Ring-ring cutaneous malignancy appears with huge bunches of grapes

an introduction

Signet cell carcinoma (SRCC) is a mucin-secreting adenocarcinoma that contains an abundant amount of intracytoplasmic mucus that pushes the nucleus into the periphery. Cutaneous malignancy of the signet ring is extremely rare and indicates a poor prognosis, which previously manifested itself as a nodular papular plaque, as well as scar-like and red lesions. This case study demonstrated a rare signet ring-shaped cutaneous malignancy present with massive bunches of grapes. The condition was only diagnosed by a skin biopsy.

Status Report

A 58-year-old woman was admitted to our hospital in April 2021 due to a massive painful mass in the abdominal wall, along with a rapid decline in general health. An edematous plaque in the abdominal wall inexplicably started about 13 months before her admission, when she experienced simultaneously stomach pain and dizziness. During this period, she experienced a gradual weight loss of 5 kg. The plaque layer gradually thickens and hardens, forming numerous grape-like nodules on the surface.

in a physical examination (shape 1), the patient had a massive mass with grape-like clusters in the abdominal wall. When the nodules resembling grapes were punctured, a clear yellow liquid came out. The skin at the base of the tumor appeared dark red, thick, and hard, extending down the chest, upper thighs, and buttocks. No frank edema, swelling, erosions, or hemorrhagic lesions were found. The patient was pale and emaciated. Dullness of the rhythm and a decrease in breath sounds are observed in the lower lungs.

shape 1 Multiple, dense, hard nodules appear on and around the lower chest, abdominal wall, upper thighs, and buttocks.

Initial diagnostic examination revealed that hemoglobin levels were 75 g/L. Other findings were as follows: decreased total protein (51.5 g/l) and albumin (29.1 g/l), lactic dehydrogenase (LDH) (247.5 units/l), carcinoembryonic antigen (CEA) (6.37 ng/ml), carbohydrate antigen. (CA) 125 (248.15 IU/mL), CA 199 (>400 IU/mL), CA 50 (392 IU/mL), CA 242 (25.7 IU/mL), CA 724 (116 IU/mL) , β-human chorionic gonadotropin (β-HCG) (8.07 mIU/mL), cytokeratin 19 fraction 21-1 (CYFRA 21-1) (10.6 ng/mL), pro-gastrin peptide (ProGRP) (551 pg) / Ml) ). This set of findings suggested the presence of tumors derived from the gastrointestinal tract.

Computerized tomography revealed extensive swelling and effusion on the walls of the chest, abdomen, and pelvis, as well as interstitial pulmonary edema in both lungs, and lobed nodules in the upper part of the right lung, as well as a few mucus plugs. in the trachea.

Multiple vegetations on the anterior abdominal wall and bilateral thighs were observed by positron emission tomography/computed tomography (PET/CT), along with intense fluorodeoxyglucose (FDG) uptake. Other FDG-positive pathological lesions were also observed in the upper apical part of the right lung, multiple enlarged lymph nodes in the bilateral neck roots, and the left upper and lower clavicular fossa (Figure 2a), mediastinum, double hilum, tibia, sternum, retroperitoneal (Figure 2b), the left side of the rectum and bilateral iliac vessels, nodules in the upper right posterior lobe of the liver, as well as the left femur and abdominal wall nodules (Figure 2b). Thoracentesis was performed and the result of tumor biomarkers from pleural effusion was consistent with that of serum.

Figure 2 PET/CT: A high uptake of 18F-FDG was observed in some left clavicular fossa ganglia (a), retroperitoneal lymph nodes, and abdominal wall nodules (B) (red arrows).

A skin biopsy was made of grape-like nodules and dark red spots. There was lymphatic expansion, and cutaneous mucin deposition in both lesions, but with scattered ring-shaped cells within the deep retinal dermis and subcutaneous only in the dark red macula (Figure 3A). Lesion cells are stained with cytokeratin (CK), Cam 5.2, CK 7, CK 20 and Villin (Figure 3b-d), while negative with S100, homeopathic caudal type 2 (CDX 2), thyroid transcription factor-1 (TTF-1), estrogen receptor (ER), and gross cyst disease fluid protein 15 (GCDFP-15).

Figure 3 Histological staining: signet ring cells (white arrows) and dilated lymphatic vessels (a) (Hematoxylin-eosin staining, ×200). The lesioned cells were immunoprecipitated for CK7 (B), CK20 (c) and evil (Dr) (immunity, x 200).

Elevated tumor biomarkers in both pleural and serum effusions, together with immunophenotypic findings indicated the presence of diffuse sarcoma of gastrointestinal origin. Therefore, esophagogastroduodenoscopy with biopsy has been suggested. Unfortunately, the patient developed atrial fibrillation upon completion of the esophagogastroduodenoscopy and died despite all rescue efforts. Ultrasound-guided transtracheal needle aspiration (EBUS-TBNA) and left clavicular lymph node biopsy cannot be completed. Under esophagogastroduodenoscopy, multiple ulcers were found in the gastric antrum and duodenal bulb, but some infiltration of inflammatory cells without tumor cells was found in the gastric tissue, histologically.


SRC is a morphological description of a cell whose nucleus is pushed into the periphery by excessive intracytoplasmic mucus. The condition is most commonly found in adenomas, particularly in the gastric epithelium.1 According to the classification of the World Health Organization, gastric CSCs are a subtype of adenomas. In addition, signet ring cells can be found in primary cutaneous SRCC of exocrine or secretory origin, basal cell carcinomas of primary cutaneous signet ring, melanomas, and squamous cell carcinomas.2 Cutaneous malignancy of the signet ring is extremely rare, usually occurring in the late stage of the disease, indicating a poor prognosis. Clinical manifestations of SRCC skin metastases such as papular plaques, erythema, as well as scar-like and erythrodermic lesions have been reported.3And the4 This case demonstrated in this study a rare signet ring-shaped cutaneous malignancy presenting with lesions resembling the shape of massive grapevines, which has not been described in all the literature, to the best of our knowledge. In our case we speculated that the path of cutaneous metastasis to visceral tumors was via the lymphatic vessels. Cutaneous metastasis of visceral tumors occurs by invading adjacent tissues in the hematological, lymphatic, and iatrogenic transplantation pathways.5 In our case, some dilated lymphatic vessels in hematoxylin-eosin staining suggested that the patient’s skin lesions were probably due to an accumulation of cancerous lymphangitis.

It is difficult to identify primary carcinoma of SRCC cutaneous metastasis, but gross histopathological evaluation and immunohistochemical stains can be particularly helpful.4And the8 Given that the malignant cells would go on to synthesize tissue-specific proteins that could be identified by targeted immunoblotting, these cells maintained an adequate level of differentiation from the primary tumor. For example, positive CK and CAM 5.2 in particular may help differentiate adenocarcinomas. In our case, the presence of CSCs enhanced immunity to common gastrointestinal malignancies with CK 7, CK 20 and Villin.6 The negative CDX 2 staining reduced the possibility of thinking about the origins of the colon and rectum.7 In addition, S100 negativity, SMA, NSE, TTF-1, ER, and GCDFP-15 helped exclude melanoma, gynecological, lung, and breast cancer stem cell origins, respectively.6-8

Although the incidence of cutaneous metastases from gastrointestinal cancers is low, the liver, lung and bone involvement in this case also provided clear evidence for the gastrointestinal origin of SRCC.8 Some cases failed to reveal the primary site of origin for CSCs.4And the9 About 30-40% of unknown primary tumors are poorly differentiated adenocarcinomas or carcinomas. It has been proposed that primary tumors acquire a special phenotype and/or occur due to inborn errors, leading to negative effects on primary growth.10 Furthermore, due to the rich intracytoplasmic mucin, membrane glucose transporter-1 deficiency, and thus low FDG uptake, the 18F-FDG PET/CT assay has limited efficacy in diagnosing gastrointestinal SRCC.11

In conclusion, we presented the patient with rare manifestations of lesions that appear as massive clusters in the abdominal wall. This was diagnosed as metastatic SRCC of gastrointestinal origin. It is suggested that skin biopsy and immunohistochemical staining are not only useful, but necessary for the diagnosis of SRCC and identification of primary cancer, which should be taken without hesitation when a suspicion of carcinoma arises.


CA, carbohydrate antigen. CDX 2, homeobox caudal type 2; CEA, carcinoembryonic antigen; CK, cytokeratin. CYFRA 21-1, cytokeratin 19 fragment 21-1; EBUS-TBNA, ultrasound-guided transbronchial needle aspiration; Estrogen receptor ER. FDG, fluorodeoxyglucose; GCDFP-15, gross cystic fluid protein-15; LDH, lactic dehydrogenase; PET/CT, positron emission tomography/computed tomography; ProGRP, a pro-gastrin-release peptide; SRC, signet ring cell; SRCC, signet ring cell carcinoma; cancer stem cells, signet ring cells; TTF-1, thyroid transcription factor-1; β-HCG, β- human chorionic gonadotropin.

Statement of Ethics and Consent

All patient samples and clinical data used were approved by the Southwest Medical University Hospital Ethics Committee. Written informed consent for case publication was provided by the patient’s spouse for publication of all patient photographs, specimens, and clinical data.

Thanks and appreciation

We would like to thank the patient and her family. Zhenyu Hao and Yongqiong Deng are the co-authors of this study.


The authors do not state any conflict of interest in this work.


1. Wu SJ, Chen XT, Zhang W, et al. Survival in signet ring cell carcinoma varies based on the location of the primary tumor: surveillance, epidemiology, and end-results database analysis. Expert Pastor Gastroenterol Hepatol. 2018; 12 (2): 209–214. doi: 10.1080/17474124.2018.1416291

2. Kiyohara T, Kumakiri M, Kouraba S, Tokuriki A, Ansai S. Primary cutaneous annular cell carcinoma expressing cytokeratin 20 immunoreactivity. J Am Acad Dermatol. 2006;54(3):532–536. doi:10.1016/j.jaad.2005.04.039

3. Cokgezer S, Samanci NS, Bektas M, Kepil N, Demirelli FH. Cutaneous metastasis of signet cell infectious carcinoma. Indian J Dermatol. 2020; 65 (2): 148-150. doi: 10.4103/ijd.IJD_263_18

4. Raval N, Shmoilovich L, Strickley J, Chen TY, Roseman ES, Mosik A. Signet ring cutaneous malignancy presents with massive anasarca. serious case actor. 2021; 10: 123-125. doi: 10.1016/j.jdcr.2021.02.009

5. Hu SC, Chen GS, Wu CS, Chai Si, Chen WT, Lan CC. Rates of cutaneous metastases from various internal malignancies: a trial from a Taiwanese medical center. J Am Acad Dermatol. 2009;60(3):379–387. doi:10.1016/j.jaad.2008.10.007

6. Habermehl G, Ko J. Skin metastases: a review and diagnostic approach for tumors of unknown origin. Pathol Lab Med Arch. 2019; 143 (8): 943–957. doi: 10.5858/arpa.2018-0051-RA

7. Alcaraz I, Cerroni L, Rütten A, Kutzner H, Requena L. Cutaneous metastases from internal malignancies: a clinical and immunohistochemical review. I J Dermatopathol. 2012; 34 (4): 347–393. doi: 10.1097/DAD.0b013e31823069cf

8. Gündüz Ö, Emeksiz MC, Atasoy P, Kidir M, Yalçin S, Demirkan S. Dermatol rep. 2017; 8 (1): 6819. doi: 10.4081/d.2016.6819

9. Gregoire C, Muller G, Maciels JP, Goeminne JC. Diffuse signet ring cell carcinoma of unknown primary origin. Acta Clean Belgium. 2014; 69 (2): 135-138. doi: 10.1179/0001551213Z.0000000002

10. van de Wouw AJ, Jansen RL, Speel EJ, Hillen HF. The biology of an unknown primary tumor: a review of the literature. Anne Oncol. 2003; 14 (2): 191-196. doi: 10.1093/declared/mdg068

11. Yamada A, Oguchi K, Fukushima M, Imai Y, Kadoya M. Evaluation of 2-deoxy-2-[18F]Fluoro-D-glucose positron emission tomography in gastric cancer: relationship between histological subtypes, depth of tumor invasion, and glucose transporter-1 expression. Ann Nucle Med. 2006; 20 (9): 597–604. doi: 10.1007/BF02984657