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PubMed2004

Intraabdominal desmoplastic small round cell tumor: results of ifosfamide-based chemotherapy.

Intraabdominal desmoplastic small round cell tumor (IDSRT) is a rare neoplasm, which is malignant and typically occurs in young adults. Although IDSRT is chemotherapy-sensitive, most cases do not achieve a complete response (CR). Even if some cases achieve a CR, they often relapse and result in poor prognosis. We report two cases of IDSRT, in a 24-year-old man and a 23-year-old man, who were treated with ifosfamide-based chemotherapy. Case 1, a 24-year-old man, presented with an abdominal mass, and the diagnosis of the biopsy specimen at laparoscopy was IDSRT. He received 7 courses of ifosfamide-based chemotherapy, which obtained a partial response (PR). He had no surgical resection, except for the biopsy procedure, and he underwent a total of 21 courses of chemotherapy. He died 36 months after diagnosis because of tumor regrowth and peritoneal bleeding. Case 2, a 23-year-old man, whose biopsy material allowed a diagnosis of IDSRT, was treated with 18 courses of chemotherapy, using ifosfamide, that resulted in a PR. This was followed by resection of the abdominal lesions, and he received an additional 2 courses of adjuvant chemotherapy. Four months after, completion of these 2 courses, the tumor recurred, and he died of diffuse pulmonary metastasis 36 months after diagnosis. This case report examines the results of ifosfamide-based chemotherapy in our two patients.

Abdominal Neoplasms↗
PubMed1999

Metaplastic breast cancer: prognosis and response to systemic therapy.

BACKGROUND: Metaplastic breast cancer is a rare disease with little information available to guide therapy. The goals of this study were to describe the patient characteristics, systemic therapies and clinical outcomes of all patients with primary metaplastic breast cancer treated at Mayo Clinic between 1976 and 1997. PATIENTS AND METHODS: Patients were identified through the medical index of Mayo Clinic. Clinical information was abstracted from the medical record of each patient. A literature search using MEDLINE and CANCERLIT for the years 1966-1997 was performed to identify all previously reported case series in the English language containing 10 or more patients. RESULTS: Twenty-seven patients were identified with a median age at diagnosis of 59 years (range 39-90 years). The median tumor size was 3.4 cm (range 0.5-7.0 cm). One patient had metastatic disease at presentation. Twenty-three patients had information available on nodal status, estrogen receptor (ER) and progesterone receptor (PR) status. Twenty patients (87%) were node-negative and three patients (13%) were both ER and PR positive. Disease-free survival (DFS) and overall survival (OS) were assessed for those who presented with local-regional disease. The three-year DFS was 40% (95% CI: 23%-73%) and the three-year OS was 71% (95% CI: 51%-97%). In univariate analysis, those patients 60 years of age or older at diagnosis were found to have an increased DFS (P = 0.011). Among those with prior estrogen use, both DFS (P = 0.022) and OS (P = 0.003) were decreased. Thirteen patients (50%) developed metastases with a median DFS time of 2.4 years. Ten different chemotherapy regimens were utilized for metastatic disease and one partial response was observed. There were no responses to tamoxifen in four patients with metastatic disease. Median survival after the development of metastases was eight months. CONCLUSIONS: Despite presenting more commonly as node-negative disease, DFS and OS in metaplastic breast cancer is decreased compared to typical adenocarcinomas. Systemic therapy also appears to be less effective. Patients with metaplastic breast cancer, particularly those with metastatic disease could be appropriate candidates for innovative therapeutic regimens.

Adult↗
PubMed2000

Benign renal angiomyoadenomatous tumor: a previously unreported renal tumor.

We describe a unique benign tumor of the kidney in a 93-year-old man. Microscopically the tumor was composed of an intimate intermixture of epithelial component and smooth muscle tissue, which formed the stroma of the tumor. In some parts the epithelial cells in adenomatous tubular formations were endowed with clear snouts. These clear snouts had a blister-like quality and grew on the secretory cells lining the tubules. No atypias, mitoses, or pleomorphism were present in the tumor. The muscular component consisted of poorly cellular, HMB-45-negative, leiomyomatous bundles, which greatly differed from that of angiomyolipoma. It encircled the whole tumor and intimately intermingled with the epithelial component. These leiomyomatous bands formed focally abortive vessels, which had incomplete and irregular walls and lacked an elastic layer. Even more interesting was a peculiar vascularization of the tumor. All epithelial tubular structures of the tumor revealed an intimate association with small capillaries. A fine labyrinth of the capillaries rimmed the rows of the epithelial cells. To the best of our knowledge this tumor differs from all previously described.

Adenoma↗
PubMed2005

Primary gastrointestinal stromal tumor of the esophagus in an HIV-positive patient.

We describe a rare case of malignant gastrointestinal stromal tumor (GIST) of the esophagus presenting in an HIV-positive man. Not only did the tumor arise from an unusual anatomic site for GIST, namely, the esophagus, but it also had a predominant epithelioid cell morphology that is uncommon and preferentially associated with aggressive behavior. Exhaustive immunohistochemical studies showed strong reactivities to the classic GIST marker, CD34, and to the current more sensitive and more specific GIST marker, CD117/ c-kit protein. This immunophenotype corresponded to that of stromal tumors arising in the more common sites like stomach and small intestine as well as to that of a reported series of esophageal GISTs in the general population. Mutations of the c-kit protein was detected in the tumor, confirming previous observations. This further documents that esophageal GIST and the more common benign esophageal spindle cell lesions are pathologically distinct entities and despite its rarity, esophageal GIST should be recognized by pathologists and clinicians. The occurrence of this tumor in an HIV-positive patient is coincidental, and it resulted in an extremely unusual metastatic site that has not been reported for GISTs.

Antigens, CD34↗
PubMed2004

Large cell neuroendocrine carcinoma of the ampulla of Vater with glandular differentiation.

Large cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare. A 55 year old woman presented with an ampullary tumour causing pancreaticobiliary obstruction and a pancreaticoduodenectomy was performed. Microscopically, the tumour was diagnosed as a CD117 positive large cell neuroendocrine carcinoma with glandular differentiation. Four months later the patient developed a general recurrence. The metastatic tumours showed CD117 negativity and pure neuroendocrine features. The patient died of disease six months after diagnosis. It is postulated that the two components originated from a common multipotential stem cell. The clinical behaviour of ampullary large cell neuroendocrine carcinomas appears to be highly aggressive, with early metastases and a fatal outcome.

Ampulla of Vater↗
PubMed2007

Mutation, replicative infidelity of DNA and aneuploidy sequentially in the formation of malignant pleomorphic tumors.

Mutations are thought to be involved in tumor formation because (i) tumor cells transmit their abnormalities to their descendants; and (ii) many carcinogens are mutagens. Aneuploidy is thought to be involved in tumor formation because (i) it is a common phenomenon, especially among malignant neoplasms; (ii) certain particular types of tumors are associated with specific karyotypic changes; and (iii) many immortal tumor cell lines are hyperploid. In recent years, acquired somatic cell replicative infidelity of DNA ("mutator phenotype") has been suggested as a mechanism of tumor formation, because more somatic genomic events occur in malignant tumor cells than could be caused by repeated exogenous mutagenic insults. Previously, theories of the genomic pathogenesis of tumors have involved these mechanisms individually. Here it is suggested that all three mechanisms may play roles in the formation of certain tumor types. For example, a sequence could occur such that first, a mutation affects genomic elements for control of growth, and for replicative fidelity of DNA, leading to "mutator phenotype". Second, when replicative infidelity of DNA results in mutation of genomic elements for mitotic-and-chromosomal stability, aneuploidy develops. Third, an asymmetric mitosis (in the course of the aneuploid stage) could produce occasional cells in which the "bad copy" is lost (or an extra "good copy" is gained) of the original genomic element which had supported replicative fidelity of DNA. These resulting cells would regain fidelity of replication of DNA, and hence could give rise to populations which are relatively genomically stable, hyperploid and immortal.

Aneuploidy↗
PubMed2000

Peptide amidating activity in human bronchoalveolar lavage fluid: relationship to lung cancer, inflammation and infection.

The most common post-translational modification of peptide hormones, present in half of all neuroendocrine (NE) peptides, is alpha-amidation and this is necessary for the biological activity of the peptides. Peptides are alpha-amidated by the action of two enzymes: peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidylamidoglycolate lyase (PAL). As the common pathway for the formation of amidated peptides, the enzymes may provide a better indication of the NE status of a tumour or tissue than the presence of any single amidated peptide. PHM and PAL enzyme activities were measured in 39 BL fluid specimens from patients undergoing bronchoscopy for diagnosis of lung cancer. The assays revealed that PHM levels were higher in a group of specimens from patients undergoing bronchoscopy for chest infection, inflammation, asthma, or pneumonia compared to a group of specimens in which malignant cells were seen. The presence of elevated levels of amidating enzymes in specimens with non-cancerous conditions may reflect events of promotional phase cancer biology occurring simultaneously with inflammatory and infectious processes.

Amidine-Lyases↗
PubMed2000

Divergent differentiation in neuroendocrine tumors of the adrenal gland.

Composite tumors of the adrenal medulla usually consist of pheochromocytoma admixed with ganglioneuroma or ganglioneuroblastoma. These neoplasms reflect phenotypic plasticity shown by primitive sympathetic cells and mature chromaffin cells in vitro. They may give rise to metastatic neuroblastoma in adults and may cause signs and symptoms attributable to both catecholamine and neuropeptide production. Schwann cells and sustentacular cells are typically numerous in these tumors but it is not known whether they are neoplastic. Immunohistochemical staining for catecholamine biosynthetic enzymes, secretory vesicle proteins and S-100 protein tends to recapitulate staining of the normal adrenal medulla or sympathetic ganglia. Sparsity of chromogranin A in the cell bodies of immature and mature neurons is a diagnostically useful characteristic.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Ectomesenchymoma: case report and review of the literature.

Ectomesenchymoma (EMCH) is a rare tumor that may arise in the brain or soft tissue. This tumor type is defined as a form including ectodermal components represented by neuroblasts or ganglion cells and differentiated mesenchymal structures of various types. The mesenchymal component is most often a rhabdomyosarcoma, but liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, chondrosarcoma, malignant schwannoma, and osseous elements have also been recorded. We report a case of an abdominal malignant ectomesenchymoma, containing three components, schwannoma, embryonal rhabdomyosarcoma, and ganglion cells, in a four-month-old infant. We also review 43 previously reported cases.

Abdominal Neoplasms↗
PubMed1984

The epithelial origin of a malignant mesodermal mixed tumor of the bladder: report of a case with long-term survival.

Malignant mesodermal mixed tumors of the bladder are complex neoplasms consisting of elements of carcinoma and differentiated sarcoma. They are rare, aggressive and usually rapidly fatal. We report on a patient who remained free of disease 7 years after resection by partial cystectomy of a malignant mesodermal mixed tumor. Only 1 other long-term survivor has been reported. Our case is of particular interest because urothelial carcinoma in situ was found in the bladder epithelium on the surface and at the periphery of the invasive tumor, strongly suggesting an epithelial origin of this and similar tumors of other organs.

Carcinoma in Situ↗
PubMed1997

Involvement of chromosome 6 in endometrial cancer.

Cytogenetic investigation was performed on direct preparations of 15 endometrial cancers showing different histotypes. Clonal abnormalities were found in 11 out of 13 analysable cases. The modal chromosome number was near diploid in all cases. The abnormal karyotypes contained relatively simple numerical or structural aberrations in the majority of tumours. In contrast, two neoplasms with serous papillary and mixed mullerian morphological features shared multiple complex changes as well as cytogenetic evidence of intratumoral heterogeneity. The most frequent chromosome abnormality in our series of endometrial neoplasms was 6q deletion, which was detected in serous papillary, endometrioid and mixed mullerian tumours. The loss of the 6q region, which is also frequently involved in ovarian carcinoma, suggests a relationship between endometrial and ovarian cancers based on a common histogenesis.

Adenocarcinoma↗
PubMedDate not supplied

Immunocytochemical detection and characterization of intrahepatic human pancreatic islets after combined liver-islet allotransplantation.

The unique availability of an explanted liver-islet allograft, removed for primary nonfunction of the liver, led us to evaluate distribution and phenotype of exocrine and endocrine components of the pancreatic graft. Immunocytochemistry was used to map patterns of gene products for islet hormones, proprotein processing enzymes, panneuroendocrine markers, and pancreatic exocrine markers. When compared with age-matched control pancreases, insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-producing cells were similarly represented and distributed within the grafted islet. We also demonstrate that the intrahepatic transplanted islets retained the enzyme machinery able to process the hormone precursors into bioactive fragments. In the clinical setting, this resulted in an immediate functioning of the graft and insulin-independence of the patient one month after transplantation. The purity in islets, as assessed by immunocytochemistry with antibodies to tissue constituents of endocrine and exocrine lineages, was around 40%. Despite the massive intraportal presence of pancreatic acinar tissue, no signs or symptoms attributable to ectopic hypersecretion of exocrine enzymes occurred. In fact, when tested with antibodies to such enzymes, low levels of immunoreactivity were observed in the grafted acinar cells.

Biomarkers↗
PubMed1993

Biochemical characterization of peptide alpha-amidation enzyme activities of human neuroendocrine lung cancer cell lines.

Peptide alpha-amidation is a posttranslational modification of approximately half of all endocrine and neuroendocrine peptide hormones, including several hormones with mitogenic effects for tumor cells, and is typically essential for complete hormonal bioactivity. alpha-Amidated peptide hormones have been reported to be autocrine growth factors for small cell lung cancer cells. We report here that a variety of human lung tumor cell lines express both enzymes required for the two-step conversion of inactive glycine-extended peptides into their active COOH-terminal alpha-amide analogues. Human tumor cell peptidylglycine alpha-amidation enzymes are present in multiple molecular forms. Both proteins are metalloenzymes which are present at highest concentrations in secretory granules in neuroendocrine cell lines. The expression of these enzymes is positively correlated with expression of other markers of the neuroendocrine phenotype, such as DOPA decarboxylase. Peptidylglycine alpha-amidating enzyme-specific activities are approximately 50-fold higher in extracts of endocrine cell lines (lung small cell and carcinoid) than of nonendocrine lines. Biochemical characterization of the peptidylglycine alpha-amidating enzymes will enable development of tools for detection of endocrine processes in the early stages of neoplasia and for interruption of autocrine stimulation pathways in tumor cells.

Amidine-Lyases↗
PubMed2006

Squamous differentiation in primary urothelial carcinoma of the urinary tract as seen by MAC387 immunohistochemistry.

Squamous differentiation (SqD) is variably present in urinary tract tumours, but its significance remains unclear. In this study, SqD was assessed by immunohistochemistry using the monoclonal antibody Mac387 in 145 urothelial tumours (bladder, n = 115; renal pelvis, n = 30). Mac387 detects the myelomonocytic L1 antigen; a member of the calgranulin family shared by epithelial cells and keratinocytes. L1 antigen was shown in SqD in urothelial carcinomas of the bladder or the renal pelvis, including 11 cases with focal SqD unrecognised by conventional analysis. SqD is more frequent in renal pelvic tumours (p = 0.027) and increases with grade/stage mainly in bladder carcinoma (grade, p = 0.05; stage, p = 0.005). Stage Ta/T1 bladder carcinomas with SqD recurred more (p = 0.021). In conclusion, Mac387 efficiently shows SqD in urothelial tumours.

Aged↗
PubMed1991

Alpha-amidation of peptide hormones in lung cancer.

Small-cell lung cancer (SCLC), the most common neuroendocrine tumor in humans, provides an excellent model system for analyzing the role of growth factors in lung cancer. SCLCs secrete a wide range of peptide hormones, including some that stimulate tumor cell growth, such as gastrin-releasing peptide and insulin-like growth factor I. Many of these peptides are synthesized as prohormones that acquire biological activity only after specific post-translational modifications. Here, we review our current understanding of the biological role of neuroendocrine peptides in lung carcinogenesis and consider how a mechanistic knowledge of one particular modification, carboxy-terminal alpha-amidation, may permit identification of novel growth factors for lung cancer cells. We also describe potential applications of this knowledge as a basis for prevention-oriented approaches to the disease.

Amides↗