10 Pearls About Pigmented Lesions from the Perspective of the Dermatopathologist: Whitney A. High, MD, JD, MEng

  • There are distinct histologic differences between wholly bland nevi, and what has come to be known as an “atypical nevus,” a “dysplastic nevus,” or a“Clark’s nevus.”
  • There is no single criterion (not even mitoses or pagetoid spread) that is diagnostic of only melanoma. There is not a “melanoma stain” that wholly discriminates between atypical nevi and melanoma. “Borderline” lesions represent subjective assessments that are impacted by the viewpoint and skill of the examiner.
  • Biopsy use is increasing. In nine geographic areas of the USA, over 1986-2001, the biopsy rate among those persons >65 years of age rose 5-fold, while the melanoma rate rose 2.4-fold.
  • In many areas of the country, atypical nevi are graded “mild,” “moderate,” or “severe,” but this is not universalyl employed. Some dermatopathologists “lump” mild and moderate together, and have just two categories. In other areas of the county nevi are not formally graded, or are graded in a less straight-forward way (i.e. “nevus,” “Clark’s nevus,” and “Clark’s nevus, re-excise”).
  • The dermatopathologist is examining only a small portion of your biopsy, and this must be considered with regard to the “representative” nature of the results. A 2010 study showed the odds of misdiagnosis for pigmented lesions were considerably higher when a punch biopsy technique was employed in comparison to an excisional biopsy (see: Ng et al. 2010).
  • There are special situations where the diagnosis of melanoma is challenging, such as:
Nevoid melanoma Desmoplastic melanoma
Spitz nevi Atylical Spitz nevi (Spitz tumors)
Recurrent nevi (“pseudomelanoma”) Nevi on the scalp of children
Pigmented lesions of the nail unit Pigmented lesions of the genitalia

 

  • There are some immunostains that can “assist” in the assessment of melanoma, or “bolster” the one’s confidence in a diagnosis, and these include: Mart1/Ki67 (a combination stain), P16, and HMB45, but again, there is, however, no singular “melanoma” stain.
  • Spitz nevi, in particular, may be confused with melanoma, and vice versa. Generally, if the patient is older than 20 years of age, it is wise to ensure that the dermatopathologist examining a case of a Spitz nevus or spitzoid melanoma has experience with difficult pigmented lesions.
  • Desmplastic nevi may be difficult to distinguish from other malignant processes (such as an atypical fibroxanthoma or spindle cell squamous cell carcinoma), and desmoplastic melanoma may also be confused with simple scarring, particularly in a shallow specimen. Stains and careful examination may often be employed in such a case.
  • Synoptic reporting (a “grid-like” summary) of characteristics that allow for the pathologic staging of melanoma is an emerging standard in dermatopathology, and probably more rapidly and more accurately transmits key therapeutic and prognostic information to the clinician.

Core Principles of Cutaneous Surgery – Victoria Lazareth

Victoria Lazareth MA, MSN, NP-C, DCNP

Increased Risk for Bleeding

High Risk Sites (acral)

Scalp, Face (ears, nose, eyes, lips), Digits, genitals

Danger zones

temple (temporal artery), base of ala (angular artery), mandible (mental artery)

 

Increased Risk for Nerve damage

Facial nerve (temporal branch of CN VII)

over zygomatic arch through temporal fossa

Innervates the frontalis & orbicularis oculi & anterio-superior muscles of the ear

Damage: eyebrow ptosis (impaired eyelid elevation & closure)

Spinal accessory nerve (Cranial Nerve XI)

emerges near Erb’s point

posterior triangle of neck behind the sternocleidomastoid ~2cm above clavicle

Innervates the trapezius muscle

Damage: shoulder droop & winged scapula

Trigeminal nerve (Cranial Nerve V)

Opthalmic V1 division                  (scalp, forehead, nose)

Maxillary V2 division                  (lateral forehead, medial cheek, upper cutaneous lip)

Mandibular V3 division (lateral temple, lateral cheek, upper ear, cutaneous lower lip)

Damage: sensory innervation of face, motor innervation of mastication muscles

 

 

Increased Risk for Tumor Recurrence

NMSC at High-Risk for recurrence

Location

Scalp, eyes, ears, nose, lips, genitalia, hands, feet

Size      

> 6 mm at scalp, eyes, ears, nose, lips, genitalia, hands, feet

>10 mm at the head, forehead, cheeks, neck

>20 mm at all other areas

History           

Recurrent tumor, Older age, male gender, Immunocompromised pt

History of XRT, PUVA at site, arsenic ingestion

Histology

Recurrent BCC

clinical extension

Micronodular, Morpheaform, Sclerosing, Infiltrative, Basosquamous

Metastatic BCC

very large tumor (>10cm sq)

peri-neural invasion. Basosquamous or Morpheaform sub-types

Recurrent / Metastatic SCC

peri-neural invasion, perivascular invasion

moderately differentiated, poorly differentiated, single cell sub-types

 

Performing the Eliptical Excision

Excise the ellipse through full-thickness skin to appropriate depth

Hold scalpel perpendicular to skin surface to avoid beveling the wound margins

Common mistake   leaving more fat & dermal tissue at the tip & tail of the ellipse than at the center  

     à leads to redundancies & elevations at the ends of the ellipse

 

 

Anatomic Level of Undermining

SCALP

subgaleal space: virtually avascular plane

Large vertically-oriented FOREHEAD wounds

beneath frontalis muscle

Sebaceous areas of the NOSE

subdermal

Dorsum of the NOSE, FOREHEAD, EYELIDS, LIPS, LIMBS

fat-fascia interface   ! Temporal branch of Facial n. (CN VII) @ zygomatic arch

CHEEK, NECK

beneath deep plexus in high subcutis   ! Spinal accessory nerve (CN XI) @ Erb’s point

BEARD, SIDEBURN

deep subcutis beneath follicles   ! Facial nerve (CN VII) @ marginal mandibular

 

Electrosurgery

Includes 3 types of procedures

  1. Electrolysis
  2. Electrocautery

Hot tip, Direct current, Mono-terminal, Tissue touched, Degree of damage ++++

  1. High Frequency Electrosurgery

Electrocutting (Bi / damage ++++)

Electrocoagulation

Cold tip, Alternating high frequency current, Bi terminal, Degree of damage +++

Electrodesiccation (Mono / damage +) Electrofulguration (Mono / damage +)
Planning the Closure

Ensure complete extirpation of malignant lesion

Malignant cells left behind can grow

along undermining plane, in scar tissue, along nerves, long before becoming visible!

            May not be able to identify original lesion site to clear persistent tumor cells if tissue is       moved with a flap for closure

Know the Anatomy, Have a Back-up Closure Plan, Assure meticulous Hemostasis

Use Surgical Techniques to avoid dead space, avoid blunt trauma, avoid flap elevation

 

Closure Techniques

Advancement Flaps: Epidermis plus full thickness of dermis

Full Thickness Skin Graft: Best choice when clearance of malignancy is uncertain

 

Ways to Speed Healing

Stiches / Adhesive bandage strips establish apposition of wound edges; minimizing distance cells need to migrate

Aseptic technique             minimizes bacterial contamination

Proper hemostasis                       prevents hematoma formation

Close dead space                          prevents seroma formation

Avoid suture strangulation            prevents tissue necrosis

Pigmented Lesions: Clinical Pearls from Hensin Tsao, MD, PhD

  • For the diagnosis of melanoma, best procedure is excision with 2-3mm margins;
  • Treatment of primary melanoma is excision with 1-2cm margins;
  • Sentinel lymph node biopsy should be seriously considered in anyone with melanoma >1mm;
  • Interferon approved for Stage IIC and III melanoma;
  • Anti-BRAF and anti-MEK treatments highly effective for BRAF-mutated melanomas;
  • Checkpoint therapy exploding onto the scene.

Cutaneous Oncology Pearls from David Ozog, MD

  1. Have a low biopsy threshold for “growing scar” which can suggest dermatofibrosarcoma protuberans (DFSP)
  2. Eyelid “bump/lesion” which does not resolve after a few weeks should be considered for biopsy to evaluate for sebaceous carcinoma (particularly elderly)
  3. Desmoplastic Trichoepithelioma can be a challenging clinical and histologic diagnosis
  4. Adjuvant radiation improves outcomes in Merkel Cell Carcinoma in retrospective studies

10 Pearls on the Basic Structure of Skin from Whitney A. High, MD, JD, MEng

  • The skin consists of “three layered cake.” The epidermis (an outer protective outer layer), the dermis (a middle layer that provides “tensile” strength), and the subcutis with insulating fat.
  • The epidermis gets all its nutrition and sustenance from the dermis. The dermis contains all the “supportive” structures of the skin, such as blood vessels, nerves, and many “adnexal structures.”
  • The epidermis consists chiefly of keratinocytes (“skin cells”). These cells are arranged in layers to form a “maturing” protective layer that replaces itself every ~28 days:
    • stratum basal = the germinative layer of the skin that divides to regenerate the epidermis
    • stratum spinosum = names for the intraspinous properties that bind the keratinocytes
    • straum granulosum = the granular layer where keratohyaline granules are produced
    • stratum corneum = the “dead” outer layer the provides the most barrier function
  • The dermis is comprised of three main building blocks: collagen, elastic fibers, and “ground substance. Collagen is the material that provides the tensile strength to the skin. Elastic fibers provide skin resiliency. Ground substance facilitates the diffusion of nutrients and oxygen.
  • The “dermoepidermal junction” is where the epidermis attaches to the dermis. This is also the location of melanocytes that make protective melanin for the skin. The DEJ is where most nonmelanoma skin cancer invades the dermis, the place where nearly all melanoma originates, and the place where many bullous and “interface” diseases transpire.
  • When confronted with a skin disease, one must ask themselves, “where do I believe that that pathology is occurring?” For example, the pathologic process might be:
    • epidermal – such as the spongiosis (intraepidermal edema) and weeping of dermatitis, or the yeast/hyphae of tinea versicolor/pityriasis versicolor growing in the stratum corneum
    • dermal – such as the histiocytic/macrophagic infiltrate of granuloma annulare, or the neutrophilic inflammation of small blood vessels in leukocytoclastic vasculitis
    • subcuticular – such as the panniculitis of erythema nodosum
  • Being able to predict where the likely pathology is occurring also facilitates the securing of a “representative” biopsy, which is always the responsibility of the clinician.
  • Adnexal structures may be the site of inflammatory pathologic processes (acne, hidradenitis), may be the site of neoplastic processes (sebaceous carcinoma), or these structures may simply behave in an undesired way (seborrhea, hyperhidrosis).
  • Uncontrolled and unchecked growth of certain components of the skin leads to cancer, such as basal cell carcinoma (from basilar keratinocytes), squamous cell carcinoma (also from keratinocytes) and melanoma (from melanocytes).
  • Skin structure and function changes with age, such as dyspigmentation and facial wrinkling, formation of “solar elastosis” (damaged elastic), and increased water loss to the environment.

Advanced Systemic Therapies: Clinical Pearls from Ted Rosen, MD

Prednisone, Acitretin

  1. Acitretin: General
    • Vitamin A derivative
    • Better in keratinizing disorders than acne
    • High bioavailability, but absorption enhanced by fatty meal
    • Alcohol converts it into etretinate, with much longer half life; Alcohol avoidance!
  2. Acitretin: Use
    • Approved for plaque psoriasis
    • Used for PsO variants, and many other disorders (off label)
    • Chemoprevention (off-label)
  3. Acitretin: AEs (most common)
    • Teratogen: adequate contraception one month before and three years after taking
    • “Sticky skin” and cheilitis and onycholysis
    • Hyperlipidemia
  4. Acitretin dose
    • Supplied as 10, 17.5, 25 mg color-coded capsules
    • 25-50mg daily initial and maintenance, titrated to response
  5. Prednisone: one of many “steroids” with similar basic structure
  6. Prednisone: General
    • Dose alterations due to change in binding globulin: thyroid dysfunction, obesity, pregnancy, OCP ingestion, hepatic dysfunction
    • Immunosuppressive and anti-inflammatory
  7. Prednisone: Use
    • Bullous diseases
    • Connective tissue diseases
    • Reactive states (EM, SJS)
    • Dermatitis, including neutrophilic dermatoses and Vasculitis
    • Miscellaneous diseases (eg. Sarcoid)
  8. Prednisone AEs (most common)
    • Increased appetite, weight, fluid retention, edema
    • Menstrual irregularities (40%)
    • Gastritis, Glaucoma
    • Agitation and insomnia
    • Loss of bone density
    • Steroid acne
    • (Risk of worsening infections, Pseudotumor cerebri)
    • Relative safety in pregnancy (Class C): risk of cleft lip/palate

Psoriatic Arthritis: Pearls from Arthur Kavanaugh, MD

  • There is increasing evidence that early diagnosis and treatment of PsA results in improved outcomes
  • There exists a large gap and unmet need in PsA, with many patients not being evaluated by doctors or receiving appropriate therapy
  • Because skin manifestations usually precede joint involvement, often by years, Dermatologists play a key role in PsA diagnosis. However, this can present challenges.
  • New guidelines for PsA treatment are under development, and may provide some assistance to clinicians.
  • TNF inhibitors have allowed improved outcomes in PsA, and there continues to be great interest in optimizing therapy with these agents.
  • There is great interest in new targets and agents for the treatment of PsA. Recently revealed data with IL-17 inhibition show promise for treatment of all the various domains of PsA, including peripheral arthritis, skin and nail disease, enthesitis and dactylitis, and axial/spinal arthritis.
  • The IL-12/23 inhibitor ustekinumab was approved last year in PsA and has been shown to be effective across domains of disease.
  • The PDE4 inhibitor apremilast received FDA approval for PsA 3/21/14 and for psoriasis 9/23/14. Its use is increasing in the clinic, for diverse PsA patients. Safety is a particularly attractive feature of this drug.
  • Additional agents are in development for PsA.
  • Optimal management of PsA depends on the levels of activity and severity across the various domains of disease.

Pediatric Dermatology: Clinical Pearls

James Treat, MD

3 points to remember about pediatric dermatology:

  • It may be possible to prevent atopic dermatitis with emolliation started before 3 weeks of age
  • Excess Hair around congenital scalp lesions may indicate ectopic brain tissue
  • Topical timolol can be very effective for early superficial hemangiomas.

Acne: Clinical Pearls

James Treat, MD

5 things to remember about treating acne in pediatric patients:

  • Children who develop acne between the ages of 1 and 7 should have an endocrine workup
  • When needed oral erythromicin can be used off-label as a systemic antibiotic in children under 8.
  • Neonatal acne is in part caused by malassezia yeasts.
  • Pre-adolescent acne can be treated similarly to adolescent acne except that doxycycline should not be used in children under 9 or those who have not developed their secondary teeth
  • Isotretinoin MUST be given with food

Infectious Disease: Clinical Pearls

James Treat, MD

5 pearls for treating infectious disease in children:

  • Gianotti Crosti can be induced by molluscum contagiosum and may mark the end of the infection
  • Tonsillectomy should be considered in children with severe psoriasis that correlates with GRoup A Streptococcal infection
  • ‪If you see Guttate psoriasis in children under 5, look at their perianal area for the Strep infection
  • Leishmaniasis can present as a non-healing ulcer in patients who have traveled to Central AMerica or Middle East
  • Exuberant hand foot and mouth is caused by coxackie A6