Dr. Ashfaq A. Marghoob
WAIKOLOA, HAWAII – Nodular melanoma is one of a handful of morphologic subtypes of melanoma that are difficult to diagnose in a timely way because they lack the conventional features associated with melanoma. But certain clinical and dermoscopic clues are helpful in avoiding misdiagnosis, Dr. Ashfaq A. Marghoob said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.
He provided tips on how to recognize nodular melanoma and other difficult-to-diagnose morphologic subtypes, including desmoplastic, amelanotic, nevoid, and epidermotropic metastatic melanoma.
These diagnostically challenging melanoma subtypes have several things in common: clinically, they don't look like melanomas, and dermoscopically, they display specific tell-tale features that speak of malignancy, including atypical polymorphous blood vessels and crystalline structures. Dermoscopy can be a big help in deciding whether to biopsy a clinically unremarkable-looking lesion, observed Dr. Marghoobof Memorial Sloan Kettering Cancer Center in New York.
Here's the rundown on how to avoid delayed diagnosis of these melanomas:
Nodular melanoma: The big challenge posed by nodular melanoma is that it grows at a very high rate, a median of 0.5 mm per month, "so it's really not a subtype of melanoma that's amenable to screening," the dermatologist said.
"Think about this: A patient comes in for screening today and you see nothing on their skin. Then a month from today they start a nodular melanoma. Their next appointment with you is a year from now. By the time they come back, that nodular melanoma is going to be a life-threatening cancer," he explained. "It requires patient engagement in self-examination to bring these lesions to our attention, and we have to be perceptive enough to see these patients in a timely manner when they call. Otherwise these are melanomas that are really the killer tumors."
Nodular melanomas often lack the "ABCD" features associated with most melanomas: asymmetry, border irregularity, color, and diameter greater than one-quarter of an inch. Instead, the lesions may exhibit the modified ABCDs described in pediatric melanoma: amelanotic, bump showing symmetry, color homogeneity in a shade of either pink or blue-black, and de novo, meaning the lesion didn't arise in association with a nevus, Dr. Marghoob continued.
Roughly 60% of nodular melanomas are pigmented, the other 40% amelanotic. Dermoscopically, pigmented nodular melanomas are characterized by a greater degree of symmetry than that seen with other melanomas. Atypical vessels that exhibit tortuosity, a cork screw pattern, or an irregular hairpin shape are prominently visible. The lesions are multicolored, often blue-black, and may exhibit a blue-white veil. Notably absent are regression structures, streaks, and networks.
An amelanotic nodular melanoma also features prominent atypical vessels, symmetry, and sometimes crystalline structures, which appear as shiny white lines. Comma vessels and arborizing vessels are absent.
A more detailed description of the dermoscopic findings in nodular melanoma is available in a study coauthored by Dr. Marghoob (JAMA Dermatol. 2013;149[6]:699-709).
Desmoplastic melanoma: Seventy percent of desmoplastic melanomas are amelanotic. They often present as an unremarkable firm subcutaneous papule or nodule. Indeed, desmoplastic melanomas often have such a banal clinical appearance that in one-third of cases, melanoma is not even in the differential diagnosis.
"You're thinking cyst, lipoma, dermatofibroma ... something other than a malignancy," Dr. Marghoob said.
Suspicion is raised by a benign-looking lesion that's symptomatic and/or exhibiting growth on chronically sun-damaged skin in an older patient. A scar with no history of trauma that's located on chronically sun-damaged skin is another tipoff. Also, desmoplastic melanoma can arise in association with a lentigo maligna component.
"It is this knowledge of the association between lentigo maligna and desmoplastic melanoma that for the first time has enabled us to diagnose desmoplastic melanomas that are thin – not 5 or 10 mm, but more like 0.6 mm in thickness," Dr. Marghoob said.
The main dermoscopic clue is the presence of atypical vascular structures.
For a fuller account of the dermoscopic characteristics of desmoplastic melanomas, Dr. Marghoob recommended a study he coauthored (JAMA Dermatol. 2013;149[4]:413-21).
Amelanotic melanoma: An indication of how difficult these cancers are to diagnose was provided by the international Genes, Environment, and Melanoma Study of nearly 3,500 invasive melanomas, 8% of which were amelanotic. They were at a more advanced tumor stage at diagnosis. As a result, the mortality risk during a median 7.6 years of follow-up was an adjusted twofold greater for patients with amelanotic as compared with pigmented melanomas (JAMA Dermatol. 2014;150[12]:1306-314).
Dr. Marghoob coauthored a retrospective review of 20 consecutively diagnosed amelanotic melanomas. The lesions lacked any of the classic ABCD features. Most were symmetric, oval to round in shape, had regular borders, and were pink in color. Dermoscopically, a consistent finding was a polymorphous vascular pattern (J Eur Acad Dermatol Venereol. 2012;26[5]:591-6).
In an earlier five-continent study comparing dermoscopic features of 222 amelanotic melanomas, 105 pigmented melanomas, and 170 benign melanocytic lesions, investigators came up with a simple model that distinguished melanomas from nonmelanomas with 70% sensitivity and 56% specificity. The take-home message: Amelanotic melanomas often feature more than one shade of pink upon dermoscopic examination, along with dotted and linear irregular vessels and predominant central vessels (Arch Dermatol. 2008;144[9]:1120-7).
Nevoid melanoma: Clinically they often resemble an intradermal nevus, and they're often amelanotic. Dermoscopically, however, an intradermal nevus displays a mammillated surface, with each individual mammillated area being associated with an isolated comma or hairpin vessel. In contrast, the surface of a nevoid melanoma is more undulating in appearance and lacks the classic vascular pattern seen in intradermal nevi. If there's pigmentation present in a nevoid melanoma it will be distributed heterogeneously. The dermoscopic finding of irregular blood vessels and/or crystalline structures tips the balance in favor of biopsy.
Dr. Marghoob referred dermatologists interested in the dermoscopic features of nevoid melanoma to a recent study by members of the International Dermoscopy Society; he was one of the authors (Br J Dermatol. 2015;172[4]:961-7).
Epidermotropic metastatic melanoma: These lesions lack the ABCDs, are often amelanotic, and look like nondescript papules. If such a lesion is new, especially in a patient with a history of melanoma, think epidermotropic metastatic melanoma.
Spanish dermatologists have described five different dermoscopic patterns of melanoma metastases in an informative retrospective study: blue nevus-like, angioma-like, nevus-like, vascular, and unspecific. The vascular type is the most common form, characterized by amelanotic papules 2-3 mm in diameter and tortuous corkscrew vessels within the lesions (Br J Dermatol. 2013;169[1]:91-9).
Dr. Marghoob reported having no financial conflicts of interest regarding his presentation. SDEF and this news organization are owned by the same parent company.
Dermatology
Adherence to Biologics
Making the diagnosis of psoriasis is not difficult for dermatologists. Now that we have biologic treatments, finding an effective treatment for even horrific psoriasis is not difficult, either. But a key issue we now face is how long that biologic treatment will last. Patients may do well on biologic treatment for a time, but too often the great results don't last.
The Outcome and Retention Rate of Biologic Treatments for Psoriasis (ORBIT) study gives us some quantitative information on how long patients persist on treatment.1 After about 2 to 3 years, half of the patients on a biologic stop that particular treatment. Obese patients tended to come off faster, although that finding was not observed in a much larger trial, PSOLAR,2 which also looked at treatment persistence. In both studies, patients on ustekinumab stayed on treatment longer than on TNF inhibitors.
Why do people stop treatment? Mostly it is because either the drug stopped working or because it never worked in the first place. Adverse events are a much less common reason for patients to stop a biologic treatment.
What can we do about poor persistence? First, making sure that patients take their medication regularly may help. Second, giving a biologic with methotrexate potentially could reduce formation of antibodies that reduce a biologic's effectiveness. Finally, and perhaps most importantly, we ought to feel comfortable with all of the available options because there's a very good chance that even if we get patients well with one biologic, someday they may need another.
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