Colorectal cancer remains the third most common cancer and second most common cause of cancer deaths, often from metastatic disease.^1-6 While liver metastases are most common, other sites of metastases include lung, peritoneum, ovary, and brain.^1-6 We report the presentation of cutaneous skin metastases in a patient with history of recent renal transplant. 

Clinical Scenario

A 68-year-old man who had undergone kidney transplant two years prior presented to clinic with weeks of constipation, decreased flatus, and malaise. Ongoing abdominal pain and bloating led to poor oral intake and a 15-pound weight loss over three months. On physical exam, his abdomen was distended and tender on the right side. He was noted to have multiple firm, nontender, pink papules in the right lower quadrant (Figure 1). The patient reported that the papules had been present for several months. He was admitted to the hospital and underwent a noncontrasted CT of his chest, abdomen, and pelvis. This scan demonstrated pulmonary nodules, retroperitoneal lymphadenopathy, dilated small bowel, and narrowing of the ascending colon with decompressed distal colon (Figure 2). Carcinoembryonic antigen (CEA) was 398 ng/ml (normal = 0-5.4 ng/ml). No masses in the liver were identified.

A presumptive diagnosis of obstructing colon cancer was made, and the abdominal skin nodules were biopsied. Histopathologic examination showed an adenocarcinoma consistent with metastasis from a colonic primary (Figure 3). Due to pain, obstruction, and concern for potential perforation in the setting of malnutrition, he underwent a palliative resection with end ileostomy. Pathology for this tumor revealed poorly differentiated, mucinous adenocarcinoma with multiple positive lymph nodes. Final stage was pT4b pN2a pM1a. The tumor was found to be MLH1/PMS2 deficient by immunohistochemistry and molecular testing revealed a BRAF V600E mutation. The patient decided to focus on comfort driven measures and did not receive adjuvant chemotherapy and immunotherapy. He succumbed to the disease four months after diagnosis.

Clinical Pearls

Prior to being listed for kidney transplant, patients undergo extensive medical evaluation to ensure fitness for the operation and immunosuppression.⁷ These include cancer screening tests, such as colonoscopy and dermatological skin exam.⁷ This patient had undergone colonoscopy at a referring institution four years prior to this presentation, two years before his transplant. Findings at his colonoscopy included five polyps, measuring 0.3-1 cm, from his ascending, transverse, and descending colon. Pathology of each polyp was consistent with tubular adenoma. At the time, it was recommended to repeat screening colonoscopy in three years, but that was never completed.

This case highlights the increased rates of cancer in transplant patients due to immunosuppression, the varied metastatic patterns of colon cancer, and the importance of timely screening and surveillance colonoscopies as well as their false negative rate.

Immunosuppression prevents transplanted organ rejection but also increases risk of malignancy in the transplant recipient.⁷ The two major ways this occurs is by decreasing immune surveillance and increasing susceptibility to viruses such as BK polyomavirus, cytomegalovirus (CMV), human papillomavirus (HPV) and Epstein Barr virus (EBV) which are associated with cancer development.⁷ Cell lines including T-lymphocytes, naïve B-lymphocytes and natural killer cells (NK cells) are reduced which in turn reduces the recognition of dysregulated cellular replication and viral reproductions.⁷ While the rate of cancer rises with age, the risk elevation is not proportional to age. Younger transplant patients have a three to five times greater relative risk of developing a malignancy than older transplants since they are immunosuppressed; this contributes to their increased risk of cancer compared to the general population.⁷ Regardless, colorectal cancer rates are still elevated by 1.5-to-3-fold.⁷ Therefore, there needs to be a high index of suspicion for cancer in transplant recipients, and screening guidelines must reflect that.

Colonoscopy remains the gold standard for colorectal cancer. However, around 1% of colorectal cancers occur within the interval between colonoscopies.¹ Currently, the most cited reason for post-colonoscopy colorectal cancer is a missed lesion, representing up to 57% of cases.¹ It is suggested that a quarter of colonoscopies have missed adenomas or precancerous lesions.¹ Wallace et al. demonstrated this in their evaluation of artificial intelligence (AI) enhanced screening colonoscopies followed by a short interval repeat colonoscopy (frequently same day) with 15-32% adenoma miss rate in AI and non-AI screening colonoscopies.¹ 

Around 20-35% of patients with colorectal cancer present with metastatic disease at diagnosis.^4,5 Cutaneous metastases in CRC are uncommon, occurring in 4-5% of cases.^2,3 They are often associated with BRAF V600E mutations.³ Cutaneous metastases are an independent predictor of poor survival, with around two-thirds of patients dying within six months of diagnosis.^2,3

Immunotherapy has shifted the treatment paradigm of high microsatellite instability (MSI-H) colorectal cancers and has significantly improved progression-free survival.⁵ MSI-H, found in up to 20% of colon cancers, is due to a deficiency in mismatch repair (MMR) proteins and subsequent unrepaired alterations in DNA sequences.⁵ While this patient had an MLH1/PMS2 deficiency that may have responded to immunotherapy, he was not offered it due to his renal transplant. In transplant patients, immunotherapy risks triggering graft rejection. Furthermore, its efficacy in the setting of maintenance immunosuppression may be reduced.⁸ As this patient did not wish to risk allograft rejection and need for hemodialysis, he transitioned to hospice care. 

References

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