Table Of ContentManagement of Rare Adult Tumours
Springer
Paris
Berlin
Heidelberg
New York
Hong Kong
Londres
Milan
Tokyo
Management of Rare Adult Tumours
Editors
Yazid Belkacémi
René-Olivier Mirimanoff
Mahmut Ozsahin
Yazid Belkacémi MD PhD
Professor Radiation Oncology
Deputy Head of the Department of Radiation Oncology
Hôpital Henri-Mondor
51, avenue du Maréchal-de-Lattre-de-Tassigny
94000 Créteil Cedex
France
René-Olivier Mirimanoff MD
Professeur Radiation Oncology
Head of the Department of Radiation Oncology
Centre hospitalier universitaire Vaudoir
Rue du Bugnon
CH-1011 Lausanne
Switzerland
Mahmut Ozsahin MD PhD
Associate Professor in the Department of Radiation Oncology
Centre hospitalier universitaire Vaudois
Rue du Bugnon
CH-1011 Lausanne
Switzerland
ISBN-13:978-2-287-92245-9 Springer Paris Berlin Heidelberg New York
©Springer-Verlag France,Paris,2009
Imprimé en France
Springer-Verlag France est membre du groupe Springer Science + Business Media
Cet ouvrage est soumis au copyright. Tous droits réservés,notamment la reproduction et la représentation,la traduction,la réimpression,
l’exposé,la reproduction des illustrations et des tableaux,la transmission par voie d’enregistrement sonore ou visuel,la reproduction par
microfilm ou tout autre moyen ainsi que la conservation des banques de données. La loi française sur le copyright du 9septembre 1965
dans la version en vigueur n’autorise une reproduction intégrale ou partielle que dans certains cas,et en principe moyennant les paiements
des droits. Toute représentation,reproduction,contrefaçon ou conservation dans une banque de données par quelque procédé que ce soit
est sanctionnée par la loi pénale sur le copyright.
L’utilisation dans cet ouvrage de désignations,dénominations commerciales,marques de fabrique,etc. même sans spécification ne signifie
pas que ces termes soient libres de la législation sur les marques de fabrique et la protection des marques et qu’ils puissent être utilisés
par chacun.
La maison d’édition décline toute responsabilité quant à l’exactitude des indications de dosage et des modes d’emplois. Dans chaque cas
il incombe à l’usager de vérifier les informations données par comparaison à la littérature existante.
Maquette de couverture:Jean-François Montmarché
Preface: Paul Levine........................................................................................................................................... 1
Foreword: Robert Miller..................................................................................................................................... 3
SECTION 1. CNS TUMORS
1. Germinal tumours of the central nervous system in adult patients, S. Villà, M. Caro, V. Tuset.................... 7
2. Atypical and malignant meningiomas, D. Pasquier, N. Rezvoy..................................................................... 19
3. Primary central nervous system lymphoma, P. Poortmans........................................................................... 29
4. Traitment of Medulloblastoma in adults, N. Penel, C. Ferte, E. Le Rhun, Y. Belkacémi.............................. 41
5. Cerebellar glioblastoma multiforme, D. Weber............................................................................................. 45
6. Chordoma and chondrosarcoma of the skull base, A. Pica, R.-O. Mirimanoff............................................ 51
7. Primary spinal epidural lymphoma, V. Monnard, R.-O. Mirimanoff............................................................. 57
SECTION 2. HEAD AND NECK TUMORS
1. Esthesioneuroblastoma, O. Matzinger........................................................................................................... 67
2. Extranodal NK/T - cell lymphoma, nasal type, Y. Li.................................................................................... 73
3. Uncommon tumours of the nasopharynx, E. Ozyar, M. Gültekin................................................................. 87
4. Uncommon tumours of the oral cavity and oropharynx, A. Sefik Hosal...................................................... 97
5. Rare malignant tumours of the larynx and hypopharynx, C. Ikonomodis, L. Bron...................................... 105
6. Primary Orbital Lymphoma, G. Ugurluer, A. Zouhair, M. Ozsahin.............................................................. 117
7. Primary MALT lymphoma of the salivary glands, Y. Anacak, S. Kamer...................................................... 123
SECTION 3. GASTRO-INTESTINAL TUMORS
1. Mucosal melanoma of the upper aero-digestive tract, M. Krengli, L. Masini, F. Pia................................... 129
2. Gastrointestinal stromal Tumours, M. Montemurro, J.-Y. Blay, S. Levraz.................................................... 137
3. Small cell carcinomas of the gastrointestinal tract, M. Shilkrut, A. Peer, A. Kuten ...................................... 149
4. Anorectal melanoma, S. Vieillot, D. Azria..................................................................................................... 159
5. Primary adenocarcinoma of the anal canal, Y. Belkacémi, P. Rouanet, M. Jafari......................................... 167
6. Anal margin tumours, M Schlienger, E. Touboul.......................................................................................... 175
7. Uncommon Hepatobiliary Tumours, M. Hübner, N. Halkic, N. Demartines................................................ 183
8. Unusual pancreatic tumours, F. Nguyen, A.-N. Dupont-Gossart................................................................... 195
SECTION 4. GENITOURINARY
1. Rare tumours of the renal pelvis and ureter, M. Ozsahin, A. Zouhair........................................................... 209
2. Rare tumours of the urethra, F. Öner Dincbas.............................................................................................. 215
3. Uncommon bladder cancers, C. Durdux, O. Mir........................................................................................... 225
V
VI Management or Rare Adult Tumours
4. Neuroendocrine small cell carcinoma of the prostate, M. Stein, A. Kuten.................................................... 235
5. Uncommon tumours of the testis, I. Alexandre, E. Horn, F. Selle................................................................ 245
6. Primary Testicular lymphoma, A Zouhair, R.O. Mirimanoff, M. Ozsahin..................................................... 255
7. Human chorionic gonadotropin-producing seminoma, R.O. Mirimanoff, A. Zouhair.................................. 261
SECTION 5. GYNECOLOGICAL
1. Rare ovarian cancers, F. Gligorov, I. Ray-Coquard, P. Pautier, E. Pujade Lauraine, F. Selle, C. Lhommé,
J.-P. Lotz, P. Morice, P. Duvillard................................................................................................................... 271
2. Extraovarian primary peritoneal carcinoma, C. Nay Fellay, M. Fiche, J.-F. Delaloye, J. Bauer.................... 279
3. Uterine papillary serous carcinoma, V. Samouelian, M.-C. Baranzelli, A. Lesoin......................................... 293
4. Uterine sarcomas and rare endometrial carcinomas, H. Boussen, K. Rahal, N. Bouaouina.......................... 301
5. Rare Tumours of the uterine cervix, H. Lamallem, A. Toledano, P. Tsoutsou................................................ 307
6. Tumours of the vagina and tumours of the vulva, C. Haie-Meder................................................................. 317
SECTION 6. BREAST
1. Invasive breast cancer and ductal carcinoma in situin young women, G. Grüber, S. Aebi.......................... 331
2. Tubular carcinoma of the breast, T. Sullivan, A. Taghian.............................................................................. 341
3. Adenoid Cystic Carcinoma of the Breast, K. Khanfir................................................................................... 349
4. Primary squamous cell carcinoma of the breast, L. Scandolaro................................................................... 353
5. Primary breast lymphoma,W. Jeanneret Sozzi, R.-O. Mirimanoff................................................................. 357
6. Phyllodes tumours of the breast, G. Bousquet, J. Bonneterre, Y. Belkacemi................................................. 367
7. Primary Breast Sarcoma, L. Zelek, M. Spielmann, A. Le Cesne................................................................... 373
8. Angiosarcoma of the breast, Y. Kirova, A. Fourquet...................................................................................... 379
9. Male breast cancer, B. Cutuli ........................................................................................................................ 385
SECTION 7. LUNG AND INTRATHORACIC MALIGNANCIES
1. Primary uncommon tumours of the lung : lymphomas, sarcomas and melanomas, K. Peignaux, F. Maingon.... 395
2. Thymoma and thymic carcinoma, N. Girard, F. Mornex, P. van Houtte, J.-F. Cordier................................. 401
3. Large Cell Neuroendocrine Carcinoma of the Lung, J.-Y. Perentes, H.-B. Ris............................................. 415
4. Neuroendocrine tumours of the loung, A. Bonnichon, H. Le Floch, F. Rivière, J. Margery, F. Vaylet.......... 423
5. Pleural mesothelioma, E. Dansin, S. Dewas, H. Porte.................................................................................. 435
6. bronchioalveolar carcinoma and adenocarcinoma, J. Cadranel, M. Antoine, M. Wislez............................... 445
7. Primary adenoid cystic carcinoma of the trachea and bronchus, M. Roelandts, P. van Houtte.................... 453
8. Tracheal cancers, E. Touboul, F. Hughet........................................................................................................ 461
SECTION 8. MALIGNANCIES OF THE SKIN
1. Unusual cutaneous malignancies, B. Guillot................................................................................................. 471
2. Kaposi’s sarcoma, Y. Kirova........................................................................................................................... 479
3. Dermatofibrosarcoma protuberans, R. Panizzon........................................................................................... 485
4. Merkel cell carcinoma, K. Beer..................................................................................................................... 491
5. Langerhans cell histicytotis, M. Heinrich Seegenschmiedt........................................................................... 499
SECTION 9. OTHER MALIGNANCIES
1. Primary bone lymphoma (Osteolymphoma), D. Christie.............................................................................. 515
2. Erdheim-Chester disease, R.C. Miller........................................................................................................... 523
3. Solitarylasmacytoma, R. Tsang...................................................................................................................... 531
4. Neuroendocrine tumours, K. Oberg............................................................................................................... 539
The importance of Studying Rare Malignancies
Rare cancers play an important role in the epidemiology of cancer in view of the
clues they give us to cancer etiology in general. The most obvious example is the
study of cancer clusters, which provide excellent opportunities to identify etiologic
agents. The study of cancer clusters has many problems and is usually unproduc-
tive [8] usually because reported clusters involve large numbers of common tumors
with long latent periods, but the most dramatic successes involve rare malignancies.
In such cases, alert clinicians play an important role as exemplified by Gottlieb in
1981 [3] who noticed the unusual new occurrence of Kaposi’s sarcoma in gay San
Francisco males which eventually led to the identification of Acquired
Autoimmune Deficiency Syndrome (AIDS) as a potential public health problem
and subsequent identification of Human Immunodeficiency Virus (HIV) as the
etiologic agent. A non-infectious danger was recognized in Boston with the appear-
ance of a rare cancer in young women, vaginal cancer, which was eventually traced
to the administration of a hormone, diethylstilbestrol (DES) to the mothers to main-
tain a pregnancy [5]. DES proved to be unsuccessful in maintaining pregnancies but
more important, the danger of this hormone being given to pregnant women was
quickly identified.
Another important consideration in cancer epidemiology is the study of a rare
tumor in one country that is not rare in other countries. The etiology or an etiologic
component may or may not be known but it is important to understand the co-
factors that increase or decrease the incidence of a specific malignancy after expo-
sure to the suspected agent. Such studies these days involve the integration of
laboratory studies into the development of epidemiologic protocols, and it now
seems to be the exception rather than the rule that a large epidemiologic study does
not include the collection of biospecimens for multiple laboratory investigations.
Our experience in this area began with Burkitt’s lymphoma (BL), a malignancy first
described by Denis Burkitt in Sub-Saharan Africa geographically limited by
climate and altitude to areas of holoendemic malaria. Because BL was unknown in
England, where Burkitt had practiced as an experienced surgeon, he was fascinated
by this rare tumor which led to extensive international collaborative studies involving
clinicians, epidemiologists and laboratory investigators culminating in the discovery
of the Epstein-Barr virus (EBV) [1, 4]. One of the epidemiologists-statisticians
focusing on BL was Malcolm Pike who, noting the occasional clusters of the
disease, proposed a “Factor X”, an etiologic agent in addition to EBV and malaria,
which could contribute to the etiology. He suggested that a comparison of the
endemic African disease be compared with non-endemic cases where malaria was
not a factor and thus the American Burkitt’s Lymphoma Registry was initiated [6].
1
2 Management or Rare Adult Tumours
More than 143 cases of BL in the US were reported in eight years [7] and bio-
specimens, particularly paraffin blocks, revealed that at least two distinct forms of
BL could be identified [2], the prototypical EBV-associate BL, the most common
form in sub-Saharan Africa but rare in the US, and the non-EBV-associated form,
the more common form in the U.S. with distinct chromosomal and clinical dif-
ferences from African BL.
The identification of patients with rare tumors is now greatly facilitated by the
internet, which is now being used to investigate a number of rare tumors, as demon-
strated by the many interesting chapters in this book. The Rare Cancer Network
(RCN) has been using the WEB to connect clinicians to improve the management
of rare cancers, as described in these chapters. This is an important beginning, since
much more needs to be done to understand the pathobiology and control of a
variety of rare malignancies. As advances occur in the laboratory, more sophisti-
cated studies are now feasible, such as the use of oral rinses to collect DNA for
sophisticated analysis. The findings resulting in the study of rare tumors can be
expected to have major implications for cancer etiology in general.
References
1. Burkitt DP, Charles S, Mott Award (2006) The discovery of Burkitt’s Lymphoma.
Cancer 10: 1772-86
2. Barriga F, Kiwanuka J, Alvarez-Mon M et al.(1988) Significance of chromosome 8
breakpoint location in Burkitt’s lymphoma: correlation with geographical origin and
association with Epstein-Barr virus. Curr Top Microbiol Immunol 141: 128-37
3. Centers for Disease Control and Prevention (CDC) (1981) Kaposi’s sarcoma and
Pneumocystis pneumonia among homosexual men–New York and Californa.
MMWR Morb Mortal Wkly Rep 30: 305-8
4. Epstein MA, Achong BG, Barr YM (1969) Virus particles in cultured lymphoblasts
from Burkitt’s lymphoma. Lancet 1 702-3
5. Herbst AL, Ulfeder H, Poskanzer DC (1971) Adenocarcinoma of the vagina:
Association with maternal stilbestrol therapy with tumor appearance in young
women. N Eng J Med 284: 878-81
6. Levine PH. Wanted: Case reports of Burkitt’s lymphoma in the U.S. (1971) Med
Times99 (2): 124-6
7. Levine PH, Kamaraju LS, Connelly RR et al. (1982) The American Burkitt’s
lymphoma registry: eight years’experience.Cancer49 (5): 1016-22
8. Rothenberg RB, Steinberg KK, Thacker SB (eds) (1990) National Conference on
Clustering of Health Events. Am J Epidemiol 132 (suppl) S1-S202
This work addresses the problem of rare tumour management. By definition, these
are uncommon malignancies whose diagnosis and treatment are made more
complicated by a relative absence of information in the medical literature. A
uniform definition of a “rare tumour” does not currently exist. In some instances,
terminology even for individual disease entities remains indeterminate because of
their infrequent occurrence. The National Institute of Health’s Office of Rare
Disease Research defines a “rare disease” as one effecting less than 200,000 indi-
viduals in the United States [2]. In contrast, the European Commission has more
broadly defined rare diseases as those diseases which “are life-threatening or
chronically debilitating diseases which are of such low prevalence that special
combined efforts are needed to address them” or those that affect less than 5 per
10,000 persons. Although individually the incidence of any given rare disease is
low, it is estimated that 6% to 8% of the population of the European Union has a
disease classified as “rare” when all entities meeting this definition are considered
in aggregate [3]. The unusual neoplastic processes presented in Management of
Rare Tumours of the Adult range from the very rare, where the cases reported in the
medical literature consist only of a few dozens of patients, such as Erdheim-Chester
disease and primary spinal epidural lymphoma, to more common entities that clini-
cians may occasionally encounter, but where a low incidence has left their best
management incompletely defined, such as thymoma and ductal carcinoma in-situ
in very young women. The European Commission has identified rare diseases as a
subject where cooperative action within the international community may be of
benefit. On November 11th, 2008, the European Commission published proposed
recommendations for European action in the field of rare diseases, calling for
global action in concert given the rarity of these conditions and the often complex
requirements of their diagnosis and management. Management of Rare Tumours of
the Adultis a timely addition towards that effort.
In an era where evidence based medicine (EBM) has become the focus of clini-
cal research and medical practice, the treatment of rare diseases presents a unique
challenge. EBM practice is founded on a hierarchy of evidence, with the greatest
value being assigned to evidence derived from sources with robust statistical power,
such as meta-analyses and randomized clinical trials. By definition, the study of
rare tumours is problematic from the EBM perspective given that their infrequent
occurrence prevents their study through prospective means. Despite the challenges
of dealing with patient populations too small for testing research questions through
randomized controlled trials, these problems are not insurmountable [1-4]. The
internet has proved to be important in increasing communication and awareness of
rare diseases, as well as providing a powerful tool for fostering cooperative investi-
3
