seventy-FIFTH issue
December 11, 2024
Merkel cell carcinoma and immunosuppression, UV radiation, and Merkel Cell polyomavirus
JAMA Dermatology
JAMA Dermatology
Shedding “light” on UV radiation and polyomavirus as drivers of Merkel cell carcinoma
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer. Identifying the contribution of modifiable risk factors such as immunosuppressive conditions (e.g., HIV, solid organ transplant, chronic lymphocytic leukemia [CLL]), ambient UV radiation (UVR), and Merkel cell polyomavirus (MCPyV) can inform prevention strategies. This study aimed to quantify the population-attributable fraction of MCC cases in the US related to these major risk factors using data from cancer registries and MCC case series.
What did they find?
Skin cancer is the most commonly diagnosed cancer in the United States. With the emergence of innovative diagnostic tools such as artificial intelligence, tape sampling, and dermoscopy, establishing baseline diagnostic accuracy of current methods is essential for meaningful comparisons of new technologies. Previous studies have assessed the diagnostic accuracy of skin cancers; however, they are often heterogeneous. This systematic review and meta-analysis examines diagnostic accuracy by lesion type, practitioner type, dermatologist experience level, and examination modality.
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer. Identifying the contribution of modifiable risk factors such as immunosuppressive conditions (e.g., HIV, solid organ transplant, chronic lymphocytic leukemia [CLL]), ambient UV radiation (UVR), and Merkel cell polyomavirus (MCPyV) can inform prevention strategies. This study aimed to quantify the population-attributable fraction of MCC cases in the US related to these major risk factors using data from cancer registries and MCC case series.
What did they find?
- MCC incidence was elevated among people with HIV (SIR, 2.78), solid organ transplant recipients (SIR, 13.1), and CLL patients (SIR, 5.75). Despite this, only 2.5% of MCC cases were attributable to these conditions (0.2% to HIV, 1.5% to solid organ transplant, and 0.8% to CLL).
- MCC incidence was strongly associated with UVR exposure, especially in non-Hispanic White individuals. 65.1% of MCC cases were attributable to ambient UVR exposure.
- Based on a meta-analysis, 63.8% of MCC cases were attributable to MCPyV.
- Incidence rates were higher in non-Hispanic White populations compared to other racial/ethnic groups.
Skin cancer is the most commonly diagnosed cancer in the United States. With the emergence of innovative diagnostic tools such as artificial intelligence, tape sampling, and dermoscopy, establishing baseline diagnostic accuracy of current methods is essential for meaningful comparisons of new technologies. Previous studies have assessed the diagnostic accuracy of skin cancers; however, they are often heterogeneous. This systematic review and meta-analysis examines diagnostic accuracy by lesion type, practitioner type, dermatologist experience level, and examination modality.
Keratinocyte carcinomas in survivors of childhood cancer: A report from the childhood cancer survivor study
Journal of the American Academy of Dermatology
Journal of the American Academy of Dermatology
Small patients, big risks: investigating factors contributing to childhood skin cancer
Basal cell and squamous cell carcinoma (BCC and SCC), categorized as keratinocyte carcinomas (KCs), are the most common neoplasms in childhood cancer survivors (CCSs). Established risk factors for KCs in CCSs include ionizing radiation therapy, hematopoietic stem cell transplantation, and cancer- and treatment-related immunosuppression. This study utilized data from the Childhood Cancer Survivor Study to examine KC incidence and associated risk factors in CCSs.
What did they find?
Main Takeaway: Among childhood cancer survivors, there is an increased risk of multiple KC lesions, while a history of radiation therapy and hematopoietic stem cell transplantation confers an increased KC risk. These findings can inform targeted screening practices and recommendations.
Basal cell and squamous cell carcinoma (BCC and SCC), categorized as keratinocyte carcinomas (KCs), are the most common neoplasms in childhood cancer survivors (CCSs). Established risk factors for KCs in CCSs include ionizing radiation therapy, hematopoietic stem cell transplantation, and cancer- and treatment-related immunosuppression. This study utilized data from the Childhood Cancer Survivor Study to examine KC incidence and associated risk factors in CCSs.
What did they find?
- 5.64% of the cohort (n=25,658) developed a total of 5,363 KCs, most commonly BCC (93.5%), followed by SCC (6.7%).
- The cumulative incidence of KC was 1.5% (95% CI 1.3-1.6) at 20 years after cancer diagnosis, while those exposed to radiation therapy had a 2.6% (CI 2.3-2.9) 20-year cumulative incidence.
- Participants developed a mean of 3.7 KCs (range 1-182), with 26.1% developing ≥ 4 KCs.
- Higher rates of KC were associated with radiotherapy (RR 4.5, CI 3.5-5.9), allogeneic (RR 3.4, CI 2.4-4.8) and autologous (RR 2.3, CI 1.2-4.2) hematopoietic stem cell transplants. Radiotherapy was the strongest risk factor for developing ≥ 4 KCs (RR 9.4, CI 5.0-16.9).
- Lower rates of KC were associated with the highest cumulative doses of anthracyclines (RR 0.7, CI 0.6-0.8) and epipodophyllotoxins (RR 0.5, CI 0.3-0.9).
Main Takeaway: Among childhood cancer survivors, there is an increased risk of multiple KC lesions, while a history of radiation therapy and hematopoietic stem cell transplantation confers an increased KC risk. These findings can inform targeted screening practices and recommendations.
The role of PRAME in melanoma progression
Journal of Investigative Dermatology
Journal of Investigative Dermatology
Is PRAME to blame?
The mechanisms driving melanoma progression remain largely unknown. Recent studies suggest melanoma tumor cells communicate with surrounding cells by releasing extracellular vesicles (EVs). PRAME (Preferentially Expressed Antigen in Melanoma) is a cancer-testis antigen that promotes tumor cell proliferation and survival. In this study, researchers investigated whether melanoma-derived EVs contain PRAME and if these EVs transmit oncogenic signals to primary melanocytes, potentially promoting tumor-supportive phenotypes.
What did they find?
Main Takeaway: PRAME plays a significant role in melanoma progression and survival. Researchers found that PRAME can influence primary melanocytes by releasing melanoma EVs, promoting tumor growth. Targeting PRAME via these pathways could be a potential therapy to inhibit melanoma progression.
The mechanisms driving melanoma progression remain largely unknown. Recent studies suggest melanoma tumor cells communicate with surrounding cells by releasing extracellular vesicles (EVs). PRAME (Preferentially Expressed Antigen in Melanoma) is a cancer-testis antigen that promotes tumor cell proliferation and survival. In this study, researchers investigated whether melanoma-derived EVs contain PRAME and if these EVs transmit oncogenic signals to primary melanocytes, potentially promoting tumor-supportive phenotypes.
What did they find?
- PRAME protein was highly expressed in melanoma cells and absent in primary melanocytes.
- PRAME proteins were detected in melanoma-derived extracellular vesicles.
- When normal melanocytes were exposed to EVs from melanoma cells containing PRAME with enhanced green fluorescence protein, they absorbed PRAME, which was found in the cytoplasm and nucleus of the recipient melanocyte.
- When one PRAME allele was deleted using CRISPR, the melanoma cells proliferated slower than wild-type cells with two PRAME alleles. (P<0.001).
Main Takeaway: PRAME plays a significant role in melanoma progression and survival. Researchers found that PRAME can influence primary melanocytes by releasing melanoma EVs, promoting tumor growth. Targeting PRAME via these pathways could be a potential therapy to inhibit melanoma progression.
Immunohistochemistry for immunoglobulin G4 on paraffin sections as a diagnostic test for pemphigus
Dermatopathology
Dermatopathology
IgG 4 the win
Pemphigus is a group of autoimmune blistering diseases characterized by IgG autoantibodies against desmosomal adhesion proteins in the skin. Previous studies suggest that IgG4 is the predominant pathogenic antibody in pemphigus. Direct immunofluorescence is the gold standard in diagnosing pemphigus; however, this method requires special equipment. In this study, researchers compared IgG4 immunoreactivity in tissue biopsies of active lesions from pemphigus patients (n=50) and non-pemphigus control patients (n=50).
What did they find?
Main Takeaways: Immunohistochemical examination of IgG4 is a potential tool to diagnose pemphigus in tissue biopsies of active lesions when direct immunofluorescence is unavailable.
Pemphigus is a group of autoimmune blistering diseases characterized by IgG autoantibodies against desmosomal adhesion proteins in the skin. Previous studies suggest that IgG4 is the predominant pathogenic antibody in pemphigus. Direct immunofluorescence is the gold standard in diagnosing pemphigus; however, this method requires special equipment. In this study, researchers compared IgG4 immunoreactivity in tissue biopsies of active lesions from pemphigus patients (n=50) and non-pemphigus control patients (n=50).
What did they find?
- 48 (86%) of the pemphigus samples showed immunoreactivity to IgG4
- Immunoreactivity to IgG4 was negative in 45 (90%) of the control samples
- 5 (10%) of the controls with bullous pemphigoid were immunoreactive to IgG4
- IgG4 immunoreactivity as a diagnostic test for pemphigus has a sensitivity of 98% and specificity of 90%
Main Takeaways: Immunohistochemical examination of IgG4 is a potential tool to diagnose pemphigus in tissue biopsies of active lesions when direct immunofluorescence is unavailable.
Plant extracts show anti-hair loss properties in human in vitro and ex vivo models
Journal of Cosmetic Dermatology
Journal of Cosmetic Dermatology
A new elixir as a hair fixer!
Hair loss arises from disrupted hair cycle phases, significantly affects quality of life, and remains challenging to treat, prompting exploration of cosmetic active ingredients to promote growth. This study evaluated the effects of Silybum marianum extract (SME), manganese PCA (MnPCA), and Lespedeza capitata extract (LCE) on hair growth markers in human follicle dermal papilla cells (HFDPCs) by analyzing receptor tyrosine kinase phosphorylation, Wnt/β-catenin pathway activation, versican, VEGF, DKK1 secretion, and 5α-reductase activity. Hair growth improvement was further assessed using ex vivo human scalp biopsies by measuring hair shaft elongation, keratinocyte proliferation/apoptosis, and HF cycle stage and score.
What did they find?
Main Takeaway: The combination of plant extracts demonstrated synergistic anti-hair loss properties, suggesting that a serum incorporating these ingredients could be an effective treatment for hair loss.
Hair loss arises from disrupted hair cycle phases, significantly affects quality of life, and remains challenging to treat, prompting exploration of cosmetic active ingredients to promote growth. This study evaluated the effects of Silybum marianum extract (SME), manganese PCA (MnPCA), and Lespedeza capitata extract (LCE) on hair growth markers in human follicle dermal papilla cells (HFDPCs) by analyzing receptor tyrosine kinase phosphorylation, Wnt/β-catenin pathway activation, versican, VEGF, DKK1 secretion, and 5α-reductase activity. Hair growth improvement was further assessed using ex vivo human scalp biopsies by measuring hair shaft elongation, keratinocyte proliferation/apoptosis, and HF cycle stage and score.
What did they find?
- MnPCA treatment at a dose of 0.009% stimulated the Wnt/β-catenin pathway in HFDPCs by up to 80% (P < 0.05) compared to untreated controls.
- DKK1 levels in the culture medium were 72% lower in 0.001% LCE-treated HDFPCs than in untreated cells (P < 0.01).
- Elongation of the hair shaft was 2.0-fold greater in scalp skin samples treated 4 days with the study serum than in untreated controls (P < 0.001).
- After 5 days of treatment, the study serum led to significant stimulation of hair matrix keratinocyte proliferation compared to the untreated control.
Main Takeaway: The combination of plant extracts demonstrated synergistic anti-hair loss properties, suggesting that a serum incorporating these ingredients could be an effective treatment for hair loss.
Is Dr. Google helping or hurting patients with Hidradenitis Suppurativa?
Journal of Dermatologic Surgery
Journal of Dermatologic Surgery
When your “rash” search leads to more confusion than clarity, who do you trust—Google or your doctor?
Patients with Hidradenitis Suppurativa (HS) often rely on online searches to understand their condition. A systematic evaluation of 95 websites was conducted to assess the quality of online information available to patients with HS. Researchers used popular search engines--Google, Yahoo, and Bing—and evaluated the top results using the Ensuring Quality Information for Patients (EQIP) instrument. Websites were rated based on content accuracy, readability, and inclusion of key patient-centric information. The aim was to determine how accessible and reliable this information is for patients seeking to better understand their condition.
What did they find?
Main Takeaway: Patients with HS face significant challenges in finding high-quality, reliable online information, emphasizing the need for healthcare providers to guide patients toward trusted resources.
Patients with Hidradenitis Suppurativa (HS) often rely on online searches to understand their condition. A systematic evaluation of 95 websites was conducted to assess the quality of online information available to patients with HS. Researchers used popular search engines--Google, Yahoo, and Bing—and evaluated the top results using the Ensuring Quality Information for Patients (EQIP) instrument. Websites were rated based on content accuracy, readability, and inclusion of key patient-centric information. The aim was to determine how accessible and reliable this information is for patients seeking to better understand their condition.
What did they find?
- Only 26.3% of websites achieved high EQIP scores, with none scoring the maximum 36 points.
- Many websites failed to include critical treatment risks (76.8%) or quantify these risks (94.7%).
- Websites from news services generally outperformed those from hospitals, industries, or academic centers in content quality.
- Popularity (measured by website traffic) was not linked to higher-quality information.
Main Takeaway: Patients with HS face significant challenges in finding high-quality, reliable online information, emphasizing the need for healthcare providers to guide patients toward trusted resources.
Geographic barriers to dermatology access for American Indian/Alaskan Native communities
Skin of Color
Skin of Color
Are rural communities left behind in dermatologic care? Looks like it's time for a little more support
Access to dermatology remains a significant challenge for American Indian/Alaskan Native (AIAN) populations, largely due to their rural locations and socioeconomic factors. This geospatial study highlights the vast distances and travel times many AIAN community members face to reach board-certified dermatologists, especially those from reservations with elevated poverty rates.
What did they find?
Access to dermatology remains a significant challenge for American Indian/Alaskan Native (AIAN) populations, largely due to their rural locations and socioeconomic factors. This geospatial study highlights the vast distances and travel times many AIAN community members face to reach board-certified dermatologists, especially those from reservations with elevated poverty rates.
What did they find?
- Reservations with poverty rates below the national average (12.8%) had a median travel distance of 18.08 miles and a travel time of 22.78 minutes.
- In contrast, reservations with poverty rates above the national average faced a median travel distance of 34.70 miles and a travel time of 43.80 minutes, nearly double those of lower-poverty areas.
- The study revealed significant disparities in healthcare access that align closely with poverty levels.
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