Molavi Chapter 28 - Skin Flashcards
Stainings for melanocytic lesions
- S100 (but also stains Langerhans cells)
- SOX10
- HMB-45*
- Melan-A*
- Tyrosinase*
- *These stains do not work on spindle-cell or desmoplastic markers.
The pigmented component of skin
Basal keratinocytes
These absorb the melanin produced by melanocytes to take on color.
It is only the atypical melanocytes that will accumulate pigment (and hungry macrophages)
Lentigo simplex
A linear proliferation of single benign melanocytes along the dermoepidermal junction.
This is the earliest, simplest form of a melanocytic nevus
“Lentigo-“ or “Lentiginous-“
Along the dermoepidermal junction
Junctional, compound, and intradermal nevi
Junctional: Little melanocyte nests (called theques) sitting at the DEJ.
Compound: Dermal and junctional component. At this point the intradermal component causes a little nodule in the skin, which is colloquially called a “mole.”
Intradermal: The juctional component of a compound nevus regresses with age, leaving the intradermal component alone.
Compound nevus
In a compound nevus, the cells at the deepest point should appear smaller and more bland than those at the DEJ due to maturation.
Intradermal nevus
Similar to compound nevi, cells should be smaller and more mature at the base. May be pedunculated, hyperkeratotic, or contain hair follicles. Often have fine brown pigment.
Melanoma arising from a benign intradermal nevus is vanishingly rare.
Histologic features of a benign nevus
- Symmetry
- Size < 3mm diameter
- Lateral borders defined by nests, not individual trailing melanocytes
- Lack of atypia (nuclei no larger than keratinocyte nucleus, have small dense nucleoli. Multiple nuclei are okay, that is normal.)
- Maturation into the dermis
- Chunky brown-black pigment
Blue nevus
Small, indistinct, pigmented cells cattered throughout dermal collagen.
The cells are elongated and fusiform or stellate and do not make rounded nests like typical nevus cells. Macrophages (larger cells with chunky pigment) are also present in a typical blue nevus.
Spitz nevus
Benign. Found on the head and neck of children and adolescents. The same pattern of growth would be concerning if found in an adult.
At low power: circumscribed and symmetric, large nests of melanocytes are found between skinny elongated rete. Eosinophilic globules seen at the DEJ.
Melanocytes may be large, spindled, pleomorphic, or atypical – even showing rare mitoses or pagetoid spread. This can make it appear malignant even though it is benign in kids.
The distinction of Spitz nevus from the rare pediatric melanoma, or from atypical Spitz nevi and spitzoid melanoma, is left to dermatopathology experts.
Dysplastic nevus / Nevus with “architectural disorder”
A nevus with some of the features associated with melanoma. Clinically distinct-looking, but are not considered actual precursors to melanoma. There is bridging across rete ridges and shouldering.
But, dysplastic nevus is a clinical diagnosis, not a pathologic diagnosis. A pathologist would sign this out as: compound nevus with architectural disorder and cytologic atypia.
Four features or “architectural disorder”
- Lentiginous spread of atypical melanocytes
- Shouldering (lentiginous component is wider than the dermal component)
- Bridging of rete (nests attached to adjacent rete ridges fuse)
- Fibroplasia (feathering of the dermal collagen that looks like pink cotton candy)
Features of cytologic atypia in melaocytes
- Hyperchromatic nuclei
- Increased N/C ratio
- Large red nucleoli (cherry red nuceolus)
- Accumulation of dusty gray-brown melanin
- Atypical mitoses
Grading of atypia in melanocytes
Mild
Focally severe
Severe
Melanoma in-situ
Malignant melanocytes along the DEJ and percolating up through the epidermis in a pagetoid fashion – this is something that benign melanocytes do NOT do.
Lentigo maligna
A subset of melanoma in-situ in which malignant melanocytes proliferate only along the DEJ. There is a confluent layer of melanocytes that also spreads down into the cutaneous appendages. The cells are small and hyperchromatic. There is always associated solar elastosis (solar-associated elastin deposition).
“Starburst” giant cells are sometimes seen. They can be seen in other forms of melanoma, but are ~80% specific for lentiginous forms.
Solar elastosis, aka actinic elastosis
Note the bluish elastin fibers in the superficial dermis
Caused by sun damage.
Superficial spreading melanoma
A form of invasive melanoma. Clinically this is a flat lesion. In superficial spreading melanoma, the melanoma grows “horizontally,” spreading laterally along the DEJ but also involving the dermis.
There is characteristically a haphazard distribution of atypical melanocytes within the epidermis, including abundant single melanocytes.
Nodular melanoma
A form of invasive melanoma. Demonstrates a “vertical” growth pattern. It primarily grows down, into the dermis, producing a raised lesion. These lesions are typically very well circumscribed within the dermis. The dermoid component demonstrates immature, epithelioid melanocytes with a high rate of mitotic activity.
Even when controlled for Breslow depth, these melanomas show a worse prognosis.
Lentigo maligna melanoma
This is when lentigo maligna actually becomes invasive. Like lentigo maligna (the melanoma in-situ form), there is invariably solar elastosis. The dermal component is often characterized by spindle-like melanoma cells (shown) with a prediliction for perineural invasion.
This can make some cases easy to see on low power, like this one, where the melanin pigment is clearly seen within the web of dermal, blue, elastin fibers
A starburst giant cell
This suggests melanoma along the lentigo maligna spectrum, however is not entirely specific for this form of melanoma.
Acral lentiginous melanoma
Note the thickness of the keratin and presence of a stratum lucidum, indicating that we are in a palm, sole, or nailbed. There are atypical melanocytes with extensive upward Pagetoid migration. They have a tendency to surround sweat glands and blood vessels.
The dermal component of acral lentiginous melanoma is composed fascicles of spindle-shaped melanocytes with fibrotic stroma.
Desmoplastic melanoma
Spindle-cell, loosely cellular form of melanoma within the dermis, in a background of dense collagen. It looks very similar to scar. A slightly “busy” dermis (presence of bands or clumps of lymphocytes) should prompt you to look closely at nearby stroma.
On high power, enlarged, hyperchromatic cells (arrow) are present. These will be positive for S100, unlike fibroblasts.
Solar lentigo (in the context of solar elastosis)
Finger-like projections of hyperpigmented rete growing down from the epidermis. Keratinocytes, not melanocytes, are the pigmented cells here.
The clinical correlate is the liver spot, shown here.
Actinic keratosis
May develop from an existing solar lentigo. Characterized by the following:
- Squamous atypia of varying thickness
- Alteration of keratinization (to become pink and parakeratotic)
- Sparing of the keratin above the hair follicles (producing alternating columns of parakeratosis and orthokeratosis)
- Underlying solar elastosis
Regarded as a form of carcinoma in-situ, however its natural history is unpredictable. It may invade before reaching full-thickness atypia, unlike cervical squamous lesions.
Bowen’s disease
Gross picture shown here.
A form of carcinoma in-situ. Describes a particular clinical presentation occuring in non-sun-damaged skin (and thus will not have solar elastosis) that does not spare the hair follicles, unlike actinic keratosis.
Displays acanthosis, hyperkeratosis, and cellular atypia. Note that the cells here are not maturing as they climb towards the surface and that there is prominent parakeratosis.
Bowenoid papulosis
A form of HPV-driven carcinoma in-situ in genital sites (penile shaft, foreskin, scrotum, glans, or vulva). Associated with HPV strains 16 and 18. Sexually transmitted. Occurs in young individuals and clinically resembles a condyloma accuminata. Despite its classification, it usually regresses spontaneously. Less than 1% progress to invasive cancer.
Clearly HPV-mediated with koilocytes and the classical features from the cervix, but this time with more keratinization.
Invasive squamous cell carcinoma
Most likely to arise from the sun damage -> actinic keratosis pathway, so solar elastosis is often seen nearby.
Features that suggest invasion include penetration of nests deep into the dermis and aberrant keratinization (sometimes with keratin pearls). If single squamous cells (B, arrow) are seen within the dermis, this is fairly conclusive for SCC.
Invasive basal cell carcinoma
Most common cutaneous malignancy. Has a wide variety of appearances. Features include:
- Lobules of small, dark blue, basal-type keratinocytes with peripheral palisading arrays of oblong nuclei
- Formation of clefts (cracks) between the tumor nests and the stroma
- Sometimes desmoplasia, focal keratinization, or mucin production
- On high power: Dark chromatin, high rate of mitosis and apoptosis
Superficial-type basal cell carcinoma
Often described as “hanging off of the epidermis like stalactites.” Does not form a discrete dermal mass.
Sclerosing basal cell carcinoma
Cause you know. . . it’s BCC and it’s sclerosing.
Seborrheic keratosis
Convoluted, confluent cords of epidermis. Horn cysts (entrapped whorls of orthokeratin) are common. Hyperkeratosis is present without parakeratosis.
These are not necessarily associated with sun damage.
Verruca vulgaris – the common wart
Virally-induced by HPV. Circumscribed, usually occurs on the hand or feet. Histology shows a characteristic “church spire” epidermal proliferation with overlying hyperkeratosis. The tips of the spires are often topped by parakeratosis, giving a “striped” appearance. Condyloma accuminata shares a similar architecture.
Koilocytes may be present, but can be hard to identify.
Poroma
These adenxal eccrine tumors are continuous with the epidermis. The cells are uniform, small, round, and pale. Some areas may form rudimentary duct spaces.
Eccrine spiradenoma
Adnexal tumor often described as “blue cannonballs in the dermis.”
Tumor balls consist of two basaloid cell lineages and have noticeable cords and droplets of hyaline basement membrane running through them.
Cylindroma
Adnexal tumor closely related to eccrine spiradenomas.
Sometimes desribed as having a “jigsaw puzzle” appearance. Also has blue, basaloid nests in the dermis with two cell populationos and basement membrane matrix woven in. Tumor nests are mosaic in shape.
Syringoma
Adnexal dermal tumor.
Collection of round, dilated tubules in the dermis with characteristic comma-like or tadpole tails.
Microcystic adnexal carcinoma, also called sclerosing sweat duct carcinoma
Rare, but a malignant skin tumor you don’t want to miss.
Looks similar to syringoma, with tubules, cords, and bland cells, and also has horn cysts. What differentiates the two is the deep infiltration into the dermis.
Merkel cell carcinoma
Primary neuroendocrine tumor of the skin.
Nuclei are small and round, but larger than a lymphocyte nucleus. They have finely textured chromatin and a deep blue color due to the absennce of cytoplasm.
Display a unique dot-like staining pattern with CK20.
Dermatofibroma
Appear as an ill-defined, light blue haze in the dermis on low power.
On high power, this is made up of tiny swarming nondescript cells that infiltrate the collagenous fibers and packet it into thick bundles.
The overlying epidermis may be hyperpigmented and hypertrophic (hence its clinical presentation as a light brown nodule).
Dermatofibrosarcoma protuberans (DFSP)
The sarcoma form of dermatofibroma. More deeply infiltrative than a dermatofibroma – wrapping around subcutaneous fat is characteristic. They are also much more cellular than a benign dermatofibroma and can display a storiform pattern.
Most dermatofibromas are associated with t(17:22), a translocation of COL1A1 on chr 17 and PDGFB on chr 22. This translocation causes exon 2 of PDGFB to be placed under the promoter of COL1A1, resulting in PDGFB overexpression. (PDGFB is also known as c-sis, the cellular equivalent of the v-sis oncogene)
Neurofibroma
These tumors arise from the endoneurium and connective tissue of peripheral nerve sheaths. They appear as a pale or gray nodule against the background epidermis, but are more defined than the amorphous dermatofibroma.
It displaces the dermis rather than infiltrating it. Individual cells have wavy nuclei and wavy collagen, like over-stretched elastic fibers.
Hemangioma
A proliferation of well-formed, dilated capillaries in the dermis. There are many variants.
Features that would suggest angiosarcoma over hemangioma are increased cellularity and anastomosing channels lined by plump cells.
Angiosarcoma
Note the high cellularity and interweaving, anastamosing vascular channels within this lesion. On high power the cells look plump with pink cytoplasm and multiple mitoses – nothing like the endothelial cells from which they were derived.
Kaposi’s sarcoma
The classic HHV8-driven endothelial tumor.
Histologically these lesions can be easily missed. All you see on low power is a slight increase in cellularity within the dermis. But, when you zoom in to high power and pay careful attention, you may notice that some of what you thought was white space between collagen fibers was actually tiny well-differentiated endothelial lumens.
These slit-like vascular spaces are accentuated around the existing capillaries (referred to as the “promontory sign”).
Trichoblastoma (aka trichoepithelioma)
Well-circumscribed basaloid cell nests in the superficial dermis surrounded by fibrous stroma, usually with some peripheral palisading and sometimes with keratin pearls/cysts.
Collagenoma
A rare hamartomatous malformation characterized by the predominant proliferation of normal collagen fibers. Can have normal, decreased, or increased elastic fibers.
There is often a web of fibroblasts weaving through the collagen fibers, much like in a dermatofibroma – however in a collagenoma these fibroblasts are benign.
Civatte body
Suggestive of disorders characterized by interface dermatitis. Characteristic finding in skin lesions of patients with various dermatoses, particularly lichen planus (LP) and discoid lupus erythematosus (DLE)
Generated by damaged basal keratinocytes through apoptotic cell death, consist largely of keratin intermediate filaments, and are almost invariably covered with immunoglobulins, mainly IgM
Lichen sclerosus
Vacuolar interface reaction pattern in conjunction with dermal sclerosis (homogenized and hyalinized eosinophilic collagen bundles) of any thickness intervening between inflammatory infiltrate and epithelium or vessel walls. Often some intervening epidermal-dermal edema is present.
Syringocystadenoma papilliferum
A benign hamartomatous adnexal tumor, often presents as an exophytic, verrucous epidermal mass in the head or neck. Cystic invaginations of the infundibular epithelium projecting into the dermis, covered by a double cell layer. There is an inner columnar cell layer and outer cuboidal cell layer. Plasma cells are common in the stroma of each frond. Many irregular duct-like structures and cystic spaces – often formation of gland/duct structures with connection to the epidermis.
50% of cases during early childhood, 15-30% at puberty. If present prior to puberty, may grow or become exophytic at puberty.
Clear cell acanthoma
Bland, intraepithelial tumor of clear keratinocytes with abrupt transition to and from normal epidermis, often in a pattern of psoriasiform hyperplasia +/- intraepidermal neutrophils
Proliferation is thought to be driven by keratinocyte growth factor, and clear cell cytology is due to a phosphorylase defect leading to glycogen accumulation.
