What are the other Names for this Condition? (Also known as/Synonyms)

• Acanthosis Nigricans Maligna (ANM)
• Acanthosis Nigricans, Malignancy-Associated Type
• Malignant Acanthosis Nigricans

What is Malignancy-Associated Acanthosis Nigricans? (Definition/Background Information)

• Acanthosis Nigricans (AN) is a skin condition that causes thick, velvety, and darkened skin areas (due to increased thickness of epidermis). It commonly affects the skin of the armpits, the groin region, head and neck (back of the neck), and anal/genital region.
• Acanthosis Nigricans is not contagious and it cannot be transmitted from one individual to another. It is associated with many disorders, such as obesity, diabetes, and malignancy
• Malignancy-Associated Acanthosis Nigricans is one among the 7 types of type Acanthosis Nigricans. Acanthosis Nigricans associated with malignancy (or cancer) shares similar features to other types of Acanthosis Nigricans but has a rapid onset. Hence, this type of Acanthosis Nigricans is not a disease by itself, but rather a sign of cancer (known as a paraneoplastic syndrome)
• Stomach cancer is the most common type of cancer causing Malignancy-Associated Acanthosis Nigricans. It is usually diagnosed by a thorough clinical history and physical examination
• Even though the skin condition is benign, a dermatologist consultation and testing is necessary to rule out other causes of Acanthosis Nigricans. If malignancy is suspected as an underlying cause, then appropriate workup including imaging studies and blood tests are necessary
• The treatment of cancer is more important than treatment of the skin lesions caused by Acanthosis Nigricans. The skin lesions may regress with treatment of cancer
• The prognosis of Malignancy Associated Acanthosis Nigricans depends on several factors, but most importantly on the type of cancer, the stage of cancer, and treatment response of the individual

Who gets Malignancy-Associated Acanthosis Nigricans? (Age and Sex Distribution)

• Malignancy-Associated Acanthosis Nigricans is usually seen in individuals over 40 years of age, because cancer is more common with increasing age
• However, individuals of any age (including children) may be affected
• Both males and females of all races and ethnicities can be affected
• Acanthosis Nigricans is seen all over the world; there is no particular geographical restriction observed. Nevertheless, the condition is more common in individuals with darker skin tone

What are the Risk Factors for Malignancy-Associated Acanthosis Nigricans? (Predisposing Factors)

Malignancy-Associated Acanthosis Nigricans is caused by an underlying cancer. The common cancers associated with the condition include:

• Stomach cancer
• Colon cancer
• Liver cancer
• Endometrial cancer
• Pineal gland tumor (located in the brain)

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Malignancy-Associated Acanthosis Nigricans? (Etiology)

Malignancy-Associated Acanthosis Nigricans can be caused by multiple mechanisms.

• The Acanthosis Nigricans type that is associated with malignancies is caused by mutation of a substance, called transforming growth factor-alpha (TGF-alpha), which is either secreted by the tumor cells or by the body in response to the tumor. Increased levels of TGF-alpha causes a proliferation of the epidermal skin cells. TGF-alpha levels in blood and urine may drop after the malignant tumor is removed
• Some scientists also believe that it is caused by other growth factors which stimulate the proliferation of cells of the skin (namely keratinocytes and dermal fibroblast)
• Insulin resistance and increased insulin levels, which plays a role in other types of Acanthosis Nigricans, may play a role in Malignancy-Associated Acanthosis Nigricans

What are the Signs and Symptoms of Malignancy-Associated Acanthosis Nigricans?

The signs and symptoms of Malignancy-Associated Acanthosis Nigricans may include:

• It most commonly presents as hyperpigmented, velvety, poorly-defined skin lesions, most commonly on the skin folds such as axilla (armpits), groin, back of the neck, and anal/genital region
• Sometimes, it can affect areas behind the knees, front of the elbows, under the breasts, or navel
• Some have reported that Acanthosis Nigricans associated with cancer can involve the entire skin in the body
• In case of Malignant Acanthosis Nigricans, the severity of skin lesion is generally greater (than when not associated with a malignancy). The condition may also involve the mucosal membranes, palms, and the soles of the feet; features that are not observed with other types of Acanthosis Nigricans
• The hyperpigmentation can be either brown or black in color. The skin lesions may cause itching and may even have a foul smell
• In individuals with Malignant Acanthosis Nigricans, the lesions may appear suddenly, unlike the other subtypes where the lesions appear gradually over a period of time
• The skin lesions may appear before, during, or after the cancer is diagnosed
• Individuals with Malignancy-Associated Acanthosis Nigricans are usually ill from the systemic effects of cancer

Additionally, signs and symptoms due to the underlying cancer may also be observed.

How is Malignancy-Associated Acanthosis Nigricans Diagnosed?

The following may be used to diagnose Malignancy-Associated Acanthosis Nigricans:

• Thorough evaluation of the individual’s medical history and a complete physical examination
• During history-taking, the physicians may enquire about the following:
  • When the symptoms began and whether they are becoming worse
  • List of prescription and over-the-counter medications currently being taken
  • About one’s personal and family history of cancer, diabetes, thyroid abnormalities, ovarian and adrenal gland problems, etc.
• Dermoscopy: It is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Workup for cancer is warranted, if there is any suspicion for malignancy. The tests may include blood workup, endoscopy, and other radiological imaging studies via CT and MRI scans
• Measuring insulin levels in blood may be necessary, if insulin resistance is suspected. The insulin levels in such individuals may be high
• A skin biopsy (of the affected skin area) is performed and sent to a laboratory for a pathological examination, who examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis

Note: A skin biopsy is only rarely performed, when the diagnosis is questionable, or if it resembles other similar skin conditions.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Malignancy-Associated Acanthosis Nigricans?

Complications due to Malignancy-Associated Acanthosis Nigricans may include:

• The skin lesions of AN generally do not cause any medically-related problems, but it can result in low self-esteem due to cosmetic concerns
• In many individuals, with effective cancer treatment, the skin lesions may regress. However, a return of the skin lesions may indicate the reversion of the cancer. The cancer may recur and form, either at the same site or in other distant organs

How is Malignancy-Associated Acanthosis Nigricans Treated?

Treatment measures for Malignancy-Associated Acanthosis Nigricans may include the following:

• Dermatologist consultation: It is often necessary, as they are the experts in dealing with various skin conditions
• Topical retinoid, bleaching cream, dermabrasion therapy, and long-pulsed alexandrite laser skin therapy are used for addressing the cosmetic issues only. However, they are not a definitive treatment for Acanthosis Nigricans
• If Acanthosis Nigricans presents with bad odor, then antibacterial soap or antibiotic cream may be helpful
• Treatment of cancer may help resolve the lesions of Acanthosis Nigricans. The treatment may involve surgery, chemotherapy, and/or radiation therapy, based on the assessment of the healthcare provider

How can Malignancy-Associated Acanthosis Nigricans be Prevented?

Currently, it is not possible to prevent Malignancy-Associated Acanthosis Nigricans. However, an early diagnosis and adequate treatment of cancer may help avoid or prevent the formation of the skin lesions.

What is the Prognosis of Malignancy-Associated Acanthosis Nigricans? (Outcomes/Resolutions)

• In general, Acanthosis Nigricans is a skin sign, which in itself is benign. Thus, the prognosis of Acanthosis Nigricans is excellent with adequate (skin) treatment. However, the overall prognosis depends upon the underlying cause of the condition
• The overall prognosis of Malignancy-Associated Acanthosis Nigricans depends on a set of factors that include:
  • The type of cancer
  • The stage and grade of the underlying cancer
  • Response of the cancer to treatment
  • Age of the individual and their health status
• If the underlying cancer is of high-grade and in an advanced stage, then the overall prognosis is generally guarded

Additional and Relevant Useful Information for Malignancy-Associated Acanthosis Nigricans:

• When the biopsied skin tissue is seen by a pathologist under the microscope, the lesions may demonstrate a benign epidermis with hyperkeratosis, papillomatosis, thickening of epidermis (Acanthosis), hyperkeratosis, increased number of melanocytes (melanocytic hyperplasia), and lymphocytic inflammation
• Interestingly, there are only fewer acanthosis with no hyperpigmentation that do not fit the histologic terminology. The hyperpigmented appearance is actually due to hyperkeratosis
• Microscopically, all the 7 types of Acanthosis Nigricans share similar features