Rosai Chapter 12 - Mediastinum Flashcards
Most common causes of superior vena cava syndrome in adults (2)
- Metastatic lung carcinoma
- Malignant lymphoma
Most common causes of superior vena cava syndrome in children (2)
- Malignant lymphoma
- Acute leukemia
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
-Acute mediastinitis
Acute mediastinitis predominantly involves the:
Posterior mediastinum
Typical location of chronic mediastinitis
Anterior mediastinum, in front of the tracheal bifurcation
The organism most commonly identified in those cases of fibrosing mediastinitis for which a specific etiology can be determined
Histoplasma capsulatum (Histoplasmosis)
Characterized by coarse, keloid-like, collagen deposition that can invade the superior vena cava, resulting in SVC syndrome, and can also invade the pulmonary hilum, resulting in complete occlusion of hilar vessels
Fibrosing mediastinitis
Formed by the fusion of multiple disconnected lacunae
Pericardial sac
Congenital cyst that occur along the tracheobronchial tree
Bronchial cyst
Most common location of Bronchial cyst
Posterior to the carina
Probably arise from a persistence, in the wall of the foregut, of vacuoles that form during the solid tube stage of development
Esophageal cysts
Best evidence that a cyst in the location of the esophagus is of esophageal type
Presence of a definite double layer of smooth muscle in the wall
Symptomatic congenital cysts (2)
- Gastric cysts
- Gastroenteric cysts
Asymptomatic congenital cysts (3):
- Bronchial cysts
- Esophageal cysts
- Enteric cysts
Largest lymph vessel in humans
Thoracic duct
Most common pathologic change in mediastinal thyroid glands
Nodular hyperplasia
Major cell types of the thymus (2)
- Epithelial cells
- Lymphocytes
A major cell type of the thymus that is endodermally derived with a possible minor ectodermal contribution
Epithelial cells
A major cell type of the thymus that is bone marrow-derived
Lymphocytes
Normal location of B-cells in the thymus
- Thymic medulla
- Perivascular compartment
Most salient features of Thymic dysplasia (5)
- very small size (less than 5 grams)
- primitive appearing epithelium without segregation into cortical and medullary regions
- presence of tubules and rosettes
- absence of Hassall corpuscles
- almost total absence of lymphocytes
Diseases with accompanied Thymic dysplasia (3)
- X-linked or Autosomal recessive form of (S, A, R)
- Nezelof syndrome
- incomplete form of DiGeorge syndrome (dysplastic and located ectopically)
X-linked or Autosomal recessive forms of these diseases has an accompanied Thymic dysplasia (3)
- Severe combined immunodeficiency
- Ataxia-Telangiectasia
- related chromosomal instability syndromes
Main differential diagnosis of Thymic dysplasia
Acute Thymic involution
Best evidence against the diagnosis of primary thymic dysplasia
identification of well-formed hassall corpuscles in a thymus biopsy
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Developmental origin arise from remnants of the 3rd branchial pouch-derived thymopharyngeal duct
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
usually Small
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
can be seen mostly in the Neck than in the mediastinum
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
This cervical thymic cyst is elongated and can be found anywhere along a line extending from the angle of the mandible to the manubrium sternum
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Wall is thin and translucent
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Lacking inflammation
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Rarely has squamous lining
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Thymic tissue present in the wall
Unilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Acquired process of reactive nature
Multilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Always accompanied by inflammation and fibrosis
Multilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
Often has squamous lining
Multilocular
UNILOCULAR / MULTILOCULAR
Thymic cysts:
An acquired cystic dilation of medullary duct epithelium-derived structures, induced by an inflammatory reaction of the thymic parenchyma
Multilocular
Most commonly associated tumors with multilocular thymic cyst (2)
- Hodgkin lymphoma
- Seminoma
Ectopic thymic tissue in the skin of the neck
Branchio-oculo-facial syndrome
A term that should be restricted to neoplasms of thymic epithelial cells, independently of the presence of number of lymphocytes
Thymoma
Usual location of thymoma
Anterosuperior mediastinum
A patient with myasthenia is more likely to have a thymoma if (2):
- Male; and/or
- developing symptoms after the age of 50
Most accurate way to predict the likelihood of myasthenia in a patient with Thymoma
find Lymphoid follicles in the adjacent non-neoplastic thymic tissue, or, exceptionally, even in the thymoma itself
Features suggestive of organoid differentiation in Thymoma (5):
- perivascular spaces containing lymphocytes, proteinaceous fluid, RBCs, foamy macrophages, or fibrous tissue
- Rosettes without central lumens
- Glandlike formations within the tumor or, more often, in the tumor capsule
- True glandular structures
- Whorls suggestive of abortive Hassall corpuscle formation
Thymoma vs. Thymic carcinoid:
rosette-like structures with well-defined lumens
Thymic carcinoid
Important clue to the diagnosis of lymphocyte-rich (type B1) thymoma
find round, lighter foci of medullary differentiation
Most frequent aberration found in thymoma are located on:
chromosome 6 (6q25.2)
IHC with highest sensitivity for thymic carcinoma (2)
- MUC-1
- GLUT-1
IHC showing greater specificity in separating carcinoma from thymoma
CEA
IHCs that stain strongly with thymic carcinoma than thymoma (3)
- p53
- BCL-2
- p16
Most common recurrent mutations, occurring in about 30% of cases of thymic carcinoma
TP53
Main differential diagnosis of Basaloid carcinoma of Thymus
Thymic carcinoma with adenoid cystic carcinoma-like features
Most common histologic appearance of NUT (midline) carcinoma of the Thymus
a highly undifferentiated carcinoma with variably conspicuous foci of abrupt squamous differentiation
Two important factors for the new nomenclature of thymic tumors:
- Thymus is unique, can be viewed as two different organs
- Presence, as an expression of differentiation, of a non-neoplastic lymphocytic component in the tumors composed of functional thymic tissue
“Thymus is unique, can be viewed as two different organs”
-The active, functional gland of the (2)
- Fetus
- Infant
“Thymus is unique, can be viewed as two different organs”
-the inactive, “post mature” structure of:
-Adult life
Better differentiated tumors of thymus (2)
- Lymphocyte-rich
- predominantly cortical types
Two major types of thymoma are based on (2):
- cytological characteristics of neoplastic epithelial cells
- relative contribution of non-neoplastic immature T-lymphocytes typical of normal thymic cortex
Subdivision of type B thymomas is based on (2):
- proportional increase (in relation to the lymphocytes) of the neoplastic epithelial cells
- emergence of atypia of the neoplastic epithelial cells
Most reproducible features for identifying this extremely rare variant for which the term atypical type A thymoma has been proposed (2):
- Mitotic activity (more than or equal to 4/10 hpf)
- Necrosis
Only feature that predicted for higher tumor stage in a large retrospective cohort of type A and AB thymomas
necrosis
type AB / type B1 Thymoma:
-spindled / oval morphology
type AB
type AB / type B1 Thymoma:
-immunoreactivity for CD20 in epithelial tumor cells within lymphocyte-rich areas
type AB
type AB / type B1 Thymoma:
-presence of Hassall corpuscles
type B1
type B1 / type B2 Thymoma:
-absence of epithelial cell clusters
type B1
type B1 / type B2 Thymoma:
-presence of medullary islands
type B1
Micronodular / type AB thymoma:
-the lymphocytes are composed mainly of B-cells and mature T-cells
Micronodular thymoma
Micronodular / type AB thymoma:
-Negative staining for CD20
Micronodular Thymoma
Most important criterion for the cytologic recognition of a thymoma
-identification of a distinct population of epithelial cells admixed with lymphocytes, preferably confirmed by a positive immunostain for keratin
Primary treatment of Thymoma (2)
- en-bloc surgical excision
- complete thymectomy
Remains the single most important prognostic determinant, regardless of the system used, and applies equally to thymomas and thymic carcinoma
Stage
Directly related to the tumor stage and is also an important prognostic parameter
Completeness of excision
Main differential diagnosis for SETTLE
Synovial Sarcoma
SETTLE should be favored over Synovial sarcoma in the presence of (5):
- Stromal hyalinization
- Lower overall grade
- presence of glomeruloid glandular structures
- absence of intraglandular necrotic debris
- diffuse expression of HMW keratin
More significant predictors of outcome of thymic neuroendocrine tumors (3):
- Stage
- Resectability
- presence of paraneoplastic endocrinopathies
The presence of these features favor a diagnosis of Seminoma vs other thymic neoplasms (5):
- fibrous septa infiltrated by lymphocytes and plasma cells
- epithelioid granulomas
- numerous germinal centers
- large amounts of cytoplasmic glycogen
- an irregular, skein-like nucleolus
Accounts for the majority of germ cell tumors in children
Mature cystic teratoma
Second most common mediastinal germ cell tumor in children less than 15 years of age
Yolk sac tumor (Endodermal sinus tumor)
Only other type of mediastinal germ cell tumor showing trophoblastic differentiation reported in a 14-year-old boy 2 years after resection of a teratoma
Placental site trophoblastic tumor
Most common primary neoplasm of the middle portion of the mediastinum
Malignant Lymphoma
Older term for Lymphoblastic Lymphoma
Convoluted cell lymphoma
Other reasons for the frequent misdiagnosis of Primary mediastinal (Thymic) Large B-cell Lymphoma (5):
- perivascular collections of Lymphocytes (which may be misinterpreted as the perivascular spaces of thymoma)
- artifactual clearing of the cytoplasm induced by formalin fixation (not present in B5 or Zenker’s fixed material) simulating seminoma
- presence of a large number of reactive T-cells
- rosette-like formations mimicking Thymoma and Thymic carcinoma
- Entrapment of thymic epithelium
A diagnosis of large cell lymphoma should be favored in the presence of (4):
- 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
- the fact that the fibrosis is manifested not only in the form of wide hyaline bands but also as a fine network that entraps individual cells
an integral membrane protein located in glycolipid-enriched membrane microdomains called lipid rafts
MAL
A distinct molecular marker for primary mediastinal (Thymic) large B-cell lymphoma
MAL
Primary diseases associated with Extramedullary hematopoiesis in most patients
- Hereditary spherocytosis
- Thalassemia
Two major categories of Neurogenic Tumors (2):
- tumors of the Sympathetic Nervous System
- tumors of Peripheral Nerve Sheath
Anterior boundary of the mediastinum
Sternum
Posterior boundary of the mediastinum
Spine
Superior boundary of the mediastinum
Thoracic inlet
Inferior boundary of the mediastinum
Diaphragm
Most common lesions in the Superior Mediastinum (4)
- Thymoma and Thymic cyst
- Malignant Lymphoma
- Thyroid lesions
- Parathyroid adenoma
Most common lesions in the Middle Mediastinum (3)
- Pericardial cyst
- Bronchial cyst
- Malignant Lymphoma
Most common locations of Thymoma and Thymic cyst in the mediastinum (2)
- Superior
- Anterior
Most common locations of Malignant Lymphoma in the mediastinum (3)
- Superior
- Anterior
- Middle
Most common locations of Thyroid lesions in the mediastinum (2)
- Superior
- Anterior
Most common locations of Parathyroid adenoma in the mediastinum (2)
- Superior
- Anterior
Most common locations of Paraganglioma in the mediastinum (2)
- Anterior
- Posterior
Failure of one of the lacunar cavities to merge with the others results in the development of a:
Pericardial (coelomic) cyst
Usual location of Pericardial (coelomic) cyst
Right cardiophrenic angle
Usual lining of Bronchial cyst
Pseudostratified ciliated respiratory epithelium / ciliated columnar epithelium
Congenital cysts that are usually located in the posterior mediastinum in a paravertebral location, attached to the wall of the esophagus or even embedded within the muscle layer of this organ (2)
- Gastric cyst
- Enteric cyst
Generic term that has been proposed for a congenital thymic alteration thought to be expression of a failure and/or arrest in the development of the organ
Thymic dysplasia
Main differential of thymic dysplasia that is characterized by marked lymphocytic depletion accompanied by preservation of the lobular architecture and of Hassall corpuscles
Acute Thymic Involution
Microscopic features of thymic involution in HIV infection (4):
- effacement of the corticomedullary junction
- marked lymphocytic depletion
- variable degrees of plasma cell infiltration and fibrosis
- inconspicuous Hassall corpuscles
