Treating Rare Skin Cancers


The importance of accurate diagnosis and adjuvant radiation in treatment success. Research discussed at recent medical conferences offered insights to practitioners treating elderly patients with rare forms of skin cancer. Patients with Merkel cell carcinoma, the most aggressive form of skin cancer, do better when given radiation therapy, research suggested, as do those patients with melanoma. Those with the rare and usually indolent skin lymphoma mycosis fungoides, on the other hand, can benefit when physicians and pathologists use a form of cell examination known as blood flow cytometry. In all these cases, early and correct diagnosis can affect treatment, contributing to better results, the research showed. The import for the practicing physician: Specialization in skin diseases is helpful. The Deadliest Skin Cancer The most aggressive known form of skin cancer, Merkel cell carcinoma, is especially vulnerable to radiation, according to research presented at this year’s annual meeting of the American Society for Therapeutic Radiation Oncology (ASTRO) in Chicago. The upshot for practitioners: Learn how to recognize Merkel cell carcinoma, and consider radiation as a treatment for those patients with the disease. While Merkel cell carcinoma does have a characteristic clinical appearance, that won’t help the average general practitioner recognize the disease, according to Michael Poulsen, MD, who co-authored a study on the disease presented at ASTRO. “The average general practitioner won’t see one of these in their lifetime, because the vast majority are diagnosed at the time they are excised,” explains Dr. Poulsen, professor of radiation oncology in the department of surgery at Queensland Health Service in Brisbane, Australia. “Typically, the disease occurs as a red or violaceous papule on the skin, which may have some features of an atypical melanoma and some features of a basal cell carcinoma,” says Mathew Foote, MD, the lead author on the poster. “However, basal cell disease is more like a reddish, pearly papule, shiny, round and raised, and in comparison to melanoma, Merkel cell disease would have a much more rapid growth,” adds Dr. Foote, who is also a clinical fellow at Princess Margaret Hospital in Toronto. “Only a pathologist can give a confident diagnosis,” explains Dr. Poulsen. “Not that many malignant skin lesions have that characteristic red or violaceous color, and on staining, the cells are actually quite small in diameter, with lots of cells in active growth and lots of myotic bodies. In particular, the cytokeratin 2 stain is quite helpful in diagnosis.” Diagnosis is important, because patients with Merkel cell disease need either an aggressive surgical approach or radiotherapy, Dr. Poulsen explains. Merkel cell disease is 100 times less common than melanoma, but in the last decade, incidence has tripled from 0.15 per 100,000 to 0.44 per 100,000. The disease is fatal in about half of those who get it. While the disease is usually found in Caucasian men in their 70s in sun-exposed areas around the equator, there are cases of it in people in their 30s and 40s, which may offer some clue to its effective treatment. Interestingly, infection with the polyoma virus may explain why some who get the disease are a little bit younger. According to Dr. Poulsen, “Eighty to 90% of people have some exposure to the polyoma virus by the age of 12, but those who test positive for the virus have a 45% chance of surviving Merkel cell cancer, compared to 13% of those who test negative for the virus. The genetic makeup of the virus makes Merkel cell carcinoma more prone to the effects of radiation.” The poster1 at ASTRO reported on 112 Merkel cell patients given radiotherapy. Patients who had radiotherapy to the nodal basin experienced a relapse rate of 11%, compared to about 20% for those who didn’t have the nodes treated. A Rare Disease with an Unusual Nature Another rare form of skin cancer is mycosis fungoides, diagnosis of which is made difficult because of the chronic nature of the disease as well as its rarity. Although the disease becomes life-threatening in only about 5% of those who get it, use of specialized diagnostic techniques is necessary to diagnose it so the disease can be monitored. About 1 in 300,000 people are diagnosed yearly with the skin lymphoma mycosis fungoides, according to Frank Parker, MD, professor of dermatology at Oregon Health and Science University in Portland. The disease makes up about half the cases of T-cell lymphomas that can affect the skin, such as lymphomatoid papulosis (which can be a precursor of mycosis fungoides) and anaplastic large cell lymphoma. The disease is difficult to diagnose at times because of its chronic nature and because the affected skin can resemble a rash or other relatively benign skin diseases. “Some of these patients have 20 or 40 years of pre-existing skin rash that can look like eczema or even psoriasis and eventually turn into mycosis fungoides,” Dr. Parker says. “One of the theories is that some environmental substance stimulates this inflammation of the lymphocytes for 20 or 40 years, and people speculate that it is this constant stimulation that is benign, but eventually out of constant stimulation these lymphocytes turn malignant.” While the form of cancer is not especially aggressive, doctors should be aware of some signs that suggest a case may be malignant. “If more than 10% of the skin is involved with mycosis fungoides, that’s a sign you might be headed for trouble. Or, if some of the lesions are big lumps or ulcerate, that’s a sign things could be going bad internally, or if you do a physical exam and find enlarged lymph nodes, or especially if they have an enlarged liver or spleen, it makes you much more likely to be worried about circulating malignant cells,” Dr. Parker says. The solution: specialized diagnostic techniques, such as the early use of blood flow cytometry to correctly diagnose the disease. (A poster presented at this year’s annual meeting of the American Society for Clinical Pathology used blood flow cytometry to improve accuracy in diagnosis, as well as shed light on the etiology of mycosis fungoides.) “For a general practitioner, generally speaking, if the condition appears to be eczema, it might not be a bad idea to at least have a dermatologist check it out, as dermatologists are trained to recognize mycosis fungoides. Skin changes can take a wide range of configurations, and it really takes someone who has studied 2 or 4 extra years to pick some of these up. Go for the lesions that are thickest and most advanced,” Dr. Parker suggests. “It may take several biopsies taken from several different areas to make the diagnosis early on.” Alternatives to Chemotherapy for Melanoma Patients Meanwhile, melanoma, being the most common skin cancer, happens to be a disease for which no really satisfactory chemical treatment exists, at least in its advanced stages. A poster2 presented at this year’s ASTRO meeting explained that radiation may help some of these patients, at least with management. “At the moment, 50% of those patients with the high-risk type of melanoma get radiation therapy,” says Bryan Burmeister, MD, director of radiation oncology at Princess Alexandra Hospital, Brisbane, Australia, lead author on the poster, “Adjuvant Radiotherapy Improves Regional (Lymph Node Field) Control in Melanoma Patients after Lymphadenectomy: Results of an Intergroup Randomized Trial.” Prognosis for the disease is poor, with 60% developing distant second secondary metastasis within 3 years, and 80% of recurrences occurring within 12 months, Dr. Burmeister says. In addition to contributing to local management and quality of life, radiation therapy is also a cost measure. “Surgery in our country costs 20,000 Australian dollars per patient, and is associated with considerable morbidity, plus a week in the hospital,” he explains. The study examined 250 patients randomized to receive either radiation therapy or observation. By the close of the trial, the study included 217 patients from 16 centers, with a median follow-up of 27 months; 109 received radiation while 108 received observation, the poster reported. The poster found a statistically significant improvement in lymph node field control with radiotherapy, with 20 radiation patients compared to 34 patients in the observation arm relapsing regionally. While radiotherapy is not a gold standard for melanoma patients, it appeared to benefit some patients, Dr. Burmeister says. “While opponents cite an absence of Phase III data, radiation improves regional control in the lymph node basin, which has an impact on patient quality of life, if patients do recur,” Dr. Burmeister explains. Additionally, regional control is much easier to measure in clinical trials, as a trial needs to enroll thousands of patients to measure survival, he adds. While there was no difference in overall or relapse-free survival between groups, those with radiation still benefitted, Dr. Burmeister says. “Radiation can’t be used to cure people with metastatic disease because it is impossible to treat all the metastases at once, but it is very useful for the palliation of brain or bone metastases and it can be very useful in relieving the symptoms from those conditions.”