Carcinoid tumors of the pancreas. Status report based on two cases and review of the world's literature.

CONCLUSION: The diagnosis of a pancreatic carcinoid should be based on the measurement of serotonin in serum or its demonstration in the tumor and/or by the measurement of its derivative (5-HIAA) in urine. Carcinoid of the pancreas is a rare but definite entity; usually having metastasized by the time of diagnosis. The term "serotonin-producing tumor of the pancreas" has been suggested as an alternative designation for "pancreatic carcinoid." BACKGROUND: The literature on carcinoid tumors of the pancreas is confusing because much of it preceded the development of the more specific immunological, chemical and staining techniques currently available. METHODS: 43 case reports were collected from the world's literature, based on a demonstrable pancreatic neuroendocrine tumor plus a positive finding of at least one of the following without another dominant hormone being demonstrated: elevation of 5-Hydroxytryptamine (5-HT) (serotonin) in the serum or detected in tumor tissue, and/or elevation of 5-Hydroxyindole acetic acid (5-HIAA) in the urine. In addition to these two hormone-specific assays, information was collected on the silver-staining properties of the tumor; properties which have traditionally been associated with carcinoid tumors. Positive silver staining in tumor cells (argyrophilic and/or argentaffin reaction) is strongly indicative of the carcinoid tumor but the findings are less specific than the hormone assays and immunohistologic stains. RESULTS: In this review of 43 cases, including two current ones, the pancreatic carcinoid tumor has the following important features: 1. It is a rare tumor that is usually diagnosed late when the tumor is large and has metastasized. Thirty-eight (88.4%) have been malignant. They are, therefore, associated with a high incidence of the "carcinoid syndrome." 2. To date, prognosis in therapy is poor, based on delayed diagnosis, a resultant low incidence of resectability, and an uncertain duration of survival after resection. 3. Pancreatic carcinoid tumors remain difficult to differentiate from other endocrine tumors. The measurement of urinary 5-HIAA excretion or the demonstration of elevated serotonin level in the tumor or in serum is essential to its distinction. Silver staining of the tumor, although of historic importance, has been superceded by the hormone-specific studies. 4. To distinguish it from other endocrine tumors of the pancreas, the terms "pancreatic serotoninoma" or "serotonin-producing tumor of the pancreas" have been suggested as possible alternatives. Its growth characteristics may be related more to its cell of origin than to its extent of hormone secretion. Not all of the tumors result in recognizable hyperserotoninemia.

Metastatic pancreatic neuroendocrine carcinoma causing Cushing's syndrome. ACTH secretion by metastases 3 years after resection of nonfunctioning primary cancer.

CONCLUSION: Following resection of a nonfunctioning neuroendocrine carcinoma of the pancreas, subsequent metastases, in the absence of a primary cancer (resected), developed the capacity to secrete ACTH and create the Cushing syndrome. BACKGROUND: Although neuroendocrine carcinomas of the pancreas may produce one or more hormones and may switch secretion to a different hormone, no report is identified of a metastasis, in the absence of the primary tumor, developing de novo the capacity to secrete ACTH. METHODS: A nonfunctioning islet cell carcinoma was resected and immunochemically stained for multiple hormones. Three years later hepatic metastases were partially resected and stained as before. RESULTS: The primary cancer stained negative for ACTH and cortisol, positive for serotonin, and focally positive for gastrin. Three years later, after the development of a florid Cushing syndrome, the metastasis stained strongly for ACTH and negative for serotonin.

Adenocarcinoma of duodenum and ampulla of Vater: clinicopathology study and expression of p53, c-neu, TGF-alpha, CEA, and EMA.

Oncogenes, tumor suppressor genes, and growth factors are being explored as to their role in the initiation and progression of most neoplasms, but little information exists on the expression of oncoproteins or growth factors in adenocarcinoma of the duodenum or ampulla of Vater. This report covers expressions of p53, c-neu, TGF-alpha, CEA, and EMA in duodenal adenocarcinoma and ampullary adenocarcinoma, as well as correlations between expressions and tumor stage, histological grade and patient survival. The expression of p53, c-neu, TGF-alpha, CEA, and EMA has been studied in 15 duodenal adenocarcinomas and in eight ampullary adenocarcinomas by avidin-biotin-peroxidase complex indirect immunoperoxidase technique. The positive reaction for p53, c-neu, TGF-alpha, CEA, and EMA in duodenal adenocarcinoma was 20%, 60%, 60%, 73%, and 100%, respectively, and in ampullary adenocarcinoma, 13%, 100%, 50%, 63%, and 100%. Among the duodenal tumors, C-neu and p53 expression was noted more frequently in groups with high histological grades. Patients with c-neu positive duodenal adenocarcinoma had a shorter survival than the patients with c-neu negative duodenal adenocarcinoma (P < 0.01). C-neu product may serve as an unfavorable prognostic indicator in duodenal adenocarcinoma. No statistically significant correlation was found between the expressions of CEA, EMA, p53, and TGF-alpha and patient survival, tumor stage, or histological grade in either duodenal or ampullary adenocarcinomas.

Papillary cystic and solid tumors of the pancreas: a pancreatic embryonic tumor? Studies of three cases and cumulative review of the world's literature.

BACKGROUND: The papillary cystic and solid tumor of the pancreas is rare. It occurs predominantly in young women, and most present a benign behavior. The pathogenesis of this tumor has attracted a number of investigations but remains unclear. METHODS: We present three patients with this tumor and a review of 289 others from the world's literature, a total of 292 cases. On the basis of the analyses of the clinical and pathologic features from the reported cases, the pathogenesis of this unusual tumor has been further explored. RESULTS: Ninety percent of the patients were female, with a mean age of 23.9 years. The tumors were usually quite large with a mean diameter of 10.3 cm. Ninety-two percent of these tumors were totally or partially cystic. Rupture of the capsule resulted in hemoperitoneum in eight cases, five of which were without any identifiable cause. Forty-three tumors (14.7%) have been recognized as malignant. The overall prognosis has been excellent and an aggressive approach to resection is indicated. CONCLUSIONS: The results of immunohistochemical staining and electromicroscopy were rather diverse, but most, including the current cases, support the hypothesis that the tumor originates from pleuripotential embryonic stem cells. Thus the term pancreatic embryonic tumors seems preferable to papillary cystic and solid tumor of the pancreas to delineate the origin of the tumor and to reflect some of its biologic characteristics.

Observations on the developmental patterns and the consequences of pancreatic exocrine adenocarcinoma. Findings of 154 autopsies.

OBJECTIVE: To improve our future care of the patient with exocrine pancreatic cancer by seeking, within the limitations of our present approaches, additional information on the growth and spread of the cancer and its influences on the patient. DESIGN: Consecutive autopsies of all patients with exocrine pancreatic cancer were reviewed retrospectively by two surgeons and three pathologists. SETTINGS: Three teaching hospitals of the Medical College of Ohio, Toledo. MATERIALS: One hundred fifty-four consecutive autopsies of patients with exocrine pancreatic cancer during the period between 1952 and 1992. RESULTS: Intrapancreatic metastases or multicentric cancers were found in 12 patients. In 32 patients, pancreatic cancer skipped the lymph nodes, primarily draining the respective areas of the pancreas to metastasize to the secondary chain of nodes. In 13 patients, pulmonary metastases occurred without hepatic metastasis. Intrapancreatic contiguous extension was identified in 34 patients. Carcinoma of the body and/or tail of the pancreas was characterized by transperitoneal as well as hematogenous dissemination to a greater extent than was carcinoma of the head of the pancreas. Seven of 11 small tumors (< 2 cm in diameter) were associated with remote metastases. Relatively severe chronic obstructive pancreatitis was found to have resulted from pancreatic carcinoma in 18 cases, whereas in seven patients, pancreatic carcinoma probably developed in preexisting chronic pancreatitis. Thromboembolic disease was found in 30 patients, more frequently in the patients with the mucin-producing tumors of the pancreatic body and tail. In 21 patients, the amount of ascites was not proportional to the severity of peritoneal dissemination, vessel invasion, or recognizable hepatic dysfunction. Thromboembolic disease, severe infection, stress ulcer, and acute hemorrhagic erosive gastroenteritis were frequent systemic complications contributing to death. Malnutrition in the form of cachexia was undoubtedly a major, even dominant, feature in many patients that could not be quantitated from this data. CONCLUSIONS: Metastasizing cells frequently bypass the initial filters in lymph nodes, liver, or lung to become established in secondary or tertiary sites. Intrapancreatic metastases or multicentric tumors also may develop more frequently than generally has been recognized. Small cancers (< 2 cm in diameter) are often associated at autopsy with remote metastases. These facts would appear to limit the usefulness of the current staging of resected cancers of the pancreas. Cancers of the body or tail are characterized by transperitoneal and hematogenous spread to a greater extent than are those of the head. Anatomical studies often do not explain the cause or the extent of ascites associated with pancreatic adenocarcinoma. As previously indicated, chronic pancreatitis appears to be further confirmed as a precursor of pancreatic cancer.

Overexpression of HER2/neu oncogene in pancreatic cancer correlates with shortened survival.

For the purpose of determining the prognostic significance of HER2/neu oncogene in pancreatic and ampullary cancers, 21 pancreatic cancers of ductal origin and six cancers of the ampulla of Vater were studied immunohistochemically using the monoclonal antibody (MAb) CB11, specifically reactive with HER2/neu product. Staining of the epithelium of the normal duct and acini was negative or weakly positive. Moderately and strongly positive reactions indicated the overexpression of this gene, and were found in 10 of 21 (47.6%) pancreatic cancers of ductal origin and in 2 of 6 (33.3%) ampullary adenocarcinomas. Overexpression of HER2/neu was closely and inversely related to the survival of the patients with pancreatic cancer of ductal origin: 19.1 +/- 11.7 mo for those not overexpressing vs 7.3 +/- 3.8 mo for the overexpressors (p < 0.01). Among the pancreatic cancer group, 11 patients underwent cancer resection. The average survival for the 7 with nonoverexpressing cancer was 21.4 +/- 14.3 mo vs 10.5 +/- 3.6 mo for those with overexpressing tumor. Among those not undergoing resection, the average survival for the 4 with nonoverexpressing cancer was 15.0 +/- 3.8 mo as contrasted to 5.2 +/- 2.1 mo for the overexpressors (p < 0.01). Although the number of patients is small, these findings suggest that the overexpression of HER2/neu gene product may be frequently found in pancreatic cancer of ductal origin and may be one of the useful prognostic biomarkers for this cancer.

Intrahepatic biliary cystadenoma with intracystic gallstone formation.

Biliary cystadenoma is a rare tumor of the liver. We describe a biliary cystadenoma of the left lobe of the liver with intracystic gallstone formation. This is the first report of stone formation in biliary cystadenoma of the liver.

Pigmented villonodular synovitis of the spine. Case report.

Pigmented villonodular synovitis commonly occurs in synovial joints of the appendicular skeleton, but rarely affects the synovial joints of the spine. It has both neoplastic and benign features, and the etiology is thought to be posttraumatic. The case of a young man presenting with paraparesis and a large thoracic lesion is reported.

Pseudoleukemia in Down's syndrome. Analysis of immunophenotype and gene rearrangement.

This report demonstrates a case of transient abnormal myelopoiesis (TAM) evolving in a patient with Down's syndrome. A diagnosis was established after the patient's blast cell count decreased considerably three weeks after the initial leukemic phase. The blast population in the authors' case expressed Leu-9 (CD7), 6D1, and TdT+. Cytochemistries showed some of the blast population to be peroxidase positive and Sudan black positive. Platelet peroxidase by electron microscopic examination showed some positive blasts. Therefore, surface markers and cytochemical studies in this case suggested an abnormal proliferation involving a pluripotential stem cell capable of expressing myeloid and lymphoid characteristics. Cytogenetics was performed at birth and showed 47,XY,+21/48,XY,+21,+mar, confirming the diagnosis of Down's syndrome. The origin of the chromosomal fragment was uncertain. It was of interest that during the remission phase of his pseudoleukemia there was a concomitant decrease in the extra chromosomal fragment. Immunoglobulin and T-cell antigen receptor gene rearrangement studies showed only germline patterns, indicating that the lymphoid cells in the blast population were not clonally expanded. Therefore, immunoglobulin and T-cell antigen receptor rearrangement analysis and immunophenotyping are extremely valuable techniques in distinguishing between TAM and acute lymphoblastic leukemia in patients with Down's syndrome.

Acute lymphoblastic leukemia-hand mirror variant. Analysis for endogenous retroviral antibodies in bone marrow plasma.

Two unusual cases of acute lymphoblastic leukemia-hand mirror variant (ALL-HMV) are presented. One patient demonstrated a mixed immunophenotype with HLA-DR, My7, transferrin receptor surface markers, and terminal deoxynucleotidyl transferase positivity. To the authors' knowledge, this is the first ALL-HMV reported with myeloid antigen. The patient died during induction and did not demonstrate the indolent course noted in the female subgroup with this disorder. The second case initially was not an ALL-HMV but presented as a non-T non-B ALL, and the patient had a relapse six years later with numerous hand mirror cells (HMCs). In the authors' experience, this is the first case of ALL that presented as a non-HMC and relapsed as an ALL-HMV. The patient's immunophenotype revealed he was HLA-DR, transferrin receptor, and TdT positive. Both patients' leukemic cells showed a diffuse granular periodic acid-Schiff on a clear background and acid phosphatase-positive pattern. Immunogenetics revealed a clonal rearrangement of one of the two Ig heavy chain loci in the one patient evaluated. Western blot analysis of the bone marrow plasma of both patients with ALL-HMV showed an increase of cross-reactive IgG to the envelope gp70 and IgM against the core p30 proteins of the baboon endogenous virus (BaEV) and simian sarcoma-associated virus (SSAV). Furthermore, their bone marrow plasma demonstrated IgM antibodies to the gp70 that were not present in any of the other non-hand mirror leukemic patients or the normal controls. These findings strengthen the concept that HMCs in ALL are formed in relation to an immunologic response to increased proteins related to BaEV and/or SSAV.

Diagnosis of acute megakaryoblastic leukemia by flow cytometry and immunoalkaline phosphatase techniques. Utilization of new monoclonal antibodies.

This report demonstrates a case of acute megakaryoblastic leukemia evolving in a patient with idiopathic myelofibrosis with myeloid metaplasia. A presumptive diagnosis was made by cytochemical stains, alpha-naphthyl acetate esterase, and alpha-naphthyl butyrate esterase. The diagnosis was established by electron microscopic platelet peroxidase studies of the peripheral blood blast cells and supported by flow cytometry and immunoalkaline phosphatase studies. Specific monoclonal antibodies directed against platelet glycoproteins Ib (6D1) and IIb/IIIa (10E5), which have not been described frequently in analyzing leukemia, were used for flow cytometry and direct immunoalkaline phosphatase technique. Cytogenetic studies demonstrated a deletion of the long arm of chromosome 6 with breakpoints at bands q15 and q23, and ring chromosome 6 (p25, q27). The diagnosis of megakaryoblastic leukemia requires accurate cytochemical stains, platelet peroxidase by electron microscopic examination, and studies employing specific monoclonal antibodies directed against platelets and megakaryoblasts. The exact origin of the circulating megakaryoblasts in these cases is not known and needs additional investigation.