4. Pigmented Pathology Flashcards
(37 cards)
1
Q
Amalgam tattoo
• Most common oral ____ pigmentation
• ____
• ____ tattoo looks similar
• Looks brownish blue clinically ○ Not bc of \_\_\_\_ production ○ Bc of amalgam particles which has persisted after treatment from years prior • Consequence of iatrogenic dentistry > only a dentist could have done this to a patient ○ Clamp impinged gums and tore through gingival tissue > amalgam particles enter the tissue; or via extraction socket • Can only develop if \_\_\_\_ particles into the underlying tissue > tissue heals and particles disperse • Best guess diagnosis from picture: amalgam tattoo ○ Amalgams located regionally ○ No teeth (extractions) and these lesions are on the \_\_\_\_ § If on buccal mucosa > wouldn't think amalgam tattoo • Clinical description: not amalgam tattoo > would be a \_\_\_\_ lesion or coloration clinically ○ Could be a \_\_\_\_ ○ Could be \_\_\_\_ (will look exact same way) • Biopsy: ○ Show foreign colored material deep in the connective tissue § Not true pigment - metallic fragments/shavings • Graphite tattoo ○ May look similar to amalgam tattoo (clinically and definitely microscopically) ○ Develops year as well ○ BR: graphite tattoo • Once diagnosed nothing needs to be completed, but warrants a diagnosis ○ Doesn't require surgical removal or follow-up • For pigmented lesion you will always \_\_\_\_ ○ One exception: if amalgam tattoo and they're large enough > can see them on a \_\_\_\_; no biopsy required!
A
focal iatrogenic graphite melanocyte amalgam ridge pigmented nevus melanoma biopsy radiograph
2
Q
Metal-induced pigmentation
• ____
• ____
• ____
• Amalgam alloy can cause clinical \_\_\_\_ • Systemic poisoning with heavy metals can also result in pigmentation • Flint, MI > oral coloration around the gingival margin ○ In addition to \_\_\_\_ effects ○ Gray, black around the margins • Not clinically \_\_\_\_ ○ The neurologic changes are consequential bc of the poisoning • Treatment: \_\_\_\_ therapy for those who are severely affected ○ Won't resolve the deposits - they'll resolve by \_\_\_\_ months/years afterwards • Won't see anything \_\_\_\_ • In Caucasian - any and all oral pigmentation is \_\_\_\_ ○ Focal or diffuse ○ Not always clinically \_\_\_\_ - won't always cause harm or death • In patient with skin color - is it physiology? Or is it something that's more significant ○ \_\_\_\_ and diagnostic skills play a role ○ If in doubt > biopsy
A
iron
mercury
arsenic
pigmentation neurologic consequential chelation themselves radiographically
physiologic
history
3
Q
Ephilis (Freckle)
• Increased ____ pigment
• NOT melanocytic ____
• True focal pigmentation - pigmentation caused by melanin • Most common example: freckle ○ Variation of normal § Not \_\_\_\_ • Microscopically: ○ Increased melanin pigment, but not melanocytic hyperplasia § Not increased number of melanocytes! ○ Melanocytes found in the \_\_\_\_ layer within the epithelium § Not continuously throughout the entire basal layer, \_\_\_\_ and orderly § Produce melanin □ Derived from \_\_\_\_ □ Made up of a couple molecules ® Eumelanin ® \_\_\_\_ ® Give rise to yellow-tan color of melanin □ Gets taken up by adjacent basal epi cells ® All the basal cells look \_\_\_\_ via phagocytosis ® Only 4-5 melanocytes in the entire area □ More melanin =/= more \_\_\_\_ If melanocytic hyperplasia > potentially a preoneoplastic or \_\_\_\_ proliferation
A
melanin hyperplasia pathologic basal scattered tyrosine pheomelanin brown melanocytes neoplastic
4
Q
Causes of diffuse melanocytic pigmentation
- Physiologic
- Smoker’s melanosis
- Laugier-Hunziker pigmentation
- Post-inflammatory hyperpigmentation
- Drug-induced
- Hormone-induced
- Heavy-metal poisoning
- Submucous fibrosis
- Adrenal insufficiency
- Hyperthyroidism
- Cushing syndrome / Cushing disease • Primary biliary cirrhosis
- Hemochromatosis (early stages)
- Genetic disease
- Vitamin B12 deficiency
- HIV/AIDS (late stages)
Malignant melanoma
• Melanoma is the great \_\_\_\_ ○ Can present \_\_\_\_ or as a \_\_\_\_ pigmentation ○ Patient with pigmentation of any nature > warrants a biopsy • \_\_\_\_ pigmentation > most common cause of diffuse oral pigmentation
A
mimicker
focally
diffuse
physiologic
5
Q
Pigmentation
physiologic
drug-induced
idiopathic
vitamin B12
ornamental
malignant melanoma
• \_\_\_\_ > african woman gums pigmented using a dye ○ Not under melanocyte pigmentation - it's \_\_\_\_ pigmentation ○ Mimics physiology
A
ornamental
exogeneous
6
Q
Pigmentation
restorative materials
smoker’s melanosis
addison’s disease
• L two patients - coloration secondary to restorative materials • Addison - systemic disease; \_\_\_\_ • Smoker's melanosis (v. nicotinic stomatitis) ○ Non-\_\_\_\_ relevant pigment ○ Won't cause any kind of harm > reaction to cigarette smoking and due to the heat of the smoke § Smokers who are prone to pigment in skin, often time \_\_\_\_ (estrogen and prog stimulate pigmentation production) § \_\_\_\_ occuring condition, but it's now it's melanocytic pigment production because of thermal stimulation § Stop smoking > pigmentation will go away □ Doesn't warrant \_\_\_\_
A
genetic clinically female chronically therapy
7
Q
Medications associated with pigmentation
• Do not memorize • Large array of drugs that are known to cause oral and cutaneous pigmentation • Only three drugs we should know: ○ Plaqunil (hydroxychloroquine) § Used to treat \_\_\_\_ § Only one that has a characteristic \_\_\_\_ pattern □ Occurs on the \_\_\_\_ □ This patient has history of malaria, and has been in remission > what's diagnosis > best guess is drug-induced pigmentation ® Still biopsy patient because it can still be melanoma ○ Premarin § \_\_\_\_ □ May induce pigmentation bc altering \_\_\_\_/prog levels in that person □ \_\_\_\_ can also induce pigmentation based on the same reasoning ○ Minocycline § \_\_\_\_ § Used to treat \_\_\_\_ § Can induce pigmentation
A
malaria
pigmentation
hard palate
birth control
estrogen
pregnancy
tetracycline
severe acne
8
Q
Brief introduction to endocrinology
• Host of systemic diseases that can cause pigmentation ○ Addison's disease § Result of disruption of endocrine pathway § Links \_\_\_\_ to \_\_\_\_ gland to \_\_\_\_ gland □ Hypo produces \_\_\_\_) and acts on pit gland to trigger production of \_\_\_\_ > leaves brain to act on adrenal glands to produce \_\_\_\_ > systemic effects □ When these links are disrupted things can go poorly ® May include overproduction of pigment ○ Cushing's syndrome
A
hypo pit adrenal CRH ACTH glucocorticoids
9
Q
- Pit gland > ACTH; adrenal glands produce CS
- ACTH secreted > adrenal glands > CS secretion from the adrenal glands > once CS are released and reach threshold > ____ feedback on pit to shut down ACTH secretion
A
negative
10
Q
Addison disease
• In Addison's disease: • Both adrenal glands are \_\_\_\_ (disrupted by tumor, maybe cancer, a viral disease, genetic dysfunction) ○ Can be \_\_\_\_ or acquired • Adrenal glands aren't responding properly in response to the ACTH > brain senses to produce more \_\_\_\_ to stimulate the adrenals to produced CS • Part of ACTH protein contains \_\_\_\_ (melanocyte stim hormone) > as ACTH increases > MSH increases also > acts on melanos to produce more \_\_\_\_ > clinical pigmentation
A
hypofunctioning congenital ACTH aMSH pigment
11
Q
• Cushing disease
• Caused by a ____ tumor
○ Usually ____
○ Can be ____ > tumor cells can produce whatever they produce at high quantities
§ Producing massive amounts of ____ that cannot be controlled by negative feedback mechanism
§ Adrenals are functioning ____
□ Also increasing to high levels of ____ > pathology by itself
§ Same result as Addison’s disease > clinical pigmentation
A
pit benign hyperfunctioning ACTH properly CS
12
Q
Addison’s disease (Hypoadrenocorticism)
- Insufficient production of ____
- ____ accumulates within blood
- Treat by ____ therapy
Cushing syndrome • Prolonged exposure to high \_\_\_\_ levels • ACTH-dependent or ACTH-\_\_\_\_ • Most cases are \_\_\_\_ • Cushing disease due to \_\_\_\_ tumor
• Addison's treatment ○ Add \_\_\_\_ - give the patient prednisone to replace the CS that they're not getting physiologically • Cushing's caused by pit tumor ○ Excessive CS > more broad condition > Cushing syndrome § Can be caused by Cushing disease § Only Cushing disease is the form of the syndrome that causes \_\_\_\_ □ Bc only that form is caused by \_\_\_\_ production from the brain
A
corticosteroids
ACTH
replacement
corticosteroid
independent
iatrogenic
pituitary
steroids
pigmentation
ACTH
13
Q
Clinical manifestations of Cushing syndrome
- Weight gain
- Easy bruising
- Moon facies
- Abdominal striae
- Muscle weakness
- Fatigue
- Osteoporosis
- Acne and other infections
- Mood disorders
- Hypertension
- Diabetes
- Irregular menstruation
- Hirsutism
- Back pain
- Buffalo hump
- Erectile dysfunction
- Mucocutaneous pigmentation• Differ addison’s from cushing
○ Cushing - ____, take on a lot of water, big fat face (____), diabetes mellitus, ____ (not seen in addison’s), hair development (hirsutism), ____ (pituitary adenoma producing GH)
○ Everything else is common to both
• Treat addisons > give patients sytemic ____
• Treat Cushings > reduce the amount of coritcosterois
○ ____ - stop prescribing
○ By tumor - excise the ____
A
edema
moon facies
weight gain
gigantism
prednisone
iatrogenic
tumor
14
Q
Peutz-Jeghers syndrome
- ____ dominant
- ____-like lesions
- Intestinal ____
- ____ predisposition• ____ DISEASE
○ Diffuse pigmentation
• Oral facial > ____ thing seen clinically > initial diagnosis of patient
○ Freckling of the lips and perioral skin
§ Not pathogneumonic - highly characteristic (only one other disease that has this clinically)
§ Not any real significance beyond the ____
○ Distinct pattern
• Intestinal polylps
○ Rectal bleeding, and pain
• At risk for cancer
○ Intestinal, GU, pancreas, and ____ (most common site!)
• No ____!!!
○ Symptomatic relief
• Freckling on finger tips and toes!
○ ____ for the disesase
A
autosomal
freckle
polyposis
cancer
genetic initial esthetics breast treatment pathognomonic
15
Q
Seborrheic keratosis
• ____ tumor
• ____ or multiple
• Often ____
• Not melanocytic in nature, but pigmented ○ Epithelial tumor § But the pigment is from the \_\_\_\_ ○ Benign
A
epithelial
soliatry
pigmented
melancoyte
16
Q
Dermatosis papulosis nigra
• ____ form of multiple facial seborrheic keratoses
* Smaller bumps, but masses (paps and nods) on the upper or lower cheek * Genetically inherited * Each papule represents a discrete \_\_\_\_
A
hereditary
seborrheic keratosis
17
Q
Melanocytic nevus
• ____
• Nodular or ____
• ____ pigmented
• The above can be confused with a nevus! • Classic mole • Mole that isn't uniformly pigmented > get it checked out! ○ Uniformly pigmented tends to be \_\_\_\_ and not malignant • Nevi can be macular (flat) or nodular (raised) • Not common in oral cavity, but if they do occur > biopsy > because \_\_\_\_ can mimic a nevus • BR: warrants more evaluation > irregularly pigmented > benign
A
benign macular uniformly benign melanoma
18
Q
Melanocytic nevus
• Neoplastic melanocytes are the cells • Junctional nevus ○ The melanocytes are all confined to the level of the \_\_\_\_ where the basal cells meet the BM (where the melanocytes live) ○ Confined to same area where they're found • Compound nevus ○ Melanos at \_\_\_\_ and in the CT ○ Not \_\_\_\_ the CT (didn't break the BM) § Just drop from the junction into the CT • Intradermal or intramucosal nevus ○ All found in the \_\_\_\_, not in the junction • The first three (junctional, compound, and intramucosal) are part of the same \_\_\_\_ spectrum of lesion. The blue nevus is its own animal altogether. • Blue nevus
A
BM junction invaded CT biological/clinical
19
Q
Nevus • 3 main types – \_\_\_\_ – \_\_\_\_ – \_\_\_\_ • Natural progression of junctional -> compound -> \_\_\_\_
• Junctional > compound > intramucosal (intradermal) • Once diagnosed > at level of intramucosal nevus ○ Where all cells are in the CT ○ Most \_\_\_\_ nevus! § Most people don't pay attention to their moles • Don’t have to eecongize junctional nevus ○ Ball structure are neoplastic \_\_\_\_ that are confined to the junctional area
A
junctional compound intramucosal intramucosal diagnosed melanos
20
Q
Blue nevus
• ____, gingiva
• ____ most common nevus
• Second most common to be diagnosed • Has to do with how light reflects against the melanin • On skin they can occur \_\_\_\_ they want • If diffuse pigmentation > other story ○ If single lesion > \_\_\_\_
A
hard palate
second
anywhere
biopsy
21
Q
Malignant melanoma
Malignant tumor of ____
____ most common skin cancer
____ melanomas rare but deadly – < 50% 5-year survival rate
• Melanoma can manifest as anything > no features to diff small pigmented lesion to a benign one; can look like anything • Only cancer of melanos • Third most common form of skin cancer; most \_\_\_\_ form ○ Basal is \_\_\_\_ common, squamous second, melanoma third • Not common - rare > more deadly in \_\_\_\_ cavity than they are in the skin ○ Poor survival rate! • In oral cavity can look like anything! Nevus, etc
A
melanocytes third mucosal deadly most oral
22
Q
Risk factors for malignant melanoma • \_\_\_\_ history – First degree relatives • \_\_\_\_ (atypical) nevi • High number of \_\_\_\_ • \_\_\_\_/sun exposure
• Most common on skin • Risk factor: \_\_\_\_ exposure ○ Not chronic, but can increase risk ○ More \_\_\_\_ history of acute exposure > sunburn ○ Extrinisc • Intrinsic: family history, \_\_\_\_ generation relative (bro, sis parent) • Dysplastic nevi ○ Pre-cancerous nevi ○ 1-10 > at risk for melanoma • Dozens of moles on body ○ Each mole on its own low risk ○ 25 moles > \_\_\_\_-fold transformation
A
family dysplastic nevi sunburns sun repeated first 25
23
Q
- ____ of shape: one half does not look like the other
- ____ is irregular: scalloped, notched, discontinuous
- ____ is uneven: multiple shades ranging from white to tan to brown to black occasionally some red as well
- ____ is larger than 6mm
- ____: gradual increase in size and elevation
• Hallmark of melanoma: ABCDE ○ Asymmetric ○ Poorly irregular border ○ Unevenly colored ○ >6 mm diameter ○ Enlarged/evolving over time • Line through the center ○ Not symmetric; border is \_\_\_\_; color is \_\_\_\_; diameter is larger (1cm); raised area above the surface (there for 6 months)
A
asymmetry border color diameter enlargement
irregular
irregular
24
Q
Role of pathologist
• Critical in ____
• Can predict ____
• \_\_\_\_ pigmented • Border is not completely \_\_\_\_ • Relatively \_\_\_\_ • Pretty small • Still a \_\_\_\_! • As pathologist ○ \_\_\_\_ features to help predict prognosis - not absolute!
A
diagnosis prognosis uniformly irregular symmetric melanoma microscopic
25
```
Melanoma prognostic features
• Breslow thickness
– Most important ____ parameter
– Measures ____ of melanoma
– Measure from ____ cell layer to ____ tumor cell
– Measure in ____
```
• There are several microscopic features used to help predict prognosis of a melanoma:
• 1) Breslow Thickness
• The pathologist takes a ruler and measures from the granular cell layer down to what looks like the
very last tumor cell in the biopsy.
• The thicker the lesion, the worse the ____ (a 2mm lesion has a better prognosis than a 5mm
lesion)
• *This is the most defining parameter used to gauge prognosis*
```
prognostic
thickness
granular
deepest
millimeters
```
prognosis
26
* This cartoon illustrates the Breslow thickness measurement
* Thin melanomaà____ chance of survival
* Thick melanomaàsurvival rate ____ dramatically
* We are not talking about cm here, we are talking about mm (the difference between 0.5mm and 4.9mm is enough to increase the death rate by ____%
good
drops
70
27
Melanoma prognostic features
• Clark level of invasion
– How ____ are tumor cells
– LevelsI-V
Level I: Melanoma in situ with pagetoid growth
• Another microscopic paramter
• Use knowledge of CT and tissues of dermis
○ Not about how thick
○ But how ____ the cells are going
• Five levels
○ I
§ Tumor cells are confined ot the ____
§ Lentigo maligna
□ ____ lesion - the cells are combined in the epithelium
□ Still a ____
® Will start invading into the CT if allowed to invade
§ In Clark level 1 we get something known as ____, which implies that the tumor cells in the basal layer begin growing up into the epithelium (see my amazing artwork below)
```
deeper
deep
epithelium
macular
cancer
pagetoid spread
```
28
Melanoma prognostic features
• Clark level of invasion
– How deep are tumor cells – LevelsI-V
2) Clark Level of Invasion
• There are five levels (I-V) to the Clark level of invasion:
• Level II – the tumor cells are now within the ____ (remember that the lamina propria is composed of the papular lamina propria which is superficial CT, and the reticular lamina propria which is deep CT)
papillary lamina propria
29
Level III: Malignant cells filling the papillary dermi
2) Clark Level of Invasion
• There are five levels (I-V) to the Clark level of invasion:
• Level III – The tumor cells make up most of the ____ (they ____ up the papillary lamina propia)
papillary lamina propria
| fill
30
Level IV: Malignant cells extend Into the reticular dermis
Clark Level of Invasion
• There are five levels (I-V) to the Clark level of invasion:
• Level IV – the tumor cells are now within the ____ (which is ____ than the papillary)
reticular lamina propria
| deeper
31
Level V: Malignant cells in the subcutaneous fat
2) Clark Level of Invasion
• There are five levels (I-V) to the Clark level of invasion:
• Level V – the tumor cells are now within the ____ (subcutaneous fat) • The deeper they go, the worse prognosis.
subdermis
32
Melanoma prognostic features
____ – poor prognosis
____ – poor prognosis
____ invasion – poor prognosis
Tumor infiltrating ____ – good prognosis
• If see lymphocytes embedded in the tumor > good prognosis
○ Melanomas are highly ____ tumors > have ability ot provoke immune response > can use the response therapeutically
§ Therapy now: no reposne to surgery/chemo > direct immunogenic approach to treatment > given ____ mediated treatments to hekp reduce tumor burden
• All micro and clinical features are important in determinign skin melanomas > don't apply to ____ melanomas!
○ All the below photos are melanomas
○ R: is nevus > biopsy > cancer
mitosis
ulceration
lymphovascular
lymphocytes
immunogenic
antibody
oral
33
Mucosal melanoma can mimic other pathologies therefore pigmented lesions always warrant ____!!
* As we’ve discussed, the microscopic features are critical for diagnosing skin melanoma, as are the clinical parameters (A, B, C, D, and E). However these do not apply to ____ melanoma.
* Shown in these three images are all examples of malignant melanoma (note the far right image was thought to be a nevus, a small benign lesion, but upon biopsy it was found to be cancer).
* There is no microscopic criteria we can use to predict prognosis of a ____ melanoma
biopsy
oral
mucosal
34
Treatment of primary melanoma
```
• Surgical excision
– Standard of care for all ____ melanomas
• Sentinel lymph node biopsy (staging)
– Dependent on tumor ____
– ____ mm or greater
• Standard ____ chemotherapy
```
• First surgery and remove bulk/entire tumor!
• Look for regional lymph nodes in proximity to the tumor site
○ Sentinel lymph node biopsy
○ Making sure no invasion of the lymph nodes
○ No lymph nodes.> ____ prognosis
• Will undergo ____ after surgery (STANDARD FOR MOST PATIENTS)
• This all first-line therapy
primary
thickness
1
cytotoxic
good
chemo
35
Treatment of metastatic melanoma
Melanomas are ____ cancers
```
Anti ____ (ipiluminab)
– Builds immune response against melanoma
```
Targeted therapy
• No response to fhirst-line thearpy > immunloigc therapy
○ Target approaches that are based on tumor cells be immunogenic > trigger a ____ > to help kill the tumor cells
• Ipiluminab (Anti CTLA-4)
○ Treat patients whose melanomas aren't response, or metastatic disease
immunogenic
CTLA-4
cytokine storm
36
Treatment of metastatic melanoma
* Melanomas may have ____ mutation
* Can be treated with BRAF-inhibitors (____)
• All patients are sequenced
○ Like lung cancers > have BRAF mutation
○ Same drug (vem) can be used to treat some melanomas as well
BRAF
| vemurafemib
37
Cutting edge medicine
• October 2015 FDA approved modified HSV-1 for melanoma treatment
– Kills ____ cells
– Triggers ____ system
* Approved using ____ as a means of a targeted immunogenic approach to treating melanomas
* Modify virus slightly to help induce a stronger immune response to it > tumor vaccine
cancer
immune
herpes simplex virus
