Cutaneous metastases of signet cell carcinoma of the rectum without accompanying visceral involvement.

Abstract: Cutaneous metastasis of rectal carcinoma is a rare event. It occurs in fewer than 4% of all patients with rectal cancer. Although skin metastasis of rectal cancer is usually detected around surgical scars or on the abdominal wall, especially in the periumbilical region, it rarely presents at other sites. The early diagnosis of skin metastases in these patients is very important because it can alter treatment. A case of signet cell carcinoma of the rectum with cutaneous metastases without accompanying visceral involvement is presented, occurring 14 months after completion of adjuvant therapy.

Key Words: rectal carcinoma, metastasis, skin, thorax, signet cell carcinoma

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The occurrence of cutaneous metastasis is a rare event. Although the true incidence is unknown, cutaneous metastasis from visceral carcinoma is estimated to range between 0.7% and 10.4% of all malignancies. (1-3) Cutaneous metastasis of rectal carcinoma occurs in fewer than 4% of all patients with rectal cancer. (3) When it is present, it generally signifies widespread disease and carries a poor prognosis with shortened survival. Although skin metastasis from rectal cancer is usually detected around surgical scars or on the abdominal wall, especially in the periumbilical region, it rarely presents at other sites. Sometimes patients present with skin metastasis without any evidence of visceral involvement. The early detection of metastasis in these patients is very important because it can alter treatment.

We present a case of signet cell carcinoma of the rectum with cutaneous metastasis without accompanying visceral involvement, occurring 14 months after completion of adjuvant therapy.

Case Report

A 29-year-old male was admitted to the hospital with crampy abdominal pain, fatigue, weight loss and hematochezia. Digital examination revealed a rectal mass. Virtual colonoscopy showed a mass that invaded the perirectal fat tissue. The patient underwent low anterior resection. Histopathological examination revealed a signet cell carcinoma originating from the rectum with metastatic lymph nodes. Because the distal surgical margin was invaded with tumor, he was reoperated and an abdominoperineal resection was performed. He was diagnosed to have TNM stage IIIA disease and received 5-fluorouracil (5-FU) and concomitant pelvic radiotherapy (total 5,000 cGy) and adjuvant chemotherapy for six months.

Fourteen months after completion of the adjuvant treatment, the patient's tumor markers (carcinoembryonic antigen--CEA) were found to be slightly elevated (12.9 ng/mL, normal range: 0.2-4.8 ng/mL). Neither a metastatic site nor residual/recurrent tumor could be identified with thoracoabdominal computed tomography or colonoscopy examination respectively. Physical examination was normal with the exception of two cutaneous nodules, approximately 1 X 2 cm in dimension, which were hard on palpation. The nodules were located on the chest wall and left midaxillary line. They were excised and pathologic examination revealed a roughly nodular mass within the subcutaneous (SC) adipose tissue. The tumor was composed of signet ring cells within a desmoplastic stroma, displaying an Indian file pattern of infiltration (Fig. 1). The neoplastic cells displayed prominent intracytoplasmic mucin (Fig. 2) and were immunohis-tochemically positive for CK20 and negative for CK7, supporting their colorectal origin. The patient was again evaluated for visceral metastases and local recurrences, but none were found. The patient began chemotherapy for the metastatic disease (oxaliplatin 130 mg/[m.sup.2], folinic acid 400 mg/[m.sup.2], and fluorouracil 2,600 mg/[m.sup.2] on the first and fifteenth days). Four months after the occurrence of skin metastases, the patient developed liver and recurrent skin metastases (Fig. 3) while receiving the chemotherapy.

Discussion

Cutaneous metastases from carcinoma are relatively uncommon in clinical practice, but it is very important that they are recognized since the appearance of cutaneous metastases signals widespread metastatic disease, resulting in a poor prognosis. The most common cancers associated with cutaneous metastases are breast and lung cancers and malignant melanoma. (2,4-6) Only 4% of all cutaneous metastatic disease originates from colorectal cancers. (5,7) Skin metastases from colorectal cancer without visceral involvement are very rare and relate to short survival. Cutaneous metastases from colorectal carcinomas usually occur in the surgical region. (8,9) There are only a few reports of isolated skin metastases similar to the present case. (7-9) Stavrianos et al (8) reported a case of cutaneous metastases to the head and neck from colon cancer. The patient was treated with radiotherapy and surgical resection. He died due to pulmonary metastases after approximately one year. Similarly, Koklu et al (9) reported a case of thyroid metastases from colorectal cancer. Reingold (10) noted that 32 of their 2,300 patients with carcinoma had cutaneous metastases. However, only three of these cases originated from the colon (two cases) and rectum (one case). In a study performed by Lookingbill et al, (1) 420 (10.4%) of 4,020 patients were found to have cutaneous metastases. The colon and rectum were the primary site in only 4.4% of the cases. All of the cutaneous metastases were located at the abdominal incision site and all metastases were described as nodular lesions.

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Rectal carcinoma metastases to the skin usually present as small subcutaneous or intradermal nodules that vary from pink violaceous to brown-black hues. They may sometimes mimic cysts, lipomas, neurofibromas, granulomas or alopecia. (4,5) The metastatic lesions often occur on the abdominal wall and around the umbilicus. It is also common for tumor cells to migrate to the pelvic or perianal region following rectal carcinoma surgery. (6) Cutaneous metastases from rectal carcinoma can reach the skin by four main routes. (4,11) Most commonly, tumor cells may spread to the skin by lymphatic and hematogenous disseminations. However, direct extension from the underlying tumor to the skin or accidental implantation of tumor cells in surgical wounds and the surgical tract is also frequently reported. (12) The number of visceral organs invaded by tumor metastasis at the time of diagnosis determines the patient's survival. (13)

Cutaneous metastasis of rectal cancer usually occurs within two years of primary tumor resection. (14) The average survival of a patient with cutaneous metastases varies from 3 to 18 months. (14) Once the isolated cutaneous metastasis is diagnosed, the patient should undergo excision of the lesion. Local radiotherapy is another treatment modality. But all patients with cutaneous metastases from colorectal cancer without visceral involvement should also be treated with systemic chemotherapy to prevent additional metastases.

In short, any new skin nodule should be suspected as metastatic in a patient with a history of malignant disease. Patient education and careful examination by the physician can lead to early detection, which may help alter the treatment and hence, the patient's prognosis.

References

1. Lookingbill DP, Spangler N, Helm KF. Cutaneous metastases in patients with metastatic carcinoma: a retrospective study of 4020 patients. J Am Acad Dermatol 1993;29:228-236.

2. Spencer PS, Helm TN. Skin metastases in cancer patients. Cutis 1987;39:119-121.

3. Gottlier JA, Schermer DR. Cutaneous metastases from carcinoma of the colon. JAMA 1970;213:2083.

4. Lookingbill DP, Helm KF. Metastatic tumors. In: Demis J, ed. Clinical Dermatology. Philadelphia, Pa, Lippincott-Raven, 1997, pp 1-7.

5. Healey PM, Malott K, Chalet MD. Cancers metastatic to the skin. In: Friedman RJ, Rigel DS, Harris MN, Baker D, eds. Cancer of the Skin. Philadelphia, Pa, WB Saunders Co, 1991, pp 347-363.

6. De Friend DJ, Kramer E, Prescott R, et al. Cutaneous perianal recurrence of cancer after anterior resection using the EEA stapling device. Ann R Coll Surg Engl 1992;74:142-143.

7. Rendi MH, Dhar AD. Cutaneous metastases of rectal carcinoma. Dermatol Nurs 2003;15:131-132.

8. Stavrianos SD, McLean NR, Kelly CG, et al. Cutaneous metastases to the head and neck from colonic carcinoma. Eur J Surg Oncol 2000;26:518-519.

9. Koklu S, Barista I, Altundag MK, et al. An unusual case of metastatic rectal carcinoma presenting as thyroid nodule. Am J Gastoenterol 2000;95:3689.

10. Reingold IM. Cutaneous metastases from internal carcinoma. Cancer 1966;19:162-168.

11. Resnik KS. Spread, mechanism, and rotes of a cutaneous metastases or simply put: how did it get to the skin of the thigh? Am J Dermatopathol 1999;21:208-209.

12. Kauffman CL, Sina B. Metastatic inflammatory carcinoma of the rectum: tumor spread by three routes. Am J Dermatopathol 1997;19:528-532.

13. Herrera-Ornelas L, Petrelli N, Mittelman A. Subcutaneous metastases visceral metastases from an adenocarcinoma of the rectum. Dis Colon Rectum 1985;28:523-525.

14. Adani GL, Marcello D, Anania G, et al. Subcutaneous right leg metastases from rectal adenocarcinoma without visceral involvement. Chir Ital 2001;53:405-407.

Saadettin Kilickap, MD, Sercan Aksoy, MD, Murat Dincer, MD, Emine Arzu Saglam, MD, and Suayib Yalcin, MD,

From the Departments of Medical Oncology and Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Reprint requests to Dr. Saadettin Kilickap, Hacettepe University Institute of Oncology, Department of Medical Oncology, Sihhiye, 06100, Ankara, Turkey. Email: [e-mail]

Accepted February 28, 2006.

RELATED ARTICLE: Key points:

* Cutaneous metastases from carcinoma are relatively uncommon in clinical practice, but it is very important that they are recognized since the appearance of cutaneous metastases signals widespread metastatic disease, resulting in a poor prognosis.

* The skin metastasis of colorectal cancer without visceral involvement is very rare and relates to short survival. Cutaneous metastases from colorectal carcinomas usually occur in the surgical region.

* Cutaneous metastasis of rectal cancer usually occurs within two years of resection of the primary tumor. The average survival of a patient with cutaneous metastasis varies from 3 to 18 months.

* Any new skin nodule should be suspected as metastatic in a patient with a history of malignant disease, and patient education and careful examination by the physician can lead to early detection which may help alter the treatment and hence, the prognosis.