pathology of mediastinal tumors

1. Mediastinal tumors
Presenter: Dr Rashmi Budha

2. layout
• Introduction and brief anatomy
• Inflammatory diseases
• Cysts(other than thymus)
• Thymus
• Malignant lymphoma
• Neurogenic tumors
• Tumors of paraganglia
• Mesenchymal tumors
• Metastatic tumors

3. Anatomy
The mediastinum is the
space between the pleural
cavities
– Anteriorly: Sternum
– Posteriorly: Vertebral
column
– Superiorly: Thoracic inlet
– Inferiorly: Diaphragm

4. Compartments:
– Anterior
– Superior
– Middle
– Posterior

5. Lesions of the mediastinum

6. Inflammatory Diseases
ACUTE MEDIASTINITIS:
• It is usually the result of traumatic perforation
of the esophagus, or descent of infection from
within the neck through the “danger space”
anterior to the prevertebral fascia.
• In both cases, it involves predominantly the
posterior portion of the mediastinum.
• Superior vena cava syndrome is an uncommon
complication of acute mediastinitis.

7. CHRONIC MEDIASTINITIS:
• It can produce compression of mediastinal
structures and simulate a malignant process.
• The typical location is the anterior mediastinum,
in front of the tracheal bifurcation.
• Microscopy:
– one may find necrotizing granulomatous infection
(granulomatous mediastinitis), fibrosis (fibrosing
mediastinitis), or a combination of both.
– Histoplasma capsulatum (histoplasmosis) is the
organism most commonly identified in those cases of
fibrosing mediastinitis.

8. Fibrosing mediastinitis:
• It is characterized by coarse,
keloid-like, collagen
deposition that can invade
the superior vena cava,
resulting in superior vena
cava syndrome, and can also
invade the pulmonary
hilum, resulting in complete
occlusion of hilar vessels.
• The latter may result in
complete obstruction of
venous outflow, resulting in
a peculiar pattern of
microscopic subpleural and
paraseptal infarction
(“venous infarcts”).

9. • The fibrosis is accompanied by a variable but
generally mild, patchy infiltrate of
lymphocytes and plasma cells.
• In selected cases a lymphoplasmacytic
infiltrate is accompanied by other changes
characteristic of IgG4-related disease.
• IgG4-related disease: Storiform fibrosis,
obliterative phlebitis/arteritis, and an increase
in IgG4-positive plasma cells above proposed
diagnostic threshold.

10. Fibrosing Mediastinitis. Dense ropey collagen bundles
surround nerves and vessels

11. Causes of Fibrosing Mediastinitis:
A group of fibrosing (sclerosing)
inflammatory conditions such as
• Pulmonary hyalinizing granuloma
• Retroperitoneal fibrosis
• Sclerosing cholangitis
• Riedel struma
• Inflammatory pseudotumor of the orbit

12. Cysts(other than thymic)
• Pericardial (Coelomic) Cysts
• Foregut cysts
• Other cysts
–Cysts arising from thoracic duct
–From Mullerian origin
–Adenomatoid tumor

13. Thyroid lesions
• Thyroid tumors and tumorlike conditions of
several types can present as superior
mediastinal masses.
• The most common pathologic change in
mediastinal thyroid glands is nodular
hyperplasia, which can reach huge proportions
and cause compression symptoms.

14. • From a pathogenetic
standpoint, the nodular
hyperplasia in most
instances probably does
not arise from ectopic
thyroid tissue but rather
from cervical thyroid that
has been pulled down
either into the anterior
prevascular compartment
or the retrotracheal
compartment(so-called
posterior descending
goiter) by the nodular
enlargement.

15. Parathyroid lesions
• Parathyroid tumors and tumorlike conditions
can also occur in the mediastinum, a not
surprising event in view of the embryologic
origin of the parathyroid glands and their
intimate relationship with the thymus.
• About 7% of parathyroid adenomas are found
in the superior mediastinum, and most of them
can be excised through a suprasternal incision.

16. • Because of their location, these adenomas can grow to a
much larger size than their equivalents in the neck.
• Like their cervical counterparts, mediastinal parathyroid
adenomas can be accompanied by a heavy lymphocytic
infiltrate.
• Mediastinal parathyroid carcinomas have also been
reported, some of them being nonfunctioning.
• Parathyroid cysts of the mediastinum are usually located
in the anterosuperior compartment, and are often
functioning.

17. Thymus
• The thymus is a lobulated organ covered by a capsule and
divided into cortical and medullary portions, the cortex
being further subdivided into a subcapsular (outer) and a
deep region.
• The thymus undergoes normal involution after puberty,
although it never disappears completely.
• Islands of thymic tissue are consistently found on
microscopic examination of the prepericardial fat and
sometimes also in the retrocarinal fat.

18. Primary Immunodeficiencies
Thymic dysplasia:
• It is the generic term that has been proposed for a
congenital thymic alteration thought to be the expression
of a failure and/or arrest in the development of the organ.
• Salient features:
– Very small size (less than 5 g)
– Primitive-appearing epithelium without segregation
into cortical and medullary regions
– Presence of tubules and rosettes
– Absence of hassall corpuscles
– Almost total absence of lymphocytes

19. Associated Diseases With Thymic Dysplasia:
• X-linked Or Autosomal Recessive Form Of
– Severe Combined Immunodeficiency
– Ataxia–telangiectasia
• Related Chromosomal Instability Syndromes
• Nezelof Syndrome
• The Incomplete Form Of Digeorge Syndrome

20. Differential diagnosis of thymic dysplasia:
• Acute thymic involution:
– Due to stress and superimposed infections
– Characterized by marked lymphocytic depletion
– Preservation of the lobular architecture and of hassall
corpuscles
– the size of the vessels is large for the size of the lobules
– A scattering of inflammatory cells is present in the
interlobular and perilobular tissue, sometimes with a
marked predominance of plasma cells.
– This acute involution process can proceed at a rapid rate,
leading to almost complete lymphocytic depletion of the
cortex within 1 week.

21. Thymic cysts
• Thymic cysts can be divided into two distinct types.
– Unilocular thymic cyst
– Multilocular thymic cyst
Unilocular thymic cyst:
– Developmental origin
– Arises from remnants of third branchial pouch-
derived thymopharyngeal duct
– Size- small; Site- Neck>Mediastinum

22. Gross:
• Thin walled & contain only sero us fluid
Microscopy:
• The wall is thin and translucent
• Inflammation is usually lacking
• The epithelial lining is flattened, cuboidal,
columnar, or (rarely) squamous.
• Thymic tissue is present in the wall, some of it
connecting with the lining epithelium.

23. Multilocular thymic cyst:
– Result from acquired cystic dilatation of medullary
duct epithelium- derived structures
– induced by inflammatory reaction of thymic
parenchyma
– Infection – congenital syphilis, HIV
– Prior thoracotomy
– Neoplasms like: Thymoma, Germ cell tumor,
Lymphoma

24. • Gross:
– Pericystic fibrous adhesion and thick walled filled
with cheesy, turbid or haemmorhagic material

25. • Microscopy:
– Proliferative epithelial component
– multiple layers of squamous cells seen or admixture of
simple cuboidal, simple columnar, multilayered cuboidal
and columnar, or micropapillary glandular epithelium
– Small area of parathyroid areas present
– Salivary glandular epithelium may be present
– Hassals corpuscules & remanant thymic tissue can be seen
– Never – specialized mesenchyme (cartilage, smooth
muscle)
– Abundant lymphocytes, granulation tissue, hemorrhage and
cholesterol granulomas are seen in the fibrous wall and cyst
cavities of multilocular thymic cysts

26. Other non-neoplastic diseases
1. ECTOPIC THYMUS:
• With an entirely normal microscopic appearance
can present as a mass in the neck or pleural
surface.
• The maldescended thymic tissue in the neck can
be unilateral or bilateral.
• It is often located adjacent to the thyroid gland
and usually associated with a parathyroid gland.
• Ectopic thymic tissue in the skin of the neck can
be a clue to the branchio-oculo-facial syndrome.

27. 2. ECTOPIC TISSUES:
• Sometimes found in a normally located thymus
include parathyroid gland and sebaceous
glands.
3. ACUTE THYMIC INVOLUTION
4. DIFFUSE THYMIC FIBROSIS
• It is occasionally seen in the absence of
another primary thymic lesion or features of
IgG4-related disease.

28. 5. TRUE THYMIC HYPERPLASIA:
• It is defined as thymic enlargement beyond the
upper limits of normal for the age but
accompanied by a microscopically normal
gland.
• Often described in infants and children
• Also found in adults secondary to therapeutic
manipulation

29. 6. THYMIC FOLLICULAR HYPERPLASIA:
• It is defined as the presence of more than an occasional
lymphoid follicle in the thymus independent of the size of
the gland.
• These follicles are of secondary type, with germinal
center formation, and are largely composed of B
lymphocytes.
• A few germinal centers also may be found in the
apparently normal thymus, especially during infancy and
childhood; therefore only their presence in a substantial
number in adult patients can be viewed as a distinctly
abnormal finding.

30. 7. LANGERHANS CELL HISTIOCYTOSIS:
• It can present as a thymic mass, either alone
or with involvement of other sites.
• The microscopic appearance is characteristic,
and the overall prognosis is excellent.
Exceptionally, it is seen in association with
myasthenia gravis.
• It may also coexist with multilocular thymic
cyst.

31. 8. EOSINOPHILIC GRANULOMATOSIS
WITH POLYANGIITIS (CHURG–
STRAUSS DISEASE)
9. CASTLEMAN DISEASE (GIANT
LYMPH NODE HYPERPLASIA)

32. thYMOMA
• Thymoma is a term that should be restricted to
neoplasms of thymic epithelial cells, independently of
the presence or number of lymphocytes.
• Age of onset- Adults>Children(rarely)
• Location- Antero-superior mediastinum
• Other sites- Neck, Thyroid gland, Pericardial cavity,
Cardiac myxoma, Pulmonary hilum, Lung parenchyma,
Pleura.

33. Gross:
• Well encapsulated
• the typical thymoma is largely or entirely solid
• Yellowish-gray and separated into lobules by
connective tissue septa
• Focal areas of necrosis, hemorrhagic changes
and Cystic degeneration seen

34. MICROSCOPY:
• Majority of thymomas are composed of a mixture of
neoplastic epithelial cells and non-neoplastic lymphocytes
• The epithelial cells may have a round–polygonal
(“plump”), stellate or spindle/oval shape.
• Nuclei- vesicular and of smooth contour
• Nucleolus- conspicuous, particularly when the nuclei are
round or polygonal
• Lymphocytes- appear mature (inactive) or show varying
degrees of activation manifested by a larger nuclear size,
open chromatin pattern, visible nucleolus, identifiable
cytoplasmic rim, and mitotic activity

35. Classification of thymomas

36. cytology
• The most important criterion for the cytologic
recognition of a thymoma is the identification of a
distinct population of epithelial cells admixed
with lymphocytes, preferably confirmed by a
positive immunostain for keratin.
• Limitations of the procedure include the difficulty
in separating the various subtypes of type B
thymoma (not very important clinically) and the
inability to detect invasion (a critical prognostic
factor).

38. Cervical Tumors of Thymicor Related
Branchial PouchDerivation
• As mentioned previously, ectopic thymic tissue
and unilocular thymic cysts can be found in the
lateral aspects of the neck as a result of a
malformation related to the third or possibly
fourth branchial pouch.
• In addition, the following neoplasms can
develop in a similar location and on a
presumably similar histogenetic basis.

40. Neuroendocrine tumors
• The thymus is the site of several types of
neuroendocrine neoplasm, many of which
were previously misinterpreted as variants of
thymoma.

41. TYPICALAND ATYPICAL CARCINOID
TUMORS:
• Malignant neoplasms
• Gross:
– Solid, usually well circumscribed but not
encapsulated
– Lacks the distinct lobulations of thymoma
– Highly vascularized and may be frankly
hemorrhagic, including ectatic blood-filled spaces

42. • Microscopy:
• thymic carcinoid tumor exhibits ribbon and
• festoon formation, rosette-like glands with
central lumina, “balls”
• or nests of cells, and a delicate highly vascular
stroma
• The tumor cells have a more granular
cytoplasm than
• those of thymoma, the nuclear chromatin is
slightly coarser, and
• mitotic activity is frequent.

43. • Immunohistochemically, there is reactivity for
keratin, chromogranin, synaptophysin,
neuron-specific enolase, and other general
endocrine markers.
• About a third stain for PAX8, while staining for
TTF-1 is rare, a finding sometimes helpful in
separating primary thymic neuroendocrine
tumors from metastatic pulmonary lesions

44. Morphologic variants of thymic carcinoid tumor:
• Lesions with spindle cell pattern, a prominent
oncocytic component and melanin pigment
• Tumors containing amyloid and calcitonin
• Carcinoid tumors accompanied by a high-
grade sarcomatoid component

45. Stromal and Other Tumors
I THYMOLIPOMA:
• It is an encapsulated benign thymic lesion that can attain a
huge size and can simulate radiographically cardiomegaly or
pulmonary sequestration.
• Grossly, the lesion has the appearance of a lipoma except for
the focal presence of whitish solid areas.
• Microscopically, there is an admixture in various proportions
of mature adipose tissue and unremarkable thymic tissue.
• Isolated case reports have described associated myoid cells,
fibroconnective tissue (“thymofibrolipomas”) or vessels
(“thymohemangiolipoma”), sebaceous differentiation, and
even thymoma and thymic carcinoma.

46. II THYMIC STROMAL SARCOMAS:
• Low-grade malignant mesenchymal tumors
seemingly arising from the thymic stroma.
• Microscopy:
• Well-differentiated liposarcoma/atypical
lipomatous tumor is the predominant
component (“thymoliposarcoma”)
III KAPOSIFORM HEMANGIOENDOTHELIOMA
IV MALIGNANT MELANOMA

47. Germcell tumors
• Germ cell tumors account for approximately
20% of the mediastinal tumors and cysts.
• Histogenesis: a primary origin from
extragonadal germ cells.

48. GERMINOMA:
• Cause: Chromosome 12p abnormalities, most
commonly 12p amplification
• Morphology:
– fibrous septa infiltrated by lymphocytes and
plasma cells
– Epithelioid granulomas
– numerous germinal centers
– large amounts of cytoplasmic glycogen
– an irregular, skein-like nucleolus
• IHC: staining for OCT3/4 and SALL4

49. MATURE CYSTIC TERATOMA:
• One of the most common types of mediastinal
germ cell neoplasms in adults and accounts for
the majority of mediastinal germ cell tumors in
children.
• Gross:
– Large size and has a distinct, sharply delineated
wall that often becomes calcified.
– The cut surface is predominantly cystic.
– Adherence to surrounding structures is common

50. • Microscopy:
–The cysts are lined by stratified squamous
epithelium and contain sebaceous glands
and hair follicles.
–Other common components are neural
tissue, gastrointestinal tract, cartilage, and
respiratory structures.
–Pancreatic tissue is particularly frequent in
this location; it may be accompanied by islet
cell elements and result in hypoglycemia.

51. IMMATURE TERATOMA IS DEFINED:
• Contains immature epithelial, mesenchymal, or neural
elements without a component of embryonal carcinoma.
EMBRYONAL CARCINOMA:
• It is an invasive, highly necrotic neoplasm.
• Its microscopic appearance is, by definition, poorly
differentiated.
YOLK SAC TUMOR:
• Mediastinal yolk sac tumors may have prominent spindle
cell features
• contain a hepatoid component or be accompanied by
secondary multilocular cystic changes in the adjacent
non-neoplastic thymus.

52. TERATOCARCINOMA:
• It is an older term used to describe mixed germ cell
tumors characterized by a combination of embryonal
carcinoma and teratoma (mature and/or immature).
CHORIOCARCINOMA OF THE MEDIASTINUM:
• It occurs, for the most part, in the third decade of life.
• It is often associated with gynecomastia and
invariably accompanied by elevated serum levels of
human chorionic gonadotropin (hCG).

53. Malignant lymphoma
• Malignant lymphoma can present as an
anterior, superior, or middle mediastinal mass,
in this order of frequency.
• It represents the most common primary
neoplasm of the middle portion of the
mediastinum.

54. CLASSICAL HODGKIN LYMPHOMA:
• Mediastinal Hodgkin lymphoma can involve
primarily the thymus, mediastinal lymph
nodes, or both.
• Most patients are young adults, and there is a
predilection for females.
• Primary Hodgkin lymphoma of the
mediastinum is nearly always of the nodular
sclerosis subtype.

55. Gross:
• Sharply outlined and sometimes surrounded by a thick capsule
• The nodules may be multiple and residual thymic tissue is
usually identified.
• The consistency is hard, and the cut surface is vaguely or
distinctly nodular.

56. Microscopy:
• 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 intimate association with epithelial-
lined cysts, hassall corpuscles, and isolated thymic epithelial
cells.
• Immunohistochemical stains for CD15 or CD30 and keratin
sharply delineate the lymphoid neoplastic and epithelial
reactive components, respectively.

57. Lymphoblastic Lymphoma
• Lymphoblastic lymphoma occurs primarily in children and
young adults in whom it has a particular predilection for the
thymic region.
• It is usually of immature (precursor) T-cell type, but a certain
degree of phenotypic heterogeneity occurs including cases of
precursor B-cell and natural killer cell lineage.
• The disease is usually restricted to the supradiaphragmatic
region, with frequent involvement of cervical, supraclavicular,
and axillary nodes but sparing of peripheral blood or bone
marrow.

58. Gross:
• The tumor is generally solid, soft, and non-encapsulated.
Microscopy:
• The infiltrate involves the thymic parenchyma and can be
confused with a lymphocyte-rich (type B1) thymoma.
• However, the 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.

59. • Fibrosis and formation of multilocular thymic
cysts can be seen in thymic lymphoblastic
lymphoma.
• Necrosis can be very extensive, whether
spontaneous or induced by radiation or
steroid therapy, to the extent that the entire
biopsy may show only necrotic lymphoma
tissue.

60. Primary Mediastinal (Thymic) Large
B-Cell Lymphoma
• presents as bulky locally invasive anterior
mediastinal disease without bone marrow
involvement and nodal disease limited to
contiguous cervical and intrathoracic sites.
• Most patients are young adult females.
• The tumor has grossly 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.

61. • Microscopy:
• presence of wide bands of fibrosis, which results in
compartmentalization of the tumor cells.
• Perivascular collections of lymphocytes
• Presence of a large number of reactive T cells; rosette-
like formations
• and entrapment of thymic epithelium
• diagnosis of large cell lymphoma should be favored in
the
• tumor cells with large, vesicular, irregularly shaped
nuclei (indented, kidney-shaped, polylobated)
• entrapment of intrathymic and perithymic fat
• invasion of blood vessel wall, pleura, or lung

62. • Immunohistochemistry:
• Expression of
– CD45
– CD20
– CD30
– CD23
– BCL6
– CD10
– MAL

63. Marginal Zone B-Cell Lymphoma
• F>M
• Microscopically, the tumors are predominantly
composed of small lymphocytes with a
variable admixture of monocytoid cells and
plasma cells.
• Prominent lymphoepithelial lesions are
present, and there may be cystic formations.

64. Other HematolymphoidConditions
• Composite lymphomas of various types
• Anaplastic large cell lymphoma
• Myeloid sarcoma
• Plasmacytoma
• Castleman disease
• Extramedullary hematopoiesis
• Follicular dendritic cell tumor

65. Neurogenic tumors
• Neurogenic tumors make up a high proportion of the
posterior mediastinal neoplasms, in both adults and
children, but they can also occur in other mediastinal
compartments.
• The two major categories are
– Tumors of the sympathetic nervous system
– Tumors of peripheral nerve sheath.

66. NEUROBLASTOMA:
• It is rather unusual in this location, appearing as
an infiltrative mass with areas of necrosis and
calcification, usually high in the posterior
mediastinum and seen almost exclusively in
children, although notable exceptions occur.
GANGLIONEUROBLASTOMA:
• It is a tumor that has an intermediate degree of
differentiation and that is related to differentiating
neuroblastoma and immature ganglioneuroma.
• Gross:
– Well-circumscribed
– sometimes surrounded by a well-formed capsule

67. • GANGLIONEUROMA: