Cutaneous Neural Tumors Flashcards
What are the two major groups of neural tumors?
Peripheral nerve sheath tumors and neural heterotopias
What 4 types of neural tissue are neural heterotopias associated with?
meningeal (meningoceal, reudimetary menigocele, meningioma), neuroglial (nasal glioma), neuroblastic/ganglionic (neuroblastoma, primary primitive neuroectodermal tumor, ganglioneuroma), miscellaneous (pigmented neuroectodermal tumor of infancy)
What is a/w multiple mucosal neuromas?
MEN2b –> neuromas occur on all mucosal surfaces (lips, tongue, conjunctiva, nasal and laryngeal). You get pheochromocytoma, aggressive medullary thyroid cancer, marfanoid appearance, blubbery lips, CALM, circumoral lentigines.
What mutation is seen in multiple mucosal neuromas?
RET (MEN2b)
Ddx for cutaneous tumors that hurt?
BANGEL or blend an egg blue rubber bleb nevus syndrome, angiolipoma/angioleiomyoma, neurilemmoma/schwannoma, glomus, eccrine spiradenoma, leiomyoma
Which neurofibroma is pathognomonic for neurofibroma?
Plexiform neurofibroma
What stain is + when a neural tumor has a capsule?
EMA
What stain is positive if a neural tumor as axons?
NSE/Axon
What inflammatory cell can be seen in neurofibromas that can help you distinguish them?
Mast cells
What are the 2 types of neurothekeoma?
Cellular and myxoid
What is the difference in staining between myxoid and cellular neurothekeoma?
Myxoid (nerve sheath myxoma): s100 + S100A6 +; cellular neurothekeoma s100-, S100A6 +
What are some notable cutaneous lesions that are S100A6 + ?
Cellular neurothekeoma, histiocytic tumors, spitz, AFX
What stains help distinguish cellular neurothekeoma?
s100 -, desmin -, s100A6 +
what causes the granules in the granular cell tumor?
lysomal dysfunction
What is the staining for a perineurioma?
s100 -, NSE/AXON -, EMA + (becuase capsule)
What are the two types of perineurona?
Soft tissue and sclerosing
What entity should you suspect in rapidly growing nodule in plexiform nodule
Malignant peripheral nerve sheath tumor
What margins should be achieved on Merkel cell carcinoma?
2-3cm
What is the IHC staining for Merkel cell carcinoma?
TTF -; CK20+; EMA and enolase +, CK7 + (maybe), CK5/6 + (low molecular weight keratins)
What is the DDx for small cell blue tumors?
LEMONS: lymphoma, Ewing’s sarcoma, Merkel, oat cell, neuroblastoma, small cell endocrine carcinoma
What is the presentation of a nasal glioma?
Occurs on the midline of the face in babies, or the medial canthus. Can present w/ nasal cartilage or have eyes spaced far apart. (along cranial suture lines)
What are the 3 categories of peripheral nerve sheath tumors?
Hamartomas (neuromas), true nerve sheath neoplasms (schwannomas, neurofibromas, nerve sheath myxoma, cellular neurothekeoma, perineuroma, malignant peripheral nerve sheath tumor); miscellaneous (Merkel cell and granular cell tumor).
Where are the perineurium cells derived from and what do they stain for?
They are modified fibroblasts of mesodermal origin. Stain for epithelial membrane antigen, not with S100
Clinical presentation of traumatic/amputation neuroma?
Uncommon tumor, usually solitary, skin-colored firm papule or nodule, painful. Is on sites of wounds, surgical scars, and amputations
What is the histology of a traumatic/amputation neuroma?
Composed of chaotic, poorly organized tangles of nerve fascicles embedded within a fibrous scar
There are clefts between fascicles, located in any level of the dermis or subcutis
Stains: s100+, MBP+, Bodian stain+, NSE/Axon +, EMA +/-
What is the histology of a rudimentary digit/polydactyly?
Numerous nerve fiber bundles in connective tissue in the upper dermis; oval corpuscles present (looks like Meissner corpuscles)
Key differences between palisaded encapsulated neuroma and and traumatic neuroma?
Perineural tissue capsule surrounds the tumor in traumatic neuroma and there is clefting around the bundles in PEN
Also, there is no fibrous tissue sheath around fascles in PEN which is unlike truamatic neuroma.
What is the mutation in Men2b?
RET protooncogene on chromosome 10q11.2
Multiple mucocutaneous neuromas with a predilection for the face and distal extremities occur in what syndromes?
PTEN harmartoma tumor syndromes: Cowden, Bannayan-Riley-Ruvalcaba
What is the histologic and clinical presentation of a schwannoma?
These are m/c on the flexural aspects of extremities and are often painful
Histologically these only have Schwann cells in it no axons, so there is a well-encapsulated deep dermal or subQ tumor that has both hypercellular Antoni A tissue and hypocellular myxoid type B tissue
What is the IHC staining pattern for schwannoma?
s100+, NSE/AXON -, EMA + Myelin basic protein -, s100, vimentin, EMA, type IV collagen all +
What is the histology of a neurofibroma?
Non-encapsulated, loosely textured tumor centered in the dermis; grenz zone, thin fascicles of cells w/ a wavy spindle. S-shaped or comma-shaped cells with sharp pointed ends. Mitoses rare. bubblegum stroma and mast cells
What is the clinical presentation of neurofibroma?
Clinical: Very common, usually solitary skin-colored soft or rubbery papulonodules w/ “buttonhole sign”, found on trunk/head
Can be pruritic, associated with NF-1
What type of neurofibroma is pathognomonic for NF-1?
Plexiform Neurofibroma
What is the IHC staining for neurofibroma?
s100+, myelin basic protein +, Bodian stain shows axons, no capsule (EMA -)! so s100 +, NSE/axon +, EMA -
What are the key features of plexiform neurofibroma?
Bag of worms feel on the clinical exam. On histology, they show irregular cylindrical or fusiform enlargement of subQ or deep nerves. So large fascicles of neurofibroma surrounded by perineurium often embedded within a diffuse neurofibroma. Essentially large fascicles on a background of neurofibroma
What is the malignant transformation potential of plexiform neurofibroma?
Higher than solitary neurofibroma
What chromosome is altered/abnormal in plexiform neurofibroma?
chr 17
What is the clinical and histologic presentation of nerve sheath myxoma?
Occurs in middle-aged women with lesions on the hand’s knees and extremities.
Histology: hypocellular myxoid stroma with rare, scattered, spindled, stellate, or dendritic cells
Scant, pale cytoplasms with indistinct cytoplasmic contours
Hyperchromatic, ovoid, or angulated nuclei
S100+, vimentin +
Staining for neurothekeoma?
Think “neurofreakoma” bc it doesn’t stain with S100 like the others
S100A5 +, s100 -, NK1/C3
What are the clinical and histologic features of cellular neurothekeoma?
Clinical: Occurs on young women (20’s) on the face/extremities, asymptomatic
Histology: ill-defined multilobular fascicles of mainly epithelioid cells and spindle cells with a whorled appearance; possible dystrophic calcification and ossification.
What is the clinical presentation of a granular cell tumor?
Rare, well-circumscribed, slow-growing asymptomatic or occasionally tender/pruritic, solitary, firm dermal or subcutaneous papulonodule, with brownish-red or flesh-colored smooth glistening surface
Most on head/neck, especially tongue (30-40%)
Adult women of color: 2/3 AA, 2/3 female
What is the IHC staining of a granular cell tumor?
S100+(unlike xanthoma), CD68+, PAS/diastase resistant +, myelin basic protein +
What is the unique IHC staining of a perineuroma?
Tumor of only perineural cells as a result it is
s100 -, NSE/axon negative and EMA +, vimentin +, CD34 +, enolase +
What disease are perineuromas a/w?
NF-1 and NF-2
What is the histology of a perineuroma?
Circumscribed, non encapsulated lesion; storiform pattern. spindle cells with elongated bipolar cytoplasmic processes. Concentric onion bulb whorls.
What dz is malignant peripheral nerve sheath tumor often associated with?
NF-1 (50% of cases)
Clinical presentation of malignant peripheral nerve sheath tumor?
Soft tissue mass on flexor aspects of limbs. Suspect if neurofibroma becomes enlarged and painful. 2-13% of plexiform NF’s can become this. It will be a rapidly growin nodule within the NF. May have large overlying CALM
-Prognosis is poor: 2-3 yrs.
What is the pathology/histology of malignant peripheral nerve sheath tumor?
Intersecting fascicles of atypical cells in herringbone pattern w/ myxo sarcomatous areas and areas of necrosis and hemorrhagee. very hypercellular and this is more important than atypia. Mitoses are present but not frequent.
What is the staining pattern of malignant peripheral nerve sheath tumor?
s100+, enolase + MBP+, neurofilament +
What is the histologic presentation of Merkel cell carcinoma?
Composed of small blue cells with scant cytoplasm and tightly packed nuclei in sheets or a trabecular array. Nuclear molding, apoptotic cells, and mitoses are often present
Poorly defined dermal mass, frequently infiltrating
Various growth patterns
Sheet-like > nested > trabecular
Monotonously uniform, small, round to oval cells abut 2-3x larger than mature lymphocytes
Extensive areas of necrosis, individual cell necrosis, and characteristic crush artifact
M/c locations for merkel cell carcinoma?
Older adults: head/neck region>exremities>buttocks
What virus is Merkel cell carcinoma a/w?
Merkel cell polyomavirus (50% exhibit trisomy 6)
Staining for merkel cell carcinoma?
CK20+, EMA, enolase+, key for CK20 is that it shows paranucelar dots or globules. s100 is negative and TTF is negative (differs from lung small-cell cancer)
also stains for CD20, CK5/6, CK7
What is the staging of Merkel cell carcinoma?
stage 1 = primary lesion <2cm
stage 2= Primary lesion >2cm
Stage III= Regional lymph node dz
Stage IV= Distant meastatic dz.
3 main tumor-like conditions of ectopic and heterotopic neural tissue of skin?
- neuroglial
- meningeal
- neuroblastic/ganglionic abnormalities
What is the clinical presentation of a nasal glioma?
Usually along cranial closure lines w/o apparent communication with underlying structures. Firm, smooth, noncompressible skin-colored to red-purple nodule, 1-3cm
Rare, benign, affects neonates, most commonly near the root of the nose but can be intranasal. This may widen nasal bone leading to hypertelorism
Should you bx a nasal glioma?
NO - can be associated w/ encephalocele –> image and send to neurosurg.
Stains for nasal glioma?
s100+ and GFAP + glial fibrillary acid protein
What is the clinical appearance of a cutaneous meningioma/rudimentary meningocele?
Failure of neuroectoderm to properly separate from surface ectoderm in early gestation
psammoma bodies often seen histology depends on type
type I: confined to subcutis, irregular strands of meningothelial cells in a collagenous stroma
type II and III: may also involve dermis, circumscribed and more cellular than type I
What is the clinical presentation of a cutaneous meningioma?
Soft to firm, compressible, skin-colored nodule, cyst or plaque, that transilluminates
Rare, usually present in neonates and infants, favors the scalp, forehead, and paravertebral region
Often with partial alopecia or the “hair collar” sign
Other assoc. include brain malformation, hypertelorism, and facial clefting
Enlarge with increased intracranial pressure (crying, straining) as a result of connection to CNS
What can cutanoeus menigioma be a/w?
Neurofibromatosis or other developmental anomalies
What IHC stains can be used for malignant primitive neuroectodermal tumor/neuroblastoma?
CD99+, enoase+, EMA -, CK20 -
What is a key distinctive histologic feature of neuroblastoma?
Small, round, blue cells in nested or infiltrative growth pattern, with the formation of Homer Wright rosettes (fibrillary material in center of rosettes characteristic)
Clinical presentation of neuroblastoma?
Cutaneous mets seen more in kids; primary cutaneous tumors more often in adults
Cutaneous mets (from adrenals of ganglionic chain) presents as multiple, purple-blue dermal nodules (“blueberry muffin”)
Peripheral blanching after stroking (release of catecholamines)
“Racoon eyes” (periorbital darkening/purpura) –> orbital mets
Assoc. w/ elevated serum and urine catecholamines
What factors affect the prognosis of neuroblastoma?
Clinical stage, specific genetic factors like MYCN oncogene amplification, and age
What percentage of Merkel cell tumors are CK20 negative?
~20%
What two things do you need to prove a Merkel?
Staining for neuroendocrine and keratin (CK20 most specific, so CK19 (second most specific), CAM5.2, other keratin stains.
KEY the keratin stains need to show a perinuclear dot.
How do you prove the neuroendocrine origin of Merkel Cell carcinoma
Chromogranin-a (most sensitive), Synaptophysin, NSE
NSE is the least useful, but you can use CD56
What is the importance of TTF-1 in Merkel cell vs small cell lung cancer, gastric, etc
Most Merkel’s are negative, but metastatic dz can be positive.
so once you have established a neuroendocrine tumor, then you check for the TTF-1 to see if it is metastatic
What are the 3 main DDx for Merkel cell carcinoma on histology?
BCC and lymphoma, and other neuroendocrine tumors
What type of virus is the polyomavirus?
DNA virus
How does the polyomavirus work in cutaneous cells?
Incorporates viral DNA into the genome of the affected cells only
What types of tumors are a/w immunosuppression due to viral origin?
SCC (HPV), Merkel (polyomavirus), Kaposi sarcoma (HHV-8)
What markers are important for prognosis in Merkel Cell Carcinoma?
p63+, Survivin +, Ki-67+ (high Ki-67 labeling index)
How do we use p63 in dermatopathology?
it is + in the tissues of origin of the tumor, lost in metastasis.
Ex: squamous cell from the lung vs primary skin? primary skin p63 + and the lung would be -
What percent of Merkel cell carcinomas have metastasis at dx?
~50%
What is the definition of satellite lesions and in-transit metastasis?
Satellite = these are within 2 cm of the original tumor
In-transit metastasis = between the 2cm and the basin of the sentinel lymph nodes
What is the histology of a granular cell tumor?
Superficial non encapsulated irregular arrange sheets of large polyhedral cells with a central hyperchromatic nucleus and coarse granular eosinophilic cytoplasm. Induces pseudoepitheliomatous hyperplasia above the tumor. Large cytoplasmic granules are from lysosome dysfunction and are surrounded by clear halos.
What is the histology of a nasal glioma?
Lobulated neural tissue (glial cells, astrocytes, rarely true neurons)
Result of embryological displacement of brain tissue
