Peculiar Cutaneous Findings in a Patient With Rectal Adenocarcinoma

Question: A 44-year-old woman was diagnosed with stage IIIa rectal adenocarcinoma in 2015. The initial colonoscopy and biopsy revealed a 1.5-cm polypoid lesion in the anal canal with high-grade dysplasia, and subsequent transanal endoscopic resection revealed a mixed adenoneuroendocrine tumor with focal invasion of the muscularis propria and nodal involvement on endorectal ultrasound. She was treated with 3 months of cisplatin/irinotecan and 1 month of capecitabine followed by abdominoperineal resection with colostomy and 3 months of FOLFOX, finally achieving remission in January 2017. By May 2018, her carcinoembryonic antigen levels increased and a computed tomography scan revealed prominent right external iliac lymph nodes, suggestive of metastasis. She underwent 12 cycles of FOLFIRI, but subsequent imaging revealed new lung nodules and enlargement of the external iliac lymph nodes, leading to right iliac vein compression. She developed significant right lower extremity swelling and underwent right iliac stent placement in January 2019. She continued to have worsening swelling with associated pain and was restarted on FOLFOX + bevacizumab. In April 2019, her swelling became painful and continued to worsen, and a new cutaneous eruption developed prompting referral to dermatology. Skin exam was notable for non∖pitting edema of the right lower extremity with hyperpigmented, firm papulonodules and indurated plaques across the right medial thigh and inguinal fold, as well as a verrucous pink to skin colored papules in the right inguinal and genitocrural folds (Figure A, B). There was also mild maceration of the skin folds and a small erosion on the right labium majus. Given the laterality and known malignant lymphadenopathy, the lesions were felt most likely to be secondary changes from lymphedema and were treated unsuccessfully with compression therapy. In June 2019, angioplasty was performed and a second stent was placed in the right iliac vein. Her lymphedema and skin eruption continued to worsen; the lesions increased in number and became exquisitely tender with near constant pain, recalcitrant to ibuprofen and acetaminophen. Owing to the worsening of her symptoms, a hyperpigmented plaque and verrucous papule were sampled for histopathologic examination (Figure C, D). What is your diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Given the nonspecific characteristics, the differential diagnosis for the patient’s skin findings was broad, including inflammatory, infectious, and neoplastic etiologies. Histopathology revealed glandular structures lined by epithelium characterized by hyperchromatic columnar nuclei, consistent with metastatic adenocarcinoma from her primary rectal tumor (Figure C, D). Cutaneous metastases from colorectal adenocarcinoma are rare, and have been reported to occur in only 2%–6% of cases.1Krathen R.A. Orengo I.F. Rosen T. Cutaneous metastasis: a meta-analysis of data.South Med J. 2003; 96: 164-167Crossref PubMed Scopus (308) Google Scholar,2Hashimi Y. Dholakia S. Facial cutaneous metastasis of colorectal adenocarcinoma.BMJ Case Rep. 2013; 2013Crossref Scopus (13) Google Scholar Rectal tumors metastasize to the skin even less commonly and represent only a small portion of these cases. Cutaneous metastasis of abdominal malignancies signifies widespread disease with intralymphatic and/or intravascular tumor dissemination, and portends a poor prognosis. The median life expectancy from diagnosis of cutaneous metastasis ranges from 3 to 18 months.2Hashimi Y. Dholakia S. Facial cutaneous metastasis of colorectal adenocarcinoma.BMJ Case Rep. 2013; 2013Crossref Scopus (13) Google Scholar Cutaneous metastases have a varied clinical presentation, but most frequently present as solitary lesions.3Wong C.Y. Helm M.A. Kalb R.E. et al.The presentation, pathology, and current management strategies of cutaneous metastasis.N Am J Med Sci. 2013; 5: 499-504Crossref PubMed Scopus (51) Google Scholar When secondary to colorectal cancer, the skin of the abdomen is most often affected, and they commonly present as asymptomatic firm or rubbery subcutaneous nodules.2Hashimi Y. Dholakia S. Facial cutaneous metastasis of colorectal adenocarcinoma.BMJ Case Rep. 2013; 2013Crossref Scopus (13) Google Scholar Cutaneous metastases may also be characterized by bullae, ulcerations, or indurated plaques.3Wong C.Y. Helm M.A. Kalb R.E. et al.The presentation, pathology, and current management strategies of cutaneous metastasis.N Am J Med Sci. 2013; 5: 499-504Crossref PubMed Scopus (51) Google Scholar Having multiple morphologies, such as our patient’s verrucous eruption and hyperpigmented plaques, and associated pain are somewhat atypical, but highlight the broad clinical manifestations of cutaneous metastases. The treatment of cutaneous metastases is focused on the underlying disease, but may also involve surgical excision or local radiotherapy and chemotherapy. Pain control is also indicated as needed. Prompt treatment may minimize any further spread of cutaneous disease and also extend life expectancy.3Wong C.Y. Helm M.A. Kalb R.E. et al.The presentation, pathology, and current management strategies of cutaneous metastasis.N Am J Med Sci. 2013; 5: 499-504Crossref PubMed Scopus (51) Google Scholar This patient was not a surgical candidate owing to the large area of distribution and likelihood of poor wound healing secondary to lymphedema. Her pain was managed with oxycodone. Unfortunately, the patient’s visceral disease progressed, despite continued treatment with chemotherapy, and she was shifted toward palliative treatment. Cutaneous lesions progressed to involve the vulva and were targeted with external beam radiation. She died about 12 months after the onset of her cutaneous disease. Although cutaneous manifestations of rectal adenocarcinoma are rare, it is important they be identified early to optimize treatment and survival. New-onset skin lesions in a patient with rectal adenocarcinoma should raise suspicion for cutaneous metastases and warrants skin biopsy for diagnosis.