Clinical Reference / Clinical Atlas / Acanthosis Nigricans

Acanthosis Nigricans

Definition

Lightly pigmented thin plaques formed by closely apposed papules, initially and sometimes only tiny, but sometimes large and polypoid. The plaques are often traversed by skin folds. There is a predisposition for intertriginous areas. The condition is due to metabolic disturbances, such as endocrine disorders, obesity, or malignancy. Medications that influence insulin metabolism may rarely be implicated (i.e., corticosteroids, estrogen, protease inhibitors, somatotrophin, and niacin). So-called malignant acanthosis nigricans is a misnomer, as it is not malignant per se, but due to an underlying malignancy. In such cases, the condition can be the presenting sign, or can follow detection of the tumor. A variety of tumors can cause acanthosis nigricans, but gastric adenocarcinoma is the most common. The clinical and pathologic appearance of the condition is identical, regardless of cause, but a generalized distribution or rapid onset can point to an underlying tumor. In this setting, velvety thickening may occur in dermatoglyphics of palmar skin, referred to as tripe palms or “acanthosis palmaris.” Tripe palms may be observed independently or in association with acanthosis nigricans. Whether this is a disease sui generis or a unique variant of acanthosis nigricans remains unclear. The histopathologic image of acanthosis nigricans shows narrow papillations with thin suprapapillary plates.

Course

Acanthosis nigricans tends to persist unless its cause is identified and corrected. For example, acanthosis nigricans due to diabetes mellitus will only regress if the patient’s blood glucose levels are brought under control. Lesions secondary to an underlying malignant neoplasm may regress if the primary tumor is resected— unless metastases are already present.

Integration: Unifying Concept

No matter whether acanthosis nigricans is due to an endocrine disturbance or a visceral neoplasm, its clinical and histopathologic attributes are identical. As noted above, both endocrine- and neoplasia-induced acanthosis nigricans wane when the underlying condition is addressed.

There is a morphologically identical condition to acanthosis nigricans—confluent and reticulated papillomatosis of Gougerot and Carteaud. This condition causes plaques on the anterior trunk, seemingly unrelated to the metabolic disturbances that cause acanthosis nigricans. The larger papules and polypoid excrescences that are seen in acanthosis nigricans do not occur in confluent and reticulated papillomatosis.

While the exact cause of most cases of acanthosis nigricans is not known, some evidence suggests that insulin resistance is a major factor. This may also be true for confluent and reticulated papillomatosis of Gougerot and Carteaud as well. Obesity is the most common cause of insulin resistance and acanthosis nigricans. Insulin resistance can enhance cellular proliferation and inhibit apoptosis, but the exact way in which it leads to over-production of keratin as well is not known. Some familial cases of acanthosis nigricans are due to mutations in fibroblast growth factor receptor 3.

Therapy

Most therapies for acanthosis nigricans are ineffective, but correction of the underlying metabolic problem can lead to remission. Fasting blood glucose and insulin levels should be obtained in all patients. Consideration for polycystic ovarian syndrome is essential in women. An extensive search for malignancy should ensue if metabolic disorders or medications are unrelated to the clinical vignette. Age-appropriate malignancy screening is imperative with a low threshold for gastric endoscopy and pelvic ultrasonography. Topical agents such as retinoids, ammonium lactate, or vitamin D analogs may lessen the surface changes of acanthosis nigricans. Metformin may also be utilized. Treatment of confluent and reticulated papillomatosis of Gougerot and Carteaud with minocycline may slowly lead to resolution.

Distribution

Fig. 1-1

Widespread acanthosis nigricans. This implies concurrence of an internal malignancy.


Fig. 1-2

Confluent papillomatosis of the lips and buccal mucosa.


Fig. 1-3

Bilateral involvement of the axillae in this obese young man with an endocrine disorder.


Fig. 1-4

The neck is a favorite site.


Individual Lesions

Fig. 1-5

Closely set tiny papules in linear array.


Fig. 1-6

Lesions situated over joints. Note how dark are the fingers in contrast to the rest of the skin.


Fig. 1-7

Pigmented plaque with mammillated surface.


Fig. 1-8

Pigmented, slightly elevated plaque with a gently papillated smooth surface, in this instance punctuated by atrophic striae.


Fig. 1-9

Polypoid excrescences, as well as subtle papules. Grooves that traverse plaques represent accentuation of skin lines.


Fig. 1-10

Ill-defined plaque, thrown into folds, made up of prominent, smooth-surfaced papules, some of them polypoid.


Fig. 1-11

Pigmented plaque in which skin folds are accentuated.


New! Additional Images

Fig. 1-12

Acanthosis nigricans: Brown papules, some of which have become confluent to form a plaque, are intersected by lines normal for skin. The dark brown macule is a Clark’s nevus.