Table of Content


Spring 2021, Vol. 29 No. 1

Hong Kong J. Dermatol. Venereol. (2021) 29, 26-31

Case Report

Oral malignant acanthosis nigricans associated with serous endometrial carcinoma: a case report and review of the literature


HK Ozden and D Bayramgürler


Malignant acanthosis nigricans is a paraneoplastic cutaneous syndrome. Clinical findings such as tripe palms and mucocutaneous papillomatosis in atypical sites such as the oral mucosa are strong indicators of a visceral malignancy. We report on a rare case of oral acanthosis nigricans who presented with a 2.5-month history of diffuse hyperkeratotic verrucous papillomatous lesions in the entire oral mucosa which were symptomatic only when eating. Based on the clinical and histopathological findings, acanthosis nigricans with serous type endometrial carcinoma was diagnosed. However; the patient defaulted follow-up after the diagnosis and she died two months later.


Keywords: Endometrial carcinoma, malignant acanthosis nigricans, tripe palm

關鍵詞: 子宮內膜癌、惡性黑棘皮病、牛胃掌


Acanthosis nigricans (AN) consists of reactive changes and be divided into two forms: Benign AN, which is frequently induced by endocrine disorders or medications, and malignant AN (MAN), which is rare and associated with malignancies. It is characterised by dark pigmented, velvety thickening of the skin observed symmetrically in the flexural areas of the skin such as axilla, inguinal and cervical areas.1 MAN is a paraneoplastic cutaneous syndrome, which is most often associated with gastric adenocarcinomas. Paraneoplastic findings such as tripe palms and excessive mucocutaneous papillomatosis that occur in atypical locations such as oral mucosa are strong indicators of a visceral malignancy.1

We report a case of MAN in association with serous endometrial carcinoma. This has not been reported in the literature previously.

Case report

A 65-year-old female presented with an acute onset of intraoral swelling that emerged 2.5 months ago to dermatology outpatient clinic. She was diagnosed with diabetes mellitus three years previously and was treated with insulin lispro (humagol 100 IU/ml sc). There was no other significant past medical, drug or family history of malignancy. Patient stated she attended our clinic for the first time and had not received any treatment in the previous 2.5 months. She stated that there was discomfort while she was eating and as a result, she avoided consuming solid food. There was no history of weight loss, fever, night sweating, or weakness.

On examination, there were non-pigmented hyperkeratotic verrucous papillomatous lesions in the entire oral mucosa from vermilion border of upper and lower lips, extending along the buccal mucosa, gingiva and dorsum of tongue. There were findings consistent with tripe palms including exaggerated dermatoglyphic areas in both palms and multiple wart-like verrucous papillomatous lesions on dorsum of the hand (Figure 1). Nail examination and all other systems examinations were normal. Velvety hyperpigmented and hyperkeratotic plaques were observed in bilateral axillary areas and inguinal folds (Figure 2). Routine biochemistry tests, fasting blood glucose, thyroid function tests and viral serology tests were within normal limits. Fasting blood sugar: 143 mg/dl, HbA1c: 44.72 mmol/mol (normal range: 20-44), Alanine Aminotransferase (ALT): 17 U/L, Alkaline Phosphatase (ALP): 32 U/L; HIV, syphilis and hepatitis serology values were negative. The carcinoembryonic antigen (CEA), alpha fetoprotein (AFP) and carbohydrate antigen (CA) 19-9 were within normal limits while Ca 15-3: 378.6 U/ml (normal range: 0-32.4) and Ca 125: 1789.1 U/ml (normal range: 0-30) levels were elevated. Computed tomography of the abdomen showed increased uterus size, multiple calcifications and soft tissue areas consistent with lymphadenopathy in paraaortocaval area and parailiac spaces. PET/CT studies revealed a severely thickened uterine wall with markedly increased hypermetabolic activity from uterine cavity to the cervix and multiple lymph node involvements were detected. It was therefore reported that a primarily gynaecological malignancy should be considered.

Figure 1 (a,b) Papillomatous and velvety oral lesions. (c) Multiple wart-like verrucous papillomatous lesions on the dorsum of the hand. (d) Tripe palms consisting of exaggerated dermatoglyphic areas in the palmar region.

Figure 2 (a) Velvety hyperpigmented and hyperkeratotic plaques in bilateral axillary areas and (b) inguinal folds.

Two punch biopsy samples were taken from axillary and buccal lesions of the patient. Histological examination showed prominent acanthosis, hyperkeratosis, papillomatous with minimal subepithelial inflammation (Figure 3).

Figure 3 (a) Oral specimen shows, acanthosis, papillomatous and minimal subepithealial inflammation (H&E x 100). (b) Axillary biopsy: Epidermal hyperkeratosis and dermal finger-like papillomatous hyperplasia (H&E x 100).

As the clinical and histopathological findings were consistent with MAN, a gastroenterology consultation was requested. Endoscopy and colonoscopy findings were normal. Patient was also referred to the gynaecology department for evaluation of gynaecological malignancy. However, the patient refused any intervention or treatment. Patient presented to our outpatient clinic with abdominal swelling approximately three months later. Ascites in the abdomen was detected during physical examination and nodular masses. After review by the gynaecology department, USG and abdominal tomography detected calcification in some of the nodular masses in the endometrial cavity. Biopsy findings of these lesions was consistent with stage 4 serous endometrial carcinoma. The patient defaulted follow-up appointments for treatment after the diagnosis and she died two months later.


Malignant acanthosis nigricans associated with abdominal malignancy was first reported by Pollitzer in 1890.1 MAN is very rare compared to the benign form. Although most frequently associated with gastric adenocarcinoma, MAN can be associated with several intra-abdominal malignancies such as pancreas, ovarian, bladder, cervix, endometrial, and esophageal malignancies.2 The pathogenesis of excessive verrucous papillomatous formations in mucocutaneous areas in MAN which is considered to be due to epidermal hyperproliferation emerging from stimulation by Insulin-like-growth-factor 1 (IGF-1), Transforming Growth Factor (TGF-α) and Epidermal Growth Factor (EGF).1,2 Tripe palms is a characterised by prominent dermatoglyphics and with rugose hyperkeratotic areas likened to stomach lining of beef in the palmar area and is regarded as a variant of AN. It accompanies paraneoplastic malignancies at a rate of 90%, most notably and frequently gastric cancers.2 The clinical diagnosis can be confirmed with skin biopsy. It does not have any specific histopathological findings but it can be frequently accompanied by hyperkeratosis, papillomatosis and hyperpigmentation at basal layer.2 Endometrial cancer (EC) is the most frequently associated gynaecological malignancy and can be divided into two groups: Type 1 EC has good prognosis while type 2 EC (serous and clear cell carcinoma) is very aggressive although it is very rare and seen frequently in women with older age.3

As far as we know, our case is the first MAN case accompanied by serous type EC. Oral MAN cases accompanied by gynaecological malignancies in the literature are summarised in Table 1. It is resistant to conventional treatments such as systemic corticosteroids, etretinate, topical corticosteroids, calcipotriol and salicyclic acid. The most efficacious treatment method is treatment of the underlying primary cancer with subsequent regression of the cutaneous findings.2 The clinicians' role is to detect acanthosis nigricans and tripe palms as early indicators and precursors of cancer. A high index of suspicion for malignancy, in particular abdominal malignancy with the appropriate screening is essential.

Table 1 Previously reported cases of oral malignant acanthosis nigricans associated with gynaecological malignancies
Article Patient Clinic presentation MAN locations Malignancy
Dingley4 1957 56/F Dry, sore tongue Axillae, face, oral involvement, palms and soles, arms, legs Ovarian adenocarcinoma
Mikhail5 1979 58/F Wart-like growth on the perineal region Oral, face, axillae, palmoplantar, vulvar, perineal region Cervical squamous cell carcinoma
Gorisek6 1997 54/F Postmenopausal menorrhagia Oral involvement, tripe palms, axilla, inframammary region, abdominal folds, inguinal and forearms Endometrial adenocarcinoma
Kebria7 2006 52/F Lesar Trelat sign and weight loss Oral involvement, neck, axillae, inframammary region, tripe palms Ovarian adenocarcinoma
Oh8 2010 57/F Hyperpigmentation of whole body and thickened palms and soles Buccal mucosa, tongue, axillae, neck, groins, palms and soles Ovarian adenocarcinoma
Chu9 2014 59/F Oral papillomatosis and sialorrhoea Oral, face, axillae, nipples, elbows, pudendum Endometrial adenocarcinoma
Garzitto10 2015 60/F Vitiligo and acanthosis nigricans Perioral involvement, axillae, inframammary region, inguinal, genital and tripe palms Ovarian adenocarcinoma


1. Singh GK, Sen D, Mulajker DS, Suresh MS. Acanthosis nigricans associated with transitional cell carcinoma of the urinary bladder. Indian J Dermatol 2011;56:722-5.

2. Pentenero M, Carrozzo M, Pagano M, Gandolfo S. Oral acanthosis nigricans, tripe palms and sign of leser-trélat in a patient with gastric adenocarcinoma. Int J Dermatol 2004;43:530-2.

3. Colombo N, Creutzberg C, Amant F, Bosse T, González-Martín A, Ledermann J, et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: Diagnosis, Treatment and Follow-up. Int J Gynecol Cancer 2016;26:2-30.

4. Dingley ER, Marten RH. Adenocarcinoma of the ovary presenting as acanthosis nigricans. J Obstet Gynaecol Br Emp 1957;64:898-900.

5. Mikhail GR, Fachnie DM, Drukker BH, Farah R, Allen HM. Generalized malignant acanthosis nigricans. Arch Dermatol 1979;115:201-2.

6. Gorisek B, Krajnc I, Rems D, Kuhelj J. Malignant acanthosis nigricans and tripe palms in a patient with endometrial adenocarcinoma – a case report and review of the literature. Gynecol Oncol 1997;65:539-42.

7. Kebria MM, Belinson J, Kim R, Mekhail TM. Malignant acanthosis nigricans, tripe palms and the sign of Leser-Tre'lat, a hint to the diagnosis of early stage ovarian cancer: a case report and review of the literature. Gynecol Oncol 2006;101:353-5.

8. Oh CW, Yoon J, Kim CY. Malignant Acanthosis Nigricans Associated with Ovarian Cancer. Case Rep Dermatol 2010;2:103-9.

9. Chu HW, Li JM, Chen GF, Ma JY. Oral malignant acanthosis nigricans associated with endometrial adenocarcinoma. Int J Oral Sci 2014;6:247-9.

10. Garzitto A, Ricceri F, Pescitelli L, Tripo L, Prignano F. Vitiligo masks malignant acanthosis nigricans in a woman with ovarian cancer. Int J Dermatol 2015;54:1300-2.