Rare Tumors in Children and Adolescents

Preface
Contents
Part I: Introduction
	1: Rare Tumors: A Different Perspective on Oncology
		1.1	 What Defines a Rare Tumor?
		1.2	 The Issue of Adult Cancers in Children
		1.3	 Clinical Issues in the Diagnosis and Treatment of Rare Pediatric Tumors
		1.4	 Delays in Diagnosis
		1.5	 The Challenge of Referral and Treatment
		1.6	 Biology
		1.7	 Possible Strategies in Pediatric Oncology Rare Tumors
			1.7.1	 Possible Solutions: “Collaboration, Find Friends!”
		1.8	 Perspective
		References
Part II: Epidemiology and Etiology of Rare Cancers
	2: Epidemiology
		2.1	 Introduction
		2.2	 Classification
		2.3	 How to Define Rare Tumors in Children and Adolescents?
		2.4	 Incidence-Based Definition of Rare Tumors in Children and Adolescents
		2.5	 Rare Pediatric Cancer Age-Specific Incidence
		2.6	 Conclusion
		References
	3: Biology and Etiology of Rare Pediatric Tumors
		3.1	 Introduction
		3.2	 Rare Pediatric Tumors
		3.3	 Etiological and Biological Characteristics of Rare Pediatric Tumors
			3.3.1	 Rare Typical Childhood Cancers
			3.3.2	 Rare Malignancies with Different Biology in Childhood and Adulthood
			3.3.3	 Adult-Type Cancer in Children
			3.3.4	 Conclusion
		References
	4: Childhood Cancer Predisposition
		4.1	 Incidence
		4.2	 Relevance
		4.3	 Diagnostics of Childhood Cancer Predisposition
		4.4	 Care for Children with Cancer Predisposition Syndromes
		References
Part III: National and International Study Groups
	5: National Initiatives in Europe
		5.1	 The Italian TREP Project
		5.2	 The Polish Paediatric Rare Tumours Study Group
		5.3	 The German STEP Project
		5.4	 The French FRaCTurE
		5.5	 The UK
		5.6	 From National Initiatives to a Comprehensive European Project
		References
	6: EXPeRT: The European Cooperative Study Group for Pediatric Rare Tumors
		6.1	 ExPO-r-Net
		6.2	 JARC
		6.3	 PARTNER
		References
	7: The United States
		7.1	 Introduction
		7.2	 Children’s Oncology Group (COG) Rare Tumor Group
			7.2.1	 Infrequent Tumor Subcommittee Projects
				7.2.1.1	 Clinical Trials
				7.2.1.2	 Children’s Oncology Group Registry and Rare Tumor Banking Protocol
				7.2.1.3	 Diagnostic and Therapeutic Recommendations
		7.3	 Rare Tumor Registries Outside of Children’s Oncology Group
			7.3.1	 Individual Rare Tumor Registries
			7.3.2	 Rare Tumors Tumor Board
		References
Part IV: Rare Tumors of the Head and Neck
	8: Epidemiology of Head and Neck Tumors
		References
	9: Thyroid Carcinomas
		9.1	 Introduction
		9.2	 Differentiated Thyroid Carcinoma
			9.2.1	 Epidemiology and Etiology
			9.2.2	 Clinical Presentation and Diagnosis
				9.2.2.1	 Overdiagnosis/Disease Increase
			9.2.3	 Special Considerations
			9.2.4	 Pathology
			9.2.5	 Therapy
				9.2.5.1	 Surgery
				9.2.5.2	 Radioiodine Therapy and Hormonal Manipulation
			9.2.6	 Follow-Up
			9.2.7	 Postoperative Complications and Their Treatment
				9.2.7.1	 Treatment at Relapse
			9.2.8	 Prognosis
		9.3	 Medullary Thyroid Carcinoma
			9.3.1	 Pediatric Thyroid Cancer: A Model for Collaboration
		References
	10: Nasopharyngeal Carcinoma
		10.1	 Introduction
		10.2	 Symptoms
		10.3	 Pathogenesis
			10.3.1 Environmental Factors
			10.3.2 Genetic Factors
			10.3.3 Epstein–Barr Virus
		10.4	 Pathology
		10.5	 Staging System
			10.5.1 Primary Tumor (T)
			10.5.2 Regional Lymph Nodes (N)
			10.5.3 Distant Metastasis (M)
			10.5.4 Definition of Risk Groups
		10.6	 Diagnosis
			10.6.1 EBV DNA
			10.6.2 EBV Serology
			10.6.3 Magnetic Resonance Imaging
			10.6.4 Positron Emission Tomography
		10.7	 Therapy
			10.7.1 Chemotherapy
			10.7.2 Radiotherapy
			10.7.3 Interferon Therapy
		10.8	 Metastatic Disease
		10.9	 New Treatment Strategies
			10.9.1 T Cell Therapy
			10.9.2 Checkpoint Inhibition
			10.9.3 Targeted Therapy
		10.10	 Long-Term Sequelae
		10.11	 Juvenile Nasopharyngeal Angiofibroma
			10.11.1 Introduction
			10.11.2 Symptoms
			10.11.3 Pathogenesis
			10.11.4 Diagnosis
			10.11.5 Therapy
		References
	11: Esthesioneuroblastoma
		11.1	 Pathology
		11.2	 Clinical Manifestations and Staging
		11.3	 Prognosis and Therapy
		References
	12: Germ Cell Tumors of the Head and Neck
		12.1	 Introduction
		12.2	 Clinical Diagnosis
		12.3	 Therapy
		12.4	 Prognosis
		References
	13: Odontogenic Tumors
		13.1	 Ameloblastoma
		References
	14: Salivary Gland Tumors
		14.1	 Introduction
		14.2	 Differential Diagnosis and Management of Rare Head and Neck Tumors
			14.2.1	 Hemangioma
			14.2.2	 Epithelial Salivary Gland Neoplasms
			14.2.3	 Very Rare Entities
		References
	15: Laryngeal Tumors
		References
Part V: Rare Tumors of the Head and Neck
	16: Pathological Aspects of Mediastinal Tumors in Children and Adolescents
		16.1	 Introduction
		16.2	 Peculiarities of Mediastinal Tumors in Children and Adolescents
		16.3	 Lymphomas and Other Hematologic Malignancies
			16.3.1	 T-Lymphoblastic Lymphoma (T-LBL)
			16.3.2	 Differential Diagnosis of T-LBL
			16.3.3	 Primary Mediastinal Large B-Cell Lymphoma (PMBL)
			16.3.4	 Differential Diagnosis of PMBL
			16.3.5	 Classical Hodgkin Lymphoma (cHL)
		16.4	 Germ Cell Tumors (GCTs)
		16.5	 Neurogenic Tumors
		16.6	 Mesenchymal Tumors
		16.7	 Thymomas, Thymic Carcinomas, and Thymic Neuroendocrine Tumors
		16.8	 Mediastinal Cysts
		References
	17: Mediastinal Germ Cell Tumors
		17.1	 Introduction
		17.2	 Clinical Diagnosis
		17.3	 Therapy
		17.4	 Principles of Surgical Resection of Mediastinal Germ Cell Tumors
		17.5	 Multimodal Therapy in Malignant Germ Cell Tumors
		17.6	 Prognosis
		References
	18: Pleuropulmonary Blastoma
		18.1	 Background
		18.2	 Manifestations of PPB
		18.3	 Pathology Overview
		18.4	 PPB Treatment
		18.5	 Prognosis
		18.6	 DICER1 Pathogenic Variation
		References
	19: Bronchial Carcinoids and Carcinomas
		19.1	 Introduction
		19.2	 Clinical Diagnosis, Pretherapeutic Assessment in Lung Tumors, Staging
		19.3	 Treatment
		19.4	 Results and Comment
		References
	20: Pediatric Pleural Mesothelioma
		20.1	 Introduction
		20.2	 Epidemiology
		20.3	 Clinical Presentation
		20.4	 Radiological Presentation
			20.4.1	 CT
			20.4.2	 MRI
			20.4.3	 PET Scan
		20.5	 Pathology
		20.6	 Treatment
			20.6.1	 Surgery
			20.6.2	 Chemotherapy, Targeted Therapies, Immunotherapies
			20.6.3	 Radiotherapy
			20.6.4	 Outcome
		20.7	 Conclusion
		References
	21: Thymoma and Thymic Carcinoma in Children and Adolescents
		21.1	 Introduction
		21.2	 Symptoms
		21.3	 Paraneoplastic Autoimmune Syndromes
		21.4	 Pathologic Classification and Staging
		21.5	 Diagnosis
			21.5.1	 Laboratory Studies
			21.5.2	 Radiological Studies
		21.6	 Surgical Approach to Establishing a Diagnosis
			21.6.1	 Biopsy
			21.6.2	 Immunochemistry
			21.6.3	 Molecular and Genetic Changes
		21.7	 Differential Diagnosis
		21.8	 Treatment
		21.9	 Surgical Management
		21.10	 Chemotherapy
		21.11	 Radiotherapy
		21.12	 Summary
		References
	22: NUT Carcinoma
		22.1	 Definition
		22.2	 Clinical Features
		22.3	 Molecular Genetics
		22.4	 Histology/Immunohistochemistry (IHC)
		22.5	 Diagnosis
		22.6	 When to Consider the Diagnosis of NC
		22.7	 Demographics/Prevalence
		22.8	 Pathogenesis (BRD4-NUT Function)
		22.9	 Treatment of NC
		22.10	 New Treatment Strategies
		22.11	 Conclusions
		References
Part VI: Rare Tumors of the Gastrointestinal Tract
	23: Pathology and Differential Diagnosis
		23.1	 Gastrointestinal Stromal Tumor (GIST)
			23.1.1	 Introduction
			23.1.2	 Presentation
		23.2	 Pathology/Molecular Biological Findings
		23.3	 GANT
		23.4	 Colorectal Adenocarcinoma (CRAC)
			23.4.1	 Cancer of the Stomach
			23.4.2	 Cancer of the Pancreas
			23.4.3	 Carcinoid Tumor
			23.4.4	 Cancer of the Bladder, Cervix, and Vagina
		References
	24: Tumors of the Esophagus and the Stomach
		24.1	 Tumors of the Esophagus
		24.2	 Tumors of the Stomach
		References
	25: Tumors of the Small Intestine, Colon, and Rectum
		25.1	 Epidemiology
		25.2	 Gastrointestinal Cancer Predisposition Syndromes
			25.2.1	 Adenomatous Polyposis Syndrome (FAP)
			25.2.2	 Hamartomatous Polyposis Syndromes
			25.2.3	 Peutz-Jeghers Syndrome
			25.2.4	 PTEN Hamartoma Tumor Syndrome: Cowden Syndrome and Bannayan-Riley-Ruvalcaba Syndrome
			25.2.5	 Juvenile Polyposis Syndrome
			25.2.6	 Serrated Polyposis Syndrome (SPS)
		25.3	 Polymerase Proofreading-Associated Polyposis (PPAP)
		25.4	 Other Polyposes
			25.4.1	 NTHL1-Associated Polyposis
			25.4.2	 MSH3-Associated Polyposis
		25.5	 Lynch Syndrome
		25.6	 Multigene Panel
			25.6.1	 Pediatric Series on Intestinal Carcinoma: Peculiarities of Disease When Arising in Children
			25.6.2	 Diagnosis
		25.7	 Systemic Treatment
			25.7.1	 Adjuvant Therapy
			25.7.2	 Metastatic Disease and Molecular Features
			25.7.3	 Risk Factors
		References
	26: Neuroendocrine Tumors (Carcinoids) of the Appendix
		References
	27: Gastrointestinal Stromal Tumors in Children and Adolescents
		27.1	 Introduction
		27.2	 Pathology and Biology
		27.3	 Syndromic/Inherited GIST
		27.4	 Symptoms
		27.5	 Diagnosis
		27.6	 Treatment
		27.7	 Prognosis
		27.8	 Conclusion
		References
	28: Pancreatic Tumors
		28.1	 Introduction
		28.2	 Differential Diagnosis
		28.3	 Biology, Pathology, and Tumor Characteristics
			28.3.1	 Pancreatoblastoma
			28.3.2	 Solid-Pseudopapillary Neoplasm (SPN)
			28.3.3	 Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) and Congenital Hyperinsulinism
				28.3.3.1	 Congenital Hyperinsulinism
			28.3.4	 Acinar Cell Carcinoma (ACC)
			28.3.5	 Ductal Adenocarcinoma
			28.3.6	 Benign Tumors
				28.3.6.1	 Inflammatory Myofibroblastic Tumor (IMT)
				28.3.6.2	 Teratoma
				28.3.6.3	 Mucinous Cystic Neoplasm (MCN)
				28.3.6.4	 Fibrous Focus
				28.3.6.5	 Pancreatic Pseudocysts
		28.4	 Diagnosis of Pancreatic Tumors
			28.4.1	 Clinical Presentation
			28.4.2	 Laboratory
			28.4.3	 Imaging
			28.4.4	 Biopsy
			28.4.5	 Staging
		28.5	 Treatment of Pancreatic Tumors
			28.5.1	 Surgical Therapy
				28.5.1.1	 Surgical Approach
			28.5.2	 Therapy and Prognosis of Specific Entities
				28.5.2.1	 Pancreatoblastoma
				28.5.2.2	 Prognosis
				28.5.2.3	 SPN
				28.5.2.4	 Prognosis
				28.5.2.5	 GEP-NETs
				28.5.2.6	 Prognosis
				28.5.2.7	 Other Rare Malignant and Low-Malignancy Pancreatic Tumors
				28.5.2.8	 Benign Tumors
				28.5.2.9	 Focal Congenital Hyperinsulinism
				28.5.2.10	 Laparoscopy
		28.6	 Summary and Conclusions
		References
	29: Liver Tumors
		29.1	 Genetics and Etiology
		29.2	 Pathology and Cellular Classification
			29.2.1	 HCC
			29.2.2	 Sarcomas and Undifferentiated Embryonal Sarcoma of the Liver
		29.3	 Clinical Diagnosis
			29.3.1	 Diagnosis and Evaluation
		29.4	 Tumor Staging
		29.5	 Prognostic Factors
		29.6	 Treatment
		29.7	 Outcome
		29.8	 Practical Strategy for Liver Tumors
		References
	30: Paediatric Peritoneal Mesothelioma
		30.1	 Introduction
		30.2	 Epidemiology
		30.3	 Clinical Presentation
		30.4	 Radiological Presentation
		30.5	 Pathology
		30.6	 Treatment and Outcome
			30.6.1	 Surgery
			30.6.2	 Chemotherapy
			30.6.3	 Radiotherapy
			30.6.4	 Targeted Therapy
			30.6.5	 Immunotherapy
		30.7	 Conclusion
		References
Part VII: Germ Cell Tumors and Genitourinary Tumors
	31: Gonadal and Extragonadal Germ Cell Tumors, Sex Cord Stromal and Rare Gonadal Tumors
		31.1	 Overview on Epidemiology, Biology, Histology, and Clinic
			31.1.1 Histogenesis and Biology of Extragonadal Germ Cell Tumors
			31.1.2 Sex-Chromosomal Abnormalities in Germ Cell Tumors
			31.1.3 The Primordial Germ Cell Hypothesis of Extragonadal Germ Cell Tumors
			31.1.4 Complex Correlation of Biology, Site, and Histology
			31.1.5 Genetics of Prepubertal Germ Cell Tumors
			31.1.6 Genetics of Postpubertal Germ Cell Tumors
				31.1.6.1	 Pathology
				31.1.6.2	 Mature Teratoma
				31.1.6.3	 Immature Teratoma
				31.1.6.4	 Yolk Sac Tumor
				31.1.6.5	 Germinoma
				31.1.6.6	 Embryonal Carcinoma
				31.1.6.7	 Choriocarcinoma
			31.1.7 Serum Tumor Markers
				31.1.7.1	 Other Markers
			31.1.8 Treatment Overview
			31.1.9 Surgical Treatment of Germ Cell Tumors in the Context of Multimodal Therapy
				31.1.9.1	 Radiotherapy
			31.1.10 Chemotherapy
			31.1.11 Salvage Therapy
			31.1.12 Late Effects
		31.2	 Extragonadal Germ Cell Tumors
			31.2.1 Histogenesis, Biology, and Histology of Extragonadal Germ Cell Tumors
			31.2.2 Pathology
			31.2.3 Clinical Diagnosis
				31.2.3.1	 Clinical Symptoms
			31.2.4 Diagnostic Assessment
			31.2.5 Staging of Extracranial Extragonadal Germ Cell Tumors
			31.2.6 Clinical Staging Systems for Extracranial Extragonadal Germ Cell Tumors
			31.2.7 Germ Cell Tumors of the Central Nervous System
			31.2.8 Treatment Overview
			31.2.9 Principles of Surgery of Extragonadal Extracranial Germ Cell Tumors
			31.2.10 Principles of Chemotherapy for Extragonadal Germ Cell Tumors
			31.2.11 Treatment of Sacrococcygeal Germ Cell Tumors
				31.2.11.1	 Sacrococcygeal Tumors
				31.2.11.2	 Resection of Neonatal Sacrococcygeal Teratomas
				31.2.11.3	 Resection of Malignant Sacrococcygeal Germ Cell Tumors in Toddlers
			31.2.12 Surgical Resection of Intra- and Retroperitoneal Germ Cell Tumors
				31.2.12.1	 Surgical Resection of Vaginal Germ Cell Tumors
				31.2.12.2	 Germ Cell Tumors of the Central Nervous System
			31.2.13 Salvage Strategies
			31.2.14 Prognosis and Late Effects
		31.3	 Testicular Germ Cell Tumors
			31.3.1 Introduction
				31.3.1.1	 Testicular Germ Cell Tumors of Young Children: Genetics
				31.3.1.2	 Testicular Tumors in Adolescents and Adults: Genetics
				31.3.1.3	 Pathology
			31.3.2 Clinical Diagnosis
			31.3.3 Staging
			31.3.4 Therapy
				31.3.4.1	 Teratoma
				31.3.4.2	 Seminoma
				31.3.4.3	 Embryonal Carcinoma
			31.3.5 Prognosis
		31.4	 Germ Cell Tumors of the Ovary
			31.4.1 Introduction
			31.4.2 Ovarian Tumors GCT in Adolescents and Adults: Genetics
				31.4.2.1	 Teratomas
				31.4.2.2	 Immature Teratomas
				31.4.2.3	 Malignant Ovarian Germ Cell Tumors
			31.4.3 Histopathology
			31.4.4 Clinical Diagnosis
			31.4.5 Staging
			31.4.6 Therapy
				31.4.6.1	 Teratoma and Immature Teratoma
				31.4.6.2	 Yolk Sac Tumor and Embryonal Carcinoma of the Ovary
				31.4.6.3	 Dysgerminomas
			31.4.7 Prognosis
		31.5	 Sex Cord Stromal Tumors of the Testis and Ovary
			31.5.1 Introduction
			31.5.2 Biology
			31.5.3 Pathology
				31.5.3.1	 Clinical Presentation
			31.5.4 Diagnostic Assessment and Differential Diagnosis
			31.5.5 Treatment and Prognostic Markers: Review of the Literature
			31.5.6 Proposed Therapeutic Strategy
				31.5.6.1	 Testicular Sex Cord Stromal Tumors
				31.5.6.2	 Ovarian Sex Cord Stromal Tumors
				31.5.6.3	 Stage Ic
				31.5.6.4	 Stages II–III
			31.5.7 A Call for International Collaboration
		31.6	 Ovarian Adenomas, Ovarian Carcinoma, and Ovarian Small Cell Carcinoma
			31.6.1 Introduction
			31.6.2 Clinical Presentation and Diagnostic Assessment
			31.6.3 Therapy
			31.6.4 Review on Multimodal Therapy of OSCHHT in Adults and Children
			31.6.5 Approach to a Multimodal Therapy of OSCCHT of Children and Adolescents
		References
			Overview on Epidemiology, Biology, Histology, and Clinic
			Extragonadal Germ Cell Tumors
			Testicular Germ Cell Tumors
			Germ Cell Tumors of the Ovary
			Sex Cord Stromal Tumors of the Testis and Ovary
			Ovarian Adenomas, Ovarian Carcinoma, and Ovarian Small Cell Carcinoma
	32: Rare Tumors of the Urinary Tract
		32.1	 Differential Diagnosis of Urinary Tract Tumors
		32.2	 Rare Kidney Tumors
		32.3	 Renal Cell Carcinoma (RCC)
			32.3.1	 Epidemiology
			32.3.2	 Diagnosis
			32.3.3	 Pathology and Classification
			32.3.4	 TFE3/MiTF Translocation Family of RCCs
		32.4	 Principles of Treatment
		32.5	 Rhabdoid Tumor of the Kidney (RTK)
			32.5.1	 Molecular Genetics
			32.5.2	 Diagnosis
			32.5.3	 Histopathology
			32.5.4	 Treatment and Prognosis of RTK
		32.6	 European Rhabdoid Registry (EU-RHAB)
		32.7	 Clear Cell Sarcoma of the Kidney (CCSK)
			32.7.1	 Molecular Genetics
			32.7.2	 Diagnosis
			32.7.3	 Histopathology
			32.7.4	 Treatment and Prognosis of CCSK
		32.8	 Differential Diagnosis and Treatment of Urothelial and Bladder Tumors
		References
	33: Breast Cancer
		33.1	 Breast Lesions in Children and Adolescents: Clinical Approach and Differential Diagnosis
		33.2	 Breast Cancer in Adults: Current Concepts
		33.3	 Diagnosis and Treatment
		33.4	 Management of Breast Cancer in Children and Adolescents
		References
Part VIII: Rhabdoid Tumors
	34: Extracranial Rhabdoid Tumours
		34.1	 Introduction
		34.2	 Epidemiology
		34.3	 Age and Gender
		34.4	 Location
		34.5	 Signs and Symptoms
		34.6	 Pathology
		34.7	 Molecular Genetics
			34.7.1	 The SWI/SNF Complex in Rhabdoid Tumours
			34.7.2	 Molecular Subgroups of Extracranial Rhabdoid Tumours
		34.8	 Genetic Predisposition to Rhabdoid Tumours
		34.9	 Imaging and Other Staging Procedures
		34.10	 Differential Diagnosis
		34.11	 Treatment and Risk Factors
			34.11.1	 Rhabdoid Tumours of the Kidney (RTK)
			34.11.2	 Extracranial, Extrarenal Malignant Rhabdoid Tumours (eMRT)
			34.11.3	 High-Dose Chemotherapy Approaches
			34.11.4	 Treatment of Recurrence and Experimental Approaches
		References
Part IX: Rare Tumors of the Peripheral Nervous System
	35: Rare Tumours of the Peripheral Nervous System: Intra-adrenal (Phaeochromocytoma) and Extra-adrenal Paraganglioma
		35.1	 Introduction
		35.2	 Phaeochromocytomas in the United Kingdom National Registry of Childhood Tumours 1971–2002 (Spoudeas and Harrison 2005)
		35.3	 Clinical Presentation
		35.4	 Diagnostic Investigations
			35.4.1	 Biochemical
			35.4.2	 Imaging/Localising Investigations
			35.4.3	 Other Investigations
		35.5	 Pre-operative Medical Management
		35.6	 Operative Management
		35.7	 Malignant Paragangliomas
		35.8	 Carotid Body Tumours
		35.9	 Genetic Management
			35.9.1	 Multiple Endocrine Neoplasia Type 2 (MEN 2)
			35.9.2	 Von Hippel–Lindau (VHL) Disease
			35.9.3	 Neurofibromatosis Type 1 (NF 1)
			35.9.4	 Paraganglioma Syndrome (SDH)
		35.10	 Conclusions
		References
	36: Adrenocortical Tumors in Children
		36.1	 Epidemiology of Adrenocortical Cancer
		36.2	 Biology of ACT
		36.3	 Clinical Characteristics of Pediatric ACT
		36.4	 Diagnosis
		36.5	 Prognostic Factors
		36.6	 Treatment of Pediatric ACT
		36.7	 A Collaborative Research Initiative for Childhood ACT
		References
	37: Medulloepithelioma
		37.1	 Clinical Presentation
		37.2	 Diagnosis
		37.3	 Treatment and Prognosis
		References
	38: Chordoma
		38.1	 Clinical Characteristics
		38.2	 Diagnosis
		38.3	 Treatment
		38.4	 Prognosis and Survival
		References
Part X: Rare Tumors of the Skin and Subcutaneous Tissue
	39: Epidemiology and Differential Diagnosis of Cutaneous Tumors
		References
	40: Cutaneous Melanoma
		40.1	 Risk Factors
		40.2	 Genomic Subtypes of Melanoma
		40.3	 Clinical Manifestations
		40.4	 Establishing the Diagnosis of Pediatric Melanoma
		40.5	 Histological Diagnosis
		40.6	 Histological Diagnosis: MELTUMP
		40.7	 Histological Diagnosis: Melanoma
		40.8	 Staging
		40.9	 Treatment
		40.10	 Survival
		References
	41: Skin Carcinoma
		References
	42: Other Rare Tumors of the Skin and Subcutaneous Tissue
		42.1	 Dermatofibrosarcoma Protuberans
		42.2	 Giant Cell Fibroblastoma
		42.3	 Angiomatoid Fibrous Histiocytoma
		42.4	 Plexiform Fibrohistiocytic Tumor
		42.5	 Dermoid Cysts
		References
Part XI: Vascular Tumors
	43: Vascular Tumors Including Kaposi Sarcoma
		43.1	 Introduction
		43.2	 Infantile Hemangioma
		43.3	 Congenital Hemangiomas
		43.4	 Infantile Hepatic Hemangiomas
		43.5	 Spindle Cell Hemangioma
		43.6	 Epithelioid Hemangioma
		43.7	 Pyogenic Granuloma (Lobular Capillary Hemangioma)
		43.8	 Kaposiform Hemangioendothelioma (and Tufted Angioma)
		43.9	 Kasabach-Merritt Phenomenon
		43.10	 Pseudomyogenic Hemangioendothelioma
		43.11	 Retiform Hemangioendothelioma
		43.12	 Epithelioid Hemangioendothelioma
		43.13	 Angiosarcoma
		43.14	 Kaposi Sarcoma
		References
Part XII: Rare Mesenchymal Tumors
	44: Soft Tissue Sarcomas
		44.1	 The Pathological Characterization
		44.2	 Soft Tissue Tumors with Intermediate Prognosis
			44.2.1	 Fibromatoses
			44.2.2	 Inflammatory Pseudotumors
			44.2.3	 Infantile Fibrosarcoma and NTRK1 Mesenchymal Tumors
		44.3	 Malignant Soft Tissue Tumors
			44.3.1	 Treatment Strategy
			44.3.2	 Fibroblastic/Myofibroblastic Malignancies
			44.3.3	 Leiomyosarcoma
			44.3.4	 Liposarcoma
			44.3.5	 Malignant Peripheral Nerve Sheath Tumors
			44.3.6	 Malignant Tumors of Uncertain Differentiation
				44.3.6.1	 Epithelioid Sarcoma
				44.3.6.2	 Extrarenal Rhabdoid Tumor
				44.3.6.3	 Alveolar Soft Part Sarcoma
				44.3.6.4	 Clear Cell Sarcoma of Tendons and Aponeuroses
			44.3.7	 The PEComa Family Tumors
				44.3.7.1	 Desmoplastic Small Round Cell Tumor
				44.3.7.2	 Synovial Sarcoma
				44.3.7.3	 Myoepithelial Tumors
			44.3.8	 Unclassifiable Sarcomas
				44.3.8.1	 CIC-DUX4 Sarcomas
			44.3.9	 BCOR Family of Undifferentiated Sarcomas
				44.3.9.1	 Pleomorphic Malignant Fibrous Histiocytoma/Undifferentiated High-Grade Pleomorphic Sarcoma
				44.3.9.2	 Extraosseous Chondrosarcoma
			44.3.10	 Other Recently Identified Entities
				44.3.10.1	 Epithelioid-Spindle Cell Tissue Tumors with GLI1 Rearrangements or Amplifications
		44.4	 Targeted Therapies
		44.5	 The Challenge of Adolescents
		References
	45: Rare Bone Tumors
		45.1	 Enchondromatoses (Ollier Disease, Maffucci Syndrome)
		45.2	 Osteosarcoma
		45.3	 Ewing Sarcoma
		References
Part XIII: Tumors of Unknown Primary Site
	46: Tumors of Unknown Primary Site
		46.1	 Cancers of Unknown Origin: Adult Patients
		46.2	 Cancers of Unknown Origin: Pediatric Patients
		46.3	 Diagnostic Staging
		46.4	 Pathology: Cellular Classification
		46.5	 Treatment Strategy
		References
Part XIV: Rare Tumors as Second Malignancies
	47: Rare Subsequent Primary Cancers in Pediatric Cancer Survivors
		47.1	 Introduction
		47.2	 Study Findings
			47.2.1	 Surveillance, Epidemiology, and End Results (SEER) Program
			47.2.2	 Population-Based Studies
			47.2.3	 Childhood Cancer Survivor Study (CCSS)
		47.3	 Synopsis of Above Data
		47.4	 Treatment of Rare Tumors as Secondary Tumors
		References