An unexpected cause of elevated prostate specific antigen.

To the Editor: It is known that markedly elevated tumor markers are sensitive for malignancies and may indicate a poor prognosis requiring aggressive therapy. (1) Although rare, it can also be due to nonmalignant conditions. This was highlighted in the case report by Sanchez et al (2) published in the February issue of the Southern Medical Journal. However, a mild elevation can be very nonspecific and associated with many conditions. (1)

A 56-year-old gentleman presented with a long history of intermittent dyspepsia and lower abdominal pain. Two years before his current presentation, he was evaluated in a specialty center abroad. Abdominal ultrasound scan and endoscopic evaluations were normal apart from mild proctitis, a small transverse colon polyp and marked gastritis with intestinal metaplasia. A polypectomy was performed. Histology only showed nonspecific colitis and an adenomatous polyp. He was positive for Helicobacter pylori which was successfully eradicated. He was also treated with a course of antibiotic for presumed infective colitis with some symptom improvement. However, his symptoms remained with intermittent exacerbations. He had no other colonic complaints. A repeat evaluation showed similar findings. A tumor marker panel consisting of prostate specific antigen (PSA), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and alpha fetoprotein (AFP) showed a mildly elevated PSA and CA 19-9. An ultrasound revealed an enlarged prostate gland. The patient was referred for further evaluation that included a transrectal ultrasound and biopsy. The biopsies showed some abnormal cells but no evidence of malignancy. Because of ongoing abdominal complaints and persistent tumor marker elevation, a repeat colonoscopy was performed to assess the proctitis that was noted earlier. This showed progression to involve the sigmoid colon. Biopsy at this time was consistent with ulcerative colitis with goblet cell depletion, chronic inflammatory infiltration and crypt abscesses. He was started on aminosalicylate therapy with marked symptom improvement. Serial follow up of the tumor markers showed normalization (Fig). Other blood investigations, including erythrocyte sedimentation rate, were all normal.

PSA is very specific for prostate pathology. (1) Unlike PSA, other markers such as CA 19-9, CEA and CA-125 can be elevated in many conditions. (1-5) However, these elevations are usually mild. Apart from the marked gastritis and some abnormal prostate cells, there was no evidence of malignancy or any other pathology that may account for the elevated tumor markers. The normalization after initiating therapy for ulcerative colitis (UC) indicated that the underlying UC was the most likely cause. It is possible that chronic prostate irritation by the proctitis caused the elevated PSA. CA 19-9 elevation is usually due to upper gastrointestinal tract pathology, particularly the pancreaticoiliary system. Again, the mild elevation in our patient is likely to be due to the ulcerative colitis, as after initiating specific treatment, the level decreased.

Despite the nonspecificity of some tumor markers, evaluation needs to be considered, particularly in a patient of advancing age, as the risk of underlying malignancy is higher than in a younger patient. It is well known that a proportion of tumors do not have elevation of tumor markers, even at advanced stages. This case highlights the need to consider inflammatory bowel disease as a cause of elevated PSA.

Vui Heng Chong, MRCP, FAMS 

Gastroenterology Unit

Department of Medicine

Raja Isteri Pengiran Anak Saleha Hospital 

Bandar Seri Begawan BA 1710

Brunei Darussalam

References

1. Perkins GL, Slater ED, Sanders GK, et al. Serum tumor markers. Am Fam Physician 2003;68:1075-1082.

2. Sanchez M, Gomes H, Marcus EN. Elevated CA 19-9 levels in a patient with Mirizzi syndrome: case report. South Med J 2006;99:160-163.

3. Soardo G, Basan L, Intini S, et al. Elevated serum CA 19-9 in hepatic actinomycosis. Scand J Gastroenterol 2005;40:1372-1373.

4. Obayashi Y, Fujita J, Nishiyama T, et al. Role of carbohydrate antigens sialyl Lewis (a) (CA19-9) in bronchoalveolar lavage in patients with pulmonary fibrosis. Respiration 2000;67:146-152.

5. Ruffini E, Rapellino M, Delsedime L, et al. Pulmonary carcinoembryonic antigen (CEA) production in patients with end-stage lung diseases submitted to lung transplantation. Int J Biol Markers 1997;12:44-45.

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                        Level (IU/mL)
Timeline (Month /Year)  PSA   CA 19-9

10/03                   11.1  40.3
 3/04                   11.3  34.6
 7/04                   10.3  37.7
 8/04                   11.2  37.9
 3/05                   11.9  45.4
 6/05                    2.6   1.6
 2/06                    1.6  23.6

Note: Table made from line graph.