Ch12-Nervous cont.

Question 1

What are the FIRST sign of MEN2B? When do they develop? WHERE do they typically develop?

Answer 1

Oral mucosal neuromas, detectable during infancy…lips and anterior tongue

Question 2

MEN2B: BILATERAL neuromas of the _________ are HIGHLY characteristic

Answer 2

commisural mucosa

Question 3

MEN2B: 50% of pts develop this, esp w age, causing profuse sweating, intractable diarrhea, headaches, flushing, heart palpitations, and severe hypertension.

Answer 3

pheochromocytomas

Question 4

MEN2B: 40% present with __________ in the GI tract which results in abdominal distention, megacolon, constipation, and diarrhea.

Answer 4

ganglioneuromas

Question 5

MEN2B: The most significant aspect of this condition is the development of ______, which occurs in virtually ALL cases.

Answer 5

MTC

Question 6

MEN2B: MTC is an aggressive tumor that arises from the ________ cells (___ cells) of the thyroid gland, which are responsible for ________ production

Answer 6

parafollicular…C cells…Calcitonin

Question 7

MEN2B: MTC silently develops EARLY in life and, without prophylactic thyroidectomy before WHAT AGE?, most patients will develop metastatic tumor during childhood or adolescence.

Answer 7

before 1 year of age!!

Question 8

MEN2B: What lab values are elevated in MTC?

Answer 8

serum or urinary Calcitonin

Question 9

MEN2B: Pheochromocytomas can result in elevated urine levels of what 2 markers?

Answer 9

VAN-ILL-YL-MAN-DELIC acid (VMA) and increased Epi:NorEpi ratios

Question 10

What is the average age of MEN2B pts that do not have the thryroidectomy prophylaxis?

Answer 10

21 years

Question 11

Which form of the MEN2B RET mutation is said to have a less aggressive form of MTC?

Answer 11

A883F less aggressive than M918T

Question 12

What is a fatal complication of Pheochromocytomas and general anesthesia?

Answer 12

hypertensive crisis

Question 13

The ___________ is a rare pigmented neoplasm that usually occurs during the first year of life.

Answer 13

melanotic neuroectodermal tumor of infancy

Question 14

It is generally accepted that melanotic neuroectodermal tumor of infancy is of _______ origin.

Answer 14

neural crest

Question 15

Melanotic neuroectodermal tumor of infancy almost always develops in young children during what age?…only
9% of cases are diagnosed after.

Answer 15

1 year

Question 16

Melanotic neuroectodermal tumor of infancy..where does it show up? Gender? What color is it clinically?

Answer 16

anterior maxilla 69% of cases (skull,epididymus,testis,mandible,brain)…slight male…blue or black

Question 17

What entity can Melanotic neuroectodermal tumor of infancy mimic on a radiograph?

Answer 17

osteosarc..makes a sun ray appearance - Destroys bone and displaces developing teeth

Question 18

High urinary levels of _______ often are found in patients with melanotic neuroectodermal tumor of infancy.

Answer 18

vanillylmandelic acid (VMA)

Question 19

melanotic neuroectodermal tumor of infancy histo: what are the two main cell morphologies seen?

Answer 19

small hyperchromatic round cells (neuroblastic) and larger epithelioid cells with vesicular nuclei

Question 20

Although IHC is not typically needed for Melanotic neuroectodermal tumor, what do the epithelioid cells stain positive for (3)?

Answer 20

CK, HMB-45, neuron-specific enolase

Question 21

Although IHC is not typically needed for Melanotic neuroectodermal tumor, what do the neuroblastic cells stain positive for (3)?

Answer 21

neuron-specific enolase, CD56, synaptophysin

Question 22

Melanotic neuroectodermal tumor: benign or malignant?

Answer 22

MOST benign (despite rapid growth and bone distruction)

Question 23

Melanotic neuroectodermal tumor: recurrence?

Answer 23

20%

Question 24

What location has an association with malignancy in Melanotic neuroectodermal tumor? What % of cases?

Answer 24

brain/skull….7% (probably high)

Question 25

What are the 4 names for a PARAGANGLIOMA?

Answer 25

1.Carotid body tumor 2.Chemo-dec-toma 3.Glomus Jugulare Tumor 4.Glomus Tympanicum Tumor

Question 26

The paraganglia are specialized tissues of ______ origin

Answer 26

neural crest

Question 27

The paraganglia are associated with the _______ nerves and ganglia throughout the body

Answer 27

autonomic

Question 28

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.

Answer 28

chemoreceptors

Question 29

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).

Answer 29

30%...succinate dehydrogenase

Question 30

Four hereditary paraganglioma syndromes (PGL1-4) have been recognized, all of which show an ________ inheritance pattern.

Answer 30

autosomal dominant

Question 31

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)

Answer 31

``` PGL1 and PGL2 PGL1 syndrome (SDHD) and PGL2 syndrome (SDHAF2) ```

Question 32

Due to the unique inheritence pattern of paragangliomas 1 and 2 (PGL1,PGL2) the trait may appear to ________ within a family

Answer 32

skip generations

Question 33

Head and Neck paragangliomas can develop in what 3 genetic conditions (besides PGL1-4)?

Answer 33

NF1, MEN2, von Hippel-Lindau syndrome

Question 34

What is the most common region for paragangliomas?

Answer 34

head and neck

Question 35

Isolated, mutation-_____ tumors show a 4 : 1 female:male ratio, whereas mutation-______ examples have an EQUAL sex distribution.

Answer 35

negative = female...positive equal

Question 36

paragangliomas usually occur in middle-aged adults (mean age of ___ to ____ years), although inherited cases tend to develop in patients over a decade younger.

Answer 36

41 to 47 years

Question 37

What % of hereditary paraganglioma patients will develop more than one tumor?

Answer 37

37%

Question 38

What is the most common type of paraganglioma?

Answer 38

carotid body paraganglioma

Question 39

What is a geographic risk factor for the development of a carotid body paraganglioma? Why?

Answer 39

people live at high altitues and have hyperplasia of the carotid body in response to lower oxygen levels

Question 40

The paraganglioma is characterized by round or polygonal epithelioid cells that are organized into nests or _______

Answer 40

zellballen | Nesting (Zellballen)

Question 41

The nests in a paraganglioma consist primarily of _____ cells, which demonstrate centrally located, vesicular nuclei and somewhat granular, eosinophilic cytoplasm.

Answer 41

chief paraganglioma=chief and sustentacular cells arranged in a characteristic nesting ("Zellballen") pattern

Question 42

The chief cells in a paraganglioma are stain positive for ________ and _______

Answer 42

chromogranin and synaptophysin

Question 43

The chief cells in a paraganglioma are surrounded by a flattened layer of _________ cells that are immunoreactive for _____.

Answer 43

sustentacular...S-100 protein

Question 44

Are paragangliomas encapsulated? What % of paragangliomas metastasize?

Answer 44

Yes, usually a thin fibrous capsule (they are also vascular)......6%

Question 45

What is the gene mutation in paraganglioma syndrome 4? What % (range) of these can become malignant?

Answer 45

SDHB...13-23%

Question 46

What are the two proposed cells of origin for granular cell tumor?

Answer 46

thought it was skeletal (granular cell myoblastoma) or neural (schwann cells) (granular cell schwannoma)

Question 47

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

Answer 47

on the skin...tongue...1/3 to 1/2....buccal mucosa

Question 48

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?

Answer 48

4th-6th...FEMALE...mostly pink, sometimes yellow

Question 49

The granular cell tumor is usually solitary, although multiple, separate tumors sometimes occur, especially in what race?

Answer 49

black patients

Question 50

Granular cell tumors are NOT _________ and often intermingle with the adjacent connective tissues.

Answer 50

encapsulated

Question 51

What are the 4 IHC stains that are positive in Granular Cell Tumors?

Answer 51

1. S100 2.CD68 3.Calretinin 4.Neuron-specific enolase

Question 52

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

Answer 52

pseudoepitheliomatous (pseudocarcinomatous) hyperplasia...50%

Question 53

GCT recurrence? Malignant transformation?

Answer 53

RARE...extremely rare

Question 54

What are the 2 alternate names for Congenital Epuils?

Answer 54

Congenital epulis of the newborn and congenital granular cell lesion

Question 55

Congenital epulis is almost always found on the maxillary alveolar ridge, where else has it been found?

Answer 55

tongue (hence calling it congenital granular cell lesion)

Question 56

Congenital epulis: multiple tumors present in __% of cases

Answer 56

10%

Question 57

Congenital epulis gender?

Answer 57

FEMALE...90% of cases

Question 58

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 _______

Answer 58

pseudoepitheliomatous hyperplasia...S-100 protein

Question 59

Congenital epulis: recurrence?

Answer 59

NEVER. can even regress on its own

Question 60

What are the 3 old names for neuroectodermal tumor of infancy?

Answer 60

1.pigmented ameloblastoma 2.retinal anlage tumor 3. melanotic progonoma (the names are inaccurate and should not be used)

Question 61

What are 3 old names for granular cell tumor?

Answer 61

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)