5. pigmented lesions part 4

endocrine abnormality and melanin disruption

The pituitary gland's melanocyte-stimulating hormone (MSH) is a key endocrine factor in melanin production, directly influencing skin and hair pigmentation. Other hormones like adrenocorticotropic hormone (ACTH) and estrogen can also affect melanin by influencing MSH levels or the activity of the tyrosinase enzyme, a key component in melanin synthesis. These hormones are linked to various pigmentation changes, from tanning to conditions like melasma and Addison's disease. 

Addison’s disease

• hypoadrenocorticism

• insufficient production of adrenal corticosteroids

• diffuse or patchy hyperpigmentation, especially of sun-exposed sin

what are some characteristics of Addison disease?

• bronze pigmentation of skin

• changes in distribution of body hair

• GI disturbances

• weakness

• weight loss

• postural hypotension

• hypoglycemia

what are characteristics of adrenal crisis?

• profound fatigue

• dehydration

• vascular collapse (↓bp)

• renal shutdown

• ↓serum NA

• ↑serum K

which autoimmune melanin-associated pigmented lesion?

Addison’s

what are the types of metabolic/systemic melanin-associated pigmented lesions?

melasma, acanthosis nigricans, cushings 

which type of metabolic/systemic melanin-associated pigmented lesions?

• brown or gray-brown patches of hyperpigmentation on the face (sometimes a mylar pattern)

• aka mask of pregnancy = chloasma  

melasma

what are the types of neoplastic melanin-associated pigmented lesion?

• melanotic neuroectodermal tumor of infancy (MNTI, rare but distinct)

• oral melanotic nevus

which neoplastic melanin-associated pigmented lesion?

• Krompecher in 1918 as a congenital "melanocarcinoma”

• 90% in head and neck and within the first 6 months of life

• Male predilection (1.5:1), 60% on the palatal mucosa

• Brownish-red mass of alveolar mucosa

• High levels of vanillylmandelic acid in urine

• BRAF V600E mutation identified in some cases (targeted therapies yay!)

• surgically excised

MNTI

BRAF V600E

MNTI

MNTI

T or F: MNTI usually in maxilla

true

MNTI

what is the treatment for MNTI?

• surgical resection (~20% recurrence rate; some intentionally left to be removed later)

• radiation

• chemotherapy

what is this: benign developmental malformation(s), variants can be acquired or congenital ex: melanocytic (blank)

nevus

features of which neoplastic melanin-associated pigmented lesion?

• 2nnd-4th decade 

• locations: 

  • hard palatal mucosa 44%

  • buccal mucosa 22%

  • vermillion border 18%

  • gingiva 12%

  • retromolar pad 4%

oral melanocytic nevus

describe most common types of oral melanocytic nevi

• intramucosal nevus 64%

• blue nevus 16.5%

• compound nevus 16.5%

• junctiona; 3%

• combined 

• balloon cell

• spitz

features of which neoplastic melanin-associated pigmented lesion?

• Diagnosed and biopsied in the 2nd -4th decades, females (2:1)

• Pigmented, raised (nodular/papular)

• Hard palatal mucosa and buccal mucosa…. Lip mucosa, gingiva, vermilion

• Intramucosal ➔ blue and compound ➔ others

• BRAFV600E mutation and GNAQ209 (blue nevus)

BRAFV600E and GNAQ209 gene mutations 

oral melanocytic nevus, blue nevus

4 types of oral melanocytic nevi and their macule, plaque, and nodule status

nevi vs macule

nevi = developmental, flat or raised VS macule = reactive, flat

which melanocytic nevus histopathological features?

• Unencapsulated proliferation of nevus cells, organized in theques

• Lack dendritic processes of melanocytes

• Migrate from junctional to compound to intradermal

acquired melanocytic nevus

intramucosal nevus, (unique nevus cells)

nest of melanocytes, unique 

Type B to Type C morphology is a key characteristic of benign nevi and a sign of normal cell maturation, which helps pathologists distinguish them from melanoma, where this organized maturation process is typically lost

blue nevus, 1:subtle 2: not subtle

common blue nevus

compound nevus

combined nevus

what is the differential diagnosis for a pigmented lesion (nevus)?

• amalgam tattoo

• medication-induced pigmentation

• melanoma (hopefully not)

treatment for pigmented lesion (nevus)

excision

Melanomas are a type of cancer that occurs in both the skin and oral mucosa. It however occurs far less commonly intraorally and the palate and gingiva are high risk sites.

A. both statements are true

describe the evolution of a melanoma (hint)

nevi vs melanoma (ABCDE)

melanoma rates

• 87,100 cases, 5.2% of all new cancer cases

• 9,730 deaths, 1,6% of all cancer deaths 

• 97.1% survival (death stable over the years)

what are some melanoma risk factors?

• use of immunosuppressants

• large number of freckles

• presence of red hair

• skin that burns easy

• exposure to sunlight

• presence of atypical moles

which gene mutation BRAF?

acquired nevi and cutaneous melanoma (BRAF V600E MNTI)

what are the major clinicopathological types of cutaneous melanoma?

1. superficial spreading melanoma

2. lentigo maligna melanoma

3. acral lentiginous melanoma

4. nodular melanoma

which premalignant/malignant melanin-associated pigmented lesion?

• More prevalent in African Americans and Japanese

• Arise de novo

• 7th decade, slight male predilection

• Palatal mucosa, maxillary gingiva (>70%)

• Breslow and Clark criteria (skin criteria) do not correlate with clinical behavior/prognosis

• can be heterogenous or homogenous

oral melanomas

primary oral melanomas are less than (blank)% of all melanomas

1%

oral mucosal melanoma

KIT gene mutation

oral mucosal melanoma

heterogenous oral melanoma

oral melanoma

describe site distribution in primary head and neck mucosal melanoma

nasal cavity (47.5%), hard palate and gingiva (15%), alveolus (11.5%), sinonasal cavity (10%)

what are the five levels in Clark tumor invasion?

• level I: in situ melanoma

• level II: invasion of the papillary dermis by single cells or small nests

• level III: invasive tumor usually as expansile nodule abutting on reticular dermal interface

• level IV: invasion of reticular dermis

• level V: invasion of subcutaneous fat 

describe microstaging of primary head and neck mucosal melanoma

level I: pure in situ melanoma w/o evidence of invasion or in situ w microinvasion 

level II: invasion up to lamina propria

level III: deep tissue invasion into skeletal muscle, bone, or cartilage

how is microinvasion defined in the context of primary head and neck mucosal melanoma ?

invasive or individual or clusters of < 10 atypical melanocytes near the epithelial-subepithelial junction

oral melanoma

what is the management for oral melanoma management?

• Primary rx – excision with clear margins or radiation

• 50% recurrence

• Nodal and distant mets in upto 65%

• 5 year survival is 10-20% (from mets)

oral pigmented lesions are considered ?

melanoma until proven otherwise

high risk sites of oral pigmented lesions include

maxillary gingiva and hard palate

multifocal lesions may suggest

systemic conditions

describe flow of finding a pigmented lesion: differential diagnosis, history, etc

what are some endogenous and exogenous reasons for pigmented lesions?

• foreign material

• melanin

• vascular

• saliva/mucin

• cystic fluid

Which of the following cutaneous melanoma is found more commonly in the oral cavity?

a) Superficial Spreading Melanoma

b) Acral Lentiginous Melanoma

c) Nodular Melanoma

d) Metastatic Melanoma

e) Lentigo Maligna Melanoma

b) Acral Lentiginous Melanoma

describe the differences between:

appearance, growth pattern, and location

• Superficial Spreading Melanoma is the most common type, growing horizontally before invading deeper

• Nodular Melanoma grows vertically from the start and is more aggressive

• Acral Lentiginous Melanoma is found on the palms, soles, and under nails, and is not strongly linked to sun exposure

• Lentigo Maligna Melanoma typically affects older people on sun-damaged skin like the face, and has a prolonged horizontal growth phase before becoming invasive

• Metastatic Melanoma is a later stage where the cancer has spread to other parts of the body.