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A unique case of breast carcinoma producing pancreatic-type isoamylase
GASTROENTEROLOGY
1988;94:519-20
A Unique Case of Breast Carcinoma Producing Pancreatic-Type Isoamylase JEFFREY N. WEITZEL, PETE A. POOLER, RAJI MOHAMMED, MICHAEL D. LEVITT, and JOHN H. ECKFELDT IJniversilv
of Minnesota
and Veterans Administration
A i’l-yr-old woman with a widely metastatic lipidrich variant of breast cancer was found to have striking hyperamylasemia (85fold normal). By isoelectric focusing, agarose gel electrophoresis, and a wheat protein inhibitor assay, the predominant serum amylase appeared to he identical to pancreatic isoamylase. Serum trypsin, serum lipase, and an abdominal computed tomography scan were normal, excluding the possibility of pancreatitis. Furthermore, both the primary breast tumor and skin metastases that developed 10 yr later stained immunohistochemically for amylase. Thus, breast carcinoma must be added to the list of tumors causing ectopic hyperamylasemia, and this case shows that nonpancreatic malignancies may produce pancreatic-type hyperamylasemia. mylase in normal serum can be fractionated by various means into “pancreatic” isoamylase, derived from the pancreas, and “salivary-type” isoamylase, derived mainly from salivary glands and various other organs (1). Several malignancies have been reported to produce amylase and cause marked hyperamylasemia (l-3). Nonpancreatic cancers almost always produce salivary-type isoamylase. Pancreatic (cancers sometimes cause striking hyperamylasemia, which is usually solely of salivary type, but is occasionally of mixed pancreatic and salivary type. We present a case of malignancy-associated hyperarnylasemia with two previously unreported features: (a) a breast carcinoma causing hyperamylasemia and (b) a nonpancreatic cancer producing what appears by all available methods to be pancrcatic isoamylase.
A
Materials
and
Methods
We determined total serum amylase by a coupled enzymic method using p-nitrophenylmaltoheptaoside as substrate (4). We identified isoamylase type with a wheat protein inhibitor assay (4). by agarose gel electrophoresis (5), and by isoelectric focusing (6). We measured lipase
Medic:al Ct:nter. Minneapolis.
Minnewt;~
with a turbidometric assav containing added porcine colipase and trypsin with a commercial radioimmunoassay (7). We examined tissue with routine hematoxylin and eosin staining and immunohistochemically with a peroxidase-antiperoxidase technique with antibodies to cylactalbumin (Dako Patts Company, Santa Barbara, Calif.), c:arcirloembryonic antigen (Hybritech Laboratories, San Diego, Calif.), and amylase (Nordic: Immunologic: Laboratories, El Toro, Calif.) (8). This antibody to amylase stains a~nylase. both salivary-type and pancreatic,-type
Case
Report
The patient is a 71-yr-old woman who had a lobular breast carcinoma of the lipid-rich variant diagnosed ill 197.5. She underwent left modified radical mastectomy. Lymph nodes were negative but in 1981 bony metastases developed and in 1984 hepatic metastases were discovered. She received multiple chemotherapeutic agents therapy was from 1975 until March 1985, when additional stopped because of refractory anemia. During her most recent admission in July 1985. physical examination revealed cachexia, surgically ahsent left breast, nontender hepatomegaly. and several firm, nontender skin nodules on her back. Laboratory tests were normal except for a 7.4 g/d1 (74 g/L) hemoglobin, a 98,000/~1 (98 x 1O”iL) platelet count, and a threefold elevation of alkaline phosphatase and aspartate aminotransferase. The SWurn amylase was elevated to 18,000 1J’L (normal -‘212 [J/L). By the wheat protein inhibitor assay, the serum pancreatic isoamylase was 17,700 IT/L [normal ~105 LJ/I,). representing 98’3, of the total amylase. On isoelectric focusing and gel electrophoresis, the predominant seru~n isoamylase also appeared to be pancreatic. Serum lipase was 24 [l/L [normal Cl20 U/L) and serum trypsin was 8 j.q$L (normal
Gastroenterological OOl&5085/88/$3.50
Association
520
WEITZEL
ET AL.
ing of paraffin-embedded tissue from the 1975 mastectomy specimen and the new skin metastases showed strong staining for amylase, cw-lactalbumin, and carcinoembryonic antigen.
Discussion Many cancers have been reported to produce elevations in serum and urinary amylase (1~3). In our experience and, to our knowledge, in all rcported cases, tumor-associated hyperamylasemia is always of salivary type, except for occasional pancreatic carcinomas and 1 case of colon cancer (2). In the 1 reported case of colon cancer, the serum amylase elevation was only minimal (
normal serum trypsin and normal lipase, in the face of the massive amylase elevation, excluded pancreatitis as the source of the hyperamylasemia. A normal computed tomography scan of the pancreas further excluded it as the source of this marked hyperamylasemia. Morphologic evidence and immunohistochemical staining show that the metastatic cancer originated from the breast, and positive amylase staining of the tumor indicated that the tumor produced amylase. Although human milk and colostrum are reported to contain amylase (1.2). in our experience normal breast tissue and >50 other breast carcinomas showed no immunohistochemical staining for amylase. The lipid-rich variant of breast cancer of our patient accounts for ~1% of all breast cancers (9). Whether this type of tumor is particularly prone to have positive amylase staining, to produce clinical hyperamylasemia, or to synthesize pancreatic-type rather than salivary-type isoamylase is not known. However, metastatic breast carcinoma must be added to the list of nonpancreatic disorders that can cause striking pancreatic-type hyperamylasemia.
References 1.
Zakowski JJ, Bruns DE. Biochemistry of human isoenzymes.
alpho-amylase CRC Crit Rev Clin Lab Sci 1985:21:28:1-322.
2.
Martin PC. Sarma JIP. Amvlase-l_)rorluc:ing lung C~IICXX. J Surg Oncol 1982:21:30-2.
3
Perk JE. Shemamura 1, Fridhandlsr 1.. Tumc~r assoclatetl h~l)eralnylas~lnia. Am J Gastroentcrol 1977:fX:572-7. Okabe H. tlji Y. Netsu K. Noms A. Automated measurement (11 amylase isoonzymes with 4-nitropht?nylmaltohHptaosidr: as substrate and a selective amylase inhibitor. (:lin Chem 1984;30:1219-22. L.eclorc: I’. Forest J-C. Electrophowtir: determination of isoamylases in swum with c:ommc:rc:ially available reagents. Clin Chem 1982:28:37-40. I.evitt MI). Ellis CJ. Isoelwtri(. focusing studies of human serum and tissue isnamqlasfrs. J 1,ab (:lin Med 1977:90:141-52. Levitt ML). Eckfeltlt JH. IXagnosis of acute pancreatitis. In: Go \‘LiY. Gardner JD. Brooks FP. Lebnnthal E. I)iMagno EP. S(:hrt:le GA. ctis. The exocrino pancreas: biology, pathohiology, and diseasr:s. New York: Kawn, 1!1~6:481-502 Strtrnbergt:r I.A. Hardy PH. Cuculis 11. ?~ley:r HC;. ‘l‘hn uulabc~lnd antibody method of irnmllnohistol.ht:mistr~. Preparation and properties of soluble antigen-antibody complex (horseradish I’eroxiciast:.anti-horsprarlish pProxidasc:) and its use in the identification of spirochetes. ] Histoc:hem (:ytochrm 1970:18:315-33. Kamos (3’. Taylor HH. Lipiti-rich carc.inoma of the breast. (:anc:rr 1974::J:Hl 2-!1.
4.
5.
6. 7.
8.
9.
-
Received March 2, 1987. Accepted September 20. 1987. Address requests for reprints to: lohn Eckfeldt. M.D., Ph.D.. IJniversity of Minnesota Hospital anti (:linic. Hox 198. Harvard Street at East River Road. Minneapolis. Minnesota 55455.
1988;94:519-20
A Unique Case of Breast Carcinoma Producing Pancreatic-Type Isoamylase JEFFREY N. WEITZEL, PETE A. POOLER, RAJI MOHAMMED, MICHAEL D. LEVITT, and JOHN H. ECKFELDT IJniversilv
of Minnesota
and Veterans Administration
A i’l-yr-old woman with a widely metastatic lipidrich variant of breast cancer was found to have striking hyperamylasemia (85fold normal). By isoelectric focusing, agarose gel electrophoresis, and a wheat protein inhibitor assay, the predominant serum amylase appeared to he identical to pancreatic isoamylase. Serum trypsin, serum lipase, and an abdominal computed tomography scan were normal, excluding the possibility of pancreatitis. Furthermore, both the primary breast tumor and skin metastases that developed 10 yr later stained immunohistochemically for amylase. Thus, breast carcinoma must be added to the list of tumors causing ectopic hyperamylasemia, and this case shows that nonpancreatic malignancies may produce pancreatic-type hyperamylasemia. mylase in normal serum can be fractionated by various means into “pancreatic” isoamylase, derived from the pancreas, and “salivary-type” isoamylase, derived mainly from salivary glands and various other organs (1). Several malignancies have been reported to produce amylase and cause marked hyperamylasemia (l-3). Nonpancreatic cancers almost always produce salivary-type isoamylase. Pancreatic (cancers sometimes cause striking hyperamylasemia, which is usually solely of salivary type, but is occasionally of mixed pancreatic and salivary type. We present a case of malignancy-associated hyperarnylasemia with two previously unreported features: (a) a breast carcinoma causing hyperamylasemia and (b) a nonpancreatic cancer producing what appears by all available methods to be pancrcatic isoamylase.
A
Materials
and
Methods
We determined total serum amylase by a coupled enzymic method using p-nitrophenylmaltoheptaoside as substrate (4). We identified isoamylase type with a wheat protein inhibitor assay (4). by agarose gel electrophoresis (5), and by isoelectric focusing (6). We measured lipase
Medic:al Ct:nter. Minneapolis.
Minnewt;~
with a turbidometric assav containing added porcine colipase and trypsin with a commercial radioimmunoassay (7). We examined tissue with routine hematoxylin and eosin staining and immunohistochemically with a peroxidase-antiperoxidase technique with antibodies to cylactalbumin (Dako Patts Company, Santa Barbara, Calif.), c:arcirloembryonic antigen (Hybritech Laboratories, San Diego, Calif.), and amylase (Nordic: Immunologic: Laboratories, El Toro, Calif.) (8). This antibody to amylase stains a~nylase. both salivary-type and pancreatic,-type
Case
Report
The patient is a 71-yr-old woman who had a lobular breast carcinoma of the lipid-rich variant diagnosed ill 197.5. She underwent left modified radical mastectomy. Lymph nodes were negative but in 1981 bony metastases developed and in 1984 hepatic metastases were discovered. She received multiple chemotherapeutic agents therapy was from 1975 until March 1985, when additional stopped because of refractory anemia. During her most recent admission in July 1985. physical examination revealed cachexia, surgically ahsent left breast, nontender hepatomegaly. and several firm, nontender skin nodules on her back. Laboratory tests were normal except for a 7.4 g/d1 (74 g/L) hemoglobin, a 98,000/~1 (98 x 1O”iL) platelet count, and a threefold elevation of alkaline phosphatase and aspartate aminotransferase. The SWurn amylase was elevated to 18,000 1J’L (normal -‘212 [J/L). By the wheat protein inhibitor assay, the serum pancreatic isoamylase was 17,700 IT/L [normal ~105 LJ/I,). representing 98’3, of the total amylase. On isoelectric focusing and gel electrophoresis, the predominant seru~n isoamylase also appeared to be pancreatic. Serum lipase was 24 [l/L [normal Cl20 U/L) and serum trypsin was 8 j.q$L (normal
Gastroenterological OOl&5085/88/$3.50
Association
520
WEITZEL
ET AL.
ing of paraffin-embedded tissue from the 1975 mastectomy specimen and the new skin metastases showed strong staining for amylase, cw-lactalbumin, and carcinoembryonic antigen.
Discussion Many cancers have been reported to produce elevations in serum and urinary amylase (1~3). In our experience and, to our knowledge, in all rcported cases, tumor-associated hyperamylasemia is always of salivary type, except for occasional pancreatic carcinomas and 1 case of colon cancer (2). In the 1 reported case of colon cancer, the serum amylase elevation was only minimal (
normal serum trypsin and normal lipase, in the face of the massive amylase elevation, excluded pancreatitis as the source of the hyperamylasemia. A normal computed tomography scan of the pancreas further excluded it as the source of this marked hyperamylasemia. Morphologic evidence and immunohistochemical staining show that the metastatic cancer originated from the breast, and positive amylase staining of the tumor indicated that the tumor produced amylase. Although human milk and colostrum are reported to contain amylase (1.2). in our experience normal breast tissue and >50 other breast carcinomas showed no immunohistochemical staining for amylase. The lipid-rich variant of breast cancer of our patient accounts for ~1% of all breast cancers (9). Whether this type of tumor is particularly prone to have positive amylase staining, to produce clinical hyperamylasemia, or to synthesize pancreatic-type rather than salivary-type isoamylase is not known. However, metastatic breast carcinoma must be added to the list of nonpancreatic disorders that can cause striking pancreatic-type hyperamylasemia.
References 1.
Zakowski JJ, Bruns DE. Biochemistry of human isoenzymes.
alpho-amylase CRC Crit Rev Clin Lab Sci 1985:21:28:1-322.
2.
Martin PC. Sarma JIP. Amvlase-l_)rorluc:ing lung C~IICXX. J Surg Oncol 1982:21:30-2.
3
Perk JE. Shemamura 1, Fridhandlsr 1.. Tumc~r assoclatetl h~l)eralnylas~lnia. Am J Gastroentcrol 1977:fX:572-7. Okabe H. tlji Y. Netsu K. Noms A. Automated measurement (11 amylase isoonzymes with 4-nitropht?nylmaltohHptaosidr: as substrate and a selective amylase inhibitor. (:lin Chem 1984;30:1219-22. L.eclorc: I’. Forest J-C. Electrophowtir: determination of isoamylases in swum with c:ommc:rc:ially available reagents. Clin Chem 1982:28:37-40. I.evitt MI). Ellis CJ. Isoelwtri(. focusing studies of human serum and tissue isnamqlasfrs. J 1,ab (:lin Med 1977:90:141-52. Levitt ML). Eckfeltlt JH. IXagnosis of acute pancreatitis. In: Go \‘LiY. Gardner JD. Brooks FP. Lebnnthal E. I)iMagno EP. S(:hrt:le GA. ctis. The exocrino pancreas: biology, pathohiology, and diseasr:s. New York: Kawn, 1!1~6:481-502 Strtrnbergt:r I.A. Hardy PH. Cuculis 11. ?~ley:r HC;. ‘l‘hn uulabc~lnd antibody method of irnmllnohistol.ht:mistr~. Preparation and properties of soluble antigen-antibody complex (horseradish I’eroxiciast:.anti-horsprarlish pProxidasc:) and its use in the identification of spirochetes. ] Histoc:hem (:ytochrm 1970:18:315-33. Kamos (3’. Taylor HH. Lipiti-rich carc.inoma of the breast. (:anc:rr 1974::J:Hl 2-!1.
4.
5.
6. 7.
8.
9.
-
Received March 2, 1987. Accepted September 20. 1987. Address requests for reprints to: lohn Eckfeldt. M.D., Ph.D.. IJniversity of Minnesota Hospital anti (:linic. Hox 198. Harvard Street at East River Road. Minneapolis. Minnesota 55455.