| What is adrenal gland? | Paired exocrine organs consisting of two regions cortex and medulla, differ in development, structure and function.
Cortex is of three layers of distinct cell types, beneath the capsule (zona glomerulosa (mineralocorticoids)
zona reticularis abuts the medulla (Sex steroids).
Zona fasciculata (75% of adrenal gland, glucocorticoids)
Adrenal medulla composed of chromaffin cells synthesize and secrete catecholamines (EPI 70% NE) |
| What is the paraganglion system? | The adrenal medulla is embryologically, functionally, and structurally distinct from the adrenal cortex.
It is populated by cells derived from the neural crest (chromaffin cells) and their supporting (sustentacular) cells.
The chromaffin cells, synthesize and secrete catecholamines in response to signals from preganglionic nerve fibers in the sympathetic nervous system.
Similar collections of cells are distributed throughout the body in the extraadrenal paraganglion system.
The most important diseases of the adrenal medulla are neoplasms: Neuronal neoplasms (neuroblastomas and more mature ganglion cell tumors) and neoplasms composed of chromaffin cells (pheochromocytomas). |
| What are adrenal cortical lesions? | Morphological modifications (Heterotopia, Cortical Nodule, Congenital Hyperplasia, Acquired Hyperplasia, Tumors)
Adrenocortical Hyperfunction (Hyperadrenalism)
Adrenal Insufficiency |
| What is adrenal cortical heterotopia? | Encountered in
Rtropéritonéal fat
Kidneys
The celiac plexus
Along the spermatic and ovarian veins
The testes and the tail of the epididymis
The broad ligament
The ovary
Hernary sacs
The appendicular meso
Liver
Lung
Intra dural space
Brain
may undergo hyperplasia/tumor |
| What is adrenal cortical nodule? | Micronodule made of normal adrenal cortex in the adjacent capsule or fat.
Round shped, Non-encapsulated
Often multiple
Very small size (up to 3mm)
May increase in number with age
No clinical significance
To be distinguished from nodular hyperplasia and adenomas |
| What is adrenal cortical congenital hyperplasia? | Congenital metabolic dysfonction
Autosomal recessive
F = H
Responsible for the majority of androgenital syndromes in the first year of life
Clinically: in 95% pure virilizing syndrome with in 30% of electrolyte disturbances
The changes in CS are identical regardless of the enzymatic defect: diffuse hyperplasia of the RZ |
| What is adrenal cortical acquired hyperplasia? | Always bilateral
Diffuse (by hyperproduction of ACTH by the pituitary gland or by a tumor) or nodular
Weight> 6g (without fat)
Microscopy: thickening of Zona fasciculata and reticularis
Nuclear pleomorphism with a few large hyperchromic nuclei may exist |
| What is a particular form of adrenal cortical acquired hyperplasia? | Primary nodular pigmented CS Hyperplasia
Cushing's disease + pigmented skin lesions +
cardiac myxoma + pituitary adenoma with GH
+ psammomatous schwannoma + Multiple AF
(F) / T. Sertoli cells (H)
Multiple cortical pigmented nodules
Atrophy of the cortex between the nodules
Nodules are made of eosinophils, low in lipids (like those in ZR) |
| What are adrenal cortical tumors? | Primary tumors can be benign/malignant, difficult to differentiate, no morphological difference whether functional or not
Adenomas more common associated with hyperaldosteronism and Cushing's syndrome.
Virilization more common in carcinomas
Adult pt (50 yrs for Ca), F=M, maybe incidentaloma or due to signs of secretory dysfunction, if extensive necrosis occurs pt gets fever, palpable masses almost always malignant |
| What is adrenal cortical adenoma? | Macroscopy:
Patients are Often Not symptomatic Well-circumscribed tumor. Average size 2.5cm (rarely 5cm or 50g). Protrud on the surface of the adrenal gland. May or may not be functional: if it is functional it is associated with atrophy of the residual and controlateral cortex, Orange-yellow cut / homogeneous aspect
Microscopy :
Cells identical to normal CS cells
Cells can be eosinophilic or clear vacuolated cytoplasm (ZF and / or ZR)
Nuclear pleomorphism (endocrine atypia)
Exceptional or absent mitosis |
| What is adrenal cortical carcinoma? | Macroscopy (rare neoplasm, at any age, 2 rare inherited (Li-Fraumeni syndrome and Beckwith-Weidmann), most cases large invasive lesions efface native adrenal gland, on cut surface typically variegated poorly demarcated lesions with areas of necrosis, hemorrhage and cystic change)
Microscopy (well-differentiated cells resemble adenoma, or bizzarre pleiomorphic cells almost like undifferentiated carcinoma metastasis to adrenal, invade adrenal vein, vena cava and lymphatics, regional lymph nodes and periaortic ones, distant hematogenous spread to lungs and other organs, bone metastasis unusual.
Median survival 2 years, metastatic ones are more frequent than primary ones. |
| What are other adrenal cortical tumors than adenoma and carcinoma? | Cysts (rare), myelolipoma (adipose, hematopoietic, small size), lipoadenoma, Corticomedullary tumor |
| What is acute adrenocortical insufficiency? | Massive adrenal hemorrhage may destroy enough of the adrenal cortex to cause acute adrenocortical insufficiency.
This condition may occur in patients maintained on anticoagulanttherapy, in postoperative patients who develop disseminated intravascular coagulation, during pregnancy, and in patients suffering from overwhelming sepsis;
Waterhouse- Friderichsen Syndrome
Neisseria meningitidis +++; but also pseudomonas, pneumococci, haemophilus influenzae.
Rapidly progressive Hypotension
IVDC with purpura
Massive adrenal hemorrhage .
Any age preferentially in children |
| What is chronic adrenocortical insufficiency/Addison's disease? | an uncommon disorder resulting from progressive destruction of the adrenal cortex.
More than 90% of all cases are attributable to one of four disorders:
autoimmune adrenalitis,
tuberculosis,
acquired immune deficiency syndrome (AIDS),
metastatic cancer
Symptomes appear once 90% of AC tissue is destroyed |
| What is autoimmune adrenilitis? | Addison's disease, Accounts for 60% to 70% of cases
is by far in developed countries.
there is autoimmune destruction of steroidproducing cells, and autoantibodies to several key steroidogenic enzymes have been detected in affected patients.
Inflammatory infiltrate in the cortex
In addition to loss of all but a subcapsular rim of cortical cells, there is an extensive mononuclear cellinfiltrate. |
| What are adrenal medullary diseases? | The major pathology of AM is tumor in nature
Arising from either chromaffin cells (Pheo) or neuronal cells (neuroblastoma |
| What is pheochromocytoma? | Rare neoplasms composed of chromaffin cells, which, like their non-neoplastic counterparts, synthesize and release catecholamines.
These tumors are of special importance because although uncommon, they (like aldosterone-secreting adenomas) give rise to a surgically correctable form of HT.
0.2 à 0.3 % Of patient with HT have phéochromocytoma |
| What is the rule of 10s of pheochromocytoma? | One “traditional” 10% rule that has since been modified
pertains to familial cases. It is now recognized that as
many as 25% of persons with pheochromocytomas and paragangliomas harbor a germ line mutation in one of at leastsix known genes,
10% are extra adrenal (organ of Zuckerkandl and the
carotid body), where they usually are called paragangliomas
10% are malignant
10% familial
10% bilateral (may rise to 50%) |
| How is macroscopy of pheochromocytoma? | Pheochromocytomas range in size from small, circumscribe lesions confined to the adrenal to large, hemorrhagic masses weighing several kilograms (100g to 4 Kg).
On cut surface, smaller pheochromocytomas are yellow-tan, well-defined lesions that compress the adjacent adrenal
Larger lesions tend to be hemorrhagic, necrotic, and cystic and typically efface the adrenal gland.
Incubation of the fresh tissue with potassium dichromate solutions turns the tumor dark brown |
| How is microscopy of pheochomocytoma? | pheochromocytomas are composed of polygonal to spindle-shaped chromaffin cells and their supporting cells, compartmentalized into small nests, or Zellballen, by a rich vascular
The cytoplasm of the neoplastic cells often has a finely granular appearance, highlighted by a variety of silver stains, because of the presence of granules containing catecholamines.
Electron microscopy reveals variable numbers electron-dense granules, representing catecholamines and sometimes other peptides.
They show positivity to NE markers (chromogranin A, Synaptophysine, CD56) |
| How is definitve dx by microscopy of pheochromocytoma? | The nuclei of the neoplastic cells are often quite pleomorphic.
Both capsular and vascular invasion may be encountered in benign lesions, and the mere presence of mitotic figures does not imply malignancy.
Therefore, the definitive diagnosis of malignancy in pheochromocytomas is based exclusively on the presence of metastases.
These may involve regional lymph nodes as well as more distant sites including liver, lung, and bone |
| What are other AM tumros? | Neuroblastoma
Ganglioneuroma
Ganglioneuroblastoma |
| What is neuroblastoma? | Derived from primordial neural crest cells
Neuroblastomas demonstrate several unique features in their natural history, including spontaneous regression and spontaneous or therapy-induced maturation.
Most occur sporadically, but 1% to 2% are familial, with autosomal dominant transmission, and in such cases the neoplasms may involve both of the adrenals or multiple primary autonomic sites |
| How is neuroblastoma present? | Neuroblastoma is the most common extracranial solid tumor of childhood.
These neoplasms occur most commonly during the first 5 years of life and may arise during infancy.
Neuroblastomas may occur anywhere in the sympathetic nervous system and occasionally within the brain, but they are most common in the abdomen;
a majority of these tumors arise in either the adrenal medulla or the retroperitoneal sympathetic ganglia |
| How is macroscopy of neuroblastoma? | Range in size from minute nodules (the in situ lesions) to large masses weighing more than 1 kg.
In situ neuroblastomas are reported to be 40 times more frequent than overt tumors.
The great preponderance of these silent lesions spontaneously regress, leaving only a focus of fibrosis or calcification in the adult.
Some neuroblastomas are sharply demarcated with a fibrous pseudocapsule, but others are far more infiltrative and invade surrounding structures, including the kidneys, renal vein, and vena cava, and envelop the aorta
On transection, they are composed of soft, gray-tan, brainlike tissue.
Larger tumors have areas of necrosis, cystic softening, and hemorrhage.
Multifocal in 10% des cas |
| How is microscopy of neuroblastoma? | Small, primitive-appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders growing in solid sheets
Mitotic activity, nuclear breakdown (karyorrhexis), and pleomorphism may be prominent.
The background often demonstrates a faintly eosinophilic fibrillary material (neuropil) that corresponds to neuritic processes of the primitive neuroblasts.
Typically, so-called Homer-Wright pseudo-rosettes can be found in which the tumor cells are concentrically arranged about a central space filled with neuropil (the absence of an actual central lumen garners the designation “pseudo-”). |
| What are microscopic sings of neuroblastoma? | Larger cells having more abundant cytoplasm with large vesicular nuclei and a prominent nucleolus, representing ganglion cells in various stages of maturation, may be found in tumors admixed with primitive neuroblasts (ganglioneuroblastoma).
Some neoplasms show signs of maturation, either spontaneous or therapy-induced.
Even better differentiated lesions contain many more large cells resembling mature ganglion cells in the absence of residual neuroblasts; such neoplasms merit the designation ganglioneuroma
Maturation of neuroblasts into ganglion cells usually is accompanied by the appearance of Schwann cells
Larger |
| How is invasion of neuroblastoma? | Locally aggressive tumor invading the kidney
Most common metastasis are to the liver, bones, ovaries, lymph nodes, testes and paratesticular area
Bone metatstasis are multiple, sometimes symmetrical (differential Dg with Ewing)
The osteomedullar biospy enters the routine work upof a NB
Age, stage, and NMYC amplification are the most important prognostic features; children younger than 18 months usually have a better prognosis than older children, while children with higher-stage tumors or NMYC amplification fare worse. |
| What is ganglioneuroma? | The best differentiated tumor of this group
Older patient
Represents the most common tumor of the sympathetic system in adults
Can be multiple
Rarely in the adrenal gland (rather posterior mediastinum and retroperitoneum)
Microscopy: like a neurofibroma encompassing mature neuroganglion cells |
| What are AM hyperplasia? | Nodular or diffuse
Always bilatéral
Usually occurs in MEN IIb
Metastasis: Often bilateral.
Most frequent origins :
Lung
Breast
Melanoma
Kidney |
