Ebook Atlas of anatomic pathology Part 1

Part 1 book Atlas of anatomic pathology presentation of content: Reactive, developmental, inflammatory and tumorlike conditions, thymic epithelial neoplasms, neuroendocrine neoplasms of the thymus. Invite you to consult.

Atlas of

Mediastinal

Pathology

123 Saul Suster

Editor

For further volumes:

http://www.springer.com/series/10144

Atlas of Anatomic Pathology

ISBN 978-1-4939-2673-2 ISBN 978-1-4939-2674-9 (eBook)

DOI 10.1007/978-1-4939-2674-9

Library of Congress Control Number: 2015941333

Springer New York Heidelberg Dordrecht London

© Springer Science+Business Media, LLC 2015

This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction

on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed

The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use

The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed

to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made

Printed on acid-free paper

Springer Science+Business Media LLC New York is part of Springer Science+Business Media (www.springer.com)

for always being there for me, and to our children, David Ilan and Dana Deborah, for bringing light and meaning to our lives (B’H’)

immunohistochemical and molecular techniques Many new clinically important logic entities and variants have been described using these techniques Established diagnostic entities are more fully defi ned for virtually every organ system The emergence of personalized medicine has also created a paradigm shift in surgical pathology Both promptness and preci- sion are required of modern pathologists Newer diagnostic tests in anatomic pathology, how- ever, cannot benefi t 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

histopatho-is needed Thhistopatho-is Atlas histopatho-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 “fi rst knowledge base” in the quest for defi nitive and effi cient 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 classifi cation of benign, congenital, infl ammatory, nonneoplastic, and neoplastic lesions organized by organ systems Normal and variations of “normal” histology are illus- trated for each organ The Atlas focuses on visual diagnostic criteria and differential diagnosis The organization is intended to provide quick access to images and confi rmatory tests for each specifi c organ or site The Atlas adopts the well-known and widely accepted terminology, nomenclature, classifi cation schemes, and staging algorithms

This book Series is intended chiefl y for use by pathologists in training and practicing cal pathologists in their daily practice It is also a useful resource for medical students, cyto- technologists, 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

surgi-in many ways We hope that the new Series will serve as a virtual pathology museum for the edifi cation of our readers

contents of this volume are the result of personal experience and observations the author accrued over a period of more than 20 years, during which circumstances and opportunities allowed me to be exposed to a wealth of material from many sources on this topic

My interest in mediastinal pathology was initially sparked during my fellowship at Yale University with Dr Juan Rosai, who introduced me to the study of thymic epithelial neoplasms and generously shared with me his vast collection of consultation cases accumulated over the years My interest in this topic was rekindled when I became an attending pathologist at the Mount Sinai Hospital of Greater Miami due to the opportunity to collaborate with Dr Cesar Moran, at the time the Director of Mediastinal Pathology at the Armed Forces Institute of Pathology in Washington, D.C., who generously made available to me the inexhaustible fi les

of mediastinal pathology stored at that institution

It is inevitable that in a work like this the personal bias of its author should be introduced

It is also inevitable that the terminology and the specifi c approach to many of the entities cussed will change with time This volume expresses my current understanding of the fi eld with the acknowledgement that newer discoveries or observations may require that we adjust our terminology or our point of view The book is intended as a text and pictorial atlas but does not presume to be comprehensive or to explore every topic in every detail; it is simply meant

dis-to provide guidance and assistance for practicing pathologists for the diagnosis of mediastinal conditions

I am indebted to my teachers, colleagues, and students who have guided, taught, lenged, and stimulated me over the years I am also in debt to the many pathologists who have shared their diffi cult and challenging cases of mediastinal pathology with me in consultation

chal-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 absentee- ism and self-absorption during the writing of this book and selfl essly stimulated me to com- plete it

6 Germ Cell Tumors 157

7 Lymphoproliferative Disorders 185 Index 219

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

A variety of reactive, developmental, infl ammatory, and

tumorlike conditions can occur in the mediastinum

(Table 1.1 ) Congenital and developmental cysts can present

as a mass lesion in the mediastinum and may occur in a

vari-ety of settings Congenital cysts usually occur in younger

patients and are unilocular and small; they can arise

any-where along the anatomic course of embryonic descent of

the thymus, including the neck Developmental cysts can

arise from displaced or ectopic remnants, such as foregut

cysts and enteric duplication cysts Acquired cysts can arise

as a result of underlying infl ammatory processes and can

grow to be quite large and multiloculated Thymic

hyperpla-sia is another reactive process that presents as enlargement of

the thymus and clinically can simulate a malignancy

Infl ammatory conditions affecting the mediastinum include acute and chronic infl ammation (mediastinitis), granuloma- tous processes related to sarcoidosis (affecting primarily mediastinal lymph nodes) or fungal infection, and end-stage

fi brosing infl ammation resulting in idiopathic sclerosing mediastinitis Other developmental abnormalities that occur with some frequency in the mediastinum are the presence of ectopic thyroid or parathyroid tissue, which may give rise to 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, thymofi brolipoma, and Castleman’s disease.

Reactive, Developmental, Inflammatory, and Tumorlike Conditions

1

Tumorlike conditions Thymolipoma

Thymofi brolipoma Castleman’s disease

Fig 1.1 Congenital thymic cyst shows a distended, unilocular cavity

lined by thin translucent walls and fi lled with fl uid Notice the portion

of normal thymus attached at the end of the cyst This tumor developed

in a 15-year-old boy who presented with stridor and shortness of breath

owing to the large size of this particular cyst (approximately 10 cm in

greatest diameter)

Fig 1.2 Histologic appearance of a congenital thymic cyst, showing a

single layer of fl attened cuboidal epithelium The lining in congenital thymic cysts can also contain stratifi ed squamous epithelium and some-times columnar ciliated epithelium The contents of the cyst usually consist of clear, serous fl uid Note the absence of infl ammation in the wall of the cyst

Fig 1.3 Another area in the wall of a congenital thymic cyst Notice a

small island of involuting thymic remnants beneath the lining in the

wall of the cyst ( arrows ) This thymic remnant is composed of bland-

appearing spindle cells with dispersed nuclear chromatin and scant

cytoplasm reminiscent of the involuting thymus Thymic remnants are

rarely identifi ed in the walls of congenital thymic cysts

Fig 1.4 Foregut cyst of the mediastinum This 4-cm cyst was

inciden-tally found in a 23-year-old woman during a routine chest X-ray and

showed a thickened, fi brous 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

Fig 1.5 Histologic examination of a foregut cyst shows a lining

com-posed of columnar ciliated epithelium, with hyaline cartilage, smooth muscle, and mucus glands in the walls of the cyst Infection is a com-mon complication and may lead to lung abscess formation in cases associated with a tracheobronchial fi stula

Fig 1.6 At higher magnifi cation, a portion of a foregut cyst shows

immature (spindled), stratifi ed squamous epithelium with well- developed intercellular bridges showing partial maturation of the lumi-nal surface toward ciliated columnar epithelium ( arrow ) The

identifi cation 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

1 Reactive, Developmental, Infl ammatory, and Tumorlike Conditions

Fig 1.7 Foregut cyst showing a lining composed of columnar ciliated

epithelium in close proximity with clusters of residual involuting

thy-mic epithelium in the wall of the cyst ( arrowheads ) The thythy-mic

epithe-lium in such instances can undergo hyperplastic changes, not to be

confused with the development of thymoma

Fig 1.8 Example of a foregut cyst of an enteric type presenting as a mass

in the posterior mediastinum in a 15-year-old boy with dysphagia The

lining of the cyst is composed of gastric-type epithelium with a readily

identifi able muscularis propria Occasionally, ciliated columnar

epithe-lium can be identifi ed in these cysts when they arise from the esophagus

Another term used for these cysts is “enteric duplication cyst.” The lining

can be of either a gastric or enteric type Rarely, some foregut cysts show

admixtures of gastric, enteric, and bronchial epithelium

Fig 1.9 Mesothelial (pericardial) cyst incidentally found at autopsy

( arrows ) The cyst shows a smooth, translucent wall bulging from the

pericardium The cyst was fi lled with clear, serous fl uid Similar cysts can occur higher in the anterior mediastinum and arise from the pleural refl ection; these are designated as “pleural mesothelial cysts”

Fig 1.10 Histologic appearance of a mesothelial cyst of the anterior

pericardium shows a single layer of round to polygonal mesothelial cells Rarely, the mesothelium can show foci of papillary mesothelial hyperplasia, not to be confused with malignant mesothelioma

Fig 1.11 Cut surface of an acquired multilocular thymic cyst in a

56-year-old woman, showing multiple distended cystic cavities fi lled

with hemorrhagic fl uid The walls of the cyst are thickened and

edema-tous and show pinpoint foci of hemorrhage and cholesterol granulomas

These cysts can grow to very large proportions and become

symptom-atic Extensive sampling is required to rule out the possibility of cystic

degeneration of an underlying malignant neoplasm

Fig 1.12 Histologic appearance of multilocular thymic cyst, showing

dilated cystic cavity surrounded by dense lymphoid aggregates The

lin-ing of the cyst is made up of simple cuboidal epithelium to stratifi ed

squamous epithelium Focal areas of hemorrhage and infl ammation are

commonly present in the wall of the cysts

Fig 1.13 Acquired multilocular thymic cyst at higher magnifi cation,

showing the lining of the cyst in continuity with residual thymic

lium inside the walls of the cyst ( arrows ) The residual thymic

epithe-lium is accompanied by a small lymphocytic component and can be seen to be in continuity with dilated Hassall’s corpuscles

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

1 Reactive, Developmental, Infl ammatory, and Tumorlike Conditions

Fig 1.15 More advanced stage in a multilocular thymic cyst, showing

dense fi brosis of the walls of the cyst secondary to chronic infl

amma-tion and netlike branching of hyperplastic thymic epithelium

sur-rounded by the fi brous tissue

Fig 1.16 Higher detail from an area of fi brosis in a multilocular

thy-mic cyst, showing complex branching of thythy-mic epithelium displaying

a sieve-like architecture, with thin, elongated strands of thymic

epithe-lial cells circumscribing dense areas of collagen in a fi

broepithelioma-tous fashion This appearance is very distinctive in long-standing

multilocular thymic cysts with prominent fi brotic changes in the walls

Fig 1.17 Acquired multilocular thymic cyst showing severe infl

am-mation of the walls with pseudoepitheliomatous hyperplasia Notice the tongues and strands of squamous epithelium arising from the luminal

surface of the cyst and infi ltrating into the wall of the cyst ( arrows )

These reactive changes can sometimes be quite prominent and display mild cytologic atypia and even mitotic fi gures, simulating an invasive squamous cell carcinoma arising from the wall of the cyst

Fig 1.18 Cholesterol cleft granuloma in the wall of an acquired

mul-tilocular thymic cyst In addition to hemorrhage, fi brosis, and acute and chronic infl ammation, cholesterol cleft granulomas are a prominent fea-ture often encountered in thymic cysts Notice the admixture of foamy macrophages and multinucleated giant cells with the cholesterol clefts

Fig 1.19 Acquired multilocular thymic cyst of lymphoepithelial type

shows thickened, fl eshy, and edematous walls with a fi sh-fl esh

appear-ance due to dense lymphoid infi ltrates Such cysts are very similar to

lymphoepithelial cysts of the pancreas or salivary glands and are a

com-mon feature in children with AIDS, but they can also be seen in adult

patients who are not immunosuppressed

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

lym-phoid follicles but which will have a monotonous population of mildly

atypical small lymphocytes infi ltrating residual Hassall’s corpuscles to

form lymphoepithelial lesions

Fig 1.21 At higher magnifi cation, the thymic lymphoepithelial cyst

shows a cystic cavity lined by low cuboidal to stratifi ed squamous thelium and surrounded by a dense cuff of lymphoid tissue In one area, the lymphoid tissue is surrounding residual atrophic Hassall’s corpus-

epi-cles ( arrows )

Fig 1.22 Thymic lymphoid follicular hyperplasia in a 45-year-old

patient with myasthenia gravis shows a slightly enlarged and thickened thymus gland that weighed 65 g (normal for age, 25 ± 12 g) Notice the normal-appearing, smooth outer surface and conserved normal shape of the gland

1 Reactive, Developmental, Infl ammatory, and Tumorlike Conditions

Fig 1.23 Histologic appearance of lymphoid follicular hyperplasia in

a patient with myasthenia gravis, showing an enlarged lymphoid

folli-cle 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

Fig 1.25 Histologic appearance of the thymus in “pure” thymic hyperplasia shows an essentially normal thymus, with preservation of the cortical-medullary architecture and no evidence of lymphoid fol-licular hyperplasia The only abnormality is the increased size and weight of the gland The absence of sheeting and confl uence of the lymphocytes, the preservation of the normal architecture with abundant Hassall’s corpuscles, and the absence of a thick fi brous capsule sur-rounding the organ distinguish this condition from a well-differentiated lymphocyte-rich thymoma

Fig 1.26 Involuting thymus of the adult in a 54-year-old woman who

died of other causes The reverse process of thymic hyperplasia is mic involution, which is a normal physiologic process that starts after puberty and progresses into adulthood The thymus loses volume and becomes almost entirely replaced by fat, with only scattered micro-scopic islands of residual, atrophic thymic epithelium seen on histo-logic examination It must be emphasized that the thymus does not disappear under normal physiologic conditions; it remains as a well- defi ned structure in the mediastinum

Fig 1.27 Histologic appearance of the thymus in normal involution

shows small, residual islands of thymic epithelium surrounded by scant

lymphocytes Notice that the thymic islands are separated by abundant

fatty tissue, which is replacing the original thymic parenchyma Loss of

thymic parenchyma is experienced mainly at the expense of the

imma-ture T-lymphoid cell population, which is no longer being actively

recruited to the thymus for the programming of T-memory cells

Fig 1.28 At higher magnifi cation, an involuting island of thymic

epi-thelium from an adult shows residual strands of epithelial cells admixed

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 1.29 An elongated strand of involuting thymic epithelium

( arrows ) is seen arising from a small island of residual thymus ( lower

right ) Sometimes these elongated strands of atrophic thymic

epithe-lium can show complex branching and adopt a netlike confi guration like that observed in acquired multilocular thymic cysts

Fig 1.30 At higher magnifi cation, 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

1 Reactive, Developmental, Infl ammatory, and Tumorlike Conditions

Fig 1.31 Another microscopic residual island of involuting thymic

epithelium shows cystic dilatation of a gland-like structure Small

cys-tic structures like these are commonly present in the involuting thymus

of adults but seldom grow to a signifi cant size

Fig 1.32 Sclerosing mediastinitis encroaching on the trachea shows

dense, fi brous tissue replacing the mediastinal fat and containing

scat-tered islands of infl ammatory cells

Fig 1.33 At higher magnifi cation, idiopathic sclerosing mediastinitis

shows extensive deposition of fi brous connective tissue, with sparse infl ammatory infi ltrate chiefl y composed of plasma cells and small lymphocytes

Fig 1.34 Entrapment of large nerve trunks by the fi brosing process is

a common feature observed in idiopathic sclerosing mediastinitis

Fig 1.35 Ropelike, linear strands of keloidal collagen fl anked by scant

fi broblastic and infl ammatory cells can sometimes be seen in idiopathic

sclerosing mediastinitis, creating a superfi cial resemblance to a solitary

fi brous tumor—a pitfall to be avoided in small biopsy samples

Fig 1.36 The gross appearance of mediastinal thyroid goiter shows a

multinodular thyroid with a smooth outer surface Ectopic goiters can

undergo the same spectrum of changes seen in thyroid goiters,

includ-ing the development of thyroiditis and malignant transformation

Fig 1.37 Scanning magnifi cation of a mediastinal thyroid goiter

shows large, unencapsulated lobules containing follicles of varying sizes fi lled with colloid

Fig 1.38 At higher magnifi cation, a hyperplastic nodule in a

medias-tinal thyroid goiter shows thyroid follicles fi lled with colloid and lined

by normal-appearing thyroid follicular cells with small, round nuclei containing dispersed chromatin and small nucleoli

1 Reactive, Developmental, Infl ammatory, and Tumorlike Conditions

Fig 1.39 Gross appearance of mediastinal ectopic parathyroid

ade-noma Notice the smooth outer surface and pale tan-brown color of the

gland Ectopic mediastinal parathyroid tissue can be an incidental

microscopic fi nding in tissues containing involuting thyroid removed

during thyroid surgery or mediastinal exploration for lymph nodes

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

parathy-roid carcinoma

Fig 1.40 This mediastinal ectopic parathyroid adenoma shows a

homogeneous, red-brown cut surface

Fig 1.41 The histologic appearance of an ectopic parathyroid

ade-noma in the mediastinum shows typical clear cell acinar architecture

Notice remnants of involuting thymus in the vicinity ( bottom left )

Fig 1.42 At higher magnifi cation, 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 spin-

dle cells admixed with scant lymphocytes

Fig 1.43 The gross appearance of the cut surface of a mediastinal

thy-molipoma (lipomatous hamartoma) shows a well-circumscribed tumor

mass surrounded by a thin capsule and primarily composed of yellow,

lobulated fatty tissue

Fig 1.44 The histologic appearance of a thymolipoma shows small

residual islands of involuted thymic epithelium, with normal

preserva-tion of corticomedullary architecture surrounded by abundant mature

adipose 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 “thymofi brolipoma”

Fig 1.46 At higher magnifi cation, thymofi brolipoma shows slender,

elongated strands of thymic epithelial cells composed of small oval to spindle cells with scant cytoplasm and dispersed nuclear chromatin, surrounded by abundant paucicellular, fi brous connective tissue

1 Reactive, Developmental, Infl ammatory, and Tumorlike Conditions

Fig 1.47 Castleman’s disease, hyaline-vascular type, presenting as a

mediastinal mass in a 54-year-old woman The cut surface shows a tan-

white, homogeneous appearance with slight lobularity and a rubbery

consistency

Fig 1.48 Castleman’s disease of the mediastinum, hyaline-vascular

type, shows striking lymphoid hyperplasia, with some of the follicles

showing expanded mantle zones containing more than one germinal

center within each follicle

Fig 1.49 Another area of mediastinal lymph node involved with Castleman’s disease shows scattered small, dysplastic follicles with

burned-out germinal centers admixed with a larger follicle ( center )

showing prominent vessels within the germinal center

Fig 1.50 A dysplastic germinal center in Castleman’s disease shows

stromal hyalinization and concentric “onionskin” layering of mantle lymphocytes; a tangentially sectioned blood vessel traversing the ger-minal center results in the so-called lollipop sign

Fig 1.51 This view of another dysplastic follicle in Castleman’s

dis-ease shows multiple tangentially cut vessels traversing the follicle, with

extensive sclerosis and perivascular hyalinization of the germinal

center

Fig 1.52 Another aspect of hyaline-vascular Castleman’s disease of

the mediastinum shows a dysplastic follicle in the center surrounded by

a hypervascular interfollicular zone composed of small vessels lined by

plump endothelial cells

Fig 1.53 Higher magnifi cation of the interfollicular region in

Castleman’s disease of the hyaline-vascular type shows prominent hypervascularity with numerous, branching small vessels lined by plump endothelial cells The infi ltrate is composed of small lympho-cytes admixed with scattered eosinophils and plasma cells

Fig 1.54 Abnormal follicle in hyaline-vascular type of Castleman’s

disease, showing two hyalinized germinal centers within the same licle Notice that the germinal centers are lymphocyte depleted, and one

fol-of them shows a “lollipop” vessel traversing it from the interfollicular compartment

1 Reactive, Developmental, Infl ammatory, and Tumorlike Conditions

Fig 1.55 Extensive interfollicular sclerosis and hyalinization in

inter-follicular areas in Castleman’s disease of the mediastinum, hyaline-

vascular type

Fig 1.56 Higher magnifi cation of the germinal center in mediastinal

Castleman’s disease shows focal sclerosis and hyalinization in a small

vessel surrounded by epithelioid endothelial cells simulating a Hassall’s

corpuscle On small biopsy samples, this appearance may be confused

with thymic hyperplasia or thymoma

Fig 1.57 Mediastinal Castleman’s disease, plasma cell variant,

show-ing a small follicle ( left ) surrounded by a dense population of mature,

polytypic plasma cells

Fig 1.58 Higher magnifi cation of mediastinal Castleman’s disease,

plasma cell type, shows a dysplastic lymphoid follicle with typical lipop” sign and concentric, onionskin arrangement of mantle lymphocytes

Fig 1.59 Higher magnifi cation of mediastinal Castleman’s disease,

plasma cell type, shows a dense population of mature plasma cells

admixed with small vessels

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ME Foregut cysts of the mediastinum Results in 20 consecutively surgically treated cases J Thorac Cardiovasc Surg 1985;90:776–82 Suster S, Rosai J Multilocular thymic cysts: an acquired reactive pro-cess Study of 18 cases Am J Surg Pathol 1991;15:388–98 Suster S, Rosai J The thymus In: Mills SE, editor Histology for pathologists 3rd ed Philadelphia: Lippincott Williams & Wilkins;

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Suggested Reading

S Suster (ed.), Atlas of Mediastinal Pathology, Atlas of Anatomic Pathology,

DOI 10.1007/978-1-4939-2674-9_2, © Springer Science+Business Media, LLC 2015

tumors of the anterior mediastinum The terminology and

clas-sifi cation of these tumors have been a topic of debate for many

years and have continued to evolve as we have gained a better

understanding of their pathogenesis and biologic behavior

Thymic epithelial neoplasms comprise a spectrum of lesions

that can range from very low-grade, well- differentiated tumors

to high-grade, poorly differentiated neoplasms, with a wide

range of morphologies in-between The most widely used

clas-sifi cation is that proposed by the World Health Organization

(WHO), which consists of several categories and utilizes

mostly a combination of numbers and letters to designate the

various types; however, a more simplifi ed classifi cation scheme

has been proposed by Suster and Moran that stratifi es these

tumors into three categories based on their degrees of

differen-tiation and clinical behavior (Table 2.1 ) A confusing situation

also exists with the persistent use of the terms “thymoma” and

“thymic carcinoma” to refer to the ends of the morphologic

spectrum in these tumors, implying that one is malignant and

the other benign, when in reality all primary thymic epithelial

neoplasms have the potential for aggressive or malignant

behavior irrespective of their histologic appearance For the

time being, we will utilize the term “thymic carcinoma” in this

chapter for tumors that are cytologically obviously malignant,

following the standard and traditional nomenclature utilized by

the majority of investigators and reserve the term “thymoma”

for those tumors that fall mainly in the low-grade and

interme-diate range of the morphologic spectrum

Well- and moderately differentiated (low- and intermediate-

grade) tumors are traditionally designated as thymomas

These tumors represent slow-growing, low- to

intermediate-grade neoplasms that retain at least some of the organotypical

features of the normal thymus (e.g., lobulation, biphasic cell

lymphocytes, and dilated perivascular spaces) The tumors are often bulky and usually surrounded by a thick fi brous capsule that can contain calcifi cations They usually manifest in the anterosuperior mediastinum, although rare cases can occur in ectopic locations, including the lung and perihilar, pleural, and posterior mediastinal locations Thymomas are associated with paraneoplastic syndromes in up to 50 % of cases, par- ticularly in myasthenia gravis but also in aplastic anemia, essential thrombocytosis, hemolytic anemia, hypogamma- globulinemia, mixed collagen-vascular diseases, myopathies, pure red-cell aplasia, systemic lupus erythematosus, and oth- ers Thymomas can also undergo progression to malignancy and give rise to full-blown thymic carcinoma arising from a preexisting, more benign-appearing thymoma

Poorly differentiated (high-grade) primary thymic lial neoplasms are designated by the conventional name of thymic carcinoma and are seldom associated with myasthe- nia gravis or other paraneoplastic syndromes These tumors usually manifest a much more aggressive behavior and have

epithe-a generepithe-ally poor prognosis despite epithe-aggressive therepithe-apy Thymic carcinomas histologically resemble their counter- parts in other organs (i.e., squamous cell, adeno-, clear cell, spindle-cell, and anaplastic carcinoma) A large number of histologic variants have been described, some of which have shown a tendency to be associated with secondary cystic changes such as basaloid and mucoepidermoid carcinoma The diagnosis of thymic carcinoma is, in general, a diagnosis

of exclusion, since there is very little that is distinctive or pathognomonic about these tumors other than their location

in the mediastinum Morphologically, it can be very diffi cult

to separate them from similar cancers occurring at other organs.

epithelial neoplasms (atypical

thymoma)

Thymoma type B1 Thymoma type B2 Thymoma type B3 Poorly differentiated thymic

epithelial neoplasms (thymic

carcinoma)

Special types of thymoma (various)

Thymic carcinoma

Fig 2.1 Thymoma at autopsy; incidental fi nding in a 54-year-old man

who died of complications of hypertension and pulmonary embolism shows a large, fl eshy, anterior mediastinal mass that is focally infi ltrat-ing adjacent pleura and lung parenchyma

Fig 2.2 Cytologic appearance of the two basic types of thymoma in

the WHO classifi cation: ( a ) WHO type A is composed of elongated

cells with spindle or oval nuclei, dispersed nuclear chromatin, and an

inconspicuous rim of cytoplasm The cells are devoid of atypia ( b )

Thymomas WHO type B are composed of cells with round vesicular nuclei with prominent, single eosinophilic nucleoli surrounded by an ample rim of lightly eosinophilic or amphophilic cytoplasm Notice the abundance of small lymphocytes surrounding the larger epithelioid cells

2 Thymic Epithelial Neoplasms

Fig 2.3 Gross appearance of spindle-cell thymoma (WHO type A) shows

a nodular fl eshy appearance with homogeneous rubbery tissue Notice that

the tumor is well circumscribed and surrounded by a thin fi brous capsule

Fig 2.4 Typical histologic appearance of spindle-cell thymoma (WHO

type A) shows a fascicular proliferation of spindle cells arranged in

short fascicles with no discernible atypia A few scant small

lympho-cytes are seen scattered among the spindle cells

Fig 2.5 Higher magnifi cation of spindle-cell thymoma shows sheets

and fascicles of small, bland-appearing spindle cells containing

scat-tered small lymphocytes

Micronodular thymoma with B-cell hyperplasia

Fig 2.6 Spindle-cell thymoma with storiform pattern The tumor is

characterized by short storiform structures resembling the pattern of growth of cutaneous dermatofi brosarcoma protuberans Notice, how-ever, the bland appearance of the spindle cells with a sprinkling of small lymphocytes Tumors with these features can be mistaken for sarcomas

of fi brohistiocytic type or solitary fi brous tumors

Fig 2.7 A s pindle-cell thymoma with a whorling pattern shows

dis-crete rounded areas composed of concentrically aligned spindle cells superfi cially resembling meningothelial whorls

Fig 2.8 Variation in the theme of spindle-cell thymoma with whorling

pattern showing gradual sclerosis and hyalinization of the cellular

whorls, resulting in a giant rosette-like structure

Fig 2.9 Higher magnifi cation of the preceding image shows discrete,

rounded areas of stromal sclerosis containing a sparse population of

small round to oval cells surrounded by fascicles of spindle cells

Fig 2.10 Spindle-cell thymoma with prominent rosette-like tures The tumor shows numerous small, round structures containing spindle to oval nuclei showing a palisaded arrangement toward the periphery of the rosette-like structures that is reminiscent of neuroblas-tic and primitive neuroectodermal neoplasms

Fig 2.11 Higher magnifi cation of rosette-like structures in spindle- cell

thymoma The central portions of the structures contain eosinophilic material that resembles the fi brillary material in Homer-Wright rosettes Thymomas with these features can be confused with metastases from neuroblastoma and other neuroectodermal neoplasms or with neuroen-docrine neoplasms (carcinoid tumors and large cell neuroendocrine car-cinoma) The cells in these structures stain positive for cytokeratin and p63 but are unreactive to neuroendocrine and neural markers

2 Thymic Epithelial Neoplasms

Fig 2.12 Spindle-cell thymoma with numerous small gland-like

spaces, some of which are fi lled with eosinophilic proteinaceous

mate-rial The gland-like spaces can impart to the lesion a biphasic

appear-ance that is reminiscent of biphasic synovial sarcoma

Fig 2.13 Higher magnifi cation of spindle-cell thymoma with gland-

like structures The gland-like structures are lined by a layer of large,

epithelioid cells resembling a glandular lining Notice the monotonous

spindle cells surrounding the gland-like structures; both stained positive

with cytokeratin and p63

Fig 2.14 Spindle-cell thymoma with papillary architecture Notice the

solid spindle-cell thymoma component ( top left ) that transitions abruptly into areas with well-developed papillary tufts protruding into empty spaces

Fig 2.15 Higher magnifi cation of spindle-cell thymoma with

papil-lary architecture Notice that the cells populating the stroma of the papillae are oval- to spindle-appearing and look bland Tumors with similar features but with invasive properties have been described as

“papillary thymic carcinoma”

Fig 2.16 Spindle-cell thymoma with stromal sclerosis The tumor

shows strands of spindle thymic epithelial cells embedded in an

abun-dant fi brocollagenous matrix Tumors with these features can be

mis-taken for schwannian neoplasms with prominent stromal degenerative

changes

Fig 2.17 Higher magnifi cation of spindle-cell thymoma with stromal

hyalinization shows that the areas of stromal sclerosis correspond to

hyalinized dilated perivascular spaces

Fig 2.18 Spindle-cell thymoma with “adenoid” growth pattern The

tumor resembles a skin adnexal tumor and is composed of thin lae of round to oval tumor cells growing with a sieve-like architecture with intervening loose myxoid stroma

Fig 2.19 Higher magnifi cation from spindle-cell thymoma with

ade-noid growth pattern shows large, round to oval tumor cells with dant cytoplasm admixed with a sprinkling of small lymphocytes Notice that the intervening gland-like spaces correspond to dilated perivascular spaces with stromal hyalinization

abun-2 Thymic Epithelial Neoplasms

Fig 2.20 Spindle-cell thymoma can often undergo cystic degenerative

changes In this particular example, the tumor is characterized by

mul-tiple small cystic spaces, resulting in a reticular pattern of growth

Fig 2.21 Spindle-cell thymoma with reticular and microcystic growth

patterns Notice that the cells in the walls of the cysts are small and

spindled and there are scattered small lymphocytes admixed with the

cells and in the cystic lumina

Fig 2.22 Spindle-cell thymoma with microcystic growth pattern Higher magnifi cation shows that the microcystic spaces correspond to abortive perivascular spaces Notice the central vessel in the larger cyst

on the left

Fig 2.23 Another variation on the topic of microcystic thymoma shows a dense spindle-cell proliferation dotted by numerous small empty spaces suggestive of adipocytes on scanning magnifi cation Notice the scattering of small lymphocytes admixed with the spindle cells in the background

Fig 2.24 Higher magnifi cation from spindle-cell thymoma with

microcysts shows small empty lumina scattered among the spindle cells

that contain a rare small lymphocyte The cells lack the features of

adi-pocytes but may also not be recognized as perivascular spaces because

of the absence of a centrally located vessel

Fig 2.25 Another aspect of spindle-cell thymoma with a microcystic

growth pattern shows evenly spaced small cystic cavities surrounded by

bland-appearing monotonous spindle-cell proliferation

Fig 2.26 Higher magnifi cation from microcystic spindle-cell

thy-moma shows that the small cystic spaces contain small lymphocytes

Fig 2.27 A spindle-cell thymoma with a macrocystic growth pattern

shows numerous small dilated perivascular spaces that have focally coalesced to form larger, macrocystic spaces The process can advance

to form a large multicystic mass that can be grossly confused for a tilocular thymic cyst

mul-2 Thymic Epithelial Neoplasms

Fig 2.28 A s pindle-cell thymoma with a hemangiopericytoma-like

growth pattern is characterized by multiple branching vascular spaces

with open lumina surrounded by a dense spindle-cell population On

cursory examination, tumors with these features can be mistaken for

solitary fi brous tumors or monophasic synovial sarcomas

Fig 2.29 A different appearance of spindle-cell thymoma with a

hemangiopericytoma-like growth pattern shows dilated, anastomosing,

and branching vascular spaces lined by round to oval cells simulating

hemangiopericytoma

Fig 2.30 Trabecular growth pattern in spindle-cell thymoma shows

elongated strands of cells that are several layers thick separated by cular stroma simulating a neuroendocrine neoplasm The tumor cells in this case were p63 positive and negative for neuroendocrine markers

Fig 2.31 Ribbon-like growth pattern in spindle-cell thymoma shows a

lobulated growth surrounded by connective tissue that contains nous cords of tumor cells; the pattern can be highly reminiscent of a neuroendocrine neoplasm such as thymic carcinoid

Fig 2.32 Higher magnifi cation from ribbon-like growth pattern in

spindle-cell thymoma shows spindle to oval cells with hyperchromatic

nuclei aligned in parallel arrays forming serpiginous cords of cells

Fig 2.33 Spindle-cell thymoma showing prominent basaloid

periph-eral palisading of nuclei similar to that observed in large cell

neuroen-docrine carcinomas of the lung The nuclear morphology, however, is

bland and does not show the stippling of chromatin or prominent

nucle-oli of large cell neuroendocrine carcinoma

Fig 2.34 Spindle-cell thymoma showing a subtle “tzellballen” pattern

composed of small nests of cells separated by fi brovascular stroma Such cases need to be distinguished from mediastinal paragangliomas, well-differentiated neuroendocrine carcinoma, and metastatic melanoma

Fig 2.35 Another histologic appearance in spindle-cell thymoma that

can be confused with metastases of melanoma or primary crine carcinoma is characterized by large clusters of spindle cells dis-playing a prominent nesting pattern

neuroendo-2 Thymic Epithelial Neoplasms

Fig 2.36 Spindle-cell thymoma with pseudosarcomatous stroma (the

so-called “metaplastic” thymoma) is an unusual variant characterized

by anastomosing strands and islands of cohesive epithelioid cells

sepa-rated by a highly cellular spindle-cell stroma simulating a biphasic

malignant neoplasm (i.e., carcinosarcoma)

Fig 2.37 Spindle-cell thymoma with pseudosarcomatous stroma

shows a discrete island composed of oval to polygonal epithelioid cells

with minimal cytologic atypia surrounded by a cellular spindle-cell

stroma The epithelial cells test positive for cytokeratins, p63, and

PAX8; the stromal spindle cells are positive for vimentin and may also

display focal weak actin and EMA positivity

Fig 2.38 Higher magnifi cation of epithelial cell island in spindle-cell

thymoma with pseudosarcomatous stroma shows cells with oval nuclei and abundant eosinophilic cytoplasm; note that the cells are devoid of mitotic activity

Fig 2.39 Focal areas in spindle-cell thymoma with

pseudosarcoma-tous stroma may display squamoid features and degenerative atypia; these features should not be confused with evidence of malignancy or the development of thymic carcinoma