Ch12-Nervous cont. Flashcards
What are the FIRST sign of MEN2B? When do they develop? WHERE do they typically develop?
Oral mucosal neuromas, detectable during infancy…lips and anterior tongue
MEN2B: BILATERAL neuromas of the _________ are HIGHLY characteristic
commisural mucosa
MEN2B: 50% of pts develop this, esp w age, causing profuse sweating, intractable diarrhea, headaches, flushing, heart palpitations, and severe hypertension.
pheochromocytomas
MEN2B: 40% present with __________ in the GI tract which results in abdominal distention, megacolon, constipation, and diarrhea.
ganglioneuromas
MEN2B: The most significant aspect of this condition is the development of ______, which occurs in virtually ALL cases.
MTC
MEN2B: MTC is an aggressive tumor that arises from the ________ cells (___ cells) of the thyroid gland, which are responsible for ________ production
parafollicular…C cells…Calcitonin
MEN2B: MTC silently develops EARLY in life and, without prophylactic thyroidectomy before WHAT AGE?, most patients will develop metastatic tumor during childhood or adolescence.
before 1 year of age!!
MEN2B: What lab values are elevated in MTC?
serum or urinary Calcitonin
MEN2B: Pheochromocytomas can result in elevated urine levels of what 2 markers?
VAN-ILL-YL-MAN-DELIC acid (VMA) and increased Epi:NorEpi ratios
What is the average age of MEN2B pts that do not have the thryroidectomy prophylaxis?
21 years
Which form of the MEN2B RET mutation is said to have a less aggressive form of MTC?
A883F less aggressive than M918T
What is a fatal complication of Pheochromocytomas and general anesthesia?
hypertensive crisis
The ___________ is a rare pigmented neoplasm that usually occurs during the first year of life.
melanotic neuroectodermal tumor of infancy
It is generally accepted that melanotic neuroectodermal tumor of infancy is of _______ origin.
neural crest
Melanotic neuroectodermal tumor of infancy almost always develops in young children during what age?…only
9% of cases are diagnosed after.
1 year
Melanotic neuroectodermal tumor of infancy..where does it show up? Gender? What color is it clinically?
anterior maxilla 69% of cases (skull,epididymus,testis,mandible,brain)…slight male…blue or black
What entity can Melanotic neuroectodermal tumor of infancy mimic on a radiograph?
osteosarc..makes a sun ray appearance - Destroys bone and displaces developing teeth
High urinary levels of _______ often are found in patients with melanotic neuroectodermal tumor of infancy.
vanillylmandelic acid (VMA)
melanotic neuroectodermal tumor of infancy histo: what are the two main cell morphologies seen?
small hyperchromatic round cells (neuroblastic) and larger epithelioid cells with vesicular nuclei
Although IHC is not typically needed for Melanotic neuroectodermal tumor, what do the epithelioid cells stain positive for (3)?
CK, HMB-45, neuron-specific enolase
Although IHC is not typically needed for Melanotic neuroectodermal tumor, what do the neuroblastic cells stain positive for (3)?
neuron-specific enolase, CD56, synaptophysin
Melanotic neuroectodermal tumor: benign or malignant?
MOST benign (despite rapid growth and bone distruction)
Melanotic neuroectodermal tumor: recurrence?
20%
What location has an association with malignancy in Melanotic neuroectodermal tumor? What % of cases?
brain/skull….7% (probably high)
What are the 4 names for a PARAGANGLIOMA?
1.Carotid body tumor 2.Chemo-dec-toma 3.Glomus Jugulare Tumor 4.Glomus Tympanicum Tumor
The paraganglia are specialized tissues of ______ origin
neural crest
The paraganglia are associated with the _______ nerves and ganglia throughout the body
autonomic
Some paraganglia cells act as ________, such as the carotid body (located at the carotid bifurcation), which can detect changes in blood pH or oxygen tension and subsequently cause changes in respiration and heart rate.
chemoreceptors
Most head and neck paragangliomas occur as sporadic
tumors, although __% of cases are associated with heritable germline mutations of genes that encode for subunits or cofactors of _________ (mitochondrial complex II).
30%…succinate dehydrogenase
Four hereditary paraganglioma syndromes (PGL1-4) have been recognized, all of which show an ________ inheritance pattern.
autosomal dominant
PGL__ and PGL__ exhibit an unusual “parent-of-origin—dependent effect” consistent with maternal imprinting of the disease gene. (Although the gene can be inherited from either the father or mother, only paternal transmission will result in development of tumors in the offspring)
PGL1 and PGL2 PGL1 syndrome (SDHD) and PGL2 syndrome (SDHAF2)
Due to the unique inheritence pattern of paragangliomas 1 and 2 (PGL1,PGL2) the trait may appear to ________ within a family
skip generations
Head and Neck paragangliomas can develop in what 3 genetic conditions (besides PGL1-4)?
NF1, MEN2, von Hippel-Lindau syndrome
What is the most common region for paragangliomas?
head and neck
Isolated, mutation-_____ tumors show a 4 : 1 female:male ratio, whereas mutation-______ examples have an EQUAL sex distribution.
negative = female…positive equal
paragangliomas usually occur in middle-aged adults (mean age of ___ to ____ years), although inherited cases tend to develop in patients over a decade younger.
41 to 47 years
What % of hereditary paraganglioma patients will develop more than one tumor?
37%
What is the most common type of paraganglioma?
carotid body paraganglioma
What is a geographic risk factor for the development of a carotid body paraganglioma? Why?
people live at high altitues and have hyperplasia of the carotid body in response to lower oxygen levels
The paraganglioma is characterized by round or polygonal epithelioid cells that are organized into nests or _______
zellballen
Nesting (Zellballen)
The nests in a paraganglioma consist primarily of _____ cells, which demonstrate centrally located, vesicular nuclei and somewhat granular, eosinophilic cytoplasm.
chief
paraganglioma=chief and sustentacular cells arranged in a characteristic nesting (“Zellballen”) pattern
The chief cells in a paraganglioma are stain positive for ________ and _______
chromogranin and synaptophysin
The chief cells in a paraganglioma are surrounded by a flattened layer of _________ cells that are immunoreactive for _____.
sustentacular…S-100 protein
Are paragangliomas encapsulated? What % of paragangliomas metastasize?
Yes, usually a thin fibrous capsule (they are also vascular)……6%
What is the gene mutation in paraganglioma syndrome 4? What % (range) of these can become malignant?
SDHB…13-23%
What are the two proposed cells of origin for granular cell tumor?
thought it was skeletal (granular cell myoblastoma) or neural (schwann cells) (granular cell schwannoma)
Granular cell tumors are most common in the oral cavity
and _______. The single most common site is the ______, which accounts for ____ to ____ of all reported cases…the ______ is the second most common site intraorally
on the skin…tongue…1/3 to 1/2….buccal mucosa
Granular cell tumors most frequently occur in the ___ to ___ decades of life and is rare in children. There is a 2 : 1 ______ predilection….what two colors are they clinically?
4th-6th…FEMALE…mostly pink, sometimes yellow
The granular cell tumor is usually solitary, although multiple, separate tumors sometimes occur, especially in what race?
black patients
Granular cell tumors are NOT _________ and often intermingle with the adjacent connective tissues.
encapsulated
What are the 4 IHC stains that are positive in Granular Cell Tumors?
- S100 2.CD68 3.Calretinin 4.Neuron-specific enolase
An unusual and significant microscopic finding in granular cell tumors is the
presence of acanthosis or ___________ of the overlying epithelium…its reported in __% of cases
pseudoepitheliomatous (pseudocarcinomatous) hyperplasia…50%
GCT recurrence? Malignant transformation?
RARE…extremely rare
What are the 2 alternate names for Congenital Epuils?
Congenital epulis of the newborn and congenital granular cell lesion
Congenital epulis is almost always found on the maxillary alveolar ridge, where else has it been found?
tongue (hence calling it congenital granular cell lesion)
Congenital epulis: multiple tumors present in __% of cases
10%
Congenital epulis gender?
FEMALE…90% of cases
In contrast to the granular cell tumor, the overlying epithelium of a congenital epulis never shows __________ and immunohistochemical analysis shows the tumor cells to be NEGATIVE for _______
pseudoepitheliomatous hyperplasia…S-100 protein
Congenital epulis: recurrence?
NEVER. can even regress on its own
What are the 3 old names for neuroectodermal tumor of infancy?
1.pigmented ameloblastoma 2.retinal anlage tumor 3. melanotic progonoma (the names are inaccurate and should not be used)
What are 3 old names for granular cell tumor?
1.Granular cell myoblastoma (believed to be skeletal muscle origin 2. Graunular cell schwannoma 3. granular cell neurofibroma (more recently believed to be of neuro origin)
