Acanthosis nigricans disease (AN) is a dermatological disorder characterized by hyperpigmentation, hyperkeratosis, verrucous hyperplasia, and velvety thickening, often occurring in a specific area of the skin, such as the neck, axillae, and areola of the groin area. A few patients with acanthosis nigricans with intrinsic malignancy are called malignant acanthosis nigricans [1], which is rarely reported in China [2]. 1. The patient was diagnosed with acanthosis nigricans on biopsy without gastroscopy or serologic tumor markers at that time. The patient had a history of diabetes mellitus for more than 10 years, and was taking Damacell to lower the sugar level. On examination, the patient’s skin was rough and thickened with dark brown color, with diffuse warty hyperplasia, most obvious in the cheeks (Figure 1), bilateral axillae, periareolar area and perineum. Blood count: WBC 5.58×109/L, RBC 3.94×1012/L, Hb 87.8g/L, PLT 229.2×109/L. Biochemistry: aspartate aminotransferase (AST) 15U/L, alanine aminotransferase (ALT) 12U/L, urea nitrogen (BUN) 5.7mmol/L, creatinine (Cr) 96μmol/L. Tumor markers: AFP 0.97μg/L, CEA 18.86μg/L, ferritin 3.6μg/L, CA125 5.19kU/L, CA15?3 14kU/L, CA19?9 >500kU/L. CT showed a pancreatic mass about 6cm in diameter and a small omental sac with suspicious enlarged lymph node shadow, combined with gastroscopy. 1.2 Treatment and study methods Preoperative neoadjuvant chemotherapy (interventional) was administered twice: 5?FU750 mg + oxaliplatin 200 mg + famasin 50 mg via the right femoral artery puncture to the abdominal artery, and skin pigmentation was reduced immediately after chemotherapy. The tumor was located in the inferior cardia (Figure 2), about 8.0 cm × 6.0 cm × 3.0 cm, invading the plasma membrane and involving the tail of the pancreas, which could still be pushed, and there were no enlarged lymph nodes in front of the abdominal aorta. The patient was treated with 5?FU 750mg intravenously throughout the operation, and cisplatin 80mg was infused intraperitoneally for 6 h. He was discharged from the hospital 10 d after surgery. Immunohistochemistry was performed to detect the expression of TGF?α and EGF receptors in tumor tissue specimens and compared with 10 specimens of non-malignant acanthosis nigricans.2. The patient was discharged 10 d after surgery. One month after discharge, the patient was admitted to the hospital with liver discomfort and high fever, and CT showed a middle lobe liver abscess. The postoperative pathology showed (Figure 3 and 4) ulcerated carcinoma of the cardia – tubular adenocarcinoma (moderately differentiated) with squamous cell combination; the tumor invaded the extra-plasma membrane, and the lymph nodes had 0/7 on the small curved side and 1/5 on the large curved side with squamous cell metastasis. The patient came to the hospital for regular follow-up, which has continued for more than 2 years so far, with no signs of tumor recurrence on imaging and serum examination (Table 1) and complete regression of skin lesions (Figure 1). In the specimens of gastric cancer with malignant acanthosis nigricans, the expression of TGF?α and EGF receptors was positive, while in the specimens of other gastric cancers, there was only one case with weakly positive expression of TGF?α and EGF receptors, two cases with positive expression of EGF receptors but no expression of TGF?α, and the rest were negative (Figure 5).3. In 1994, Schwartz divided acanthosis nigricans into 8 types: benign, obese, malignant, syndromic, acral, unilateral, drug-induced and mixed. Our medical community is accustomed to 3 types, namely benign type, malignant type and symptomatic type. The skin tissue is characterized by a significant increase in melanocytes, marked hypertrophy of the dermal papillae and hyperkeratosis under the microscope. Non-malignant lesions are mild and some patients can heal spontaneously, mostly in newborns, adolescents or adults, and are associated with genetics, obesity and endocrine diseases. Malignant acanthosis nigricans mainly affects middle-aged and elderly people, and is often associated with adenocarcinoma of the digestive tract, with gastric cancer being the most common. It is generally believed that patients with severe lesions have a poor prognosis, often with early metastasis and a short survival period. The etiology and pathogenesis of the disease are unknown, but it may be due to the production of certain cytokines by malignant tumors, which directly or indirectly induce acanthosis nigricans through signal transduction pathways at the cell receptor level [2-3]. However, due to the very low incidence of this disease, it cannot be supported by a large amount of data, and this case is consistent with its report. In patients with acanthosis nigricans, the physician should be vigilant and perform some necessary ancillary examinations and laboratory tests to exclude possible hidden malignant tumors. For patients with no improvement or even progressive worsening of skin lesions after repeated visits to the clinic or with progressive wasting, malignant acanthosis nigricans should be considered as a possibility. In this case, the patient’s serum AFP and CEA were normal, while CA19?9 was >500kU/L, which highly suggested the possibility of malignancy. Through the retrospective study of this case, we believe that early serological examination of patients considered to have malignant acanthosis nigricans and corresponding imaging or endoscopic examination according to the serum tumor indicators are beneficial to the early detection of tumor and improve the prognosis of patients. Treatment should be aimed at early surgical removal of the primary tumor. As long as the tumor can be completely removed, the skin lesion will be significantly improved. If the tumor stage is late, neoadjuvant chemotherapy can be administered before considering surgery [1]. Some patients are sensitive to chemotherapy and can achieve good results with chemotherapy alone. In this case, the skin damage improved rapidly after surgery, and the serum tumor marker level also decreased immediately, suggesting that the changes of skin lesions and serum tumor markers can be used as an auxiliary reference index to observe the clinical efficacy of malignant acanthosis nigricans tumors and whether they recur. From the treatment process of this case, we can find that the skin damage of malignant acanthosis nigricans is reversible, and when the malignant tumor is eradicated, the skin damage can completely fade away and return to normal state.