Mediastinal lesions

Mediastinal Lesions
Presented By: Dr Himani Rai
Moderator: Dr Rajni Choudhary

Mediastinum Gross anatomy
Boundaries –
Anterior:sternum
Posterior:vertebral column
Superior:thoracic inlet
Inferior:diaphragm
Lateral:parietal pleura

Compartments
• Superior
•Anterior
• Middle
• Posterior

Mediastinal Lesions:
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1. Cystic Lesions of the thymic region and mediastinum
2.Thymic hyperplasia
3.Thymic epithelial neoplasm
4.Neuroendocrine,Germ cell and nonepithelial neoplasms
5.Miscellenious lesions

Thymus: Normal Anatomy
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Flattened lymphoid organ located in the
upperanterior mediastinum and lower
part of the neck.
Most active during childhood, reaching
a weight of about 30 to 40 g at puberty.
After which it undergoes slow involution
so that in the middle-aged or older adult
it may be diﬃcult to differentiate from
adipose tissue macroscopically

Infant Thymus: Normal Histology
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Lobulated organ
Loose collagenous capsule
from which interlobular septa
containing blood vessels
radiate into the substance of
the organ
Two distinct zones:
1)a deeply basophilic outer
cortex
2) an inner eosinophilic medulla
Capsul
e
Septa
Cortex
Medull
a

Adult Thymus: Normal Histology
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Process of involution: fatty
inﬁltration and lymphocyte
depletion.
In the mature thymusislands
of lymphoid tissue are
separated by areas of
adipose tissue.
Elderly: only small islands of
lymphoid tissue lost in a sea
of adipose tissue
Islands of
lymphoid
tissue
Adipose
tissue

Thymic Cortex
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Packed with immature and
maturing T cells,
(thymocytes).
Several mitotic figures can
be seen in the outer cortex
in this micrograph.
Note also in this micrograph
a small capillary lined by
flattened endothelial cells
entering the cortex from the
capsule .
Capsule
Mitotic
figures
Endothelial
cells
Macrophage
s

Thymic Medulla
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The dominant histological feature is
epithelial component .
Epithelial cells have large pale-stained
nuclei, eosinophilic cytoplasm and
prominent basement membranes.
A particular feature is lamellated Hassall
corpuscles that ﬁrst appear in fetal life
and increase in number and size
thereafter.
These are formed from groups of
keratinised epithelial cells, often with
fragments of debris at their centre, and
probably represent a degenerative
phenomenon.
Hassall
corpuscles
Epithelial
componen
t

Part I: Cystic lesions of thymic region
and medistinum
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5.
Thymic cysts
Pericardial cysts
Mediastinal Bronchogenic cysts
Esophageal cysts
Gastroenteric cysts

1. Thymic cysts
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Age:20-50yrs
Mostlyasymptomatic
Two types:
1.Unilocular : Developmental origin
2.Multilocular : Acquired
always accompanied by
inflammation and necrosis
Gross:
Unilocular: enclosed by thin fibrous wall
Content: serous fluid
Multilocular: thick wall & pericystic fibrous
adhesions
Content: keratinous, turbid, hemorrhagic material

Histology:
Unilocular thymic cyst :
• may be lined by squamous, cuboidal,
or columnar epithelium
• Thymic tissue is present within the
cyst wall
• Lacks inflammation
Multilocular thymic cyst:
• lined by squamous epithelium but can
have ciliated columnar epithelium.
• Fibrosis and inflammatory infiltrate in
cyst walls
• Residual thymic tissue within wall of
cyst

2.Pericardial (Coelomic)
Cysts
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Usually congenital but can be acquired
Due to failure of all the lacunae that form
the pericardial sac to merge.
Uncommon lesion
fourth to fifth decade
Located at the cardiophrenic angle.
Soft and unilocular
contain clear fluid unless infected.
inner surface of the cyst wall is covered by
a single layer of flat or cuboidal
mesothelium

3.Mediastinal
Bronchogenic cysts
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A congenital cyst that develops as a result of a ventral
foregut malformation.
Age of presentation:birth to 56 years
Can arise in the anterior, superior, middle or posterior
mediastinum.
Most often located above the tracheal bifurcation.
usually asymptomatic but may experience chest pain,
dysphagia, coughing, dyspnea, or fever
Gross : • Usually unilocular and thin-walled
• Filled with serous ﬂuid, blood, or purulent material (if
infected)
Histology: • Cyst lined by ciliated columnar epithelium
Squamous metaplasia is common
Wall of the cyst contains varying amounts of hyaline
cartilage, mucinous glands, and smooth muscle

4.Esophageal cysts
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Congenital or acquired cystic lesions that do
not communicate with the esophagus.
Symptoms: chest pain, diﬃculty swallowing,
or breathing problems
Three types:inclusion cyst, retention cyst/
mucocele, and duplication cyst
Mostlyunilocular
Mostly embedded in the wall of the lower half
of the esophagus.
The lining may be squamous, ciliated,
columnar, or a mixture of these.
Double layer of smooth muscle (in
duplication cyst)

5.Mediastinal
Gastroenteric cysts
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Uncommon cystic lesion of the posterior mediastinum
usually lined by gastric epithelium
Congenital foregut malformation
males>females
Symptoms: respiratory distress, dysphagia, coughing,
recurrent pneumonia, chest pain, or hematemesis.
Often associated with vertebral malformations
Gross: Usually unilocular but can be multilocular
may have areas of ulceration and hemorrhage
Can be filled with serous, mucoid, or hemorrhagic fluid
Histology: Lining is usually gastric epithelium but can be
squamous, ciliated columnar, or intestinal-type epithelium
Nerve fibers and ganglia often present
May contain pancreatic tissue or an adrenal rest

Part 2: Thymic Hyperplasias
1. True thymic hyperplasia
2.Lymphoid hyperplasia of thymus

1.True Thymic Hyperplasia
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Enlarged thymus (weight greater than upper limit of normal for
age) with normal histological appearance.
Most common cause of an anterior mediastinal mass in infants
and children
Can occur in adults, often after stress such as chemotherapy,
severe burns, irradiation, or steroid therapy (referred to as rebound
hyperplasia)
Usually asymptomatic and detected on chest x-ray ﬁlms
Can be associated with autoimmune diseases, myasthenia gravis,
or hyperthyroidism

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Gross:
Increased size and weight (as
compared with age-matched control
subjects)
Histology:
Normal thymic tissue
Lobular architecture and
corticomedullary junction are preserved
Main differential diagnoses:
1)Lymphoid hyperplasia of thymus :
usually of normal size and weight;
lymphoid follicles with germinal centers
are seen on histological analysis
2)Thymoma : normal architecture effaced

2.Lymphoid Hyperplasia of The Thymus
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Presence of increased lymphoid follicles in an otherwise
normal thymus
Present in up to 75% of cases of myasthenia gravis.
Gross:
• Usually normal size and weight
Histology:
• Increased density of lymphoid follicles with germinal centers
(2 to 19 per low-power field)
• Preserved thymic architecture
• May have a plasma cell infiltrate or increased reticulin fibers
Main differential diagnoses
1)Thymoma : architecture not preserved
2)True thymic hyperplasia : increased weight and size without
lymphoid follicles

Part3: Thymic Epithelial Neoplasms
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Thymoma
Thymic Carcinoma

1)Thymoma:General features
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Neoplasms of thymic epithelial cells
Mostly present in adult life.
No gender predilection.
Anterosuperior mediastinal mass; rarely ectopic in posterior mediastinum,
neck, pleura, or lung
Local symptoms: chest pain, coughing, dyspnea, dysphagia, hoarseness,
or superior vena cava syndrome
Up to half of the tumors are associated with myasthenia gravis,on the
other hand, 20% to 30% of MG patients have thymoma
Rarely associated with paraneoplastic syndromes
(hypogammaglobulinemia and pure red cell aplasia) or connective tissue
diseases (systemic lupus erythematosus and rheumatoid arthritis)

Thymoma: GROSS
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Typical thymoma is largely or entirely
solid, yellowish gray, and separated
into lobules by connective tissue
septa.
In approx. 80% of cases, the tumor is
well encapsulated
Foci of necrosis and cystic
degeneration are common,
particularly among larger tumors.

Thymoma: Histology
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Broad lobulation is seen in all
thymomas, and ﬁbrous tissue
separates the tumor into cellular
lobules.
Biphasic cell population:
1)Neoplastic epithelial cells :a round–
polygonal,plump(epithelioid), stellate,
or spindle/oval shape. The nuclei are
vesicular and of smooth contour; the
nucleolus may be conspicuous,
particularly when the nuclei are round or
polygonal.
2)Non-neoplastic lymphocytes.

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Show one or more features
suggestive of organoid
differentiation. These include:
Perivascular spaces containing
lymphocytes, proteinaceous ﬂuid,
red blood cells, foamy
macrophages, or ﬁbrous tissue
Rosettes without central lumens
Gland like formations within the
tumor or, more often, in the tumor
capsule
True glandular structures (an
exceptional event)
Whorls suggestive of abortive
Hassall corpuscle formation

Thymoma: Types (WHO Histological
classiﬁcation)
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1.Conventional thymoma:
Type A: neoplastic epithelial cells are spindle shaped
Type B: neoplastic epithelial cells are round polygonal or plump
(epithelioid) cells
– Type B1: with most amount of lymphocytes
– Type B2: with moderate amount of lymphocytes
– Type B3: lymphocyte poor
• Type AB (mixed A and B features)
Most common subtypes: B2 and AB
Rare subtypes: B1 and A

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2.Nonconventional and rare thymomas:
Micronodular thymoma
Metaplastic
Microscopic
Sclerosing
Lipoﬁbroadenoma

Immunopathology/special stains
Tumor epithelial cells:
• Positive for cytokeratins (e.g., AE1/AE3, CAM5.2, and CK7)
• Frequently positive for p63 and CK5/6
• Usually negative for CD5 and CD70
• Lymphoma: usually positive for LCA and negative for
cytokeratin
• Neuroendocrine carcinoma: neuroendocrine features with
positive neuroendocrine markers
• Germ cell tumors: positive for OCT3/4 and PLAP

Prognosis:
• For stage I and II tumors: complete removal of thymoma as well as
thymus is recommended
• For higher stage tumor: surgical resection with chemotherapy or
radiation therapy
• The prognosis depends on tumor stage, World Health Organization
(WHO) histological subtype, and completeness of resection
• Types A and AB thymomas are considered to be clinically benign
tumors with exceptionally rare recurrence and metastases
• Type B1: low grade malignant potential
• Types B2 and B3: moderate malignant potential

Type A Thymoma (Spindle Cell;
Medullary)
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A benign type of thymoma composed of
bland spindle or oval epithelial tumor
cells with few or no lymphocytes
Rosette-like formations (without a
central lumen), foci with a storiform
pattern of growth, and gland like
formations may be present.

Type AB Thymoma (Mixed)
• Foci having the features of type A
thymoma are admixed with foci
rich in lymphocytes including a
signiﬁcant proportion of immature
T cells.

Type B1 Thymoma (Lymphocyte-Rich;
Lymphocytic; Predominantly Cortical; Organoid)
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Normal thymic cortex like areas
Few small scattered neoplastic epithelial cells surrounded by
dense population of nonneoplastic immature T lymphocyte.
•Dispersed epithelial cells
–Do not from groupings
•Scant small epithelial cells
–Pale nuclei
–Small nucleoli
•Medullary differentiation always present
•Hassall corpuscles may be present
Absence of epithelial cell clusters and presence of medullary
islands are especially helpful in separating B1 from B2 thymoma

Type B2 Thymoma (Cortical)
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Composed of epithelial cells intermixed
with multiple background small
lymphocytes
Neoplastic epithelial component appears
as scattered plump cell, often including
small clusters, with vesicular nuclei and
distinct nucleoli among a heavy
population of immature T cells.
Perivascular spaces are common.
Medullary differentiation and rare Hassall
corpuscles may be present but less
conspicuous than in B1 thymoma

Type B3 Thymoma (Epithelial;
Atypical; Squamoid; Well-
Differentiated Thymic Carcinoma)
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Predominantly composed of mildly
atypical epithelial cells having a
round or polygonal shape admixed
with a minor component of
immature T cells,
resulting in a sheetlike growth of
the neoplastic epithelial cells.

Thymoma: Noncoventional and Rare subtypes
• 1)Micronodular thymoma: Micronodular
growth pattern in which epithelial
islands are separated by lymphoid
stroma.
The lymphocytes are composed mainly
of B cells and mature T cells, and the
epithelial cells are generally negative for
CD20,(two ﬁndings that may be helpful in
distinguishing micronodular thymoma
from type AB thymoma)

2)Metaplastic thymoma: rare subtype
biphasic tumor in which solid areas of epithelial cells are variably
well demarcated from cytologically bland, ﬁbroblast-like spindle
cells

2)Thymic Carcinoma
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A malignant thymic epithelial tumor with overt invasion,
cytological atypia, and lack of organotypic (thymus-like)
histological features
Middle to old age
Often asymptomatic; May present with chest pain,
dyspnea, or occasionally, superior vena cava syndrome
Very rarely associated with myasthenia gravis.
May arise from preexisting long-standing thymoma
Gross:
• Usually not encapsulated and without broad internal
ﬁbrous septa
• Yellow to gray-white ﬁrm tumor with gritty cut surface
and areas of hemorrhage and necrosis

Thymic Carcinoma: Histology
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Morphologically similar to carcinomas in other organ systems
Clear cytological atypia and lack of organotypic features of thymic
differentiation distinguish it from thymoma
May have background lymphocytes, usually mature B cells instead of
cortical-type immature T lymphocytes
Variants of thymic carcinoma:
1) Squamous cell carcinoma
2)Basaloid carcinoma
3)Mucoepidermoid carcinoma
4)Lymphoepithelioma like carcinoma
5)Clear cell carcinoma
6) Sarcomatoid carcinoma

Squamous Cell Carcinoma
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Most common subtype of primary
thymic carcinoma
composed of atypical polygonal
epithelial cells arranged in characteristic
epidermoid growth patterns often with
associated intercellular bridges.
Well, moderately and poorly
differentiated forms.
frequently positive for CD5 and CD70,
which indicates thymic origin and
distinguishes from metastatic
squamous cell carcinoma

Basaloid Carcinoma
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Resembles basaloid carcinoma
of other organs with characteristic
peripheral palisading and a
basophilic staining pattern
Low-grade malignancy

Mucoepidermoid Carcinoma
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Areas of squamous and mucin-
producing glandular differentiation
alternate in this neoplasm.
The histologic features are identical
to mucoepidermoid carcinomas
arising in major salivary glands and
lung.
Mostly low-grade tumors and
associated with a good prognosis.

Lymphoepithelioma-Like Carcinoma
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Resembles the same tumor from
other organs (e.g., nasopharyngeal
carcinoma) with syncytial sheets
of large polygonal undifferentiated
carcinoma cells intermixed with
abundant background
lymphocytes and plasma cells.
may be positive for Epstein-Barr
virus

Clear cell carcinoma
• Rare variant characterized by large amounts of glycogen-rich,
clear cytoplasm in the tumor cells, which results in a striking
resemblance to renal cell carcinoma

Sarcomatoid Carcinoma
(Carcinosarcoma)
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Simulates a mesenchymal neoplasm by
virtue of its diffuse pattern of growth and
the prominent spindling of tumor cells.
foci with an epithelial appearance or
evidence of an epithelial phenotype in
neoplastic spindle cells.
The sarcoma-like areas may include foci
of cartilaginous and skeletal muscle
differentiation (rhabdomyosarcomatous
thymic carcinoma).

Thymic carcinoma:Immunopathology/special
stains
• Tumor cells are diffusely or focally positive for cytokeratins and
EMA
• Epithelial cells in 60% of cases show CD5 and CD70 expression
(markers of thymic origin)
• Tumor cells in squamous cell carcinoma, basaloid carcinoma,
and lymphoepithelioma-like carcinoma subtypes and squamoid
cells in mucoepidermoid carcinoma are positive for squamous
cell markers p63 and CK5/6

1) Metastatic carcinoma:
• Far more common than primary thymic carcinoma; therefore, metastatic carcinoma
must be ruled out before a diagnosis of primary thymic carcinoma can be made
• Negative for CD5 and CD70
2) Germ cell tumors:
• Often with elevated serum AFP or β-hCG
• Positive for OCT 3/4 and PLAP
3)Lymphoma:
• Most common lymphomas involving mediastinum include Hodgkin lymphoma,
diffuse large B-cell lymphoma, and lymphoblastic lymphoma
• Tumor cells negative for epithelial markers and variably positive for lymphoid markers

Part4: Neuroendocrine, Germ cell
tumours and non-epithelial neoplasms
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1)Neuroendocrine tumours
2)Germ cell tumours
3)Malignant lymphomas

1)Neuroendocrine Tumours
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Uncommon
• Majority of thymic NECs are atypical carcinoids
• Affects middle age adults; rarely children
• Strong male predilection (male to female ratio, 2-7:1)
Associated with endocrinopathies, most commonly
Cushing syndrome.
Also occur as a component of multiple endocrine
neoplasia (MEN) type 1 or 2a
Gross
• Unencapsulated mass with homogenous gray-white, ﬁrm
cut surface
• Usually with areas of hemorrhage, necrosis, and
calciﬁcations

NET: Histology
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Ribbon and festoon formation
Rosette-like glands with central lumina,
“balls” or nests of cells
Lymphocytes, perivascular spaces, and
other features of thymoma are absent
Nuclear chromatin is slightly coarser and
mitotic activity is frequent.
Areas of necrosis, calciﬁcations, invasion
of lymphatic and blood vessels are other
common ﬁndings.
Almost all cases are atypical carcinoids.

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Immunopathology/special stains:
Reactivity for keratin, chromogranin, synaptophysin, neuron-speciﬁc
enolase, and other general endocrine marker
negative for TTF-1
1) Metastatic NECs:
Metastasis or direct extension from pulmonary NECs is far more
common than primary thymic NECs; these would be positive for TTF-1
more often
2)Type A thymoma:
• Mimics spindle cell carcinoids
• Positive for cytokeratin and negative for neuroendocrine markers

2)Germ Cell Tumors of mediastinum
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Two theories exist about origination of GCTs; they come from ectopic germ
cells or from primitive somatic cells of the thymus through anaplasia
Mediastinum in general (and thymus in particular) is the most common
extragonadal site for GCTs
20% of the mediastinal tumors and cysts.
Bimodal age distribution: infancy and adolescence
The usual location is the anterior mediastinum.
Mature teratoma:70% Immature:30%
Mediastinal GCTs are commonly associated with hematological
malignancies (acute myeloid leukemia, malignant histocytosis, anaplastic
large-cell lymphoma) or Klinefelter syndrome (30-40 times higher incidence)

Seminoma
Gross : large, solid, lobulated tan-yellow
mass
Histology: nests of tumor cells with
abundant pale cytoplasm, central round
nuclei, distinct cell borders; ﬁbrous
septae separating tumor nests and
containing abundant lymphocytes

Mature Teratoma
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Gross: large uniloculated or
multiloculated encapsulated cystic
mass ﬁlled with greasy or fatty
material, hair, degenerating debris,
and calciﬁcation; may erode into
adjacent structures
Histology: cysts lined by any type of
epithelium; often containing cartilage,
bone, smooth muscle,
gastrointestinal and respiratory
mucosa, salivary gland, and central
nervous system elements; 50% to 60%
of tumors contain exocrine and
endocrine pancreas, a feature not
seen in gonadal teratomas

Immature Teratoma
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Germ cell tumor similar to mature
teratoma but also containing immature
epithelial, mesenchymal, or neural
elements without a component of
embryonal carcinoma.
Gross: often large solid mass; presence
of necrosis or hemorrhage
Histology: tissue derived from all three
germinal layers in various stages of
maturation from embryonic to fetal

Other NSGCT (Embryonal carcinoma,
Yolk sac tumor & Choriocarcinoma)
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Gross: Large solid inﬁltrative tumor with areas
of coagulation necrosis or cystic degeneration
• Extensive hemorrhages are typical for
choriocarcinoma
Histology:
Embroyonal carcinoma: solid sheets, tubules,
or papillary proliferations of large polygonal
anaplastic cells with indistinct cell borders;
prominent nucleoli, abundant pale cytoplasm,
and frequent mitosis and “dirty” necrosis

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Yolk Sac tumour:
Variable patterns include reticular, myxoid,
microcystic, tubular, papillary, hepatoid,
polyvesicular, or sarcomatoid features
Variable tumor cytological features ranging
from small round cells to polygonal to large
pleomorphic cells
Schiller-Duval bodies are characteristic but
not necessary for diagnosis
Choriocarcinoma: composed of
cytotrophoblastic cells intermixed with
multinucleated syncytiotrophoblastic cells

• Useful Positive and Negative Immunohistochemical Markers for
Germ Cell Tumors

1) For teratoma :
• Bronchogenic cyst: contain epithelial lining, bronchial glands, smooth muscle and
cartilage; neural and other tissue elements are absent
• Foregut cysts: cyst with smooth muscle wall devoid of ectopic elements and
connected to upper gastrointestinal tract
2)For seminoma :
• Primary gonadal seminoma: clinical evaluation and history
• Diffuse large-cell lymphoma: LCA(+), CD20(+), CD117(–)
• Hodgkin lymphoma: CD15(+), CD30(+), PLAP(–); atypical Hodgkin and Reed-Sternberg
cells; inﬂammatory inﬁltrate with plasma cells and eosinophils
• Lymphoepithelioma-like carcinoma of the thymus: EMA(+), PLAP(–)

3)For NSGCT:
• Metastatic adenocarcinoma: AFP(–), hCG(–), history and imaging
• Thymic carcinoma: hCG(–), PLAP(–), AFP(–); usually older
patients; tumor with squamous and/or neuroendocrine
differentiation

3)Malignant Lymphoma
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Present as an anterior, superior, or middle mediastinal mass, in
this order of frequency. It represents the
Primary neoplasm of the middle portion of the mediastinum.
Appear in this area as a manifestation of a disseminated
process, or it may present as a primary mediastinal disease.

Hodgkin Lymphoma of mediastinum
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B-cell lymphoma comprising two distinct disease entities: nodular
lymphocyte predominant Hodgkin lymphoma (NLPHL) and classic
Hodgkin lymphoma (cHL)
Nearly 95% of all Hodgkin lymphomas are represented by cHLs
(most common nodular scelorsing)
Involve primarily the thymus, mediastinal lymph nodes.
typically show a bimodal age prevalence peaking at 15 to 35 years
and later in life.
Female>Males
Present with local pressure symptoms (dyspnea, cough, chest pain).

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Gross:
Sharply outlined and sometimes surrounded
by a thick capsule.
The consistency is hard, and the cut surface is
vaguely or distinctly nodular.
Histology:
The inﬁltrate of Hodgkin lymphoma tends to
be polymorphic, with lymphocytes, plasma
cells, eosinophils, histiocytes, and the
elements that provide the diagnosis, that is,
Reed–Sternberg cells, their mononuclear
variants, and lacunar cells.
These are often seen in association with
epithelial-lined cysts, Hassall corpuscles, and
isolated thymic epithelial cells

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CHL: express CD30, CD15, and PAX-5 (weak) with variable CD20
expression.
NLPHL:express CD20, CD79a, PAX-5, BCL-6, Oct-2, Bob.1
B-cell lymphoma
Peripheral T-cell lymphoma (PTCL)

Mediastinal T-Lymphoblastic Lymphoma (T-LBL)
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Neoplasm of lymphoblasts committed to T-cell lineage.
Approx. 85% to 90% of all lymphoblastic lymphomas
Most frequent in adolescent males but may be seen in any age group.
Primarily involves the thymus and lymph nodes in the mediastinum;
Also extranodal involvement
Present as mass in the anterior mediastinum
Typical presentation includes symptoms resulting from compression of
mediastinal structures.
Grossly; the tumor is generally solid, soft, and nonencapsulated. Some
preservation of the thymic shape can be appreciated in early cases.

Histology
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Microscopically, the infiltrate involves the
thymic parenchyma and can be confused
with a lymphocyte-rich (type B1) thymoma.
lymphocytes are atypical, with a very fine
chromatin pattern, frequent nuclear
convolutions, numerous mitotic figures,
and equally numerous necrotic cells.
There is usually extension into the
perithymic fat, and invasion of blood
vessel walls is frequent.
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T lymphoblasts usually positive for and variably express CD1a, CD2,
CD3, CD4, CD5, CD7 and CD8; CD7 and CD3 are most often positive.
Tumor cells express TdT, CD99, CD34, and CD1a consistent with
their precursor nature.
• Burkitt lymphoma: composed of intermediate size B cells with
prominent nucleoli negative for TdT and CD34
• B-ALL: positive for B-cell markers
• Mature T-cell lymphoproliferative process: negative for CD34 and
TdT

Primary Mediastinal (Thymic) Large B-
Cell Lymphoma
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B-cell lymphoma involving predominantly the thymus and anterior
mediastinum
Composed of large or medium-sized B lymphocytes;
Believed to originate from thymic B lymphocytes
Most patients are young adult females.
Presents as bulky locally invasive anterior mediastinal disease.
Presentation with superior vena cava syndrome is frequent.
Gross: invasive features: extension into pericardium, pleura, lung,
sternum, and chest wall is common.
The consistency is generally ﬁrm, and there are frequent foci of
necrosis.

Histology
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Tissue inﬁltrated by sheets of large
lymphoid cells
Can have centroblastic,
immunoblastic, anaplastic, or Reed-
Sternberg–like appearance
Sclerosis is common, varying from
strands to broad septae
In all large-cell lymphomas, mitoses,
both typical and atypical, are frequent
Remnant thymic epithelium
occasionally identiﬁed

• Lymphoma cells are positive for CD19, CD20, CD79a, and CD22
• Also frequently positive for CD23
• Can be positive for CD10, CD30, and BCL6
1)Nodular sclerosis Hodgkin lymphoma : large CD30+ and/or CD15+ cells with
conspicuous nucleoli and background of predominantly small mature
lymphocytes, eosinophils, and plasma cells
2)Thymic carcinoma : cohesive growth, sometimes with squamoid features;
cytokeratin positive
3)Seminoma : CD45 negative; placental alkaline phosphatase positive
4)Anaplastic large-cell lymphoma : mostly of T-cell type, with nests of CD30+
anaplastic cells with pleomorphic nuclei and numerous mitoses; expresses
anaplastic lymphoma kinase protein, and epithelial membrane antigen

Differential features of tumours of
anterior mediastinum
Features Thymoma Large Cell
Lymphoma
Lymphoblas
tic
lymphoma
Thymic
Hodgkins
lymphoma
Thymic
Seminoma
Thymic
carcinoid
Patterns (Low
power
observation)
Sharply defined, angular
lobules, Fibrous bands
and capsule.
Diffuse
growth.
Variable
fibrosis with
occasional
compartme
ntalizing
sclerotic
pattern
Diffuse
growth or
pseudonod
ular pattern
(both in
lymph
nodes and
in thymus)
Extensive
fibrosis with
rounded
lobules of
tumor.
Subdivided
by fine
fibrous
trabeculae
into variable
sized
compartme
nts
Ribbons,
festoons,
punctate
calcified
necrosis
producing
discrete and
rounded
masses of
tumor

Lymphoma
Lymphoblasti
c lymphoma
Thymic
Hodgkins
lymphoma
Thymic
Seminoma
Thymic
carcinoid
Nuclei Often fine
chromatin
contrasting
with well-
defined
nuclear
membrane:
Mitosis rare
Vesicular with
prominent
nucleoli,
Marked
folding of
nuclei (“clover
leaf”) Variable
chromatin
pattern,
Mitotic
figures
variable
Even
chromatin
(“dusky” at
low power)
Scant
insoncpicuou
s nucleoli
Numerous
mitotic
figures
Cytologic
features-
those of
nodular
sclerosing
Hodgkin
lymphoma
Coarse
chromatin,
marked
prominence
of nucleoli,
variable no. of
mitotic
figures
Rounded
nuclei with
sharp
stippling
chromatin;
variable
number of
mitotic
figures
Cytoplasm Great
variation from
scant to
squamoid to
squamous
Variable,
occasionally
abundant and
rich in DNA
Scant Lacunar cells
often
prominent
Marked
retraction of
cytoplasm;
often
glycogen rich
Polyhedral
cells with
finely granular
eosinophilic
cytoplasm;

Lymphoma
Lymphoblastic
lymphoma
Thymic
Hodgkins
lymphoma
Thymic
Seminoma
Thymic
carcinoid
Associated
features
Germinal
centers in
surrounding
thymus(in
case of
myasthenia
gravis)
Incorporation
of non-
neoplastic
thymus (13%)
Residual
lymphocytes
often form
tight
perivascular
cuffs.
Necrosis
frequent
Markedly
invasive
Residual
Hassall
corpuscles
_ Germinal
centers,
epithelioid and
giant cells
_
Electron
microscopy
Well- formed
desmosomes
Nuclear blebs
Absence of
epithelial
features
Nuclear blebs
Fine
chromatin
Absence of
epithelial
features
Absence of
epithelial
characteristics
in Reed-
Sternberg
cells
Even
chromatin
Prominent
nucleoli
Glycogen rich
scant
desmosomes
Only rare
tonoﬁlaments
Dense core
granules
Desmosomes
inconspicuous
or poorly
formed.
Tonoﬁlaments
only rarely
prominent

Lymphoma
Lymphoblast
ic lymphoma
Thymic
Hodgkins
lymphoma
Thymic
Seminoma
Thymic
carcinoid
Immunohist
ochemistry
Keratin B-
lymphocyte
markers
T-
lymphocyte
markers
CD15, CD30 PLAP,CD117 Chromogran
in,
Synaptophy
sin

Part5:Miscellenious lesion of
mediastinum
•
•
•
•
•
•
•
•
•
•
•
1)Mediastinal ectopic throid
2) Ectopic parathyroid
3)Mediastinal Lymphangioma
4)Mediastinal Schwannoma
5)Mediastinal Neuroﬁbroma
6)Malignant peripheral nerve sheath tumour
7)Mediastinal Neuroblastoma
8)Mediastinal Ganglioneuroblastoma
9)Mediastinal Ganglioneuroma
10) Mediastinal Paraganglioma
11)Mediastinal Metastases

1)Mediastinal Ectopic Thyroid
•
•
•
•
•
•
•
•
•
•
Functioning thyroid tissue found in the
mediastinum rather than the usual location of
the thyroid gland
normal, asymptomatic, and found incidentally
Gross
Encapsulated or nonencapsulated mass
Histology
• Same as main thyroid gland
Same as main thyroid gland: TTF-1 positive
Thyroid carcinoma metastasis

2)Ectopic Parathyroid
•
•
•
•
•
•
•
•
Functioning parathyroid tissue found anywhere
other than the usual location of the parathyroid
glands
Undescended superior parathyroid glands: located
in the carotid sheath or behind the cervical or
thoracic esophagus
Undescended inferior parathyroid glands:located in
the thymus, pharynx, or the vagus nerve
responsible for persistent hyperparathyroidism
Histology
Same as normally descended parathyroid glands
• PTH positive

3)Mediastinal
Lymphangioma
•
•
•
•
•
Benign malformation of dilated lymphatic channels.
Comprises up to 5% of mediastinal masses
More common in pediatric patients
Usually seen as an anterosuperior mediastinal mass
Histology
• Irregular spaces lined by flat lymphatic endothelial cells
• Lumina may be filled with proteinaceous fluid,
lymphocytes, or erythrocytes
• Loose connective tissue stroma often with lymphocytic
infiltrate
• Mast cells and hemosiderin deposits in the stroma are
common
• Scattered bundles of smooth muscle in the walls of larger
channels

•
•
• D2-40: membranous stain highlights lymphatic endothelial cells
• Variable expression of CD31, CD34, and FVIII in endothelial cells
1)Hemangioma: endothelial cells are CD34 positive (membranous) and
D2-40 negative
2)Bronchogenic cyst: lined by ciliated columnar epithelium. May have
islands of cartilage, smooth muscle fascicles, and scattered bronchial
glands. Ulceration of epithelial lining can occur, making it diﬃcult to
distinguish from other lesions
3)Pericardial cyst: lined by ﬂat to cuboidal mesothelial cells; strongly
keratin positive

4)Mediastinal Schwannoma (Neurilemmoma)
•
•
Benign neoplasm of peripheral nerve root origin.
most common neurogenic tumor of the
mediastinum, accounting for about 15% of
mediastinal tumors overall
• Most often occurs in the posterior mediastinum,
may be found in the middle and, rarely, the anterior
mediastinum
• Patients are generally young to middle-aged adults;
men and women are affected equally
Gross:well-circumscribed and sometimes
demonstrate a ﬁbrous capsule. The cut surface is
glistening and tan-white with areas of yellow
discoloration

• Histology
• Proliferation of Schwann cells with
wavy or buckled nuclei arranged in a
palisading pattern
• Areas of both hypercellularity and
hypocellularity (classic Antoni A and
Antoni B areas, respectively)
• Verocay bodies (palisading tumor cells
alternating with eosinophilic cellular
processes) may be found.

•
•
S100 protein:diffuse positivity in the
neoplastic cells
EMA stain: capsule
• Neuroﬁbroma: usually not encapsulated.
Histologically, the lesion shows
edematous matrix and some collagen
deposition. No Antoni A or Antoni B areas
are present
• Malignant peripheral nerve sheath
tumor: will demonstrate at least some
mitotic activity; S100 is only weakly
positive

5)Mediastinal Neurofibroma
•
•
•
•
•
Benign neoplasm of peripheral nerve origin
composed of Schwann cells, fibroblasts, and
axons; occurring largely in the posterior
mediastinum
5% of tumors of the mediastinum overall
Gross:
Tumors are extremely well-circumscribed and
often lobulated to spherical. They are
unencapsulated, in contrast to schwannomas
Proliferation of all elements of the nerve,
including Schwann cells, fibroblasts, and axons

•
•
Histology
• Variable amount of wavy, intersecting collagen ﬁbrils,
resembling “shredded carrots” between the dark-staining
buckled nuclei of Schwann cells
• Often, a myxoid change with mucoid material separating
the collagen
• Immunopathology/special stains
• Immunohistochemical test against S100 protein shows
only variable positivity in the neoplastic cells,
• Immunohistochemical stain for neuroﬁlament protein
shows positive staining in the axons
• Schwannoma: usually encapsulated; Antoni A and Antoni
B areas are present, and Verocay bodies may be found
• Malignant peripheral nerve sheath tumor: will
demonstrate at least some mitotic activity, atypia, and
often necrosis

6)Mediastinal Malignant Peripheral Nerve
Sheath Tumor (MPNST)
•
•
•
•
•
A rare malignant neoplasm of peripheral nerve origin occurring largely in the
posterior mediastinum
Men and women are affected equally; most patients are in their third to fifth
decades
About half of all patients with MPNST have neurofibromatosis (NF)
presenting symptoms of pain or nerve deficits
Gross:
• The lesion causes enlargement of the nerve with the cut surface demonstrating a
fairly well-circumscribed fleshy, tan appearance
• Central necrosis and/or hemorrhage is often present
• A pseudocapsule may be present

•
•
•
•
•
•
•
•
•
Histology
Spindle cells are arranged in a fascicular pattern with large, wavy
nuclei
Frequent mitoses and sometimes bizarre cells
Bony or cartilaginous metaplasia may be present
Necrotic areas are surrounded by tumor cells in a palisading pattern
Immunohistochemical test against S100
p53 and CD99 may show positivity
1)Schwannoma: Antoni A and Antoni B areas are present, and Verocay
bodies may be found. Necrosis, atypia, and mitotic activity are not
appreciable
2)Neuroﬁbroma: no atypia, necrosis, or mitoses
3)Other sarcomas should be considered if tumor shows very weak or
no S100 staining

7) Mediastinal Neuroblastoma
•
•
•
•
•
Pediatric embryonal tumor of either benign or malignant behavior
arising from precursor cells of sympathetic nervous system origin
Most common cancer of children younger than 1 year
More often arise from the adrenal medulla (about 40% of cases)
and less commonly along the sympathetic ganglion chain;
thoracic lesions account for about 20% of cases
Some patients have an asymptomatic mass whereas others may
have life-threatening compressive symptoms or widespread
metastatic disease
may present with Horner’s syndrome (unilateral ptosis, miosis,
and anhidrosis), pain, paresthesias, paralysis, or even respiratory
distress as the mass may impinge on nearby thoracic structures

•
•
•
Gross:
Tumors are large and encapsulated; cut section
demonstrates lobulated architecture and a soft to ﬂeshy
consistency. Hemorrhage is often present
Histology
• Proliferation of small, round blue cells with hyperchromatic
nuclei, “salt and pepper” chromatin, and indistinct cytoplasm. Up
to 50% of the stroma may resemble Schwannian stroma, but it
may also be composed of neuropil (Schwannian stroma-poor)
• Divided into differentiating, poorly differentiated, and
undifferentiated subtypes
• Differentiating tumors: ganglionic differentiation of 5% to 50%
of neoplastic cells
• Poorly differentiated tumors: <5% ganglionic differentiation
• Undifferentiated tumors:no ganglionic differentiation and lack
ﬁbrillary network of neuropil

small rosettes with central
neuropil (arrows) are seen.
shows cells with abundant pink
cytoplasm and vesiculated, eccentric,
large nuclei (ganglionic
differentiation)

• Immunopathology/special stains
•positive against antibodies for chromogranin, synaptophysin,
PGP 9.5, and NSE. ALK may be positive in some cases
• CD56 is positive: it is a sensitive but not speciﬁc marker
Main differential diagnosis:
1)Rhabdomyosarcoma: may see rhabdomyoblasts; muscle
markers (e.g., desmin, myogenin) positive.
2)Lymphoma: no “salt and pepper” chromatin; LCA, B cell and T
cell markers positive

8)Mediastinal Ganglioneuroblastoma
•
•
•
Rare pediatric neoplasm of neural crest
origin arising from the sympathetic ganglia;
with differentiation between neuroblastoma
and ganglioneuroma
Female to male ratio is about equal
Gross: encapsulated and have a
homogenous cut surface or demonstrate
areas of hemorrhage and necrosis.

•
•
•
•
•
Histology:
Proliferation of neuroblast-like cells akin to
neuroblastoma but accompanied by a variable
proportion of ganglion cells and intermediate
cells.
Schwannian stroma accounts for >50% of the
tumor
Immunopathology/special stains :Not contributory
• Neuroblastoma: the ganglioneuromatous
component is less than 50%
• Ganglioneuroma: no neuroblastic component;
Schwannian stroma

9)Mediastinal Ganglioneuroma
•
•
•
•
Rare benign neoplasm of neural crest
origin arising from the sympathetic
ganglia
Composed of mature ganglion cells in
a dense Schwannian stroma
Typically affects older children,
adolescents, and young adults
Gross:Tumors are often large, oblong,
and encapsulated. The cut surface is
bulging and yellow-tan with areas of
trabeculation

•
•
•
•
•
Histology
There are ganglion cells (large cells with
eccentric nuclei, vesicular chromatin, a
prominent nucleolus, and amphophilic
cytoplasm) arranged singly or in clusters
Stroma is characteristically Schwannian with a
ﬁbrous appearance and no neuropil
Immunopathology/special stains: Not
contributory
1)Neuroblastoma: will not have many ganglion
cells;
2)Ganglioneuroblastoma: the stroma constitutes >
50% of the tumor in contrast to ganglioneuromas
and demonstrates foci of neuroblastic cells

10)Mediastinal Paraganglioma
•
•
•
•
•
Rare neoplasm of neural crest chromaffin cell origin associated
with the paraganglia of the sympathetic and parasympathetic
nervous systems
Associated with various hereditary syndromes such as multiple
endocrine neoplasia type 2 (MEN2A and MEN2B),
neurofibromatosis type 1, and von Hippel-Lindau disease.
Average age at presentation is 45 years
Men and women are about equally affected
Gross: Tumors are of variable size and show partial encapsulation.
On sectioning, fleshy to firm areas are seen with some hemorrhage
and/or fibrosis and a gray-brown cut surface

•
•
•
Histology
Classically, the tumor shows a “zellballen” architecture of
cells with nests surrounded by delicate, sometimes
abundant, fibrovascular stroma
Nuclei may be round and uniform or show pleomorphism
with dense, sometimes vesicular chromatin
Cytoplasm is granular and eosinophilic to amphophilic
• The tumor cells may stain positively for neuron-specific
enolase, chromogranin, synaptophysin, neurofilaments, and
various peptides such as serotonin and somatostatin
• The surrounding sustentacular (supporting stromal) cells
stain for S100 protein
1)Neuroendocrine carcinoma: will have large cells, brisk
mitotic activity, and positive keratin stains (e.g., CAM5.2)
2)Metastatic carcinoma: may not have zellballen pattern;
cytokeratins will be positive

11)Mediastinal Metastases
•
•
•
•
Mediastinal lymph node metastases from bronchogenic
carcinomas frequently occur (more often from
adenocarcinomas than from squamous-cell carcinomas).
Oesophageal carcinomas
Mediastinal metastases from extrathoracic neoplasms are less
frequent (develop mostly from head and neck, breast and
genitourinary cancers )
Metastases from malignant melanomas, or as the initial
manifestation of malignant mesotheliomas can also occur

Mediastinal lesions

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