Download ELEVATED SERUM AMYLASE ASSOCIATED WITH

ELEVATED SERUM AMYLASE ASSOCIATED WITH
BRONCHOGENIC CARCINOMA
REPORT OF CASE*
M U R R A Y J . W E I S S , M.D., H U G H A. E D M O N D S O N , M . D . , AND
M A X I N E YVERTMAN, A.B.
From the Laboratory of the Los Angeles County Hospital and the Departments of Pathology
and Medicine, School of Medicine, University of Southern California, Los Angeles,
'
California
Almost any disease process that involves the pancreas or salivary glands directly or indirectly may produce an elevation of the blood amylase. Deviation
from the normal amylase values (50-150 units) has been reported in many diseases foreign to these two structures. Among these is an unexplained elevation
of serum amylase occasionally seen in pulmonary diseases such as pneumonia
and tuberculosis. Adrenal insufficiency (in dogs),10 retroperitoneal tumors, 10
mesenteric cyst,10 thyroid lesions,1, 10 cholecystic disease,6 7 intestinal obstruction,10 portal or mesenteric vein thrombosis,10 perforated peptic ulcer,3 appendicitis,0 and hypophysectomized animals3 have also been reported as being associated with elevated blood diastase. In addition we have observed high amylase
values in myocardial infarction and dissecting aneurysm.4 Because amylase
is excreted in the urine, high blood levels can be expected in many diseases coincidental with impaired renal function.6, s> 10
In our experience serum amylase values above 500 units are almost exclusively
related to pancreatitis or salivary gland disease. High values in other associated
diseases are usually below this figure. Perusal of the American literature revealed
the highest reported amylase value to be 25,600 units.2 This was associated with
an acinar cell carcinoma of the pancreas. It has been stated that the occasional
elevated amylase value not caused by pancreatic or salivary gland disease will
rarely be a source of diagnostic confusion. The problem presented by the patient
of the case herein reported was that of exceptionally high amylase values without
pancreatic disease.
R E P O R T O F CASE
Clinical Data
A 45-year-old housewife was admitted to the hospital on May 11, 1949. She had been in
fair health until J a n u a r y 1949, when she experienced vague aching pain in the epigastrium
and right upper q u a d r a n t , radiating around the right (lank and into the right shoulder.
This pain was not related to meals or breathing. There was no cough, hemoptysis or j a u n dice. She had lost 25 pounds a t the time of admission.
On physical examination she was pale and cachectic, but not icteric. Decreased resonance was elicited at the base of the right lung. The edge of the liver was nodular, irregular,
hard and palpable 6 cm. below the right costal margin.
T h e laboratory findings were as follows: hemoglobin, 14.5 Gm. per 100 ml. blood; leukocytes, 31,250 per cu. mm. with 84 per cent polymorphonuclear neutrophils; erythrocytic
* Received for publication, J u n e 11, 1951.
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sedimentation rate (Wintrobe), 26 mm. in one hour; nonprotein nitrogen, cephalin flocculation, blood sugar, and icterus index within normal limits; serum albumin 3.1 and serum
globulin 3 Cm. per 100 ml.; thymol turbidity, 8 units; serum calcium (repeated), 7.7 rag.
per 100 ml. Blood amylase and urinary diastase levels ranged as follows: May 5, blood
amylase, 5450 units;* May 11, blood amylase 16,000 units, urinary diastase 19,04S units;
May 14, amylase 8400 units and urinary diastase 17,400 units with a total urinary output in
24 hours of 153,000 units. Foci of infiltration were seen in the right upper lung field by x-ray.
Upper gastrointestinal roentgen studies with barium revealed no abnormalities.
The patient received symptomatic care but slowly became worse and died on May 21,
1949. The clinical diagnosis was pancreatic carcinoma with metastases.
Pathologic Findings
At necropsy the upper lobe of the right lung was densely adherent by fibrous
adhesions to the parietal pleura. In the anterolateral segment there was a hard
indurated lesion 2.5 cm. in diameter over which the visceral pleura was puckered.
On section the indurated lesion was composed of gray-white tumor tissue.
Thick fibrous strands coursed through the entire apical segment. The middle
and lower lobes were without change. The lower lobe of the left lung contained
an embolus which had produced an extensive hemorrhagic infarct. Both pleural
cavities were free of fluid.
The liver weighed 2750 Gm. and was filled with circular to irregularly shaped
masses of tumor, some discrete, others confluent. Their average diameter was 8
mm. The twelfth thoracic vertebra and the right ilium were infiltrated with
gray-white tumor. There was no evidence of metastasis to the retroperitoneal
lymph nodes.
The pancreas was normal in size and appearance. The ducts were patent
and free of any abnormality. Because of autopsy restrictions the salivary glands
were not dissected, but no changes were noted on palpation.
Tissue amylase study. A portion of the tumor from the liver was ground and
assayed for amylase. It contained 4100 units per 103 Gm. of tissue. Unfortunately other organs were not assayed as a control.
Histologic findings. In sections through the tumor the neoplastic cells to a
large extent had used the lung parenchyma as scaffolding for their growth.
Most of the tumor had an adenomatous arrangement, the cells being tall columnar, with moderate sized hyperchromatic nuclei. Mitoses were numerous and
vacuoles in the cytoplasm were present to a variable degree (Fig. 1). Fat stains
disclosed some of these vacuoles to be fat. Mucin stains were negative. The
neoplastic cells tended to grow into the small bronchi and bronchioles, replacing
normal epithelium (Fig. 2). Not infrequently neoplastic cells with granular
hyaline cytoplasm were noted. These were believed to represent primitive
squamous cells. In two sections wide areas of old pigmented scar tissue contained
tumor, thus raising the possibility of origin of the cancer in a healed subapical
tuberculous lesion. In other sections of lung the tumor had grown widely into
* The test for amylase activity in our laboratory is done by a modification of Somogyi's
method." It is measured by the hydrolysis of a starch solution under given conditions and
1 unit is equivalent to 1 rag. of sugar per 100 ml. of the fluid in question.
HIGH SERUM AMYLASE AND LUNG CANCER
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F i e . 1 (upper). Adenocarcinoma with intracytoplasmic vacuoles. Hematoxylin and
eosin. X 320.
F I G . 2 (lower). Growth of cancer cells into bronchiole. Hematoxylin and eosin. X 4S0.
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vascular channels; here the arrangement was not adenomatous but medullary.
Sections of the left lower lobe disclosed only hemorrhage and necrosis.
The metastases in the liver were numerous, large, and likewise more medullary
in character. Intravascular growth was obvious.
In sections of the pancreas there was no dilatation of the ducts, but many of
the ducts contained pink-staining debris and a few, areas of epithelial hyperplasia. No evidence of obstruction to the duct system or of pancreatitis was
perceived.
The presence of a unilateral lung tumor composed of both columnar and
squamous cells with the metastatic pattern described was considered good
evidence for a primary lung cancer.
COMMENT
No previous reports of elevated serum amylase values associated with bronchogenic carcinoma were noted in the literature. However, it has been reported
TABLE 1
SERUM AMYLASE IN PULMONARY D I S E A S E
CLINICAL DIAGNOSIS
Bronchogenic carcinoma
Bronchogenic carcinoma
Bronchogenic carcinoma
Bronchogenic carcinoma
Bronchial asthma or bronchogenic carcinoma
Lung abscess
Far-advanced pulmonary tuberculosis
Bronchial asthma
Hemoptysis, etiology undetermined
SERUM AMYLASE (UNITS)
102
246
<100
<100
575
<100
<100
<100
<100
that other pulmonary diseases, such as pneumonia, not infrequently are associated with elevation of serum amylase.9
The possibility that the mucosal secretions of the bronchi and trachea might
play a role in amylase production was entertained by us. Thus neoplasms originating from the bronchial mucosa epithelium might occasionally form enough of
the enzyme to elevate the serum amylase. Values ranging from 600 to 12,000
units were obtained from material aspirated at bronchoscopy and from bronchial scrapings at necropsy. However, amylase determinations on material aspirated from the trachea through a tracheotomy tube in patients on whom a
laryngectomy had been performed, gave values of less than 100 units. In these
patients there was no possibility of contamination with saliva. This is important,
as the diastatic activity of saliva is extremely high: by our methods the range
was between 50,000 and 125,000 units.
Blood amylase determinations were done on a group of unselected patients
with varied pulmonary diseases. The results are listed in Table 1. Although an
occasional elevated value was noted, no conclusions could be drawn.
HIGH SERUM AMYLASE AND LUNG CANCER
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Another source of error in differential diagnosis in patients with elevation of
serum amylase has recently been publicized by Gross and associates.6 They •noted that the administration of codeine and other opiates would result in
an elevated blood amylase. This factor was not operative in our patient, as
aspirin was the only analgesic administered until late in the disease when narcotics were necessary.
The mechanism involved in the elevation of serum amylase has not been established. Ligation of the pancreatic or parotid duct results in a transient elevation. Pancreatectomy causes a transient fall, following which the diastatic
activity soon returns to normal.3 Liver disease is usually associated with normal
or low blood amylase values.3 There was no evidence that the pancreas or salivary glands caused the high amylase in our patient. Therefore the mechanism
responsible for the amylase elevation is unknown. The possibility that the tumor
cells might have formed the enzyme is to be considered, but since determining
the amylase content in the liver metastasis we have been unable to detect any
amylase activity in several bronchogenic carcinomas procured at autopsy. That
bronchogenic carcinoma may occasionally be associated with a high value of
serum amylase is of some clinical importance in a negative sense in that search
for other causes of the condition need not necessarily be made.
SUMMARY
A case of bronchogenic carcinoma with exceptionally high serum amylase
values is reported. No explanation can be offered concerning the mechanism
of its production.
REFERENCES
1. BARTLETT, W., J R . : Effects upon blood amvlase of variations in thvroid activity.
Proc. Soc. Exper. Biol, and Med., 36: S43-S4S, 1947.
2. C O M F O R T , M. W., B U T T , H . R., BAGGENSTOSS, A. H . , O S T E R B E R G , A. E . , AND P R I E S T L Y ,
J. T.: Acinar cell carcinoma of pancreas: Report of case in which function of carcinomatous cells was suspected. Ann. I n t . Med., 19: S0S-S16, 1943.
3. COMPORT, M. W., AND OSTERBERG, A. E.: Serum amylase and serum lipase in the diagnosis of disease of the pancreas. M. Clin. N o r t h America, 24: 1137-1149, 1940.
4. EDMONDSON, H . A., B E R N E , C. J., H O M A N N , R. E . , J R . , AND W E R T M A N , M . : T h e calcium,
potassium, magnesium, and amylase disturbances in acute pancreatitis. Am. J. Med.,
in press.
5. G R O S S , J. B . , COMFORT, M. W., M A T H I E S O N , D . R., AND P O W E R , M . H . : E l e v a t e d values
6.
7.
8.
9.
10.
11.
for serum amylase and lipase following the administration of opiates: A preliminary
report. Proc. 'Staff Meet., Mayo Clin., 26: S1-7S, 1951.
L E W I S O N , E . F . : T h e clinical value of the serum amvlase test. Surg., Gynec. and Obst.,
72: 202-212, 1941.
M C C A L L , M. L., AND R E I N H O U ) , J. G . : An evaluation of the clinical significance of
serum amylase and lipase determinations. Surg., Gynec. and Obst., 80: 435-440, 1945.
M C C O R K L E , H., AND GOLDMAN, L.: T h e clinical significance of the serum amylase test
in the diagnosis of pancreatitis. Surg., Gvncc. and Obst., 74: 439-445, 1942.
POLOWE, D . : Blood amylase. Am. J . Clin. P a t h . , 13: 2SS-301, 1943.
POLOWE, D . : Blood amvlase activity in pancreatitis and other diseases; a simple diagnostic aid. Surg., Gynec. and Obst., 82: 115-130, 1946.
SOMOGYI, M.: Micromethods for estimation of diastase. J. Biol. Chem., 125: 399-414,
1938.