Small Cell Carcinoma Of The Prostate Research Articles

Correlation of non-random chromosomal aberrations in lymphocytes of prostate cancer patients with specific clinical parameters.

The purpose of this research was to correlate non-random chromosomal aberrations in the peripheral blood lymphocytes (PBLs) of prostate cancer patients with specific clinical parameters. Peripheral blood samples were analyzed from 59 informative prostate cancer patients. Non-random chromosomal alterations detected in the PBLs and their correlation with any specific clinical parameters were analyzed statistically. A comparison was made between specific chromosomal abnormalities in the patients having an early (<65 years) or late (> or =65 years) age at disease onset, low-grade (Gleason grade <7) or high-grade (Gleason grade > or =7) tumors, a low (<10 ng/ml) or high (> or =10 ng/ml) prostate-specific antigen (PSA) level, and androgen-sensitive or -insensitive disease. In examining the specific chromosomal breakpoints, the regions 1p13, 2q21, 3p21, 4q13, 5q31, 6p21, 7p15, 7p13, 7q32, 10p11, 10q26, 11p15, 11p11, 14q12, and 16q12 showed breaks in at least four cases. Chromosome 15 (P=0. 045) was significantly altered in patients having a PSA value greater than or equal to 10, while it (P=0.017) and chromosome 19 (P=0.036) were significantly altered in patients having a PSA value greater than or equal to 20. In addition, chromosomes 5 (P=0.032), 8 (P=0.020), 16 (P=0.009), and 20 (P=0.047) were significantly altered in patients having a Gleason grade greater than 7. Also, chromosomes 2 (P=0.020) and 3 (P=0.044) were significantly altered in patients who had early disease onset. Additionally, chromosome 10 (P=0.041) was significantly altered in patients having metastasis, and chromosomes 4 (P=0.006) and 7 (P=0.028) were significantly altered in patients having androgen-insensitive disease. In spite of the small subset of patients, chromosome 8 (p=0.003) was significantly altered in patients having small cell carcinoma of the prostate. From these results we conclude that non-random chromosomal aberrations present in PBLs of prostate cancer patients can be correlated with specific clinical parameters. These correlations can be used to identify a prostate cancer patient's risk response to therapy.

Metastatic small-cell carcinoma of the prostate diagnosed by fine-needle aspiration biopsy.

Fourteen fine-needle aspiration biopsies (FNABs) of metastatic small-cell carcinoma done on 12 patients who had histologically documented primary small-cell carcinoma of the prostate are described. The FNABs were of lymph node (four cases), liver (four cases), bone (two cases), pancreas (one case), perirectal soft tissue (one case), perineum (one case), and lung (one case). One patient underwent three FNABs. No patient had a second primary tumor elsewhere. Cytologic smears were cellular with numerous single tumor cells, many apoptotic bodies, and variable numbers of mitotic figures. Tight cell clusters with molded nuclei and finely stippled chromatin were seen in all cases. An organoid pattern of tumor cells was seen focally in two cases. Features distinguishing small-cell carcinoma from poorly differentiated prostate carcinoma were cell size, finely stippled chromatin, inconspicuous nucleoli, and numerous single tumor cells. Distinction from small-cell carcinoma of other primary sites requires clinical and radiologic correlation. We conclude that cytologic specimens are useful for documenting metastatic small-cell carcinoma of the prostate and for differentiating between it and conventional prostate carcinoma in metastatic sites.

Pure small cell carcinoma of the prostate

Pure small cell carcinoma of the prostate is a rare anaplastic tumour. This report presents the clinicopathological findings of two patients presenting with this disease. Immunohistochemistry was positive for protein gene product 9.5, neurone specific enolase and calcitonin. Staining was negative for prostate specific antigen and prostate acid phosphatase. Androgen ablation has no place in the management of this lesion and patients with this disease should be managed as if they have a neuroendocrine tumour.

Small Cell Carcinoma of the Prostate: A Case Report

Small Cell Carcinoma of the Prostate: A Case Report

Small Cell Carcinoma of the Prostate

An 82-year-old man, who 7 years previously had been treated for adenocarcinoma of the prostate, was found to have developed a small cell (oat cell) carcinoma of prostate, which presented with liver metastases. The expression of different neuroendo crine markers in these carcinomas is presented, the histogenesis of small cell carcinoma is discussed, and the relevant literature is reviewed. The importance of the recognition of small cell carcinoma of the prostate is emphasized because of the influence of small cell carcinoma on the prognosis. Int J Surg Pathol 2(3):237-244, 1995

PRIMARY SMALL CELL CARCINOMA OF THE PROSTATE: UNUSUAL MODES OF PRESENTATION

Primary small cell carcinoma of the prostate is an uncommon condition. Between August 1989 and July 1991 seven patients with this pathology presented to the Repatriation General Hospital, Melbourne. Four of these patients presented by means not previously described. Included in this group is the first reported case of this tumour localized to the prostate gland and apparently cured by radical prostatectomy. The generally poor prognosis and lack of hormonal response associated with this condition warrant a greater awareness of the diagnosis among urologists.

Do neuroendocrine cells in human prostate cancer express androgen receptor?

The presence of androgen receptors (AR) in neuroendocrine cells was investigated in benign tissue of 10 prostatectomy specimens, in 12 prostatic adenocarcinomas with focal neuroendocrine differentiation and in 1 case of a pure neuroendocrine small cell carcinoma of the prostate. Neuroendocrine cells were defined by their reactivity with an antibody to chromogranin A. Monoclonal antibody F39.4 directed against the amino-terminal domain of the AR molecule was used to detect AR. AR and chromogranin A were simultaneously visualized with a double immunofluorescence technique. The results indicate that chromogranin positive cells in both benign and malignant prostatic tissue lack detectable expression of AR. No effect of endocrine therapy was noted. These results are in agreement with the hypothesis that prostatic neuroendocrine tumour cells represent an androgen insensitive cell population, which incidentally may expand to replace the androgen-sensitive tumour cell population during androgen ablation therapy.

Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.

Small cell carcinoma of the prostate

Primary small cell carcinoma of the prostate gland is a rare disease entity with a poor prognosis. Even more unusual than primary disease is a metastasis from a lung primary (Johnson et al, 1974; Hodge &amp; Carson, 1985). We confine ourselves in this paper to primary disease, which has to be differentiated clinically from a pulmonary metastasis. Primary small cell carcinoma of the prostate has been described as occurring after a diagnosis of adenocarcinoma of the prostate (Schron et al, 1984), as a combination of the two histologies at the time of initial diagnosis (Tetu et al, 1987) or on its own (Sarma &amp; Weilbaecher, 1989).Though it has been suggested that small cell carcinoma of the prostate reflects a terminal aggressive phase of adenocarcinomatous disease (Schron et al, 1984), the occurrence of “pure” small cell carcinoma presents an argument against this in at least a proportion of cases (Tetu et al, 1987; Sarma &amp; Weilbaecher, 1989). The origin of small cell carcinoma of the prostate is not clear. It has been suggested that this malignancy derives from the argyrophil and argentaffin cells found in the normal prostatic epithelium (Wenk et al, 1977). However, Schron et al (1984) noted that the small cell carcinoma in their three patients developed in association with, and during the course of progression of, “normal” prostatic adenocarcinoma.

Small cell carcinoma of prostate: Effectiveness of hormonal versus chemotherapy

Small cell carcinoma of the prostate is rare and associated with a rapidly fatal course. Since 1977, 47 cases have been reported in the world literature with data from 3 additional cases presented herein. The purpose of our review was to determine the effectiveness of hormonal versus chemotherapy. Thirty-four of the 50 cases have known clinical histories. Four patients were not treated, and all were dead of their disease within an average of 2.75 months. Six patients were eliminated from our review because small cell carcinoma was discovered at autopsy. Another 5 cases were omitted because hormonal ± chemotherapy had already been given for a previous diagnosis of adenocarcinoma, but no specific therapy was given once the small cell carcinoma developed. Of the remaining 19 cases, only 2 have survived. One is still alive forty-three months after hormonal treatment, and another is alive with disease six months after the initiation of hormonal therapy and chemotherapy. Five patients were given hormonal therapy only, and none of them responded. In 4 patients chemotherapy was given after hormonal therapy had failed, and they too died of their disease within a short period of time. However, an additional 8 patients were treated with immediate chemotherapy ± hormonal therapy and had substantially longer clinical remissions. Therefore, although small cell carcinoma is a uniformly fatal disease, immediate chemotherapy should be considered to promote better clinical remissions.

Chemotherapy for Small Cell Carcinoma of Prostatic Origin

A total of 21 patients with metastatic small cell carcinoma of the prostate was treated with combination chemotherapy, either following initial hormonal therapy (15) or as initial therapy (6). Of the patients 13 (62%) had pure small cell carcinoma, whereas 8 (38%) had mixed histology of small cell carcinoma and adenocarcinoma. Patients presented with a characteristic clinical picture of a large primary mass (16 cases) with a high frequency of visceral metastases to the liver (9), lungs (7) and brain (2). The majority of the patients did not have an elevated serum prostate specific antigen (1 of 14, 7%) or prostatic acid phosphatase (2 of 21, 10%). Serum carcinoembryonic antigen was elevated in 13 patients (62%).Of the 21 patients 13 (62%) responded to chemotherapy. Survival after the diagnosis of small cell carcinoma of the prostate resulted in a median of 9.4 months with a range of 1 to 25 months. The regimens used were those considered active in the treatment of small cell carcinoma of the lung (vincristine, doxorubicin and cyclophosphamide, or etoposide and cisplatin with or without doxorubicin). Small cell carcinoma of the prostate has a characteristic clinical picture and a high response rate to cytotoxic therapy. Early introduction of chemotherapy in the treatment of small cell carcinoma of the prostate may increase the survival rate.

The inhibition of the paracrine progression of prostate cancer as an approach to early therapy of prostatic carcinoma.

The prevalence of neural elements in prostatic carcinoma and their effects on the behavior of the lesion have recently been recognized. Recent reports suggest that chromogranin-A- and neuron-specific enolase-expressing tumors have an earlier progression and a lower response rate to hormonal therapy. The extreme presentation of this tumor is presumed to be small cell carcinoma of the prostate. This bombesin-secreting tumor, which has a characteristic clinical picture of early visceral involvement, wide-ranging metastases, and a relatively low rate of expression of PSA and PAP, is highly responsive to chemotherapy. The relatively high rate of expression of neural elements in primary prostatic carcinoma is discordant with the low frequency of clinical small cell carcinoma of the prostate. In order to account for these differences, one can assume that neural elements may play a role in the progression of this disease by either developing their own neoplastic process (small cell carcinoma of the prostate) or, in the majority of cases, causing paracrine progression of the tumor. Bombesin is typically secreted by small cell carcinoma of the lung and possibly by the prostate. It has been shown to be a growth factor mediating the progression of this disease in a number of experiments. Preclinical data demonstrate increased invasiveness and increased proliferation associated with bombesin in the treatment of prostatic carcinoma. Based on the hypothesis that neural peptides may be important mediators of androgen-independent growth of prostatic carcinoma as well as predicting poor prognosis, inhibition of these factors may represent a therapeutic strategy of relevance for the treatment of patients with prostatic carcinoma.

Analysis of retinoblastoma (RB) gene deletion in human prostatic carcinomas.

The retinoblastoma tumor suppressor gene (RB gene) has been reported to be deleted and/or modified in a number of human cancers, indicating that dysfunction of this tumor suppressor gene is perhaps critical in the development of many human tumors. In addition to deletion of one copy and/or mutational inactivation of the RB gene, this gene has also been reported to be altered by a small deletion in the promoter sequence in one case of small cell mixed adenocarcinoma of the prostate. A deletion of 105 nucleotides of the RB gene in exon 21, leading to an aberrant short-sized mRNA transcript, has also been reported in one cell line (DU 145) derived from brain metastasis of prostatic adenocarcinoma. We have analyzed tissues from 10 prostate specimens (3 hyperplastic and 7 neoplastic) and one prostate cancer cell line (DU 145) for the presence of short-sized mRNA transcript (exon 21 alterations) by polymerase chain reaction (PCR) using total RNA extracted from frozen tumors and the cell line. None of the prostate tissue showed any evidence of aberrant short-sized mRNA, although it was confirmed in the DU 145 cell line. Simultaneously, we have used DNA-PCR to investigate RB promoter deletion in 23 adenocarcinomas and one small cell carcinoma of the prostate. We also failed to demonstrate any indication of RB promoter deletion at the DNA level in adenocarcinomas. The single case of small cell carcinoma failed to show evidence of any aberration in RB promoter. We therefore conclude that neither RB promoter alterations nor the exon 21 deletion are associated with typical prostate adenocarcinoma.

Small Cell Carcinoma of the Genitourinary Tract: An Immunohistochemical, Electron Microscopic and Clinicopathological Study

We examined 13 cases of small cell carcinoma of the genitourinary tract to evaluate and compare the immunocytochemical and ultrastructural features as well as the clinicopathological behavior. Immunohistochemical stains revealed that neuron specific enolase and chromogranin showed differences in staining between the bladder and prostate, as well as between the small cell and adenocarcinomatous components of the prostate. Also, synaptophysin was negative over-all in 12 of 13 cases. Epithelial membrane antigen, carcinoembryonic antigen and keratin showed strong focal positivity within the small cell component. Electron microscopy was performed in 4 cases, with 3 demonstrating neurosecretory granules. Clinically, 6 of the 7 patients with adenocarcinoma/small cell carcinoma of the prostate did poorly, all with a survival of 15 months or less. Of 5 patients with transitional cell/small cell carcinoma of the bladder 2 fared better (both had no evidence of disease at 12 months and 11 years, respectively).Based upon the immunostaining and electron microscopic findings, small cell carcinoma of the genitourinary tract is heterogeneous in appearance and, therefore, may arise from a multipotential cell of origin. This cell of origin may be organ-specific, as demonstrated by the variability in staining characteristics among the prostate, bladder and kidney, as well as by the differences in the clinical behavior of these malignancies. Small cell carcinoma of the prostate has a poor prognosis, while small cell carcinoma of the bladder may portend a better prognosis if diagnosed at an early stage.

Small cell carcinoma of the prostate

This report details clinical and pathologic aspects of a patient with small cell undifferentiated carcinoma of the prostate and systemic hyperglucagonemia. A panel of potential serologic markers was evaluated in order to document additional evidence of ectopic hormonal production. Immunocytochemical markers were sought in tissue samples from the primary neoplasm and a lung metastasis. Stains were positive for corticotropin (ACTH) and gastrin in both the prostate and in the lung, but no evidence of excess secretion was documented. These findings are consistent with the notion that neuroendocrine activity is common in undifferentiated small cell carcinomas, regardless of their site of origin.

Small Cell Carcinoma of the Prostate: Implications for Management

Small Cell Carcinoma of the Prostate: Implications for Management

Small Cell Carcinoma of the Urinary Tract

Small cell carcinomas of the urinary tract are rare, but lethal. We report 3 cases of primary small cell carcinoma of the kidney, urinary bladder and prostate with light microscopic, immunohistochemical and electron microscopic findings. One patient with small cell carcinoma of the prostate died of disseminated disease 2 years after diagnosis and another patient with small cell carcinoma of the urinary bladder was free of tumour after 6 months. A partial remission was induced in the third patient with distant metastases of small cell carcinoma of the kidney by using chemotherapy protocols similar to the drug regimens for small cell carcinomas of the lung; the patient survived for 5 months. Immunohistochemical studies revealed the absence of argyrophilic immunostaining of tumour cells in all 3 cases, positive staining for keratin in 2 and staining for neuron-specific enolase in all 3. In the third patient, reactivity for prostate-specific antigen was negative. Dense-core, membrane-bound granules were identified in the cytoplasm of 2 patients. The paraneoplastic syndrome was not found, indicating that in considering the occurrence of ectopic hormones, specific cytoplasmic granules of origin need not be implicated. Recognition of this distinct entity requires full consideration of morphological, immunohistological, ultrastructural and biological features. In order to define the origin of this tumour more clearly and to evaluate the effectiveness of chemotherapy, larger series of patients are needed.

Unusual Prostatic Carcinomas

Over 90% of malignant epithelial tumors of the prostate are common carcinomas. Uncommon or rare prostate carcinomas can histogenetically be related to 4 epithelial types of the prostate: the secretory epithelium, the basal cells, the endocrine cells and the transitional epithelium. The rare, purely mucinous carcinoma and the ductal papillary carcinoma belong to the type of secretory epithelium. The latter is rarely seen in the large central prostatic ducts, it develops more frequently in peripheral ducts and is combined with common prostate carcinoma. The so-called endometrioid carcinomas of the utriculus described in the literature are probably ductal prostate carcinomas. To date no carcinoma has been found in the utriculus. The adenoid cystic carcinoma of the prostate is a basal cell tumor with preponderantly good prognosis. Endocrine cells are disseminated in most common prostate carcinomas. Thereby mixed forms showing both portions of a common adenocarcinoma and of a carcinoid may occur. Pure carcinoids of prostate are rare findings. The small cell carcinoma of the prostate is the highly malignant variant of the endocrine cell type. Immunohistochemically, a multitude of proteohormones are demonstrable in endocrine tumor cells. The ectopic ACTH production with Cushing's syndrome is of particular clinical significance.

Small-cell carcinoma of prostate

Small-cell carcinoma of the prostate is rare, but lethal. We report on 2 cases and review another 6 cases reported in the English literature. Microscopically the tumor may be pure small-cell carcinoma like that seen in the lung or may have a mixed pattern of adenocarcinoma with small-cell carcinoma. This tumor most probably arises from the basal or reserve cells of the prostatic acini. The totipotential basal cells have dual capacity for differentiation into adenocarcinoma and small-cell carcinoma.

Small cell carcinoma of prostate associated with myasthenic (eaton-lambert) syndrome

A fifty-eight-year-old white man was diagnosed as having an adenocarcinoma of the prostate (grade III by the U. T. M. D. Anderson Hospital grading system). Five years after the initial diagnosis and three months after signs and symptoms of the myasthenic syndrome of Eaton-Lambert (MSEL), he was found to have a small cell carcinoma of the prostate. Histologic examination showed adenocarcinoma merging into a small cell carcinoma component of intermediate cell type. Immunostaining was positive for neuroendocrine markers—namely, neuron-specific enolase and serotonin-and was limited to the small cell carcinoma component. This is the first report of a patient with small cell carcinoma of the prostate presenting with MSEL. Our findings support prior observations of a strong propensity for small cell carcinoma to be associated with paraneoplastic syndromes, regardless of the initial location of the tumor.