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Pathology of  Mediastinal Pathology of  Mediastinal

Pathology of Mediastinal - PowerPoint Presentation

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Pathology of Mediastinal - PPT Presentation

tumors MT Dr FHajmanoochehri 931025 introduction Appropriate therapy for various mediastinal tumors differs considerably according to the histological type and it may significantly impact on survival ID: 779683

carcinoma cell mediastinal thymic cell carcinoma thymic mediastinal type thymoma tumors cells common carcinomas tumor lymphoma epithelial grade large

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Slide1

Pathology of

Mediastinal tumors (MT)Dr F.Hajmanoochehri93/10/25

Slide2

introduction

Appropriate therapy for various mediastinal tumors differs considerably according to the histological type and it may significantly impact on survival

minimally

invasive sampling is usually to establish a

tumor as a

thymic

epithelial tumor and therefore a

candidate for

resection, as opposed to a lymphoma in which

surgical resection

is not indicated

Slide3

MT : a Challenge in

surgical pathologymany different types of lesions and overlapping histologic features

difficulty in obtaining good biopsies

&

may be non-diagnostic because: not adequate

sample

, crush

artifact

,

extensive necrosis, fibrosis, or cystic change

overlapping histologic

features

E.g

: Differentiation between

thymoma

,

neuroblastoma

, seminoma

, metastatic

small cell

carcinoma and lymphoma

-----------------------------------------------------------------------------------------

It needs significant

experience with

mediastinal

pathology because specimens from this location are relatively uncommon.

Slide4

C

t,p: cysts, thymic and parathyroid; C

p,b

: cysts,

pericardical

and bronchogenic; C g: cysts,

gastroenteric

;

GV: germ cell and vasular tumors

Anatomic Distribution of

Mediastinal

Masses

Slide5

Slide6

Thymoma

defined as a low-grade epithelial neoplasm arising in the thymus

Most common primary anterior (

anterosuperior

)

mediastinal

tumor,

also the mediastinum, the neck, pulmonary hilum, thyroid gland, lung, or pleuramost common cause of a thymic massM=F, most >40

Most patients are asymptomaticAlthough they may seed the pleural space, pleural effusions are rareLymphatic and hematogenous metastases are rare

Up to 1/3 are invasive into

mediastinal

fat, pleura, pericardium, great vessels, heart and lung

Slide7

Thymoma

& parathymic syndromesHalf of patients

suffer have associated

parathymic

syndromes

myasthenia gravis

hypogammaglobulinemia

pure red cell aplasia

30-45

% of pts with thymoma have MG10% of pts with MG have a thymoma65% of pts with MG have thymic

follicular

hyperplasia

25

% of

pts

with MG have normal

thymuses

Slide8

Slide9

Gross features

encapsulated, circumscribed, tan, firm lobulated massesfrom microscopic to over 30 cmcut surface:, bands of fibrous stromaCystic changes may be extensive, and in such cases, the cyst wall should be sampled carefully to search for tumor foci

Slide10

Morphology 

a fibrous capsule (may be calcified)typical low power : thick collagen bands connected to the capsule divide the tumor into

multiple lobules

of varying

size

mixture

of neoplastic

epithelial cells

and non-neoplastic T lymphocytes, admixed in varying proportionsepithelial

component : two type :the polygonal, round, or oval cell type, or the spindle cell type

Slide11

Slide12

Morphology

characteristic feature (in 70 %) :Prominent, dilated perivascular spaces filled by plasma fluid and may contain a few lymphocytes, plasma cells, or foamy

macrophages

Small

vessels with

hyalinized

walls are often present in the center of these spaces. Neoplastic cells surrounding these spaces may show a palisading arrangement.

Hassall's corpuscles (14

%), cystic change (19 %), a "starry-sky" pattern, and squamous differentiation (10 %)

Slide13

Morphology

storiform pattern (like in fibrous histiocytoma) staghorn-shaped vessels (resembling solitary fibrous tumors)

rosettes (

similar

neuroendocrine tumors

)

gland-like

structures, or a papillary growth patternProminent plasma cell infiltratesmicrocystic patternsprominent myoid cells (

rhabdomyomatous thymoma)

Slide14

Slide15

Slide16

Slide17

Prevalence

&Prognostic Features of SubtypesPrevalence:

Type

B2 and AB

(

each 20% to 35

%).

Type

B1 ,B3 and Type A rare (5% to 10%) Type C 10% to 25%.Prognosis :

(most relevant are :tumor stage, WHO-based histologic type, resection status)Type A and AB thymomas in stages I and II almost always follow a benign clinical courseType B1 :low malignant potential(local

recurrences or

metastases may

occur

>20

yrs

Type

B2, B3, and C

thymomas

are clear-cut malignant

tumors

Slide18

A: spindle epithelial cells (arrows) with lymphocytes (arrowheads)

Slide19

AB: A (asterisk) and B (star) type lobules

Slide20

B1: immature T cells (arrows), epithelial tumor cells with large nuclei (arrowheads)

Slide21

B2: abundant epithelial cells with irregular nuclei (arrowheads) and fewer lymphocytes (arrows) than B1

Slide22

B3: polygonal epithelial cells (arrows) with irregular nuclei

Slide23

Prognostic factors

multifactorial but invasion is most important factor the

best determination of

invasive is

by the

surgeon

at the time of

operation(better than

CT imaging )capsular invasion : Inking of the tumor capsule at the time of gross evaluationadherent to adjacent structures

without invasion: surgeon should designate the site of adhesion on the specimen, so the pathologist can take careful sections from that area. An inflammatory fibrous reaction can also lead to the false impression of tumor invasion.completeness of resection

Slide24

Slide25

A

, Spindle cell thymoma infiltrating skeletal muscle (H&E, ×10). B, Spindle cell thymoma infiltrating lung parenchyma (H&E, ×10).

Slide26

staging purposes

thymomas can be divided into encapsulated, invasive, or metastatic tumors Invasion :grossly or microscopically. invasion needs to be

transcapsular

with microscopic invasion into adjacent

mediastinal

tissue before it impacts upon

outcome

Slide27

Slide28

Differential Diagnosis of

thymoma1- malignant lymphomas : if thymoma was predominantly lymphocytic (>2/3) ( epithelial cells are inconspicuous

)

Recommendation: use

of keratin stains

2-thymic carcinomas

, S.C.C ,

metastatic :when Predominantly epithelial thymomas

Slide29

Thymic

carcinoma & thymoma may be found synchronously

or carcinoma may develop within a

preexisting

thymoma

after an interval of 10 to 14 years

but mostly de

novodistinctive morphology and biologyTC :highly atypical cells with cytoarchitectural features of carcinoma similar to those seen in other

organs ;lack encapsulation, presence of invasion and metastasis, frequent areas of cystic change and necrosis ,encapsulated ( 15 %), mucoid cut surface (MEC)many lymphocytes can be seen in TC

stroma

(B

cell type and mature T cell

type

but no immature

T cell

)

fail to

recapitulate features

of normal thymus

, such as medullary

differentiation

Carcinomas express

CD5

, unlike Type A, AB, and B

thymomas

Slide30

Thymic

carcinomas subtypeslow-grade (W.D) and high-grade (P.D)well-differentiated tumors : squamous cell

carcinomas(most),

mucoepidermoid

carcinomas

(W.D) and

basaloid

carcinomas. High-grade tumors :lymphoepithelial-like carcinomas (non-keratinizing squamous cell

carcinomas)(most), mucoepidermoid carcinoma(P.D), clear cell carcinoma, sarcomatoid carcinoma, and anaplastic/undifferentiated carcinoma

Slide31

well-differentiated

thymic carcinomacontroversial :Many of these =epithelial-predominant thymoma in traditional classification. According to WHO : is classified among

thymomas

rather than

thymic

carcinomas.

considerable

overlap with epithelial-predominant

thymoma because :1- The high frequency of myasthenia gravis 2-excellent survival in patients

Slide32

Slide33

thymic

carcinoma.

A

, Squamous cell carcinoma with

B

, High-grade undifferentiated carcinoma

C

, Lymphoepithelioma-like carcinoma D, Spindle cell (sarcomatoid) carcinoma showing fusiform cells arranged in intersecting fascicles

Slide34

E

, Mucinous adenocarcinoma

F

, papillary carcinoma.

G

, clear cell carcinoma.

H

,

Rhabdoid carcinoma featuring cells with

rhabdoid cytoplasmic inclusions. I, Anaplastic carcinoma with

Slide35

Thymic

carcinoma VS thymomaMacroscopicaly : large, firm, infiltrating masses, with frequent areas of cystic change and necrosis ,encapsulated ( 15 %),

mucoid

cut surface (MEC),

Multilocular

thymic

cysts

thymic carcinoma aganist thymoma :no paraneoplastic

syndromes.no immature T lymphocytic ( but B lymphocytes, plasma cells, or mature T lymphocytes )No lobulated pattern separated by thick fibrous bands (instead it has a desmoplastic stroma

)

No characteristic histologic features

: perivascular

spaces, medullary differentiation, and Hassall's

corpuscles

Slide36

Thymic

carcinoma VS metastatic carcinoma no histologicaly pathognomonic featuresexceptions :obvious transition (eg, from preexisting

thymic

epithelium)

some special variant :

basaloid

carcinoma with cystic changes, carcinoma

with rhabdomyomatous cellsPrimary thymic carcinomas are rare,clinical evaluation : search for a primary tumor, especially lung

cancerIHC study

Slide37

immunohistochemical

studiesCD5: 80% Positive in thymic carcinomas, Negative in : thymoma (B3) and Met.C-kit

(CD117)

:

GluT-1 :

TTF-1 : Positive in Lung cancer , Negative in

Thymic

cancer

A high frequency of p53 protein expression has been reported in thymic carcinoma but not in thymoma,Bcl2 and P53 are signs for more clinically

agrassiveness

Slide38

Prognostic

implications of histology low-grade vs high-grade tumors .Squamous cell carcinoma also may have a better prognosis

Morphologic worse

prognosis

:

infiltrative

tumor margin

,

absence of a lobular growth pattern,high grade nuclear atypia

Necrosis >10 mitoses / 10 HPF

Slide39

NEUROENDOCRINE TUMORS(NET)

1-well-differentiated NETs : a-typical carcinoid b- atypical carcinoid (necrosis

and the proliferative rate )

2-poorly-differentiated carcinomas (small cell ,and large cell variants).

The

histological criteria similar to pulmonary

neuroendocrine tumors.

Slide40

Thymic

carcinoid  uncommon neoplasm (2 % mediastinal & 5

%

thymic

)

in

adults,

mean

age =50 yrs , male preponderance. Rarely associated with carcinoid syndrome

Associated endocrine abnormalities: Cushing’s syndrome due to ectopic ACTH or MEN(25 %)vary in size from 1 to 18 cm well-circumscribed or encapsulated tumorssolid, gray tan with frequent areas of hemorrhage and necrosis

Microscopy :

organoid

nests,

trabeculae

, rosettes, or palisading

,

homogeneous

cytologic

features with finely granular nuclear

Slide41

Slide42

Small cell neuroendocrine carcinoma

rarely occur as a primary thymic lesion.similar morphologically to its counterpart in the lung. Immunohistochemistry : keratin ,

neuroendocrine markers (

chromogranin

, CD56, or

synaptophysin

)

electron microscopy :dense core granules

Slide43

GERM CELL TUMORS 

1-isolated metastases from occult primary gonadal neoplasms 2- true extragonadal origin has (most

mediastinal

GCT) :In primary form :

Thymic

origin?

: PLAP positive

cells in normal thymus support20% of mediastinal tumor , mostly anterosuperior Account

for up to 10% of all germ cell tumors in menUsually occur in young adults particularly in men typically spread via lymphatics but can metastasize anywhere, especially choriocarcinomaserum AFP (yolk sac tumour

) and

HCG

(

choriocarcinoma

)

Associated with hematologic disorders,

(M7,MDS)

Slide44

Mediastinal

Germ Cell TumorsTeratoma :

Most common

type,Occurs

in children and young

adults,Usually

asymptomatic, but if large enough : symptoms of mediastinal compressionMature

: benign, well-differentiatedImmature: contains >50% immature components, may recur or metastasizeMalignant: a mature teratoma that contains a focus of carcinoma, sarcoma or malignant GCT------------------------------------------------------------------------------------------------

Seminoma

;

Represents 40% of

GCTs,

alomstly

in thymus,

Nonseminomatous

Germ Cell

Embryonal

cell carcinoma

Endodermal sinus tumor

Choriocarcinoma

Malignant

teratoma

Mixed

Slide45

Lymphadenopathy

most common cause of mediastinal masses Causes: depending on the patient (age, medical history etc) and the clinical setting :

metastatic

carcinoma, especially lung cancer

lymphoma

infectious/inflammatory

conditions, especially granulomatous process such as

tuberculosis,

histoplasmosis (or other fungal infections depending on the geographic location) and sarcoidosis

Slide46

lymphoma

Most types can involve the mediastinum the commonest as a mediastinal

mass

are:

1. Nodular sclerosis Hodgkin's disease: classically in young women

2. Lymphoblastic

lymphoma(

Lymphoblastic

leukemia/lymphoma) : occurs in children, can grow very rapidly3. Diffuse large cell: can occur at any age4-Low-grade B-cell lymphomas of the thymus are rare, most common type :MALT type

Slide47

Primary

Mediastinal Hodgkin’s Lymphoma

Presentation

Incidental

mediastinal

mass on chest

xray

is common presentation

Mass is usually large, (may be cystic)rarely causes retrosternal chest pain, cough, dyspnea, effusions or SVC syndrome

“B” symptoms,Generalized pruritus prominent mixed inflammatory background, often rich in eosinophils and neutrophilsneoplastic cells in HL are

CD30 and

usually CD15 positive and are negative for CD45

and CD20

DDX; Large B cell lymphoma

Slide48

Lymphoblastic Lymphoma

1st/2nd decade, M>FAggressive, high grade

Often present as a rapidly enlarging

mediastinal

mass which may cause compression of

mediastinal

contents

Morphologicaly

Similar to ALL(may be the initial clinical presentation)

are usually, and in the thymus are nearly exclusively, of T-cell lineageresemble cortical thymocytes morphologically and immunophenotypically (double CD4+ 8+,CD1a+, TdT+) Unlike normal thymus

or type

B 1

thymomas

: infiltrate

the fat and form solid sheets rather than lobules

Slide49

Primary Mediastinal

large cell Lymphoma

3rd decade,

F>M,

.

Presents as a rapidly expanding mediastinal mass which may invade the airway, chest wall and/or adjacent

structures (superior

venacava

syn.)

Extrathoracic involvement is uncommonMostly B cell , positive for B-cell markers such as CD20, CD30, CD 45, and are negative for cytokeratinDDx : perivascular position

thymoma

(B2), entrapment of normal thymus tissue (

thymoma

),

artifactual

cytoplasmic

clearning

(seminoma )

Slide50

Flow

cytometry :distinguishing low-grade B-cell lymphomas vs reactive lymphoid proliferationsgene rearrangement studies on frozen tissue

Distinguishing MLBCL

from Hodgkin lymphoma in difficult

cases

cytogenetics

unusual

types of thymic carcinoma

Slide51

mesenchymal

tumoursrare mediastinal neoplasms (< 2 %)Lymphangioma, Hemangima, lipomas

,…

anywhere ,but most

common in

anterior part

sarcomas

are distinctly uncommon

Slide52

Mediastinal

GoiterThe inferior poles of the thyroid normally lie superior to the thoracic inlet

Growth through the thoracic inlet can produce symptoms related to compression of normal thoracic inlet contents

Pathology

Most are benign

Multinodular

goiter and large follicular adenoma account for 95%

Large

multinodular

goiters have little functioning tissue. Usually have cystic degeneration, fibrosis, calcification, hemorrhageMany are found to have areas of papillary thyroid cancer

Slide53

PARATHYROID

MASSESEctopic parathyroid tissue is not uncommonly found adjacent to the thymus glandmediastinum :most common location for ectopic parathyroid adenomas

Slide54

Neurogenic

tumours19 to 39 %of all mediastinal tumors most common cause of a posterior

Med.mass

, rarely arise elsewhere

Mostly

benign, malignant ones generally occurring in younger

patients

can cause neurologic symptoms by compression(

Pancoast syndrome, and Horner's syndrome)They are classified as1-Tumours

of sympathetic nervous systemi) neuroblastoma - rare, malignant, occur in those under age 10 usuallyii) ganglioneuroblastoma - more common, intermediate prognosisiii) ganglioneuroma - most common, benign, can occur in young adults2.

Tumours

of peripheral nerve and nerve sheath

i

)

schwannoma

most

common of all

mediastinal

neurogenic

tumours

, third and fourth decade

ii)

neurofibroma

-

may

be associated with Von Recklinghausen's disease

iii) malignant nerve sheath

tumours

/

schwannomas

- very rare

Slide55

MEDIASTINAL CYSTS

Mostly developmental benign and incidental on imaging. Note

: variety of

thymic

tumors, such as Hodgkin

lymphoma,germ

cell tumors, and, rarely,

thymomas

and thymic carcinomas,may present as a thymic ‘cyst’. The most common types

: Anterior: thymic, cystic thymoma, parathyroid, lymphangioma, cystic teratoma Middle: pericardial, bronchogenic (the most common congenital mediastinal cyst) Posterior: gastroenteric

Slide56

SUMMARY

  Interpretation of pathologic specimens from the mediastinum requires familiarity with a wide range of neoplasms and careful clinical correlation. It is critical for surgeons, radiologists, and pathologists to communicate well.If tumors originally treated by non surgical means do not respond as expected, additional biopsies, special studies, or consultations may be necessary to achieve the correct diagnosis

Slide57