Correspondence

Small-Cell Lung Cancer and Necrolytic Migratory Erythema

N Engl J Med 2008; 359:2731-2732December 18, 2008

Article

To the Editor:

Necrolytic migratory erythema is a rare inflammatory dermatosis, first described by Becker et al.,1 which occurs in 70% of patients with the glucagonoma syndrome.2 Its clinical features are polymorphic mucocutaneous manifestations, encompassing multiple annular erythematous scaling and crusting patches with hyperpigmentation. These lesions can affect the entire body with a predilection for the perineum, buttocks, groin, abdomen, and limbs — in other words, areas that are subject to increased pressure and friction.2,3 The only two reported oral findings are angular cheilitis and atrophic glossitis.2-5

A 73-year-old man was referred to our oral medicine unit for persistent and progressive mucocutaneous lesions. The oral mucosa showed bullous, erosive mucositis with several areas having lichenoid clinical features (Figure 1A and 1BFigure 1Mucocutaneous Manifestations of Necrolytic Migratory Erythema.). His body, including the genital area, was covered in purplish confluent erythematopapulous scaling and crusting lesions with a keratotic surface (Figure 1C). Histologic analysis of lesions from skin and oral mucosa revealed mild hyperparakeratosis, spongiosis, necrotic keratinocytes, and a prominent neutrophilic, eosinophilic, and plasmacellular infiltrate (Figure 1D).

The patient's nutritional status was normal. Routine hematologic tests revealed mild hyperglycemia, hypoalbuminemia, a glucagon level of 73 pg per milliliter (normal range, 25 to 250), and a zinc level of 134 μg per deciliter (normal range, 60 to 250). Tumor markers showed a CA-125 level of 232 U per milliliter (normal range, 0 to 35) and a β₂-microglobulin level of 2924 ng per milliliter (normal range, 600 to 2600). Total-body computed tomography revealed the presence of an ovoid mass measuring 40 mm in diameter in the upper lobe of the right lung, with prominent striae hooking the apical and costal homolateral pleura. No evidence of a pancreatic tumor was detected. Needle biopsy of the lung with ultrasonographic guidance revealed a small-cell lung cancer. A diagnosis of nonglucagonoma-associated necrolytic migratory erythema was made. The patient died 2 months later.

The pathogenesis of this disorder remains unclear. Nonetheless, it appears that hypoaminoacidemia, a nutritional lack of zinc and fatty acids, or hepatocellular dysfunctions might be involved in triggering these mucocutaneous lesions.2,3 Less frequently, necrolytic migratory erythema has been seen with no glucagon-producing tumor, a condition that is termed the pseudoglucagonoma syndrome4 and is associated with various systemic diseases, such as celiac disease, ulcerative colitis, Crohn's disease, hepatic cirrhosis, and various extrapancreatic malignant neoplasms, such as hepatocellular cancer, bronchial cancer, tumors that secrete insulin or insulin-like growth factor II, and duodenal cancer.5 As in the case of our patient, necrolytic migratory erythema with oral bullous, erosive mucositis and lichenoid features can also be associated with small-cell lung cancer.

Michele Davide Mignogna, M.D., D.M.D.
Giulio Fortuna, D.M.D.
Federico II University of Naples, 80131 Naples, Italy
mignogna@unina.it

Alfredo Rocco Satriano, M.D.
Second University of Naples, 80138 Naples, Italy

5 References

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   Becker SW, Kahn D, Rothman S. Cutaneous manifestations of internal malignant tumors. Arch Dermatol Syph 1942;45:1069-1080
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   van Beek AP, de Haas ER, van Vloten WA, Lips CJ, Roijers JF, Canninga-van Dijk MR. The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. Eur J Endocrinol 2004;151:531-537
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   Pujol RM, Wang CY, el-Azhary RA, Su WP, Gibson LE, Schroeter AL. Necrolytic migratory erythema: clinicopathologic study of 13 cases. Int J Dermatol 2004;43:12-18
   CrossRef | Web of Science | Medline

4. 4

   Marinkovich MP, Botella R, Datloff J, Sangueza OP. Necrolytic migratory erythema without glucagonoma in patients with liver disease. J Am Acad Dermatol 1995;32:604-609
   CrossRef | Web of Science | Medline

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   Colombo E, Zuccoli R, Ugolini M, Dardano F, Leigheb G. Pancreatic glucagonoma presenting as necrolytic migratory erythema. J Clin Oncol 2007;25:2135-2136
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Benjamin D. Ehst, Karen Minzer-Conzetti, Amy Swerdlin, Theresa Schroeder Devere. (2010) Cutaneous Manifestations of Internal Malignancy. Current Problems in Surgery 47:5, 384-445
   CrossRef