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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5192_Библиотеки_им_академика_М_И_Перельмана.pdf
■
Rhipicephalus—dog tick
Identication: brown with brown legs
Transmits boutonneuse fever, RMSF
■
Ticks should be removed with gentle traction; DEET
repellant 1 permethrin-treated clothing is very
effective for prevention
• Mites
■
Demodex (Demodicidae)
Live in hair follicles of humans
Possible association with rosacea/perioral
dermatitis/blepharitis
■
Free-living mites
Chigger/harvest mite (Trombicula alfreddugesi)
♦ Vector for R. tsutsugamushi, which n scrub typhus
♦ Causes grouped pruritic papules on lower
extremities/ankles and waistband
♦ Causes summer penile syndrome in boys
■
House mouse mite (Allodermanyssus sanguineus)
Vector for R. akari n rickettsialpox
■
Dust mite (Dermatophagoides)
Involved in indoor allergies in atopic patients
■
Fowl mite (Dermanyssus and Ornithonyssus)
Vector for western equine encephalitis
■
Walking dandruff (Cheyletiella)
Caused by contact with dogs/cats—asymptomatic in
dogs/cats but itchy eruption in humans
■
Grain mite (Acarus siro)
Agent of Baker’s itch
■
Cheese mite (Glyciphagus)
Agent of Grocer’s itch
• Spiders
■
Latrodectus mactans—black widow spider; has
characteristic red hourglass on body
Acute pain and edema at site
Systemic symptoms: chills, abdominal pain/
rigidity, rhabdomyolysis, chest pain, sweating,
hypertension, and shock, muscle spams
a-Lactotoxin depolarizes neurons
Treatment: IV calcium gluconate; antivenin;
benzodiazepine supportive
■
Loxosceles reclusa—brown recluse (Fig. 5.30) spider;
characteristic dark brown-black violin/ddle-shaped
marking
Necrosis with eschar formation at site of bite
(which is painless; erythema n ischemia n
thrombosis)
Toxins: sphingomyelinase D and hyaluronidase
(allows eschars to spread)
Can have hemolytic anemia/thrombocytopenia,
shock, DIC and death
Treatment: do not debride; supportive; antivenin;
prednisone
■
Phidippus formosus—jumping spider
Dark and hairy with four eyes (two larger centrally
and two smaller ones laterally)
Toxin: hyaluronidase
Is aggressive and bites, but no systemic symptoms
■
Lycosidae—wolf spider
Large brown spider with black patterns and eight
eyes
Toxin: histamine
5.5 Parasites and Other Creatures
Fig. 5.30 Loxosceles reclusa (brown recluse spider). A characteristic “violin” or
“ddle” marking appears on the head and thorax. (Courtesy, Dr. Robert G.
Breene, American Tarantula Society, South Padre Island, Texas.)
■
Chiracanthium—sac spider
Yellow-colored
Toxin: lipase
■
Tegenaria agrestis—hobo spider
Herringbone pattern on abdomen
Painless bite n local necrosis/eschar
Web is funnel-shaped
■
Peucetia viridans—green lynx spider; has unique neon
green color with red spots
Green colored with red spots
Painful bite without systemic symptoms
■
Theraphosidae—tarantula
Urticating hairs ejected when threatened; can n
ophthalmia nodosa (chronic granulomatous
reaction in eyes; may result in blindness)
• Scorpions (Centruroides sculpturatus and gertschi)
■
Pain and paresthesia out of proportion to skin lesions
■
Systemic symptoms: convulsions, hemiplegia,
temperature instability, tremor, arrhythmia, pulmonary
edema, and hypertension
Millipedes and centipedes
• Centipedes (Chilopoda class; Scolopendra spp.)
■
One pair of legs per segment
■
Bites produce pain and paresthesia
Two puncture wounds
• Millipedes (Diplopoda)
■
Two pairs of legs per segment
■
Chemical irritant contact dermatitis from secretions n
burn and blistering
Snake bites
• Viperidae/Crotalidae (copperhead and rattlesnake):
triangular head with deep nostril pits
■
Multiple toxins, including thrombin-like glycoproteins
■
Thrombocytopenia and DIC
• Elapidae (coral snake) round eyes, characteristic red,
yellow and black banding (mnemonic: “red on yellow
kills a fellow”)
335
CHAPTER 5 • Infectious Diseases
■
a-Neurotoxin—causes neurologic symptoms, nausea,
headache, abdominal pain, and paresthesia
■
Phospholipase A2 causes wound effects
Marine injuries
• Cnidarians (jellysh, Portuguese man of war, coral, and
anemones)
■
Produces specialized cells—nematocysts
■
Flagellate eruption in affected areas (Fig. 5.31)
■
Physical or osmotic trigger releases a coiled lament
that discharges toxins
Vinegar (dilute acetic acid) denatures nematocysts
in some, but not all species
■
Chironex eckeri (Pacic box jellysh) stings can n
shock and associated fatality
■
Portuguese man of war (Pysalia spp.) contain a heatlabile toxin that produces cardiac disturbances and
paralysis
Skin lesions are hemorrhagic and vesicular
• Echinoderms
■
Sea urchins have fragile spines that break off in wounds
n foreign body reaction
■
Sea cucumbers eject an irritating liquid (holothurin) n
conjunctivitis
Fig. 5.31 Linear plaques, erythema, and edema in a girl following contact with
the tentacles of a Portuguese man of war. (Courtesy, Dr. Vidal Haddad, Jr.)
336
6
Neoplastic Dermatology
Monisha N. Dandekar, Roberto A. Novoa, and
Phillip C. Hochwalt
CONTENTS LIST
6.1 KERATINOCYTIC NEOPLASMS
6.2 CYSTS
6.3 MELANOCYTIC NEOPLASMS
6.4 ADNEXAL NEOPLASMS AND HAMARTOMAS
6.5 HAIR FOLLICLE NEOPLASMS/HAMARTOMAS
6.6 SEBACEOUS PROLIFERATIONS
6.7 NEURAL NEOPLASMS
6.8 SMOOTH MUSCLE NEOPLASMS
6.9 HEMATOLYMPHOID NEOPLASMS
6.10 FIBROHISTIOCYTIC NEOPLASMS
6.11 VASCULAR PROLIFERATIONS
6.12 NEOPLASMS OF ADIPOCYTIC LINEAGE
6.13 DERMOSCOPY
NEOPLASTIC DERMATOLOGY
• General features of a benign neoplasm:
■
Clinically: well-demarcated, uniform color, unchanged
for years, and lack of concerning symptoms (bleeding,
ulceration, and pain)
■
Histologically: well-circumscribed, bland cytology;
lacks all of the following: architectural disorder,
necrosis, cytologic atypia, and atypical mitotic gures
• General features of a malignant neoplasm:
■
Clinically: rapid growth or new-onset lesion with
concerning features, such as pigment variegation,
ulceration, pain, and bleeding
■
Histologically: poorly-circumscribed proliferation of
cells with atypical cytology (nuclear pleomorphism,
hyperchromatic cells, ↑ N:C ratio, prominent
nucleoli, and abnormally shaped nuclei);
architectural disorder (inltrative, destroys
neighboring structures, and perineural/intravascular
invasion); signs of hyperproliferative state
(↑ mitotic gures for given tissue type and tumor
necrosis), atypical mitoses (do not resemble any
normal phase of cell division)
6.1 KERATINOCYTIC NEOPLASMS
Seborrheic keratosis (SK)
• Very common, benign; onset fourth decade
• Familial predisposition, autosomal dominant (AD)
inheritance w/ incomplete penetrance
• a/w sun exposure (↓ incidence on “double-clothed areas”
such as buttocks and genitalia), FGFR3 and PIK3CA
activating mutations
• Well-demarcated, waxy/verrucous brown “stuck-on”
papules on hair-bearing skin; spares mucosal sites
• Histology: acanthosis, papillomatosis, hyperkeratosis
with pseudohorn cysts, at base (“string sign”), bland
keratinocytes without atypia or many mitotic gures
(if present will be mild and a/w irritation/inammation);
many histologic variants exist (Table 6.1)
337
CHAPTER 6 • Neoplastic Dermatology
Table 6.1 Seborrheic Keratosis Histologic Variants
Acanthotic Most common type; presents as a dome-
shaped papule; mostly acanthotic with less
papillomatosis/hyperkeratosis; small basaloid
keratinocytes with increased melanin,
prominent horn pseudocysts
Hyperkeratotic Prominent hyperkeratosis/papillomatosis
(“church spires”) w/ less acanthosis/
pseudocysts/pigmentation
Reticulated Thin interlacing strands of basaloid cells,
often pigmented, with horn pseudocysts, 1/–
lentigo at edges (these may evolve from lentigo)
Irritated Less sharply demarcated base with lymphoid
infiltrate; whorls of pink keratinocytes
(“squamous eddies”)
Clonal Well-defined nests of paler/monotonous
cells (Borst-Jadassohn phenomenon)
mimicking Bowen’s disease, melanoma, or
hidroacanthoma simplex
Melanoacanthoma Heavy pigment mostly in dendritic
melanocytes (.keratinocytes)
■
Linear porokeratosis: onset in newborns; linear lesion on
extremities, follows lines of Blaschko (Fig. 6.1); highest
risk of progression to squamous cell carcinoma (SCC)
■
Punctate porokeratosis: onset in adolescence; 1- to
2-mm “seed-like” papules on palms/soles
■
Porokeratosis palmaris, plantaris, et disseminata:
onset in childhood/adolescence; occurs on palms/soles
initially
■
Porokeratotic eccrine ostial and dermal duct nevus:
clinically resembles a nevus comedonicus of palm or
sole, but histology shows abundant cornoid lamellae
arising from acrosyringium
• Histology: cornoid lamella (angled column of parakeratosis
w/ underlying hypogranulosis and dyskeratotic cells);
centrally between two cornoid lamellae the epidermis may
be atrophic, hyperplastic, normal, or benign lichenoid
keratosis-like
■
Boards tip: cornoid lamellae may be at edge → MUST
look at entire slide!
• SCC can develop in any subtype except punctate
porokeratosis (0% risk); second lowest risk in DSAP;
highest risk in linear porokeratosis
• Sign of Leser-Trelat: widespread eruption of SKs on
trunk; a/w underlying adenocarcinoma (GI #1)
• Multiple clinical variants (Table 6.2)
Epidermal nevus
• Hamartoma of epidermis and papillary dermis; onset in
rst year of life
Porokeratosis
• Subtypes
■
Porokeratosis of Mibelli: onset in infancy or childhood;
extremities; large (often . 3 cm) circinate plaque with
keratotic border
■
Disseminated supercial actinic porokeratosis (DSAP):
most common subtype; onset in middle age; F . M;
numerous brownish-red macules w/ keratotic borders
in sun-exposed areas; most common on legs (rare on
face); immunosuppression is risk factor; some
inherited cases linked w/ mevalonate kinase mutations
Table 6.2 Seborrheic Keratosis Clinical Variants and Other Benign Keratoses
Dermatosis papulosa nigra
Stucco keratosis
Lichenoid keratosis Often represents an inflamed/regressing lentigo/SK ; clinically mimics BCC or SCCIS; solitary pink/brown scaly
Inverted follicular keratosis Endophytic variant of irritated SK; white-pink firm solitary papules on face/neck (especially cheek and upper lip);
Large cell acanthoma Likely represents an early macular SK/solar lentigo; flesh-colored to brown patch/plaque on sun-exposed areas in older
Acrokeratosis verruciformis of Hopf Tan-flesh colored warty papules on dorsal hands/feet; Autosomal dominant disorder of keratinization often a/w Darier
Clear cell acanthoma (Degos
acanthoma)
Darkly pigmented individuals, often African Americans; onset in young adulthood; F . M; familial tendency;
hyperpigmented keratotic papules on face; histology identical to SK, except horn pseudocysts are not common
White scaly variant of SK; onset after 40 years old; M . F (4:1); white to gray hyperkeratotic papules/plaques
symmetrically distributed on lower legs, ankles, feet; a/w HPV-23b, HPV-9, HPV-16, and HPV-37
papule on trunk or forearms; fourth to seventh decade; F . M; histologically resembles lichen planus (but may have
parakeratosis), often adjacent lentigo or SK
middle-aged/older adults; histology: endophytic SK with prominent squamous eddies
individuals; histology: papillomatosis, hyperkeratosis, elongation of epidermal rete with large and slightly atypical
keratinocytes 1/– basal pigmentation
disease; ATP2A2 mutations; histology: “church spire” hyperkeratosis and papillomatosis (identical to stucco keratosis)
Solitary erythematous papule on lower leg with “wafer-like scale” at the periphery; histology: sharply demarcated zone
of pale keratinocytes (PAS1; as a result of phosphorylase deciency → glycogen accumulation), psoriasiform
hyperplasia, parakeratosis, loss of granular layer, and intraepithelial neutrophils
Mnemonic: “looks like a well-demarcated papule of psoriasis composed of clear keratinocytes”
• Papillomatous, pigmented, linear plaques along
Blaschko’s lines
• Variants:
■
Nevus unius lateris: extensive unilateral plaques on
trunk
■
Ichthyosis hystrix: extensive bilateral lesions on trunk
■
Inammatory linear verrucous epidermal nevus
(ILVEN): along lines of Blaschko without associated
neurologic defects
■
Epidermal nevus syndrome (Schimmelpenning
syndrome): a/w developmental abnormalities
(neurologic and musculoskeletal most commonly)
338
Fig. 6.1 Linear porokeratosis with squamous cell carcinoma. (From James WD,
Elston DM, Treat JR, Rosenbach MA, Neuhaus IM. Genodermatoses and congenital anomalies. In: Andrews’ Diseases of the Skin. 13th ed. Philadelphia:
Elsevier; 2020:547–586.)
• Histology: epidermal papillomatosis; orthohyperkeratosis
■
May see epidermolytic hyperkeratosis due to genetic
mosaicism (defects in keratins 1 and 10) → ↑ risk of
bullous congenital ichthyosiform erythroderma in
offspring
• Mutations in FGFR3, KRAS, NRAS, and PIK3CA have also
been identied
Nevus comedonicus
• Hamartoma; onset in childhood; worsens during puberty
• Comedones in a linear array on face . trunk
• FGFR2 mutations involved
■
FGFR2 also involved in Alagille syndrome, Apert syndrome,
cardiocranial syndrome, and Crouzon syndrome
• Histology: dilated epidermal invaginations lled w/
cornied debris
Flegel disease (hyperkeratosis
lenticularis perstans)
• Rare disorder with AD inheritance; adult onset
• Absent/altered lamellar granules (Odland bodies;
important for normal desquamation) on electron
microscopy n a decrease/absence of these membranecoating granules n g desquamation of the stratum
corneum n retention hyperkeratosis
• Small (1–5 mm), disc-shaped keratotic papules in
symmetric distribution; distal extremities (dorsal
foot . lower legs, dorsal hands)
• Histology: discrete orthohyperkeratosis overlying atrophic
epidermis; lichenoid dermal inammation
6.1 Keratinocytic Neoplasms
Fig. 6.2 Warty dyskeratoma. The outward growth is verrucoid. The inwardgrowing component shows suprabasilar acantholysis. (From Wyatt AJ, Busam
KJ. Tumors of the epidermis. In: Busam KJ, ed. Dermatopathology: A Volume in
the Series: Foundations in Diagnostic Pathology. 2nd ed. Philadelphia: Elsevier;
2016:339–387.)
• Histology: cup-like epidermal invagination with
acantholytic dyskeratosis and corps ronds/grains (Fig. 6.2)
■
“Cup-shape” and solitary nature distinguishes from Darier’s
Premalignant/malignant
Actinic keratosis (AK)
• Scaly, red papules/plaques on sun-damaged areas; a/w
chronic sun exposure, male sex, older age, and fair skin
phenotypes
• UVB responsible for AK development → induces
thymidine dimers (C→T or CC→TT)
■
p53 mutations within keratinocytes → impaired apoptosis
• Histology: basal layer atypia (lower 1/3 of epidermis) with
budding/nger-like projections into dermis; “Flag sign”:
overlying parakeratosis (pink) alternating with
orthohyperkeratosis (blue); atypia and parakeratosis often
spares adnexal structures; solar elastosis in dermis
• Treatment: destructive measures (cryotherapy, ED&C,
CO
ablation, topical 5-FU 1/ calcipotriene,
2
imiquimod, photodynamic therapy, tirbanibulin,
ingenol mebutate, topical diclofenac, and TCA peel)
■
Topical 5-FU 1/– calcipotriene appears most effective
in recent head-to-head trials
• Rate of transformation to SCC 5 0.075%–0.096% per year
Bowen’s disease (squamous cell carcinoma in situ)
Warty dyskeratoma
• Onset in fth to seventh decade; M . F
• Solitary verrucous papulonodule w/ central keratotic plug
usually on head/neck
• Can progress from AK or occur de novo
• Risk factors: elderly, chronic sun exposure, lightly
pigmented skin, immunosuppression, arsenic exposure,
ionizing radiation, human papillomavirus (HPV), and
chronic irritation
339
CHAPTER 6 • Neoplastic Dermatology
• Hyperkeratotic erythematous patch or plaque; may affect
any site
• Histology: acanthosis with full-thickness keratinocytic
atypia, disorganized (“windblown”) architecture,
↑ mitoses, dyskeratotic keratinocytes, and parakeratosis
• Variants: pigmented, pagetoid, verrucous, Bowenoid
papulosis (multiple hyperpigmented penile/vulvar
papules, 2% progress to invasive SCC, HPV-16 and
HPV-18 are #1 causes), and erythroplasia of Queyrat
(juicy red, erosive plaque on glans penis; .30% progress
to invasive SCC, HPV-16 is #1 cause)
• Treatment: destructive therapies (e.g., C&E), 5-uorouracil
(off-label), excision, and Mohs
Invasive cutaneous squamous cell carcinoma (cSCC, “SCC”)
• Second most common skin cancer after basal cell
carcinoma (BCC)
• Traditional teaching: “SCC accounts for 20% of NMSCs
and is much less deadly than melanoma”
• New Teaching: “SCC is more prevalent and more
dangerous than previously recognized!”
■
SCC incidence has increased by 263% since 1970s →
current ratio of BCC:SCC is now closer to 1:1
■
SCC mortality rate now approximates that of melanoma!
• Clinical presentation: erythematous scaly papulonodule/
plaque; most commonly on head/neck and dorsal
extremities
■
Oral SCC: most common sites are posterior lateral tongue
. oor of mouth . soft palate
• Risk factors: chronic sun exposure, M . F (3:1), older age, fair
skin phenotypes, genetic syndromes, immunosuppression
(degree/duration → ↑ risk), solid-organ transplant recipient
(65x–250x ↑ incidence; heart/lung . liver . renal;
switching to sirolimus may help), HPV-16 and HPV-18,
ionizing radiation (→ more aggressive course w/ ↑ recurrence
and 10%–30% metastatic rate), CLL (↑ incidence and
severity), chronic nonhealing wound (Marjolin ulcer → 25%
metastatic rate), hypertrophic LE/LP, arsenic exposure,
chronic lichen sclerosus et atrophicus (LS&A; genital), RA
patients on treatment, TNF-a inhibitors, azathioprine,
tobacco use, vemurafenib (wart-like appearance common),
long-term voriconazole usage, vismodegib (8x ↑ SCC risk)
• Molecular:
■
Mutations: TP53 (most common) .CDKN2A, RAS,
NOTCH1
UVB → thymidine dimers (C→T or CC→TT)
Cutaneous SCC has a very high mutational burden
compared with most malignancies (5x higher than
lung cancer and melanoma) → may be more sensitive
to immunotherapy-based treatment approaches
• Histology: full-thickness keratinocytic atypia w/ dermal
invasion; tumor often “paradoxically differentiated”
(tumor cells are MORE eosinophilic/keratinizing than
surrounding keratinocytes)
■
High-risk subtypes: desmoplastic, poorlydifferentiated, adenomatous, sarcomatous, spindle cell
■
Low-risk subtypes: verrucous carcinoma,
keratoacanthoma (KA)
• Staging
■
Due to ↑ SCC incidence and mortality rates → tumor
staging for SCC has become one of the “hottest” areas
of research in dermatologic surgery
■
Goal of cancer/tumor staging 5 risk stratication
We need good tumor staging criteria to predict
which patients w/SCC are at high risk of morbidity
and mortality → allows for better clinical decisionmaking, clinical trial enrollment, etc.
■
Two major staging systems for SCC: American Joint
Committee on Cancer (AJCC; 8th edition) and
Brigham and Women’s Hospital (BWH)
■
AJCC staging system (8th edition)
Only applies to SCC located on head, neck, and
vermillion lip → cannot be used for staging SCC on
other anatomic locations
All three TNM characteristics (tumor, nodes,
metastatic disease) are required for cancer staging
(vs. only T for the BWH staging system) → ↓ ease of
use, especially for dermatologists
T stage scoring system
♦ T1 5 tumor diameter , 2 cm
♦ T2 5 tumor diameter between 2 and 4 cm
♦ T3 5 tumor diameter $ 4 cm or any high-risk
feature (minor bone erosion, perineural invasion
[PNI] of nerves $ 0.1 mm in caliber or PNI
beneath the dermis, deep invasion [$ 6 mm or
beyond subcutaneous fat])
♦ T4 5 strictly reserved for major bone
involvement or invasion of skull base
■
BWH staging system
Shown to be more effective at risk stratication
than AJCC staging system (higher specicity [93%]
and positive predictive value [30%] for identifying
cases at risk for metastasis and death)
T (tumor) staging only! → very easy for
dermatologists to use
♦ Staging does not require any information about
the status of the lymph nodes (N) or presence of
metastatic disease (M)
Four high-risk features (each counts as 1 point): PNI
($ 0.1 mm caliber nerve), diameter $ 2 cm, invasion
beyond SQ fat, and poorly differentiated histology
T stage scoring system
♦ T1 5 zero high-risk features
♦ T2a 5 one high-risk feature
♦ T2b 5 two to three high-risk features
(metastatic rate 35%; mortality rate 20%)
♦ T3 5 all four high-risk features or bone invasion
(automatically upgrades stage to T3, regardless of
other features)
Stage T2b are “rare but deadly!”
♦ Only 5% of all SCC are classied as BWH stage T2b
♦ However, these 5% of tumors (T2b) account for
72% of ALL nodal metastases and 83% of ALL
deaths from cSCC n very important to identify
T2b lesions!
• NCCN Treatment Guidelines (important for Mohs Board
Exam)
■
Low-risk
340
6.1 Keratinocytic Neoplasms
Treatment
♦ Curettage and electrodesiccation (except terminal
hair-bearing areas) → transition to excision if
C&E (curettage and electrodessication) extends
beyond dermis
♦ Excision with 4 to 6 mm clinical margins
If margin positive → Mohs or other peripheral
and deep en face margin assessment (PDEMA),
re-excision, or radiation therapy (RT)
♦ Mohs or other PDEMA
♦ RT for non-surgical candidates
■
High-risk
Treatment
♦ Mohs or other PDEMA
♦ Excision with wider margin
If margin positive → Mohs or other PDEMA,
re-excision, or RT
♦ RT 1/– systemic therapy for non-surgical candidates
or systemic therapy alone if RT not feasible
■
If positive margins with Mohs or excision and reresection not feasible → multidisciplinary consult →
RT 1/– systemic therapy or systemic therapy alone if
RT not feasible
■
If extensive perineural, large, or named nerve
involvement, or other poor prognostic features →
consider adjuvant RT even with negative margins
■
Lymph node (LN) metastasis 1/– distant metastasis
Palpable or abnormal LNs on imaging → neneedle aspiration (FNA) or core biopsy
♦ If negative FNA or core biopsy → consider
excisional LN biopsy
♦ If positive FNA or core biopsy → further imaging
(CT with contrast or PET/CT)
If operable → excision of primary tumor and
LN dissection as indicated AND often RT
(especially if multiple nodes or large node or
extracapsular extension [ECE])
If ECE or incompletely excised nodal
disease → RT and consider concurrent
systemic therapy
Regional LN recurrence or distant mets →
multidisciplinary consultation
If inoperable → multidisciplinary consultation →
RT 1/– systemic therapy or systemic therapy alone if
RT not feasible
■
Systemic therapy
Systemic therapy options for use with RT:
♦ Cisplatin preferred
♦ Useful in certain circumstances:
Epidermal growth factor receptor (EGFR)
inhibitor (cetuximab)
Cisplatin 1 5-FU
Carboplatin 1/– paclitaxel
Options for systemic therapy alone:
♦ Cemiplimab or pembrolizumab preferred (if
curative RT or surgery not feasible for locally
advanced, recurrent, or metastatic disease)
If ineligible for (i.e., SOTR) or progressed on
immune checkpoint inhibitors and clinical
trials → carboplatin 1 paclitaxel
• Prognosis: metastatic rate (all-comers with SCC) 5 5%;
mortality rate 5 3.5%
■
↑ Risk of metastasis: immunosuppressed state, location
on lip/ear, diameter . 2 cm, Breslow depth . 2 mm,
extension beyond SQ fat, SCC arising in burn/scar
(Marjolin ulcer), PNI ($0.1 mm), and poorly
differentiated histology
■
LN metastases from head and neck SCC have a high
cure rate when identied and treated early
■
High stage SCC (BWH T2b/T3) has $ 30% metastatic
rate → management requires greater consideration
■
Oral mucosal SCC has a worse prognosis than SCC
of the lip which has a worse prognosis than cSCC
• Additional Boards Fodder
■
Which factor is most strongly associated with ____?”
Disease-specic death? Diameter . 2 cm
♦ Mnemonic: “Die 5 DIE-ameter”
♦ 19-fold ↑ mortality rate, compared with tumors
, 2 cm
Recurrence and metastasis? Depth . 2 mm
♦ Breslow depth , 2 mm → 0% metastasis rate
♦ Breslow depth 5 2.1 to 6.0 mm → 4% metastasis
rate
♦ Breslow depth . 6.0 mm → 16% metastasis rate
♦ Also, extension beyond SQ fat → high rates of
local recurrence (28%) and nodal metastasis
(27%)
■
Genetic syndromes associated with SCC:
Oculocutaneous albinism
Xeroderma pigmentosum
Dystrophic epidermolysis bullosa (DEB; SCC is #1
cause of death)
Epidermodysplasia verruciformis
Dyskeratosis congenita
Porokeratosis, linear type
Keratitis, ichthyosis, deafness (KID) syndrome
Rothmund-Thompson syndrome
Werner syndrome
Chronic mucocutaneous candidiasis
Bloom syndrome
Verrucous carcinoma
• Low-grade, locally destructive SCC a/w HPV-6 and
HPV-11
• Large exo-endophytic nodule; three clinical variants:
■
Epithelioma cuniculatum: slow-growing mass on
plantar foot (Fig. 6.3)
■
Buschke-Lowenstein tumor (giant condyloma): large
cauliower-like growth in anogenital region
■
Oral orid papillomatosis: widespread oral lesions
• Histology: very well-differentiated (minimal to no
cytologic atypia); bulbous/pushing border, massive size
and ↑ depth of base 5 clues to malignancy
Keratoacanthoma
• Variant of SCC with unique features: initial rapid growth
over weeks → self-resolves/involutes over months
■
Subungual KAs are the exception (do NOT involute)
341
CHAPTER 6 • Neoplastic Dermatology
Fig. 6.3 Verrucous carcinoma of the foot (epithelioma cuniculatum). Verrucous
carcinomas often reach large sizes before diagnosis because they are often
treated as warts.
• Clinical variants: solitary, multiple, giant, intraoral,
subungual, and KA centrifugum marginatum (can reach
several centimeters)
• KA syndromes:
■
Ferguson-Smith: AD inheritance; rapid onset of
multiple KAs; onset third decade, sun-exposed areas,
and resolves spontaneously
■
Grzybowski: sporadic; 1000s of milia-like KAs in later
adulthood; can involve airway; a/w scarring,
ectropion, and mask-like facies. Mnemonic: “Old
(later onset) Grizzlies Growl (airway affected)”
• Other associations: Muir-Torre syndrome (classic KAs, or
KAs w/ sebaceous differentiation), immunosuppression,
and HPV
• Histology: crateriform, endophytic nodule w/ well-
differentiated keratinocytes (lacks signicant atypia),
central keratin plug, and peripheral inammation w/
eosinophils
• Treatment: excision or Mohs; may observe if certain
involuting
Basal cell carcinoma
• THE most common human malignancy!
• Onset typically 50s to 60s, but can occur earlier; slow/
indolent growth; locally destructive (esp. morpheaform,
inltrative, and micronodular subtypes)
• Due to UV exposure (intermittent and intense . chronic
and cumulative); certain medications (e.g., sphingosine
1-phosphate receptor modulators for multiple sclerosis)
may increase risk
• Boards Fodder: PTCH mutations (chromosome 9q;
most common) . TP53 mutations (p53 tumor
suppressor; second most common) (Fig. 6.4; Box 6.1)
• Sun-exposed skin; rare on palms, soles, and mucous
membranes
• Numerous clinicopathologic variants (Table 6.3)
• General histologic features: nests of basaloid, uniform
cells w/ high N:C ratio, peripheral palisading, epidermal
connection (at least focally), myxoid stroma, stromal–
epithelial retraction, and mitotic/apoptotic activity
■
High-risk subtypes: inltrative, micronodular,
morpheaform, basosquamous, sclerosing,
carcinosarcomatous
■
Other high-risk features: poorly dened borders,
recurrent, site of prior RT, immunosuppressed patient,
perineural involvement, mask areas of face/genitals/
hands/feet, .10 mm on cheeks/forehead/scalp/neck/
pretibial, .20 mm on trunk/extremities
• Very low metastatic potential (,0.1%; dependent on
stroma for growth)
■
Basosquamous subtype may behave more like SCC →
↑ metastatic potential
• Niacinamide 500 mg BID reduces BCC and SCC risk by 23%
• NCCN treatment guidelines
■
Low-risk
Treatment
♦ C&E (except terminal hair-bearing areas) →
transition to excision if C&E extends beyond
dermis
A B C
Sonic hedgehog
Smo
Cell
surface
GLI
SUFU
Nucleus
Fig. 6.4 The hedgehog inhibitor pathway. (A) Non-proliferative state: patched receptor (PTCH) inhibits the activity of smoothened (Smo), allowing suppressor of
fused (SUFU) to bind to and inactivate GLI transcription factors. (B) Binding of the sonic hedgehog ligand to PTCH allows activation (dis-inhibition) of Smo n
activated Smo inhibits the binding of SUFU to GLI n GLI transcription factors are then free to enter the nucleus and modulate transcription of hedgehog pathwayassociated genes. (C) Vismodegib and Sonidegib act like “articial PTCH” by inhibiting Smo activation n SUFU is free to to bind to and inactivate GLI transcription
factors. (Redrawn from Lear JT, Corner C, Dziewulski P, et al. Challenges and new horizons in the management of advanced basal cell carcinoma: a UK perspective.
Br J Cancer. 2014;111[8]:1476–1481: From Fitzpatrick JE, Morelli JG. Dermatology Secrets Plus, 4th ed. Philadelphia: Elsevier, 2011)
SUFU
GLI
Transcription
PTCH
Inhibitor
SmoPTCHSmo
SUFU
GLI
Sonic hedgehog
PTCH
342
Box 6.1 Mnemonic: Genetic Syndromes a/w Multiple BCCs
“Green Berets Rarely Buy eXtra Shoes … but they get a lot of BCCs from
being in the sun!”
• Gorlin’s
• Bazex-Dupré-Christol
• Rombo
• Brooke-Spiegler
• Xeroderma pigmentosum
• Schöpf-Schulz-Passarge
Table 6.3 Basal Cell Carcinoma Variants
Nodular Favors head/neck; histology: large nests
Superficial Erythematous scaly patch, most common type
Morpheaform Scar-like pink to white plaque; histology: small
Micronodular Smaller nests than nodular type; micronodules
Fibroepithelioma of
Pinkus
Pigmented Nodular pattern BCC with aggregates
Infundibulocystic
(keratotic, follicular)
Basosquamous Ambiguous term w/ variable meanings;
♦ Excision with 4 mm clinical margins
If margin positive → Mohs or other PDEMA,
(centrally 1/– necrosis, cystic spaces);
cells lack organization centrally, prominent
peripheral palisading, and may be ulcerated
in younger patients, trunk and extremities
(.head/neck); histology: multiple buds from
epidermis do not extend beyond papillary
dermis
angulated nests and cords within a sclerotic
stroma; retraction not prominent; may be
more deeply invasive
are separated by normal intervening collagen,
and does not form a circumscribed contour at
the deep aspect
Pedunculated, “soft/fleshy” lesion on lower
back; histology: thin anastomosing strands
form a network within pinker stroma; retraction
and myxoid material are less prominent
of melanin in the nests and dermal
melanophages
Well-circumscribed, comprised of basaloid and
squamoid cells in anastomosing cords, w/
horn cysts → resembles benign follicular
tumors (trichoepithelioma and basaloid
follicular hamartoma)
may refer to: (1) BCCs with “squamoid
appearance” (pinker cells, more cytoplasm,
and keratinization); (2) carcinomas with
features indeterminate between BCC and
SCC; or (3) collision lesions of BCC 1 SCC
re-excision, or RT
♦ RT for non-surgical candidates
■
High-risk
Treatment
♦ Mohs or other PDEMA
♦ Excision with wider margin
If margin positive → Mohs or other PDEMA,
re-excision, or RT
♦ RT or systemic therapy (vismodegib, sonidegib,
cemiplimab) for non-surgical patients
■
If positive margins with Mohs or excision and reresection not feasible → RT and multidisciplinary
consult (systemic therapy if curative RT not feasible)
6.2 Cysts
■
Primary or recurrent nodal metastasis: multidisciplinary
consult
Surgery if feasible
RT or systemic therapy with hedgehog inhibitors
(vismodegib .. sonidegib) or cemiplimab
if surgery not feasible
■
Distant metastasis: multidisciplinary consult
Systemic therapy with vismodegib (NOT
sonidegib) or cemiplimab
RT or surgery for limited metastasis
Palliative/supportive care
6.2 CYSTS
Epidermoid cyst (epidermal
inclusion cyst)
• Clinical features
■
Firm dermal nodule with central punctum; any site,
but most commonly head/neck/upper trunk
• Pathogenesis/histopathologic features
■
Derived from follicular infundibular epithelium; may
arise primarily, or secondary to follicle disruption/
traumatic implantation; lined by stratied squamous
epithelium w/ intact granular layer and no adnexal
structures in the wall (vs. vellus hair cyst and dermoid
cyst); laminated/aky keratin centrally
• Comments
■
Multiple epidermoid cysts may be a/w Gardner
syndrome (often have pilomatricoma-like areas
histologically)
Trichilemmal (pilar) cyst
• Clinical features
■
Firm dermal nodule; 90% on the scalp; usually
multiple (70%); subset AD inheritance
• Pathogenesis/histopathologic features
■
Derived from isthmic follicular epithelium; stratied
squamous epithelium lacking granular layer; dense pink
homogenized keratin with frequent calcication centrally
Proliferating trichilemmal cyst/tumor
• Clinical features
■
Slow-growing dermal nodule; scalp (90%); usually
elderly women
• Pathogenesis/histopathologic features
■
Resembles trichilemmal cyst but more proliferative
centrally w/ areas of multicystic architecture; well-
circumscribed at periphery; variable cytologic atypia
and mitotic activity
• Comments
■
Small percentage behave aggressively → complete
removal recommended
Dermoid cyst
• Clinical features
■
Infants; occur along embryonic fusion lines (most
commonly lateral eyebrow)
343
CHAPTER 6 • Neoplastic Dermatology
• Pathogenesis/histopathologic features
■
Derived from entrapment of epidermis during
embryogenesis; lined by stratied squamous
epithelium with granular layer and adnexal structures
(hair follicles and sebaceous glands) in cyst wall
• Comments: be careful if biopsying b/c may have
intracranial connection
Vellus hair cyst
• Clinical features
■
Multiple (“eruptive”) domed and esh-colored or
hyperpigmented papules; trunk; subset AD inheritance
• Pathogenesis/histopathologic features
■
Same histology as epidermoid cyst, but has multiple
vellus hairs in cyst cavity (ip condenser to see)
• Comments
■
Can occur as part of Lowe syndrome (XLR inheritance,
Fanconi-type renal failure, mental retardation, various
eye issues)
Steatocystoma
• Clinical features
■
Single or multiple (multiplex; AD inheritance) lesions;
chest/axilla/groin; drain oily uid if punctured
• Pathogenesis/histopathologic features
■
Lined by thin stratied squamous epithelium with no
granular layer and thin bright pink corrugated
(“shark-tooth” or “dragon scale”) cuticle; sebaceous
glands in wall
• Comments
■
Multiplex form with KRT17 mutations; a/w
pachyonychia congenita type 2
Hidrocystoma
• Clinical features
■
Translucent bluish cysts; face (eyelids #1); solitary or
multiple
• Pathogenesis/histopathologic features
■
Unilocular or multilocular cyst with low cuboidal
lining 1/– decapitation secretion (if apocrine); lumen
appears empty
• Comments
■
May be a/w Schöpf-Schulz-Passarge (multiple
hidrocystomas, syringobroadenomas, palmoplantar
keratoderma, hypodontia, and hypotrichosis)
Bronchogenic cyst
• Clinical features
■
Solitary; present at birth; suprasternal notch/anterior neck
• Pathogenesis/histopathologic features
■
Sequestration of respiratory epithelium during
embryogenesis; pseudostratied, ciliated columnar cells
with goblet cells; 1/– smooth muscle/mucous
glands/cartilage in wall
• Comments
■
Main clues for Boards: cartilage, smooth muscle, and
↑ ↑ goblet cells
Thyroglossal duct cyst
• Clinical features
■
Children/young adults; midline anterior neck; moves
w/ swallowing
• Pathogenesis/histopathologic features
■
Columnar, cuboidal, or stratied squamous lining with
thyroid follicles in the wall (low cuboidal epithelium
with bright pink contents)
• Comments
■
Main clue for Boards: pink thyroid follicles
(pathognomonic)
Median raphe cyst
• Clinical features
■
Men; ventral penis between urethral meatus and anus;
pain during intercourse
• Pathogenesis/histopathologic features
■
Variable lining of cyst; “dirty debris” within cyst; genital
skin features (e.g., smooth muscle and small nerves)
Branchial cleft cyst
• Clinical features
■
Second or third decades; lateral neck (anterior
sternocleidomastoid, preauricular, and mandibular)
• Pathogenesis/histopathologic features
■
Pseudostratied columnar or stratied squamous
epithelium with surrounding dense lymphoid tissue
including lymphoid follicles w/ germinal centers
(main clue for Boards!) → Mnemonic: “You can see the
immune system’s ‘branches’ in a branchial cleft cyst”
Pseudocyst of the auricle
• Clinical features
■
Middle-aged men; scaphoid fossa
• Pathogenesis/histopathologic features
■
Cystic space in cartilage with uid, no epithelial lining
and no inammation in cartilage
• Comments
■
a/w chronic trauma from cell phones or wrestling
Omphalomesenteric duct cyst
• Clinical features
■
Umbilical polyp in children
• Pathogenesis/histopathologic features
■
Occurs as a result of a failure to obliterate the connection
between midgut and yolk sac during embryogenesis;
ectopic columnar gastrointestinal mucosa
6.3 MELANOCYTIC NEOPLASMS
Ephelides (freckles)
• 1- to 3-mm macules of ↑ pigmentation; darken w/ sun-
exposure; sun-exposed areas of body, mainly face, dorsal
upper extremities, and upper trunk
344