The 79-year-old female patient was admitted to the hospital due to a black mass on the bigger toe of the right foot for more than 4 years, the radical excision of the skin lesion after completing a relevant investigation was done and diagnosed postoperatively pathologically as a freckled malignant melanoma. Amputation of the toe was performed after 10 days. she was admitted to the hospital again one month after surgery for adjuvant therapy. There have been no special symptoms such as loss of appetite, fatigue, shortness of breath, palpitations, and weight loss since this onset.
The patient has had hypertension for over 40 years with no history of diabetes, coronary heart disease, or tuberculosis; the most severe hypertension is 160/90mmHg, which is well controlled by oral antihypertensive medications. Underwent resection of bone tumor in left-hand middle finger 45 years ago, cholecystectomy for gallbladder stones 39 years ago, and resection of bladder malignant tumor followed by adjuvant chemotherapy15 years ago, the exact pathological diagnosis and systemic treatment are unknown at that time. Since then, the patient has lived in a good state without clinical manifestations of tumor recurrence and metastasis. Denying a family history of malignancy.
There were no yellow stain, rash, or bleeding spots on the skin and mucosa of the whole body, and superficial lymph nodes were not touched. Surgical scars were seen on the right abdomen and the fingers of the left hand. The first metatarsophalangeal of the right foot was missing with a well-healed surgical incision.
Serum tumor markers were detected as follows: CEA 184.00 ng/ml, CA125 778.00U/ml, CA199>1000.00U/ml, CA72-4 22.10U/ml, NSE 16.10ng/ml and CY211 11.0ng/ml. No significant abnormalities were found in other laboratory tests.
Prior to postoperative adjuvant therapy, a PET/CT ( Figure 1 ) scan revealed a mild hypodensity mass with a maximum SUV value of 12.0 in the lateral segment of the left hepatic lobe, which was diagnosed as a malignant tumor. In addition, enlarged lymph nodes were visible in the left parotid gland, hilar hepatic and retroperitoneal regions, and FDG metabolism is elevated, which was considered as metastasis. CT scan showed a wedge-shaped and slightly hypodense mass in the lateral segment of the left hepatic lobe. MRI revealed an irregular soft tissue mass in the lateral segment of the left hepatic lobe with a slightly low signal intensity on T1WI and a heterogeneous slightly high signal intensity on T2WI, as well as dilated adjacent bile ducts.
The resected mass of the right toe was submitted to undergo histology and immunochemistry. Histologically, the freckle-like tumor tissue invaded the superficial dermis with a 0.6 cm of maximum diameter and 0.2 mm Breslow thickness, which was identified as grade Clark IV without residual tumor cells in transverse and longitudinal margins. Pathological diagnosis of acral freckle-like malignant melanoma. Immunoperoxidase stains were performed on a Ventana NEXES Automated Immunohistochemistry System (Fuzhou Maixin Biotech Co., Ltd., Fuzhou, China) Vimentint, HMB45 and Melan A were positive in the tumor cells, while CKp, S-100, SOX-10, and CD68 were negative. Ki-67 was reactive in approximately 40% of the tumor cells ( Figure 2 ). Pathological diagnosis is a freckled malignant melanoma of the extremities. Immunohistochemical features of liver aspiration biopsy tissue are as follows ( Figure 3 ): CK19, CK7, CKp, and MUC5AC were positive in tumor cells, while Hepatocyte, CDX-2, TTF-1, HMB45, Melan-A, S100, and SOX10 were negative. The pathological diagnosis of a liver tumor is intrahepatic cholangiocarcinoma. Serum NGS testing suggested a potentially clinically significant missense mutation in exon 2 of the KRAS gene, namely P.G12V.
Based on medical history and double Primary Cancer confirmed this time, four primary tumors were comprehensively diagnosed, including bone tumors, bladder malignancies, malignant melanoma, and hepatic cholangiocarcinoma.
Based on NGS (P.G12V) and coexisting Acral melanoma(AM) and intrahepatic cholangiocarcinoma as well as systemic lymph node metastasis, there is currently no sensitive Class A targeted drugs. 6 cycles of GP (gemcitabine hydrochloride 1.5g, d1,8/cisplatin 40 mg, d1, 8) combined with anti-PD-1 inhibitors (Camrelizumab 200 mg, d1) system therapy From April 2021 to August 2021, Followed by 3 cycles of Camrelizumab (200 mg, q3w) maintenance therapy during September to October 2021, and efficacy evaluation (RECIST version 1.1) as SD throughout treatment. she was re-admission because of mild yellowing sclera in December 2021, laboratory tests showed abnormal liver function indicators such as DBIL 40.1 umol/L, IBIL 48.1 umol/L, ALT 205 U/L, and AST 181 U/L. MRCP indicated ( Figure 4 ) multiple liver metastases and biliary obstruction, and tumor progression was considered, so the 4th cycle of immune maintenance therapy was suspended. To improve liver function, endoscopic retrograde cholangiography (ERCP) and biliary stenting were also carried out. The tumor continued to progress 1 month after ERCP surgery, and the patient and family refused to continue anti-tumor therapy. Infectious shock and multiple organ failure caused the patient's death in March 2022. The patient had a satisfactory curative effect and lived for up to a year after being diagnosed with double primary cancers.