25 - Benign Skin Neoplasms Flashcards
Skin is composed of 3 layers
- Epidermis
- Dermis
- Hypodermis
Benign epithelial tumors – Seborrheic keratoses
- Tumors occur most frequently in middle-aged or older individuals (rare before 30)
- Round, flat, coin like, waxy plaques that vary in diameter from mm to several cm (with or without pigment)
Treatment of seborrheic keratoses
Not necessary unless lesions are bothersome o Surgery o Chemical peeling agents o Electrocautery o Cryotherapy
What do you NEED TO KNOW about seborrheic keratoses?
- Separating these from melanoma can be tricky
- VERY HARD TO LOOK AT SOMETHING AND KNOW WHAT IT IS
- Biopsy is very important – don’t treat things until you have a diagnosis
- Seborrheic keratoses can MIMIC OTHER LESIONS*** - NEED TO KNOW
Laser-Trelat sign
o Sudden onset of numerous seborrheic keratoses may indicate an underlying visceral malignancy
Biopsy image of seborrheic keratoses
o Can see microcysts of keratosis
o It is NOT invading the dermis – this is how you know it is not a squamous cell carcinoma
o If you do too shallow of a biopsy, the pathologist would not be able to distinguish
o Need to be able to see normal dermis
Fibroepithelial polyp-acrochordon
- Morphology = fibrovascular core covered by benign squamous epithelium
- Covered by a benign epithelial
- Can sometimes be HPV driven tumors in the genital region
Epithelial cysts
Epithelial cysts are divided into several histological types:
o Epidermal inclusion cyst (Epidermoid Cyst)
o Pilar or trichilemmal cysts
o Dermoid cyst
o Steatocystoma multiplex
Epidermoid cyst
Not typically recommended to drain them – risk of infection, usually recur
Trichilemmal cyst
- Tend to be seen on the scalp
- Hot pink core – very densely compacted hyperkeratosis
- Only exists in the hair follicle
Dermoid cyst
- Common presentation: Single subcutaneous nodule at birth on lateral aspect of upper eyelid
- Embryologically has a different origin
Steatocystoma
- Multiplex (autosomal Dominant mutation in Keratin 17, seen in sternal, axillae, groin regions)
- Simplex = solitary lesion
- Kind of looks like an epidermal cyst, but there are attached sebaceous nodules
- Very thin layer of keratosis over top
Tumors of the hair follicle
Types o Trichoadenoma o Trichilemmoma o Pilomatrixoma o Trichofolliculoma o Trichoepithelioma o Fibrofolliculoma o Trichodiscoma
We will only go through some of them
Some are associated with different mutations or cancers, so just know those
Cowden’s disease and trichilemmoma
There is a nodule of squamous cells with a clear, pale cytoplasm
Cowden’s Disease
o Autosomal Dominant disease with mutation of tumor suppressor PTEN
o High risk for breast and thyroid carcinomas
o Oral Lesions, acral keratoses, macrocephaly all seen
Trichilemmoma
Can be solitary or multiple (multiple is diagnostic of Cowden’s disease)
Pilomatrixoma
- Solitary firm nodule on head>upper limbs>neck>trunk
- Cheek most common location
- 60% before age 20
Birt-Hogg-Dube Syndrome
- Mutation to BHD gene on chromosome 17
- Encodes protein folliculin – function unknown
- Multiple fibrofolliculomas, trichodiscomas, and acrochordons
- Association with internal disease
- Renal tumors – benign and malignant
- Lung disease – spontaneous pneumothorax
Benign tumors of sebaceous glands
- Sebaceous hyperplasia
- Sebaceous adenoma
- Sebaceoma
- Sebaceous carcinoma
- Nevus sebaceous
Nevus sebaceous
- Also called organoid nevus
- Not a melanocytic proliferation
- Often presents at birth, M=F
- Presents on head/neck, particularly scalp
-
**SECONDARY TUMORS CAN ARISE WITHIN THESE ** This is why they are important clinically
o Benign syringocystadenoma papilliferum and trichoblastoma
o BCC
Sebaceous hyperplasia
- Common on the face of older adults
- Misdiagnosed as BCC
- Yellowish dome shaped papules
Sebaceous adenoma
- Rare, mistaken for BCC
- Face and scalp of older people
- Can be seen in Muir-Torre Syndrome
Sebaceoma
- Intermediate aggression
- No metastasis reported
- Also related to MTS
Muir-Torre syndrome
- Related to Hereditary Non-polyposis Colorectal Carcinoma cancer syndrome
- Inherited defect in a DNA mismatch repair gene (MMR)
- Loss of genetic stability during replication leads to microsatellite instability (repetitive sequences of DNA)
- Most common gene MSH2
- Autosomal Dominant
- Need the family to be screen early for colorectal tumors
- Notes: when mismatch repair genes are defective, they cannot repair inappropriate sequences – you get a buildup of mutations
Cutaneous findings in Muir-Torre syndrome
Sebaceous tumors
- Adenoma, sebaceoma, and carcinoma
- Keratoacanthoma
Visceral malignancies in Muir-Torre syndrome
GI tract (colon)
- Colon tumors tend to be more proximal
- Tends to be less aggressive than other colon CA
Bladder
Endometrium
Breast
Diagnosing MTS
o Immunostaining for Mismatch repair enzymes
o Loss of staining is ‘positive’
o Follow up positive result with genetic sequencing
Benign tumors of sweat glands
- Syringocystadenoma papilliferum
- Nipple adenoma
- Poroma
- Chondroid Syringoma (mixed tumor)
- Hidrocystoma
- Syringoma
- Hidradenoma
- Hidradenoma papilliferum
- Cylindroma
- Spiradenoma
Cylindroma
- 90% occur on head and neck
- Pink/red nodule
- F:M 9:1
- Brooke-Spiegler Syndrome*
- Can be referred to as “Turban tumor”
- On microscopy, appear like a “jigsaw puzzle”
What is Brooke-Spiegler syndrome?
o Familial cylindromas o Trichoepitheliomas o Milia o Spiradenomas o Autosomal Dominant: CYLD gene on chromosome 16 (lack of CYLD results in NF-kb pathway activation)
Histiocytic “tumors”
- Xanthomas/Xanthelasma
- Juvenile Xanthogranuloma
- Reticulohistiocytoma
- Langerhans cell histiocytosis
Xanthomas
Less a tumor and more of a benign aggregate of histiocytes with cytoplasmic lipid
Five clinical types o Eruptive o Tendinous o Tuberous o Planar o Disseminated (Only one with normal serum lipid levels)
Xanthogranuloma
- Often called Juvenile Xanthogranuloma (JXG)
- Usually arises in first 5 years (20% of cases in young adults)
- Solitary lesions on head/neck>trunk>upper limbs
- Yellow brown/orange papule or nodule (Differential diagnosis: Spitz nevus, mastocytoma)
- Rare association with chronic myelogenous leukemia (CML) and neurofibromatosis – boards question
- Spontaneously regress within several years
- JXG pathology (Granulomous eruption, “Tuton” giant cells)
Reticulohistocytoma
- Age: middle age
- F>M
- KEY WORD = “ground glass histiocytes” on microscopy
Two forms:
o Solitary
o Multicentric reticulohistiocytosis
Multicentric reticulohistiocytosis
- Cutaneous nodules, destructive arthritis, intermittent pyrexia
- 25% have concurrent malignancy
- Also associated with vasculitis and connective tissue disease
Langerhans cell histocytosis (LCH)
- Variable clinical presentation
- All characterized by proliferation of Langerhans cell-type histiocytes in tissue
3 types
o Acute Generalized LCH (Letterer-Siwe Disease)
o Multifocal Chronic LCH (Hand-Schuller-Christian Disease)
o Focal chronic LCH (eosinophilic granuloma)
Most aggressive – high morbidity/mortality
o Skin and internal organ involvement
o Infancy
Multifocal chronic LCH (Hand-Schuller-Christian disease)
- First 5 years of life, can affect older
- Multisystem but more chronic course
- Regionally localized disease (head)
- Triad: lytic skull lesions, diabetes insipidus, and proptosis
- Treatment: radiation and chemotherapy
Eosinophilic granuloma
- Most benign – very good prognosis
- Older children and adults
- Solitary
- Treatment: Excision or radiation
LCH pathology
- Classically have a nuclear groove
- DC1a positive
- “Birbeck granules” on electron microscopy
Benign connective tissue tumors
- Dermatofibroma
- Lipoma
- Hemangioma
- Peripheral Nerve Tumors
- Leiomyoma
- Giant cell tumor of tendon sheath
- Ganglion Cyst
- Fibromatosis
- Numerous Others
Benign fibrous histiocytoma (dermatofibroma)
- Refers to a heterogeneous family of morphologically and histogenetically related benign dermal neoplasms of fibroblasts and histiocytes
- Firm, tan to brown papules = great mimicker of other things
- Asymptomatic or tender, size may increase or decrease slightly over time
Histogenesis of Benign fibrous histiocytoma (dermatofibroma)
o Remains a mystery
o Many cases have a history of antecedent trauma, suggesting an abnormal response to injury and inflammation
Microscopy of Benign fibrous histiocytoma (dermatofibroma)
- Microscopy shows dermis is affected by proliferation of spindle cells, lesion cells form “donut sign” of collagen trapping
Induction phenomenon
o Looks like a basal cell carcinoma
o If you took a biopsy that is not deep enough, we would diagnose a basal cell carcinoma
o Need to get a deep enough shave biopsy
Lipoma
- Most common connective tissue tumor
- Benign, excision is curative
Hemangioma
Tumors of benign blood vessels
Multiple subtypes
o Pyogenic granuloma is something related – it is ulcerated– common on nail bed
o Cavernous hemangioma
o Arteriobenous hemangioma
Peripheral nerve tumors
Reactive Lesions and Hamartomas o Traumatic neuroma o Morton’s neuroma o Digital Pacinian Neuroma o Mucosal Neuroma
Benign Tumors o PEN o Schwannoma o Neurofibroma o Granular cell tumor
Traumatic neuroma
- Arise where a peripheral nerve is severed and does not heal (ie amputation)
- Clinically painful nodule
- Disorderly proliferation of bundles of peripheral nerves
- All components: Schwann cells, nerve fibers, perineural cells, fibroblasts)
- Basically normal nerves that are haphazardly arranged
Morton’s neuroma
- Severe pain in sole of foot
- Region of metatarsal heads (high-heeled shoes)
- Exacerbated by walking
- Lesion is usually not palpable
Mucosal neuroma
- Typically multiple and clustered around the mouth
-
Part of multiple endocrine neoplasia syndrome (MEN IIb)
o Patients should be evaluated for genetic testing and thyroid imaging
Palisaded encapsulated neuroma (PEN)
- Solitary painless nodule
- Face is most common site
- Although can be found on any mucocutaneous site
- Middle aged-elderly
- PEN on microscopy = Well-circumscribed, subtotal capsule, nerve of origin can often be id’d at base, fascicles of small wavy cells
Schwanomma
- AKA neurilemmoma
- Wide distribution
- Extremities slightly more prevalent
- No association with neurofibromatosis
- Solitary painless subcutaneous mass
- Little capacity for recurrence
- Encapsulated
- Prominent blood vessels (thick hyaline walls)
Two components of a schwanomma
****TEST QUESTION****
o **Antoni A: cellular with nuclear palisading (Verocay bodies) = CELLULAR –> Know that VEROCAY bodies occur here
o **Antoni B: also Schwann cells but hypocellular, myxoid matrix = HYPOCELLULAR
**KNOW THIS FOR EXAM**
Neurofibroma
- Common, solitary polypoid or nodular lesion
- Wide distribution
- Deeper lesions more often associated with NF-1
Plexiform neurofibroma
- Pathognomonic of NF-1
- Children and young adults, can become large and disfiguring
- Thick convoluted cords of expanded nerve fibers – myxoid change common
FOR EXAM…
**KNOW Schwannoma and neurofibroma **
Granular cell tumor
- Middle aged, Female > Male
- Any anatomic site, trunk and tongue most common
- Slow growing, recurrences are rare
- Excision
Microscopy
o Variable circumscription, can be infiltrative
o Tumor cells in nests
o Large, polygonal cells with finely granular cytoplasm
o Nuclei small
o Rare mitoses OK
Leiomyoa
- Pilar leiomyoma and angioleiomyoma
- Images were shown of these two
Giant cell tumor of tendon sheath
- AKA: Nodular tenosynovitis
- Localized form of pigmented vilonodular synovitis
- Can occur at any age, typically adults
- Typically hands, feet, wrists, knees, and rarely other joints.
- Benign, but can recur in 5-30% of cases.
- Treatment: Complete excision
Microscopy
o Well circumscribed, lobulated, partially encapsulated
o Variable proportions of mononuclear cells (small, round to spindled, with pale cytoplasm and round or grooved nuclei), osteoclast-like giant cells with 3-50 nuclei, foam cells, siderophages, epithelioid cells with glassy cytoplasm, round vesicular nuclei
o Varying amounts of dense collagenous stroma
Ganglion cyst
- Common, but not technically a tumor
- Myxoid degeneration of joint capsule or tendon sheath
- Sites: Wrist, hand, foot, and ankle
- Secondary to injury or overuse, symptoms are pain, weakness
Microscopic appearance
o Not a true cyst because not lined by epithelial lining
o Cystic space lined by histiocytes and granulation tissue with moderate acute and chronic inflammation of cyst wall
o Mucin pockets within wall
Superficial fibromatosis
- Hand = Dupuytren contracture
- Plantar = Ledderhose disease
- Penile = Peyronie disease
- Not associated with Beta-catenin mutations
- These are seen in desmoid fibromatosis (this is DIFFERENT than superficial fibromatosis)
- That would be a familial cancer system – we are NOT talking about that here
- Nodular proliferation of fibroblasts
- Can be infiltrative (even though it is benign and not malignant)
- Not malignant, but can recur
- Treatment is surgical incision
Exam questions
- Very straight forward questions
- Nothing tested that isn’t written out in the slides
- Only things you will see on the lower extremity will be tested
