This month’s news from across the specialty
What’s hot
October 1, 2024
In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.
How highly hereditable is melanoma? Prior studies have estimated that genetic predisposition is rare, with as few as 2.5% of individuals with melanoma having an inherited germline mutation. This data arose from prior studies on melanoma-predominant families, mostly comprised of CDKN2A carriers. In contrast, a recent Nordic twin study found melanoma to have the highest heritability among all cancers, even higher than breast, ovarian, and colon cancers.
To assess the true incidence of hereditary melanoma, a recent JAAD study performed germline testing for more than 80 cancer predisposition genes on 400 individuals with melanoma and personal or family history of cancers (J Am Acad Dermatol. 2024; 91: 265-72). Germline pathogenic and likely pathogenic variants were identified in 15.3% of individuals and most involved genes that had previously been considered unrelated to melanoma (including BRCA1/2 and Lynch syndrome genes).
The authors thus conclude a high heritability of melanoma and note that identification of an early germline diagnosis can result in diagnosis of secondary primary cancers at earlier stages. Further, the authors propose a more relaxed criteria for testing individuals with melanoma for hereditary predisposition to cancer and recommend that we obtain family history inclusive of all noncutaneous cancers and consider genetics referral for melanomas in any individual.
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We often think of pathology as a black box: A biopsy specimen goes into the bottle and a pathology report returns. In reality, dermatopathology is similar to other forms of medicine. Sometimes the physician is confident of the diagnosis, and in other instances, we offer our best efforts/diagnosis often with some level of doubt.
Difficulty in diagnosis was highlighted in a recent paper that utilized multiple dermatopathologists to evaluate 3,317 melanocytic lesions (J Cutan Pathol. 2024; 51(8): 624-633). After review, 23.8% of the lesions received an equivocal diagnosis, while the remaining were classified as either benign or malignant. In pathology, the use of ancillary special stains may be helpful in these equivocal cases. In a different study, SEER data was used to evaluate the use of immunohistochemistry in the diagnosis of melanoma (JAMA Dermatol. 2024;160(4):434-440). They evaluated more than 132,000 cases of melanoma from 2000 to 2017. In the year 2000, 11% of melanomas were associated with an immunohistochemical billing claim (for example MelanA, SOX10, S100). In contrast 51% of melanomas in 2017 had an immunohistochemical claim. They also noted yearly increases in the intervening years.
The number of available immunohistochemical stains has markedly increased over the years and this study shows increased utilization for the diagnosis of melanoma. Why is this occurring? For many cases, this improves the accuracy of diagnosis: melanoma in situ versus early invasive melanoma, or melanoma versus atypical nevi. This result may also be from fear of litigation, differing trends in training programs, or financial reasons. Closer scrutiny is likely in our future.
A patient was started on hydroxychloroquine. Two weeks later, she developed numerous pustules on top of erythematous patches and plaques. She was seen by the dermatology hospital consult team that concluded that this was not AGEP because the latency period was too long. In a literature search they found an article about a rare skin condition (only 20 published cases): generalized pustular figurate erythema (GPFE) due to hydroxychloroquine (Dermatol Ther. 2020. May;33(3):e13380). The article stated that GPFE is different from AGEP because the latency period is longer, and eruption lasts longer than that of AGEP. The case was then presented at a teaching conference as GPFE, the 21st case in the world. What is the lesson here? Think of horses before thinking of zebras — GPFE is AGEP. In a more recent article on AGEP due to hydroxychloroquine, the authors found that the latency period for hydroxychloroquine-induced AGEP could be up to 25 days, the average being 12 days (doi: 10.3389/fmed.2023.1161837). The average time to resolution was 25 days, longer than the up to 15 days for AGEP induced by a beta-lactam antibiotic.
More What’s Hot!
Check out more What’s Hot columns from the DermWorld Editorial Advisory Workgroup.
Calling it a bad hair day is an understatement. A case series published in 2023 described 26 patients in Israel with severe acute kidney injury (AKI) after undergoing “Brazilian” hair-straightening treatments with products containing glycolic acid derivatives. Kidney biopsies showed acute oxalate nephropathy, which the authors hypothesized was caused by absorption and metabolism of glycolic acid derivatives.
A more recent report from France discussed the case of a previously healthy woman who had three AKI episodes, each one occurring the same day that she underwent hair-straightening treatments with 10% glycoxylic acid that caused burning sensations on application and subsequent scalp ulcers. AKI fortunately resolved rapidly after each episode.
To understand the potential mechanism of AKI, the authors applied the hair-straightening product or control cream to mice. One day after application, elongated calcium oxalate monohydrate crystals, similar to crystals observed following ethylene glycol intoxication, were seen in urinalyses of mice exposed to the hair-straightening product. Those mice also experienced increases in creatinine, and CT scans showed calcium oxalate monohydrate deposits in kidneys. Mice treated with control cream were normal.
The authors concluded that the glycoxylic acid-containing hair-straightening products caused AKI. Glycoxylic acid had been considered safer than potentially carcinogenic formaldehyde-containing hair-straightening products, which FDA has proposed banning. Given the apparent potential of glycoxylic acid-containing hair straighteners to cause AKI, however, the authors recommend that these products be avoided and, preferably, removed from the market.
