Robbins Flashcards
two morphologically and functionally distinct components of the pituitary gland
anterior lobe (adenohypophysis) and posterior lobe (neurohypophysis)
Of these cells in the anterior pituitary, give the hormone they synthesize:
SOMATOTROPHS
growth hormone (GH)
Of these cells in the anterior pituitary, give the hormone they synthesize:
MAMMOSOMATOTROPHS
GH and prolactin (PRL)
Of these cells in the anterior pituitary, give the hormone they synthesize:
LACTOTROPHS
PRL
Of these cells in the anterior pituitary, give the hormone they synthesize:
CORTICOTROPHS
adrenocorticotropic hormone
(ACTH), pro-opiomelanocortin (POMC), and melanocyte-
stimulating hormone (MSH)
Of these cells in the anterior pituitary, give the hormone they synthesize:
TYROTROPHS
thyroid-stimulating hormone (TSH)
Of these cells in the anterior pituitary, give the hormone they synthesize:
GONADOTROPHS
follicle-stimulating hormone (FSH)
and luteinizing hormone (LH)
Two peptide hormones secreted from the posterior pituitary
oxytocin and antidiuretic hormone (ADH)
most common cause of hyperpituitarism
adenoma arising in the anterior lobe of the pituitary
most common combination of hormones that pituitary adenomas secrete
GH and PRL
microadenoma size
<1cm
macroadenoma size
> 1cm
most common mutation in pituitary adenomas
Activating G-protein mutations
most common mutation in somatotroph cell adenomas
GNAS mutation
most common mutation in corticotroph cell adenomas
ubiquitin-specific protease 8 (USP8)
Most pituitary carcinomas are functional and secrete (2)
prolactin and ACTH
germline mutation in pituitary blastoma
DICER1
two distinctive morphologic features of most pituitary adenomas
cellular monomorphism and absence of a reticulin network
postpartum ischemic necrosis of the pituitary
Sheehan syndrome
These cysts, lined by ciliated cuboidal epithelium with occasional goblet cells and anterior pituitary cells, can accumulate proteinaceous fluid and expand, compromising the normal pituitary gland
Rathke cleft cyst
mutation in this results in combined pituitary hormone deficiency, characterized by deficiencies of GH, prolactin, and TSH
pituitary-specific gene PIT1
ADH deficiency causes
diabetes insipidus
Most common cause of Syndrome of inappropriate ADH (SIADH) secretion
secretion of ADH by malignant neoplasms (particularly small-cell carcinoma of the lung)
tumor thought to arise from vestigial remnants of Rathke pouch
craniopharyngioma
two distinct histologic variants of craniopharyngioma
adamantinomatous craniopharyngioma and papillary craniopharyngioma
craniopharyngioma that consists of nests or cords of stratified squamous epithelium embedded in a spongy “reticulum” that becomes more prominent in the internal layers. “Palisading” of the squamous epithelium is frequently observed at the periphery. Compact, lamellar keratin formation (“wet keratin”) is a diagnostic feature of this tumor and dystrophic calcification is common
Adamantinomatous
mutation in Adamantinomatous craniopharyngioma
CTNNB1 (β-catenin) gene
craniopharyngiomas that contain both solid sheets of cells and papillae lined by well-differentiated squamous epithelium and lack lamellar keratin, calcification, cysts, peripheral palisading of squamous cells, and a spongy reticulum
Papillary
mutation in Papillary craniopharyngiomas
BRAFV600E
chemical agents that can inhibit thyroid gland function are collectively known as
goitrogen
agent that inhibits the oxidation of iodide and thus blocks the production of thyroid hormones; also inhibits the peripheral deiodination of circulating T4 into T3
propylthiouracil
when given in large doses to individuals with thyroid hyperfunction, blocks the release of thyroid hormones by inhibiting the proteolysis of thyroglobulin
iodide
parafollicular cells, or C cells, synthesize and secrete the hormone __
calcitonin
most common cause of thyrotoxicosis and is associated with hyperfunction of the gland
Diffuse hyperplasia of the thyroid associated with Graves
disease
congenital hypothyroidism is most often the result of
iodine deficiency in the diet
mutations responsible for Genetic defects in thyroid development (3)
PAX8, FOXE1, TSH receptor mutations
most common cause of hypothyroidism in iodine-sufficient areas of the world
Autoimmune hypothyroidism (Hashimoto thyroiditis)
characterized by severe intellectual disability, short stature, coarse facial features, a protruding tongue, and umbilical hernia
Cretinism
hypothyroidism developing in the older child or adult
myxedema
exemplified by the presence of circulating autoantibodies against thyroglobulin and thyroid peroxidase and characterized by progressive destruction of thyroid parenchyma, Hürthle cell change, and mononuclear (lymphoplasmacytic) infiltrates, with germinal centers and variable degrees of fibrosis
Hashimoto thyroiditis
polymorphisms in these genes have a higher predisposition for Hashimoto thyroiditis
-cytotoxic T lymphocyte–associated antigen-4 (CTLA4)
-protein tyrosine phosphatase-22 (PTPN22), and -interleukin-2 receptor α chain (IL2RA)
characteristic features appear in the form of aggregates of lymphocytes, activated macrophages, and plasma cells associated with collapsed and damaged thyroid follicles. Multinucleate giant cells enclose pools of colloid
Granulomatous thyroiditis (also called De Quervain thyroiditis)
most common cause of thyroid pain
Granulomatous thyroiditis (also called De Quervain thyroiditis)
a rare disorder characterized by extensive fibrosis involving the thyroid and contiguous neck structures
Riedel thyroiditis
most common cause of endogenous hyperthyroidism characterized by the triad of thyrotoxicosis, ophthalmopathy, and dermopathy.
Graves disease
autoimmune disorder characterized by the production of autoantibodies against multiple thyroid proteins, most importantly the TSH receptor
Graves disease
most common antibody subtype observed in approximately 90% of patients with graves disease
thyroid-stimulating immunoglobulin (TSI)
exopthalmos) is caused by an increase in the volume of the retro-orbital connective tissues and extraocular muscles, which occurs for several reasons (4)
(1) marked infiltration of connective tissue by mononuclear cells, predominantly T cells; (2) inflammation, edema, and swelling of extraocular muscles; (3) accumulation of extracellular matrix components,; and (4) increased numbers of adipocytes (fatty infiltration).
Enlargement of the thyroid, or goiter is caused by
impaired synthesis of thyroid hormone
Goiters can broadly be divided into two types
diffuse nontoxic and multinodular
vegetable family that interfere with thyroid hormone synthesis at some level
Brassicaceae (Cruciferae) family (e.g., cabbage, cauliflower, Brussels sprouts, turnips, and cassava)
Two phases identified in the evolution of diffuse nontoxic goiter
hyperplastic phase and the phase of colloid involution
recurrent episodes of hyperplasia and involution combine to produce a more irregular enlargement of the thyroid, termed
multinodular goiter
development of an autonomous nodule within a long-standing goiter that produces hyperthyroidism
Plummer syndrome
3 mutations at least one being often present that cause follicular cells to secrete thyroid hormone independent of TSH stimulation (“thyroid autonomy”). This leads to hyperthyroidism and produces a functional “hot” nodule on imaging
- TSH receptor (TSHR) (more common)
- α-subunit of Gs (GNAS) (less common)
- enhancer of zeste, homolog 1 (EZH1) (1/3)
nonfunctioning follicular adenomas harbor oncogenic mutations of
RAS
histologic hallmark of all follicular adenomas
presence of an intact, well-formed capsule encircling the tumor
precursor to conventional PTC
Papillary microcarcinoma
precursor to invasive encapsulated follicular variant PTC
Noninvasive thryoid neoplasma with papillary- like nuclear features / Noninvasive follicular thyroid neoplasm with papillary-like features (NIFTP)
precursor to follicular carcinoma
Nonfunctioning follicular adenoma
Conventional PTCs have two defining genetic abnormalities namely
gene fusions of RET or NTRK, and point mutations in BRAF
most commonly observed fusion partners of RET in sporadic papillary cancers
PTC1 and PTC2
Between 50% and 80% of conventional PTCs harbor gain-of-function mutations in
BRAF gene
most common BRAF gene mutation in conventional PTCs
BRAF valine-to-glutamate change in codon 600 (BRAFV600E)
diagnostic requirement for conventional PTCs, known as “tall cell variant”
2-3X as tall as they are wide with at least >/=30% population and BRAFV600E mutation
follicular neoplasms are often associated with gain-of- function mutations in
RAS
fusion gene found in some follicular neoplasms
PAX8-PPARG fusion genes
10% of follicular carcinomas exhibit gain-of-function mutations of
PIK3CA
presence of this mutation in thyroid neoplasms is associated with reduced expression of thyroid differentiation markers (such as thyroglobulin and thyroid peroxidase) and may be associated with a higher risk of extrathyroidal extension and recurrence
BRAFV600E
presence of this mutation in thyroid neoplasms is associated retention of expression of thyroid differentiation factors (e.g., thyroglobulin, thyroid peroxidase), which may contribute to their follicular growth pattern
RAS
three recurrent genetic “hits” essentially restricted to poorly differentiated and anaplastic carcinomas
point mutations of TP53, beta-catenin (CTNNB1), and TERT
Familial medullary thyroid carcinomas occur in this hereditary conditon
multiple endocrine neoplasia, type 2 (MEN-2)
this mutation are also seen in approximately one-half of nonfamilial (sporadic) medullary thyroid cancers
RET
The major risk factor predisposing to thyroid cancer is
exposure to ionizing radiation
radiation exposure has a high chance to induce chromosome rearrangements that produce gene fusions and thus is commonly associated with this thyroid carcinomas with previous radiation exposure
PTC
most common form of thyroid cancer
PTC
is defined as an otherwise conventional papillary carcinoma, but less than 1 cm in size
Papillary microcarcinoma
4 hallmarks of papillary neoplasms
- Branching papillae
- ground-glass or Orphan Annie eye nuclei
- psammoma bodies
- Foci of lymphatic invasion by tumor
Tall cell variant papillary carcinomas almost always harbor these two aberrations and their co-occurrence may contribute to the aggressive behavior of this variant.
BRAF and RET/PTC
these translocations are found in approximately one-half of diffuse sclerosing variant of papillary carcinoma cases
RET/PTC translocations
prognosis in PTC is dependent on several factors including (3)
age (in general, being less favor- able among patients older than 40 years), presence of extrathyroidal extension, and presence of distant metastases (stage)
thyroid carcinoma that often have propensity for invading lymphatics
PTC
thyroid carcinoma that often have propensity for invading vasculature
Follicular carcinomas
Anaplastic carcinomas demonstrate variable morphology (3)
(1) large, giant cells, including occasional osteoclast-like giant cells; (2) spindle cells; and (3) mixed spindle and giant cells
one of the most aggressive thyroid cancers known; in most cases death occurs in less than 1 year
Anaplastic carcinomas
thyroid neuroendocrine neoplasms derived from the parafollicular cells (C cells)
Medullary carcinoma
common presentation in familial cases of medullary thyroid carcinomas
bilaterality and multicentricity
a feature that is usually absent in sporadic lesions of medullary carcinoma
C-cell hyperplasia
prophylactic thyroidectomy as early as possible is offered to prevent the otherwise inevitable development of medullary carcinoma in these patients
asymptomatic MEN-2 individuals carrying germline RET mutations
the most common clinically significant congenital anomaly of the thyroid
Thyroglossal duct cyst
The four parathyroid glands are composed of two cell types namely
chief cells and oxyphil cells
most common cause of primary hyperparathyroidism is
solitary sporadic parathyroid adenoma
two molecular defects that have an established role in the development of sporadic parathyroid adenomas
Cyclin D1 (CCDN1) gene inversions and MEN1 mutations
mutated in ~70% of sporadic parathyroid carcinomas, but rarely in adenomas
CDC73
only reliable criteria to distinguish parathyroid carcinoma from an adenoma
invasion of surrounding tissues and metastasis
produced in medullary bone in cases of hyperparathyroidism
dissecting osteitis
Symptomatic, untreated primary hyperparathyroidism manifests with three interrelated skeletal abnormalities namely
osteoporosis, brown tumors, and osteitis fibrosa cystica
hallmark of severe hyperparathyroidism and is known as
generalized osteitis fibrosa cystica
most frequent cause of symptomatic hypercalcemia in adults
malignancy
most common mechanism (in ~80% of cases) through which osteolytic tumors induce hypercalcemia
secretion of PTH-related peptide (PTHrP) and bone mets
most common cause of secondary hyperparathyroidism
Renal failure
Unequivocal criteria for malignancy in pancreatic neuroendocrine tumors (PanNETs) (3)
metastases, vascular invasion, and local infiltration
most common subtype of pancreatic endocrine neoplasms
insulinomas
recurrent somatic alterations in three major genes or pathways in sporadic PanNETs
MEN1, Loss-of-function mutations in tumor suppressor genes such PTEN and TSC2, and Inactivating mutations in two genes, alpha-thalassemia/
mental retardation syndrome, X-linked (ATRX) and death-domain–associated protein (DAXX)
disease associated with pancreatic islet cell lesions, hypersecretion of gastric acid and severe peptic ulceration
Zollinger-Ellison Syndrome
two familial cancer syndromes are associated with a predisposition for developing adrenocortical carcinomas
Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome
mutation in Li-Fraumeni syndrome
TP53 mutations
gene implicated in Beckwith-Wiedemann syndrome
gene for insulin-like growth factor 2 (IGF-2)
neoplasms composed of chromaffin cells, which synthesize and release catecholamines and, in some instances, peptide hormones
Pheochromocytomas
MEN-1 is characterized by abnormalities involving these organs (3)
parathyroid, pancreas, and pituitary gland
MEN-2A is clinically and genetically distinct from MEN-1 and is caused by
germline gain-of-function mutations in the RET protooncogene
T staging to Thyroid tumors:
T1a, T1b, T2, T3a,T3b, T4a, T4b
T1a </= 1cm
T1b >1cm </=2cm
T2 >2cm </=4cm
T3a >4cm limited to thyroid
T3b involved strap muscles
T4a involves subcutaneous tissues, larynx, trachea
T4b involves prevertebral fascia/ encasing the carotid artery
