Skin metastases from rectal adenocarcinoma appearing on the radiation port

ARTICLE

Skin metastases from internal cancer are uncommon. They are variably reported as occurring in 0.6% to 9% of all patients with internal cancer [1]. Cutaneous metastases are usually a late event in advanced cancer, and only rarely do they represent the first sign of internal malignancy [1, 2]. Occurrence is mostly in patients between 50 and 70 years of age, because of the elevated incidence of malignancies in this group of patients [1].

There is some correlation in the incidence of metastatic skin disease according to gender and the epidemiology of the primary cancer [2]. In men with skin metastases, the most common site of primary malignancy is the lung (24%), followed by the large intestine (19%). In contrast, for women, tumors of the large intestine account for only 9% of skin metastases, while the most common site for primary cancer is the breast (69%) [1, 2]. A case of skin metastases from rectal adenocarcinoma, occurring in an area of radiation dermatitis and corresponding to the portal of prior irradiation, is reported.

Case report

A 65-year-old woman presented for evaluation of multiple nodules which had appeared 6 weeks earlier in the perineal and inguinal regions; she also complained of intense pain and tenderness at these sites.

Past medical history revealed abdominal-perineal amputation with definitive colostomy (Miles' amputation) for a rectal adenocarcinoma 6 months earlier, followed by 1 cycle of chemotherapy with 5-FU and folinic acid, and administration of external beam radiation using the box technique in 34 fractions for a period of 7 weeks.

Local examination revealed multiple, ovoid and ulcerated nodules, not exceeding 5 cm in diameter, with firm and raised inflammatory borders, located on the labia majora and the inguinal folds; the base of the ulcers was necrotic with a grey-yellowish discharge (Fig. 1). The surrounding skin was diffusely indurated and erythematous, with a dusky, brownish hue. Skin-coloured papules of 3-4 mm in diameter were also present on the pubic area. Left inguinal adenopathy, with enlarged, firm, fixed and nontender lymph nodes, was detectable.

Histological examination of a papular lesion from the pubic area and of an ulcerated nodule from the inguinal folds showed, in both specimens, foci of metastatic adenocarcinoma in the superficial and middle dermis; inflammatory infiltrate throughout the dermis, dilation of blood vessels, edema of the collagen bundles and the presence of large, bizarre, stellate fibroblasts, consistent with radiation dermatitis, were also evident (Figs. 2 and 3).

The patient refused therapy, and died 2 months later.

Permission for an autopsy was denied.

Discussion

Cancer of the colon and rectum is a relatively common and often fatal disease. After lung and breast cancer, it is the leading cause of cancer mortality world-wide. Its incidence has slowly increased from 1973 to 1986 at an annual rate of less than 1%, and in 1988 there were, in the United States, 147,000 new cases of colorectal cancer, with 61,500 deaths attributable to this disease from a population of about 250 million people [3].

Metastatic dissemination of colorectal adenocarcinoma may take place by several mechanisms, including direct or transperitoneal spread, implantation, and through the lymphatics or blood vessels [4]. The most frequent sites of metastatization are liver and lungs. Cutaneous metastases are rare events (2%) [1], which most frequently affect skin of the abdominal, thoracic, and pelvic regions [1]; involvement of scalp [2], genital and perianal skin, as well as mucosae, is uncommon [1, 5, 6].

Cutaneous metastases on skin overlying the site of primary cancer usually occur as a consequence of lymphatic dissemination, while those located at distant sites are generally due to hematogenous spread [5].

Histologically, metastatic tumors show a pattern similar to the primary tumor, occasionally showing more anaplastic changes [7].

The case herein described presented with some unique features: skin metastases involved the genital region, which is considered a rare occurrence; its pathogenesis might be related to a retrograde lymphatic drainage of cancer cells [1, 5]. Moreover, the clinical features were striking. Localization of the cutaneous metastases was in an area of radiation dermatitis corresponding to the portal of prior irradiation. This phenomenon is uncommon, and, to our knowledge, only 34 cases have been reported in the literature; in 26 of these, the development of metastases followed breast cancer [8-10], in 2 cases uterine cancer [10], in 2 cases bladder cancer [10], in 1 case gastric cancer [8]‚ in 1 case parotid cancer [9], in 1 case pharyngeal squamous cell cancer [11], and in 1 case a poorly-defined ORL squamous cell cancer [9].

In the majority of cases, recurrence was confined to an area of previous irradiation, while in a few patients it also developed beyond the radiation port [8].

Occurrence of metastasis in an area of irradiation is intriguing. The settling of metastatic cells in the radiation field might be favoured by impairment of the lymphatic drainage in that area following irradiation [9]. Moreover, it has been suggested that endothelial cell alterations and/or inflammatory processes occurring in sites of radiation dermatitis may enhance implantation and growth of metastatic cells [7, 8, 10], and studies in animals have demonstrated that tissues damaged by various physical and chemical agents are more susceptible to development of metastases than undamaged tissues [8].

Endothelial cell alteration may lead to increased tumor cell trapping [12]. Moreover, as a result of inflammatory response, injured sites show release of chemotactic factors, increased blood flow and hypercoagulability, and fibrovascular proliferation that may be key factors in the development of metastases [13]. Several recent in vitro studies have postulated that the tumorigenic expression of colon adenocarcinoma cells may be modulated by metabolites of arachidonic acid [12 (S)-hydroxyeicosatetranoic acid] [14] or by cytokines [15-17], whose differential expression in various tissues may provide microenvironments that enhance, or, alternatively, inhibit settling of metastatic cells.

Finally, the role of local immunologic surveillance and its impairment [18, 19], as well as structural and quantitative alterations of connective tissue components resulting from irradiation [11, 19] should also be taken into consideration.

CONCLUSION

REFERENCES

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