Importance of Histopathology in Cutaneous Radiotherapy

Histology is important in cutaneous radiation to ensure the diagnosis is correct since different neoplasms are treated using different protocols. It is also important to ensure the lesion is encompassed in the field of therapy and that the energy and penetration is appropriate for the neoplasm at hand. For instance, superficial lesions may be treated differently than deep lesions.

The goals of cutaneous radiation therapy are to ensure the treatment will eradicate the cancer while delivering a therapeutic dose with minimal side effects. It is also very important that cutaneous radiation therapy not induce neoplasia.

This article focuses on several examples of challenges in diagnosis including metatypical basal cell carcinoma, combined squamous cell carcinoma and basal cell carcinoma, squamous cell carcinoma in situ, primary cutaneous carcinosarcoma, trichilemmal verruca, and inverted follicular keratosis. Additionally, the benefits and challenges of stereotactic radiation therapy (SRT) are touched upon.

Metatypical basal cell carcinoma is a variant of a basal cell carcinoma (BCC) that is an intermediate between nodular cystic BCC and squamous cell carcinoma (SCC). Histologically speaking, the cells are enlarged and are pleomorphic while lacking peripheral palisading. Abundant basophilic cytoplasm is present, but there is often no retraction artifact and a fibrous stoma may not be present. Metatypical BCC may simulate Merkel cell carcinoma, and even though it looks dangerous, it behaves like BCC. In terms of treatment, metatypical BCC is amenable to stereotactic radiation therapy.

Stereotactic radiation therapy—an advanced and modernized form of radiation therapy—allows high doses of radiation to be delivered to a small, focused area. It differs from conventional radiation in that it is able to exclude the surrounding normal tissues. SRT uses high-energy x-ray beams to shrink or control the growth of abnormal cells by either killing the cells directly or by disrupting the ability of the cells to grow.

In combined squamous cell carcinoma and basal cell carcinoma, an initial biopsy will show SCC or BCC, but upon subsequent evaluation of the excision specimen, there is evidence of both BCC and SCC. There are three possible reasons for this:

1. Collision tumor of coincidental BCC and SCC

2. Altered differentiation of BCC on recurrence may assume more aggressive histologic characteristics with squamous appearance

3. True basosquamous differentiation

It is important to recognize these reasons and ensure the biopsy is representative to avoid under-treatment.

Squamous cell carcinoma in situ is generally easily diagnosable even though there may be several variants clinically and histologically. One variant is pagetoid Bowen’s disease, which may stimulate Paget’s disease and melanoma in situ. SCC in situ may be able to be treated with a superficially penetrating beam. The most important challenge in diagnosing SCC in situ is to define the border, which may be very indistinct.

Primary cutaneous carcinosarcoma is a rare, biphasic tumor of malignant epithelial and mesenchymal components. The epithelial aspect may be keratinocytic, resembling BCC or SCC or adnexal. The sarcomatous component may resemble atypical fibroxanthoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, or fibrosarcoma. Keratinocytic carcinosarcoma has a better prognosis than adnexal types (70% versus 25% 5-year survival rate). Primary cutaneous carcinosarcoma is a more aggressive lesion than SCC that requires surgical excision and not SRT.

Trichilemmal verruca may stimulate BCC histologically while verruca with squamous eddies (inverted follicular keratosis) may simulate SCC histologically. Trichilemmal verruca presents as a pink to whitish scar-like plaque of the trunk, extremities, head, and neck area.  It is important not to over-diagnose, which could lead to over-treatment.

Inverted follicular keratosis (verruca with squamous eddies) may be confused with SCC because of whorls of keratinocytes in nests that may be asymmetrically distributed. There are usually few if any mitoses present with no atypia. Inverted follicular keratosis is clinically usually not suggestive of SCC. If it doesn’t fit clinically and diagnosis comes back malignant, be sure to obtain a second opinion.

SRT is an excellent treatment option for many different conditions, but it does come with challenges. For example, reimbursement pressures and “turf” wars create unfortunate circumstances for dermatologists who want to use SRT.  Some use SRT inappropriately due to inadequate training and supervision. To avoid confusion as to when to use SRT, we at Cockerell Dermatopathology place a note on the report stating that the neoplasm in question is one that could be treated with SRT appropriately.

An accurate and complete diagnosis is essential to SRT use. If you perform SRT, establish a relationship with a dermatopathology laboratory that understands SRT and will be involved in the treatment planning.

References

Cockerell C. (2015). The importance of histopathology in cutaneous radiotherapy. [PowerPoint Presentation]

Stony Brook Cancer Center (2015). SRS and SRT: Stereotactic RadioSurgery and RadioTherapy. Retrieved December 2, 2015, from https://cancer.stonybrookmedicine.edu/diagnosis-treatment/radiation-oncology/treatment-technology/srs.

An Olympian’s Dilemma: Polluted Waters and Staph Skin Infections in RIO

Olympic sailors find themselves very concerned about competing in the sewage-infested waters off of Rio de Janeiro in next year’s games. The waterways in which the athletes are to compete are rife with pathogens both near shore and offshore, where raw sewage flows into the waterways from fetid rivers and storm drains.

These athletes are at risk for Staph infections because bacteria can enter the skin through scrapes and cuts the sailors may sustain while working among wires and other sharp objects onboard their vessels.

Skin and soft tissue infections are commonly caused by Staphylococcus aureus bacteria. Signs and symptoms vary widely, depending on the severity and location of the infection, but typically include pus, redness, swelling, tenderness, as well as possible fever. MRSA, or methicillin-resistant Staphylococcus aureus, is a type of Staph infection resistant to many different antibiotics. Staph infections are treated with topical, oral, or intravenous antibiotics, depending upon the type and severity of the infection. However, antibiotics are not always effective in fighting Staph infections due to an increase in antibiotic resistance.

One of the Olympic sailors plans to wear plastic coveralls to protect himself while on the waters off of Rio, but this plan is not foolproof. The best course of action the sailor can take is to undertake preventive measures and work closely with a health care provider. The sailor should keep all cuts and scrapes covered well to avoid contact with polluted waters, and should immediately shower after getting out of the dirty water.  The athlete should seek immediate medical attention if a cut or scrape becomes red and tender.  Additional measures could include using bleach baths, 4% chlorhexidine washes, and/or sodium hypochlorite washes.  Bleach baths are cumbersome and chlorhexidine washes can be drying. A new alternative is the sodium hypochlorite formulated wash, which is marketed under the CLn SportWash brand (www.clnwash.com). The shower cleanser may be used daily immediately after exercise and is lathered onto the skin in the shower for 2 minutes, and then is  rinsed off thoroughly like any other cleansing soap.

The alternative to using a sodium hypochlorite cleanser is to take a bleach bath where one soaks in a tub of water for 10-15 minutes. The bath is comprised of one-quarter cup of  household laundry bleach in  a tub filled halfway  with water. Bleach baths can be cumbersome and may not be used above the neck, thus leading to poor adherence and compliance. For more information about bleach baths, please visit bleachbath.org.

References

Associated Press (2015): AP test: Rio Olympic water badly polluted, even far offshore. Retrieved December 5, 2015, from http://bigstory.ap.org/urn:publicid:ap.org:cabd453515244bf2b1063e15f6b680c9.

BleachBath.org (2015). Bleach Like Products. Retrieved December 5, 2015, from http://bleachbath.org.

Ryan, C. et al. (2013). Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis. Pediatric Dermatology. Retrieved October 18, 2015, from http://onlinelibrary.wiley.com/doi/10.1111/pde.12150/full.

Khloe Kardashian Acquires Staph Infection

Khloe Kardashian, 31, recently acquired a staph infection on her leg as a result of visting her husband and former NBA player Lamar Odom in the hospital. The lesion on her leg became painful, and Kardashian later experienced high fever and swollen glands as a result of the infection.

Staph infections are most commonly caused by Staphylococcus aureus bacteria. Signs and symptoms of Staph infections vary widely, depending on the severity and location of the infection. Skin infections caused by Staph bacteria include boils, impetigo, cellulitis, and Staphylococcal scalded skin syndrome (SSSS). Signs and symptoms of a localized Staph infection include pus, redness, swelling, and tenderness, as well as possible fever. MRSA, or methicillin-resistant Staphylococcus aureus, is a type of Staph infection resistant to many different antibiotics. Staph infections are treated with topical, oral, or intravenous antibiotics, depending upon the type and severity of the infection. However, antibiotics are not always effective in fighting Staph infections due to an increase in antibiotic resistance.

The most effective method for decolonizing topical Staph is bleach baths. However, baths with sodium hypochlorite are cumbersome and bleach may not be used above the neck, thus leading to poor patient compliance. Chlorhexidine, the second option for decolonizing topical Staph, is not as ideal as bleach baths because it is drying and irritating to the skin, doesn’t lather well, and may not be used on the face or genitals.

Dermatologists have also adopted CLn® BodyWash, a sodium hypochlorite wash that is safe to use from head to toe, as a preferred cleanser for ages 6 months and older to help maintain excellent hygiene to skin infections.  The cleanser may be used daily, and is lathered onto the skin in the shower for 2 minutes and then rinsed off (or as otherwise directed by a healthcare provider).

For more information on CLn® SkinCare, please visit: http://www.clnwash.com.

References

Mayo Clinic (2015). Staph infections. Retrieved November 19, 2015, from http://www.mayoclinic.org/diseases-conditions/staph-infections/basics/symptoms/con-20031418.

MedicineNet.com (2015). Staph infection pictures, symptoms, and causes. Retrieved November 19, 2015, from http://www.medicinenet.com/staph_infection/article.htm.

Ryan, C. et al. (2013). Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis. Pediatric Dermatology. Retrieved October 18, 2015, from http://onlinelibrary.wiley.com/doi/10.1111/pde.12150/full.

How to Use SEO to Attract New Patients

A 2012 study by Google found that 77 percent of patients search for their physician online prior to booking an appointment. This means that it is imperative that medical practices have a high-caliber website with effective search engine optimization (SEO), so that patients may quickly locate your medical practice’s website online.

What is SEO? Search engine optimization is the process of increasing a website’s ranking on search result listings generated by engines like Bing, Google, and Yahoo. The goal is to be as near the top of the search list as possible since web users tend not to click on links further down the page.

SEO is important for medical practices because patients spend their time surfing the internet for answers related to medical conditions, diagnoses, laboratory and diagnostic tests, symptoms, and treatment options. Having a website that answers these questions makes you the expert, increases familiarity with you, and increases the chances that the patient will call to schedule an appointment with you.

It is important that your website finds patients when they are in “buy” mode. Advertising on the radio or a billboard reaches a large audience, but not necessarily at a time when they are in need of your services. Investing in SEO has a high, measurable return on investment because leads that come through a practice website can be easily tracked. It is much more difficult to track leads from billboards and radio.

Before diving into SEO, know your budget and develop a strategy. SEO is an investment in your practice. For example, if a dermatological surgical procedure brings in a profit of $2,000, you only need to bring in two leads to surpass the spend of $3,500. Your strategy should include your needs. What exactly is your goal? Will SEO help you achieve that goal, or do you have other needs? A solid strategy not only includes the answers to these questions, but also a website analysis to help determine current needs from a digital marketing perspective.

According to Medical Practice Insider, steps that ensure your SEO is working for you include:

Research key terms. Find out what terms potential patients are actually looking for before creating any content. The Google Adwords Keyword Planner can help determine people’s search habits for a certain keyword, including geographic area and volume.

Sprinkle key terms throughout the content. If you would like to appear in a web user search for “Dallas dermatologist,” be sure to include this term in the text on your website. Using a keyword once per 100 words is a good rule of thumb.

Hyper-localize search terms. If you’re located in a large metropolitan area like Dallas/Fort Worth, there will be a lot of competition for the top-ranking spots. Focus on ranking well in community-centric searches, like “Park Cities dermatologist” or “dermatologist downtown Fort Worth.”

Maintain a blog. Creating and maintaining a blog is an easy way to keep creating fresh content that will help your site appear for varied search terms. This ensures you aren’t limited to the keywords on the standard pages of your website.

SEO is not the same regardless of industry; therefore, it is important to use an agency that understands the nuances of healthcare. Healthcare search behavior is different from other industry searches, so utilizing the correct keywords and search terms is very important.  Be sure to engage the services of an agency that understands healthcare and is able to develop accurate content that reaches your intended audience.

References

Medical Practice Insider (2013). Making SEO Work for Your Medical Office. Retrieved November 16, 2015, from http://www.medicalpracticeinsider.com/best-practices/technology/making-seo-work-your-medical-office.

Points Group (2015). Medical Practice SEO. Retrieved November 16, 2015, from http://www.pointsgroupllc.com/medical-practice-seo/.

Cutaneous Blistering Disorders

Blistering skin disorders are among the most interesting, but also the most challenging conditions in dermatology and dermatopathology.

Blisters are accumulations of fluid within or under the dermis. There are three types of blistering skin diseases—subcorneal, intraepidermal, and subepidermal. Subcorneal blisters have a very thin roof that breaks easily. Examples include impetigo, miliaria, and Staphylococcal scaled skin syndrome (SSSS). Intraepidermal blisters have a thin roof that ruptures and leaves a denuded surface, as seen in acute eczema, varicella, herpes simplex, and pemphigus. Subepidermal blisters have a tense roof that often remains intact. Examples of subepidermal blisters are bullous pemphigoid, dermatitis herpetiformis, erythema multiforme, toxic epidermal necrolysis (TEN), and friction blisters.

The mechanisms of intraepidermal vesiculation include:

•        Spongiosis: intercellular edema
•        Ballooning: intracellular edema
•        Acantholysis: loss of desmosomal attachments
•        Cytolysis: cell disintegration
•        Other types like epidermolytic hyperkeratosis

Several examples of common cutaneous blistering disorders are detailed in the table below.

Blistering Disorder	Key Clinical Features	Key Histologic Features
Hand, Foot, & Mouth Disease ·      May simulate irritant or toxic contact dermatitis ·      Important to distinguish from erythema multiforme and TEN: No interface changes or clinical features	·      Lancet shaped vesicles on acra & mucosa ·      Caused by Coxsackie virus A 5, 9, & 16 ·      Recent isolation of aggressive form caused by A6 with extensive involvement, onychomadesis, & extensive mucosal erosions	·      Perivascular infiltrate of lymphocytes & some neutrophils ·      Ballooning degeneration of epidermis
Necrolytic Migratory Erythema	·      Widespread erosive dermatitis with abundant crusting ·      Glucagon secreting tumor of pancreas	·      Superficial epidermal pallor with ballooning ·      Psoriasiform dermatitis late ·      Infiltrate variable ·      Identical histology in other deficiency diseases, such as acrodermatitis enteropathica & biotin responsive multiple carboxylase deficiency
Hydroa Aestivale	·      Blisters & erosions of sun-exposed surfaces ·      Children most commonly affected ·      Scarring	·      Epidermal hyperplasia ·      Spongiosis & ballooning degeneration ·      Epidermal necrosis
Parapoxvirus Infection	·      Inflamed, boggy plaque usually on hands ·      Exposure to sheep or goats (orf) or cattle (milker’s nodule)	·      Marked epidermal hyperplasia ·      Intracellular edema; pink inclusions ·      Granulation tissue; edema in dermis
Epidermolytic Hyperkeratosis	·      Widespread erythema with vesiculation in infancy (congenital bullous ichthyosiform erythroderma) ·      Systemized verrucous epidermal nevus (ichthyosis hystrix) ·      Palmoplantar hyperkeratosis ·      Widespread or solitary keratotic papules (epidermolytic acanthoma)	·      Intraepidermal vacuolar degeneration ·      Pyknotic nuclei ·      Reddish-pink keratohyalin-like granules in epidermis ·      Hyperkeratosis; some parakeratosis ·      Keratin 10 gene mutation
Pemphigus Foliaceus	·      Erythema with erosions covered by exuberant crust ·      Scalp, face, trunk most  commonly involved Mucosal surfaces less commonly involved ·      Exfoliative dermatitis in severe cases	·      Cleft in subcorneal, intragranular or upper spinous layer ·      Some dyskeratotic acantholytic keratinocytes in granular layer ·      Perivascular infiltrate of lymphocytes and eosinophils with exocytosis of eosinophils Immunopathology ·      Direct IF: Intercellular IgG & C3 in epidermis in virtually 100% of cases; rarely IgA; slight accentuation in upper epidermis often ·      Indirect IF: Circulating antibodies to desmoglein 1 (160 kD desmosomal glycoprotein) in 33% & plakoglobin (85 kD adherens junction molecule) in higher percentage ·      Correlation between antibody titer & disease  activity variable & not always reliable
Pemphigus erythematosus (Senear-Usher)	·      Pemphigus foliaceus with features of systemic lupus erythematosus (SLE); +/- myasthenia gravis ·      Photosensitivity; positive ANA	·      Similar histology with vacuolar changes at DEJ

Solid clinicopathologic correlation is the key to making accurate diagnoses and initiating treatment for cutaneous blistering disorders.

References

Cockerell C (2015).  Cutaneous blistering disorders. [PowerPoint]

DermNet NZ (2015). Blistering skin diseases. Retrieved November 17, 2015, from http://dermnetnz.org/doctors/emergencies/blisters.html.