Does medical economics bias the community standards for treatment of skin cancers? If the answer is yes, then photodynamic therapy serves as an illustrative example of this bias.

Private practice dermatology in the US and National Health Service of UK are practice settings with significantly different economics and also different treatment goals. The one’s is to achieve the best possible outcome for the patient without regard to the third party cost (insurance company or Medicare). The other’s is to to take care of a population of patients given the limitations of access to healthcare. UK’s National Health Service is a government-run system with shrinking resources.

Here is a statement an article in 2008 from British Journal of Dermatology based on clinical research performed in hospitals and clinics of the NHS. “Photodynamic therapy is a good treatment for primary superficial BCC.” In fact, the authors further segment primary superficial BCC and claim that PDT is the treatment of choice in a low risk site (not in central face) that is greater than or equal to 2 cm.

On the other hand, a minority of dermatologic practices provide PDT in the United States. In some urban areas of the US, where there are more Mohs dermatologists than in some states, finding a practice offering PDT is unusual. The reasons are not just economic disparity among competing treatments. Reimbursement for PDT is not impressive – $175 for a 15 -30 minute treatment (Medicare pricing). Things just get worse from there. MAL and LAL (the two topical photosensitizers) are not approved by the US FDA for anything other than actinic keratoses (AK), while in Canada and Europe, similar agencies approved MAL for BCC treatment. No US pharmaceutical company finds economic benefit to the costly FDA approval process of MAL for use with basal cell carcinomas.

To add insult to injury, Gladerm, the only distributor of Metvixia (methyl aminolevulinate, MAL), the best porphyrin photosensitizer, is no longer offering the drug since the first of this year. There are no approved pharmacies in the US carrying FDA approved generic drug for compounding either. This leaves ALA (aminolevulinate) as the only available photosensitizer in the US.

Photodynamic therapy has not enjoyed much clinical application in the United States due to many reasons, but all stemming from underlying economic factors. The differences across the Atlantic can be explained by differences in reimbursement for the procedure: third party payor vs government-run health care. Another explanation may be the larger goals of treatment of these different healthcare systems: maximizing individual therapy and outcome vs managing a population outcome with limited resources. The question is what would the consumer pick if their face and wallet dependent on the choice?

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Photodynamic therapy (PDT) is a unique treatment with clear benefits in non-melanoma skin cancers and precancerous lesions. It is noninvasive, selectively treats abnormal cells, and is relatively inexpensive. Despite these accolades, it is an orphan treatment often rejected for other treatment options.

Photodynamic Therapy

PDT uses porphyrin molecules that have selective penetration of abnormal epidermis. Activated by specific light frequencies, these molecules create a cytotoxic effect, selectively injuring the neoplastic lesions. Two such porphyrins have been utilized – the more common aminolevulinate (ALA, Levulan Kerastick) and possibly the more effective methyl aminolevulinate (MAL, Metvix). FDA-approved only for treatment actinic keratoses, this technology has been applied to treatment of squamous cell carcinoma in situ (SCCis) and superficial basal cell carcinomas (sBCC).

Treatment of MAL-PDT is delivered after 3 hours of MAL cream under occlusion, followed by 15 minutes of red light exposure. More common in the US, ALA-PDT uses blue light frequencies. Burning and stinging occur mostly during illumination but can persist for a day. Treatment is usually repeated 1 week later and occasionally in 3 months if complete responses is not achieved. Surface debridement or curettage can improve penetration and efficacy.red light PDT

Summarizing various studies demonstrates efficacy of PDT for AK at 85-90% complete response. Bowen’s disease is cleared in 90% of cases but at 2 years that number is reduced to 68%. Superficial BCC (sBCC) and thin nodular BCC (nBCC) are cured in 75-95% of cases after 3-5 years in various studies. Thick BCC are cleared in 80-85% of cases at 2-4 years.

It is fair to say that MAL-PDT achieves a long-term cure for BCC in 80-95% of cases, with the median falling above 85%. Although AK’s achieve a similar success, the available studies for Bowen’s disease show worse long-term cure rate than other pathologies. Cosmetic outcomes are found to be superior to all other treatments.

With this data in hand, it is no wonder that British studies form the NHS hospitals and clinics recommend PDT as “the treatment of choice” for primary sBCC in a low risk site (not in central face) that are 2cm and “generally good choice” if < 2cm. They also claim PDT as “generally good choice” in recurrent sBCC in low risk sites. The next category of “fair choice” is reserved for primary nBCC < 2cm in low risk site, primary sBCC < 2cm in high risk site, and primary sBCC 2cm in high risk site.

There are a few innovative applications for photodynamic therapy described. PDT has been successfully applied in Basal Cell Nevus Syndrome patients. Unique delivery methods have included intralesional ALA injection and an ALA patch for specific lesions. In addition to fluorescent and LED light sources, IPL (Intense Pulsed Light) has been utilized with success as stand alone and in addition to the traditional light sources.

The unique advantages of photodynamic therapy for skin cancers is the ability to treat large areas of field cancerization, the relatively low cost, and the superb cosmetic results. Its underutilization as a modality for non-melanoma skin cancer management in the United States is likely related to economics of the treatment and patient expectations.

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Mohs excision of upper lip philtrum squamous cell carcinoma left a subtotal lip defect. Bilateral nasolabial fold myocutaneous island advancement flaps were used to successfully rebuild the functional and aesthetic upper lip.  The flaps utilized the outer circumference of orbicularis oris to rebuild the muscular continuity of this large defect. Complete oral competence was restored preserving sensation as well.

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WhatIsMicroarray_02Another genetic molecular technology that has evolved tremendously is real time polymerase chain reaction (PCR). When accompanied by reverse transcription prior to PCR (RT-PCR), it has also allowed rapid multiple gene analysis useful for cancer staging such as OncotypeDx. This platform analyzes RNA for 21 genes with RT-PCR to stratify breast cancer patients according to risk of metastases and chemotherapy benefit.

In addition to risk assessment, PCR can guide specific therapy by identifying specific gene variations. KRAS gene analysis in metastatic colorectal and non-small cell lung cancer predicts response to epidermal growth factor receptor (EGFR) inhibitor – panitumumab (Vectibix) and cetuximab (Erbitux), both monoclonal antibodies. BRAF V600 mutation in melanoma identified by PCR supports the use of enzyme inhibitors such as vemurafenib (Zelboraf) in unresectable or metastatic melanoma. See Clarient’s website for a list of available PCR tests. The large national laboratories are offering a more limited selection of DNA microarray tests generally not focusing on oncology. The innovations in microarray cancer testing are in the early stages of adoption, typically offered initially by smaller companies and academic laboratories such as CombiMatrix and UCSF lab.

Not to be outdone by RT-PCR, expression microarrays are now making inroads into the realm of genetic expression with RNA identification on massive scale. Instead of searching for copy number variations with preset sequences as markers, these microarrays identify and quantitate specific RNAs expressed in tumors. These arrays not only approach the sensitivity of detection of RT-PCR, but also assess the entire expression profile of the tumor (termed transcriptome). Instead of ordering a few PCR tests as offered by laboratories, clinicians and researchers will be able to test for a large number of gene expression products using these expression arrays.

Here is an overview of various applications of microarrays – with gene expression profiling featured at 0:30.

Comprehensive DNA sequencing technology has also been accelerating at a rapid rate. This video explains some of these technologies.

Recently, researchers of the 1000 Genomes Project announced that they have sequenced the complete DNA of more than 1000 people from 14 populations groups around the world. This global project involved 700 scientists and was published in Nature, November 2012. Scientists identified 38 million variations in genes or 98% of all the estimated human variation in the world. Today, an entire person’s genome can be sequenced in less than a month. Further development of sequencing of tumor genomes will further guide cancer research.

The massive and growing database of genetic information about cancers has been derived, in part, from molecular microarrays. Matching that information with the cancer’s clinical behavior and response to specific therapies will define specific genes and their effect on tumor growth. ErbB-2 amplification, KRAS and HRAS variation, and BRAF V600 gene discovery are but small steps of many needed to discover the role of the 200 + genes responsible for cancer proliferation. As these genes and their gene products are revealed, multiple drugs can be developed and ultimately used to counteract their expression. Personalized medicine with improved cancer staging utilizing DNA analysis and with individualized targeted cancer therapies is upon us. In another 10 years, it is reasonable to assume that some of the cancers can become chronic conditions or can even be cured.

Additional References:

A good learning and teaching tool for understanding DNA microarrays

Microarray based comparative genomic hybridization

DNA Microarray

Copy number variation

BAC clone vs. Oligonucleotide arrays

Genetic testing and molecular diagnostics

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Radiotherapy was born shortly after discovery of radiation by the Marie Curie and Peter Curie in 1889. First report of radiotherapy used for malignancy was published in 1896 in Medical Record by Victor Despeignes who treated a patient with gastric cancer in France. Émil Grubbé, a medical student in Chicago at the time, would later claim to have been the first to treat cancer patients with X-rays in 1896. First successful treatment of malignant skin lesions (rodent ulcer, i.e. basal cell carcinoma, and epithelioma) were reported by Thor Stenbeck and Tage Sjogen of Sweden in 1899. Within a few months, scientific journals were inundated with reports of successful treatment using X-rays for different skin malignancies.

The following 20 years were characterized by exploration of radiation technology with various clinical applications and radiation complications. Between 1922 and 1934, Henri Coutard, working with the Radium Institute in Paris developed the first protracted, fractionated course of radiation for head and neck cancers – the concept we still employ today. In the 1940’s and 50’s the science of radiotherapy continued to be refined with appropriate dosage regimens. Data was continued to be collected and published in the 1960’s proving efficacy and safety of radiotherapy.

A comprehensive survey was performed by the Task Force on Ionizing Radiation of the National Program for Dermatology of the American Academy of Dermatology, which evaluated the usage of ionizing radiation by dermatologists in 1974. A detailed questionnaire was mailed to 4560 dermatologist in US and Canada, with 2444 responses received. At that time, 55.5% of dermatology offices (2305 replies) had superficial x-ray and/or Grenz-ray equipment. 44.3% of dermatologists used superficial x-ray or grenz rays regularly. Clinical instruction during residency training was considered good by 37.4%, adequate by 22.2% and poor by 27.1% of respondents. One-fifth (18.3%) received no practical training.

Something happened in the 1970’s as radiotherapy popularity in dermatology began to rapidly decline. Dr. Z. Charles Fixler from Cincinatti helped me fill in the blanks. He like many dermatologists at the time received training in radiotherapy during his residency in the 1950’s. Upon opening his private practice he purchased a Profex X-ray machine in 1957 and inherited a Universal X-ray machine from another dermatologist, both of which Dr. Fixler is still using. The machines has been regularly maintained and certified by physicists for 56 years and are still going strong. Dr. Fixler also owns a Grenz X-ray machine made by X-Cel, although he has not used it for benign skin conditions for many years. He currently uses his Universal and Profex X-ray machines at 80 kVp energy delivering 600 cGy 2 times per week for 3 weeks for BCCa and 700 cGy 2 times per week for 3 weeks for SCCa. His patients are mostly elderly and travel significant distances making his fractionation regimen practical and appropriate.

Universal Grenz Ray Machine

Universal Grenz Ray Machine

In the 1970’s, Dr. Fixler also noted that many dermatologists stopped using radiotherapy. At one point there were up to 30 dermatologists performing radiation therapy in the Cincinnati area. Within a few years, only 3 were left. Today, strong at 87, Dr. Fixler and his associate – his son – are the only dermatologist in the area providing radiotherapy for 100-150 patients per year.

He attributes several possible reasons for the abandonment of radiotherapy by dermatologists. As he put it, “Government scared everybody” with regulations, enforcement, and licensure. Room shielding requirements, physicist equipment calibration, and licensure fees could have been a factor. He also recalled a circulated scare of secondary radiation effects on distant organs such as the thyroid gland. That fear was unwarranted as simple shielding avoided that risk.

Another factor was economic – a reduction in payments for radiotherapy treatments discouraged many dermatologists. Emergence of Mohs surgery at the time cannot be underestimated. Its natural attraction as a hands-on surgical procedure, its increasing reimbursement, and growing acceptance may have been the coup de gras of radiotherapy. In 1967 the American College of Chemosurgery was established, and by the 1970s some dermatology Residency programs had begun offering Mohs surgical training. The rest is history.

Despite this, some 30 dermatologists are currently using superficial radiotherapy in the United States primarily for skin cancer treatment. Additionally, a significant  number of radiation oncologists also use this X-ray technology (while all radiation oncologists use LINAC electron beam therapy). In Europe, the story is substantially different, with widespread use of superficial radiotherapy in many skin cancer centers by dermatologists and radiation oncologists alike.

Control Panel for Universal Grenz Ray

Universal Grenz Ray Control Panel

Today in the US, we see a re-emergence of interest in radiotherapy for skin cancers as new equipment has been introduced to the market by companies such as Sensus and Xstrahl (Gulmay). Several academic dermatology departments have acquired these machines and re-introduced radiotherapy to their training programs. Perhaps, radiotherapy for skin cancers works in 40 year cycles. Henri Coutard in 1930’s established the first fractionated regimen for skin cancers. In 1970’s it was abandoned by dermatologists en masse, and in 2010’s it reemerged. Perhaps, by 2050’s we will have cured cancer with targeted genetic therapy making radiotherapy obsolete again.

References:
1. Advances in Radiotherapy and Implications for the Next Century: A Historical Perspective
2. History of Radiation Therapy
3. Goldschmidt H. Ionizing radiation therapy in dermatology. Current use in the United States and Canada. Arch Dermatol 1975; 111(11): 1511-7
4. Phone Interview, Z. Charles Fixler, MD, Cincinnati, OH. Oct 29, 2012.

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Over the last several years technological advancements in the molecular underpinnings of cancer have led to a revolution of cancer management by DNA molecular testing. By utilizing cancer genetics to guide the specific and customized treatment for each patient, the concept of personalized medicine has emerged. Melanoma has been one of the cancers extensively studied from a genetic and molecular aspect. This first of two articles explains genetic testing and molecular diagnostics in cancer medicine by highlighting several technologies employed in assessing tumors: cytogenetics, fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), and microarray technology.

dna_500

 

The predecessor to CGH and microarray analysis has been conventional cytogenetics where changes in chromosomes are visualized with staining under a microscope – karyotyping. This technology has been used since the 1950’s with few changes. Consider the fact that human genome has 3.2 billion base pairs. Karyotyping can easily visualize large (>10 mb, 10 megabase, 10 million base pairs or nucleotides) changes in chromosomes, such as whole chromosome duplication or deletion, but has the drawback of requiring dividing cells. Thus, it cannot be used on tissue that will not grow or has been fixed in formalin and paraffin embedded. Furthermore, genetic changes important in cancer are often below the resolution of karyotyping, for instance the amplification of Her-2/neu (ErbB2) commonly seen in breast cancer.

For these reasons, a higher resolution analysis was developed to detect submicroscopic changes in chromosomes, termed fluorescence in situ hybridization (FISH). With FISH analysis, fluorescently labeled DNA probes locate the positions of specific DNA sequences on chromosomes by hybridizing with the DNA being studied. This allows for the detection at higher resolution of mutations, deletions, and other genetic changes in cancer cells. Unfortunately, FISH is limited by the number of probes available across the genome, and the number of probes that can be used in each assay. Because of the cost, FISH is not a technology that can probe the entire genome on a routine basis.

Cytogenetics

Cytogenetics – Predecessor to CGH and Microarray Analysis

The development of comparative genomic hybridization (CGH) provided the ability for genome-wide screening for chromosomal abnormalities (or more specifically copy number variants) at much higher resolution. CGH uses two genomes, a test and a control, which are differentially labeled and competitively hybridized to specific chromosome sequences across the genome in a microarray.

Watch these YouTube video to understand how microarrays are made and how microarrays function.

This video is a good overview of microarray testing options with CGH microarray demonstration starting at 1:40.

The fluorescent signal intensity of the labeled patient or tumor DNA relative to that of the reference DNA can then be analyzed, allowing the identification of DNA abnormalities (copy number changes). Copy number variation is one of the cornerstones of genetic variability and cancer development. The “copy” refers to a segment of DNA from one kilobase to several megabases in size. These DNA segments can be deleted, duplicated, or amplified during cell division causing new traits, disease, or cancer.Gene-duplication

 

Current microarray technology utilizes several hundred thousand to several million DNA probes on each microarray, allowing the detection of aneuploidies (abnormal number of whole chromosomes, e.g. trisomy 21) and copy number changes of any evaluated DNA locus down to resolution of ~100,000 base pairs (100 kb). Thus, array CGH technique can achieve amazing efficiency of DNA analysis, with one assay equivalent to thousands of FISH experiments.

CGH with Whole-genomic DNA Probes

Another critical concept is the number of genes active in cancer growth. Of the 25,000 distinct genes in the human genome, it is estimated that only 200 to as many as 1,500 genes are important to oncology. At present, researchers understand only about 50 of the 200 + genes responsible for cancer behavior. It can be estimated that a single tumor type may have as few as 20 genes responsible for its behavior, but that number may be as high as 200 genes. Many clinical applications in oncology have emerged where whole panels of these gene expression markers can stratify patients into risk categories. For example, breast cancer management is aided by microarray technology such as MammaPrint where 70 genes that correlate with metastases are analyzed. CombiMatrix of Irvine uses DNA microarrays with up to 20,000 probes designed to target 500 genes and cancer specific loci within various cancers. Based upon changes in DNA copy number, these predictors can guide more aggressive or less aggressive clinical management. For instance, in Acute Myeloid Leukemia (AML), genetic markers help with decisions whether to treat with traditional chemotherapy or proceed straight to bone marrow transplantation. Melanoma risk analysis is also utilizing DNA microarray testing. Encouraging data suggests that MelTUMPS may be soon classified into melanomas or benign nevi based on analysis of DNA copy number variation. Thus microarray technology allows risk stratification of cancers or helps define tumors as benign or malignant thus guiding clinical management. This is primarily accomplished by evaluating copy number variations of tumor DNA. The ease of this analysis and its dropping cost usher in a renaissance in cancer management.

In our next article we will discuss reverse transcriptase polymerase chain reaction (RT-PCR) and gene expression microarrays and their effect on cancer treatment.

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Bowen’s disease or squamous cell carcinoma in situ is a cutaneous neoplasm with a 3-5% risk of invasive carcinoma. It is of particular interest due to the plethora of treatment modalities available. Sun exposure is one of the causes of Bowen’s carcinoma, but over ½ of cases have detectable oncogenic HPV types 16 and 18. The implication is that HPV-induced Bowen’s disease should be responsive to agents with antitumor and antiviral effect. Most therapeutic options for Bowen’s disease, except Mohs excision, have failure and recurrence rate of 10%-20%, and no treatment modality is best in all clinical scenarios.

Bowen's Carcinoma

5-fluorouracil (5-FU) is usually applied once or twice daily as a 5% cream for up to 2 months and can be repeated if needed. The median clearance rate with 5-FU among the studies is 80-90% with 10-20% recurrence rate. Although some show better and some worse results, the variability of treatment regimens and study design account for part of that. 5-FU can be an irritant affecting patient compliance. To limit irritation of treatment, less aggressive regimens have been employed with diminished clearance rates and long term control rates. In those cases additional cycles of treatment are needed to improve clearance and limit recurrence.

Imiquimod (Aldara) has the unique role as both an anti-tumor agent and an anti-viral agent given its immunomodulating action. This fits the large portion of Bowen’s disease, having an HPV association. Imiquimod applied daily for 16 weeks produced a cure rate between 73% and 93% in several studies. Like 5-FU, some imiquimod patients have significant skin reactions to treatment. These can be severe enough to stop the treatment prematurely.

An innovative approach obtained 100% cure rate utilizing cryoimmunotherapy in a single study. Liquid nitrogen cryospray was applied one week prior to a 6-week course of 5% imiquimod applied 5 of 7 days. A few patients required application of tretinoin 0.025% cream to incite a reaction by enhancing imiquimod penetration. The theory is that liquid nitrogen damages the integrity of the stratum corneum thereby facilitating cream penetration. (MacFarlane et al. Arch Dermatol. 2011;147(11):1326-1327)

Cryotherapy alone also has a failure rate of up to 30%. However, success rate up to 90% at 12 months has been shown, provided that an adequate freeze-thaw cycle is applied. Examples of freeze-thaw cycles (FTC) are a single 30 second FTC, two 20 second FTC with a thaw period, or up to three single treatments of 20 seconds at intervals of several weeks. Although effective for smaller lesions, treatment of broad lesions or lower leg lesions may be impractical due to discomfort and slow healing. Curettage and cautery (electrodessication and curettage, ED&C) may be preferable to cryotherapy in terms of pain, healing, and recurrence rate (up to 20% with ED&C).

Photodynamic therapy (PDT) is also successful with Bowen’s disease by the virtue of being able to treat large areas. Despite the reports of superior cosmesis and healing, PDT can have associated erythema, edema, and pain. It requires one, two, or more treatments with a clearance rate of up to 90% and recurrence rate of 10-20% or higher.

Various radiotherapy techniques have been used to treat Bowen’s disease. Response of up to 100% has been documented with recurrence rates of 0-10%. Limitations of radiotherapy has been non-healing on the lower leg of up to 20%. However, in those studies, larger energies have been utilized (100 and 120 kVa). This compares to current recommendations of 50-80 kVA of superficial radiotherapy where such complications can be avoided.

Finally, Mohs surgery remains the gold standard for treatment of Bowen’s disease except for small trunk and extremity lesions. It had a 6-8% recurrence rate. It is particularly effective for previously treated and recurrent Bowen’s disease.

Topical and destructive therapies have the potential to partially clear the lesion creating noncontiguous ‘‘skip’’ tumors. Aggressive surgical treatment would be required to achieve cure then. There is an additional risk to non-surgical treatments that must be considered – areas of invasive carcinoma within squamous cell carcinoma in situ. Additional sampling biopsies can help with that assessment, but ultimately clinical suspicion should guide the management.

For more in depth review, read
“Guidelines for Management of Bowen’s Disease: 2006 Update. Cox, et al. Br J Dermatol 2007; 156: 11-21”.
“Shimizu et al. Dermatol Surg 2011; 37:1394-1411.”

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Ambiguous melanocytic lesions – those with histopathologic findings without a diagnostic consensus – are divided into thin and thick tumors. Thin lesions appear as dysplastic nevi and have a potential of being part of melanoma in situ or superficial spreading melanoma. We have explored diagnostic and therapeutic considerations of the thin lesions in a previous blog – “Atypical Nevus – Chasing Excision Margins

This article will explore thick ambiguous melanocytic lesions: melanocytic tumors of uncertain malignant potential (MelTUMP) and spitzoid tumor of uncertain malignant potential (STUMP).

The designations MelTUMP and STUMP are provisional diagnoses representing heterogeneous groups of lesions whose behavior is yet to be determined. Similar terminology has included borderline melanoma, minimal deviation melanoma, ambiguous melanocytic lesions, Spitz nevus with atypical features (SNAF), blue nevus or deep penetrating melanocytic nevus.

STUMP and MelTUMP

Histology usually demonstrates a deep penetrating nevus with mitoses, dermal melanocytes with mitoses near the base and associated inflammatory infiltrate. These lesions lack certain features of true melanomas. Histologically differentiating severely atypical spitzoid neoplasms from spitzoid melanoma is particularly difficult in prepubertal children. These features in melanoma would correlate with metastatic capacity. In fact, a study of atypical spitzoid tumors (STUMP’s) found half of 67 cases contained tumor cells in lymph nodes. Despite that, only one patient died of progressive disease. (Ludgate MW, Fullen DR, Lee J, et al. The atypical Spitz tumor of uncertain biologic potential. A series of 67 patients from a single institution. Cancer 2009; 115: 631)

Several recent studies have looked at concurrent melanocyte deposits in lymph nodes of atypical melanocytic lesions finding that these lesions rarely progress to overt malignancy. If sentinel lymph node biopsies had not occurred, the intranodal melanocytes may have remained dormant or been eliminated. Several studies have documented that the presence of a positive sentinel lymph node in a child diagnosed with melanoma or MelTUMP does not convey the same negative prognostic information as it would for an adult patient. These lesions represent a biological entity of low-grade malignancy apart from conventional melanoma and melanocytic nevi. This suggests that atypical melanocytic neoplasms in children may be less aggressive in general and may be limited in their progression by host factors such as a more potent immune defense.

The utility of sentinel lymph node biopsy in evaluation of a MelTUMP or a STUMP remains controversial. The procedure has been found to be a staging and prognostic tool only in melanoma in adults. Extrapolating its utility with ambiguous tumors may result in potentially unnecessary medical procedures such as completion lymphadenectomy and adjuvant therapy. Sentinel lymph node biopsy in these scenarios remains controversial.

Additional information about these lesions is needed to help with decisions on further therapy. Molecular genetic testing represents the next frontier that may distinguish benign STUMP’s and MelTUMP’s from melanoma and guide treatment decisions. We will explore this technology in one of our next articles.

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Skin Cancer and Reconstructive Surgery Center is proud to introduce our newest associate – Steven Daines, MD. Dr. Daines is a gifted Facial Plastic and Reconstructive Surgeon who will be joining our team of reconstructive surgeons, head and neck surgeons, dermatologists, medical oncologists and radiation oncologists in treating skin cancers. He has completed advanced fellowship training in Facial Plastic and Reconstructive Surgery in New York. He is also board certified in Otolaryngology – Head and Neck Surgery. Dr. Daines and Dr. Madorsky will work as a surgical team on the most difficult skin cancer cases to improve the quality and decrease the surgical time of our treatments.

Steven M. Daines, M.D. recently relocated to Newport Beach after completing a fellowship in Facial Plastic and Reconstructive Surgery in Albany, New York, with Dr. Edwin Williams III. Dr. Daines graduated from the University of California – Irvine School of Medicine and completed his residency in Otolaryngology – Head and Neck Surgery at the University of Utah. Dr. Daines’ professional interests include rhinoplasty, facial rejuvenation, skin cancer and facial trauma. He has recently been involved in researching the use of Sculptra Aesthetic to restore volume to the aging midface by utilizing 3-D imaging technology to quantify treatment results. He has also investigated complications related to injectable soft tissue fillers and is seeking to define treatment algorithms for their management. An excellent clinician, surgeon, and patient advocate, Dr. Daines is a welcome addition to the Appearance Center of Newport Beach as well as the Skin Cancer and Reconstructive Surgery Center.

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PET scanning is utilized in skin cancer staging by detecting regional lymph node metastases as well as distant organ metastases. Its specificity is superior to CT and MR for N-staging, particularly with melanoma. It can be the superior modality for primary tumor staging as well.

PET scan imaging is based on the increased metabolic activity of cancer cells that more rapidly take up 18F-FDG, a glucose analog with a positron-emitting radioisotope fluorine-18. The sensitivity is limited by the minimum size of the tumor – 4mm or greater. The specificity of PET scan is limited by false-negative readings with well-differentiated tumors or by proximity to the primary tumor where resolution of imaging may not be able to visualize the lymph node as separate from the tumor. Additionally, inflammatory and infectious lesions can demonstrate increased 18F-FDG uptake, although usually at an SUV (standard uptake value) below that of cancer.

Most PET scans today are performed as fusion images with a concurrent CT – a PET / CT scan. A novel metabolic–anatomic imaging technique recently has been introduced into clinical practice – PET / MRI. It has a potential benefit in T-staging of primary bone tumors and soft-tissue sarcomas and M-staging of brain, liver, and bone metastases. PET / MRI would be a strong candidate for melanoma staging.

PET Scan Image

Recent developments in PET instrumentation is promising to deliver a 1mm detection resolution. It can be achieved by bringing the detectors closer to the patient as a locoregional (organ-specific) PET system. This  is currently under development at the Molecular Imaging Program at Stanford Department of Radiology. A new design for a submillimeter-resolution small-animal PET system is also being developed.

Such high resolution metabolic imaging would revolutionize cancer management. With submillimeter PET resolution, sentinel lymph node biopsies and staging regional lymphadenectomies can become obsolete. With better tumor assessment, primary tumor surgery can be more precise and more organ-sparing. Science may be finally catching up to the Star Trek Tricorder.

tricorder

References:

Buchbender, et al. Oncologic PET/MRI, Part 2: Bone Tumors, Soft-Tissue Tumors, Melanoma, and Lymphoma. J of Nuc Med 2012; 53:8: 1244-1252.

Levin. Promising New Photon Detection Concepts for High-Resolution Clinical and Preclinical PET. J Nucl Med 2012; 53:2: 167-170.

Lau, et al. Analog signal multiplexing for PSAPD-based PET detectors: simulation and experimental validation. Phys Med Biol 2010; 55:23: 7149-74.

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