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Widespread Thickened, Verrucous, Hyperpigmented Plaques in a Woman With Weight Loss

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 30-year-old woman presented with a 4-month history of widespread thickened, verrucous, hyperpigmented plaques distributed symmetrically on her body, especially on the axillae (Figure 1A), anogenital region, inguinal skin, and both palms, with slight itching. The verrucous plaques also involved the conjunctiva, lips, and gingiva (Figure 1B). The patient had experienced a weight loss of 6 kg during the last 3 months. Within the last month, the patient’s thyroid became enlarged, and she developed anorexia and abdominal discomfort. Laboratory test results revealed remarkably elevated levels of carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, tissue polypeptide antigen and carbohydrate antigen 242. Biopsy specimens of lesions on the axillae and lips both revealed a papillary structure with hyperkeratosis. An endoscopic examination and computed tomographic scan of the abdomen were performed.

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C. Malignant acanthosis nigricans

The keys to the correct diagnosis are the verrucous, hyperpigmented plaques in atypical sites (mucous membranes, palms and anogenital region), the additional paraneoplastic findings (tripe palms), and recent obvious weight loss. Most cases of acanthosis nigricans (AN) are benign and are associated with obesity and insulin resistance in which blood glucose and insulin levels are important for diagnosis. The disease is less commonly associated with a malignant neoplasm. Malignant AN is predominantly associated with gastrointestinal tract tumors, especially carcinoma of the stomach.1

The gastroscopy findings revealed esophageal papillomatous polyposis and a submucosal mass involving the gastric angle. Biopsy results revealed that the mass was a mix of adenocarcinoma and signet-ring cell carcinoma (Figure 2). A computed tomographic scan of the abdomen showed a thickening of the gastric wall and multiple organ metastases. The results of biopsies of the thyroid and pancreas suggested metastases of gastric cancer. The patient was then transferred for further chemotherapy without any dermatological treatment and died 4 months later due to cancer progression.

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Article Information

Corresponding Author: Mingyue Wang, MD, PhD, Department of Dermatology, Peking University First Hospital, 8 Xishiku St, Xicheng District, Beijing 100034, China (wangmy@pku.edu.cn).

Published Online: March 14, 2019. doi:10.1001/jamaoncol.2018.7153

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Ping Tu, MD and Qianxi Li, MD for the discussion of the patient’s diagnosis and treatment plan. They were not compensated for their contributions.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Liu  XK, Li  J.  Hyperpigmentation in the skin folds.  BMJ. 2018;360:j5729. doi:10.1136/bmj.j5729PubMedGoogle ScholarCrossref
2.
Zhang  N, Qian  Y, Feng  AP.  Acanthosis nigricans, tripe palms, and sign of Leser-Trélat in a patient with gastric adenocarcinoma: case report and literature review in China.  Int J Dermatol. 2015;54(3):338-342. doi:10.1111/ijd.12034PubMedGoogle ScholarCrossref
3.
Stawczyk-Macieja  M, Szczerkowska-Dobosz  A, Nowicki  R, Majewska  H, Dubowik  M, Sokołowska-Wojdyło  M.  Malignant acanthosis nigricans, florid cutaneous papillomatosis and tripe palms syndrome associated with gastric adenocarcinoma.  Postepy Dermatol Alergol. 2014;31(1):56-58. doi:10.5114/pdia.2014.40663PubMedGoogle ScholarCrossref
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Chu  HW, Li  JM, Chen  GF, Ma  JY.  Oral malignant acanthosis nigricans associated with endometrial adenocarcinoma.  Int J Oral Sci. 2014;6(4):247-249. doi:10.1038/ijos.2014.1PubMedGoogle ScholarCrossref
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Phiske  MM.  An approach to acanthosis nigricans.  Indian Dermatol Online J. 2014;5(3):239-249. doi:10.4103/2229-5178.137765PubMedGoogle ScholarCrossref
6.
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(2):353-355. doi:10.1016/j.ygyno.2005.12.024PubMedGoogle ScholarCrossref
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