Life is just a bowl of cherry angiomas

By Warren R. Heymann, MD
May 29, 2019
Vol. 1, No. 13

“Dr. Heymann, I’ve noticed a number of these spots appearing lately.”

“They’re called cherry angiomas — totally benign.”

“Why I am getting them?”

“Maturity.”

“You mean I’m getting old!”

“I did not say that — you did!”

“I don’t like them. Can you take them off?”

“Easily, especially with the laser. It would be considered a cosmetic procedure.”

“You mean Medicare won’t pay for it?”

“Correct.”

“Forget it — I’ll live with them.”

I imagine this conversation occurs daily in every dermatologist’s office. Of all the cutaneous entities I have never thought much about, cherry angiomas (CAs, aka senile angioma, Campbell de Morgan spot) top the list.
It is high time to take a fresh look at these common lesions and ask pertinent questions — notably what are they and why do they appear?

The following is the entry on CAs from the Andrews textbook (1):

These round, slightly elevated, ruby-red papules 0.5–6 mm in diameter are the most common vascular anomalies. It is a rare 30-year-old person who does not have a few, and the number increases with age. Probably every 70-year-old person has some senile angiomas. Most are on the trunk; they are rarely seen on the hands, feet, or face. Early lesions may mimic petechiae. When lesions are surrounded by a purpuric halo, amyloidosis should be suspected. Eruptive lesions have been described after nitrogen mustard therapy. Light electrodesiccation or laser ablation with intense pulsed light (IPL) and long-pulse Nd : YAG laser systems can be effective. Shave excision can also be performed, but most patients accept reassurance and do not request removal.

In a meticulous study of 488 patients who were at least 40 years old, having at least one truncal CA, Fettahlioglu Karaman observed a pale halo around CAs in 5.1% of the patients or in 2.0% of the lesions. It was more prevalent in patients aged 60 years or older with more than 4 lesions, being more frequent around lesions larger than 3 mm. (2) I am not sure if I have ever noticed these haloes, or, if so, just ignored them. It remains to be determined if haloes are associated with the evolution of CAs. 

Histologically, CAs are circumscribed vascular proliferations of venule-like blood vessels in a thickened papillary dermis. In a study of 23 lesions, Fernandez-Flores and Colmenero demonstrated that all cases showed intense expression of Wilms tumor protein 1 (WT1) in 80-100% of endothelial cells. WT1 is expressed by “actively growing” endothelia, either tumoral or reactive. Additionally, Ki67 staining displayed proliferation by the endothelia in all lesions. These findings support the theory that CAs are either vascular tumors, or reactive vascular proliferations, but not vascular malformations. (3)

Other findings challenge that conclusion. Klebanov et al sequenced 323 cancer-relevant genes in 10 CAs from 6 women and 4 men, with a median age of 54 years. Five samples (50%) revealed somatic missense mutations in GNAQ and GNA11. Individually, these mutational hot spots are known to be involved in entities that include congenital and anastomosing hemangiomas, hepatic small-vessel neoplasms (Q209), port-wine stains, and Sturge-Weber syndrome (R183). Both hot spots are associated with blue nevi, melanoma associated with blue nevus, and uveal melanoma. The authors suggest that these mutations may lead to aberrations in vessel formation rather than endothelial proliferation. Additionally, these findings could help explain the panoply of features observed in phakomatosis pigmentovascularis. (4) In an accompanying editorial, Siegel notes that the GNAQ and GNA11 mutations in CAs demonstrate how we continually acquire somatic mutations throughout life, confirming that humans are mosaics. (5)

Perhaps both mosaic mutations and a proliferative component are involved. Could angiogenic factors be at play? In a captivating article, Darjani et al performed a case-control study of 122 cases with CAs and 122 control subjects without CAs. Demographic characteristics, number of CAs, and serum lipid profile were collected for all subjects. Mean levels of the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were higher in patients with CAs compared to control subjects in which differences were significant for total cholesterol, low-density lipoprotein, and triglyceride (P < 0.05) but not for high-density lipoprotein level. The authors hypothesized that CAs may form in response to angiogenic agents that were elaborated to compensate for the occlusive effects of atherogenic agents. (6) Although I do not plan on checking a lipoprotein profile in every patient with CAs, this is an intriguing study that warrants further exploration. 

The lyrics “Life is just a bowl of cherries. Don’t take it serious; it’s too mysterious” could easily be applied to CAs. Clinically, they are not serious, but understanding their pathophysiology remains a mystery. As we learn more about the genetics and molecular pathway(s) to their appearance, novel topical therapies, akin to rapamycin for angiofibromas, could be in the offing. 

Point to remember: Although cherry angiomas appear when we get older and wiser, our knowledge about their pathogenesis is in its infancy.

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Our expert’s commentary

Jason B. Lee, MD
Clinical Vice Chair
Director, Jefferson Dermatopathology Center
Director, Residency and Dermatopathology Fellowship
Director, Jefferson Pigmented Lesion Clinic
Jefferson University Hospitals

In his current commentary, Dr. Heymann reflects on how little we know about a commonly encountered vascular lesion, namely cherry angioma. The same can be said of seborrheic keratosis, another frequently confronted lesion that we know very little about its underlying pathogenesis. Dr. Heymann, in his usual incisive and playful way, highlights 4 small studies on cherry angiomas and their relevance to our clinical practice. The study by Karaman will now make me look for a subtle halo around each cherry angioma. In the rare instances in which I observed a halo, I just assumed the phenomenon was because of a compensatory vasoconstrictive effect, nothing more. Fernandez-Flores and Colmenero affirm my view that a cherry angioma is a benign vascular neoplasm, never thought otherwise. I do not believe they are a marker of hyperlipidemic state as Durjani et al. suggest.

In my clinical practice, I have only observed an association with pregnancy on rare occasions. Though I am not as optimistic as Dr. Heymann that someday we might come up with a topical therapy for cherry angiomas by understanding the genetic basis of the proliferative process, I welcome the genetic studies on such a common banal entity. I have always asked why basic scientists often gravitate toward studying rare conditions. I understand that the idea is to apply the knowledge learned from studying the rare conditions to more common ones. Why not study the common conditions and attempt to apply the knowledge to the rare ones? By understanding the underpinning genetic basis of the proliferative process in cherry angiomas, additional insight may be gained in other rarer proliferative vascular processes, both benign and malignant such as glomeruloid hemangioma, hemangioendotheliomas, and angiosarcomas. Contrary to the suggestion by Klebanov et al. that cherry angiomas are rarely sampled, they are not infrequently removed for diagnostic and therapeutic reasons, being mistaken for pyogenic granuloma when traumatized. There are plenty of paraffin-embedded blocks of cherry angiomas in our dermatopathology laboratory for the next generation of studies.

1. James WD, et al (eds). Andrews’ Diseases of the Skin, 12th edition. Elsevier, 2015, pp 590. 
2. Fettahlioglu Karaman B. Halo formation around cherry angiomas: A rare but substantial finding. Med Sci Monit 2018 Jul 20; 24: 5050-5053. 
3. Fernandez-Flores A, Colmenero I. Campbell de Morgan spots (cherry angiomas) show endothelial proliferation. Am J Dermatopathol 2018; 40: 894-898).
4. Klebanov N, Lin WM, Artomov M, Shaughnessy M, et al. Use of targeted next-generation sequencing to identify activating hot spot mutations in cherry angiomas. JAMA Dermatol 2019; Jan 2 [Epub ahead of print].
5. Siegel DH. Cherry angiomas- further expanding the phenotype with somatic GNAQ and GNA11 mutations. JAMA Dermatol 2019; Jan 2 [Epub ahead of print].
6. Durjani A, Rafiei R, Shafaei S, Rafiei E, et al. Evaluation of lipid profile in patients with cherry angioma. Dermatol Res Pract 2018; May 13;2018:4639248.

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