Adnexal Neoplasms Flashcards
What are the differentiation types for adnexal neoplasms?
Follicular, sebaceous, apocrine, eccrine
What is the syndrome w/ sebaceous tumors?
Muir Torre
What is a hamartoma?
Benign proliferation, aberrant proportion of tissue, not neoplasm
MC site for hair follicle nevus?
By the ear on the face
MC site for trichofolliculoma?
Face, scalp, upper trunk
Clinical presentation of trichofolliculoma?
Wispy vellus hairs emerging from a skin-colored papule w/ dilated pore
Histology of trichofolliculoma?
Big momma follicle w/ surrounding little follicles they go out in a radiating type fashion.
Clinical presentation of fibrofolliculoma?
Multiple small, skin-colored to hypopigmented papules
MC located on the head and neck or upper trunk
What dz is fibrofolliculoma associated with?
Birt Hogg Dube
What is the clinical presentation of Birt Hogg Dube syndrome?
AD disorder
Fibrofolliculomas, trichodiscomas acrochordons, renal cell carcinoma chromophore and oncocytoma, colonic adenomas, pulmonary cysts, spontaneous pneumothorax
Gene mutations in Birt Hogg Dube
flcn (folliculin)
Skin lesions seen in Burt Hogg Dube
Acrochordon, fibrofolliculoma, trichodicoma, angiofibromas
What type of thyroid cancer is seen in BHD?
Medullary thyroid cancer
If you suspect Birt Hogg Dube syndrome what do you do?
Test for FLCN
Epidemiology of sebaceous nevi?
Usually present at birth
slightly raised, then more verrucous at puberty
Most common benign lesion in nevus sebaceous?
Trichoblastoma
What is the most common malignant lesion in nevus sebaceous?
BCC
What is the histology in nevus sebaceous?
Papillomatous surface w/ large sebaceous glands (enlarged, connecting directly to the skin surface). Can often see apocrine glands (unusual given usual locations)
Lacks fully formed terminal hairs within lesions
What is the mutation in nevus sebaceous?
HRS
What is the triad of Brooke Spiegler syndrome?
Brook likes cats CaTS: cylindroma, trichoepitheloma, spiradenoma
What is the gene that is mutated for Brooke Spiegler?
CYLD
What stains for desmoplastic trichoep/blastoma
PHLDHA1-positive, but - in morpheaform BCC
What is the gene mutation for pilomatricoma?
Beta-catenin (CT/NNB1) lesions have trisomy 18
What is the clinical description of a pilomatricoma?
Solitary, skin-colored or bluish nodule m/c/ on head and trunk
What is the DDx of multiple pilomatricomas?
Mrs turner’s garden: myotonic dystrophy, Rubenstein Tabey, sarcoid, Turners syndrome, Gardner’s syndrome
What two types of cells in pilomatricoma?
Matrical cells/basaloid cells and ghost cells
Baseloid cells (purple cells), and then the pink cells are ones that die and they are ghost cells
Bone can form from all the calcium in these lesions sometimes.
What is the clinical presentation of pilomatrical carcinoma?
Most commonly located on the head and neck
M/c occurs in adulthood
Often on the retroauricular area within severely sun-damaged skin
If multiple tricholemmomas are seen, what is the what dx?
Cowdens
Where do tricholemmomas arise from?
Follicular outer sheath (important, stain + for CD34)
What is the clinical presentation of tricholemmoma?
Most common on the central face, nose or upper lip (openings of the face)
Smooth skin-colored, verrucous papules
Mutation in Cowden’s
PTEN
What is found on the hand in Cowden’s
Sclerotic fibromas, acral deratoses
Adenocarcinomas found in Cowden’s?
Breast, thyroid gland (follicular), or gastrointestinal tract
Name 3 neoplasms with follicular infundibular isthmic differentiation?
Tumor of the follicular infundibulum (TFI), trichoadenoma, proliferating pilar tumor
What are the anatomical boundaries of the follicular infundibulum?
Opening on the skin to the insertion of the sebaceous gland
What are the anatomical boundaries of the isthmus of the follicle?
Sebaceous gland insertion to the insertion of the erector pili muscle
What is the clinical presentation of a proliferating pilar?
Most commonly located on the scalps of elderly women
Growing dermal nodule on the scalp
How do you treat proliferating pilar tumor?
Excise (some are malignant behaving)
What neoplasms have a sebaceous differentiation?
Sebaceous gland hyperplasia, sebaceous adenoma, sebaceoma, sebaceous epithelioma, sebaceous carcinoma
What is the difference clinically between sebaceous adenomas and sebaceomas?
Sebaceous adenomas are papules/nodules <1cm and then the sebaceoma is a deeper nodule (almost always an intradermal tumor)
What is the difference between a sebaceous adenoma and a sebaceous epithelioma
Sebaceous adenoma is more mature so the predominance of more mature sebocytes. Sebaceoma (sebaceous epithelioma) are more predominant made up of seboblasts (blue cells).
Ackerman also said the sabeceoma is more deeply situated (almost always a intradermal nodule)
What is the IHC for sebaceous carcinoma?
MSH2–> loss of function of this so it is negative in sebaceous carcinoma
What are the neoplasms w/ apocrine or eccrine differentiation?
Syringoma, poroma, hidradenoma, apocrine adeoma
What is the differentiation of syringoma?
Apocrine or eccrine lineage
What is the clincial presentation of syringoma?
Most commonly seen around the eyes (skin-colored papules)
What dz is the clear cell syringoma variant associated with?
Diabetes Mellitus
What syndrome is associated w/ syringoma?
Downs syndrome
What is the clinical presentation of eruptive syringomas?
MC on the trunk, may include extremities including palms and soles
What is the DAMES histologic DDx?
Desmoplastic trichoepithelioma, microcystic adexal carcinoma, morpheform BCC, eruptive syringoma, syringoma.
What is the clinical presentation of poroma?
MC on the palms and soles and scalp, can be associated w/ nevus sebaceous
Most common mutation in nevus sebaceous?
HRAS
What are the 2 forms of poroma?
Epidermal and dermal
What is the clinical presentation of hidradenoma?
Solitary dermal or subcutaneous nodule, sometimes cystic or serous drainage
What is the clinical presentation of syringocystadenoma papilliferum (SPAP)?
Most commonly located on the scalp and shoulders
Tend to be firm rose-red papules or papillary plaque (can be umbilicated). Superficial erosion and serous drainage is common
What is the clinical presentation of HPAP?
Most commonly located on the labia majora or anogenital lesions
Solitary, skin-colored, translucent, nodule or cyst usually less than 1cm in size
What are the undifferentiated neoplasms/carcinomas of apocrine differentiation?
Spiradenoma, cylindroma, adenoid cystic carcinoma
What is the painful tumor DDx?
“blend an egg” blue rubber bleb, leiomyoma, eccrine spiradenoma, neurofibroma, dermatofibroma, angiolipoma, neurilemoma (schwannoma), endometriosis, granular cell, glomus tumor
What gene is mutated in Brooke Spiegler Syndrome?
CYLD
What is the classic look of a cylindroma on histology?
Jigsaw puzzle pieces of blue nodules in the dermis
What is the clinical presentation of microcystic adnexal carcinoma?
Tends to occur in middle aged to elderly patients
- Presents around the mouth or located on the central face
- Usually looks like a firm skin-colored to yellowish plaque, nodule, or cystic tumor
What are the neoplasms w/ eccrine differentiation?
Eccrine nevus, syringoma, adnexal adenocarcinoma, syringofibroadenoma
Gene associated with Birt Hogg Dube
Folliculin FLCN which is a tumor suppressor gene
What tumor arises from the acrosyringium?
poroma
What tumors arise from the eccrine duct/gland?
Syringoma, hidradenoma, mixed tumor, hidrocystoma
What tumors arise from the follicular infundibulum?
Trichoepithelioma, fibrofoliculoma, trichodiscoma, trichofolliculoma, nevus comedonicus
What tumors arise from the isthmus?
Tricholemmoma, tumor of the follicular infundibulum, proliferating tricholemmal tumor, pilar sheath acanthoma
What are the tumors of the germ/matrix cells?
Basal cell carcinoma, pilomatricoma, trichoblastoma, pilomatrical carcinoma
Tumors of the apocrine duct/gland?
Syringoma, poroma, hidradenoma, syringocystadenoma papilliferum, spiradenoma, cylindroma, tubular adenoma, microcystic adnexal carcinoma, hidrocystoma, extramammary paget dz, mucinous carcinoma
Tumors of the sebaceous gland?
Sebaceous hyperplasia, nevus sebaceous, sebaceous adenoma, sebaceoma, sebaceous carcinoma
What disorder is multiple perifollicular fibromas and trichodiscomas associated with?
Birt-hogg-dube syndrome
AD, fibrofoliculomas, trichodiscomas, and acrocordons.
a/w renal cancer (chromophore and oncocytoma), colonic adenomas, pulmonary cysts, spontaneous pneumos, medullary thyroid carcinoma.
What is the clinical presentation for desmoplastic trichoepithelioma?
MC: solitary annular indurated and centrally depressed papules or plaques on the face of younger individuals
Most common benign neoplasms and malignant neoplasms that arise from nevus sebaceous?
Benign: trichoblastoma
Malignant: BCC
What is the most common location for mixed tumor (chondroid syringoma)?
MC on head and neck, may develop on trunk or within axillary or genital skin
What are the components of cowden’s dz?
Cowden’s disease: tricholemommas, sclerotic fibromas, acral keratoses, adenocarcinoma of breast, thyroid gland or gastrointestinal tract
What syndrome is associated w/ multiple trichoepitheliomas also known as epithelioma adenoides cysticum?
Brooke Spiegler Syndrome
What is the histology of the tumor of the infundibulum?
Plate-like proliferation of eosinophilic isthmic keratinocytes
arranged in a reticulate pattern in the superficial dermis
Broad intermittent continuity with surface epidermis and follicular structures.
What is the histology of trichoadenoma?
Benign, follicular neoplasm w/ sclerotic stroma, often w/ stands of basaloid cells and many small cystic spaces w/ cornifying cysts (can look like big glasses or eyes)
What is the triad of Brooke-Spiegler syndrome?
Cylindromas, trichoepitheliomas, spiradenomas.
Stains for trichoepithelioma to differentiate between that and BCC?
CK20, CK34+, androgen-R (negative), Bcl-2 (+ in BCC diffusely, only peripherally + in trichoepithelioma)
How do you distinguish desmoplastic trichoep/blastoma from morpheaform BCC?
PHLDHA1 +, negative in morpheaform BCC
if there are multiple pilomatricoma what is on the differential?
MRS turners garden
Myotonic dystrophy, Turner syndrome and Gardner syndrome, and Rubenstein-Taybi syndrome
Mutation in what gene causes pilomatricoma?
Beta-catenin (CTNNB1), lesions demonstrate trisomy 18
What is the differentiation of the tricholemmoma?
Follicular outer sheath
Most common locations for tricholemmoma?
MC on the face, nose, and upper lip
If you see multiple tricholemmomas on the face or genital skin what should we consider?
Cowden’s dz
What is the mutation in cowden’s dz?
PTEN
What is the tricholemmal carcinoma made up of?
Glycogen containing clear cells similar to follcular outer sheath. show accompanying keratinization so there is overlap with lesions that have been pigeon-holed as clear cell SCC.
What stain is the tricholemmal carcinoma + for?
CD34+ also the basement mebrane is PAS +
What is the classic triad of muir-torre syndrome?
1) Multiple sebaceous adenomas
2) Multiple keratoacanthomas
3) Visceral carcinomas especially colon adenocarcinoma
What is the immunohistochemistry of trichoepithelioma?
PHLDA1+; stroma is CD34+ and CD10+ (BCC has more epithelial staining here rather than stroma), androgen receptor-negative (vs + in BCC), BCL-2 on stains periphery vs more diffusely in BCC
What is the most common sebaceous neoplasm in Muir Torre syndrome?
Sebaceoma
Ocular sebaceous carcinoma is often misdiagnosed as what initially?
Chalazion or blepharitis
Clinical presentation of sebaceous carcinomas?
Significant metastatic potential
- Separated into ocular and extraocular types
- Most commonly located near the yes, look like nonspecific red nodule with or without ulceration
Most common locations for sebaceous carcinoma?
Periorbital area> other sites on head/neck > trunk
What is the differential of a sebaceous neoplasm that has > 50% sebaceous basaloid cells (seboblasts)?
Must either be a sebaceous carcinoma or sebaceoma
What are some key histologic features of microcystic adnexal carcinoma?
Divergent bi-lineage differentiation (follicular and sweat gland)
Deeply infiltrative throughout the dermis, SQ and into muscle
Usually has perineural invasion and lymphoid aggregates
What is the clinical presentation of eccrine poroma?
MC on the palms/soles (lots of eccrine glands)
Presents as a solitary, vascular-appearing papule/nodule that can have ulceration and bleeding. Can often be surrounded by a thin mote
What is the histology of eccrine poroma?
Circumscribed, endophytic proliferation w/ broad, multifocal epidermal connections made up of monomorphous, small cuboidal cells with intercellular desmosomal bridges (poroid cells)
Can see variably sied sweat ducts w/ pink cuticle and there is often a highly vascularized stroma resembling granulation tissue
Immunohistochemistry of eccrine poromas?
+ for CEA, EMA, and PAS highlight ducts and intracytoplasmic lumina
What are the 3 variants of poroma?
- Hidroacanthoma simplex (Intraepidermal form that is only in the epidermis, most superficial)
- Classic poroma (juxtaepidermal)
- Dermal duct tumor (wholly dermal)
Clinical features of porocarcinoma?
Most common sweat gland malignancy
- Seen in elderly, most commonly on the lower extremity, and can either arise in a longstanding poroma or de novo
- Metastasis is common (20%), and there is a 10% mortality
Histology of porocarcinoma?
Like classic poromas but with more cytologic atypia, increased mitoses, atypical mitoses, and infiltrative growth pattern at the tumor base
What is the clinical presentation of hidradenoma?
Solitary nodule (often multilobulated) with a deep red-purplish hue and cystic quality
What is the histology of hidradenoma?
- Composed of 3 cell types: Squamoid cells, poroid cells, and clear cells. Can have these in varying amounts
- Large tumor nodules, large areas of cystic degeneration of then, prominent dermal sclerosis with keloidal collagen
Can a syringomatous carcinoma arise out of a syringoma?
NO! always de novo
What is the histology of a mixed tumor (chondroid syringoma)?
Comprised of a roughly 50/50 mixture of epithelial (ectodermal) and stromal (mesodermal) cell types
- the epithelial component is usually eccrine or apocrine more than follicular, sebaceous or plasmacytoid
- The stromal component is myxoid or chondroid more than others
What is the clinical presentation of a spiradenoma?
Painful, dermal or subcutaneous nodule w/ a blue-purple hue
Favors the upper half of the body
What is the histology of the spiradenoma?
“Big blue balls in the dermis”
- Ductal formation including cystically dilated ducts can be seen. There are 2 cell types, hyperchromatic cells w/ minimal cytoplasm, and larger pale-staining inner cells with more cytoplasm.
- Intratumoral lymphocytes and PAS+ eosinophilic droplets in the middle of the tumor
Clinical presentation of cylindroma?
90% occur on the head/neck (mostly scalp)
- Solitary erythematous/purple nodule w/ telangiectasia
- Multiple cylindromas can coalesce and form a “turban-tumor” in Brooke Spiegler
What is the clinical presentation of aggressive digital papillary adenocarcinoma?
Affects the volar digits of middle-aged adults (M>>>W 7:1), dermal nodule/bluish to brown coloring
Histology of aggressive digital papillary adenocarcinoma?
Histology can look rather bland, almost like an SPAP, but if you see it on the finger take cation!
Cytologic atypia can be present, increased mitotic rate (check Ki-67)
What is the treatment for aggressive digital papillary adenocarcinoma?
Amputation (aggressive treatment needed, high metastasis and recurrence rate)
Clinical presentation of mucinous carcinoma?
Very rare, presents as a slow-growing, soft nodule on the eyelid or periocular region in an elderly patient
Histology of mucinous carcinoma?
Basaloid epithelial tumor nodules floating in a lake of mucin
Has a cribriform appearance form the intratumoral ducts
What should be considered if a mucinous carcinoma is seen on the trunk?
Lesions on the face are almost always primary, lesions on the trunk are almost always metastasis of visceral malignancy (GI, breast, lung, or ovarian)
What is the clinical presentation of adenoid cystic carcinoma?
An indolent tumor on the scalp of middle-aged adults
little metastatic risk but recurs commonly (70%) 2/2 perineural invasion
How could you tell if a mucinous carcinoma is primary cutaneous or metastatic?
Primary cutaneous will be p63+, SMA+, and calponin+ (myoepithelial cells together, myoepithelial layer is never present in metastatic tumors)
What are the staining differences between the primary cutaneous mucinous carcinoma and metastatic mucinous carcinoma from the GI tract?
Primary cutaneous mucinous carcinoma: CK7+/CK20+, ER +, PR +, AE1/AE3, CAM5.2, EMA, CEA +
Metastatic mucinous GI tumor: CK7-/CK20+, sulfomucin (alcian blue + at pH 1.0 and 0.4) vs PCMC = sialomucin (Alcian blue + @ pH 2.5)
