Cutaneous metastasis as first clinical manifestation of signet ring cell gastric carcinoma
Aneiros-Fernandez J MD1, Husein-ElAhmed H MD2, Arias-Santiago S MD2, Escobar Gómez-Villalva F MD3, Alina Nicolae MD PhD1, O’Valle Ravassa F MD PhD1, Aneiros-Cachaza J MD PhD1
Dermatology Online Journal 16 (3): 9

1. Department of Pathology, University Hospital, Granada. Spain. janeirosf@hotmail.com
2. Department of Dermatology, University Hospital, Granada. Spain
3. Department of Internal Medicine, University Hospital, Granada. Spain


Abstract

Cutaneous metastases from signet ring cell gastric carcinoma are uncommon. A 69-year-old man presented with a 15-day history of an asymptomatic indurated scar-like lesion. The biopsy revealed an infiltrating signet ring cell carcinoma consistent with gastric metastasis. Gastroscopy and biopsy showed gastric carcinoma with signet ring cells; subsequent computed tomography revealed metastatic nodules in the liver, mesentery, and retroperitoneal and peripancreatic lymph nodes. A review of the 10 cases of cutaneous metastasis from signet ring cell carcinoma in the literature revealed that cutaneous metastases of gastric origin usually appear at earlier ages than in our patient and that the primary tumor is unknown at the time of skin biopsy in 64 percent of cases. The present report describes the unusual clinical-diagnostic sequence of a patient diagnosed with cutaneous metastasis before detection of his gastric carcinoma.



Introduction

About 10 percent of all visceral malignant tumors develop cutaneous metastases, which represent 2 percent of all skin tumors. Cutaneous metastases most frequently derive from carcinomas of breast, lung, colon, rectum, ovary, head, neck, kidney, and the gastrointestinal tract [1].

Metastatic dissemination is largely via lymphatic vessels and less frequently via the blood stream (to liver, peritoneal cavity, lung, adrenal gland, and skin). The clinical presentation of cutaneous metastases from gastric adenocarcinoma is usually as single or multiple nodules; only 6.4 percent to 7.8 percent of these cutaneous metastases are the first clinical manifestation [2, 3].

We describe a patient diagnosed with gastric carcinoma after detection of cutaneous metastasis.


Case report


Figure 1
Figure 1. Superficial scar-like lesion and a deep palpable nodule

A 69-year-old man presented with a 15-day history of an asymptomatic indurated scar-like lesion on the chest that clinically resembled basal cell carcinoma (Figure 1). Histopathological study reported infiltrating neoplastic cells dispersed in the dermis with no ulcerations of the epidermis. The tumor comprised cell nests and cords and scattered cells, mostly appearing as signet ring cells surrounded by dense fibrous stroma with a predominantly eosinophilic inflammatory infiltrate (Figure 2). The signet ring cells exhibited positive mucicarmine staining in the cytoplasmatic areas (Figure 3A). Immunohistochemical studies showed positivity for AE1-AE3, CK20 (Figure 3B), and CK18 antibodies and negativity for GCDFP-15, CK7, S-100, HMB-45, MELAN A, and CD45 antibodies. The diagnosis was metastasis of signet ring cell adenocarcinoma of probable gastric origin. We therefore searched for a primary tumor in the gastrointestinal system using gastroscopy and biopsies,; a gastric signet-ring cell adenocarcinoma was detected. Computed tomography then revealed the presence of six metastatic nodules in liver, mesentery, and retroperitoneal and peripancreatic lymph nodes. Because of the advanced stage of the disease, no surgery was undertaken.


Figure 2 Figure 3
Figure 2A. Skin histology shows infiltrating tumor cells dispersed in the dermis of the tumor (H&E, x100). 2B. Higher magnification reveals cells with signet ring configuration and abundant cytoplasm pushing the nucleus to the periphery, close to the cell membrane (H&E, x400)

Figure 3. Signet ring cells with areas positive for mucicarmine stain. 3A. (H&E, x400) and 3B. CK20 (H&E, x200)

The patient showed deterioration in health status and the appearance of new lesions despite seven courses of systemic chemotherapy with CDDP, Taxotere, and Xeloda. He died at 10 months after the diagnosis.


Discussion

Ring-cell carcinoma in the skin may correspond to a primary or secondary tumor. In men, primary tumors generally appear on the eyelid or axilla [4]. Secondary tumors can derive from tumors in breast, stomach, colon, rectum, cecal appendix, lung, bladder, prostate, endometrium, and esophagus. The immunohistochemical characteristics of signet ring-cell carcinoma can assist the differential diagnosis between primary and secondary tumors. For this purpose, we consider that CK 7, CK 20, GCDFP-15, PSA, TTF-1, and estrogen and progesterone receptors should be studied. The differential diagnosis should also consider malignant tumors that can also have a signet ring cell pattern, such as melanoma and lymphoma [5].

It has been reported that cutaneous metastases tend to be close to the site of the primary tumor, e.g., abdominal wall in gastrointestinal tumor, chest in lung carcinoma, and back in renal cell carcinoma [6]. However, our group previously reported a cutaneous metastasis of renal origin in the finger [7] and the localization in the present case was the thorax. Hence, the correlation between the sites of primary and secondary tumors appears to be controversial.

Gastric adenocarcinomas represent approximately 95 percent of gastric tumors and are histopathologically classified as papillary adenocarcinomas, tubular adenocarcinomas, mucinous adenocarcinomas, or signet ring cell carcinomas. Signet ring cell carcinomas comprise only 8.7 percent of all gastric cancers [8].

Clinically, cutaneous metastases from gastric carcinoma can be red or violet; they may present as a single or multiple hyperpigmented nodules, showing zosteriform, erysipela-like, allergic contact dermatitis-like, or cellulitis-like patterns. They have been reported to appear on the neck, head, eyebrow, axilla, chest, and fingertip [3].

Previous reports described cutaneous metastasis as the first manifestation of a carcinoma in 6.4 percent to 7.4 percent [2, 3] of cases. However, a more recent review of 92 patients with cutaneous metastases reported that there had been no clinical manifestation of the primary tumor in 22 percent of cases; this review only included two cases of signet ring-cell gastric carcinoma [1]. We examined published reports on 10 cases of cutaneous metastasis from signet ring-cell gastric carcinoma in conjunction with the present data (total of 11 cases) [9-18] and found that cutaneous metastases appeared between 33 and 71 years of age (mean of 55 years), occurred preferentially in males (7:3), and presented as a single lesion in only 18 percent of cases. Multiple lesions are usually found on chest and face and single lesions on chest or abdomen. The mean interval between detection of gastric cancer and diagnosis of cutaneous metastasis was 7.3 months. However, the primary tumor was unknown at the time of diagnosis of the cutaneous metastasis in 64 percent of cases. Survival time (with or without manifestation of primary tumor) was < 1 yr.

The above data differ in some respects from reports on cutaneous metastases in general [2, 3]. Thus, the age of patients ranged from 38 to 83 years (mean of 62 years) and the interval between diagnosis of metastasis and diagnosis of the primary tumor was 3 months. Metastases were preferentially localized on the trunk, head, neck and limbs. The mean survival after the diagnosis of cutaneous metastasis was 7.5 to 34 months [2, 3]. The majority of cutaneous metastases appeared as multiple nodules; a single metastasis was infrequent and usually from lung carcinoma [3].

References

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Title:

Cutaneous metastasis as first clinical manifestation of signet ring cell gastric carcinoma

Journal Issue:

Dermatology Online Journal, 16(3)

Author:

Aneiros-Fernandez, J;
Husein-ElAhmed, H;
Arias-Santiago, S;
Escobar Gómez-Villalva, F;
Nicolae, Alina;
O’Valle Ravassa, F;
 et al.

Publication Date:

2010

Publication Info:

Dermatology Online Journal, UC Davis

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