Malignant Acanthosis Nigricans Research Articles

Clinical, Pathologic, and Molecular Characterization of Acanthosis Nigricans Maligna: A Comprehensive Analysis of a Dermatologic Entity and its Association with Underlying Neoplastic Conditions

Acanthosis nigricans maligna (ANM) is a distinctive dermatologic entity presenting with cutaneous hyperpigmentation and epidermal thickening, characteristically located in flexural areas and skin folds. Despite its apparent cutaneous nature, ANM is frequently associated with underlying neoplastic conditions, implying profound clinical significance. In this study, we undertook a comprehensive evaluation of ANM from clinical, pathological and molecular perspectives with the aim of elucidating its etiopathogenic mechanisms and its relationship with neoplastic processes. From a clinical standpoint, we retrospectively analyzed a cohort of patients diagnosed with ANM, exploring the clinical and epidemiologic features that could indicate the presence of an underlying malignant condition. In addition, histopathologic studies were performed on samples of affected skin to discern the microscopic alterations associated with ANM and their correlates with neoplastic processes. In a molecular phase, an in-depth analysis of genetic and molecular markers in skin samples and associated tumor tissues was carried out using advanced sequencing techniques. This allowed the identification of specific mutations, chromosomal alterations and gene expression profiles that could contribute to both the occurrence of ANM and the promotion of the microenvironment conducive to tumor development. The results obtained indicate a significant correlation between the presence of ANM and the abnormal activation of cell signaling pathways, as well as the altered expression of regulatory factors of cell growth and differentiation. Our study highlights the importance of considering ANM as a potential cutaneous marker of underlying neoplastic processes and suggests that its early detection could facilitate the early identification of early stage malignant conditions. Taken together, this comprehensive analysis provides an in-depth view of ANM and its clinical, pathological and molecular relevance in the context of neoplastic diseases.

Acral Acanthosis Nigricans with Concurrent Vitamin B12 Deficiency in an Indian Patient: An Atypical Presentation

Acanthosis Nigricans (AN) is characterised by velvety, papillomatous, brownish-black, hyperkeratotic plaques, typically on the intertriginous areas and neck. It is more commonly seen in the African American descent, rarely occurs in the Indian population. The present case includes 28-year-old male, who presented to the Outpatient Department with asymptomatic hyperpigmention over skin of both feet and knuckles of both hands since three months. The distribution pattern over the knuckles was suggestive of vitamin B12 deficiency however the atypical distribution over the feet leads to suspicion of a differential diagnosis of lichen planopigmentosus, vitamin B12 deficiency and acral AN. Dermoscopy was done to aid in the diagnosis and revealed linear crista cutis and sulcus cutis which are features suggestive of AN. On investigation, serum vitamin B12 levels were below 100 µg/mL and histologic sections showed hyperkeratosis with papillomatosis and mild acanthosis. The patient was treated solely with 1500 mcg mecobalamine daily for 10 days and followed-up. The dermoscopic and histopathological findings were consistent with the diagnosis of acral AN and thus a final diagnosis of acral AN superimposed with vitamin B12 deficiency was made. This case is being reported due to its rare occurrence in the Indian population, the atypical clinical presentation of AN in form of macules and to highlight dermoscopy as an essential non invasive tool aiding in the diagnosis. The diagnosis of acral AN should not be overlooked despite the finding of low serum vitamin B12 levels in such a case and the authors wish to create awareness among the clinicians to investigate the patient further.

Oral Florid Papillomatosis Associated with Malignant Acanthosis Nigricans – a Case Report with a Review of the Literature

Oral Florid Papillomatosis Associated with Malignant Acanthosis Nigricans – a Case Report with a Review of the Literature

Malignant acanthosis nigricans and diseases with extensive oral papillary hyperplasia.

Oral papillary lesions represent a variety of developmental and neoplastic conditions. Early diagnoses of different papillary lesions are challenging for oral medicine specialists. Malignant acanthosis nigricans (MAN) is a rare cutaneous disorder and a potential marker of underlying hidden tumours. It is characterized by papillary lesions that always involve the oral mucosa. In oral medicine specialities, MAN is not well understood. When the early signs of MAN are extensive oral lesions and slight cutaneous pigmentation without obvious florid cutaneous papillomatosis, the diagnosis can be incorrect or delayed. Oral medicine specialists should ask affected patients to provide details of their medical history and conduct a timely systemic examination.

26276 “Google investigates” sudden onset of skin darkening leading to the detection of a gastrointestinal cancer

We present a case of a 57-year-old woman who reported a 1-month history of darkening and thickening of the skin overlying her neck, axillae, abdomen, groin, and inframammary areas. She had explored her symptoms online and recognized that this could be indicative of an underlying malignancy. She reported intentional weight loss of 13 kg following a new diet regime, but did not complain of any other systemic gastrointestinal symptoms, such as loss of appetite, alteration in bowel habits, or rectal bleeding. On examination, she had symmetrically distributed, ill defined, velvet-textured hyperpigmented plaques over the axillae, posterior neck, groin and inframammary areas. She also had hyperpigmented patches over the sides of the face. Abdominal examination revealed a firm epigastric mass. In view of the clinical findings in keeping with acanthosis nigricans and the epigastric mass, a gastroscopy was performed which showed a suspicious gastric mass. Biopsy confirmed the presence of a gastric adenocarcinoma, and further imaging revealed metastatic spread to the lymph nodes. She was therefore started on palliative chemotherapy. Malignant acanthosis nigricans (AN) is a rare cutaneous paraneoplastic manifestation, most commonly associated with adenocarcinoma of the gastrointestinal tract. In contrast to the benign form with its insidious onset, malignant AN appears suddenly and is widespread. This case highlights that acute onset acanthosis nigricans may be the only presenting symptom of internal malignancy, and although rare, should be kept in mind. It is particularly unusual in the manner by which the patient self-diagnosed her paraneoplastic phenomenon online.

Malignant Acanthosis Nigricans as a Paraneoplastic Precursor of Metastatic Cholangiocarcinoma.

Malignant Acanthosis Nigricans as a Paraneoplastic Precursor of Metastatic Cholangiocarcinoma.

Malignant acanthosis nigricans: a case report

BackgroundTo report a case of malignant acanthosis nigricans with two unusual aspects, including the patient’s young age and the development of filiform papillomas on the eyelid margins.Case presentationA 30-year-old woman presented with dry eye symptoms. Examination revealed filiform papillomas on the eyelid margins, gums, lips, hands, and axillae and excessive pigmentation localized to the neck, axillae, and groin. Biopsies of stomach, pancreatic, and thyroid lesions revealed gastric adenocarcinoma, pancreatic adenocarcinoma, and thyroid cancer, respectively. Systemic investigations showed gastric adenocarcinoma with metastatic spread. The patient was ultimately diagnosed with malignant acanthosis nigricans and died 4 months later.ConclusionsAcanthosis nigricans on the eyelid margins with a velvety overgrowth is highly suggestive of an internal malignancy, and full systemic investigations are warranted in these cases. In this patient, early signs were ignored, leading to the loss of a timely diagnosis and treatment.

Symmetrical acrokeratoderma: A distinct disease entity from acral acanthosis nigricans?

Symmetrical acrokeratoderma: A distinct disease entity from acral acanthosis nigricans?

Simultaneous presentation of malignant acanthosis nigricans and palmar fasciitis with polyarthritis syndrome in a patient of ovarian neoplasm: A rare manifestation

Malignant acanthosis nigricans (MAN) is a paraneoplastic dermatosis associated most commonly with an underlying intra-abdominal malignancy. It may manifest either with or before the development of the malignancy prompt diagnosis of such paraneoplastic syndrome is often instrumental in early diagnosis of occult malignancy. Palmar fasciitis and polyarthritis syndrome is a rare disease characterized by palmar fasciitis, symmetric synovitis of the hands, fibrosis, and flexion contractures. We present a case of a 48-year-old female who presented with complaints of bilateral contracture of hands with diffuse hyperpigmentation over body folds, face, and trunk suggestive of MAN. On investigation, she was found to have ovarian carcinoma. The hand contracture was thought to be due to palmar fasciitis with polyarthritis syndrome. The patient underwent total abdominal hysterectomy with bilateral total salpingo-oophorectomy with subtle improvement in acanthosis nigricans.

Acantosis nigricans intraoral y su relevancia clínica como manifestación de un síndrome paraneoplásico: Reporte de un caso

Malignant-or-paraneoplastic acanthosis nigricans is a verrucous and hyperpigmented tumor affecting the mucosa and skin. In most cases malignant acanthosis nigricans is a distant manifestation of an intra-abdominal primary cancer. While the diagnosis of malignant acanthosis nigricans is challenging, some specific clinical and histopathological findings could lead to an accurate diagnosis. A rare clinical case of a 59-year-old female, who was referred to the maxillofacial surgery service due to a painful oral lesion in the palatine region, is presented. Upon examination, papillomatous lesions were observed on the hard palate, that were later diagnosed as intraoral malignant acanthosis nigricans secondary to gastric cancer. Both local and systemic evaluations are discussed, highlighting the relevance of a multidisciplinary approach consistent with the fact that these manifestations, although infrequent, should generate suspicion among clinicians and therefore motivation to perform a diligent and complete study since it can reveal the presence of a malignant pathology.

Non-HPV Papillary Lesions of the Oral Mucosa: Clinical and Histopathologic Features of Reactive and Neoplastic Conditions.

Excluding human papillomavirus (HPV)-driven conditions, oral papillary lesions consist of a variety of reactive and neoplastic conditions and, on occasion, can herald internal malignancy or be part of a syndrome. The objectives of this paper are to review the clinical and histopathological features of the most commonly encountered non-HPV papillary conditions of the oral mucosa. These include normal anatomic structures (retrocuspid papillae, lingual tonsils), reactive lesions (hairy tongue, inflammatory papillary hyperplasia), neoplastic lesions (giant cell fibroma), lesions of unknown pathogenesis (verruciform xanthoma, spongiotic gingival hyperplasia) and others associated with syndromes (for instance Cowden syndrome) or representing paraneoplastic conditions (malignant acanthosis nigricans). Common questions regarding differential diagnosis, management, and diagnostic pitfalls are addressed, stressing the importance of clinico-pathologic correlation and collaboration.

Symmetrical acral keratoderma revisited: proposal for a new term, 'pigmented carpotarsal hyperkeratosis'.

First reported from Taiwan mistakenly as acral acanthosis nigricans in 1991, pigmented carpotarsal hyperkeratosis or hyperkeratosis nigricans carpi et tarsi displays a peculiar distribution of velvety brown-grey hyperpigmented plaques symmetrically on the flexural side of the wrists and ankles and on the dorsal sides of the hands and feet. A marked epidermal hyperkeratosis with typically mild acanthosis and papillomatosis is observed in histology. Whitish maceration upon perspiration or water exposure, with exacerbation in summer but remission in winter, is common. The association with obesity, endocrine disorders, atopic dermatitis, ichthyosis or malignancy is unknown. Familial occurrence and hereditary patterns are ill-defined. There is preliminary evidence indicating a pathogenic role of missense mutation in the transcription factor 4 gene. Treatment is empirical, with good outcome with topical retinoids and keratolytic agents. Recurrence is common, and long-term prognosis is unclear. To be distinguished are acral acanthosis nigricans, palmoplantar keratoderma of the Nagashima type, palmoplantar keratoderma of the Bothnian type and aquagenic palmoplantar keratoderma. Most reported cases are from Southern China and are predominantly observed in men between the ages of 20 and 40 years. The currently used term 'symmetrical acral keratoderma' is non-specific and misleading and may lead to global unawareness, underreporting or misdiagnosis of this phenomenon. Further genetic and molecular studies are required to clarify its pathogenesis and relation to palmoplantar keratoderma.

Acral manifestations of paraneoplastic and collagen vascular diseases

The skin often signals a number of systemic disease, making skin findings of paramount significance. Paraneoplastic diseases and collagen vascular diseases are vitally important illnesses. Paraneoplastic diseases and collagen vascular diseases may also occur with many different acral skin findings. Paraneoplastic skin diseases, associated with some cancers, are by definition nonmalignant skin disorders. These diseases can occur before, simultaneously, or after the diagnosis of cancer. Acral paraneoplastic diseases include acanthosis nigricans maligna, acquired pachydermatoglyphia, acrokeratosis paraneoplastica, palmoplantar keratoderma, and paraneoplastic nail disorders. Collagen vascular diseases include the acral skin findings of lupus erythematosus, scleroderma, dermatomyositis, and rheumatoid arthritis. Any acral skin finding may be encountered as the first finding of an undiagnosed malignancy or collagen vascular diseases. The role of the dermatologist is significant for often being the first physician to suspect a malignancy or collagen vascular disease.

Acanthosis Nigricans associated with clear-cell renal cell carcinoma

Acanthosis nigricans (AN), an entity recognized since the 19th century, is a dermatopathy associated with insulin-resistant conditions, endocrinopathies, drugs, chromosome abnormalities and neoplasia. The latter, also known as malignant AN, is mostly related to abdominal neoplasms. Malignant AN occurs frequently among elderly patients. In these cases, the onset is subtle, and spreading involves the flexural regions of the body, particularly the axillae, palms, soles, and mucosa. Gastric adenocarcinoma is the most frequent associated neoplasia, but many others have been reported. Renal cell carcinoma (RCC), although already reported, is rarely associated with malignant AN. The authors report the case of a woman who was being treated for depression but presented a long-standing and marked weight loss, followed by darkening of the neck and the axillary regions. Physical examination disclosed a tumoral mass in the left flank and symmetrical, pigmented, velvety, verrucous plaques on both axillae, which is classical for AN. The diagnostic work-up disclosed a huge renal mass, which was resected and further diagnosed as a RCC. The post-operative period was uneventful and the skin alteration was evanescent at the first follow-up consultation. The authors call attention to the association of AN with RCC.

Oral Malignant Acanthosis Nigricans and Tripe Palms Associated With Renal Urothelial Carcinoma.

Oral Malignant Acanthosis Nigricans and Tripe Palms Associated With Renal Urothelial Carcinoma.

Malignant Acanthosis Nigricans, Florid Cutaneous Papillomatosis and Tripe Palms Syndrome Associated with Gastric Adenocarcinoma - a Case Report

Abstract Malignant acanthosis nigricans is a rare obligate paraneoplastic dermatosis which accounts for 20% of all acanthosis nigricans cases. The clinical features of the disease are the same as in the benign forms: symmetrical, hyperpigmented, velvety papillomatous lesions mostly involving the axillae, neck, groins, periumbilical cubital and popliteal areas, mammary areolae and less often mucous membranes. However, unlike other forms, it is characterized by sudden onset and rapid spread, commonly (80%) after the age of 40, which may be a marker of malignancy and a key to early diagnosis, indicating the need for a detailed examination. It is a disorder that has no gender differences. Most cases are detected at the moment of cancer diagnosis (61.3%), in fewer cases (about 20%) prior to cancer diagnosis, and in 21% at a later stage of malignant disease. Acanthosis nigricans is usually associated with one of the three or all three forms of paraneoplastic lesions: florid cutaneous papillomatosis, acanthosis palmaris (tripe palms, pachydermatoglyphia) involving the palms and soles, as well as multiple seborrheic keratosis (sign of Leser-Trélat). We report on a female patient with clinically established three paraneoplastic syndromes: malignant acanthosis nigricans, florid cutaneous papillomatosis, and acanthosis palmaris, which appeared before the diagnosis of advanced gastric adenocarcinoma, leading to fatal outcome.

A case of acanthosis nigricans coexisting with mycosis fungoides

Acanthosis nigricans maligna (ANM) is a paraneoplastic phenomenon most commonly associated with visceral adenocarcinoma, in particular, gastric adenocarcinoma. Clinically, AMN is characterized by rapidly progressive symmetrical skin thickening and hyperpigmentation of the intertriginous areas with peripheral acrochorda. The diagnosis is made by a detailed medical work-up for occult malignancies with particular emphasis on endocrinological diseases. We report a 67-year-old man that presented clinically with acanthosis nigricans, in which a subsequent diagnosis of mycosis fungoides was made.

Acral Acanthosis Nigricans in a Case of Scleroderma.

Acanthosis nigricans (AN) is a dermatosis characterized by velvety, papillomatous, brownish-black, hyperkeratotic plaques, typically on the intertriginous surfaces and neck. The majority (80%) of AN occurs idiopathically or in benign conditions such as endocrinopathies like diabetes mellitus, polycystic ovary syndrome; metabolic syndrome and/or heritable disease. Malignancy-associated AN is rare. AN may rarely be associated with autoimmune diseases including systemic lupus erythematosus, due to antibodies to the insulin receptor, so-called type B insulin resistance. Here we report a case of AN in a case of diffuse progressive systemic sclerosis without evidence of insulin resistance.

Oral malignant acanthosis nigricans associated with endometrial adenocarcinoma

We report a 59-year-old patient with malignant acanthosis nigricans associated with metastasis of endometrial carcinoma. The patient presented papillomatosis lesions that appeared to be benign on multiple skins of body folds, particularly on lips. The lesions in lips and axilla had histological characteristic appearances of acanthosis nigricans, while the masses in abdomen and pelvis were metastasis endometrial adenocarcinoma. The article highlights the importance of biopsy and histopathological diagnosis in presumed benign lesions and the role of doctors in screening for body internal tumors.

Acral acanthosis nigricans (acral acanthotic anomaly).

A 28-year-old female, apparently healthy and thinly built, presented with mildly itchy hyperpigmented hyperkeratotic plaques on her feet since three years. There were no systemic features suggestive of diabetes or other endocrinopathies associated with acanthosis nigricans (AN). She was not on any medication prior to onset of lesions. On examination, multiple well-defined hyperpigmented, hyperkeratotic plaques were present on the dorsum of several toes in a bilateral symmetrical manner [Figure 1]. Other skin sites, the scalp, palms, soles and mucosae were spared. Routine blood investigations, fasting and postprandial blood sugar and routine urine analysis were within normal limits. The liver enzymes, thyroid hormones and growth hormone were within normal range. Serum leptin and insulin level estimation could not be done as these were not available in our institute. Radiographic examination of the chest, skull and hands did not reveal any abnormality. Abdominal and pelvic ultrasonography was non-contributory. Biopsy of the skin showed hyperkeratosis, papillomatosis, increased pigmentation of the basal cell layer and mild acanthosis, with a sparse inflammatory infiltrate of mononuclear cells in the upper dermis [Figure ​[Figure2a2a and ​andb].b]. These histopathological findings were consistent with the diagnosis of AN. A final diagnosis of acral AN was made, considering clinical and histopathological findings. Figure 1 Hyperpigmented hyperkeratotic plaques on dorsal surface of toes Figure 2 (a) Hyperkeratosis, acanthosis, papillomatosis and sparse mononuclear cell infiltration in dermis (H and E, ×40) (b) Higher magnification (H and E, ×100) AN is a common presentation in the out-patient department and usually affects the neck, axillae, groin, inner aspects of the thighs, flexor and extensor surface of the elbows and knees, dorsal joints of the hands, umbilicus and anus. Schwartz has categorized the entity into the following eight types: benign, malignant, associated with obesity, syndromic, unilateral, drug induced, mixed and acral.[1] In acral AN, also called as acral acanthotic anomaly, the lesions are localized to the knee, ankle, phalangeal joints and tarsophalangeal joints.[1] It is apparently more common in persons with a dark complexion and affects acral areas without prominent affection of axilla and other flexures.[2] The clinical significance of acral AN is ambiguous and more studies are needed to settle this issue. According to Schwartz, this type of AN essentially occurs in healthy black people and does not, on its own, call for a vigilant work-up of those afflicted; for the possible presence of an internal malignancy. However, recently it has been reported in association with dermatofibrosarcoma protuberans, non-Hodgkin's lymphoma[3] and gastric adenocarcinoma.[4] Diagnosis is mostly clinical and can be confirmed by histopathology. In the majority of cases, improvement of the skin lesions is the primary concern of patients presenting to dermatologists. Treatment of its underlying condition often results in improvement of AN. The type occurring with obesity usually improves with weight loss. Etretinate, metformin, tretinoin, calcipotriol, urea, salicyclic acid, CO2 laser ablation and long pulsed alexandrite laser therapy have been reported as successful treatments in individual cases.[1,2]