AESOP: The ants and the grasshopper

By Warren R. Heymann, MD, FAAD
Aug. 21, 2024
Vol. 6, No. 34

Unquestionably, AESOP (Adenopathy and Extensive Skin patch Overlying a Plasmactyoma) is rare — to date, fewer than 25 cases have been reported. (1) Why write (or read) a commentary about AESOP when it is unlikely we will ever encounter a case? There are at least two valid reasons: 1) Because of its distinctive appearance, dermatologists should recognize it because of its potentially profound systemic associations; 2) Conceptually, it is a fascinating disorder.

First described in the neurological literature in 1938 in a 39-year-old man with a sternal lesion (2), it was not until 1997 when Schoenlaub et al. reported two men, aged 66 and 73, respectively, each with an erythematous scleroderma-like plaque, located over a solitary bony plasmacytoma, associated with palpable peripheral and mediastinal lymph nodes. Treatment of the plasmacytomas led to the disappearance of the cutaneous lesions, strongly suggesting a link between the two. (3) The term AESOP was coined in 2003 by Lipsker et al. in the following abstract (2):

We describe an easily recognizable and previously not individualized clinical syndrome that can reveal solitary plasmacytoma of bone. We report 4 patients with a slowly extending violaceous skin patch overlying a solitary plasmacytoma of bone, associated with enlarged regional lymph nodes. Biopsies of the cutaneous lesion and the lymph nodes were not specific, although increased dermal mucin deposition and vascular proliferation were present in all skin specimens. Three patients had associated polyneuropathy. One patient had POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes) syndrome at the time the plasmacytoma was diagnosed. Another patient developed POEMS syndrome, from which he died, 4 years after excision of the plasmacytoma. The 3 other patients were treated either with irradiation or with a combination of irradiation and surgery, and recovered completely, including from the associated neuropathy and/or POEMS syndrome. We suggest calling this unique and distinctive clinical presentation the AESOP syndrome,for Adenopathy and Extensive Skin patch Overlying a Plasmacytoma.

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Recently, Marzolf et al. (4) reviewed 21 cases of AESOP, offering the following synopsis — this paragraph will be interjected with other references from the literature, which are bracketed: “AESOP syndrome mainly affects men (90%) with an average age of onset of 55 years. Skin involvement is distinctive in most cases, to the point of evoking in itself the diagnosis. From our own clinical experience, as well as from a careful review of pictures from the review of the literature, a continuum between 2 morphologic variants can be delineated: the classic variant presents as a smooth and shiny bright red patch, with sharp borders, and through which the underlying blood vessels can be seen; the second presents as a brownish-purple infiltrated plaque with less distinct edges, skin thickening, and a sclerotic appearance [Lesions may range in size from 8 to 18 cm; and have been reported to expand at the rate of 5 to 10 cm per year. Smaller satellite lesions have been reported. (5)] The classical variant seems to occur preferentially on the thoracic region, while the morphea-like variant is generally observed in the hypochondrium regions. It can be finely scaling, warm, and itchy, and is rarely accompanied by paraesthesia.

Though skin histology is nonspecific, there is an almost constant proliferation of dilated capillaries in the dermis (79%) associated with slight inflammatory infiltration of variable composition, and often with intradermal mucin deposition (37%). [A case has been reported with multinucleated fibrohistiocytic floret cells. (6)] Firm, mobile, and homolateral enlarged lymph nodes are common (76%) but not essential to the diagnosis. In 67% of cases, an essentially sensorimotor severe polyneuropathy is associated — either demyelinating or mixed. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is associated in 38% of cases. [Castleman disease may be associated. (6)] The SBP [solitary bone plasmacytoma] is most commonly of the lambda type (82% of the 11 evaluated cases) and mostly located on the ribs (57%). [A pleural effusion may be associated. (7)] More than half of cases are accompanied by monoclonal gammopathy, most often immunoglobulin G lambda. Treatment has not been standardized, and many different strategies are used (chemotherapy, surgery, and radiotherapy). Disappearance of the skin lesion is the rule after effective SBP treatment. All the patients treated with radiotherapy had a complete response without any relapse or POEMS occurrence, while both reported deaths were related to the subsequent development of POEMS syndrome in patients not treated with irradiation.”

Although the precise etiology of AESOP is unknown, the proximity of the skin lesion with the plasmacytoma conceptualizes contiguous inflammation of the skin, where cytokines such as VEGF and transforming growth factor-beta cause vascular proliferation and sclerodermoid changes, respectively. (6,8)

It is impossible not to think of fables when AESOP is mentioned. Given the context of AESOP, a relevant fable is “The Ants and the Grasshopper” where the moral is that there is a time for work and a time for play. If you see a lesion resembling AESOP, get to work. The earlier this diagnosis is confirmed, the better.

Point to Remember: Dermatologists should consider the diagnosis of AESOP (Adenopathy and Extensive Skin patch Overlying a Plasmactyoma) presented as predominantly truncal erythematous patches or sclerodermoid plaques. A significant number of cases are associated with polyneuropathy and/or POEMS syndrome.

Our expert’s viewpoint

Dan Lipsker, MD
Faculté de Médecine, Université de Strasbourg, France

AESOP syndrome: how the puzzle was resolved

First of all, I want to thank Dr. Heymann for giving me the opportunity to share my personal view on AESOP syndrome, a term that I coined 20 years ago when I nosologically delineated this syndrome.

I shall briefly summarize how the term and the syndrome came into being.

In the early 1990s we encountered, in a very short period of time, 2 patients with a very similar presentation in our department. Both were men and had a slowly enlarging, red to brown shiny skin patch with abnormally visible vessels, located in the presternal area in one patient and below the right breast, in regard of the sixth right rib, in the other patient.

We initially suspected early (erythema migrans) or late (acrodermatitis chronica atrophicans) Lyme borreliosis, granuloma annulare, REM (reticular erythema with mucinosis) syndrome or morphea. However, multiple skin biopsies, Lyme borreliosis serology and treatment with antibiotics, ruled out those hypotheses. Histopathology revealed only capillary proliferation in the dermis with mucin deposition. Both patients also developed enlarged axillary lymph nodes, which were biopsied without revealing additional diagnostic information.

After a couple of years, one of the patients had cough and fever and was prescribed a chest X-ray which then revealed a sternal lesion located right below his skin patch. The lesion was biopsied and it was a plasmacytoma which proved to be solitary after extensive investigations. The plasmacytoma was irradiated and within a few months the skin lesion and the enlarged lymph nodes regressed. Since the 2 patients had exactly the same type of skin lesion, by analogy, we investigated the second patient, and we were surprised to also diagnose a solitary plasmacytoma below the sixth rib in the other patient. The plasmacytoma was surgically removed and the skin lesion and the enlarged lymph nodes regressed. Unfortunately, this patient was not irradiated — the treatment of choice of patients with solitary plasmacytoma — and he died 4 years later from fulminant POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes) syndrome.

We then published those 2 cases in French in 1997. (2) But it was only three years later, when I saw a 68-year-old year old lady in consultation, that the importance of this syndrome struck me. Indeed, while she undressed, I looked at her thorax, saw the red brown shiny patch with abnormally visible vessels, and I immediately made a diagnosis of what is now called AESOP syndrome. It was diagnosis on the first spot, which the Germans call “Blickdiagnose.” A plasmacytoma of the sternum was also diagnosed in her case and at that time she already met the diagnostic criteria of POEMS syndrome. She was cured with irradiation. I only then realized that this is a highly recognizable entity. I furthermore realized the important consequences of early recognition, since it allows diagnosing POEMS syndrome at an early and curable stage.

I then decided to individualize this syndrome as an entity, and to publish this information in the international literature. (3) I performed very extensive bibliographic research and found that the first case was already published by Sheinker in 1938 in the neurologic literature, a patient who also had POEMS syndrome.

I spent a whole weekend thinking about how to name the syndrome, and finally decided on the acronym AESOP: Adenopathy and Extensive Skin patch Overlying a Plasmacytoma (2), which summarizes its main clinical features. Meanwhile a similar presentation overlying other tumors has been described and the letter P of the acronym can be interpreted as either “Plasmacytoma,” the most common underlying tumor, or “Proliferations” since a few other underlying tumors have been reported. That’s the story behind the syndrome and the acronym, which I hope physicians are now able to recognize because early recognition can be lifesaving.

1. Shaker N, Sangueza OP. Evolving Chest Plaque: An Intriguing Presentation in a Female Adult With Monoclonal Gammopathy of Unknown Significance (MGUS): Challenge. Am J Dermatopathol. 2023 Dec 1;45(12):e95-e96. doi: 10.1097/DAD.0000000000002560. PMID: 37982473.

2. Lipsker D, Rondeau M, Massard G, Grosshans E. The AESOP (adenopathy and extensive skin patch overlying a plasmacytoma) syndrome: report of 4 cases of a new syndrome revealing POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome at a curable stage. Medicine (Baltimore). 2003 Jan;82(1):51-9. doi: 10.1097/00005792-200301000-00005. PMID: 12544710.

3. Schoenlaub P, Lipsker D, Massard G, Christmann D, Grosshans E. Syndrome adéno-cutané associé au plasmocytome osseux [Lymph node and cutaneous syndrome associated with bone plasmacytoma]. Ann Dermatol Venereol. 1997;124(3):228-32. French. PMID: 9686053.

4. Marzolf G, Lenormand C, Michel C, Cribier B, Lipsker D. Adenopathy and extensive skin patch overlying a plasmacytoma (AESOP): Two morphologic variants can be outlined. J Am Acad Dermatol. 2021 Nov;85(5):1286-1287. doi: 10.1016/j.jaad.2020.09.018. Epub 2020 Sep 11. PMID: 32926971.

5. Farooq U, Choudhary S, McLeod MP, Torchia D, Rongioletti F, Romanelli P. Adenopathy and Extensive Skin Patch Overlying a Plasmacytoma (AESOP) Syndrome. J Clin Aesthet Dermatol. 2012 Nov;5(11):25-7. PMID: 23198009; PMCID: PMC3509886.

6. Dagrosa AT, Cowdrey MCE, LeBlanc RE, Lansigan F, Kaur P, Carter JB. Adenopathy and extensive skin patch overlying a plasmacytoma with unusual histologic findings in a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome and Castleman disease. J Cutan Pathol. 2019 Oct;46(10):784-789. doi: 10.1111/cup.13514. Epub 2019 Jun 19. PMID: 31119772.

7. Afra TP, Namitha R, Khader A, Bishnoi A, Shahul Hameed DK, Razmi T M. Adenopathy and extensive skin patch overlying a plasmacytoma (AESOP) syndrome: erythrocyanotic vascular patches associated with an underlying rib plasmacytoma. Br J Dermatol. 2020 Aug;183(2):e33. doi: 10.1111/bjd.19037. Epub 2020 Apr 9. PMID: 32270486.

8. Rongioletti F, Romanelli P, Rebora A. Cutaneous mucinous angiomatosis as a presenting sign of bone plasmacytoma: a new case of (A)ESOP syndrome. J Am Acad Dermatol. 2006 Nov;55(5):909-10. doi: 10.1016/j.jaad.2006.04.072. PMID: 17052506.

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