or entirely of blastemal, epithelial or mesenchymal elements. The blastema! pattern shows a predominance of nests of small darkly stained primitive undifferentiated cells without tubular structures. The epi­ thelial form has tubules l~ned by primitive epithelium. The presence of tubules distinguishes this from neuroblastoma and immaturity of these cells, from renal cell carcinoma and pelvic carcinoma. The mesenchymal or stromal variety is composed typically of stromal elements mixed with some primitive nephroblastic tissue, i.e., blastema. Areas of leiomyosarcoma or may be present in the mixed form, as may papillary, mucous or squamous epithelial structures. Very rarely, foci resembling neuroblastoma (with rosettes) and ganglion cells occur in a nephroblastoma. Nephroblastomas are distinguished from persistent and massive renal blastemas by the presence of stromal elements in the neoplasms and the typical subcapsular location of the blastemas.

B. MESOBLASTIC NEPHROMA (Fig. 56-59): A tumour composed of spindle cells resembling arranged in interlacing bundles without sharp demarcation from the surrounding renal parenchyma, commonly intermingled with nephrons. These tumours typically occur in newborns and young infants.

The lesion can involve the kidney in a segmental manner extending from the renal pelvis to the capsule. It may contain scattered islands of cartilage as well as cysts. Mitoses, even if frequent, do not necessarily indicate malignancy. Although in most cases this lesion is benign and often regarded as hamartomatous in nature, recurrence and local extension have been observed. In rare cases foci of nephroblastoma or occur, and these should be recorded. The terms leiomyomatous hamartoma, fetal hamartoma, and congenital mesoblastic nephroma have also been used.

C. MULTILOCULAR CYSTIC NEPHROMA (Fig. 60-65): A solitary, multilocular cystic lesion, usually unilateral, containing mesenchymal stroma. Microscopically, the cysts vary in size and are lined by flattened or hobnail epithelium. They are set in a loose mesenchymal stroma which in adults is usually more cellular than in infants and resembles ovarian stroma. This lesion occurs predominantly in adult females and male infants and is usually HISTOLOGICAL TYPING OF KIDNEY TUMOURS 21 benign. Foci of nephroblastoma may be present and very rarely the stroma is sarcomatous. These should be recorded. This lesion has also been referred to as multilocular cyst.

IV. NON-EPITHELIAL TUMOURS

A. BENIGN l. Angiomyolipoma (Fig. 66-69): A benign tumour consisting of a mixture of fat cells, smooth muscle and tortuous vessels which may have very cellular or hyalinized thick walls. There may be cellular pleomorphism with giant cell formation. This lesion is sometimes a component of the tuberous sclerosis complex, in which case small and multiple tumours are usually present. In rare instances local extension and lymph node involvement have been noted but it is not known whether this represents multicentric development of the lesion or metastasis. The pleomorphic appearances of the cells may simulate sarcoma. The absence of lipoblasts and the paucity of mitoses help to distinguish this lesion from and , respec­ tively. 2. Fibroma (Fig. 70) These are most frequently found in the medulla. It has been suggested that some or all medullary are derived from medullary interstitial cells and may have an endocrine-like antihypertensive action. The term renomedullary interstitial cell tumour has been proposed. 3. Haemangioma (Fig. 71) These occur most commonly in the wall of the renal pelvis but also in the pyramids and may be difficult to find in the resected kidney because of collapse of the vessels. 4. Others These include , , and neurilemmomas. B. MALIGNANT (Fig. 72-74) A variety of malignant non-epithelial tumours may rarely occur in the kidney. These must be distinguished from spindle cell forms of carcinoma and from retroperitoneal invading the kidney.

V. MISCELLANEOUS TUMOURS

A. JUXTAGLOMERULAR CELL TUMOUR (Fig. 75-77): A tumour of the juxta­ glomerular apparatus. These are rare renin-secreting tumours, composed of small cells with PAS­ positive cytoplasmic granules, which are arranged in sheets and cords or in a perivascular manner. Confirmation of the diagnosis depends upon the demonstration of renin secretion, or on the identification of typical diamond­ shaped inclusions by electron microscopy. 22 INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS B. OTHERS Renal involvement may be a feature of adrenal neuroblastoma and ganglioneuroblastoma. In rare instances, the kidney has been reported to be the primary site (Fig. 78). Neuroblastoma-like areas with rosettes, and ganglion cells may occur in nephroblastomas. Carcinoid tumours (Fig. 79) and teratomas rarely occur in the kidney. Carcinosarcomas have been described in the kidney but it is probable that the majority of these are nephroblastomas or carcinomas forming spindle cells. Tubules engulfed by invading sarcoma may also lead to a mistaken diagnosis of carcinosarcoma.

VI. SECONDARY TUMOURS

·· Tumours in this category may be metastases, direct extensions, or renal involvement by systemic neoplastic processes such as lymphoma (Fig. 80) and leukaemia. Renal failure may be the first clinical manifestation of a malignant lymphoma. In rare cases the kidney may be the initial or only site of lymphoma.

VII. UNCLASSIFIED TUMOURS

These are benign or malignant tumours that cannot be placed in any of the categories described above.

VIII. TUMOUR-LIKE LESIONS

A number of non-neoplastic lesions can resemble renal tumours clinically and histologically. Abnormalities of development of the kidney may result in a mixture of primitive renal elements which may be mistaken for nephro­ blastic tumours. A. PERSISTENT RENAL BLASTEMA (Fig. 81-82): Subcapsular, usually bilateral, small, often microscopic foci of embryonal nephrogenic tissue without a primitive mesenchymal component. Varying degrees of tubular differentiation may occur. The lesions appear to regress or differentiate with age. They have been found in the non­ neoplastic portion of kidneys containing nephroblastoma, in association with trisomy 18, and in the kidneys of otherwise normal individuals. This is also known as nodular renal blastema, persistent nephrogenic blastema, nodular metanephric blastema and metanephric hamartoma. B. MASSIVE RENAL BLASTEMA (Fig. 83-84): Embryonal nephrogenic tissue extensively replacing renal cortical parenchyma. It appears to be an exaggerated form of persistent renal blastema, being bilateral, multifocal, and/or diffuse, and may occupy the greater part of the renal cortex. It may coexist with nephroblastoma; this should be recorded because of HISTOLOGICAL TYPING OF KIDNEY TUMOURS 23 the possibility of bilateral and familial tumours in this setting, and an association with congenital anomalies. This lesion has also been referred to as nephroblastomatosis, nephroblas­ tematosis, and hyperplastic renal blastema. C. RENAL DYSGENESIS (Fig. 85-86): A malformed kidney consisting of cysts and tubules surrounded by mesenchymal stroma, and admixed with varying numbers of nephrons. Cartilage is not infrequent. The lesion may involve the entire kidney or segments of the kidney, or occur as microscopic foci. In adults the stroma is more mature. This condition is also known as renal dysplasia. D. VASCULAR MALFORMATIONS (Fig. 87) Certain vascular malformations and anastomoses which are not true angiomas may simulate tumours. E. CYSTS Cysts can pose as neoplasms, clinically. Carcinoma may be found m association with cysts or arising in a cyst wall. F. RENAL TUBULAR HYPERPLASIA Focal tubular hyperplasia, e.g., adjacent to foci of pyelonephritis, may be indistinguishable from a small adenoma. G. XANTHOGRANULOMATOUS PYELONEPHRITIS (Fig. 88): An inflammatory condition characterized by the accumulation of large histiocytes with clear or granular cytoplasm. It may resemble the clear cell renal carci­ noma. H. MALAKOPLAKIA (Fig. 89) This chronic inflammatory lesion may resemble renal cell carcinoma with granular cells but there is inflammation and the histiocytes contain Michae­ lis-Gutmann bodies. A variant of this lesion, located primarily in the cortex and containing poorly defined Michaelis-Gutmann bodies, is referred to as megalocytic interstitial nephritis. I. OTHERS Squamous metaplasia, particularly in hydronephrosis and in pyelonephri­ tis, may lead to entrapment of squamous cells within the renal parenchyma, which may mimic squamous cell carcinoma. Large collections of keratin may result in the formation of a cholesteatoma (Fig. 90). Fibroepithelial polyp as described in the bladder occurs rarely in the renal pelvis. Some polypoid structures have a complex epithelial and stromal arrangement suggesting a hamartoma, so-called pelvic hamartoma (Fig. 91 ). Adrenal rests are usually subcapsular and may rarely attain a large size. Adrenal-renal fusion (Fig. 92) may simulate a tumour.

INDEX

Page Figures Adenocarcinoma, renal pelvis 19 38 Adenoma. 17 1-7 Adrenal rest . 23 Adrenal-renal fusion 23 92 Angiomyolipoma 21 66-69 Arteriovenous malformation 23 87

Blastema, hyperplastic renal, see Blastema, massive renal 22 Blastema, massive renal 22 83-84 Blastema, nodular metanephric, see Blastema, persistent renal . 22 Blastema, nodular renal, see Blastema, persistent renal 22 Blastema, persistent nephrogenic, see Blastema, persistent renal 22 Blastema, persistent renal 22 81-82

Carcinoid tumour 22 79 Carcinoma, Bellini duct 18 30--33 Carcinoma, renal cell . 17 8-29 Carcinoma, squamous cell 19 37 Carcinoma, transitional cell 19 34-36 Carcinoma, undifferentiated, renal pelvis 19 Carcinoma in situ, renal pelvis 19 34 Carcinosarcoma 22 Cholesteatoma 23 90 Cysts 23

Dysgenesis, renal 23 85-86 Dysplasia, renal, see Dysgenesis, renal 23

Fibroma 21 70

Grawitz tumour, see Carcinoma, renal cell 18

Haemangioma 21 71 Hamartoma, fetal, see Nephroma, mesoblastic 20 Harmartoma, leiomyomatous, see Nephroma, mesoblastic 20 Hamartoma, metanephric, see BlastC

Juxtaglomerular cell tumour 21 75-77

Leiomyoma 21 Leiomyosarcoma 21 74 -25- 26 INTERNATIONAL HISTOLOGICAL CLASSIFICATION OF TUMOURS

Page Figures Leukaemia 22 21 21 73 Lymphoma, malignant 22 80

Malakoplakia 23 89 Metaplasia, squamous 23

Nephritis, megalocytic interstitial 23 N ephroblastoma 20 39-55 Nephroblastematosis, see Blastema, massive renal 22 Nephroblastomatosis, see Blastema, massive renal 22 Nephroma, congenital mesoblastic, see Nephroma, mesoblastic . 20 Nephroma, mesoblastic . 20 56-59 Nephroma, multilocular cystic 20 60-65 Neurilemmoma 21 Neuroblastoma 21 78

Papilloma, transitional cell . 18 Polyp, fibroepithelial 23 Pyelitis, papillary 19 Pyelitis cystica 19 Pyelitis glandularis . 19 Pyelonephritis, xanthogranulomatous .. 23 88

Teratoma. 22 Tumour, renomedullary interstitial cell 21

Vascular malformations 23 87 von Hippel-Lindau disease 18

Wilms' tumour 20 39-55

Unless otherwise stated, all the preparations shown in the photomicrographs reproduced on the following pages were stained with haematoxylin-eosin. Fig . 1. Adenoma Papillae with prominent fibrovascular stalks. x 100.

Fig. 2. Adenoma Same tumour as Fig . 1. Uniform cells with regular nuclei and small amounts of granular cytoplasm. x 160. Fig. 3 . Adenoma Papillary and acinar structures. Small uniform tumour cells merge with renal parenchyma. x 1 25.

Fig. 4 . Adenoma Solid, tubular and papillary structures. x 1 50. Fig . 5. Adenoma Tubular pattern. Small uniform cells. Oedematous stroma. X 160.

Fig. 6. Adenoma Oncocytic variety. Nests and cords of eosinophilic cells. Oedema taus hypocellular stroma is typical of this form . x 60. Fi g. 7. Adenoma Oncocytic va riety. Same tumour as Fig. 6 . Abundant eosinophilic granular cytoplasm. Small regular nuclei. X 160.

Fig. 8. Renal cell carcinoma Clear cells in large acinar structures with proteinaceous secretions. x 160. Fig . 9. Renal cell carcinoma Clear cell s in acinar. tubular and solid arrangements. x 100.

Fig _ 10. Renal cell carcinoma Large clear cell s in solid and tubular patt erns. x 60. Fig. 11. Renal cell carcinoma Clear cells in tubular arrangement. x 100.

Fig. 12. Renal cell carcinoma Cords of clear cell s separated by thin-walled vascular channels. X 150. Fig. 13. Renal cell carcinoma Thick cords of clear cells with dilated vascular channels. x 60.

Fig. 14. Renal cell carcinoma From a large cystic clear cell tu mour. x 60. Fig . 15. Renal cell carcinoma Cords of clear cells with unusuall y abundant stroma. x 150.

Fi g. 1 6. Renal cell carcinoma Papillary pattern with small cells having scant cytoplasm. x 160. Fig. 17. Renal cell carcinoma Small granular cell s forming papill ary and tubular structures. Collections of lipid-laden histiocytes. X 160.

Fig. 18. Renal cell carcinoma Granular cell s forming papillary and tubular structures. x 160. Fig. 19. Renal cell carcinoma Large granular cells forming solid and acinar structures. X 160.

Fig. 20. Renal cell carcinoma Large granular cell s forming tubular and papillary structures. X 160 . Fig. 21 . Renal cell carcinoma Large eosinoph ilic cell s resembling oncocytes. x 1 40.

Fig. 22. Renal cell carcinoma Cells with vacuolated cytoplasm . x 110. Fig. 23. Renal cell carcinoma Mixture of clear and granular cells in tubular arrangement. X 160.

Fig . 24. Renal cell carcinoma Mixture of clear and granular cell s. x 160. Fi g. 25. Renal cell carcin oma Tubular and solid patterns. Granular ce lls. x 160.

Fi g. 26. Renal cell carcin oma Pl eomorphic cell s. x 160. Fig. 27. Renal cell carcinoma Solid and spindle cell areas. x 160.

Fig . 28. Renal cell carcinoma Spindle cell va riety. x 1 60. Fig. 29. Renal cell carcinoma Microcystic structures containing clumps of tumour cell s. X 100.

Fig. 30. Carcinoma Tumour of medulla resembling ducts of Bellini with papillary projections on renal pelvis. x 100. Fig. 31 . Carcinoma Same tumour as Fi g. 30. Typical growth pattern of ··sellini duct carcinomas." x 100.

Fig . 32. Carcinoma Papillary portion of tumou r in Fig. 30. x 100. Fig. 33. Carcinoma Tumour of medull a showing another growth pattern seen in " Bellini duct carcinomas ·. x 100.

Fig. 34. Carcinoma in situ, renal pelvis Anaplasti c cells have replaced the normal epithelium. x 160. -~ -.

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Fig. 35. Transitional cell carcinoma, renal pelvis Large papillary tumour. x 40.

Fig. 36. Transitional cell carcinoma, renal pelvis Papillary and infiltrating tumour, Grade II. x 60. Fig. 37. Squamous cell carcinoma, renal pelvis Deeply infiltrating tumour, Grade II. x 100.

Fig. 38. Adenocarcinoma, renal pelvis Superficially infiltrating tumour. x 40. Fig. 39. Nephroblastoma Blastemal, epithelial and mesenchymal components. x 60.

Fig. 40. Nephroblastoma Immature glomeruli and tubules in a predominantly blastema! fi eld. x 100. Fig. 41 . Nephroblastoma Tubules appear to arise in islands of blastema. Some are lined by mucin-producing cells. X 100.

Fig. 4 2. Nephroblastoma Islands of glial tissue in a predominantl y blastema! fi eld. x 100. Fig. 43. Nephroblastoma Striated muscle fibres adjacent to primitive epithelial elements. x 160.

Fig. 44. Nephroblastoma Wall of a cystic tumour partly lined by mucus-secreting columnar epithelium. x 160. Fig. 45. Nephroblastoma Tumour consisting entirely of blastema! elements. X 1 20.

Fig. 46. Nephroblastoma Unusual appearance of blastema! tissue: cells with abundant cytoplasm. x 1 50. Fig. 4 7. Nephroblastoma Predominantl y st romal area. x 1 30.

Fig . 48. Nephroblastoma Same tumou r as Fig. 4 7 composed of epitheli al st ructures. x 100. Fig . 49. Nephroblastoma Epithelial and blastema! components. x 1 00.

\

Fig. 50. Nephroblastoma Numerous cysts in a predominantly epithelial field . x 100. Fig. 51 . Nephroblastoma Cystic spaces in a mesenchymal tumour. x 160 .

Fig. 52. Nephroblastoma Mesenchymal tumour with rare epithelial structures. x 160. Fig. 53. Nephroblastoma Blastema! and mesenchymal components. The mesenchymal tissue is more mature than that of Fig. 52. X 100.

Fig. 54. Nephroblastoma. Cyst resembling those in multilocular cystic nephroma. x 160. Fig. 55. Nephroblastoma Blastema! and epithelial tumour tissue with smooth muscle and apparently entrapped renal tubules resembling mesoblastic nephroma. x 100.

Fig . 56. Mesoblasti c nephroma Interlacing bundles of smooth muscle with entrapped renal tissue. x 60. Fi g. 57. Mesoblastic nephroma Same tumour as Fig. 56. X 160.

Fig . 58. Mesoblasti c nephroma Poorly diffe rentiated st roma adjacent to norm al renal ti ssue. X 160. Fig. 59. Mesoblastic nephroma Mitotic activi ty in poorly differentiated stroma. x 400.

Fig. 60. Multilocular cystic nephroma Multiple cysts with varying amounts of intervening stroma surrounded by a thick fibrous capsule . Renal tissue is compressed. x 9. Fig. 61 . Multilocular cystic nephroma Characteristic hotrnail epithelium . x 115.

Fig. 62. Multilocular cystic nephroma Immature cellular stroma typical of lesions found in adult females. x 150. Fig . 63. Multilocular cystic nephroma Mature fibrous stroma usually seen in lesions of infants and children. x 40.

Fig . 64. Multilocular cystic nephroma Immature sarcomatous stroma from a predominantly cysti c tumour. X 160. Fig . 65. Multilocu lar cystic nephroma Blastematous tissue in an otherwise typical multilocular cystic nephroma. X 160.

Fig. 66. Angiomyolipoma Mature fat cells, thick-walled vessels and spindle-shaped muscle cells from a cortical tumour. x 100. Fig. 67. Angiomyolipoma Thick-walled tortuous vessels, partially hyalinized. embedded in highly cellular smooth muscle and tat. x 100.

Fig. 68. Angiomyolipoma Small vessels with thick muscular walls. x 1 30. Fig . 69. Angiomyolipoma Smooth muscle with nuclear pleomorphism. Simulates sarcoma. x 1 60.

Fig . 70. Fibroma Edge of a partially hyalinized medullary tumour with interl acing bundles of fibrous tissue. Seve ral entrapped tubules. x 100. Fig. 71. Cavern ous haemangioma From a peripelvic tumour whi ch e xtended along the ureter. x 1 5 .

Fig. 72. Malignant fibrous histiocytoma X 100. Fig. 73. Liposarcoma X 100.

Fig. 74. Leiomyosarcoma X 100. Fig. 75. Juxtag lomerular cell tumour Poorl y demarcated groups of plump cell s. x 1 50.

Fi g. 76 . Juxtaglomerular cell tumour Same tumour as Fig. 75. Abundant cytop lasm wit h ill-defined coarse granules. x 400. Fig . 77. Juxtaglomerular cell tumour Clusters of cells in a well-vascularized stroma. x 160.

Fig. 78. Neuroblastoma From a primary tumour of the kidney. x 250. Fig. 79. Carcinoid tumour Prim ary in the kidney . x 1 50.

Fig. 80. Malignant lymphoma X 60. Fig. 81 . Persistent renal bl astema Subcapsul ar primitive renal tissue from a 2-year-old. X 10.

Fig. 82. Persistent renal blastema Nod ule of primitive blastema in renal cort ex. X 100. Fig. 83. Massive renal blastema Nodules of blastema and metanephric tubules. x 10.

Fig . 84. Massive renal blastema High magnification of lesion in Fig. 83. x 160. Fig. 85. Renal dysgenesis Tubules embedded in mesenchymal stroma; cysts and nephrons. x 40.

Fig . 86. Renal dysgenesis Dilated tubules surrounded by cellular stroma. From an adult. x 100. Fig . 87. Arteriovenous malformation X 100.

Fig. 88. Xanthogranulomatous pyelonephritis. Lipid-laden macrophages simul ate carcin oma ce ll s. X 1 50 . Fig. 89. Malakoplakia Cells with large amounts of granular cytoplasm. x 250.

Fig . 90. Cholesteatoma Tumour-like collection of squamous ti ssue and keratin extends deeply into parenchyma. X 60. Fig . 91. Pelvic hamartoma Polypoid structures composed of cellular stroma, thick-walled vessels and covered by transi tional epithe­ lium . X 40.

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