Saul Suster
Editor

Atlas of
Mediastinal
Pathology

123


Atlas of Anatomic Pathology
Series Editor
Liang Cheng

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Saul Suster

Atlas of Mediastinal
Pathology


Saul Suster, MD
Department of Pathology
Medical College of Wisconsin
Milwaukee, Wisconsin
USA

Atlas of Anatomic Pathology

Series Preface

One Picture Is Worth Ten Thousand Words
– Frederick Barnard, 1927

Remarkable progress has been made in anatomic and surgical pathology during the last 10
years. The ability of surgical pathologists to reach a definite diagnosis is now enhanced by
immunohistochemical and molecular techniques. Many new clinically important histopathologic entities and variants have been described using these techniques. Established diagnostic
entities are more fully defined for virtually every organ system. The emergence of personalized
medicine has also created a paradigm shift in surgical pathology. Both promptness and precision are required of modern pathologists. Newer diagnostic tests in anatomic pathology, however, cannot benefit the patient unless the pathologist recognizes the lesion and requests the
necessary special studies. An up-to-date Atlas encompassing the full spectrum of benign and
malignant lesions, their variants, and evidence-based diagnostic criteria for each organ system
is needed. This Atlas is not intended as a comprehensive source of detailed clinical information
concerning the entities shown. Clinical and therapeutic guidelines are served admirably by a
large number of excellent textbooks. This Atlas, however, is intended as a “first knowledge
base” in the quest for definitive and efficient diagnosis of both usual and unusual diseases.
The Atlas of Anatomic Pathology is presented to the reader as a quick reference guide for
diagnosis and classification of benign, congenital, inflammatory, nonneoplastic, and neoplastic
lesions organized by organ systems. Normal and variations of “normal” histology are illustrated for each organ. The Atlas focuses on visual diagnostic criteria and differential diagnosis.
The organization is intended to provide quick access to images and confirmatory tests for each
specific organ or site. The Atlas adopts the well-known and widely accepted terminology,
nomenclature, classification schemes, and staging algorithms.
This book Series is intended chiefly for use by pathologists in training and practicing surgical pathologists in their daily practice. It is also a useful resource for medical students, cytotechnologists, pathologist assistants, and other medical professionals with special interest in
anatomic pathology. We hope that our trainees, students, and readers at all levels of expertise
will learn, understand, and gain insight into the pathophysiology of disease processes through
this comprehensive resource. Macroscopic and histological images are aesthetically pleasing
in many ways. We hope that the new Series will serve as a virtual pathology museum for the
edification of our readers.
Indianapolis, IN, USA


shared their difficult and challenging cases of mediastinal pathology with me in consultation.
I would also like to thank my Developmental Editor, Lee Klein from Springer for the patience
exhibited during the production of this volume on account of many delays. Finally, I must
make public my appreciation to my wife, Jenny Suster, who patiently put up with my absenteeism and self-absorption during the writing of this book and selflessly stimulated me to complete it.
Milwaukee, WI, USA

Saul Suster, MD

ix



Contents

1 Reactive, Developmental, Inflammatory, and Tumorlike Conditions . . . . . . . .
2 Thymic Epithelial Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3 Neuroendocrine Neoplasms of the Thymus . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4 Neurogenic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5 Soft Tissue Tumors of the Mediastinum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6 Germ Cell Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7 Lymphoproliferative Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1
19
57
89
111
157
185

tumor growths secondary to hyperplasia, benign nodules, or
development of malignancy. Finally, a variety of benign
tumorlike conditions in this anatomic compartment can lead
to tumor masses that may be confused with malignancy,
including thymolipoma, thymofibrolipoma, and Castleman’s
disease.

S. Suster (ed.), Atlas of Mediastinal Pathology, Atlas of Anatomic Pathology,
DOI 10.1007/978-1-4939-2674-9_1, © Springer Science+Business Media, LLC 2015

1


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1 Reactive, Developmental, Inflammatory, and Tumorlike Conditions

Table 1.1 Reactive, developmental, inflammatory, and tumorlike conditions of the mediastinum
Process
Reactive and developmental conditions

Inflammatory conditions

Ectopic growths
Tumorlike conditions

Condition
Congenital thymic cysts
Foregut cysts (bronchogenic, enteric)
Pericardial (mesothelial) cysts

small island of involuting thymic remnants beneath the lining in the
wall of the cyst (arrows). This thymic remnant is composed of blandappearing spindle cells with dispersed nuclear chromatin and scant
cytoplasm reminiscent of the involuting thymus. Thymic remnants are
rarely identified in the walls of congenital thymic cysts

Fig. 1.4 Foregut cyst of the mediastinum. This 4-cm cyst was incidentally found in a 23-year-old woman during a routine chest X-ray and
showed a thickened, fibrous wall with a smooth and shiny outer surface.
It was located at the bifurcation of the trachea and main bronchi and
was easily detached and removed by blunt dissection. Foregut cysts
most commonly arise in the middle or posterior mediastinum. They can
occasionally communicate with the trachea or main bronchi and are
more common in young adults and children, although older individuals
also may be affected

3

Fig. 1.5 Histologic examination of a foregut cyst shows a lining composed of columnar ciliated epithelium, with hyaline cartilage, smooth
muscle, and mucus glands in the walls of the cyst. Infection is a common complication and may lead to lung abscess formation in cases
associated with a tracheobronchial fistula

Fig. 1.6 At higher magnification, a portion of a foregut cyst shows
immature (spindled), stratified squamous epithelium with welldeveloped intercellular bridges showing partial maturation of the luminal surface toward ciliated columnar epithelium (arrow). The
identification of cartilage in the wall of the cyst is the most reliable way
to identify cysts that originate from the bronchi. Otherwise, the term
“foregut cyst” would be an appropriate designation


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Fig. 1.7 Foregut cyst showing a lining composed of columnar ciliated

56-year-old woman, showing multiple distended cystic cavities filled
with hemorrhagic fluid. The walls of the cyst are thickened and edematous and show pinpoint foci of hemorrhage and cholesterol granulomas.
These cysts can grow to very large proportions and become symptomatic. Extensive sampling is required to rule out the possibility of cystic
degeneration of an underlying malignant neoplasm

Fig. 1.13 Acquired multilocular thymic cyst at higher magnification,
showing the lining of the cyst in continuity with residual thymic epithelium inside the walls of the cyst (arrows). The residual thymic epithelium is accompanied by a small lymphocytic component and can be
seen to be in continuity with dilated Hassall’s corpuscles

Fig. 1.12 Histologic appearance of multilocular thymic cyst, showing
dilated cystic cavity surrounded by dense lymphoid aggregates. The lining of the cyst is made up of simple cuboidal epithelium to stratified
squamous epithelium. Focal areas of hemorrhage and inflammation are
commonly present in the wall of the cysts

Fig. 1.14 Detail of the lining in an acquired multilocular thymic cyst,
showing the cyst cavity lined by simple cuboidal epithelium originating
from a remnant of thymic tissue in the wall of the cyst. Notice the
admixture of the epithelium with small T lymphocytes


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Fig. 1.15 More advanced stage in a multilocular thymic cyst, showing
dense fibrosis of the walls of the cyst secondary to chronic inflammation and netlike branching of hyperplastic thymic epithelium surrounded by the fibrous tissue

Fig. 1.16 Higher detail from an area of fibrosis in a multilocular thymic cyst, showing complex branching of thymic epithelium displaying
a sieve-like architecture, with thin, elongated strands of thymic epithelial cells circumscribing dense areas of collagen in a fibroepitheliomatous fashion. This appearance is very distinctive in long-standing
multilocular thymic cysts with prominent fibrotic changes in the walls

1 Reactive, Developmental, Inflammatory, and Tumorlike Conditions

the gland
Fig. 1.20 Multilocular thymic cyst of a lymphoepithelial type shows
cystically dilated cavities surrounded by dense lymphoid tissue with
well-developed lymphoid follicles containing germinal centers. The
main differential diagnosis for these lesions involves MALT lymphoma
of the thymus, which can also show prominent cystic changes and lymphoid follicles but which will have a monotonous population of mildly
atypical small lymphocytes infiltrating residual Hassall’s corpuscles to
form lymphoepithelial lesions


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Fig. 1.23 Histologic appearance of lymphoid follicular hyperplasia in
a patient with myasthenia gravis, showing an enlarged lymphoid follicle with a prominent germinal center. Notice residual involuting
Hassall’s corpuscles at the periphery of the lymphoid follicle

Fig. 1.24 Gross appearance of “pure” (or “true”) thymic hyperplasia.
The thymus is enlarged to at least four times its normal size and weight.
The outer surface is smooth and shiny, and the enlargement is uniform.
This patient had no history of myasthenia gravis or other autoimmune
disorder; the lesion was found incidentally on a routine chest X-ray.
This process can also be seen as a complication of chemotherapy in
patients with Hodgkin lymphoma and germ cell tumors in adults. It can
also follow chemotherapy in cancer patients or antiretroviral therapy for
HIV infection

1 Reactive, Developmental, Inflammatory, and Tumorlike Conditions

Fig. 1.25 Histologic appearance of the thymus in “pure” thymic
hyperplasia shows an essentially normal thymus, with preservation of

with scant small lymphocytes. Notice a small gland-like structure,
which is a normal part of the process. Occasionally, these microscopic
glandular structures can display a rosette-like or trabecular architecture
resembling neuroendocrine rests

Fig. 1.30 At higher magnification, an island of atrophic epithelium in
thymic involution shows clusters of small, oval to spindle cells with
scant cytoplasm and nuclei displaying evenly dispersed chromatin
without nucleoli. The cells in these islands of involuting thymus are
indistinguishable from those seen in spindle-cell thymomas


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1 Reactive, Developmental, Inflammatory, and Tumorlike Conditions

Fig. 1.31 Another microscopic residual island of involuting thymic
epithelium shows cystic dilatation of a gland-like structure. Small cystic structures like these are commonly present in the involuting thymus
of adults but seldom grow to a significant size

Fig. 1.33 At higher magnification, idiopathic sclerosing mediastinitis
shows extensive deposition of fibrous connective tissue, with sparse
inflammatory infiltrate chiefly composed of plasma cells and small
lymphocytes

Fig. 1.32 Sclerosing mediastinitis encroaching on the trachea shows
dense, fibrous tissue replacing the mediastinal fat and containing scattered islands of inflammatory cells

Fig. 1.34 Entrapment of large nerve trunks by the fibrosing process is
a common feature observed in idiopathic sclerosing mediastinitis

Rarely, these adenomas can be the site for the development of parathyroid carcinoma

1 Reactive, Developmental, Inflammatory, and Tumorlike Conditions

Fig. 1.41 The histologic appearance of an ectopic parathyroid adenoma in the mediastinum shows typical clear cell acinar architecture.
Notice remnants of involuting thymus in the vicinity (bottom left)

Fig. 1.42 At higher magnification, an ectopic mediastinal parathyroid
adenoma shows sheets of clear cells (top right) and cord-like, elongated
strands of involuted thymic tissue (bottom left) composed of small spindle cells admixed with scant lymphocytes
Fig. 1.40 This mediastinal ectopic parathyroid adenoma shows a
homogeneous, red-brown cut surface


1 Reactive, Developmental, Inflammatory, and Tumorlike Conditions

13

Fig. 1.43 The gross appearance of the cut surface of a mediastinal thymolipoma (lipomatous hamartoma) shows a well-circumscribed tumor
mass surrounded by a thin capsule and primarily composed of yellow,
lobulated fatty tissue

Fig. 1.45 A histologic variation of thymolipoma is characterized by
atrophic strands of involuting thymic epithelium embedded in abundant
hyalinized stroma and admixed with lobules of mature adipose tissue.
Such cases have been designated as “thymofibrolipoma”

Fig. 1.44 The histologic appearance of a thymolipoma shows small
residual islands of involuted thymic epithelium, with normal preservation of corticomedullary architecture surrounded by abundant mature
adipose tissue