DOCTORS'

Medical Case Studies

Elevation of Ca 19-9

Short Summary

72-year-old female with elevated levels of the tumour marker CA 19-9 but none of the diagnostic tests showed any tumour finding. The levels of CA 19-9 remained in the pathologic range, although with decreasing values. Currently, the patient is not reporting any significant symptoms.

Patient's Questions

Can you please confirm the diagnostic path followed up to now? Are other tests necessary in order to exclude any possible oncological pathology?
Is it possible to formulate a diagnosis based on this tumor marker increase? If it is not possible to formulate a diagnosis, can you please clarify the reason why Ca 19-9 has increased?
What is the significance of the progressive decrease of the Ca 19-9 value since October 2005?

Medical Background

72 year old female.

Right annessiectomy for extra-uterine pregnancy.

Gastroduodenal ulcer under drug therapy.

Hepatitis C.

Bilateral gonarthrosis.

Previous surgery for right carpal tunnel.

History:

On October 2005, an elevation of the Ca 19-9 = 171,0 (0 – 33,0) value was observed, without any symptoms or clinical evidence related to any specific pathology of a target organ.

The following diagnostic tests were performed:

On November 2005, chest X-Rays with normal results.
Esophagogastroduodenoscopy: within normal limits except for “duodenal bulb with a deformed appearance due to scar tissue formation with pseudo-diverticulum of the anterior wall”;
On November 2005, liver ultrasound showing a slight hepatosteatosis;
On November 2005, colonoscopy with normal results;
On November 2005, a transvaginal ultrasound showed an endometrial thickening: “endometrium of 2.7 mm with an endocavitary fluid layer of a max. thickness of 5.8”;
December 2005, chest and abdomen CAT scan: within normal limits;
On May 2006, operative hysteroscopy with multiple biopsies: within normal range, endometrial mucosa with hypotrophic appearance.

The patient underwent periodic blood tests with the following results:

Test results of October 2006:

Ca19-9 -> 130,7 (0,4-37)
Ca125-> 13,9 (0,6-35)
Ca15-3-> 20,7 (1-25)
VES 1^st hour 30 (< 15)
AST(GOT) 35 (1-31)
ALT(GPT) 36 (1-31)
Total Bilirubin 1,5 (0,1-1)
Direct Bilirubin 0,35 (0,05-0,3)
Indirect Bilirubin 1,15 (0,05-0,7)

Test results of October 2007:
- Ca19-9 -> 108,1 (0,4-37)
- Ca125-> 14,1 (0,6-35)
- Ca15-3-> 25,4 (1-25)
- PTH 71 (15-65)
- AST(GOT) 21 (1-31)
- ALT(GPT) 48 (1-31)
- Total Bilirubin 1,4 (0,1-1)
- Direct Bilirubin 0,28 (0,05-0,3)
- Indirect Bilirubin 1,12 (0,05-0,7)

The levels of two other tumour markers ( CA 15-3 and Ca 125) were within the

normal rang.

The levels of indirect bilirubin were very slightly elevated yet steady:

1,15 ->1,12 (0,05-0,7).

The levels of ALT (GPT) were slightly elevated but practically steady:

36-> 41(1-31).

The patient underwent also follow-up diagnostic tests (transvaginal ultrasound, complete abdomen ultrasound and ECG), with results within the normal range.

Currently, the patient is not reporting any significant symptoms.

Expert's Opinion

Are there any other tests necessary in order to exclude a possible oncological pathology?

To the best of my knowledge CA 19-9 is not a specific marker of any tumour. Still, I agree with the physicians that once they recorded its significant elevation they elected to rule out the existence of several possible underlying/ occult tumours:

A carcinoma of the colon was ruled out by colonoscopy;

A carcinoma of the pancreas (or of the biliary system) was ruled out by abdominal liver ultrasound and abdomen CAT scan;

A carcinoma of the stomach was ruled out by the esophagogastroduodenoscopy;

A carcinoma of the lung (NSCLC) was ruled out by the chest CAT scan;

In view of all these negative tests and in the absence of clinical signs or symptoms of any tumour at time of first recording of the elevated tumour marker in October 2005, I agree with the chosen policy limited to follow up. I recognize that certain oncologists would have suggested at that time point to perform a PET-FDG scan, looking for an "occult tumour", such as a TCC of the urinary tract which has been correlated with elevated levels of CA 19-9. However, since the consecutive measurements of CA 19-9 showed no further increase and even a gradual decrease, that option is not valid any more.

Is it possible to formulate a diagnosis based on this tumour marker increase? If it is not possible to formulate a diagnosis, can you please clarify the reason why Ca 19-9 has increased?

Based on the medical history of the patient I would say that her Hepatitis C is a plausible diagnosis for explaining the elevated levels of CA 19-9. This possibility is consistent with the literature (especially if the non reported levels of CEA too are elevated) [Ann Clin Biochem. 1998 Jan; 35 ( Pt 1):99-103. The effect of benign and malignant liver disease on the tumour markers CA19-9 and CEA. Maestranzi S, Przemioslo R, Mitchell H, Sherwood RA.].

Besides pathologies of the liver and biliary system, also a variety of other pathological conditions have been reported with elevated levels of CA 19-9, such as interstitial pneumonia [Nihon Kokyuki Gakkai Zasshi. 2005 Feb ;43(2):77-83. Clinical characterization of CA19-9 in patients with interstitial pneumonia showing pathological nonspecific interstitial pneumonia pattern. Totani Y, Saito Y, Miyachi H, Yoneda Y, Shimizu H, Hoshino T, Hayashi M, Uchiyama Y, Isogai S, Matsui K, Hashimoto Y, Umemoto M, Sasaki F, Okazawa M, Sakakibara H.], and rheumatoid arthritis[Ann N Y Acad Sci. 2007 Jun;1108:359-71. Increased production of the soluble tumor-associated antigens CA19-9, CA125, and CA15-3 in rheumatoid arthritis: potential adhesion molecules in synovial inflammation? Szekanecz E, Sándor Z, Antal-Szalmás P, Soós L, Lakos G, Besenyei T, Szentpétery A, Simkovics E, Szántó J, Kiss E, Koch AE, Szekanecz Z.], and diverticulitis[Surg Today. 2002;32(3):282-4. Diverticulitis causing a high serum level of carbohydrate antigen 19-9: report of a case. Nakamura T, Maruyama K, Kashiwabara H, Sunayama K, Ohata K, Fukazawa A, Yasumi K, Sugimura H, Nakamura S.] and benign hydronephrorsis [J Urol. 2002 Jan;167(1):16-20 . The correlation of serum carbohydrate antigen 19-9 with benign hydronephrosis.Suzuki K, Muraishi O, Tokue A] and Hashimito's thyroiditis [ Dig Dis Sci. 2005 Apr;50(4):694-5. Elevated CA 19-9 caused by Hashimoto's thyroiditis: review of the benign causes of increased CA 19-9 level. Parra JL, Kaplan S, Barkin JS.] and renal failure and SLE[Med J Malaysia. 2003 Dec;58(5):667-72. The clinical significance of elevated levels of serum CA 19-9. Pavai S, Yap SF.].

However, as already stated, chronic Hepatitis C seems more probable in the case of the patient.

3) What is the significance of the progressive decrease of the Ca 19-9 value since October 2005?

The progressive decrease of CA 19-9 levels along the last two years, first of all supports the non-oncological origin of this marker's elevation.

In addition, although it might suggest that the underlying process, including HEPATITIS C, is currently in a "silent" phase, the persistent elevation implicates continuous follow up.

In the case of the patient I would suggest periodical measurements not only of CA 19-9 and CEA, but also of liver function tests and of A-Fetoprotein, all these being coordinated by a liver specialist.