On October 29, 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 5, 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 9, 2005, liver ultrasound showing a slight hepatosteatosis;

- On November 16, 2005, colonoscopy with normal results;

- On November 22, 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 19, 2005, chest and abdomen CAT scan: within normal limits;

- On May 5, 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 24, 2006:

o Ca19-9 -> 130,7 (0,4-37)

o Ca125-> 13,9 (0,6-35)

o Ca15-3-> 20,7 (1-25)

o VES 1^st hour 30 (< 15)

o AST(GOT) 35 (1-31)

o ALT(GPT) 36 (1-31)

o Total Bilirubin 1,5 (0,1-1)

o Direct Bilirubin 0,35 (0,05-0,3)

o Indirect Bilirubin 1,15 (0,05-0,7)

- Test results of October 18, 2007:

o Ca19-9 -> 108,1 (0,4-37)

o Ca125-> 14,1 (0,6-35)

o Ca15-3-> 25,4 (1-25)

o PTH 71 (15-65)

o AST(GOT) 21 (1-31)

o ALT(GPT) 48 (1-31)

o Total Bilirubin 1,4 (0,1-1)

o Direct Bilirubin 0,28 (0,05-0,3)

o Indirect Bilirubin 1,12 (0,05-0,7)

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.

Questions:

1) Can you please confirm the diagnostic path followed up to now? Are other tests necessary in order to exclude any possible oncological pathology?

2) 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?

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

Medical opinion report

Thank you for offering me the Medical data and for asking my opinion on her case. I had the opportunity to review the data and to write the following second opinion, at the request of Medical Opinion.

 

A) Reconstruction of the case history:

The patient is a 72 year old woman with elevated levels of the tumour marker CA 19-9 but with no demonstrable tumour whatsoever.

The increased levels of CA 19-9 were first recorded in October 2005 [171 (0 –33], without any symptoms or signs related to any specific pathology of a target organ. [What was the reason for measuring CA 19-9 levels in October 2005?]

Several diagnostic tests were carried out looking for an occult tumour which could be responsible for that tumour marker elevation, including Chest X-rays, esophagogastroduodenoscopy, liver ultrasound ,colonoscopy , trans vaginal ultrasound, chest and abdomen CAT scan, and operative hysteroscopy.

None of these tests showed any tumour finding, thus raising the question whether any other tests are necessary in order to exclude a possible oncological pathology.

Ever since October 2005 the levels of CA 19-9 remained in the pathologic range, although with decreasing values:

In October 2006: Ca19-9 ->130, 7 (0,4-37)

In October 2007: Ca19-9 ->108,1 (0,4-37)

In addition, on these two last time points:

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

normal range [No levels of another common tumour marker (CEA) were

reported].

2. the levels of indirect bilirubin were very slightly elevated yet steady:

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

3. the levels of ALT (GPT) were slightly elevated but practically steady:

36-> 41(1-31).

[ there is no report of other liver functions tests (LDH and Alkaline Phosphatase),

nor of Kidney function test (creatinine)].

The patient underwent also follow-up diagnostic tests (trans vaginal ultrasound, complete abdomen ultrasound and ECG), with results within the normal range. Currently, the patient is not reporting any significant symptoms.

B) Questions and answers:

1) 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.

2) 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 Ms. __________.

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.

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.

 

If I can be of any further help to you, please contact me through Medical Opinion.

Sincerely and wishing the patient that her hepatitis remain asymptomatic and uncomplicated,