Cutaneous metastases from gastric adenocarcinoma 15 years after curative gastrectomy^*

Abstract

We report the case of a 38-year-old man, who developed cutaneous metastases in the left inguinal groove 15 years after curative gastrectomy for advanced gastric adenocarcinoma. Histopathologic examination revealed poorly differentiated adenocarcinoma cells. They were stained positive for villin, CDX-2, CKpan (AE1/ AE3), CEA, CK8/18, CK19, CK7, EMA, Ki-67 (50%), and negative for S-100, CK20, CD34, GCDFP-15 and TTF-1. The patient underwent local excision, after the presence of other metastases was excluded. Nevertheless, local recurrence developed at the surgical bed one year later and PET/CT revealed metastases to lymph nodes, bone and skin. He died 2 years after the appearance of cutaneous metastases. We have reviewed the literature and described the immunohistochemical characteristics of cutaneous metastases from gastric adenocarcinoma.

Keywords:
Neoplasm metastasis; Skin neoplasms; Stomach neoplasms

INTRODUCTION

Gastric adenocarcinoma (ADC) is one of the most common causes of cancer deaths around the world. Cutaneous metastases from gastric ADC are rare, and generally occur at a very end-stage in the course of disease. We report an extraordinary case of a young man with gastric ADC, who developed cutaneous metastases in the left inguinal groove 15 years after gastrectomy. To our knowledge, this case represents the longest interval from gastric ADC to cutaneous metastases after curative gastrectomy.

CASE REPORT

A 38-year-old man complained of a rash and subcutaneous nodules over the inguinal groove in March 2011. He had been previously diagnosed with poorly differentiated gastric ADC and underwent total gastrectomy in May 1997, followed by subsequent adjuvant chemotherapy using cisplatin and etoposide for 2 years. Periodical gastroscopy examination did not reveal abnormalities after surgery in the following years. Physical examination showed multiple, reddish-colored, fixed nodules, measuring between 0.5 and 3cm in diameter in the left inguinal groove area (Figure 1). Moreover, there were palpable enlarged lymph nodes in the left groin. Histopathological examination revealed tumor cells with hyper-chromatic nuclei, numerous mitoses and prominent ductal formation, consistent with adenocarcinoma, and tumor nests extending from the epidermis into the dermis (Figure 2). Immunohistochemical examination showed that these cells were positive for cytokeratin pan (CKpan), carcinoembryonic antigen (CEA), villin, CK8/18, caudal type homeobox transcription factor 2 (CDX-2), Ki-67 (50%), epithelial membrane antigen (EMA), CK7, CK19, but negative for S-100 protein, CK20, GCDFP-15, TTF-1, CD34 (Figure 3). Examination with 18F-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (PET/CT) revealed lymph node metastases and skin metastases in the left inguinal groove. The nodules were surgically removed and inguinal lymph nodes were cleared. He was prescribed chemotherapy with 5-fluorouracil in combination with paclitaxel for four cycles, and paclitaxel plus capecitabine for two cycles. However, there were red papules again on the former surgical bed in October 2012. Also, the patient reported bone pain bilaterally over the knees and hip joints. PET/CT revealed multiple areas of focal activity on the femur, vertebral column and ribs. The Radiotherapy Department used stereotactic radiosurgery with total irradiated dose (TD) of 33Gy/3 fractions (fx) with 75% isodose line. The patient's pain caused by bone metastases subsided. Nonetheless, chemotherapy did not improve his general condition, skin nodules persisted, and he died in December 2013.

FIGURE 1
Multiple, reddish-colored, fi xed nodules, measuring between 0.5 and 3cm in diameter in the left inguinal groove area

FIGURE 2
Histopathological examination revealed that tumor cells had hyperchromatic nuclei, numerous mitoses and prominent ductal formation, consistent with adenocarcinoma, and tumor nests extended from the epidermis into the dermis. (A HE×100, B HE×400)

FIGURE 3
Immunohistochemistry of cutaneous metastasis from gastric adenocarcinoma. (100×): (A) CDX-2, (B) CKpan, (C) CK19, (D) CD8/18, (E) CK7, (F) EMA, (G) villin, (H) Ki-67, (I) CKpan (J) CEA

DISSCUSION

Gastric ADC usually metastasizes to the liver, peritoneal cavity and regional lymph nodes. Cutaneous metastases are rare, developing in less than 5% of gastric ADC patients. Cutaneous metastases may be the first presentation of such malignancies, or occur during follow-up.^1,2They usually manifest as solitary or multiple red or violaceous dermal or subcutaneous painless nodules, and may also appear as cellulitis-like or erysipelas-like erythematous plaques.^2-4

This case is remarkable for several reasons. Firstly, it is noteworthy for the rarity and the unusual cutaneous metastases localization in the left inguinal groove. Most cutaneous metastases usually derive from breast cancer (18.6%-50%) in females or lung cancer (3%-7.5%) in males, with gastric ADC accounting for only 6% of all skin metastases.³Cutaneous metastases from gastric ADC usually develop on the abdominal skin, including the umbilicus (sister Mary Joseph nodule). Less common sites have also been reported such as face, scalp, breast, eyelids, dorsal area, neck, extremities and palms.^3,5-8Inguinal groove metastases, however, are rare. Tumor cells metastasize to skin through several routes, including direct invasion from underlying structures, extension and embolization through lymphatic and blood vessels, and accidental implantation during surgery.

Secondly, the patient presented long-term survival and tumor-free survival after surgery. Gastric cancer is a disease with high mortality rate. This case represents, to our knowledge, the longest interval from primary cancer to cutaneous metastases after curative gastrectomy. Cutaneous metastases from gastric ADC are considered to be a predictor of poor prognosis. Therefore, cutaneous metastases must be distinguished from primary cutaneous carcinoma, which is critical for clinical diagnosis and outcome assessment. Histologic phenotype is a crucial feature in the diagnosis of cutaneous metastases, as it is similar to that of the primary tumor. The primary gastric specimen of our patient was unavailable, because the resection had been done too long ago and the sample was not saved. According to literature review, we found that tumors from gastric origin are distinguished by the expression of some adenoepithelial and/or gastrointestinal markers including Ckpan (AE1/AE3), CK7, CK8/18, CK19, CEA, CDX-2 or EMA, which were all positive in our case (Table1).^1,2,5-10The clinical history is usually helpful. Therefore, we diagnosed this patient with cutaneous metastases from gastric adenocarcinoma.

TABLE 1
Immunohistochemical characteristics of cutaneous metastases from gastric ADC in currently available reports

Year of report and REFERENCES	Age/ gender	Duration of cutaneous metastases	Location	Immunohistochemical analysis		Outcome
				Cutaneous	Gastric
20057	60/M	2y	Face, scalp, right thigh	Positive for CK 1, 5, 10, 14, 7, 8, 18, 19, CEA, weakly positive for CK20, negative for CK13	Positive for CK 1, 5, 10, 14, 7, 8, 18, 19, CEA, weakly positive for CK20, negative for CK13	Death
20091	54/M	First clinical manifestation	Scalp	Positive for CK20, CK7, MIB-1, Pancyto, negative for CDX2, TTF1,S-100	Positive for CK20, CK7, MIB-1, Pancyto, negative for CDX2, TTF1, S-100	Death
20142	61/M	8y	Left groin and thigh	Positive for CK7, partially positive for CK20, negative for S100 and LCA	Not performed	Death
20108	69/M	First clinical manifestation	Chest	Positive for AE1/AE3, CK20, CK18, negativity for GCDFP-15, CK7, S-100, HMB-45, MELAN A, CD45	Not performed	Death
20105	68/F	3 year history of gastric ulcer	Neck	Positive for CK7, negative for CK20	Not performed	Not mentioned
20089	61/M	First clinical manifestation	Neck	Positive for CK7, CEA, negative for CK20	Positive for CK7, CEA, negative for CK20	Not mentioned
20056	73/M	3.5y	Scalp and upper forehead.	Positive for AE1/AE3	Not performed	Death
200810	48/M	First clinical manifestation	Lower abdomen, thorax, left side, arms, face	Positive for EMA, CEA, AE1 /AE3, TTF-1, negative for S-100, CK20, CK7, HHF-35, AML	Not performed	Deterioration
Present case	38/M	15y	Left inguinal groove	Positive for villin, CDX-2, CKpan, CEA, CK8/18, CK19, CK7, EMA, Ki67(50%), negative for S-100, CK20, CD34, GCDFP-15, TTF-1	Not performed	Death

• Financial Support: None.
• How to cite this article: Liu F, Yan WL, Liu H, Zhang M, Sang H. Cutaneous metastases from gastric adenocarcinoma 15 years after curative gastrectomy. An Bras Dermatol. 2015;90 (3 Suppl 1): S46-50.
• *
  Work performed at the Department of Dermatology, Jinling Hospital affi liated to Nanjing University School of Medicine – Nanjing, China.

References

• ¹
  Frey L, Vetter-Kauczok C, Gesierich A, Bröcker EB, Ugurel S. Cutaneous metastases as the first clinical sign of metastatic gastric carcinoma. J Dtsch Dermatol Ges. 2009;7:893-895.
• ²
  Takata T, Takahashi A, Tarutani M, Sano S. A rare case of cellulitis-like cutaneous metastasis of gastric adenocarcinoma. Int J Dermatol. 2014;53:e122-4.
• ³
  Narasimha A, Kumar H. Gastric adenocarcinoma deposits presenting as multiple cutaneous nodules: a case report with review of literature. Turk Patoloji Derg. 2012;28:83-6.
• ⁴
  Lee CK1, Chang YW, Jung SH, Jang JY, Dong SH, Kim HJ, et al. A case of Sister Mary Joseph's nodule as a presenting sign of gastric cancer. Korean J Gastroenterol. 2008;51:132-6.
• ⁵
  Karakoca Y, Aslan C, Erdemir AT, Kiremitci U, Gurel MS, Huten O. Neurofibroma like nodules on shoulder: First sign of gastric adenocarcinoma. Dermatol Online J. 2010;16:12.
• ⁶
  Lifshitz OH, Berlin JM, Taylor JS, Bergfeld WF. Metastatic gastric adenocarcinoma presenting as an enlarging plaque on the scalp. Cutis. 2005;76:194-6.
• ⁷
  Früh M, Ruhstaller T, Neuweiler J, Cerny T. Resection of skin metastases from gastric carcinoma with long-term follow-up: an unusual clinical presentation. Onkologie. 2005;28:38-40.
• ⁸
  Aneiros-Fernandez J, Husein-ElAhmed H, Arias-Santiago S, Escobar Gómez-Villalva F, Nicolae A, O'Valle Ravassa F, et al. Cutaneous metastasis as first clinical manifestation of signet ring cell gastric carcinoma. Dermatol Online J. 2010;16:9.
• ⁹
  Hayashi K, Yamamoto T, Oyama K, Nagai T, Tsuboi R. Epidermotropic skin metastasis from gastric cancer: immunohistochemical analysis using cytokeratins. Clin Exp Dermatol. 2009;34:406-8
• ¹⁰
  Xavier MH, Vergueiro Tde R, Vilar EG, Pinto JM, Issa MC, Pereira GB, et al. Cutaneous metastasis of gastric adenocarcinoma: an exuberant and unusual clinical presentation. Dermatol Online J. 2008;14:8.

Publication Dates

• Publication in this collection
  June 2015

History

• Received
  10 July 2014
• Accepted
  22 July 2014