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Notes from the O'Leary Meeting

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Highlights of the O'Leary Meeting

by Kevin Smith M.D.

Dermatology Online Journal, December 1995
Volume 1, Number 2

O'Leary Meeting XX at Mayo Rochester - Melanoma and Clinical Cases September 8-10, 1995

Selected Highlights:

Darrel Rigel spoke very well on several occasions about:

(Epiluminescense Microscopy "dermoscopy" Photographic Diagnosis of Melanoma

(Epiluminescense Microscopy "dermascopy" is still investigational - it is certainly not "the standard of care" - and Sig Muller will testify to this as an expert witness for the defense in a melanoma malpractice trial later this year in California).

Incidence, Diagnosis and Treatment of Melanoma in the 90's

Analysis of 43 risk factors showed that the Big 6 are:

  1. Red/blond hair
  2. F Hx MM
  3. AKs
  4. Marked freckling of upper back
  5. 3 or more blistering sunburns before age 20
  6. 3 or more years with outdoor summer jobs in the teens.
Having just one or two of the above increases the relative risk of MM by 3-4x, having 3 or more increases the risk 20x - making identification of the high-risk subset practical and focussing educational and surveillance efforts.

Prognosis - if Clark's levels and Breslow"s thickness disagree, use the one which is WORST to get the most accurate prognosis.

An Australian dermatologist remarked that the incidence of MM has DOUBLED in the past several years there, so that the new statistics will be even more scary than the current data.

Dr. Rigel and Dr. Bob Swerlick from Emory had a useful debate about the pitfalls of MM statistics, and the issue of whether some of the increased incidence is more apparent than real; with Dr. Swerlick suggesting that there may have been increased detection of histologically worrisome but biologically benign lesions. That study will never be done, because it would require a Tuskegee-type thing where worrisome lesions would be left for a number of years to see what would happen.

Dr. Dan Su discussed and illustrated the CPC of MM, with emphasis on the important points in microstaging:

  1. Excisional Bx is preferred to incisional, and shaves and curettage should NEVER be done if the possibility of MM passes through your mind.
  2. Grossing the specimen should be done with transverse cuts at 2-3 mm intervals, rather than a single perpendicular cut.
  3. Ocular and objective lenses must be calibrated when making measurements.
  4. Review ALL slides and measure DEEPEST involvement.
  5. If neural or perineural involvement measure deepest involved nerve.
  6. DO NOT measure depth of sattelites, mets, or recurrent MM - this is useless.
  7. Record associated pronostically important morphologic variables: ulceration, vascular invasion, regression, and also artifacts like crush that might affect depth measurements.
Dr. Charles Perniciaro led us on a stimulating tour of the dermatopathologic faces of melanoma -- including rarely seen and treacherous entities like desmoplastic melanoma [which has a better prognosis than others of equivalent depth], neurotropic melanoma, pedunculated melanoma, metastatic melanoma including in-transit and epidermotropic mets, amelanotic melanoma, melanoma in benign nevus, regressing or "invisible" melanoma, S-100 negative melanoma, balloon cell melanoma, and minimal deviation melanoma. As a bonus he discussed histopathologic mimics of melanoma and methods to differentiate these from melanoma. A "tour de force".

Nick Rogers discussed melanoma of the mucous membranes, and pointed out the terrible prognosis of melanoma on the oral mucosa. The elderly are often slow to seek advice about genital lesions, so examination of this area is important. Larry Gibson noted that the labia majora is the most common genital site in women, and the glans and foreskin is the most important area in men.

Larry Gibson also pointed out that amelanotic lentigo maligna melanoma can resemble bowenoid SCC or eczema, so be sure to biopsy Bowen's disease before destroying it, and of course biopsy anything else that looks like eczema but does not respond to treatment.

Marian McEvoy discussed UV light and melanoma. Of interest - tanning beds were associated with increased melanoma risk in 2 recent studies [but this might be associated with other behavioral variables, because so far PUVA has NOT been associated with increased melanoma risk]. Am J Epidemiol 140:691-699, 1994.

She pointed out that people with XP have a 2000x increased risk of melanoma - ? secondary to DNA repair defect or altered immune function. People with Hodgkin's, NHL and leukemia also have increased risk of MM.

Mouse models have showed that UV is both a weak initiator and promoter of melanoma, and in addition UV accelerates development of melanoma in skin previously exposed to an initiator and a promoter. Prior irradiation of the site accelerates growth if melanoma is transplanted into skin, probably by local immune suppression.

Henry Randle gave us a well illustrated discussion of the sociology of suntanning, describing changing public and medical attitudes toward sun exposure over the last century and correlating these with the incidence of melanoma in the subsequent years. This would be a good talk to put on public TV in the spring.

Suzanne Connolly from sunny Scottsdale discussed lentigo maligna melanoma, pointing out that the risk of progression from lentigo maligna to melanoma is 5% - 50%, and that LMM represents 5% - 12% of melanoma in melanoma registries worldwide. Occasional rapid progression to invasive melanoma makes Rx mandatory.

John Zitelli spoke eloquently several times on the podium and from the audience, discussing his long and extensive experience of MOHS surgery for melanoma [>500 cases over 12 years]. He has excellent long term results with good tissue conservation. Dr. Randy Roegnik and Dave Brodland [who did his MOHS fellowship with Dr. Zitelli] are also developing a body of experience with MOHS for melanoma and spoke favorably about this. If I ever get a melanoma - God forbid - I would want MOHS, in particular if it was LMM, superficial spreading, or one of the amelanotic variants mimicing Bowen's or superficial BCC.

Of interest to managed-care types, Dr. Zitelli pointed out that radionuclide scans, CT, MRI, GI films and extensive blood work are not useful in the evaluation of patients presenting with melanoma - and in fact can do more harm than good considering the cost and the additional investigations generated by the large number of false-positive findings. The vast majority of relapses and mets are found with history and physical, and the only useful "baseline" studies are the CXR and LDH - and it is only worth repeating THOSE yearly in patients at high risk [thickness > 1 mm]. Other tests only as directed by Hx & Px. Followup Q3month for thick, Q6 for thin x 5 yrs, then annually forever.

He pointed out the GREAT importance of explaining to patients that they must check themselves every month and bring any new lesions to medical attention right away, because people who've had one melanoma are at increased risk for a second primary.

Mark Greene [speaking live by video link from Mayo Scottsdale - saving a lot of money and travel time] discussed the genetics of melanoma, pointing out that features of familial melanoma include early onset, multiple primaries, and many dysplastic nevi. Autosomal dominant in some series, not in others. A twin study showed strong concordance in the number of nevi in identical but not in fraternal twins. Where a patient has dysplastic nevi, about 80% of the time there will be at least one other family member with dysplastic nevi, so it is good to ask about this when taking a history. People with large numbers of dysplastic nevi seem to have about an 8x increased risk of melanoma, and this increases if there is also a FHx of melanoma.

Charles Balch from MD Anderson discussed surgery for metastatic melanoma. Elective lymph node dissection is still of unproven benefit. Excision of solitary pulmonary nodules can be helpful - up to 1/3 turn out to be something other than melanoma! Excision of solitary or limited skin mets with a 0.5 - 1 cm border can be helpful sometimes, along with excision of solitary nodes. Continuing on this theme, excision of solitary brain and cord mets can improve quality and duration of survival. GI mets are best left alone unless solitary or just a few. Post-op radiotherapy and chemo for mets is not useful.

Dr. Balch also led a discussion of margins: how wide is wide enough? Broadly speaking, it sounds like you want about 1 cm of margin for every mm of depth, to a maximum of 3 cm margin, and it is reasonable to take less margin in some sites to facilitate primary closure. He did not think MOHS offered any survival advantage.

Frank Sim noted that in Holland regional perfusion of mets with TNF is showing promise. He does not do elective node dissection unless there are areas clinically suspicious for mets.

Kerry Olsen noted that desmoplastic MM which make up 1% of head & neck MM have a high potential for local recurrence [they look like sarcomas histologically and behave like them clinically]. He noted that for head & neck MM elective lymph node dissection has led to improved survival, provide prognostic information, and to prevent future head and neck morbidity.

Ed "ET" Creagan/ gave a fine discussion of medical management of MM. It seems that a subset of patients [who we cannot predict] will respond well to biologic response modifiers like IFN and IL-2. DTIC, BCNU, platinum & tamoxifen in combination offers response rates of around 25% but no increased survival. We CAN predict the failures: lost >10% body weight in past 3 months, sedentary >50% of waking hours because of disease, and patients with calorie intake < 1200 / day are and GRAVE risk for treatment-induce complications and have very little chance of benefit. [Another point the managed care folks will like.] Megace, Levamisole, and Tagamet are relatively benign and sometimes useful adjuvant therapies. He strongly suggested a book called Remarkable Recoveries, about unexpected recoveries from various form of Ca. Several of us have it on order.

Larry Gibson's dad Smith Gibson generously donated $100,000 to endow the Louis A. Brunsting Memorial Lecture, and the first lecture was given very appropriately by Harold Perry, who trained under Dr. Brunsting and gave us valuable insights into the man, his times, and his role in the development of dermatology at the Mayo Clinic.

On Sunday 25 patients were presented, and with each case protocol was a color Xerox with 3 clinical photos and / or photomicrographs on it. A very helpful touch - typical of Pat Dahl the DermPath fellow [who got a big round of applause and also spoke very well]. He worked closely with Dan Su and Randy Roegnik to organize that part of the meeting.

Paraneoplastic pemphigus - it was remarked that Dr. Anhalt has recently found that patients with erythema multiforme major and oral lesions precipitate the SAME protein as patients with paraneoplastic pemphigus.

Dermatomyositis associated with infiltrative Gr. 4 ACA of breast responding well to cyclosporine after failing Imuran, prednisone, dapsone, Plaquenil and Atabrine. The patient was very pleased. Cost seems to be the big hangup with cyclosporine - Dr. Charles Dicken and I had a woman with dermatomyositis who did very well on cyclosporine in 1985 - until she ran out of money.

SCLE - Dr. Schroeter remarked that SCLE is a lot like Sjogren's, complete with oral and CNS changes. Responds well to thalidomide sometimes, but fortunately in this case the patient was doing well on Plaquenil. Nobody is enthusiastic about thalidomide, mainly because of the peripheral neuropathies it tends to cause and the cost and discomfort of monitoring for this.

Erosive oral candida - responded well to Diflucan 50 mg / day and resolved almost completely in response to itraconazole 100 - 200 mg / day. Dr. Schroeter remarked that oral LP may in some cases be related to chronic antigenic stimulation - on biopsy the T-cells are predominantly gamma and delta T-8 [memory] cells. Larry Gibson pointed out the value of also checking Hep B & C serology in oral LP.

Lymphomatoid papulosis - I pointed out that I have a patient who has done very well for the past 4-5 years on MTX 2.5 - 5 mg every 3-4 WEEKS; previously needed PUVA 2-3 times a week, flares up badly if MTX stopped.

Granulomatous T-cell lymphoma of the soles - a shocker - best keep on biopsying those "eczemas" and "plantar pustuloses" that don't respond adequately to therapy - some day one of them will be a lymphoma or a skin cancer.

Langerhans cell Histiocytosis [S100 positive but no Birbeck granules on EM] in 52 year old man - poor response to vinblastine and prednisone but EXCELLENT response to a single course of a new purine analog, 2-chlorodeoxyadenosine (2-CDA). This works both on dividing and RESTING cells, and also works for CTCL. Patient was very happy and grateful. Looked great compared with the photo in the protocol.

Dysplastic nevi - Darrel Reigel said no point using Retin-A on dysplastic nevi because it does not work very well, and anyway "you are just shooting the messenger" - dysplastic nevi are mainly just a MARKER for increased risk of melanoma and getting making them fade is not going to reduce the risk of melanoma.

Cutaneous paolyarteritis nodosa - good response to tissue plasminogen activator (tPA), but repeated courses of treatment are needed to maintain benefit. No tachyphlaxis. Coumadin, Vitamin-E 1600 units/day [as anticoagulant], ASA also used. Now on a trial of treatment with cyclosporine.

Plenty of talk over coffee about what sounds like a cold wind blowing through American dermatology. heard that Cigna just laid off 3 derms in Phoenix - derms at a big clinic in Denver have been told to start carrying pagers 24 hours a day, and they have to work nights and weekends sometimes, etc. etc. Mind you, there are quite a few others out there grossing 600 - 700K, and others not making nearly that much but very happy and living a good life.

As always it was a pleasure and an inspiration to visit Rochester and the Mayo Clinic. This was a great meeting in a wonderful, pleasant, well organized atmosphere. An inspiration to all of us.

Several of us remarked that the quality of the current crop of Mayo Derm residents [academic and personal] is so high that we'd have difficulty getting slots there if we were applying now.

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