: 86 In conjunction with increased end levels of IGF, it is likely that perspiration and friction may be necessary predeterminants for lesions, since the level of insulin is usually not enough to activate IGF receptors across the body. Diagnosis
Acanthosis nigricans is typically diagnosed clinically. A skin biopsy may be needed in unusual cases. If no clear cause is obvious, it may be necessary to search for one. Blood tests, an endoscopy, or X-rays may be required to eliminate the possibility of diabetes or cancer as the cause. : 87 On biopsy, hyperkeratosis, epidermal folding, leukocyte infiltration, and melanocyte proliferation may be seen. : 979 : 87

Differential diagnosis
Acanthosis nigricans should be distinguished from the casal collar appearing in pellagra. Classification
Acanthosis nigricans is conventionally divided into benign and malignant forms, although may be divided into syndromes according to cause:: 506 
Benign This may include obesity-related, hereditary, and endocrine forms of acanthosis nigricans. Malignant. This may include forms that are associated with tumour products and insulin-like activity, or tumour necrosis factor.An alternate classification system still used to describe acanthosis nigricans was proposed in 1994. It delineates acanthosis nigricans syndromes according to their associated syndromes, including benign and malignant forms, forms associated with obesity and drugs, acral acanthosis nigricans, unilateral acanthosis nigricans, and mixed and syndromic forms. Treatment
People with acanthosis nigricans should be screened for diabetes and, although rare, cancer. Controlling blood glucose levels through exercise and diet often improves symptoms. Topical fade creams (normally used for eliminating age spots) can lighten skin cosmetically in less severe cases.
: 86 This form of acanthosis nigricans is more likely to involve mucous membranes (25–50% of cases) Malignant acanthosis nigricans that may either precede (18%), accompany (60%), or follow (22%) the onset of an internal cancer. : 506  Malignancy-associated acanthosis nigricans is usually rapid in onset and may be accompanied by skin tags, multiple seborrheic keratoses, or tripe palms. : 676

Acral acanthotic anomaly
Acral acanthotic anomaly refers to a variant of acanthosis nigricans limited to the elbows, knees, knuckles, and dorsal surfaces of the feet, in the absence of any other findings, in otherwise healthy individuals. While the etiology remains unknown, its presence does not suggest a likelihood of malignancy. Pathophysiology
Acanthosis nigricans is caused by increased activation of growth factor receptor proteins, usually due to endocrine dysfunction. This is most commonly insulin-mediated activation of IGF receptors on keratinocytes, as a result of hyperinsulinaemia or insulin resistance, as seen in diabetes mellitus.Factors involved in the development of acanthosis nigricans include:

Increased circulating insulin. This activates keratinocyte IGF receptors, particularly IGF-1. At high concentrations, insulin may also displace IGF-1 from insulin-like growth factor-binding protein (IGFBP). Increased circulating IGF may lead to keratinocyte and dermal fibroblast proliferation. In hereditary forms of acanthosis nigricans, fibroblast growth factor receptor (FGFR) defects
Increased transforming growth factor (TGF), which appears to be the mechanism for malignancy-associated acanthosis nigricans. TGF acts on epidermal tissue via the epidermal growth factor receptor (EGFR).