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
Download The PPT/PDF document "Pathology of Mediastinal" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Pathology of
Mediastinal tumors (MT)Dr F.Hajmanoochehri93/10/25
Slide2introduction
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
Slide3MT : 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.
Slide4C
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
Slide5Slide6Thymoma
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
Slide7Thymoma
& 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
Slide8Slide9Gross 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
Slide10Morphology
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
Slide11Slide12Morphology
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 %)
Slide13Morphology
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)
Slide14Slide15Slide16Slide17Prevalence
&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
Slide18A: spindle epithelial cells (arrows) with lymphocytes (arrowheads)
Slide19AB: A (asterisk) and B (star) type lobules
Slide20B1: immature T cells (arrows), epithelial tumor cells with large nuclei (arrowheads)
Slide21B2: abundant epithelial cells with irregular nuclei (arrowheads) and fewer lymphocytes (arrows) than B1
Slide22B3: polygonal epithelial cells (arrows) with irregular nuclei
Slide23Prognostic 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
Slide24Slide25A
, Spindle cell thymoma infiltrating skeletal muscle (H&E, ×10). B, Spindle cell thymoma infiltrating lung parenchyma (H&E, ×10).
Slide26staging 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
Slide27Slide28Differential 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
Slide29Thymic
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
Slide30Thymic
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
Slide31well-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
Slide32Slide33thymic
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
Slide34E
, Mucinous adenocarcinoma
F
, papillary carcinoma.
G
, clear cell carcinoma.
H
,
Rhabdoid carcinoma featuring cells with
rhabdoid cytoplasmic inclusions. I, Anaplastic carcinoma with
Slide35Thymic
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
Slide36Thymic
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
Slide37immunohistochemical
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
Slide38Prognostic
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
Slide39NEUROENDOCRINE 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.
Slide40Thymic
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
Slide41Slide42Small 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
Slide43GERM 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)
Slide44Mediastinal
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
Slide45Lymphadenopathy
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
Slide46lymphoma
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
Slide47Primary
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
Slide48Lymphoblastic 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
Slide49Primary 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 )
Slide50Flow
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
Slide51mesenchymal
tumoursrare mediastinal neoplasms (< 2 %)Lymphangioma, Hemangima, lipomas
,…
anywhere ,but most
common in
anterior part
sarcomas
are distinctly uncommon
Slide52Mediastinal
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
Slide53PARATHYROID
MASSESEctopic parathyroid tissue is not uncommonly found adjacent to the thymus glandmediastinum :most common location for ectopic parathyroid adenomas
Slide54Neurogenic
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
Slide55MEDIASTINAL 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
Slide56SUMMARY
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