eMedicine Specialties > Oncology > Carcinomas of the Skin
Lentigo Maligna Melanoma: Treatment & Medication
Updated: Mar 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Various nonsurgical modalities are available to patients in whom surgical therapy is not feasible.
- Cryotherapy is not standard but is often used in patients who are not candidates for surgery.
- Temperatures of -4°C to -7°C selectively destroy melanocytes while preserving keratinocytes in skin and mucosal epithelia.
- The first report of cryotherapy for lentigo maligna was published in 1975.
- Most authors discourage cryotherapy for lentigo maligna because focal lentigo maligna melanoma cannot be detected clinically.
- Risks include hypopigmentation, infection, scarring, inability to detect invasive melanoma, and failure to treat periadnexal involvement.
- Radiation therapy
- Miescher first described radiation therapy in treatment of lentigo maligna in 1954. [Miescher] Others have employed similar techniques with varying results.
- Like cryotherapy, radiation therapy may miss focal lentigo maligna melanoma.
- Topical Imiquimod 5% cream has recently been described in many studies to be effective, especially in patients who are not surgical candidates. Imiquimod is an immune response modifier that is offering encouraging results, but further studies are needed to identify ideal treatment protocols. Buettiker et al, in an open-label study of 34 primary lesions in 32 patients using imiquimod, reported that all were completely cleared. The median time of imiquimod once or twice a day was 7 weeks. Only 1 lesion recurred after 30 months, and this was successfully retreated with imiquimod.10
Surgical Care
Lentigo maligna is treated with definitive surgical therapy. The actual margins of atypia usually extend beyond the clinically apparent margin; total removal may be difficult. National Comprehensive Cancer Network (NCCN) practice guidelines for melanoma in 2006 are as follows (tumor thickness, recommended clinical margin):11
- Tumor in situ, margin 0.5 cm
- Tumor less than 1 mm, margin 1 cm
- Tumor 1-2 mm, margin 1-2 cm
- Tumor 2-4 mm, margin 2 cm
- Tumor >4 mm, margin at least 2 cm
But a study by Agarwal and colleagues in 2002 suggests that 5-mm margins are not sufficient in lentigo maligna, given that only 42% of tumors were cleared after a 5-mm excision in this study.12
- Standard excisions have a recurrence rate of 8-20%. Mohs surgery and staged excision may offer better control and lower recurrence rates (4-5%).13,14,15,16
- Surgical excision with 5-mm margin is often inadequate for lentigo maligna on sun-damaged skin where a background of melanocytic hyperplasia obscure the true borders of the lesion. The cure rate is 80-94%, but staged margin excisions using frozen, or permanent sections, consistently provided much higher cure rates.17
- In a review of using staged excision as treatment of lentigo maligna, this technique provides a long disease-free survival of 95% with follow-up of 57 months. The technique included vertical excision with initial 2- to 3-mm margins examining permanent section within 24 hours. Further excisions took place as guided by the histologic findings.
- Hazan et al studied staged excision of lentigo maligna and lentigo maligna melanoma in the head and neck region of 117 cases. The mean total surgical margin for excision of lentigo maligna was 7.1 mm and was 10.3 mm for lentigo maligna melanoma.18
- Nonsurgical therapies such as cryosurgery, radiotherapy, electrodissection, curettage laser surgery, and topical medications have a recurrence rate of 20-100% at 5 years.
Consultations
Melanoma should be managed by a multidisciplinary team that includes a dermatologist, surgeon, and medical oncologist.
Medication
In the presence of nodal disease, multiple chemotherapy and immunotherapy drugs have been tested. High-dose alpha-interferon remains the standard adjuvant option, especially with stage III cancer, in which it results in a 9-month increase in disease-free survival and a 1-year increase in overall survival. In the presence of metastases, the options include high-dose interleukin-2, dacarbazine, and temozolomide.
Vaccines have been tested in various studies, but none have lead to any significant survival advantage. GM-CSF has been found to prolong time to progression compared to historical control in both node-positive and metastatic stage of the disease.
Biological response modulators
These agents have antiviral, antitumor, and immunomodulatory actions. They are used as adjuvant treatment.
Interferon alfa-2b (Intron A)
Immunotherapy that has been found to improve disease-free survival in most studies but has only been found to improve survival in 2 studies (Eastern Cooperative Oncology Group [ECOG] 1684 and 1694). The drug is quite toxic and patients are often not able to take the whole year of adjuvant treatment.
Adult
20 million U/m2 IV for 5 consecutive d/wk for 4 wk; then 10 million U/m2 SC 3 times/wk for 48 wk
Pediatric
Not established
Potential risk of renal failure when administered concurrently with interleukin-2; theophylline may increase toxicity by reducing clearance; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity
Documented hypersensitivity; patients who have anaphylactic sensitivity to mouse immunoglobulin (IgG), egg protein, or neomycin; autoimmune hepatitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Depression and suicidal ideation may be side effects of treatment; infrequently, severe or fatal GI hemorrhage reported in association with alpha interferon therapy; prior to initiation of therapy, perform tests to quantitate peripheral blood hemoglobin, platelets, granulocytes, hairy cell, and bone marrow hairy cells; monitor periodically (eg, monthly) during treatment to determine response to treatment; if patient does not respond within 6 mo, discontinue treatment; if response occurs, continue treatment until no further improvement observed; not known whether continued treatment after that time is beneficial
Aldesleukin (Proleukin)
Activates T cells and amplifies their responses. Enhances natural killer cells' antitumor activity. Affects tumor growth by activating lymphoid cells in vivo, without affecting tumor proliferation directly.
Adult
600,000-720,000 IU/kg IV q8h for up to 5 d or per protocol
Pediatric
Not established
Corticosteroids may decrease antitumor effect; NSAIDs increase capillary leak syndrome; potentiates effects of antihypertensive medications
Documented hypersensitivity; caution in patients with preexisting cardiac, pulmonary, CNS, hepatic, or renal impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause sepsislike syndrome due to "capillary leak;" other toxicities are flulike syndrome, fever, chills, fatigue, infection, myelosuppression, hepatic toxicity, neurological and neuropsychiatric findings, hypotension, erythema, rash, urticaria, and alteration in thyroid function (including hyperthyroidism and hypothyroidism); high-dose IL-2 has been associated with treatment-related deaths
Antineoplastic agents
These agents inhibit cell growth and proliferation.
Temozolomide (Temodar)
Oral alkylating agent converted to MTIC at physiologic pH; 100% bioavailable; approximately 35% crosses the blood-brain barrier. Indicated for glioblastoma multiforme combined with radiotherapy. Significant overall survival was demonstrated in patients treated with temozolomide and radiation, compared with radiotherapy alone.
Adult
Adjust dose according to nadir neutrophil and platelet counts from previous cycle and at time of initiating next cycle
Concomitant phase: 75 mg/m2/d PO for 42-49 d with concomitant radiotherapy
Maintenance cycle 1: Administer 150 mg/m2/d PO for 5 d followed by 23 d without treatment; initiated 4 wk following concomitant phase completion
Maintenance cycles 2-6: Administer 200 mg/m2/d PO for 5 d; escalate dose from phase 1 only if blood count stable
Pediatric
Not established
None reported
Documented hypersensitivity to temozolomide or DTIC, since each drug is metabolized to MTIC
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Causes bone marrow suppression resulting in thrombocytopenia, anemia, and leukopenia (check blood counts weekly during concomitant phase, then at day 1 and 21 of each cycle); common adverse effects include nausea, vomiting, and alopecia; it is not known if the drug is excreted in breast milk and because of potential serious adverse effects in infants, breastfeeding should be discontinued; PCP prophylaxis required during concomitant phase, continue if lymphocytopenia develops
Dacarbazine (DTIC-Dome)
Cell-cycle phase-nonspecific antineoplastic alkylating agent. Metabolized by cytochrome P450 system to alkylating form. Inhibits DNA replication, RNA transcription, protein synthesis, and nucleic acid function by substituting an alkyl group for a hydrogen ion in various organic compounds, forming covalent linkages with sulfhydryl groups.
Adult
2-4.5 mg/kg/d IV for 10 d; may repeat in 4 k
Alternatively, 250 mg/m2/d IV for 5 d; may repeat in 3 wk
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with bone marrow suppression, renal and/or hepatic impairment; avoid extravasation
More on Lentigo Maligna Melanoma |
| Overview: Lentigo Maligna Melanoma |
| Differential Diagnoses & Workup: Lentigo Maligna Melanoma |
 Treatment & Medication: Lentigo Maligna Melanoma |
| Follow-up: Lentigo Maligna Melanoma |
| References |
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References
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Further Reading
Keywords
skin cancer, skin cancer diagnosis, skin cancer treatment, skin cancer symptoms, malignant melanoma, skin malignancy, cutaneous malignancy, cutaneous melanoma, skin melanoma, cutaneous neoplasm, skin neoplasm, Hutchinson's melanotic freckle, Hutchinson melanotic freckle, freckle cancer, lentigo maligna, LM, lentigo maligna melanoma, LMM, melanoma in-situ, UV light exposure, ultraviolet light exposure, UV radiation exposure, ultraviolet radiation exposure, melanocytic nevus, melanocytic nevi
