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Challenging Problems in Malignancy

CASE 1. Presentation of Small-Cell Lung Cancer With Marked Hyperamylasemia

Division of Medical Oncology, Department of Oncology, Bellaria Hospital, Bologna, Italy

A 75-year-old woman presented with fatigue, cough, hemoptysis, and abdominal pain. She had a 20-year history of cigarette smoking and her past medical history was relevant only for cholecystectomy. She denied any alcohol intake. Physical examination revealed hypophonesis at the base of her left lung, pain in the upper right abdomen without palpable masses, and normal cardiac and neurologic examination. Both a chest x-ray and an abdominal ultrasound were negative. There were normal renal and liver functions, blood count, hematocrit, and sedimentation rate, but there was elevated lactate dehydrogenase (551 U/L) and serum amylase (3,719 U/L; normal value [NV], 1 to 100 U/L) levels. A computed tomography (CT) scan of the chest and abdomen excluded pancreatic lesions or liver metastases but revealed a large left hilar mass with two metastatic nodules at left lung base and enlarged mediastinal lymph nodes (Fig 1A). Bronchoscopic examination showed a neoplastic infiltration of the left main bronchus where a biopsy was performed. Brain CT scan and bone scintigraphy were negative for metastases. Histology was consistent with small-cell carcinoma of the lung (Fig 2). Further studies showed neurone-specific enolase (12 ng/mL; NV, 6 to 18 ng/mL) and a repeated serum amylase determination of 5,869 U/L. Isoamylase measurements by polyacrylamide gel electrophoresis revealed that more than 90% of the -amylase migrated like a salivary-type, while macroamylasemia was excluded. In particular, the pancreatic isoamylase value was 362 (NV, 17 to 115) and the salivary-type isoamylase value was 5,507 U/L (NV, 25 to 132 U/L). The urine amylase values ranged between 6,500 and 14,250 U/L and the calculated ratio of amylase to creatinine clearance was within normal limits (< 5%). Based on the isoamylase patterns and on the radiologic findings, an acute pancreatitis was excluded, while the neoplasm seemed the major source of the hyperamylasemia. To confirm this hypothesis, an immunostaining of the tumor tissue was performed by using the avidin-biotin-peroxidase complex method. Most of the tumor cells showed a strong cytoplasmic positivity with antisalivary gland type amylase antibody (Fig 3). The patient started standard chemotherapy for advanced small-cell lung cancer (carboplatin plus etoposide for six cycles). The serum amylase level fell to 1,920 U/L after the first cycle. After chemotherapy, radiation therapy to the chest was given, obtaining a complete objective response (Fig 1B). At this time the total amylase was normal (total amylase, 50 U/L; salivary-type amylase 5 U/L; pancreatic-type amylase, 45 U/L; Fig 4). Six months after the end of radiation therapy the patient complained of left pleuritic-type pain. At that time, blood samples revealed a total serum amylase of 1,500 U/L. A repeat CT scan of the chest and abdomen showed a relapse of the disease with two parenchymal nodules of the left lung. Second-line chemotherapy with cyclophosphamide, doxorubicin, and etoposide was given. After the first cycle, the amylasemia fell to 300 U/L (Fig 4), the patient obtained significant pain relief, but therapy had to be discontinued because of significant hematologic toxicity. Home care with analgesics, steroids, and octreotide as palliative care was started until the patient died 20 months after the diagnosis.

View larger version (107K): [in this window] [in a new window]   Fig 1.

View larger version (152K): [in this window] [in a new window]   Fig 2.

View larger version (129K): [in this window] [in a new window]   Fig 3.

View larger version (64K): [in this window] [in a new window]   Fig 4.

It has been suggested that except for rare cases of tumors producing the enzyme, increased -amylase activity in serum and pleural fluid associated with carcinoma of the lung may be due to an increase in the amylase contained in normal lung tissues but the cellular site of production is uncertain.^2,8 The presence of tumor cells may cause an inflammatory response resulting in activation and release into the blood stream of the enzyme. In every reported case of hyperamylasemia in lung cancer patients, the -amylase present in the serum or in the tumor tissue has been described as of the salivary amylase type.^3,4,9 In our case report, strong evidence indicates hyperamylasemia as a paraneoplastic phenomenon: Firstly, the marked salivary-type hyperamylasemia in the absence of inflammatory conditions of both the salivary glands and pancreas; secondly, the dramatic fall of the amylase level soon after the start of chemotherapy; and thirdly, the evidence of the strong cytoplasmic positivity with antisalivary gland type amylase antibody in the neoplastic tissue. More interestingly, in this instance, the paraneoplastic hyperamylasemia behaved like a specific tumor marker because it paralleled tumor response to chemotherapy and disease relapse.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

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5. Nakayama T, Hayashi Y, Kitamura M: Amylase isoenzyme found in lung and ovarian cancers, in Fishman WH, Sell S (eds): Onco-Developmental Gene Expression. New York, NY, Academic Press, Inc, 1998, pp 455-462

6. Ma RC, Chan WB, Chow CC, et al: A woman with vomiting and hyperamylasemia. Lancet 359:42, 2002[CrossRef][Medline]

7. Horai R, Nishihara H, Tateishi R, et al: Oat-cell carcinoma of the lung simultaneously producing ACTH and serotonin. J Clin Endocrinol Metab 37:212-219, 1973[Abstract/Free Full Text]

8. Ende N: Studies of amylase activity in pleural effusions and ascites. Cancer 13:283-287, 1960

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Benedetti, G. Articles by Crinò, L. Search for Related Content PubMed PubMed Citation Articles by Benedetti, G. Articles by Crinò, L. Social Bookmarking                            What's this?