Textbook of Uncommon Cancer ebook

Table of Contents

Cover

Title Page

Contributors

Preface

Abbreviations

Section 1: General Principles of Care of Uncommon Cancers

1 A Structured Approach to Uncommon Cancers

Introduction

Initial steps

Co‐management

Recommendations

References

2 What Patients Need to Know

Introduction

Information needs

Information sources

Importance of accessible and credible health information

Website reliability

Conclusion

References

3 Involving the Public in Rare Cancer Care and Research

Introduction

Choosing our words

Why involve the public?

Emerging issues in public involvement

Conclusion

References

Section 2: Genitourinary Cancers

4 Uncommon Tumors of the Kidney

Introduction

Classification of renal neoplasms

Molecular diagnostic techniques in renal neoplasms

Renal cell tumors

Metanephric tumors

Nephroblastic tumors

Mesenchymal tumors

Neuroendocrine tumors

Hematopoietic and lymphoid tumors

Provisional entities

Conclusion

References

5 Uncommon Cancers of the Bladder

Introduction

Diagnosis

Sarcomatoid urothelial carcinoma of the bladder

Small cell urothelial carcinoma

Micropapillary bladder cancer

Plasmacytoid variant of urothelial cancer

Lymphoepithelioma‐like urothelial cancer

Squamous carcinoma

Adenocarcinoma (nonurachal)

Urachal cancer

Sarcoma

Conclusion

References

6 Urethral Cancer

Introduction

Anatomy

Epidemiology

Pathology

Investigations

Prognosis and natural history

Treatment

Conclusion

References

7 Uncommon Cancers of the Prostate

Introduction

Neuroendocrine prostate carcinoma

Sarcomas of the prostate

Urothelial carcinoma of the prostate

Primary lymphoma of the prostate

References

8 Rare Tumors of the Testis and Paratesticular Tissues

Introduction

Non‐Hodgkin lymphoma of the testis

Gonadal (sex cord) stromal tumors

Leydig cell tumors

Sertoli cell tumors

Adenocarcinoma of the rete testis

Malignant mesothelioma of the tunica vaginalis

Paratesticular rhabdomyosarcoma

Acknowledgments

References

9 Penile Carcinoma

Introduction and epidemiology

Pathology

Risk factors

Presentation

Treatment of the primary tumor

Treatment of the lymph node basins

Radiotherapy

Chemotherapy

Conclusion

References

Section 3: Head and Neck Cancer

10 Uncommon Tumors of the Oral Cavity and Adjacent Structures

Introduction

Malignant tumors involving the oral cavity mucosa

Malignant tumors of the minor salivary glands

Soft tissue sarcomas

Tumors of the bone

Malignant odontogenic tumors

Other neoplasms

References

11 Rare Tumors of the Larynx

Introduction

Anatomy, presentation, and staging

Imaging of the larynx

Pathological subtypes

Treatment considerations

Conclusion

References

12 Nasopharyngeal Carcinoma in Nonendemic Populations

Introduction

Anatomy of the nasopharynx

Epidemiology and etiology

Pathology

Clinical presentation and diagnosis

Management

Pretreatment evaluation and follow‐up

Management of recurrent or metastatic nasopharyngeal carcinoma

Conclusion

References

13 Esthesioneuroblastoma

Introduction

Staging

Pathology

Molecular biology

Imaging studies

Treatment

Conclusion

References

Section 4: Thoracic Tumors

14 Thymoma and Thymic Carcinoma

Historical background

Anatomy

Biology and epidemiology

Pathology

Clinical presentation

Diagnostic considerations

Staging

Treatment

Prognosis

Recommendations

References

15 Primary Sarcomas of the Lung

Introduction

Epidemiology and etiology

Pathology

Clinical presentation

Differential diagnosis

Diagnostic evaluation

Prognostic factors

Treatment

Case studies

Recommendations

Acknowledgments

References

16 Mesothelioma

Introduction

Epidemiology and links with asbestos exposure

Biology

Pathology

Malignant pleural mesothelioma

Malignant peritoneal mesothelioma and other rare sites of origin of mesothelioma

Conclusion

References

17 Primary Melanoma of the Lung

Introduction

Historical background

Biology

Epidemiology

Molecular biology and genetics

Pathology

Clinical aspects

Treatment

Prognosis

Recommendations

References

18 Large Cell Neuroendocrine Carcinoma

Introduction

Incidence and epidemiology

Molecular pathogenesis

Pathology

Diagnosis

Staging

Treatment

Prognosis and survival

New treatments

Recommendations

References

19 Lung Adenocarcinoma

Introduction

History

2015 WHO classification of lung adenocarcinomas

Lung cancer diagnosis

Preinvasive adenocarcinoma

Minimally invasive adenocarcinoma

Invasive adenocarcinoma

Actionable mutated adenocarcinoma

Conclusion

References

20 Primary Adenoid Cystic Carcinoma of the Lung

Background

Pathology

Clinical features

Radiographic appearance and diagnosis

Treatment

Prognosis

Recommendations

References

Section 5: Breast Cancers

21 Metaplastic Breast Cancer

Introduction

Historical background

Epidemiology

Molecular biology/genetics

Pathology

Clinical aspects – presentation, diagnostic considerations, and techniques

Treatment

Prognosis

Conclusion

References

22 Tubular Carcinoma of the Breast

Introduction

Historical background

Biology and epidemiology

Molecular and genetic studies

Pathology

Clinical aspects: presentation, diagnostic considerations, and techniques

Treatment

Prognosis

Conclusion

References

23 Breast Sarcoma

Introduction

Epidemiology and etiology

Pathology and molecular biology

Differential diagnosis

Clinical aspects – presentation, diagnostic considerations, and techniques

Staging

Management

Surgery

Radiotherapy

Chemotherapy

Surgical management of local recurrence and metastatic disease

Prognosis

Follow‐up

Future considerations

Conclusion

References

24 Adenoid Cystic Carcinoma of the Breast

Introduction

Epidemiology and biology

Pathology

Differential diagnosis

Molecular studies

Clinical features: presentation and imaging

Treatment

Prognosis

Conclusion

References

25 Breast Cancer in Men

Introduction

Epidemiology

Risk factors

Genetics

Clinical presentation and diagnostic evaluation

Pathology

Treatment of breast cancer in men

Adjuvant systemic therapy

Prognosis

Conclusion

References

Section 6: Gastrointestinal Tumors

26 Uncommon Tumors of the Esophagus

Introduction

Esophageal embryology

Unusual tumors related to squamous cell cancers of the esophagus

Mesenchymal tumors of the esophagus

Metastatic cancer to the esophagus

Conclusion

References

27 Uncommon Cancers of the Stomach

Introduction

Neuroendocrine tumors of the stomach

Gastrointestinal stromal tumors

Mucosa‐associated lymphoid tissue

Epstein–Barr virus‐associated gastric carcinoma

Gastric tumors with hepatic and germ cell differentiation

Metastases to the stomach

Conclusion

References

28 Uncommon Cancers of the Small Bowel

Introduction

Epidemiology

Clinical presentation

Diagnosis

Staging

Adenocarcinoma

Sarcoma

Lymphoma

Uncommon neuroendocrine carcinomas

Primary small bowel melanoma

Metastatic disease to the small bowel

References

29 Uncommon Cancers of the Pancreas

Introduction

Cystadenocarcinoma

Adenocarcinoma variants

Acinar cell carcinoma

Pancreatoblastoma

Solid pseudopapillary neoplasm (SPN)

Conclusion

References

30 Uncommon Hepatobiliary Tumors

Introduction

Gallbladder and bile duct tumors

Bile duct tumors

Uncommon hepatic tumors

Conclusion

Acknowledgments

References

31 Unusual Tumors of the Colon, Rectum, and Anus

Introduction

Well‐differentiated neuroendocrine tumors of the colon and rectum

Sarcoma of the colon and rectum

Lymphoma of the colon and rectum

Malignant melanoma

Paget disease of the perianal region

Anal carcinoma

References

32 Gastrointestinal Stromal Tumors

Introduction

Epidemiology

Gross features

Microscopic features

Immunohistochemical features

Microscopic differential diagnosis

Molecular pathology

Clinical presentation and diagnosis

Risk stratification and tumor staging

Treatment

Special problems in patients with gastrointestinal stromal tumors

References

Section 7: Gynecological Cancers

33 Surgery for Uncommon Gynecological Cancers

Introduction

Surgical approach

Ovarian cancer

Uterine cancer

Cervical cancer

Carcinoma of the vulva and vagina

Gestational trophoblastic disease

References

34 Histologies That Cross Organ Types

Introduction and historical background

Endometriosis‐associated tumors

Neuroendocrine carcinomas of the gynecological tract

Extragonadal yolk sac tumor

Extrauterine endometrioid stromal sarcoma

References

35 Germ Cell Tumors of the Ovary

Introduction

Epidemiology

Pathology

Clinical presentation

Staging

Treatment

Dysgerminoma

Ovarian teratoma

Small cell carcinoma of the ovary

Acknowledgment

References

36 Sex Cord‐Stromal Tumors of the Ovary

Introduction

Historical background

Biology and epidemiology

Molecular biology and genetics

Clinical presentation, diagnostic considerations, and techniques

Treatment

Granulosa stromal cell tumors

Conclusion

References

37 Clear Cell Carcinoma of the Ovary

Introduction and historical background

Epidemiology and etiology

Histology and molecular diagnostics

Clinical presentation

Staging

Treatment

Closed and ongoing clinical trials for CCOC using targeted agents

Stage distribution and prognosis

Conclusion

References

38 Mucinous Carcinoma of the Ovary

Introduction and history

Epidemiology and etiology

Classification

Histology

Molecular diagnostics

Clinical presentation

Surgical staging

Treatment by stage

Prognosis

Conclusion

References

39 Low‐Grade Serous Carcinoma of the Ovary

Introduction and historical background

Epidemiology and etiology

Pathology

Clinical presentation

Staging

Treatment by stage

Prognosis

Conclusion

References

40 Borderline Tumors of the Ovary

Introduction and historical background

Epidemiology and etiology

Histology and molecular diagnostics

Clinical presentation

Staging

Treatment

Stage distribution and prognosis

Conclusion

References

41 Fallopian Tube and Peritoneal Cancers

Introduction

Epidemiology

Etiology

Anatomy

Staging

Pathology

Clinical presentation and diagnostic considerations

Treatment

Prognosis

References

42 Nonendometrioid Endometrial Carcinomas and Uterine Sarcomas

Nonendometrioid endometrial carcinomas

Uterine papillary serous carcinoma

Clear cell carcinoma

Carcinosarcoma

Other rare endometrial carcinomas

Uterine sarcoma

Other rare tumors

Conclusion

References

43 Tumors of the Cervix

Epidemiology

Staging of cervical cancer

Clinical presentation and management

Translational science (see Table 43.2)

Uncommon histologies and prognosis

Glandular tumors

Other epithelial tumors

Sarcomas

Miscellaneous

Summary of treatment guidelines for cancer of the cervix

References

44 Tumors of the Vulva and Vagina

Introduction

Squamous cell carcinoma of the vulva

Vulvar melanoma

Rare vulvar histologies

Squamous cell carcinoma of the vagina

Rare vaginal histologies

Conclusion

References

45 Gestational Trophoblastic Disease

Introduction

Epidemiology

Clinicopathology

Diagnosis

Treatment

Placental site trophoblastic tumor and epithelioid trophoblastic tumor

Follow‐up after treatment for GTN

References

46 Targeted Therapy in Gynecological Malignancy

Introduction

Angiogenesis

Phosphatidylinositol‐3‐kinase/protein kinase B pathway

Ras/Raf pathway

Epidermal growth factor receptor pathway

Multipathway‐targeted agents

Poly‐ADP‐ribose polymerase pathway and PARP inhibitors

Conclusion

References

Section 8: Endocrine Tumors

47 Adrenal Neoplasms

Introduction

Adrenal physiology

Adrenal incidentalomas

Malignant neoplasms of the adrenal cortex

Neoplasms of adrenal medulla

Oncocytic adrenal neoplasms

Other uncommon variants

Conclusion

References

48 Uncommon Cancers of the Thyroid

Introduction

Medullary thyroid carcinoma

Hürthle cell carcinoma

Anaplastic thyroid carcinoma

Insular thyroid carcinoma

Primary thyroid lymphoma

Sarcoma

Primary squamous cell carcinoma of the thyroid

Malignant teratoma

Malignant hemangioendothelioma

Mucoepidermoid carcinoma

Secondary thyroid malignancies

Conclusion

References

49 Parathyroid Carcinoma

Introduction

Embryology, anatomy, and physiology

Epidemiology

Etiology

Genetics

Pathology

Staging

Clinical presentation

Imaging studies

Operative findings

Treatment

Prognosis

Conclusion

References

Section 9: Hematological Malignancies

50 Rare Acute Leukemias

Introduction

Rare leukemias associated with myeloproliferative neoplasms

Rare subtypes of acute myeloid leukemia

Rare stem cell leukemias

References

51 Unusual Myelodysplastic and Myelodysplastic/Myeloproliferative Neoplasms

Introduction

Myelodysplastic syndromes

Conclusion

References

52 Rare B Cell Lymphoproliferative Disorders

Introduction

B cell prolymphocytic leukemia

Hairy cell leukemia

Lymphomatoid granulomatosis

Intravascular large B cell lymphoma

Primary effusion lymphoma

Castleman disease

High‐grade B cell lymphoma, with rearrangements of MYC and BCL2 and/or BCL6 (“double‐hit lymphoma”)

B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and classical Hodgkin lymphoma (“gray zone” lymphoma)

Nodular lymphocyte‐predominant Hodgkin lymphoma

Conclusion

References

53 Uncommon Presentations of Plasma Cell Dyscrasias

Introduction

Rare multiple myeloma subtypes

Plasma cell leukemia

Waldenström macroglobulinemia

Amyloid light chain amyloidosis

Heavy chain disease

Osteosclerotic myeloma

Solitary plasmacytomas

References

54 Rare Bone Marrow Failure Conditions

Introduction

Acquired bone marrow failure syndromes

Inherited bone marrow failure syndromes

Conclusion

References

55 Myeloproliferative Neoplasms

Introduction and classification of myeloproliferative neoplasms

Chronic myeloid leukemia

Polycythemia vera, essential thrombocythemia, and primary myelofibrosis

Risk stratification and prognosis of myeloproliferative neoplasms

Treatment of polycythemia vera and essential thrombocythemia

Treatment of primary myelofibrosis and postpolycythemia vera/essential thrombocythemia myelofibrosis

Leukemic transformation of myeloproliferative neoplasms

Chronic neutrophilic leukemia

Chronic eosinophilic leukemia

Systemic mastocytosis

References

56 Rare T Cell Lymphomas

Introduction

T cell lymphoblastic lymphoma

Hepatosplenic T cell lymphoma

Enteropathy‐associated T cell lymphoma

Subcutaneous panniculitis‐like T cell lymphoma

References

Section 10: Neurological Tumors

57 Primary Melanotic Tumors of the Central Nervous System

Introduction

Clinical presentation

Neuroimaging features

Neuropathological features

Histopathology

Molecular alterations

Treatment

Conclusion

References

58 Comprehensive Management of Chordoma

Introduction

Pathology

Diagnosis

Surgical treatment

Radiotherapy

Chemotherapy

Conclusion

References

59 Atypical and Malignant Meningiomas

Introduction

Epidemiology

Diagnosis

Pathology

Molecular epidemiology

Treatment

Conclusion

Acknowledgments

References

60 Primary Central Nervous System Lymphoma

Introduction

Epidemiology

Pathology

Clinical presentation

Diagnostic considerations

Treatment

Acknowledgments

References

61 Choroid Plexus Tumors

Introduction

Incidence and epidemiology

Presentation

Imaging appearance

Histological appearance

Clinical management

Conclusion

References

62 Diffuse Low‐Grade Gliomas

Introduction

Epidemiology

Clinical presentation

Role of surgery

Neuropathology and molecular pathology

Role of radiation and chemotherapy

Future therapies

Prognosis

Conclusion

References

63 High‐Grade Gliomas

Introduction

Grade IV glioma (glioblastoma)

Grade III gliomas

Conclusion

References

64 Ependymomas

Introduction

Epidemiology and demographics

Neuropathology

Molecular biology

Clinical presentation and neuroimaging features

Course of disease

Prognostic factors

Treatment

Challenges in clinical research in ependymomas

References

65 Medulloblastoma in Adults

Introduction

Biology and epidemiology

Clinical presentation

Medulloblastoma in children

Medulloblastoma in adults

Recommendations

References

66 Pineal Parenchymal Tumors

Introduction

Epidemiology

Pathogenesis

Pathology

Clinical presentation

Diagnostic considerations

Treatment

Prognosis

Recommendations

References

67 Craniopharyngiomas

Introduction

Anatomy

Embryology and epidemiology

Pathology

Clinical presentation and diagnostic considerations

Imaging

Treatment

Recommendations

Prognosis

Conclusion

References

68 Ophthalmic Cancers

Introduction

Eyelid

Ocular surface squamous neoplasia

Uveal melanoma

Retinoblastoma

References

Section 11: Cutaneous Malignancies

69 Unusual Cutaneous Malignancies

Introduction

Fibrous and histiocytic tumors

Tumors with glandular differentiation

Hair follicle and hair matrix tumors

Lipocyte tumors

Melanocytic tumors

Muscle tumors

Nervous tissue tumors

Neuroendocrine tumors

Vascular tumors

Conclusion

References

70 Dermatofibrosarcoma Protuberans

Introduction

Biology

Presentation

Pathology

Treatment

Recommendations

References

71 Unusual Melanomas

Introduction

Mucosal melanoma

Uveal melanoma

Desmoplastic melanoma

References

Section 12: Musculoskeletal Tumors

72 Uncommon Tumors of Soft Tissue

Introduction

Grading and staging

Treatment

Alveolar soft part sarcoma

Clear cell sarcoma

Desmoplastic small round‐cell tumor

Epithelioid sarcoma

Extraskeletal myxoid chondrosarcoma

Inflammatory myofibroblastic tumor

Myxoid/round‐cell liposarcoma

Malignant perivascular epithelioid cell tumor (PEComa)

Ewing sarcoma/primitive neuroectodermal tumor of soft tissue

Synovial sarcoma

References

Section 13: Pediatric Cancers

73 Introduction to Rare Pediatric Malignancies

Defining rare cancers

North American efforts to study rare childhood cancers

Clinical trials in rare pediatric cancers

References

74 Uncommon Tumors of the Gastrointestinal Tract in Children

Introduction

Carcinoid tumors

Colorectal carcinomas

Gastrointestinal stromal tumors

Tumors of the pancreas

References

75 Rare Pediatric Malignancies of the Head and Neck

Introduction

Salivary gland tumors

Treatment

Nasopharygeal carcinoma

Central giant cell lesions

Conclusion

References

76 Uncommon Pediatric Tumors of the Thorax

Introduction

Mediastinum

Heart, pericardium, and great vessels

Lung and airways

Chest wall, diaphragm, and pleura

References

77 Uncommon Adrenal Tumors in Children and Adolescents

Introduction

Epidemiology and pathogenesis

Clinical features

Diagnosis

Treatment

Outcome

Prognostic factors

St Jude International Pediatric Adrenocortical Tumor Registry

Children's Oncology Group Adrenocortical Tumor Trial

Acknowledgments

References

78 Uncommon Pediatric Genitourinary Tumors

Introduction

The kidney

The female reproductive tract

The male reproductive system

References

79 Uncommon Pediatric Brain Tumors

Introduction

Angiocentric glioma

Astroblastoma

Atypical teratoid/rhabdoid tumor

Clinical presentation

Medulloepithelioma

Embryonal tumor with multilayered rosettes

Pineoblastoma

Choroid plexus carcinoma

Desmoplastic infantile ganglioglioma/astrocytoma

Dysembryoplastic neuroepithelial tumor

Myxopapillary ependymoma

Pilomyxoid astrocytoma

Primary melanocytic neoplasms

Pleomorphic xanthoastrocytoma

Rosette‐forming glioneuronal tumor (of the fourth ventricle)

Subependymal giant cell astrocytoma

References

80 Malignant Tumors of the Skin and Subcutaneous Tissue in Children

Introduction

Melanoma

Malignant epithelial tumors of the skin

Histiocytoses

Primary soft tissue sarcomas of the skin and subcutaneous tissue

Metastatic tumors to the skin and subcutaneous tissues

Primary cutaneous lymphomas

Secondary skin involvement by hematological malignancies

Cutaneous mastocytosis

References

81 Rare Hematological Malignancies in Children

Introduction

Juvenile myelomonocytic leukemia

Chronic myeloid leukemia

Philadelphia chromosome‐positive acute lymphoblastic leukemia

Acute megakaryoblastic leukemia

References

Index

End User License Agreement

List of Tables

Chapter 01

Table 1.1 Schema for the management of uncommon tumors.

Chapter 02

Table 2.1 Resources for evaluating online health information.

Table 2.2 Resources for locating quality consumer rare cancer information online.

Chapter 03

Table 3.1 Examples of projects relevant to people with rare cancers.

Table 3.2 Examples of public involvement at each stage of the care and research cycle.

Chapter 06

Table 6.1 Summary of several contemporary series of urethral carcinoma.

Chapter 07

Table 7.1 Neuroendocrine prostate cancer clinical summary.

Chapter 08

Table 8.1 Prognosis of testicular lymphoma.

Table 8.2 Testicular lymphoma: stage distribution.

Table 8.3 Testicular lymphoma: sites of relapse.

Table 8.4 Testicular lymphoma: radiotherapy results.

Table 8.5 Classification and incidence of sex cord stromal tumors of the testis.

Table 8.6 Outcome of patients undergoing retroperitoneal lymph node dissection for sex cord tumors.

Table 8.7 Classification of rhabdomyosarcoma.

Table 8.8 TNM pretreatment staging system for rhabdomyosarcoma.

Table 8.9 Intergroup Rhabdomyosarcoma Study Group (IRSG) Post‐Surgical Clinical Group classification.

Table 8.10 Children's Oncology Group risk groups and outcome for rhabdomyosarcoma.

Table 8.11 Paratesticular rhabdomyosarcoma: results of treatment.

Chapter 09

Table 9.1 Pathological variants of squamous cell carcinoma of the penis.

Table 9.2 Five‐year cancer‐specific survival related to pathological stages.

Table 9.3 Risk groups for predicting lymph node metastases.

Chapter 11

Table 11.1 Primary tumor (T).

Table 11.2 Regional lymph nodes (N).

Table 11.3 Overall stage groupings.

Chapter 12

Table 12.1 Age‐adjusted incidence rates by ethnic grouping.

Table 12.2 Frequency of cranial nerve involvement in cancer of the nasopharynx.

Table 12.3 Distant metastatic sites of nasopharyngeal carcinoma: a study of 2637 patients.

Table 12.4 Stage grouping: nasopharynx.

Table 12.5 Definitions of high‐, intermediate‐, and low‐risk clinical target volumes (CTVs).

Chapter 13

Table 13.1 Staging systems for esthesioneuroblastoma.

Table 13.2 Hyams' histologic grading system for olfactory neuroblastoma.

Table 13.3 Selective immunohistochemical reactivity of various sinonasal tract malignancies.

Chapter 14

Table 14.1 Staging systems.

Table 14.2 Chromosome aberrations reported in thymic malignancies.

Table 14.3 2015 WHO classification of thymic epithelial tumors.

Table 14.4 Results of chemotherapy in patients with epithelial thymic malignancies.

Table 14.5 Survival rates for thymoma and thymic carcinoma.

Chapter 15

Table 15.1 Histological subtypes of primary pulmonary sarcomas.

Table 15.2 Immunohistochemical staining of primary pulmonary sarcomas.

Chapter 16

Table 16.1 Ten countries with the highest age‐adjusted mortality rates from mesothelioma.

Table 16.2 Key clinical or readily derived prognostic factors in mesothelioma.

Table 16.3 Brims population prognostic model for survival using clinical parameters at diagnosis.

Table 16.4 Examples of targets and drugs in malignant mesothelioma that are under investigation as of July 2016.

Chapter 17

Table 17.1 Published reports of 75 patients with primary melanomas of the trachea, bronchi, lungs, and pleura fulfilling most or all of the currently accepted diagnostic criteria.

Chapter 18

Table 18.1 Neuroendocrine differentiation in large cell carcinoma.

Table 18.2 Large cell neuroendocrine carcinoma: demographics and survival.

Table 18.3 Pathological differences between SCLC and pulmonary LCNEC.

Chapter 19

Table 19.1 2015 World Health Organization classification of lung adenocarcinoma.

Chapter 20

Table 20.1 Growth pattern and prognosis of 12 patients based on histological grade for adenoid cystic carcinoma of the tracheobronchial tree.

Table 20.2 Prognosis based on clinical stage at diagnosis for 16 patients with adenoid cystic carcinoma of the lung and tracheobronchial tree.

Chapter 23

Table 23.1 Survival outcomes of breast sarcomas.

Chapter 25

Table 25.1 Overall survival based on pathological axillary nodal status.

Chapter 27

Table 27.1 Staging and grades of neuroendocrine tumors.

Table 27.2 Clinicopathological characteristics of gastric neuroendocrine tumors.

Chapter 28

Table 28.1 Malignant tumors of the small bowel seen at the MD Anderson Cancer Center 2000–2010 (

n

 = 1360).

Chapter 31

Table 31.1 Grading of neuroendocrine tumors.

Table 31.2 Summary of large bowel cancer (nonadenocarcinoma) types.

Chapter 32

Table 32.1 Relative frequencies of gastrointestinal stromal tumor (GIST) genetic subtypes.

Table 32.2 Risk stratification of primary gastrointestinal stromal tumor (GIST) by mitotic index, size, and site.

Table 32.3 Multi‐institutional trials evaluating neoadjuvant or adjuvant imatinib in the perioperative management of resected primary gastrointestinal tumors.

Chapter 33

Table 33.1 Extent of surgery based on diagnosis of ovarian cancer.

Table 33.2 Extent of surgery for uterine cancers.

Table 33.3 Lateral margins for vulvar cancer.

Chapter 35

Table 35.1 International Federation of Gynecology and Obstetrics staging of ovarian germ cell tumors in adult patients.

Table 35.2 Children’s Oncology Group Staging for ovarian germ cell tumors.

Table 35.3 BEP regimen. Three to four courses given at 21‐day intervals.

Table 35.4 PEb regimen.

Table 35.5 Results of clinical surveillance after surgery in patients with stage IA dysgerminoma.

Table 35.6 Results of radiotherapy in dysgerminoma.

Chapter 36

Table 36.1 Classification of stromal tumors of the ovary.

Table 36.2 Protocol for BEP (bleomycin, etoposide, and cisplatin).

Table 36.3 Common dosing schedules for chemotherapy, hormonal therapy, and targeted agents.

Chapter 37

Table 37.1 Genetic alterations in clear cell carcinoma of the ovary.

Table 37.2 Treatment strategy for clear cell ovarian carcinoma.

Chapter 39

Table 39.1 Distinctions amongst the Type I and Type II epithelial ovarian carcinoma subtypes.

Chapter 40

Table 40.1 TNM and FIGO staging of ovarian cancer.

Chapter 41

Table 41.1 The FIGO staging system for ovarian, fallopian tube, and primary peritoneal carcinoma.

Table 41.2 Chemotherapy for advanced epithelial ovarian cancer: recommended regimens.

Chapter 42

Table 42.1 FIGO staging: carcinoma of the endometrium.

Table 42.2 Large retrospective studies of women with UPSC with staging information comparing survival of women with and without chemotherapy.

Table 42.3 Biological therapy in endometrial cancer.

Table 42.4 Ober classification of uterine sarcomas.

Table 42.5 Single agents studied in uterine carcinosarcoma and leiomyosarcoma.

Table 42.6 Combination regimens studied in uterine carcinosarcoma and leiomyosarcoma.

Table 42.7 Hendrickson and Kempson revised classification system for uterine smooth muscle tumors.

Table 42.8 FIGO staging: uterine sarcomas (leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma).

Chapter 43

Table 43.1 International Federation of Gynecology and Obstetrics 2009 Classification System for Clinical Staging of Carcinoma of the Cervix Uteri.

Table 43.2 Prognostic biomarkers for invasive cervical carcinoma.

Table 43.3 Histological classification of cervical cancer.

Chapter 44

Table 44.1 A summary of the International Federation of Gynecology and Obstetrics (FIGO) staging system for carcinoma of the vulva, cervix, and endometrium.

Table 44.2 The tumor, nodes, metastasis (TNM) staging system for staging of cutaneous melanoma, used for the staging of vulvar melanoma.

Table 44.3 Treatment summary: squamous cell carcinoma and melanoma of the vulva.

Table 44.4 A summary of the International Federation of Gynecology and Obstetrics (FIGO) and tumor, nodes, metastasis (TNM) staging systems used for the staging of vaginal cancers.

Chapter 45

Table 45.1 Epidemiological risk factors for gestational trophoblastic diseases.

Table 45.2 Clinicopathological features of gestational trophoblastic disease.

Table 45.3 FIGO staging for gestational trophoblastic neoplasia.

Table 45.4 FIGO (modified WHO) scoring system for gestational trophoblastic neoplasia.

Table 45.5 Chemotherapy regimens for low‐risk gestational trophoblastic neoplasia.

Table 45.6 EMA‐CO chemotherapy for high‐risk gestational trophoblastic neoplasia.

Chapter 46

Table 46.1 Ongoing and completed trials using biological and targeted agents in uncommon gynecological tumors.

Chapter 47

Table 47.1 Adrenocortical carcinoma: associated hereditary syndromes.

Table 47.2 Radiological characteristics of adrenal lesions.

Table 47.3 Comparison of the American Joint Cancer Committee/World Health Organization (AJCC/WHO) staging system and the European Network for the Study of Adrenal Tumors (ENSAT) staging system for adrenocortical carcinoma.

Table 47.4 Most commonly used agents for hormonal control in adrenocortical carcinoma.

Table 47.5 Pheochromocytoma (PHEO): associated hereditary syndromes.

Chapter 48

Table 48.1 Pretherapeutic basal calcitonin levels and extent of neck dissection.

Table 48.2 Postoperative surveillance recommendations.

Table 48.3 Summary of clinical trials of multikinase inhibitors (MKIs) in locally advanced and metastatic medullary thyroid carcinoma (MTC).

Table 48.4 Trials evaluated multikinase inhibitors (MKIs) in differentiated thyroid cancer (DTC) which included patients with Hürthle cell carcinoma (HCC).

Chapter 49

Table 49.1 Frequency of clinical manifestations of hypercalcemia with parathyroid carcinoma.

Table 49.2 Serum calcium and parathyroid hormone levels in patients with parathyroid carcinoma.

Table 49.3 Recurrence and survival rates for parathyroid carcinoma.

Chapter 50

Table 50.1 Characteristics of rare acute leukemias.

Table 50.2 Clinical features of chronic neutrophilic leukemia (CNL) versus similar disorders.

Table 50.3 The Year 2011 Working Conference on Eosinophil Disorder and Syndromes definitions of hypereosinophilia and hypereosinophilic syndrome.

Table 50.4 Characteristics of chronic eosinophilic leukemia (CEL) and hypereosinophilic syndrome disorders (HES).

Chapter 51

Table 51.1 Myelodysplastic syndrome (MDS).

Table 51.2 Classical myeloproliferative neoplasms (MPN).

Table 51.3 Chronic myelomonocytic leukemia (CMML).

Table 51.4 Therapy‐related myelodysplastic syndrome.

Chapter 52

Table 52.1 Summary of features differentiating mediastinal lymphomas according to the World Health Organization (WHO) classification.

Chapter 53

Table 53.1 Durie–Salmon Staging System.

Table 53.2 Revised International Staging System (R‐ISS).

Table 53.3 Waldenström macroglobulinemia Inter‐national Prognostic Scoring System.

Table 53.4 Treatment response criteria for Waldenström macroglobulinemia (WM).

Table 53.5 Overview of systemic therapies for Waldenström macroglobulinemia.

Table 53.6 Trials of high‐dose therapy for Waldenström macroglobulinemia.

Table 53.7 Mayo Clinic prognostic system for staging of amyloid light chain (AL) amyloidosis.

Chapter 54

Table 54.1 Distribution, clinical/genetic features, and management of select acquired bone marrow failure syndromes.

Table 54.2 Suggested diagnostic workup for patients with concern for the diagnosis of bone marrow failure.

Table 54.3 Camitta criteria for the diagnosis of aplastic anemia (AA).

Table 54.4 Clinical features of select inherited bone marrow failure (BMF) syndromes.

Chapter 55

Table 55.1 World Health Organization (WHO) 2008 diagnostic criteria for post‐polycythemia vera (PPV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).

Table 55.2 Risk scores for myeloproliferative neoplasms (MPN).

Table 55.3 Treatment options for myeloproliferative neoplasms (MPN). Listed are selected drugs with clinical trial data available on MPNs. Examples of representative studies are provided in the table, not a complete assembly of data. Experimental agents are not listed or discussed.

Chapter 56

Table 56.1 Enteropathy‐associated T cell lymphoma (EATL) subtypes.

Table 56.2 Comparison between former subtypes of SPTL: αβ (currently SPTL) and γδ (currently within CGD‐TCL).

Chapter 58

Table 58.1 Prospective studies of molecular targeted therapies for chordoma.

Chapter 59

Table 59.1 Overview of genes implicated in meningiomas.

Table 59.2 Overview of select clinical trials of targeted therapies and other systemic agents in meningiomas.

Chapter 60

Table 60.1 Therapeutic outcomes for patients with non‐AIDS primary central nervous system lymphoma.

Chapter 61

Table 61.1 Dosage and administration schedule of chemotherapy in the setting of residual or recurrent atypical choroid plexus papilloma and choroid plexus carcinoma.

Chapter 66

Table 66.1 A historical comparison of overall survival and progression‐free survival between pineocytoma, pineal parenchymal tumor of intermediate differentiation (PPTID), and pineoblastoma.

Chapter 67

Table 67.1 Radiographic differential diagnosis of craniopharyngiomas.

Table 67.2 Summary of results of conventional radiotherapy (CRT) on craniopharyngiomas.

Table 67.3 Reported results of gamma knife radiosurgery (GKRS) for craniopharyngiomas.

Chapter 68

Table 68.1 Common ophthalmic tumors classified by anatomical layers.

Table 68.2 Classification system and design of Collaborative Ocular Melanoma Trials.

Chapter 69

Table 69.1 Immunohistochemistry of Merkel cell cancer.

Table 69.2 Merkel cell cancer AJCC staging system.

Table 69.3 Merkel cell cancer AJCC staging and survival.

Chapter 70

Table 70.1 Literature review of surgical management and outcomes for dermatofibrosarcoma protuberans.

Chapter 71

Table 71.1 Localized therapies for metastatic uveal melanoma.

Table 71.2 Open clinical trials for uveal melanoma.

Chapter 72

Table 72.1 American Joint Committee on Cancer staging of soft tissue sarcomas.

Chapter 74

Table 74.1 Pediatric series of gastrointestinal tumors.

Table 74.2 Digestive system malignancies by age, SEER data 2008–2012.

Table 74.3 Clinical and pathological features of pediatric versus adult gastrointestinal stromal tumors (GISTs).

Table 74.4 Series of pediatric patients with pancreatic tumors.

Chapter 76

Table 76.1 The World Health Organization classification of thymic tumors.

Table 76.2 Masaoka–Koga staging system.

Chapter 77

Table 77.1 Constitutional genetic abnormalities associated with adrenocortical tumors (ACTs).

Table 77.2 Staging of adrenocortical tumors in children.

Table 77.3 Treatment scheme for adrenocortical tumors according to clinical stage.

Chapter 78

Table 78.1 Frequency and outcome for pediatric renal cell carcinoma by modified Robson Stage

Chapter 80

Table 80.1 Primary skin malignancies by histopathological subtype, SEER data 2000–2008.

Table 80.2 Histiocytic disorders with skin involvement.

Table 80.3 Primary soft tissue sarcomas of the skin and subcutaneous tissues.

Table 80.4 World Health Organization/European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas.

Chapter 81

Table 81.1 Diagnostic criteria of JMML.

Table 81.2 Diagnostic criteria for chronic, accelerated, and blast phases of chronic myeloid leukemia.

Table 81.3 Response to therapy for chronic myeloid leukemia.

Table 81.4 Laboratory monitoring guidelines.

Table 81.5 Tyrosine kinase inhibitor dosing in pediatric patients.

Table 81.6 Genetic events in pediatric acute megakaryoblastic leukemia.

List of Illustrations

Chapter 04

Figure 4.1 Renal oncocytoma forms a well‐circumscribed, nonencapsulated mass with homogeneous cut surface and a central scar (a). The tumor cells (oncocytes) are uniform, round to polygonal with granular eosinophilic cytoplasm and regular round nuclei with evenly dispersed chromatin. They are nested in a loose hypocellular and hyalinized stroma (b).

Figure 4.2 Collecting duct renal cell carcinoma consists of high‐grade tumor cells (a) forming complex and angulated tubules, or tubulopapillary structures embedded in a remarkably desmoplastic stroma (b).

Figure 4.3 Renal cell carcinoma associated with t(X;17) (p11.2; q25) consists of nested to pseudopapillary structures lined with tumor cells with abundant clear, sometimes eosinophilic, cytoplasm.

Figure 4.4 Metanephric adenoma is sharply demarcated from the adjacent renal parenchyma (a). The tumor cells are closely packed to form tubules with inconspicuous lumens. They have a strikingly uniform appearance with scant cytoplasm and smooth chromatin (b).

Figure 4.5 (a) Angiomyolipoma characteristically consists of three elements: blood vessels (lower right), adipocytes (lower left), and smooth muscle cells (upper). Melanocytic markers, such as HMB‐45, are positive in some tumor cells (b).

Chapter 05

Figure 5.1 Uncommon variants of urothelial carcinoma. (a) Sarcomatoid urothelial carcinoma of the bladder showing densely spindled cells with atypia, which can mimic a sarcoma microscopically. (b) Small cell urothelial carcinoma. (c) Micropapillary variant of urothelial carcinoma composed of small nests of atypical epithelial cells present within distinct lacunar spaces. (d) Plasmacytoid variant of urothelial carcinoma. Note loosely arranged oval cancer cells with distinct eosinophilic cytoplasm and eccentric nuclei. Some of the cells have a large mucin containing cytoplasmic vacuole displacing the nucleus. (e) Lymphoepithelioma‐like carcinoma of the bladder showing a syncytial growth of tumor cells containing large vesicular nuclei and prominent nucleoli. Note the obscuring inflammation.

Figure 5.2 Cause‐specific survival of patients with resectable and metastatic small cell carcinoma. Kaplan‐Meier overall survival (OS) results from a phase II clinical trial in small cell urothelial cancer. On the neoadjuvant arm, the median OS time was 58 months (95% CI, 58 months to not achieved [NA]). On the metastatic arm, the median OS time was 13.3 months (95% CI, 8.5 months to NA).

Figure 5.3 Radiographic features of plasmacytoid urothelial carcinoma and urachal carcinoma. (a) Plasmacytoid tumor diffusely involving perirectal tissue. This patient presented with rectal tenesmus and pencil thin stool. Tumor is seen extensively involving the wall of the bladder (open arrows) causing bilateral hydronephrosis (ureteral stents seen), with tumor diffusely involving perirectal tissue (solid arrows). (b) Radiographic features of urachal cancer. The appearance of a midline, cystic, bladder mass with microcalcifications, is nearly pathognomonic for the diagnosis of urachal cancer.

Figure 5.4 Nonurothelial bladder cancer. (a) Squamous cell carcinoma of the bladder with keratin formation. (b) Colonic variant of bladder adenocarcinoma composed of large glandular structures with atypical, stratified nuclei.

Chapter 06

Figure 6.1 Nephrogenic adenoma with small tubules lined by cuboidal cells (a); positive immunoreactivity with PAX‐8 (b).

Figure 6.2 Squamous cell carcinoma with islands of tumor cells with areas of keratinization.

Figure 6.3 Papillary urothelial carcinoma, high‐grade of the urethra.

Figure 6.4 Leiomyoma with bland spindle cells arranged in fascicles.

Chapter 07

Figure 7.1 Neuroendocrine prostate cancer. Low‐ (a) and high‐power (b) views of NEPC showing sheets of densely packed cells with nuclear molding, increased nucleus:cytoplasm (N:C) ratio, coarse chromatin, and irregular nuclear membranes.

Figure 7.2 Prostatic sarcoma. (a) Pathological appearance of leiomyosarcoma of the prostate. H&E section shows intersecting fascicles of atypical spindled cells with eosinophilic cytoplasm, marked nuclear pleomorphism, and hyperchromasia. (b) Pathological appearance of stromal sarcoma of the prostate. Hypercellular stroma is composed of atypical spindled cells and interspersed benign glands. The stromal cells show loosely fascicular growth pattern, nuclear pleomorphism, and hyperchromasia, and tend to show condensation beneath the glandular component.

Figure 7.3 Computed tomography image of malignant fibrous tumor of the prostate. Notice the enlarged heterogenous prostate with areas of central necrosis. The seminal vesicles are pushed posteriorly with the mass pushing into the bladder base without invasion. The trigone is elevated and the rectum spared, with tumor extending into the pouch of Douglas, consistent with a prostatic sarcoma.

Chapter 08

Figure 8.1 Diagram of testis and spermatic cord indicating sites of tumor origin. Paratesticular rhabdomyosarcoma may arise from connective tissue of the cord or of adjacent structures.

Figure 8.2 Incidence of germ cell tumors (solid line) and of lymphomas (dashed line) of the testis by age of presentation.

Figure 8.3 Leydig cell tumor composed of relatively uniform cells with rounded nuclei and abundant cytoplasm (H&E, 310×).

Figure 8.4 Diffuse B cell lymphoma involving the testis. The infiltrate is interstitial and widely separates seminiferous tubules that contain only Sertoli cells (H&E, 62×).

Figure 8.5 Sertoli cell tumor with a pattern of variably sized tubules in a loose fibrous stroma (H&E, 155×).

Chapter 09

Figure 9.1 Bimodal pathway of carcinogenesis. Differentiated penile intraepithelial neoplasia (PeIN) (a) is part of the non‐human papilloma virus (HPV)‐associated carcinogenesis pathway and is characterized by maturation of squamous epithelium, elongation of rete ridges, eosinophilic cytoplasm, basal layer atypia and overexpression of p53 (b). Usual type squamous cell carcinomas associated with differentiated PeIN commonly show prominent keratinization of the invading nests of tumor cells (c). Basaloid/undifferentiated PeIN (d) is part of the HPV‐associated carcinogenesis pathway and is characterized by lack of maturation of the squamous epithelium, high mitotic rate, numerous apopotic bodies and overexpression of p16 (e). Basaloid squamous cell carcinomas associated with basaloid/undifferentiated PeIN show solid architecture or invading nests comprised of small basaloid tumor cells (f).

Figure 9.2 A 59‐year‐old male presenting with pT2G2 squamous cell carcinoma of the penis.

Figure 9.3 Modified superficial template ilioinguinal lymphadenectomy with saphenous vein sparing.

Chapter 10

Figure 10.1 (a) Verrucous carcinoma showing an exophytic, warty lesion with preserved epithelial maturation (H&E, 40×). (b) Verrucous carcinoma showing epithelial proliferation with minimal cytological atypia and rare mitotic figures, restricted to the basal layer (H&E, 200×).

Figure 10.2 Malignant melanoma showing a heavily pigmented malignant neoplasm involving the submucosa (H&E, 200×).

Figure 10.3 (a) Mucoepidermoid carcinoma, low grade (H&E, 40×). (b) Mucoepidermoid carcinoma, intermediate grade (H&E, 40×). (c) Mucoepidermoid carcinoma, high grade (H&E, 400×).

Figure 10.4 Adenoid cystic carcinoma, predominantly cribriform pattern (H&E, 40×).

Figure 10.5 Acinic cell carcinoma (H&E, 200×).

Figure 10.6 Carcinoma ex pleomorphic adenoma, invasive type (H&E, 40×).

Figure 10.7 Polymorphous low‐grade adenocarcinoma (H&E, 200×).

Figure 10.8 High‐grade, undifferentiated pleomorphic sarcoma (H&E, 40×).

Figure 10.9 Angiosarcoma of the oral cavity (H&E, 200×).

Figure 10.10 Synovial sarcoma, monophasic type (H&E, 200×).

Figure 10.11 Leiomyosarcoma (H&E, 200×).

Figure 10.12 Rhabdomyosarcoma, botryoid type (H&E, 200×).

Figure 10.13 Chondrosarcoma, low grade (H&E, 200×).

Figure 10.14 Osteosarcoma, osteoblastic type (H&E, 200×).

Figure 10.15 Langerhans cell histiocytosis (H&E, 200×).

Figure 10.16 Ameloblastic carcinoma (H&E, 400×).

Figure 10.17 (a) Kaposi sarcoma (H&E, 200×). (b) Kaposi sarcoma (HHV8 stain, 200×).

Figure 10.18 (a) Burkitt lymphoma (H&E, 40×). (b) Burkitt lymphoma (Ki67 stain, 40×).

Chapter 11

Figure 11.1 External laryngeal skeleton.

Figure 11.2 Midsagittal section of the larynx.

Figure 11.3 Posterior view of the endolaryngeal structure.

Figure 11.4 Verrucous carcinoma of the larynx (H&E, 50×).

Figure 11.5 Spindle cell carcinoma of the larynx (H&E, 200×).

Figure 11.6 Adenoid cystic carcinoma of the larynx (H&E, 100×).

Figure 11.7 Mucoepidermoid carcinoma of the larynx (H&E, 200×).

Figure 11.8 Chondrosarcoma of the larynx (H&E, 100×).

Chapter 12

Figure 12.1 Electron micrograph of undifferentiated carcinoma of the nasopharynx showing epidermoid characteristics, for example cell junctions and tonofilaments. (Original magnification 9000 × .)

Figure 12.2 Keratinizing squamous cell carcinoma of the nasopharynx, WHO type 1 (H&E, original magnification 400×).

Figure 12.3 Nonkeratinizing carcinoma of the nasopharynx, WHO type 2. Note the sharp delimitation from surrounding lymphoid tissue and, in this example, a spindle character to the neoplastic cells (H&E, original magnification 360×).

Figure 12.4 Differentiated nonkeratinizing carcinoma, WHO type 2. This example manifests, in addition to neoplasm, stroma demarcation, clear cells, and “intermediate type” cells (H&E, original magnification 400×).

Figure 12.5 WHO type 3 NPC or undifferentiated carcinoma. Vesicular nuclei, prominent nucleoli, indistinct cell membranes, and a lymphoid‐like character are manifested. Note the intimate relationship with non‐neoplastic lymphocytes (H&E, original magnification 420×).

Figure 12.6 Sagittal T

1

‐weighted MRI image of a patient with clinically localized NPC showing invasion of the clivus by tumor. The tumor appears as a dark area within the bright signal of normal marrow.

Figure 12.7 Axial T

1

‐weighted fat‐saturated contrast‐enhanced MRI image showing bilaterally enlarged retropharyngeal lymph nodes harboring metastases from nasopharyngeal cancer.

Figure 12.8 Presentation with T2N2 disease and PET/CT‐detected oligometastasis (biopsy proven) in the right ilium. (a,b) T2N2M1 NPC. (c,d) PET/CT image demonstrating complete metabolic response after induction chemotherapy and consolidative chemoradiotherapy to the locoregional and distant bone disease.

Figure 12.9 Potential routes of spread of the primary tumor.

Figure 12.10 Representative slices demonstrating suboptimal coverage with (a) the photon/electron technique and (b) the modified Ho technique, where 90% of the planning treatment volume received only 67% and 75% of the prescription dose, respectively.

Figure 12.11 IMRT beam arrangement and dose cloud.

Chapter 13

Figure 13.1 Disease‐specific survival by

(a)

T and N classification, and

(b)

modified Kadish staging.

Figure 13.2

(a)

Respiratory epithelial lined mucosa (upper left) showing the presence of numerous submucosal lobules of tumor representing a characteristic finding in esthesioneuroblastoma (ENB).

(b)

In grade I ENBs the cells are surrounded by neurofibrillary material characterized by fibrillary cytoplasm and interdigitating neuronal processes (neuropil) creating a syncytium of cells.

(c)

At high magnification the nuclei of grade I ENBs are round to oval with dispersed nuclear chromatin lacking nuclear pleomorphism, mitotic activity, and necrosis. In addition, in grade I (as well as grade II) ENBs, pseudorosettes (also referred to as Homer Wright rosettes) characterized by cells arranged in tight annular formation without a true lumen (arrowheads) can be identified.

(d)

In grade II ENBs there is greater nuclear pleomorphism and less well defined neurofibrillary matrix.

(e)

True neural rosettes (also referred to as Flexner–Wintersteiner rosettes) characterized by cells aligned around a true lumen (arrows) can be seen in histologically higher grade ENBs, the latter characterized by hyperchromatic nuclei and greater nuclear pleomorphism as well as increased mitoses as compared with lower histological grade ENBs. In general, true neural rosettes are uncommonly identified.

Figure 13.3 Immunohistochemical staining is an invaluable aid in the diagnosis of ENB including reactivity for:

(a)

neuron‐specific enolase,

(b)

synaptophysin,

(c)

S‐100 protein with characteristic staining of cells along the periphery of the neoplastic lobules in a sustentacular cell pattern, and

(d)

calretinin.

Figure 13.4

(a)

Axial T1‐weighted (T1W),

(b)

fat‐suppressed contrast‐enhanced T1W and

(c)

T2‐weighted (T2W) MRI images at the level of the superior nasal cavity demonstrating an enhancing mass invading the left orbit (white arrow) and spheroid sinus (black arrow) with obstructed secretions filling the remainder of the spheroid sinus.

(d)

T1W sagittal and

(e,f)

contrast‐enhanced sagittal and coronal T1W MRI images demonstrating intracranial extension with the waist of the tumor at the cribriform plate (short black arrow) and marginal cysts at the tumor brain interface (short white arrow). Sagittal and coronal contrast‐enhanced images also differentiate enhancing tumor (long black arrow) from low‐signal intensity sinus secretions.

Figure 13.5

(a)

T1W,

(b)

T1W with contrast, and

(c)

T2W MRI images demonstrating tumor in the anterior cranial fossa with associated vasogenic edema and mass effect on adjacent brain with marginal cysts at the tumor–brain interface (black arrows).

(d)

Diffusion‐weighted imaging and

(e)

apparent diffusion coefficient map MRI images showing tumor demonstrating restricted diffusion.

Figure 13.6

(a)

Coronal T1W,

(b)

T1W with contrast,

(c)

T2W fat‐suppressed MRI images demonstrating tumor centered in the superior nasal cavity with extension into the anterior cranial fossa with the nasal component larger than the intracranial component.

(d)

Coronal CT image demonstrating destruction of the cribriform plate (black arrow). Tumor margins are much better visualized on MRI.

Figure 13.7

(a)

Axial CT,

(b)

axial, and

(c)

coronal T2W MRI images demonstrating fluid‐filled obstructed frontal sinus (white arrow).

(d)

Sagittal T1W MRI images without contrast and

(e)

with contrast demonstrating a small amount of tumor extending into the anterior cranial fossa (black arrow) and spheroid sinus (short white head).

Figure 13.8

(a)

T1W and

(b)

T2W axial images, and

(c)

T1W contrast‐enhanced images with fat suppression and

(d)

without fat suppression, demonstrating a small intracranial tumor extension (black arrow) which is difficult to distinguish from normal brain on the noncontrast images. Tumor margins are best visualized on the fat‐suppressed contrast‐enhanced image in

(c)

.

Chapter 14

Figure 14.1 An algorithim for the pathological classification of thymic epithelial tumors.

Figure 14.2 Histological image of a type A (epithelial‐predominant/spindle cell) thymoma. This lesion contains almost no lymphocytes, and the epithelial tumor cells have a fusiform appearance with dispersed nuclear chromatin and indistinct nucleoli.

Figure 14.3 Histological image of a type AB (mixed spindle cell) thymoma. This lesion contains numerous lymphocytes, and the epithelial tumor cells have a fusiform appearance with dispersed nuclear chromatin and indistinct nucleoli.

Figure 14.4 Photomicrograph of a type B1 (lymphocyte‐predominant) thymoma in which larger thymic epithelial tumor cells are widely separated. These show slightly vesicular chromatin and small nucleoli.

Figure 14.5 Photomicrograph of a type B2 thymoma in which larger thymic epithelial tumor cells form small clusters but do not form sheets. These show slightly vesicular chromatin and small nucleoli.

Figure 14.6 Photomicrograph of a type B3 (“pink”) thymoma in which larger thymic epithelial tumor cells form sheets of cells with small numbers of lymphoid cells. The nucleoli features do not differentiate different forms of B thymomas.

Figure 14.7 Type B3 thymoma with atypia. This rare form of B3 tumor can show scattered atypical cells. Note that this tumor does not qualify as a thymic carcinoma.

Figure 14.8 Histological image of keratinizing squamous cell carcinoma of the thymus. Interconnecting cords and nests of large tumor cells are present, with overtly atypical nuclei and foci of keratin deposition.

Figure 14.9 Nonkeratinizing squamous cell thymic carcinoma.

Figure 14.10 Neuroendocrine carcinoma (carcinoid) of the thymus. Note the uniform cells with a moderate amount of eosinophilic cytoplasm. There are no areas of necrosis and mitotic activity is low.

Figure 14.11 Photomicrograph of a primary small cell neuroendocrine carcinoma of the thymus. The neoplastic cells show dispersed nuclear chromatin, apoptosis, and the “molding” of nuclear membranes on one another.

Figure 14.12 Posteroanterior and lateral chest radiographs in a patient with a thymoma demonstrating an abnormal contour to the right heart border (arrows) and increased density in the anterior mediastinum (arrowheads).

Figure 14.13 Stage 1 thymoma (WHO mixed type B2/B1). Chest CT showing a rounded, homogenous, soft tissue mass in the anterior mediastinum with preservation of the mediastinal fat separating it from the adjacent ascending aorta.

Figure 14.14 Stage IIA thymoma (WHO mixed type B2/B3). Chest CT showing a mildly heterogeneous, lobulated, soft tissue mass in the right anterior mediastinum. There has been loss of the fat plane between the mass and the superior vena cava (SVA). At surgical resection the tumor was adherent to the SVC.

Figure 14.15 Stage IVA thymoma (WHO type B2). Chest CT showing a heterogeneous, lobulated, soft tissue mass in the right anterior mediastinum. There is mass‐like nodular thickening of the pleural in the posterior lateral right pleura representing drop metastasizes.

Figure 14.16 Stage IVB thymoma (thymic carcinoma). Sagittal chest CT image demonstrating pleural implant (white arrow), fissural pleural implants (red arrows), hematogenous lung metastasis (yellow arrow), and pleural effusion within the major fissure (blue arrow).

Figure 14.17 Stage III thymoma (WHO type B2) in a 28‐year‐old pregnant patient. T

1

and T

2

fat‐suppressed MRI sequences showing a lobulated mass in the anterior mediastinum which is an intermediate signal on T

1

(a)

and hyperintense on T2 with the presence of fine hypointense septa

(b)

.

Figure 14.18 Masaoka staging system.

Figure 14.19 A suggested algorithm to guide the evaluation and management of a patient with a mediastinal mass who is found to have a thymoma or thymic carcinoma. CXR, chest x‐ray.

Chapter 15

Figure 15.1 CT scan of the chest of a patient with a large (8–9 cm) mass in the upper aspect of the right hemithorax abutting the pleura.

Figure 15.2 Axial plane CT scan of the same patient as in Fig.

15.1

confirming the presence of a mass in the right hemithorax.

Figure 15.3 Leiomyosarcoma. Cellular spindle cell tumor with eosinophillic fibrillary cytoplasm arranged in fascicles and with scattered pleomorphic cells (H&E, 100×).

Figure 15.4 Cellular solitary fibrous tumor (formerly known as hemangiopericytoma). Cellular tumor composed of short spindle cells and branching ectatic (“staghorn‐like”) blood vessels (H&E, 100×).

Figure 15.5 Solitary fibrous tumor. Cellular tumor composed of medium‐sized spindle cells admixed with collagen and branching ectatic (“staghorn‐like”) blood vessels (H&E, 100×).

Figure 15.6 Epithelioid hemangioendothelioma. Epithelioid to spindle tumor cells arranged in cords with blister cells and myxoid stroma (H&E, 100×).

Figure 15.7 Angiosarcoma. Atypical spindled and epithelioid cells in solid sheets and lining ill‐formed vasoformative spaces (H&E, 100×).

Figure 15.8 Synovial sarcoma. Montonous cellular spindle cell tumor (H&E, 100×).

Figure 15.9 Malignant peripheral nerve sheath tumor. Cellular spindle cell tumor with tumor necrosis and variable myxoid stroma in a patient with a known history of neurofibromatosis (H&E, 100×).

Figure 15.10 CT scan of a left lower lobe pulmonary sarcoma with an endobronchial component.

Figure 15.11 CT scan showing a pleomorphic sarcoma of the left lung.

Chapter 16

Figure 16.1 Presentations of malignant pleural mesothelioma. (a) Initial presentation with dyspnea and large unilateral pleural effusion. (b) Initial presentation with chest pain and bulky pleural mass lesions. (c) Incidentally discovered small right pleural effusion on CT scan, first noted on chest x‐ray for an employment medical examination.

Figure 16.2 Posterior chest wall metastasis at a site of previous instrumentation, treated with radiotherapy (note pigmentation and tattoos).

Figure 16.3 (a) Baseline CT scan before chemotherapy with cisplatin and pemetrexed. (b) After two cycles and (c) after four cycles of chemotherapy showing a sustained partial response that was accompanied by symptomatic benefit.

Chapter 17

Figure 17.1 Primary pulmonary melanoma occurring in a male aged 61 years. Pleomorphic epithelioid melanoma cells are present, some of which are pigmented, beneath bronchial respiratory‐type mucosa. There is focal mucosal surface erosion by the tumor (H&E, original magnification 100×).

Chapter 18

Figure 18.1 Classification of neuroendocrine lung cancers.

Figure 18.2 Large cell neuroendocrine carcinoma showing organoid nesting pattern with prominent palisading at the periphery of the tumor cell nests. A few rosette‐like structures are present and focal necrosis is seen.

Figure 18.3 Tumor cells demonstrating rosette‐like structures, abundant cytoplasm, nuclei with vesicular chromatin, and scattered nucleoli. Several mitotic figures are present in this high‐power field.

Figure 18.4 Tumor cells showing a strong expression of CD56 with a membranous pattern of staining, indicating neuroendocrine differentiation.

Chapter 19

Figure 19.1 Representative histology microphotographs of lung adenocarcinomas illustrating a lepidic pattern with mucinous

(a)

and nonmucinous

(b)

features, and invasive acinar

(c)

and papillary

(d)

patterns (H&E staining).

Figure 19.2 Approximate mutation frequency in adenocarcinoma of the lung.

Chapter 20

Figure 20.1 Right endobronchial adenoid cystic carcinoma

(a)

before and

(b)

after sleeve lobectomy.

Figure 20.2 Definitive radiotherapy for inoperable primary tracheal adenoid cystic carcinoma. Comparative treatment plans for

(a)

proton therapy and

(b)

intensity‐modulated radiotherapy are depicted in the axial and sagittal (bottom right insert) planes. The gross tumor volume is delineated in red, whereas the planning target volume is delineated in cyan. Dose color wash coding from blue (50%) to red (global maximum above 100% of the prescribed dose).

Chapter 21

Figure 21.1 Fibromatosis‐like metaplastic tumor showing bland spindle cell proliferation with few glandular elements (center and left) (H&E, 200×).

Figure 21.2 Low‐grade adenosquamous metaplastic carcinoma showing islands of squamous cells merging with the spindle cells (H&E, 200×).

Figure 21.3 Matrix‐producing metaplastic carcinoma presenting groups of epithelial cells within condromyxoid stroma (H&E, 200×).

Chapter 22

Figure 22.1 Low‐power photomicrograph of tubular carcinoma showing the characteristic angulated tubules surrounded by desmoplastic and sclerotic stroma and invading adipose tissue at the periphery.

Figure 22.2 The characteristic round or bent teardrop‐shaped tubules of tubular carcinoma are lined by a single layer of epithelial cells. The intervening stroma shows areas of elastosis and sclerosis.

Figure 22.3 Higher power photomicrograph showing the small, round tumor cells lining the carcinomatous tubules to have minimal pleomorphism and essentially absent mitotic activity.

Figure 22.4 Higher power photomicrograph showing apical snouts which are present at the luminal aspect of the tumor cells in at least 30% of cases.

Figure 22.5 Immunohistochemical staining for estrogen receptor shows strong positivity in 100% of tubular carcinoma nuclei.

Figure 22.6 Low‐power photomicrograph showing the neoplastic tubules of tubular carcinoma infiltrating among normal structures including usual type hyperplasia (center) and a papilloma (upper left) within a radial scar. Note the presence of a well‐delineated myoepithelial layer surrounding the normal structures.

Figure 22.7 p63 Immunohistochemical stain for basal cells shows positive nuclear staining of myoepithelial cells in normal ducts and ductules as well as ducts with atypical ductal hyperplasia whereas the neoplastic tubules of tubular carcinoma show absence of staining.

Chapter 23

Figure 23.1 Breast sarcoma MRI.

Figure 23.2 Breast sarcoma CT.

Figure 23.3 Clinical presentation of radiation‐associated breast angiosarcoma.

Chapter 24

Figure 24.1 Adenoid cystic carcinoma with dominant cribriform pattern. The round pseudolumina contain myxoid spherules of basement membrane material.

Figure 24.2 Higher magnification shows that the pseudolumina are surrounded by small basaloid tumor cells with low nuclear grade and scant cytoplasm.

Figure 24.3 Myoepithelial stain p63 highlights the predominantly myoepithelial population within this adenoid cystic carcinoma.

Figure 24.4 Immunostain for cytokeratin 7 highlights luminal epithelial cells forming small glandular spaces. The adjacent admixed myoepithelial cells are negative for staining.

Figure 24.5 Moderate to strong staining for c‐KIT (CD117) is typical of adenoid cystic carcinoma.

Figure 24.6 Solid variant of adenoid cystic carcinoma with basaloid features demonstrating entirely solid infiltrating nests of small basaloid tumor cells. In contrast to conventional adenoid cystic carcinoma, mitotic figures and apoptotic bodies are readily identified.

Chapter 26

Figure 26.1 Squamous cell carcinoma with possible incipient invasion at the base. The long prongs of dysplastic epithelium extend deeply into the lamina propria, but only at the base of the epithelium. In the center there is invasion with irregularity of the basal epithelium and separation of small clusters of cells from the main prongs. Serial sections might be necessary to ensure that these nests are truly separated from the basal epithelium.

Figure 26.2 Spindle cell carcinoma. (a) This spindle cell carcinoma formed a polypoid intraluminal mass located above the gastroesophageal junction. (b) These tumors reveal biphasic histology, typically with a predominance of malignant spindle cells, and with only focal areas of carcinoma.

Figure 26.3 Basaloid squamous cell carcinoma. The small dark carcinoma cells form strands, trabeculae, and nests, some with central holes. The stromal spaces separating the cell groups are often uniform, as in typical adenoid cystic carcinomas.

Figure 26.4 Basaloid carcinoma of the esophagus. (a) Low‐power image showing a proliferation of well‐circumscribed nodules of basaloid cells extending beneath mildly dysplastic squamous epithelium. (b) Nest of tumor cells with central necrosis. (c) Basaloid carcinomas are characterized by cells with oval to round nuclei, an open chromatin pattern, small nucleoli, and scant cytoplasm. (d) A mucoid hyaline‐like substance is noted in some intercellular spaces. (e) In some cases, basaloid carcinomas show marked intratumoral necrosis, which gives the false appearance of gland formation and an adenoid cystic carcinoma‐like quality to the tumor nodules.

Figure 26.5 Verrucous squamous cell carcinoma. In this gross view, there is a very long plaque of carcinoma with its base in the lamina propria. Its luminal aspect has many spike‐like projections; these are the epithelial spikes covered by thick keratin.

Figure 26.6 Squamous dysplasia of the esophagus. (a) Low‐grade squamous dysplasia characterized by a proliferation of neoplastic cells involving about one‐third to one‐half of the thickness of the epithelium. (b) In contrast to (a), dysplastic cells extend to the surface of the epithelium and are associated with a significant loss of surface maturation (high‐grade dysplasia). (c) In this high‐power image, dysplastic cells are noted to have an increased nucleus‐to‐cytoplasm ratio, marked hyperchromatic nuclei, significant loss of polarity, and overlapping of the cells and their nuclei. (d) An unusual morphological appearance of squamous dysplasia, characterized by disorganized large cells with open nuclei. (e) High‐power photomicrograph of the dysplastic cells seen in (d).

Figure 26.7 True adenoid cystic carcinoma of the esophagus. In contrast to basaloid carcinomas, adenoid cystic carcinomas show a proliferation of small hyperchromatic cells with less variation of nuclear size, infrequent mitoses, and no necrosis. The glandular lumina contain basement membrane‐like extracellular material.

Figure 26.8 (a) Adenosquamous carcinoma of the esophagus characterized by a proliferation of malignant glands (left side) adjacent to malignant squamous epithelium (right side). (b) Mucoepidermoid carcinoma characterized by large aggregates of cells, which have features of malignant squamous cells toward the periphery of the cellular units intimately mixed with centrally located cells that contain mucin.

Figure 26.9 Histopathology and immunohistochemistry studies. (a) Liver specimens showing polygonal tumor cells arranged mainly in a trabecular pattern and areas of glandular formations with abundant eosinophilic cytoplasm and round nuclei (H&E, original magnification 100×). (b) Esophageal specimens showing neoplastic hepatocyte‐like cells arranged in nests and trabecular pattern with intervening fibrovascular stroma. Adjacent intestinal metaplasia (Barrett esophagus) is evident (H&E, original magnification 100×). (c) Neoplastic cells from esophageal tumor were positive for α‐fetoprotein staining (original magnification 200×). (d) Esophageal specimens showing positive staining for glypican‐3 (original magnification 200×). (e) Carcinoembryonic antigen (polyclonal) staining of esophageal specimens, although positive, did not show the definite canalicular staining pattern of hepatocellular carcinoma (original magnification 400×). (f) Esophageal specimens were positive for SALL4 staining (original magnification 200×).

Figure 26.10 Leiomyoma. (a) This leiomyoma arose from the muscularis mucosae and presented as an intraluminal nodule. (b) Histologically, this leiomyoma is paucicellular. The tumor cells are bland and have abundant, fibrillar, brightly eosinophilic cytoplasm without nuclear atypia.

Figure 26.11 (a) High‐grade neuroendocrine tumor with rosette formation and trabecular/cord‐like pattern. (b) Composite adenocarcinoma/neuroendocrine tumor (NET). In the center of moderately differentiated adenocarcinoma glands is a nest of monomorphous polygonal NET cells (arrow) that blend imperceptibly with the adjacent adenocarcinoma. The arrowhead denotes a gland with central mucin.

Figure 26.12 Granular cell tumor. (a) Endoscopically, granular cell tumors appear as small white to yellow subepithelial nodules. (b) Histologically, these lesions are composed of large cells with abundant eosinophilic granular cytoplasm and pyknotic nuclei. (c) If the diagnosis is in question, a positive immunoperoxidase stain for S‐100 can help confirm the diagnosis.

Figure 26.13 Malignant granular cell tumor. (a) Low‐power view of malignant granular cells infiltrating the submucosa and muscularis. (b) High‐power view showing granular cells with enlarged, irregular, and hyperchromatic nuclei. Mitoses were present in other areas of the tumor.

Figure 26.14 Large cell lymphoma of the esophagus. (a) Low‐power magnification of a lymphomatous infiltrate extending to the squamous epithelium. (b) High‐power magnification of the atypical large lymphocytes admixed with numerous smaller lymphocytes, many of which appear normal.

Chapter 27

Figure 27.1 Type I neuroendocrine tumor of the stomach.

Figure 27.2 Endoscopic appearance of type I G‐NET.

Figure 27.3 Low‐power H&E microscopic appearance of GIST.

Figure 27.4 Endoscopic appearance of GIST.

Figure 27.5 EUS appearance of GIST.

Figure 27.6 Endoscopic appearance of MALT.

(a)

Patch of erythema (fundus).

(b)

Narrow band imaging (fundus).

Figure 27.7 H&E microscopy of gastric carcinoma with lymphoid stroma.

Figure 27.8 Epstein–Barr virus‐encoded RNA staining of EBV‐associated gastric carcinoma.

Chapter 28

Figure 28.1 Small bowel cancer by site and histology.

Figure 28.2

(a)

Small bowel follow‐through (SBFT) showing intussuseption (arrows) from a diffuse large B cell lymphoma in the small bowel.

(b)

SBFT showing an “apple core” stricture (arrow) from a jejunal adenocarcinoma.

(c)

CT scan showing a mesenteric mass (arrows) with tethering of small bowel loops due to desmoplastic reaction representing mesenteric nodal metastasis from a small bowel carcinoid.

(d)

CT scan showing multiple heterogeneously enhancing liver metastases from a small bowel gastrointestinal stromal tumor metastatic to liver.

Figure 28.3 Schematic management of patients with small bowel adenocarcinomas. CAPOX, capecitabine plus oxaliplatin; CT, computed tomography; FOLFOX, leucovorin, 5‐FU, and oxaliplatin; FOLFIRI, 5‐FU, leucovorin, and irinotecan; FU, 5‐fluorouracil; PS, performance status; XRT, radiotherapy.

Chapter 29

Figure 29.1 Serous cystadenocarcinoma is composed of uniform cuboidal cells with clear cytoplasm forming microcysts.

Figure 29.2 (a) Grossly, mucinous cystadenocarcinoma is a well‐circumscribed, multilocular cystic mass with solid areas. (b) Microscopically, an invasive carcinoma (left) with ductal differentiation arises from cysts (right) lined by atypical epithelium associated with an underlying subepithelial ovarian‐like stroma.

Figure 29.3 Adenosquamous carcinoma has two growth patterns: (a) a squamous cell carcinoma component intimately intermixed with adenocarcinoma with luminal formation, and (b) nests of squamous cell carcinoma (right lower half) separated from adenocarcinoma (left upper corner).

Figure 29.4 (a) Grossly, colloid carcinoma presents as a well‐circumscribed mass with a soft gelatinous appearance. (b) Microscopically, there are pools of mucin associated with strips of neoplastic epithelium dissecting the stroma.

Figure 29.5 Medullary carcinoma is a poorly differentiated carcinoma with (a) a pushing border and (b) prominent intratumoral lymphocytes.

Figure 29.6 Undifferentiated carcinoma may be composed of neoplastic cells with (a) an epithelioid appearance or (b) a spindle cell appearance.

Figure 29.7 Neoplastic cells in acinar cell carcinoma have abundant eosinophilic cytoplasm and prominent nucleoli. Note that the cells with dark eosinophilic cytoplasm (upper right) are benign acinar cells.

Figure 29.8 (a) Grossly, mixed acinar–neuroendocrine carcinomas present as a large, well‐circumscribed mass with a fleshy consistency. (b) Microscopically, there are neoplastic cells with PAS diastase‐positive granules in the cytoplasm and prominent nucleoli labeled with chymotrypsin (c), and neoplastic cells labeled with chromogranin (d).

Figure 29.9 (a) Grossly, a solid pseudopapillary tumor is well circumscribed, with cystic and hemorrhagic areas on the cut surface. (b) Microscopically, it is composed of sheets of relatively uniform polygonal cells admixed with delicate capillary‐sized vessels. Extracellular hyaline globes are common. (c) Immunohistochemistry shows membranous labeling for CD10 and (d) nuclear labeling for β‐catenin in the neoplastic cells. Note the predominantly membranous labeling for β‐catenin in the benign acinar cells (left lower corner).

Chapter 30

Figure 30.1 Squamous cell cancer of the gallbladder. Note keratinization and lack of glandular features.

Figure 30.2 Fibrolamellar carcinoma of the liver. Large cells with eosinophilic cytoplasm, and prominent fibrous stroma are notable.

Figure 30.3 Primary angiosarcoma of the liver. This example shows angiosarcoma cells lining the hepatic sinusoids.

Figure 30.4 Hepatoblastoma. Extramedullary hematopoiesis, as shown in this example of fetal type hepatoblastoma, is common.

Chapter 31

Figure 31.1 Typical well‐differentiated neuroendocrine tumor. High power showing typical neuroendocrine cytology without mitosis or necrosis.

Figure 31.2 Electron microscopy of neurosecretory granules in a neuroendocrine tumor.

Figure 31.3 Neuroendocrine tissue markers include chromogranin, neuron‐specific enolase, and synaptophysin. Synaptophysin‐stained cells are seen below.

Chapter 32

Figure 32.1 Histological sections of GISTs. (a) Spindle cell GIST showing spindle cells arranged in fascicles with inconspicuous cytoplasmic borders and bland nuclei (H&E, original magnification 200×). (b) Epithelioid GIST showing sheets and clusters of epithelioid cells with round nuclei, small nucleoli, and abundant pink (eosinophilic) (H&E, original magnification 200×).

Figure 32.2 CD117 (KIT) immunohistochemistry. Spindle cell GISTs with (a) cytoplasmic immunoreactivity (original magnification 200×), (b) perinuclear dot‐like immunoreactivity (original magnification 400×), and (c) membranous immunoreactivity (original magnification 400×).

Figure 32.3 PDGFRA‐mutated, KIT‐negative GIST. (a) Epithelioid GIST consisting of sheets of epithelioid cells with abundant eosinophilic cytoplasm. The presence of a

PDFRA

D842V mutation was confirmed by Sanger sequencing. (b) CD117 (KIT) immunohistochemistry reveals very faint immunoreactivity, while DOG1 immunohistochemistry (c) is diffusely and strongly positive. (a–c, original magnification 200×.)

Figure 32.4 Succinate dehydrogenase (SDH) immunohistochemistry. (a) Spindle cell GIST with (b) retained SDHB immunoreactivity. (c) SDH‐deficient GIST with epithelioid morphology and (d) absence of SDH immunoreactivity. (a–d, original magnification 400×.)

Figure 32.5 Depiction of KIT and PDGFRA tyrosine kinase receptors. The area of the receptor where the most common exon mutations occur is shown.

Figure 32.6 Nomogram to predict the probabilities of 2‐ and 5‐year recurrence‐free survival (RFS). Points are assigned for size, mitotic index, and site of origin by drawing a line upward from the corresponding values to the “points” line. The sum of these three points, plotted on the “total points” line, corresponds to predictions of 2‐ and 5‐year RFS.

Chapter 34

Figure 34.1 Treatment algorithm for neuroendocrine carcinoma of the cervix, based on the algorithm recommended by the Society of Gynecologic Oncology clinical document.

Figure 34.2 Endometrioid adenocarcinoma, FIGO grade 1 (asterisk), adjacent to a focus of endometriosis (arrow) presenting as a pelvic mass. Tumor is characterized by back‐to‐back glands that resemble normal proliferative endometrium and is histologically similar to endometrial endometrioid adenocarcinoma. The patient had a total abdominal hysterectomy and bilateral salpingo‐oophorectomy for endometriosis.

Figure 34.3 Typical pattern of small cell carcinoma, hypercalcemic type of the ovary, composed of follicles filled with eosinophilic fluid. The tumor cells are small with minimal cytoplasm and inconspicuous nuclei.

Figure 34.4 Yolk sac tumor of the vulva with typical Schiller–Duval body characterized by a central vessel surrounded by tumor cells lying within a space also lined by tumor cells and resembling a glomerulus.

Chapter 35

Figure 35.1 Yolk sac tumor. This neoplasm displays areas of hemorrhage and cystic degeneration (a). Both a microcystic pattern and Schiller–Duvall bodies are present (b).

Figure 35.2 Choriocarcinoma. This tumor displays abundant hemorrhage (a). Microscopically, there is a plexiform pattern consisting of both syncytiotrophoblast and cytotrophoblast cells (b).

Figure 35.3 Dysgerminoma. The tumor is large, tan, and fleshy without significant hemorrhage or necrosis (a). It is composed of nests of cells with clear cytoplasm; fibrous septae separate the tumor nests (b).

Figure 35.4 Immature teratoma. This neoplasm is largely solid and encephaloid in appearance.

Chapter 36

Figure 36.1 Treatment algorithm. AMH, antimüllerian hormone; BEP, bleomycin, etoposide, cisplatin; BSO, bilateral salpingo‐oophorectomy; EP, etoposide, cisplatin; USO, unilateral salpingo‐oophorectomy; TRS, tumor reductive surgery.

Figure 36.2

(a)

Adult granulosa cell tumor, recurrent, gross. Large 30 cm mass in upper abdomen. Hemorrhagic, beefy red solid tumor metastatic to the omentum, transverse colon, and peritoneum, filling the upper abdomen inferior to the liver bilaterally.

(b)

Adult granulosa cell tumor, photomicrograph. Solid sheets of monotonous, small, cuboidal to polygonal cells resembling follicular granulosa cells are present with grooved, central nuclei.

(c)

Adult granulosa cell tumor, photomicrograph. Nests of cells form primitive follicles known as Call–Exner bodies, filled with acidophilic material and typical of adult granulosa cell tumors.

Figure 36.3

(a)

Juvenile granulosa cell tumor, gross. Recurrent disease is a perisplenic mass (left) which is solid, well circumscribed, white, and lobulated.

(b)

Juvenile granulosa cell tumor, photomicrograph, stained for inhibin. Nuclei are rounded and hyperchromatic with vacuolated cytoplasm, evident due to the stain for inhibin. Note that this tumor is dramatically positive for the inhibin stain.

Figure 36.4

(a)

Sertoli‐Leydig cell tumor, gross. Mixed cystic and solid adnexal mass with white solid components and multiple cystic areas.

(b)

Sertoli‐Leydig cell tumor, photomicrograph. Retiform pattern of Sertoli‐Leydig cell tumor, with tubules present. Sertoli cells are cuboidal with round nuclei. The stroma contains nests of Leydig cells.

Chapter 37

Figure 37.1

(a)

Ovarian clear cell carcinoma with a solid architecture demonstrating cells with clear cytoplasm and moderate to marked nuclear atypia.

(b)

Ovarian clear cell carcinoma demonstrating tubulopapillary architecture with hyalinized eosinophilic stroma, and hobnail cells with clear cytoplasm.

Chapter 38

Figure 38.1 (a) Expansive invasive mucinous carcinoma. Characterized by confluent glandular growth, back to back glands, and no intervening normal ovarian stroma. (b) Infiltrate invasive mucinous carcinoma. Characterized by small glands, nests, or cells infiltrating the stroma.

Figure 38.2 Surgical treatment algorithm.

Chapter 39