1M-SKIN Flashcards
Common, benign, pigmented, predominantly basal keratinocytic proliferations
occurring chiefly on the trunk of adults.
SEBORRHEIC KERATOSIS
Part of Paraneoplastic Syndrome
SEBORRHEIC KERATOSIS
Sudden appearance or increase in numbers and size + pruritus
Lesser Trelat sign
What malignancy is seborrheic keratosis assoc with?
Malignancy of gastrointestinal tract due to stimulation of TGF-a.
Common locations of seborrheic keratosis
Trunk, head and neck
*old trans: trunk, head, face, extremities
Seborrheic keratosis is assoc with what mutation?
FGFR-3
*FGFR3-RAS-mitogen-activated protein kinase
(MAPK) pathway
Minute pore openings, crater-like structures filled with keratin
Keratinocytic cyst
Presence of keratinocytic cysts which are called __
Horn cysts
The predominant histologic feature in seborrheic keratosis
Remarkable
hyperkeratosis
Single, benign, heavily pigmented lesion can be
confused with melanoma
SEBORRHEIC KERATOSIS
A 50y/o presented with a dark brown exophytic lesion. It has a waxy plaque appearance with crater-like openings. Px complained of pruritus.
SEBORRHEIC KERATOSIS
Elevation of the dermal region covered by skin and fibrovascular stroma surrounding the polyp.
ACROCHORDON
Other names of ACROCHORDON
● Fibroepithelial polyp
● Fibroepithelial/squamous papilloma
● Fibroma molle
● “Skin tag”
Main difference of ACROCHORDON with other tumors?
Absence of adnexal structures (in the polypoid region) in the underlying dermis
An obese, diabetic, pregnant patient complained of flesh colored polypoid lesions in her intertriginous areas
ACROCHORDON
Common locations of ACROCHORDON
Neck, trunk and intertriginous areas
Treatment for ACROCHORDON
Excision
Lesion with brown to dark gray in color, hard to rough/sandpaper-like consistency because of keratin production.
ACTINIC KERATOSIS
Pre-malignant epidermal tumor common in lightly-pigmented patients
ACTINIC KERATOSIS
Lesion due to sun-damaged skin - by ionizing radiation and industrial chemicals such as arsenic and hydrocarbons
ACTINIC KERATOSIS
Common locations of ACTINIC KERATOSIS
Face, arms, dorsum of hands
Actinic keratosis located in the lips
ACTINIC CHEILITIS
T or F: Actinic keratosis can regress.
TRUE
T or F: Actinic keratosis can progress to carcinoma.
TRUE
Actinic keratosis is assoc with what mutation?
p53 protein accumulation
Treatment of Actinic keratosis
- freezing
- superficial curettage
- application of antineoplastic chemotherapeutic agents
- surgical excision
Carcinoma-in-situ
BOWEN DISEASE
Mutation present in BOWEN DISEASE
p53 mutation
Scaly erythematous plaques seen in non-chronically sun-exposed skin
BOWEN DISEASE
Squamous cell carcinoma-in-situ in sun exposed areas
Bowenoid actinic keratosis
Actinic keratosis and bowen disease are at risk to
develop into a full blown malignancy called ____?
Squamous cell carcinoma
Brown velvety plaques
ACANTHOSIS NIGRICANS
Location of ACANTHOSIS NIGRICANS
Axillae, back of
the neck, and other flexural areas.
Mutation involved in ACANTHOSIS NIGRICANS
FGFR-3
Malignant condition associated with ACANTHOSIS NIGRICANS
GIT Adenocarcinomas
Second most common tumor arising in sun
exposed areas
SQUAMOUS CELL CA
Most common causes of SQUAMOUS CELL CA
○ UV exposure ○ Chronic immunosuppression ○ Industrial hazards ○ Chronic ulcers and diseases ○ Tobacco and betel nut chewing
Mutation involved in SQUAMOUS CELL CA
● Defects in p53
● Mutations leading to increase RAS signaling
● Mutation leading to decrease notch signaling
Histologic variants of SQUAMOUS CELL CA
○ Sarcomatoid/Spindle SCCA
○ Adenoid/Pseudoglandular SCCA
○ Verrucous carcinoma
Which histologic variant of SQUAMOUS CELL CA?
○ Continuity of tumor to basal layer of epidermis
○ Foci of clear cut squamous change
Sarcomatoid/Spindle SCCA
Sarcomatoid/Spindle SCCA variant immunoreactivity
High molecular weight keratin immunoreactivity
Histologic variant of SQUAMOUS CELL CA due to defects in desmosomes.
Adenoid/Pseudoglandular SCCA or Acantholytic type
Adenoid/Pseudoglandular SCCA variant in sun-exposed areas will require you to rule out ___?
○ Metastatic adenoCA
○ Primary adenoCA
○ Adenoquamous CA
○ Mucoepidermoid CA
Adenoid/Pseudoglandular SCCA variant immunoreactivity
Reduction of the cell adhesion molecule (CAM) syndecan-1
Which histologic variant of SQUAMOUS CELL CA?
○ Very well differentiated SCC
○ Warty/ cauliflower/ fungating lesion or ulcerated due to crater
○ (+) local/ stromal invasion
Verrucous carcinoma
Treatment of SQUAMOUS CELL CA
○ Complete excision - tx of choice
○ Alternative therapies: curettage and
electrodessication, cryotherapy, and radiation
therapy.
SCC and BCC staging
T1 = 2 cm
T2 >2 - 5 cm
T3 >5 cm
T4 (+) invasion
Most common invasive cancer
BASAL CELL CARCINOMA
BASAL CELL CARCINOMA risk factors
○ Sun exposed areas
○ Fair complexion
○ Elderly
○ Immunosuppressed
T or F: BASAL CELL CARCINOMA is locally aggressive, fast growing, and frequently metastasizes
FALSE
○ Locally aggressive
○ SLOW growing
○ RARELY metastasizes
Mutation involved in BASAL CELL CARCINOMA
Hedgehog signaling pathway
Multiple BCC in a young patient
Nevoid basal cell carcinoma syndrome
Genetic involvement of NBCCS
○ Autosomal dominant
○ Germline loss in PTCH gene
Other tumors assoc with NBCCS
○ Medulloblastoma
○ Odontogenic keratocyst
○ Ovarian fibroma
BCC histologic features
○ Basaloid tumor arising from epidermis ○ Nests of basaloid cells w/ scanty cytoplasm & elongated hyperchromatic nuclei ○ Peripheral palisading ○ Myxoid stroma ○ Peritumoral clefting
Difference of BCC from SCC histologically
○ Darker/ more bluish
○ Not seen in mucosal surfaces
BCC growth pattern: originates in epidermis and extend to the skin surface (epidermal region spread)
Multifocal growth
BCC growth pattern: downward growth to the dermal region
Nodular growth
Immunohistochemical features
○ Positive for
keratin (low-molecular-weight)
○ Negative for EMA, CEA, and involucrin
○ Other markers commonly expressed: CD10, Ber-EP4 and androgen receptors.
Tx for BCC
Excision, curettage and desiccation, and
irradiation
Tx for recurrent BCC
Radiation therapy or surgical re-excision.
Flesh-colored, solitary or multiple papules and nodules which may be disfiguring when multiple.
SKIN ADNEXA/ Appendage tumors
Mutations involved in Appendage tumors
Germline mutations in tumor suppressor genes
Appendage tumors: Benign or malignant?
Mostly benign but malignant variants exist
_____ are unusual in that
malignant forms appear to be more common than
benign forms.
Apocrine tumors
Arises from the meibomian
glands of the eyelid and may follow an aggressive
course replete with systemic metastases.
Sebaceous carcinoma
_____ can be confused
with metastatic adenocarcinoma because of their tendency to form gland-like structures.
Eccrine and apocrine carcinomas
Px presented with a nodular lesion in his palms that has a moat and hillock pattern
ECCRINE POROMA
Histologic features of ECCRINE POROMA
● Sharp junction of the
neoplastic and non-neoplastic region
● Forms anastomosing cords and nests
Origin of ECCRINE POROMA
Eccrine sweat glands
Nodular lesions in the papillary dermis with cystic component
HIDRADENOMA/ Eccrine acrosporoma
Origin of HIDRADENOMA/ Eccrine acrosporoma
Distal excretory duct
Appendage tumor described as a large multicentric lesion with ductal differentiation
CYLINDROMA
Common location for CYLINDROMA
Forehead and scalp
Sometimes seen in neck
Coalescence of nodules with time may produce
hat-like growth
Turban tumor
Cylindroma can be dominantly inherited; in such cases they appear early in life and are associated with
what mutation?
Inactivating mutations in the tumor suppressor gene
CYLD
Multiple cylindroma
○ Disfiguring
○ Assoc w CYLD gene mutation
Histologic features of cylindroma
○ Heavy accumulation of basement membrane material.
○ Appears to be very pink around and within your
tumor lobules.
○ Composed of islands of cell that fit together like pieces of a jigsaw puzzle
within a fibrous dermal matrix
Multiple, tan, small (1-3 cm) papulonodular lesions in the face and neck but more commonly in the lower eyelids
Syringoma
Origin of Syringoma
Eccrine differentiation
Histologic appearance of Syringoma
Cystic ducts lined by two
cell-layered thick
Nodular benign lesion common in children and young adults. Most cases are in the head, neck, and upper extremities.
Pilomatricoma
Origin of Pilomatricoma
Hair matrix/ hair follicle differentiation
Mutation involved in Pilomatricoma
CTNNB1 (gene encoding B-catenin)
Pilomatricoma vs BCC
Both are made up of basal cells but…
key feature is that there is abrupt keratinization leading to a shadow or
ghost cells —- Ghost cell lacks nuclei.
Proliferation of basaloid cells that forms primitive structures resembling hair follicles
TRICHOEPITHELIOMA
shows a lobular proliferation of sebocytes with increased peripheral basaloid cells and more mature sebocytes in the central portion that have
frothy or bubbly cytoplasm due to the presence of lipid
vesicles.
SEBACEOUS ADENOMA
○ Adnexal tumor showing apocrine differentiation with prominent decapitation secretion
○ Most prevalent in axilla and scalp
○ May have an infiltrative growth pattern
APOCRINE CARCINOMA
○ Dull lesions
○ Diverse and dynamic
○ Majority are acquired
MELANOCYTIC NEVI
Mutation involved in MELANOCYTIC NEVI
Activation of RAS or the
serine/threonine kinase BRAF
T or F: Not all nevi will give rise to melanoma.
TRUE
*Only very few will develop into melanoma.
Reason why nevi rarely give rise to melanomas
Oncogene-induced
senescence
There is proliferation of nevus in the rete pegs or in the junction only; considered as the earliest lesions
Junctional nevus
Progression of nevi cells proliferation downwards to the papillary dermis
Compound nevus
Complete downward progression of cells leaving the junctional region and occupy predominantly the dermal region
Intradermal melanocytic nevus
Most nevus seen in clinical practice
Compound and Intradermal
Originally polygonal cells become spindly as they go deeper into the dermis. They mature and lose their melanin pigment. This correlates with progressive loss of tyrosinase activity and acquisition of cholinesterase activity
Neurotization
Clinical significance of neurotization
It differentiates benign nevi from melanoma
*Neurotization is absent in melanoma
T or F: Junctional nevi are more elevated
FALSE
*Compound and Dermal nevi are more elevated than junctional nevi
Superficial vs deeper nevus cells
○ Superficial - larger, produce melanin, grow in nests
○ Deep - smaller, produce little or no pigment, appear as cords or single cells
○ Nevus present at birth
○ Larger variants have increased risk to develop melanoma
○ Generally benign
○ BRAF and NRAS mutation
Congenital nevus
○ Highly dendritic and heavily pigmented nevus cells
○ Confused with melanoma
○ Positive for melanin stains (S-100, HMB-45)
Blue nevus
○ Large, plump cells with pink-blue cytoplasm ○ Fusiform cells ○ Fascicular growth ○ Common in children ○ Red-pink nodule ○ Confused with hemangioma
Spitz nevus
○ Lymphocytic infiltration secondary to host immune response
Halo nevus
T or F: All melanomas arise from dysplastic nevi
FALSE
- Dysplastic nevi may be direct precursors of melanoma but are not prerequisites
- Increase risk: when multiple
T or F: Dysplastic nevi occurs exclusively in sun-exposed surfaces
FALSE
*Occur both in sun-exposed and non-exposed skin
First step to the development or progression of dysplastic nevus
Lentiginous hyperplasia
Nevus cell hyperplasia -> junctional -> compound with some degree of atypia
Nevus cells coalesce and fuse together and begin to replace the normal basal layer
Lentiginous hyperplasia
Release of melanin from dead nevus cells ; melanin is seen within macrophages
Melanin incontinence
Histologic features of dysplastic nevi
○ Atypical cells in epidermal and dermal regions (junctional and upper dermis)
○ Sparse lymphocytic infiltrates
○ Lentiginous hyperplasia
○ Linear dermo-epidermal junction fibrosis
○ Melanin incontinence
Most deadly of all skin cancers
MELANOMA
T or F: UV radiation is a prerequisite in the development of melanoma
FALSE
*UV radiation/ sunlight exposure is an important predisposing factor but not essential
T or F: There is no cure for Melanoma
FALSE
*It is curable in the early stages
Location of melanoma
○ Skin (majority) - cutaneous melanoma ○ Oral ○ Anogenital mucosa ○ Esophagus ○ Meninges ○ Uvea
Mutations involved in melanoma
○ Disruption in cell cycle control genes –CDKN2A gene
○ Activation of pro growth signaling pathway –RAS & BRAF
○ Activation of telomerase –TERT gene
● Horizontal spread within the epidermis and with very
minimal downward spread in the superficial dermis
● Seem to lack the
capacity to metastasize
RADIAL GROWTH PHASE
○ Indolent lesion, common to the face
○ May remain in the radial growth phase for
decades
Lentigo maligna
○ Most common type of melanoma
○ Seen in sun exposed areas
○ Spread in the epidermal and superficial dermis
Superficial spreading
○ Mucosal surfaces
○ Unrelated to sun exposure
Acral mucosal lentiginous
● Tumor cells invade downward into the deep dermis
● Presence of expansile mass or tumor nodule
● Neurotization is absent
● Capacity to metastasize
VERTICAL GROWTH PHASE
Depth of invasion is measured by ____ ?
Breslow thickness
Prognostic factors in melanoma
● Breslow thickness ● Number of mitoses ● Evidence of tumor progression ● Ulceration of the skin ● Presence of tumor infiltrating lymphocytes ● Gender ● Age ● Location ● Sentinel lymph node biopsy
Most powerful predictors for the prognosis of melanoma
● Breslow level
● Ulceration
Melanoma: High risk sites
scalp, mandibular area, midline trunk, upper medial thighs, hands, feet, fossae, genitalia
Prognosis of lentigo malignant melanoma
Better prognosis
Prognosis of nodular melanoma
Worse
Prognosis of superficial spreading
Intermediate
Warning signs of melanoma
○ Asymmetry ○ Irregular borders ○ Variegated color ○ Increasing diameter ○ Evolution or change over time
T or F: Melanoma may be treated medically
TRUE
*success in treating this cancer with drugs
that target the RAS and PI3K/AKT pathways.
- Firm, well-defined, nodular/polypoid non-encapsulated mass
- Common in the extremities
BENIGN FIBROUS HISTIOCYTOMA
Dermal tumor microscopic characteristics:
- Cellular: made up of spindle cells
- Fibroblastic proliferation
- Variable collagen deposition
- Delicate fibrovascular stroma
- Cluster of histiocytes
BENIGN FIBROUS HISTIOCYTOMA
Well-differentiated, primary fibrosarcoma of the skin
DERMATOFIBROSARCOMA PROTUBERANS
- Slow growing
- Locally aggressive
- Can recur
- But rarely metastasize
DERMATOFIBROSARCOMA PROTUBERANS
Molecular hallmark of DFSP
Transolation of genes encoding Collagen 1A1 (COL1A1) and platelet derived factor growth factor beta (PDGF B)
primary mode of tx for DFSP
Wide local excision
Treatment of choice for DFSP cases that are unresectable
Inhibitors of the PDGF B receptor tyrosine kinase
Dermal tumor microscopic characteristics:
- High cellularity
- Monomorphic appearance of the cells
- Diffuse infiltration into subcutaneous tissue
- Closely packed spindle cells in radial whorls -> storiform/cartwheel pattern
DERMATOFIBROSARCOMA PROTUBERANS
Immunohistochemical stains for DFSP
POSITIVE
- Vimentin
- Actin
- CD34 (strongly and consistently)
NEGATIVE
- S-100 (r/o other soft tissue tumor)
- HMB 45 (r/o melanoma)
- Keratin (r/o sarcomatoid type of SCC)
- Factor XIIIa
