A.

Normal Parathyroid Glands Brief Review

1. Anatomy: typically four, smooth, oval, tan glands situated bilaterally near the upper and lower
poles of the thyroid lobes

2. Histology: clusters of polygonal cells with centrally-placed, regular, round nuclei (chief cells
[pale cytoplasm] > oxyphil cells [eosinophilic cytoplasm]) admixed with adipose tissue

3. Function:
d serum Ca++

secretion of parathyroid hormone (PTH) by the chief cells

d levels of serum Ca++ (via osteoclastmediated bone resorption, d GI absorption and renal tubular reabsorption of
Ca++, as well as activation of vitamin D)

and d levels of serum phosphate (via d urinary phosphate excretion)

B. [edit]Hyperparathyroidism

1. Primary hyperparathyroidism

middle-aged to older adults; F > M

due to parathyroid adenoma > parathyroid hyperplasia > parathyroid carcinoma

(sporadic >> familial)

painful bones, renal stones, abdominal groans, and psychic moans although

frequently asymptomatic

genetic abnormalities pathogenesis

i. [edit]Sporadic parathyroid adenoma

a. activation of PRAD1 overexpression of cyclin D1

b. mutations and resultant inactivation of MEN1

ii. [edit]familial primary hyperparathyroidism

a. mutations and resultant inactivation of MEN1

 b. RET mutations persistent, autonomous tyrosine kinase
receptor activation (MEN-2 syndrome)

c. CASR (calcium-sensing receptor gene) mutations

pathology and clinical manifestations

i. parathyroid gland(s)

Figure 3: Parathyroid Adenoma

a. * parathyroid adenoma: solitary, enlarged parathyroid gland

containing a brown, well-circumscribed, encapsulated nodule
composed of a dense, monotonous population of chief cells

b. parathyroid hyperplasia: nodular enlargement of multiple

parathyroid glands with predominantly chief cell proliferation

c. parathyroid carcinoma: usually a single, well-differentiated

Figure 4.5: Primary Hyperparathyroidism Figure 4.6: Brown Tumors

neoplasm resembling a parathyroid adenoma, but with evidence of invasion or metastatic disease

ii. bone especially metaphyses of long bones

a. d numbers of osteoclasts d bone resorption and an

osteoblastic response formation of new, thin bony trabeculae (osteopenia) skeletal pain, as well as
potential fractures and deformities

b. radiologic features

c. osteopenia (cortical thinning more prominent than medullary

involvement, especially subperiosteal bone resorption)
 d. +/- multiple, localized, lytic lesions

e. end-stage disease "osteitis fibrosa cystica

a. osteitis d osteoclastic activity (cortical > medullary)

dissecting osteitis microscopic description of the marked trabecular bone resorption

b. osteitis fibrosa

marrow fibrosis and secondary d osteoblastic function reactive woven bone

c. osteitis fibrosa cystica

brown tumors cystic areas of hemorrhage, hemosiderin-laden macrophages and granulation tissue
due to microfractures

Figure 5: Kidney - Primary

Figure 7: Osteitis Fibrosa Cystica (Brown
Hyperparathyroidism with Metastatic
Tumors)
Figure 6: Dissecting Osteitis Calcification

ii. due to hypercalcemia

a. frequently asymptomatic, but may present with complaints such as

fatigue, weakness, lethargy, constipation, etc.

a. metastatic calcification

b. nephrolithiasis complications of urinary tract obstruction (e.g.,

colicky pain, hematuria, polyuria, renal insufficiency)

b. Secondary hyperparathyroidism

pathogenesis

persistently d serum Ca++ levels (e.g., due to d dietary intake &/or d loss of Ca++ or vitamin D; *
chronic renal failure as a result of d serum phosphate and d activation of vitamin D) longstanding
stimulation of the parathyroid glands
 anatomic pathology

chief cell hyperplasia of multiple parathyroid glands, associated with bone changes as described
above (albeit less severe) and metastatic calcification
b. [edit]Hypoparathyroidism

Uncommon

a. Etiology

surgical excision of the parathyroid glands

congenital absence (e.g., DiGeorge syndrome)

Figure 8: BONE - NORMAL (LEFT); OSTEOPOROSIS (RIGHT) Figure 9

autoimmune disease (+/- adrenal involvement)

b. Clinical features due to hypocalcemia (e.g., tetany, mental status

changes, cardiac conduction abnormalities, defective dental development)

Pathology of Metabolic Bone Disease

[edit]

A. [edit]Osteoporosis

reduced bone mass that is qualitatively normal, due to incomplete bone production following

bone resorption of each basic multicellular unit cycle

assessed by measurements of bone density

 Pathogenetic factors

a. heredity (e.g., genes involved with regulation of osteoclasts)

b. age ('d bone formation with 'ing age)

c. hormonal status (e.g., 'd estrogen levels 'd osteoclast activity with an insufficient
osteoblast response)

d. nutritional state (especially intake of calcium and vitamin D)

e. physical activity ('d mechanical resistance 'd rate of bone loss)

f. medications (e.g., corticosteroids)

Anatomic pathology: 'd cortical and cancellous bone with microfractures

Clinical features: osteopenia with 'd risk of fractures (e.g., femoral neck fractures,

compression fractures of the vertebrae) and their complications (e.g., kyphoscoliosis,

pulmonary embolism)

Figure 10

Figure 9.5: VERTEBRAE - OSTEOPOROSIS WITH

COMPRESSION FRACTURES

2. [edit]Vitamin D Deficiency - Rickets and Osteomalacia

Figure 11: VITAMIN D METABOLISM AND FUNCTIONS

Vitamin D - brief review

a. fat-soluble vitamin available in the diet (e.g., milk, fortified foods) and via conversion
of 7-dehydrocholesterol in the skin by UV irradiation

b. bound to DBP in plasma; stored in adipose tissue

c. activation to 25-OH-D in the liver and 1,25-(OH)2D (calcitriol) in the kidneys

stimulated by low serum levels of calcitriol, calcium (via PTH) and phosphorus

d. major function of calcitriol is in the maintenance of normal serum levels of calcium

and phosphorus

i. intestine - augments the absorption of calcium and phosphorus

ii. kidneys - stimulates PTH-dependent calcium reabsorption

iii. bones
 a. with low serum calcium levels, helps to mobilize calcium and
phosphorus

b. with normal serum calcium and phosphorus levels, necessary for

mineralization of osteoid and epiphyseal cartilage
[edit]Vitamin D deficiency diseases

Figure 12: PATHOGENESIS OF POOR BONE MINERALIZATION WITH VITAMIN D DEFICIENCY

a. causes

inadequate synthesis in the skin &/or insufficient dietary intake; fat malabsorption; altered metabolism
(e.g., hepatic or renal disease); 'd DBP; genetic abnormalities

b. pathogenesis

i. 'd calcitriol 'd intestinal absorption of calcium and phosphorus 'd

serum levels of calcium and phosphorus

ii. 'd serum calcium level stimulation of the parathyroid glands

mobilization of calcium and phosphorus from bone, as well as renal
wasting of P impaired bone mineralization
 c. clinicopathologic features

i. inadequate mineralization of osteoid thickened osteoid seams AND, in

growing children, inadequate provisional mineralization of the epiphyseal
cartilage its overgrowth, abnormal endochondral bone growth and skeletal
deformities (worsened by continual calcium mobilization)

Figure 20: OSTEOMALACIA - PSEUDOFRACTURE (LOOSER ZONE)

i. rickets (growing children)

a. infancy - predominantly head and chest abnormalities (e.g.,

craniotabes, frontal bossing, rachitic rosary, pigeon-breast
deformity, Harrison groove)

b. post-ambulatory age (e.g., bowing of the legs, lumbar lordosis)

ii. osteomalacia (adults)

osteopenia loss of bone density and cortical thickness ('d susceptibility to fractures, kyphoscoliosis,
weakness, bone pain)

i. severe vitamin D deficiency can lead to hypocalcemic tetany

- THICKENED OSTEOID SEAMS Figure 15: RICKETS - WIDE WRISTS

Figure 16: NORMAL (LEFT) AND RACHITIC (RIGHT) COSTOCHONDRAL J

TAL BOSSING

Figure 19: RICKETS - BOWING OF THE LEGS

Figure 18: RICKETS - HARRISON GROOVE
Figure 19.5: FEATUR

2. [edit]Paget Disease of Bone ("Osteitis Deformans")

 c

Figure 22: OSTEOLYTIC STAGE

Figure 25: OSTEOSCLEROTIC STAGE

ommon bone disease of middle-aged to older white adults in the U.S.

disorder of accelerated bone turnover

Pathogenesis

? paramyxovirus (e.g., measles virus) slow virus infection of osteoclasts also genetic susceptibility

Sites of involvement

a. usually multiple bones affected (polyostotic)

b. axial skeleton and large bones of the extremities most common

Progressive stages pathologic / radiologic features

various stages can be present in different bones or even within the same
bone

osteolytic stage excessive bone resorption

i. radiographic appearance

sharply defined lytic areas within cortical bone

ii. microscopic appearance

d number and size of osteoclasts with numerous, scattered Howship lacunae

 ii. mixed osteoclastic / osteoblastic stage

i. radiographic appearance

heterogeneous regions of d bone lucency adjacent to irregular areas of apparent new bone growth

ii. microscopic appearance

a. d number of osteoclasts, admixed with plump, tall osteoblasts

lining the bony surfaces and producing new woven bone

b. marrow replaced by granulation and fibrous tissue

iii. osteosclerotic stage disorganized and excessive bone formation

i. radiographic appearance

bone enlargement with abnormally d density (coarse, disordered bone thickening)

ii. microscopic appearance

thickened and irregular cortical and medullary bone with a pathognomonic mosaic, tile-like
arrangement of lamellar bone separated by prominent cement lines

ASE OF BONE - OSTEOLYTIC STAGE

Figure 23: PAGET DISEASE OF BONE - MIXED STAGE
Figure 24: PAGET DISEASE OF BONE - OSTEOSCLER

b. Clinical pathology

i. d serum alkaline phosphatase (reflecting osteoblastic activity)

ii. d collagen breakdown products (e.g., hydroxyproline) in the serum and

urine

c. Complications
Figure 27: PAGET DISEASE OF BONE - THICKENED SKULL

Figure 28: PAGET DISEASE OF BONE - COMPLICA

i. bone pain

ii. skeletal deformities (e.g., bowing of the lower extremities due to bone
weakening, characteristic facial and skull bone overgrowth neural deficits)

iii. d susceptibility to fractures

iv. secondary osteoarthritis

v. high-output cardiac failure (with extensive disease, due to d vascularity in

affected bones)

vi. secondary sarcomas, especially osteosarcoma

 Figure 30: PAGET DISEASE OF BONE WITH SECONDARY OSTEOSARCOMA
Figure 31: PAGET DISEASE OF
OF BONE WITH SECONDARY OSTEOSARCOMA

2. [edit]Hyperparathyroidism

(discussed earlier)

Pathology of the Adrenal Glands

[edit]

Figure 32: NORMAL ADRENAL GLAND

paired endocrine organs located in the retroperitoneum, just superior to the kidneys
A. [edit]Pathology of the Adrenal Cortex

1. Normal adrenal cortex - brief review

a. zona glomerulosa narrow layer of clear, vacuolated adrenal cortical cells directly
underneath the adrenal capsule; primarily secretes aldosterone
 b. zona fasciculata thick middle layer of clear, vacuolated adrenal cortical cells;
primarily secretes cortisol

c. zona reticularis narrow layer of eosinophilic adrenal cortical cells closest to the
medulla; primarily secretes sex steroids (especially androgens)

Figure 34: NORMAL ADRENAL CORTEX - ZONA GLOMERULOSA AND ZONA FASCICULATA

L ADRENAL CORTEX Figure 36: NORMAL ADRENAL GLAND - C

Figure 35: NORMAL ADRENAL CORTEX - ZONA RETICULARIS

2. Adrenal cortical hyperfunction (Hyperadrenalism)

a. [edit]Hypercortisolism

i. pathogenesis (Cushing syndrome)

a. exogenous (iatrogenic)

b. endogenous

*ACTH-dependent ('d ACTH secretion 'd cortisol levels)

* ACTH-secreting pituitary lesion (Cushing disease)

PITUITARY ADENOMA
 Figure 37

usually a pituitary microadenoma bilateral adrenal cortical hyperplasia (cortisol can be suppressed
by high-dose dexamethasone)

ectopic ACTH (or CRH) production

most commonly small cell carcinoma of the lung bilateral adrenal cortical hyperplasia (cortisol can't
be suppressed by high-dose dexamethasone)

*ACTH-independent ('d cortisol secretion 'd ACTH levels)

adrenal cortical adenoma

adrenal cortical carcinoma

primary adrenal cortical hyperplasia (due to overexpression of receptors for non-ACTH hormones,
gene mutations, etc.)

ii.

iii. anatomic pathology (Cushing syndrome)

a. pituitary

'd circulating cortisol degenerative changes of the

ACTH-producing cells in the anterior pituitary (Crooke
hyaline change), characterized by the accumulation of
cytoplasmic keratin filaments

+/- pituitary adenoma or hyperplasia (Cushing disease)

 b. adrenal

bilateral adrenal cortical atrophy with sparing of the zona

glomerulosa (exogenous hypercortisolism)

diffuse or nodular adrenal cortical hyperplasia (ACTH-

dependent Cushing syndrome and primary adrenal cortical

hyperplasia)

bilaterally enlarged adrenal glands with a thickened, yellow, frequently nodular cortex composed of
both lipid-laden and lipid-depleted adrenal cortical cells

adrenal cortical neoplasm (adenoma or carcinoma, to

be discussed later), associated with atrophy of the
nonneoplastic adrenal cortex

iv. clinical features (Cushing syndrome): central deposition of adipose tissue

(truncal obesity, moon facies, buffalo hump); hypertension; thin skin with
poor wound healing, easy bruising and abdominal striae; glucose
intolerance; osteoporosis; 'd risk for infections; hirsutism and menstrual
irregularities; emotional changes; weakness

Figure 39: ADRENAL - ATROPHY (TOP); NORMAL (MIDDLE); Figure 40: ADRENAL CORTICAL ADENOMA
RY - CROOKE Figure 41: NODULAR AD
AND CORTICAL HYPERPLASIA (BOTTOM) CAUSING CUSHING SYNDROME
E CORTICAL HYPERPLAS
 Figure 43: CUSHING SYNDROME - HIRSUTISM Figure 44: CUSHING SYNDRO
AND AFTER CUSHING DISEASE

c. [edit]Primary hyperaldosteronism

Figure 46

('d aldosterone secretion 'd renin levels)

i. pathogenesis and anatomic pathology

a. * bilateral idiopathic hyperaldosteronism (bilateral, diffuse &/or

nodular, adrenal cortical hyperplasia, most prominent in the
periphery)

b. aldosterone-producing adrenal cortical neoplasm (not

associated with atrophy of the non-neoplastic adrenal cortex)

adenoma (Conn syndrome)

carcinoma
 Figure 45: ADRENAL CORTICAL ADENOMA CAUSING CONN
SYNDROME

c. glucocorticoid-remediable hyperaldosteronism (rare familial

variant)

ii. clinical features: hypertension ('d aldosterone secretion 'd Na+

reabsorption 'd H2O reabsorption) +/- signs / symptoms of
hypokalemia due to renal K+ wasting (e.g., weakness, paresthesias)
d. [edit]Adrenogenital syndromes

(usually 'd secretion of adrenal androgens, such as androstenedione and DHEA)

i. adrenal cortical neoplasms (may produce excessive amounts of more than

one hormone)

a. adenoma

b. * carcinoma

ii. congenital adrenal hyperplasia (autosomal recessive disorders)

a. pathophysiology:
partial or total deficiency in an enzyme involved in the synthesis of adrenal cortical steroids (most common being 21-
hydroxylase)

'd production of cortisol (+/- aldosterone)

'd pituitary ACTH secretion

adrenal cortical hyperplasia and 'd production of adrenal androgens

b. anatomic pathology
 anterior pituitary

hyperplasia of ACTH-producing cells

adrenal

bilaterally enlarged adrenal glands with a thickened, nodular, brown cortex composed mostly of lipid-
poor cells

c. clinical features (of variable severity and age of onset) some

combination of signs / symptoms related to:

'd glucocorticoid +/- 'd mineralocorticoid synthesis:

(e.g., salt wasting with hyponatremia and hyperkalemia;

hypotension)

Figure 47: FEMALE INFANT WITH CONGENITAL ADRENAL

HYPERPLASIA

'd adrenal androgen synthesis: (e.g., virilization,

hirsutism and oligomenorrhea

 in females; precocious puberty and oligospermia in males; acne)

3. Adrenal cortical hypofunction (Hypoadrenalism)

a. [edit]Primary hypoadrenalism

(due to adrenal disease)

i. primary acute adrenal cortical insufficiency (adrenal crisis), which can

vascular collapse

a. rapid withdrawal of exogenous corticosteroids

b. inability for the adrenal glands to respond to an 'd

requirement for glucocorticoids (e.g., with stresses such as
surgery, infections and trauma)

occurs in patients with atrophic adrenal glands (due to long-term suppression by exogenous
corticosteroids) and in individuals with chronic adrenal cortical insufficiency

c. massive bilateral adrenal hemorrhage with secondary

infarction

newborns (usually precipitated by a difficult delivery)

individuals with a hemorrhagic diathesis (e.g., DIC, anti-

coagulant therapy)

patients with bacterial sepsis and DIC (Waterhouse-

Friderichsen syndrome)

classically associated with Neisseria meningitidis bacteremia

ADRENAL HEMORRHAGE AND NECROSIS DUE TO WATERHOUSE-FRIDERICHSEN SYNDROME
Figure 49
Figure 51

Figure 53: METASTASES TO THE ADRENAL GLAND

Figure 52: AUTOIMMUNE ADRENALITIS

ii. [edit]Primary chronic adrenal cortical insufficiency (Addison disease)

a. pathogenesis and anatomic pathology

* autoimmune adrenalitis

- component of:
 autoimmune polyendocrine syndrome type 1 (APS1), associated with autoimmune regulator (AIRE)
gene mutations, chronic mucocutaneous candidiasis and ectodermal dystrophy

autoimmune polyendocrine syndrome type 2 (APS2)

- small adrenal glands with a lymphocytic infiltrate and few remaining adrenal cortical cells

infections, especially in patients with

AIDS (e.g., Mycobacterium tuberculosis,

Histoplasma capsulatum, cytomegalovirus,
Mycobacterium avium-intracellulare)
destruction of the adrenal glands by the organism
&/or the host inflammatory response

metastases (e.g., lung carcinoma)

replacement of the adrenal gland architecture by

malignant cells

congenital disorders (rare)

b. clinical features (only apparent with extensive loss of the

adrenal cortex)

weakness; fatigability; nausea / vomiting; skin hyperpigmentation (due to 'd levels of melanocyte
stimulating hormone [MSH]); hypotension with hyponatremia and hyperkalemia; hypoglycemia
ADDISON DISEASE - HYPERPIGMENTATION

Figure 54
Figure 55
 b.

Figure 56: PITUITARY INFARCTION - SHEEHAN SYNDROME

[edit]Secondary hypoadrenalism

('d ACTH secretion 'd cortisol and androgen levels, with near-normal
aldosterone levels)

i. absence of skin hyperpigmentation

i. pathogenesis

pituitary or hypothalamic pathology (e.g., infarction, infection, metastatic disease), which may also
other hormone deficiencies

ii. adrenal gland pathology

small adrenal glands with a thin residual layer of the zona glomerulosa

2. Adrenal cortical neoplasms

a.

Figure 58

Figure 59: ADRENAL

CORTICAL ADENOMA
PRODUCING ALDOSTERONE
Figure 60: ADRENAL
CORTICAL ADENOMA
Figure 57: ADRENAL
PRODUCING ANDROGENS
CORTICAL ADENOMA

b. [edit]Adrenal cortical adenoma

i. anatomic pathology

relatively small, well-delineated, yellow to brown nodule composed of fairly normalappearing adrenal
cortical cells with clear, vacuolated to eosinophilic cytoplasm

ii. pathophysiology

a. * nonfunctional (no hormone production)

non-neoplastic adrenal cortex appears normal

b. functional

aldosterone-producing (Conn syndrome)

cortisol-producing (Cushing syndrome)

non-neoplastic adrenal cortex appears atrophic

c.

d. [edit]Adrenal cortical carcinoma

i. uncommon, aggressive malignancy frequently associated with lymphatic and

hematogenous dissemination

i. anatomic pathology

usually a large, infiltrative mass with areas of hemorrhage and necrosis, composed of adrenal cortical
cells with variable degrees of anaplasia

ii. pathophysiology

a. * functional (associated with excess adrenal cortical hormone

production, often including androgens)

b. nonfunctional
ADRENAL CORTICAL CARCINOMA
 Figure 62

Figure 61

ii. [edit]Pathology of the Adrenal Medulla

NAL GLAND Figure 65: NORMAL ADRENAL CORTEX AND MEDULLA Figure 64: NORMAL ADRENAL MEDUL

1. Normal adrenal medulla - brief review

central portion of the adrenal glands containing chromaffin cells (derived from the neural crest), which
produce catecholamines (epinephrine >> norepinephrine)

2. Adrenal medullary neoplasms

a. [edit]Pheochromocytoma

(uncommon neoplasm of chromaffin cells 'd catecholamine secretion)

i. 10% rule
 a. 10% arise in the extra-adrenal paraganglion system (e.g.,
carotid body, organ of Zuckerkandl)

b. 10% bilateral (of sporadic tumors)

c. 10% malignant (defined by the presence of lymphatic or

hematogenous metastases)

d. 10% not associated with hypertension (discovered incidentally)

e. 10-25% familial (germline mutation), such as MEN-2A and

MEN-2B

f.10% arise in children

ii. anatomic pathology

a. macroscopic appearance

well-delineated tan mass of the adrenal medulla (which turns dark brown with oxidation of the stored
catecholamines); occasionally contains areas of hemorrhage and necrosis

b. microscopic appearance

small clusters (zellballen) of neuroendocrine cells separated by highly vascular connective tissue;
highly variable cytologic atypia (which doesn't correlate with biologic behavior); cytoplasmic
neurosecretory granules seen by electron microscopy

Figure 68: PHEOCHROMOCYTOMA -

Figure 66: PHEOCHROMOCYTOMA
Figure 67 NEUROSECRETORY GRANULES (EM)

c. clinical pathology

24-hour urine sample &/or plasma 'd catecholamines and their metabolites, such as metanephrines
and vanillylmandelic acid (VMA)

d. clinical features
 Figure 69: NEUROBLASTOMA Figure 70: NEUROBLASTOMA - HOMER-WRIGHT PSEUDOROSETTES

hypertension, often with intermittent paroxysmal episodes characterized by features such as a sudden
rise in blood pressure, palpitations, tachyarrhythmias (catecholamine cardiomyopathy), headache,
diaphoresis, and tremor
b. [edit]Neuroblastoma

c. (malignant tumor of neural crest origin)

i. neuroblast - intermediate stage in the development of sympathetic ganglion

neurons

i. epidemiology

a. usually affects children < 5 years of age

b. sporadic >>> familial

ii. anatomic pathology

a. tumor location

adrenal medulla

paravertebral - posterior mediastinum, retroperitoneum

b. macroscopic appearance

soft, lobulated, gray mass with necrosis, hemorrhage and calcifications

c. microscopic appearance
 small, round, blue cell tumor forming Homer- Wright

pseudorosettes; cytoplasmic neurosecretory granules seen

by electron microscopy

occasionally evidence of neuronal differentiation into

Figure 72: GANGLIONEUROMA

Figure 71: NEUROBLASTOMA

mature-appearing ganglion cells, with accompanying

schwannian stroma
neuroblastoma ganglioneuroblastoma ganglioneuroma

(malignant) (intermediate prognosis) (benign)

d. tumor spread

local infiltration

lymphatic spread (lymph nodes)

hematogenous dissemination (e.g., liver, lungs, bones, skin,

periorbital region)

iii. clinical pathology

urine - 'd catecholamines and their metabolites, especially vanillylmandelic acid (VMA) and
homovanillic acid (HVA)

iv. clinical features

abdominal mass; fever; weight loss; signs / symptoms secondary to metastases (e.g., bone pain,
proptosis with ecchymosis) or tumor compression (e.g., neurologic dysfunction)
 Figure 73: METASTATIC NEUROBLASTOMA TO THE PERIORBITAL
REGION

v. prognostic indicators (occasional spontaneous remission)

a. age of the child

< 18 months old - favorable

> 18 months old - unfavorable

b. stage of the tumor

localized malignancies and those of stage IV-S (Stage I or II tumor in an infant with metastases
restricted to the liver, skin and bone marrow) - favorable

c. histopathologic features of the neoplasm (e.g., presence of

gangliocytic maturation and schwannian stroma - favorable)

d. genetic markers of the malignancy

DNA ploidy in tumors of infants (hyperdiploidy - favorable;

near-diploidy - unfavorable)
 N-MYC amplification - unfavorable

1p or 11q loss; 17q gain - unfavorable