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Q1: What is the terminology used for this dermatosis?
The condition is known as malignant acanthosis nigricans (AN).
Q2: What are the variants of this disorder?
There are several categories of AN,1,2 namely, benign hereditary, benign(insulin resistance related), obesity associated (pseudoacanthosis nigricans), syndromic, malignant, drug induced, acral, naevoid, and mixed.
Q3: How does it differ clinically when associated with malignancy?
The malignant form of the disease is sudden in onset, rapidly progressive, and there is partial or complete resolution with treatment of the original malignancy.3 The involvement is more generalised1 compared with the predominantly flexural involvement in other forms. Clinically, the lesions are more verrucous and there is a darker pigmentation than the benign form of the disorder, often extending beyond the hyperkeratotic area. Warty thickening of the periocular and perioral regions, lips, oral mucosa are present in 50% cases.2 Malignant AN may be associated with symptoms like severe irritation and localised or generalised pruritus,1 in contrast with the other forms, which are asymptomatic.
Malignant AN is one of the rare cutaneous paraneoplastic syndromes.1 It may develop concurrent with, before, or after the diagnosis of the associated internal malignancy. The commonest malignancy with such presentation is adenocarcinoma of the stomach (45%–61%).3 However, urinary bladder, kidney, bile duct, rectum, oesophagus, bronchogenic, thyroid, and lymphoreticular malignancies may also present with this clinical picture.3 Despite the name used, the cutaneous lesion itself never undergoes malignant transformation.1 Histopathologically malignant AN is indistinguishable from other variants of the disorder.
Most affected people are middle aged or older. Tylosis (palmoplantar hyperkeratosis), acanthosis palmaris or tripe palm (rugose appearance of the palmar skin), pachydermatoglyphy (exaggerated fingerprints), and brittleness of the nails are commonly associated.1,3 Malignant AN limited to the mucosa, especially oesophageal mucosal involvement, is known to occur.4 Diffuse papillomatosis of the involved mucous membrane with minimal or no hyperpigmentation is the characteristic finding. Double contrast barium study shows typical, lacy, granular shadows in the oesophagus.1,4
The possible pathomechanism involved in the development of malignant AN is not clear.3 Release of a humoral factor by the malignant cells that may activate insulin-like growth factors or their receptors in tissues may be operative. Increased levels of transforming growth factor α in urine and epidermal growth factor receptors in the lesional skin of these patients have been reported. Normalisation of the raised expression of these cytokines and related receptors in the involved tissue corresponds to the removal of the tumour.3
Once the diagnosis of malignant AN is considered, all efforts should be undertaken to locate the hidden malignancy. In most cases the occult neoplasm is highly aggressive or in an inoperable stage. Average life expectancy of the patients after the malignancy is discovered or resected is one year.1,5 The association of malignant AN in our patient was apparently unusual as the caecal malignancy was locally infiltrative without evidence of regional invasion. However, the histopathologically the higher grade of the tumour might be the responsible factor for the malignant AN in this case. Few authors believe prompt management of the underlying neoplasm may carry a better survival rate.1 Although removal of the tumour is associated with regression of the skin lesions, relapses are common with recurrence of the malignancy or metastasis.1
Malignant AN may precede, coexist, or develop subsequent to the diagnosis of an internal malignancy.
Acute onset, generalised involvement, and rapid progression are the clinical hallmarks for diagnosis of malignant AN.
The underlying malignancy may be in advanced stage; hence presence of malignant AN requires intensive search and prompt management of the neoplasm.
Malignant AN has to be differentiated from other forms of AN existing coincidentally with a malignancy. In such cases, there is no temporal correlation between the development of the two disorders and the skin lesions remain stationary.
Malignant acanthosis nigricans with underlying adenocarcinoma of the caecum.