Neoplastic Dermatology chapter 6 Flashcards
SK’s are associated with what mutations?
FGFR3 and PIK3CA activating mutations
Acanthosis, papillomatosis, hyperkeratosis with pseudohorn cysts, flat base (“string sign”), bland keratinocytes without atypia seen with?
Seborrheic keratosis
Seborrheic Keratosis Histologic Variants?
Acanthotic (most common), Hyperkeratotic (“church spire”), Reticulated, Irritated, Clonal, Melanoacanthoma
Porokeratosis onset in infancy or childhood, extremities; large (often >3 cm) circinate plaque with keratotic border?
Porokeratosis of Mibelli
Porokeratosis in middle age, F > M with numerous brownish-red macules w/ keratotic borders in sun-exposed areas; most common on legs?
Disseminated superficial actinic porokeratosis DSAP - most common
Porokeratosis onset in newborns with linear lesions on extremities, follows lines of Blaschko is?
Linear porokeratosis
Porokeratosis with onset in adolescence, 1- to 2-mm “seed-like” papules on palms/soles?
Punctate porokeratosis
Porokeratosis onset in childhood occurs on palms and soles initially is?
Porokeratosis palmaris, plantaris, et disseminata
Porokeratosis that clinically resembles a nevus comedonicus of palm or sole, but histology shows abundant cornoid lamellae arising from acrosyringium is?
Porokeratotic eccrine ostial and dermal duct nevus
Highest risk of SCC in porokeratosis in what subtype?
linear porokeratosis
White scaly variant of SK is called?
Stucco keratosis associated with HPV-23b
Endophytic variant of irritated SK is called?
Inverted follicular keratosis, appears on cheek and upper lip with histology w/ prominent squamous eddies
Tan-flesh colored warty papules on dorsal hands and feet, autosomal dominant disorder of keratinization often a/w Darier disease, ATP2A2 mutations with histology with “church spire” is called?
Acrokeratosis verruciformis of Hopf
Solitary erythematous papule on lower leg with “wafer-like scale” at the periphery is?
Clear cell acanthoma (Degos acanthoma)
Nevus comedonicus is associated with what mutation?
FGFR2
Erythroplasia of Queyrat?
Juicy red, erosive plaque on glans penis >30% progress to invasive SCC, HPV-16 is #1 cause.
Drugs that increase SCC risk?
Voriconazole
Vemurafenib
Vismodegib
AZA
Systemics for SCC?
Cemiplimab or pembrolizumab if surgery or advanced or metastatic disease
Factor related to SCC DEAth?
DIAmeter
Low-grade, locally destructive SCC a/w HPV-6 and HPV-11 is?
Verrucous carcinoma
Rapid onset of multiple KA’s with onset third decade, sun-exposed areas,
and resolves spontaneously is called?
Ferguson-Smith
1000s of milia-like KAs in later
adulthood may involve airway a/w scarring, ectropion, and mask-like facies is called?
Grzybowski - Mnemonic: “Old (later onset) Grizzlies Growl” -> airway affected
“shark-tooth” or “dragon scale” on histology is seen in?
Steatocystoma
Steatocystoma multiplex is due to mutations in?
KRT17 mutations
Midline anterior neck swelling vs. lateral neck are?
Thyroglossal duct cyst - midline anterior
Branchial cleft cyst - lateral neck
Freckles are called?
Ephelides
Multiple CALMs may be seen with?
■ NF1 > NF2
■ McCune-Albright syndrome
■ Russell-Silver
■ Noonan syndrome
■ Bloom syndrome
■ Tuberous sclerosis
■ MEN-I
■ Fanconi anemia
■ Ataxia-telangiectasias
Histology: ↑ melanin deposition in basilar keratinocytes
Conditions a/w multiple lentigines?
■ LEOPARD, most heavily “spotted” appearance*
■ Carney complex (LAMB/NAME)*
■ Peutz-Jeghers, perioral*
■ Bannayan-Riley-Ruvalcaba, penile*
■ Laugier-Hunziker
■ Cowden syndrome
■ Xeroderma pigmentosum
■ Cronkhite-Canada
Risks of nevus of Ota?
10% develop glaucoma and uveal melanoma (rare malignant degeneration)
Hori’s nevus, acquired nevus of Ota-like macules of the bilateral zygomatic region seen in East Asian females
Nevus of Ito, located on the shoulder, supraclavicular and scapular regions, no risk of progression to melanoma
Most common sites for blue nevus?
Scalp, sacral area, and distal extensor extremities
Multiple blue nevi and epithelioid blue nevi seen with?
Carney complex
Risk with blue nevi?
Uveal melanoma (GNAQ and GNA11) and metastasis and death if concomitant BAP-1 loss
Subtype of blue nevus seen in Carney complex?
Epithelioid blue nevus, PRKAR1A and PRKCA mutations
“Cellular blue nevus” Dense proliferation of plump/fusiform pale gray melanocytes containing little pigment characteristically bulges into subcutis “dumbbell configuration”
Spitz nevus mutations?
HRAS mutations/11p gain
On histology, pink clumps of basement membrane zone, material (collagen IV) within epidermis are called?
Kamino bodies seen in Spitz nevus
Immunostains in spitz nevus?
S100A61, S1001, Melan-A1, and p161
Deep penetrating nevus mutation?
Activating b-catenin mutations
Congenital melanocytic nevus mutation?
NRAS
Mutations associated with melanoma?
Sun-damaged areas, acral or mucosal -> C-KIT or CCND1/CDK4
Uveal melanoma, blue nevi, and nevus of Ota -> GNAQ/GNA11
A benign sweat gland neoplasm that presents as a solitary, vascular-appearing papule, +/- ulceration and bleeding; is called?
Poroma
Poromatosis?
widespread or acral eruption of poromas
Poroma stains?
CEA, EMA, and PAS highlight ducts and intracytoplasmic lumina
What are the 3 poroma variants?
1- Wholly intraepidermal poroma - mistaken for SK, on distal extremities
2- Juxtaepidermal poroma - classic
3- Wholly dermal poroma - “blue balls/nodules within dermis”
Most common sweat gland malignancy?
Porocarcinoma
A benign sweat gland neoplasm (apocrine>eccrine) that presents as a solitary nodule (often multilobulated) with a deep red-purplish hue and cystic quality is called a?
Hidradenoma
“Prominent dermal sclerosis with keloidal collagen” clues towards?
Hidradenoma
Hidradenoma is composed of 3 main cell types?
Squamoid cells, poroid cells, and clear cells
Most common location for Syringoma?
Periorbital region (eyelids #1), cheek > anterior trunk, genitals
Solitary, painful dermal or subcutaneous nodule with blue-purple hue; favors upper half of body is?
Spiradenoma
Cylindroma’s usually occur on the?
Scalp
A “turban tumor” seen in Brooke-Spiegler syndrome is basically a cluster of?
Cylindroma’s
Benign, painless 1- to 2-cm skin colored nodule; almost exclusively on vulva (labia majora #1) of young adult women?
Hidradenoma papilliferum
“maze-like” hits
Benign apocrine neoplasm; presents at birth or early childhood with a solitary, warty papule/plaque on scalp (. other sites on head/neck . trunk and extremities); usually a/w nevus sebaceus is a?
Syringocystadenoma papilliferum
Papillary eccrine adenoma usually occur on?
Legs #1, favors Black women
Also Syringofibroadenoma on the legs
Syringofibroadenoma are seen in?
Schöpf-Schulz-Passarge
Clouston syndrome
Chronic stasis dermatitis (reactive process)
Burns and scarring
Thin, anastomosing strands of sweat duct-
containing epithelium projecting downward from epidermis into mid dermis seen in?
Syringofibroadenoma
Firm, indurated plaque on lip >chin and cheek of middle-aged women that is locally aggressive is likely?
Microcystic adnexal carcinoma
Tx: Mohs
Microcystic adnexal carcinoma lineage?
Locally aggressive adnexal carcinoma with divergent, bi-lineage, differentiation “follicular + sweat gland”
Histo deeply-infiltrative sclerosing basaloid proliferation with divergent/bi-lineage differentiation (mixture of small sweat ducts 1 keratinizing “microcysts”); typically has PNI and prominent lymphoid aggregates?
microcystic adnexal carcinom
Tx of digital papillary adenocarcinoma?
Its aggressive digital papillary adenocarcinoma, tx: amputation
Cutaneous mucinous carcinoma on the face vs. on the trunk?
Mucinous carcinomas on the face are almost always primary, whereas lesions arising on trunk may represent metastasis of visceral malignancy, GI, breast, lung, or ovarian.
Basaloid epithelial tumor nodules “floating in lakes of mucin,” sialomucin, intratumoral ducts give rise to cribriform appearance, CK7+, CK20- is?
Primary cutaneous mucinous carcinoma
“blue balls within dermis”
Dermal duct tumor, wholly dermal poroma variant
Well-circumscribed proliferation of multiple small-to-medium-sized blue tumor lobules encircled by thick hyaline BMZ material (type IV collagen mainly) → leads to “jigsaw puzzle” pattern; scattered small ducts; biphasic cell population?
Cylindroma
Primary cutaneous mucinous carcinoma stains?
p63/p401, SMA1, calponin1, SOX101, and S1001
Extensive nevus sebaceous think of?
Schimmelpenning syndrome or phakomatosis pigmentokeratotica
Syndromes a/w multiple trichoepitheliomas?
○Brooke-Spiegler syndrome: CYLD mutation, multiple trichoepitheliomas, trichoblastomas, spiradenomas, and cylindromas
○Rombo syndrome: atrophoderma vermiculatum, hypotrichosis, acro-facial vasodilation and cyanosis, milia, and multiple BCCs
well-circumscribed; complex cystic proliferation with internal “rolls and scrolls” appearance is?
Pilomatricoma
Schwannoma (neurilemmoma) is?
Benign proliferation composed almost entirely of Schwann cells (S100+, stains Schwann cells) with perineurial capsule (EMA+, stains perineurial capsule)
Plexiform neurofibromas, “bag of worms”, stain with?
S100+, neurofilaments+
Cellular neurothekeoma stains?
Boards favorite: always S100 negative (vs. classic “neurothekeoma”); but S100A6+, NKI/C3+, and PGP 9.5+
Aggressive malignant neoplasm (deadlier than melanoma); most common in elderly on head/neck; UV exposure is major risk factor; ↑ risk w/ immunosuppression is?
Merkel cell carcinoma
densely cellular proliferation of atypical spindle cells often with large areas of necrosis (“geographic necrosis”) and a high mitotic rate is seen in?
Malignant peripheral nerve sheath tumor
Histology: infiltrative or nodular dermal/subcutaneous mass composed of sheets of uniform basaloid cells with high N:C ratio and finely speckled “salt-and-pepper” chromatin (usually without prominent nucleoli); numerous mitoses (often > 30/mm2) and apoptotic cells
Merkel cell carcinoma
Merkel cell carcinoma stains?
■ Positive stains: CK20 (paranuclear dot pattern, highly sensitive), neurofilaments (paranuclear dot pattern, highly sensitive), chromogranin/synaptophysin, NSE, EMA, and CD56; MCPyV+ (80%; polyomavirus)
■ Negative stains: TTF-1, CK7, S100, and CEA
if mcc, CK20-, THINK OF?
Small cell lung carcinoma (main consideration!
Recurrent locally advanced MCC tx?
pembrolizumab
Primitive neuroectodermal tumor (neuroblastoma) px?
metastatic disease → p/w multiple blue nodules on trunk and extremities
“Raccoon eyes” (periorbital darkening/purpura) from orbital metastases
↑ Urinary catecholamines (>90%)
Red-brown papules on trunk or extremities, Painful, especially with cold exposure, Pseudo Darier sign?
Pilar leiomyoma, Benign proliferation of smooth muscle arising from arrector pili
Multiple Pilar leiomyoma can occur as part of?
Reed syndrome, AD inheritance, fumarate hydratase mutations, multiple cutaneous and uterine leiomyomas and RCC
Pilar leiomyomas stains?
Desmin+, SMA+, and caldesmon+; smooth muscle fibers are pink-red with Masson trichrome stain
Bright pink cytoplasm and “cigar- shaped” nuclei?
Pilar leiomyoma
Painful Skin Lesions?
Most commonly middle-aged females on lower extremity; frequently painful?
Angioleiomyoma, desmin+ (differentiates from myopericytoma), SMA+, calponin+ and h-caldesmon+
MF immunophenotype?
■ Typical phenotype: CD3+/CD4+/CD8- mature T-lymphocytes
■ Variable loss of pan T-cell markers: CD7 loss (most common, least specific) > CD5 and CD2 loss (less common, more specific)
Hypopigmented MF immunophenotype?
CD4- /CD8+
Adult T-cell leukemia/lymphoma px with?
leukemia, lymphadenopathy, organomegaly, hypercalcemia, and skin lesions
Sezary syndrome histology?
Histopathology resembles MF, but has characteristic “floret” or “clover-leaf” malignant T cells
■ Immunophenotype: CD4+/CD8-/CD25+, PD-1+
Wedge-shaped infiltrate with clusters of large, atypical, Reed-Sternberg-like CD30+ (Ki-1) lymphocytes are seen in?
Type A Lymphomatoid papulosis
Lymphomatoid papulosis ALCL-type?
Type C (ALCL-type, 10%)
Angioinvasive LyP?
Type E, CD8+/CD30+
What associated malignant lymphoma associated with LyP?
MF > Hodgkin disease, ALCL > others
Extranodal NK/T-cell lymphoma, nasal type immunophenotype?
CD2+/CD56+ and CD3+
Leukemia cutis is most commonly due to?
Acute myeloid leukemia
Violaceous, usually solitary papule or nodule on the scalp/forehead or back (“Crosti lymphoma”) is what type of cutaneous B-cell lymphoma?
Primary cutaneous follicle center cell lymphoma
Dermatofibroma positive stains?
Factor XIIIa
CD10 strong, diffuse
Stromelysin-3, distinguishes from DFSP
Negative stains: CD34, S100, and pan-keratin
Translocation for Dermatofibrosarcoma protuberans?
t(17;22) COL1A1-PDGFB fusion
Mnemonic: “DFSP affects people 17 to 22 years old Called Pat”…
Remember young age (17–22) and the order of the fused genes:
17 = COL1A1
22 = PDGFB
Monotonous spindle cells (cells are more bland and uniform than DF!) with a storiform architecture in dermis and throughout SQ fat; characteristic “honeycomb” infiltration of fat; 5% with melanin (Bednar tumor)
■ CD34 strongly positive
Dermatofibrosarcoma protuberans
Zycomycosis, Bull’s –eye cutaneous infarcts
Cell types in atypical fibroxanthoma?
1) spindle cells
2) histiocyte-like cells
3) xanthomatous cells
4) bizarre, multinucleated giant cells
Atypical fibroxanthoma differential?
“SLAM” DDx
■ SCC (sarcomatoid/spindle cell variant): stains positively with high-molecular-weight keratin (CK903 and CK5/6) or broad-spectrum keratin (MNF-116), p63 and p40 (newest and most specific marker)
■ Leiyomyosarcoma: desmin+, SMA+
■ AFX: negative for high-molecular-weight keratin, p63, p40, S100, SOX10, and desmin
■ Melanoma
Histology of Sclerotic fibroma?
“plywood” or “starry night” pattern
Pleomorphic fibroma clinically resemble?
Skin tags
Multiple, grouped red papules on dorsal hands or legs of women in their 40s; benign?
Multinucleate cell angiohistiocytoma
w/ characteristic multinucleated giant cells and prominent proliferation of dilated vessels in dermis
Solitary, pyogenic granuloma-appearing papules; most
common on thighs of 50-year-old women?
Epithelioid cell histiocytoma
Resembles spitz nevus histologically w/ epidermal collarette
A protruding, skin tower from fingers or feet?
Acral fibrokeratoma
Fibromatosis types?
Superficial variants:
○Palmar (Dupuytren’s)
○Plantar (Ledderhose)
○Penile (Peyronie’s)
○Knuckle pads
Deep desmoid tumors a/w Gardner syndrome, b-catenin mutations, and stain b-catenin+
What histology looks like pseudo sarcoma?
Nodular fasciitis
Biphasic proliferation, with hypo cellular and hyper cellular areas, staghorn (“hemangiopericytoma-like”) vessels, SMA+ tram-track seen in?
Myofibroma
Numerous osteoclastic giant cells?
Giant cell tumor of tendon sheath
Buschke-Ollendorf ?
Elastomas + osteopoikilosis
Angiokeratoma’s in children?
Angiokeratoma of Mibelli: 10 to 15 years old; fingers and toes
Angiokeratoma’s in vulva or scrotum?
Angiokeratoma of Fordyce: older men (scrotum) or females (vulva)
Angiokeratoma’s in Fabry’s disease?
Angiokeratoma corporis diffusum: multiple lesions in childhood/adolescence; bathing suit distribution; seen in Fabry disease and other enzyme deficiencies
Angiokeratoma’s that aggregate and form a plaque?
Angiokeratoma circumscriptum
Epithelioid hemangioma is also known as?
Angiolymphoid hyperplasia with eosinophils
Angiolymphoid hyperplasia with eosinophils is usually seen on?
Ear* Head/neck
Red-brown papules with “target-like” appearance (dark centrally → pale area is first ring → bruise-like patch in outer ring) is called?
“hobnail hemangioma” or “targetoid hemosiderotic hemangioma”
“cannonball” pattern; a characteristic empty-appearing “crescent” surrounds the periphery of each lobule?
Tufted angioma
Histology (Boards favorite): well-circumscribed dermal proliferation comprised of dilated vessels that are filled centrally with a small ball of well-formed capillary loops → resultant architecture resembles renal glomeruli
Glomeruloid hemangioma
Rare vascular tumor of childhood; a/w Kasabach-Merritt phenomenon; GLUT-1 negative?
Kaposiform hemangioendothelioma
- Positive for CD34 and CD31
- Negative for Factor VIII
Stewart-Treves syndrome?
Angiosarcoma seen in chronic lymphedema associated, mostly following breast cancer treatment with axillary LN dissection
Angiosarcoma immunostains?
ERG+ (most sensitive and specific), CD31+, CD34+, and FLI-1+
c-MYC amplications (detected by
immunostaining or FISH)
Genetic lipoma?
↑ HMGA2 gene
Conditions a/w multiple lipomas?
■ Familial multiple lipomatosis: AD; multiple painless
lipomas on trunk/extremities
■ Madelung disease: multiple large lipomas around neck/
shoulders; generally in middle-aged alcoholic males
■ Gardner syndrome
■ Bannayan-Riley-Ruvalcaba syndrome
■ Proteus syndrome
■ CLOVES syndrome (Congenital Lipomatous
asymmetric Overgrowth, Vascular malformations,
Epidermal nevi, Skeletal and spinal anomalies)
■ PTEN hamartoma tumor syndrome
Benign tumors of brown fat?
Hibernoma
Histo of Hibernoma?
Hibernoma cells (polygonal cells with
eosinophilic, multivacuolated cytoplasm) admixed with
normal appearing adipocytes
“floret-like” cells seen in?
Pleomorphic lipoma
Has thick “ropey” collagen fibers
Mutation detected in well-differentiated liposarcoma?
MDM2 amplification (12q13-15 ring/giant chr)
Rare type of liposarcoma; most testable point is its characteristic histology (buzzword: “chicken-wire” vessels)?
Myxoid/round cell liposarcoma
Kasach-Merritt syndrome seen with?
Tufted hemangioma
Kaposiform hemangioendothelioma
Dermoscopy of SK?
- Milia-like cysts
- Comedo-like openings
- Fissures and ridges
- Moth-eaten borders
- Sharp demarcation
- Fingerprint-like pattern
“Strawberry pattern” is seen on dermoscopy of what lesion?
Actinic keratosis
Dermoscopy of BCC?
- Leaf-like structures at periphery
- Blue-gray ovoid nests and globules
- Pigmented specks
- Spoke-wheel structures/concentric structures
- Arborizing(branch-like) telangiectasias (non-superficialBCCs)
- Serpentine vessels (superficial BCCs)
- Ulceration/erosion
Vessels seen on dermoscopy of SCC in situ?
Clusters of glomerulus-like (coiled) vessels
