Amylase-producing ovarian cancer treated with postoperative QF chemotherapy--a case report

A case of an amylase-producing ovarian cancer in 69-year-old woman has been investigated by light and electron microscopy, as well as by amylase isozyme analysis. Serum and urinary amylase levels were found to be elevated, especially by an amylase isozyme analysis of the tumor homogenate which revealed a salivary type of cancer. The serum amylase level and its isozyme pattern returned to normal following therapy. Pathological examination revealed a serous cystadenocarcinoma. The ultrastructure of this tumor resembled that of other ovarian serous cystadenocarcinomas. No zymogen granules were recognized. Thus, a biochemical analysis of amylase isozyme was found to be a useful tumor marker for diagnosis and treatment of an amylase-producing ovarian serous neoplasm.     

Acinar-endocrine cell tumor of the pancreas. Report of a pancreatic tumor containing both zymogen and neuroendocrine granules

A case of pancreatic tumor with features of both an acinar cell and an endocrine cell tumor is presented. The histologic appearance of the tumor by light microscopy was consistent with the appearance of either an islet cell tumor or an acinar cell tumor. Electron microscopy revealed two distinct populations of membrane bound granules within the same tumor cells; namely, a small granule measuring 100-200 nanometers in diameter with a narrow halo separating it from the granule membrane, and a large granule measuring 400-500 nanometers in diameter and having a closely applied membrane. The smaller granules have the characteristic appearance of gastroenteropancreatic (GEP) endocrine-cell granules. The large granules are greater in size than neuroendocrine granules, their morphologic structure is most consistent with that of zymogen granules, and a positive lipase stain supported the presence of zymogen granules within the tumor. The occurrence of both neuroendocrine and zymogen granules within the same cell has been previously described in the "intermediate cell" of the pancreas, but not to our knowledge in a tumor of the pancreas. The finding of both endocrine and exocrine granules within a single cell indicates a histogenetic relationship between the pancreatic endocrine and exocrine cells, and may represent the first reported case of a neoplastic proliferation of intermediate cells.     

Simultaneous production of amylase and adrenocorticotropin by lung cancer--with special reference to electron microscopic and immunohistochemical studies

The tumor tissue from a lung cancer patient who showed elevated serum amylase and adrenocorticotropin was investigated ultrastructurally and immunohistochemically. On microscopic examination, the tumor was diagnosed as small-cell carcinoma. Electron microscopy revealed that some of the tumor cells possessed small endocrine-like dense cored granules. The tumor cells also contained large zymogen-like granules within the cytoplasm, which possessed microvilli and formed the lumen, indicating their adenocarcinomatous differentiation. An electrophoretic analysis of the serum amylase showed that the major amylase elevated was of the salivary type. Immunohistochemical staining by the antihuman salivary amylase antibody disclosed that various portions of the tumor actually contained the salivary amylase. The evidence suggests that the small-cell carcinoma cells showed "confused differentiation", thereby expressing amylase and ACTH simultaneously.     

Duct-like morphogenesis of Longnecker pancreatic acinar carcinoma cells maintained in vitro on seminiferous tubular basement membranes

We have investigated the behavior of dissociated cells of a moderately differentiated Longnecker transplantable pancreatic acinar carcinoma (Longnecker et al., Cancer Lett., 7: 197-202, 1979) maintained in vitro on acellular seminiferous tubular basement membranes of rat testis. The tumor cells, which grow as solid masses in vivo with little organization, undergo organogenesis in vitro into distinct duct-like structures with lumina in the presence of basement membrane scaffoldings. These duct-like structures were formed by flattened epithelial cells, which exhibited poorly differentiated acinar cell characteristics with few or no zymogen (secretory) granules. The cells lining the duct-like structures retained the pancreatic acinar cell specific antigen as determined by indirect immunofluorescence. DNA synthesis did not accompany duct-like organization; however, all of the cells lining these structures continued to incorporate [3H]leucine for up to 4-5 days of culture. They continued to synthesize and secrete amylase, a marker protein of pancreatic acinar cells, into the medium. These results demonstrate that neoplastic epithelial cells of Longnecker pancreatic tumor differentiate into duct-like structures when they come into contact with a basement membrane scaffolding and do not accumulate well-formed secretory granules. This is in marked contrast to the previously reported in vitro differentiation of cells derived from another transplantable rat pancreatic acinar cell carcinoma where the neoplastic cells were fully cytodifferentiated on seminiferous tubular basement membrane without forming duct-like structures but accumulated abundant well-developed zymogen granules (Watanabe et al., Cancer Res., 44: 5361-5366, 1984). Although the basal lamina promotes differentiation of cells of two different pancreatic carcinomas in vitro, we conclude that the in vitro expression of morphogenetic and cytodifferentiation patterns is dependent upon the intrinsic properties of cells of these two transplantable pancreatic tumors.     

Acinic cell adenocarcinoma arising in the breast of a young male: A clinicopathological, immunohistochemical and ultrastructural study

A 23-year-old man with acinic cell adenocarcinoma of the breast is reported. He presented with a 4.8 × 4.2 cm mass in his left breast, and excisional biopsy was performed. Under the light microscope, tumor cells had abundant periodic acid-Schiff-positive secretory granules and eosinophilic cytoplasms. Electron microscopy revealed the granules to have various electron densities, a finding characteristic of acinic cell adenocarcinoma. Immunohistochemically, the tumor cells were stained with salivary-type amylase. Electron microscopic and immunohistochemical investigation greatly facilitated the diagnosis of this acinic cell adenocarcinoma, which was in an unusual location. We believe this is the first case report of acinic cell adenocarcinoma of the mammary gland studied utilizing light microscopic, ultrastructural and immunohistochemical techniques.     

Ultrastructural, cytochemical, and biochemical characterization of alpha-amylase produced by human gastric cancer cells in vitro

Ectopic production of salivary-type amylase was demonstrated in a human gastric carcinoma cell line (KMK-2) maintained in vitro for more than 3 years. Electron-dense granules, which appeared as zymogens, were observed in the tumor tissue, in cancer cells in the peritoneal fluid (from which the present cell line had been derived), and in cultured cells in early passages. These granules, however, decreased and gradually disappeared during cultivation. Although such a morphologic alteration was recognized, the property of amylase synthesis has been maintained. The presence of alpha-amylase in the cultured cells was demonstrated cytochemically by the immunoperoxidase method. The enzyme secreted and accumulated in the culture medium was partially purified and characterized. Alpha-amylase of KMK-2 cells closely resembled salivary-type amylase in gel filtration profile and disk gel electrophoresis. Immunologic cross-reaction was observed between these enzymes. Secretion into the medium was constant, and the enzyme concentration in the cytoplasm was relatively high when the cells had reached confluence. Prednisolone increased the amylase production two-fold in the cells.     

Argyrophil cell carcinoma of the uterine cervix with ectopic production of ACTH, beta-MSH, serotonin, histamine, and amylase.

The case of a 38-year-old female with primary argyrophil cell carcinoma of the uterine cervix is reported. Two years after operation the patient developed widespread metastases with typical Cushing's syndrome. Microscopically, the tumor consisted of solid anaplastic cells, adenocarcinoma, and squamous cells. The plasma levels of ACTH and cortisol were elevated. Many cells of both the primary and metastatic tumors showed argyrophilia. Almost all the cells of the metastases contained numerous round secretory granules measuring about 117 micrometers in diameter. Small rod-shaped or larger round secretory granules, measuring 250 and 430 micrometers respectively, were also found in a few of these cells. The tumors in the right lung, pancreas, and kidney contained high levels of ACTH, beta-MSH, serotonin, histamine, and amylase. This is the first report of ectopic production of these five substances from argyrophil cell carcinoma of the uterine cervix.     

Solid and cystic tumor of the pancreas--report of a case in a 13-year-old girl

A case of adenocarcinoma of the body of the pancreas in a 13-year-old girl is reported. The gross appearance of the tumor revealed apparent encapsulation, cystic degeneration and hemorrhagic necrosis. Microscopically, the tumor resembled an islet cell tumor, but immunohistochemically there was no evidence of endocrinic activities. Ultrastructurally, tumor cells contain numerous mitochondria but no secretory or zymogen granules. This peculiar type of tumor usually arises in young women and shows a favorable prognosis. Diagnosis should be established immunohistochemically and ultrastructurally.     

Adenocarcinoma of the pancreas in childhood. Report of a case and a review of the English language literature.

A case of adenocarcinoma of the head of the pancreas in a 13-year-old girl is reported. Some areas simulated an islet cell tumor by light microscopy, but contained numerous eosinophilic granules which were PAS-positive and diastase resistant. Ultrastructurally, the granules were large (960 mum-3000 mum in diameter) and electron-dense, resembling zymogen granules. These granules often showed focal to complete degeneration, occassionally being continuous with a myelin figure. The granules of true islet cell tumors are ultrastructurally distinctive and it is urged, therefore, that all pancreatic neoplasms in children be studied by histochemistry and electron microscopy. Carcinoma of the pancreas in childhood is a rare tumor, often with a rapid clinical course resulting in death. Morphologic separation of cases reported in the English language literature can be made on the basis of acinar differentiation. This feature has been suggested as a peculiarity of childhood pancreatic carcinoma. However, there is a suggestion that this phenomenon occurs in a small percentage of adult tumours as well. More extensive morphologic studies in adult pancreatic cancer may be warranted.     

A case of serous papillary cystadenocarcinoma of the ovary with hyperamylasemia

A case of serous papillary cystadenocarcinoma of the ovaries with hyperamylasemia has been studied immunohistochemically, electron microscopically, and biochemically. Cellular localization of amylase in the tumor tissue was determined by biochemical analysis, using an indirect immunoperoxidase method. Electron microscopy revealed electron-dense granules located in the peripheral region of the cytoplasm of most tumor cells.     

Amylase-producing ovarian neoplasm with pseudo-Meigs' syndrome and elevated pleural fluid amylase: case report and ultrastructure.

Elevated amylase activity was noted in the pleural effusion of a patient who was later found to have a stage I low-grade serous papillary ovarian neoplasm. The effusion resolved spontaneously after resection of the ovarian tumor, which contained large amounts of amylase activity. The ultrastructure of the tumor epithelium resembled that of normal salpinx. Secretory-type cells were present with apical, variably electron-dense secretory granules and cytoplasmic glycogen deposits. Amylase activity in the ovarian neoplasm probably resulted from the presence of functioning endosalpingeal-type epithelium in the tumor. In cases of effusion with unexplained amylase elevations, the possibility of serous ovarian neoplasia should be considered, even in the absence of demonstrable extra-ovarian dissemination.     

涎腺硬化性多囊性腺病的临床病理及影像学分析

目的:探讨涎腺硬化性多囊性腺病（SPA）的影像学、临床病理特征及预后。方法:对1例SPA进行影像学、组织学形态及免疫组化染色观察,随访26个月并结合文献复习,探讨该病的临床病理特征及预后。结果:SPA临床上主要表现为涎腺缓慢生长的无痛性肿块。组织学特征与乳腺纤维囊肿性病变相似,表现为不规则的导管及腺泡分布于丰富的硬化性胶原间质中,形成模糊的小叶状结构。腺上皮细胞形态多样,有的呈大汗腺样化生,有的胞质内含丰富的嗜伊红酶原颗粒,导管上皮可以增生并伴有非典型性。免疫组化染色显示腺上皮EMA弥漫强阳性,导管及腺泡周围肌上皮SMA及Calponin阳性。Ki-67指数＜1%。影像学表现:彩超结果表现为边界相对清楚或不清楚的低回声团,可以探及稀疏的血流信号。CT:表现为软组织密度肿块影,边缘较光滑,与正常腮腺分界清楚,也可边界不清。结论:硬化性多囊性腺病是一种罕见的涎腺疾病。主要发生于腮腺,预后较好。影像学缺乏特征表现,界限不清时易误诊为恶性肿瘤。需与黏液表皮样癌、多形性低度恶性腺癌、慢性涎腺炎等鉴别。     

Acinar cell cystadenocarcinoma of the pancreas

An unusual tumor of the pancreas occurred in a 42-year-old man who presented with a gradually enlarging abdominal mass and weight loss. The mass was a 2 kg/25 cm diameter encapsulated multicystic tumor closely attached to the body and tail of the pancreas. On light microscopy it showed a predominantly tubular architecture and ultrastructurally numerous zymogen granules could be demonstrated in the tumor cells. It is therefore presumed to be of acinar cell origin. This tumor has features similar to the so-called acinar cell cystadenocarcinoma described in 1981 by Cantrell et al. Sixteen months after resection of the primary tumor a solitary liver metastasis was removed at a second operation.     

Isolation and characterization of cytotoxic granules from human lymphokine (interleukin 2) activated killer cells

Cytotoxic granules were isolated from human lymphokine-activated killer (LAK) cells and analyzed for their biochemical properties. Isolated granules of approximately 85-95% purity were obtained by differential centrifugation followed by discontinuous Percoll gradient centrifugation. The murine lymphocyte granule marker N-alpha-carbamazepine-L-lysine thiobenzyl ester-esterase as well as cytotoxic activity toward the human tumor cell lines K562, Raji, Daudi, and CEM were associated with LAK granule fractions. Granule-associated N-alpha-carbamazepine-L-lysine thiobenzyl ester-esterase activity increased in recombinant interleukin 2 expanded human LAK cells in parallel with cytotoxic activity for Raji tumor cell targets. Cytotoxic LAK cell granules mediated calcium-dependent killing of the tumor cell lines K562, Raji, Daudi, and CEM. However, no calcium-dependent hemolytic activity was found. Preincubation of human granules with calcium, a treatment which totally inactivates the hemolytic and cytotoxic activity of murine lymphocyte granules [perforin 1 (P1)] had no effect on human LAK granule cytotoxicity for nucleated cells. Human LAK granules appear to contain P1 detected as cross-reactive antigen detected by mouse anti-P1 and human anti-C9 in Western blot analysis. In addition, Northern blot analysis of polyadenylated RNA isolated from human LAK cells using a murine P1 complementary DNA probe showed a cross-hybridizing 2.8- to 3.0-kilobase mRNA species identical in size to murine P1 mRNA. These results demonstrate that despite similar biochemical composition, functional differences exist between human and murine cytotoxic granules. Human LAK granules were synthesized in response to recombinant interleukin 2 activation and appeared in parallel with cytotoxicity for tumor targets, suggesting an important role for LAK granules in tumor cell cytotoxicity by human LAK cells.     

Relationship of ectopic ACTH production to tumor differentiation: a morphologic and immunohistochemical study of prostatic carcinoma with Cushing's syndrome

A case of Cushing's syndrome in a patient with an ACTH-producing prostatic carcinoma is presented. Initial transurethral biopsy showed a moderately well-differentiated adenocarcinoma. The development of Cushing's syndrome was associated with a change in the morphology of the tumor; repeat transurethral prostatic biopsy and autopsy showed an admixture of moderately well-differentiated adenocarcinoma and anaplastic carcinoma. Immunoperoxidase studies revealed ACTH only within the anaplastic component of the tumor, which also showed strong argyrophilia. Electron microscopic studies revealed abundant dense-core granules within the anaplastic portion of the tumor with only very scanty granules in the differentiated portion. This case strongly supports the contention that cells with APUD characteristics can differentiate within epithelial tissues of multiple embryologic origins, and that the possession of APUD features does not necessarily imply origin from any specific neuroendocrine progenitor cell.     

Neuroendocrine carcinoma of the paranasal sinus: a morphological and endocrinological study

Four cases of small cell carcinoma of the paranasal sinuses were studied histologically, ultrastructurally, and endocrinologically. All tumors showed features of undifferentiated carcinoma with alveolar patterns but without acinar or squamous differentiation and contained cells possessing endocrine-type small secretory granules, which were indistinguishable from non-neoplastic neurosecretory granules. The three cases also possessed a small number of microtubules, and in one of these fine cytoplasmic filaments were observed. One case showed elevated plasma levels of cortisol and adrenocorticotropic hormone associated with adrenocortical hyperplasia and Crooke's changes of the pituitary gland. Another case showed hypercalcemia with bone metastasis, hypercalcitonemia with a high content of calcitonin in the tumor tissue, calcitonin-positive tumor cells, and C-cell hyperplasia of the thyroid. It was concluded that all four cases should be called neuroendocrine carcinoma, which might be related to neoplasms derived from amine precursor uptake and decarboxylation cell series rarely encountered in the paranasal sinuses.     

Amylase-producing lung cancer: case report and review of the literature

A case of hyperamylasemia with lung cancer is described. Macroamylasemia was excluded by a normal amylase/creatinine clearance ratio and by a sedimentation constant obtained by sucrose density gradient centrifugation. Positive immunofluorescent staining of tumor cells with a specific antibody against human salivary amylase and significant amylase activity in the primary tumor and metastases support the hypothesis of independent production of amylase by the lung tumor. Cellulose--acetate membrane electrophoresis demonstrated three bands of amylase activity. The major component corresponded to normal salivary amylase in electrophoretic mobility, isoelectric point and molecular size. The minor bands, one of which occupied about 10% of the total amylase activity in serum, urine and tissue homogenates, demonstrated a lower electrophoretic mobility and a more acidic isoelectric point. Gel filtration and electrophoresis disclosed that these minor bands were derived from an amylase isozyme with a larger molecular size than that of normal salivary amylase. The results suggest ectopic tumor production of heterogenous amylase isozymes, with the larger form being secreted into the circulation.     

Carcinoid tumor of the gallbladder associated with adenocarcinoma

A case of carcinoid tumor of the gallbladder associated with adenocarcinoma in a 56-year-old man is reported and a review of the literature is made. The tumor was a polypoid mass with a size of 5.5 X 4.0 X 2.8 cm. Histologically, the tumor showed carcinoid and adenocarcinoma with areas of mucous change. Tumor cells containing argyrophil granules were observed in both carcinoidal and adenocarcinomatous areas, but no argentaffin granules were detected in either of the neoplastic areas. Some of the tumor cells had both argyrophil granules and mucin in the same cytoplasm. The electron microscopic study revealed several tumor cells containing neurosecretory granules; however, no clinical signs of hormonal activities of the tumor were observed. The patient died of generalized bone metastases 16 months after surgery. This appears to be the second case of composite tumor of the gallbladder.     

Amylase-producing lung cancer

A bronchioloalveolar carcinoma of lung associated with hyperamylasemia occurring in a 40-year-old woman is described. Another 13 cases of such a tumor from the English literature are reviewed. A majority of the lung tumors associated with hyperamylasemia were adenocarcinomas. When the amylase isoenzymes were determined, the amylase appeared to be salivary-gland type (S-type). Electron microscopic studies had revealed membrane-bound electron-dense granules within the tumor cells.