Sarcomatoid renal tumors. Clinicopathologic correlation of three cases

The clinical, light and ultrastructural features of three renal neoplasms demonstrating a sarcomatous appearance on light microscopic examination are reported. At the time of radical nephrectomy, all three tumors displayed aggressive features with capsular invasion and either metastases or invasion of adjacent organs. Ultrastructural examination revealed epithelial features in a pure spindle cell tumor and in a malignant fibrous histiocytoma-like tumor (sarcomatoid renal carcinoma) and smooth muscle differentiation (leiomyosarcoma) in a lesion showing features of malignant fibrous histiocytoma. All three patients died from 1 to 9 months after nephrectomy. Renal tumors with a sarcomatous histologic appearance are aggressive neoplasms that cannot be classified accurately solely by employing light microscopic criteria.     

Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma.

BACKGROUND: Methylation of regulatory sequences near GSTP1, which encodes the pi class glutathione S-transferase, is the most common epigenetic alteration associated with prostate cancer. We determined whether the quantitation of GSTP1 methylation in histopathologically distinct prostate tissue samples could improve prostate cancer detection. METHODS: We used a fluorogenic real-time methylation-specific polymerase chain reaction (MSP) assay to analyze cytidine methylation in the GSTP1 promoter in prostate tissue samples from 69 patients with early-stage prostatic adenocarcinoma (28 of whom also had prostatic intraepithelial neoplasia lesions) and 31 patients with benign prostatic hyperplasia. The relative level of methylated GSTP1 DNA in each sample was determined as the ratio of MSP-amplified GSTP1 to MYOD1, a reference gene. We also performed a prospective, blinded investigation to quantitate GSTP1 promoter methylation in sextant prostate biopsy specimens from 21 additional patients with elevated serum prostate-specific antigen levels, 11 of whom had histologically identified adenocarcinoma and 10 of whom had no morphologic evidence of adenocarcinoma. All data were analyzed by using nonparametric two-sided statistical tests. RESULTS: The median ratios (and interquartile ranges) of MSP-amplified GSTP1 to MYOD1 in resected benign hyperplastic prostatic tissue, intraepithelial neoplasia, and adenocarcinoma were 0 (range, 0-0.1), 1.4 (range, 0- 45.9), and 250.8 (range, 53.5-697.5), respectively; all of these values were statistically significantly different (P< .001). The median ratios of MSP-amplified GSTP1 to MYOD1 in the prospectively collected sextant biopsy samples were 410.6 for the patients with adenocarcinoma and 0.0 for the patients with no evidence of adenocarcinoma (P< .001). CONCLUSION: Quantitation of GSTP1 methylation accurately discriminates between normal hyperplastic tissue and prostatic carcinoma in small samples of prostate tissue and may augment the standard pathologic/histologic assessment of the prostate.     

Small cell carcinoma of the prostate. Part I. A clinicopathologic study of 20 cases

Clinical information and histological slides of 20 cases of small cell carcinoma of the prostate seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston over a 23-year period were reviewed. Patient's ages ranged from 30 to 89 years (median, 67 years). In nine cases, pure adenocarcinoma of the prostate preceded recognition of the small cell component by 7 months to 8 years (median, 18 months); five of these were initially at Stage A. There was a small cell component at presentation in 11 cases (10, Stage D). Small cell carcinoma was merging with the adenocarcinoma in 11 cases and represented 30% to 90% of total tumor volume. Eleven of 20 patients died of their disease. Those presenting initially with a pure adenocarcinoma survived between 7 months and 9 years (median, 24 months). After the recognition of the small cell carcinoma component, regardless of a prior history of adenocarcinoma, death followed within 1.5 years (median, 5 months). This study suggests a biologic difference in behavior in prostatic carcinoma containing a small cell carcinoma component. The small cell component may manifest early or late in the disease.     

An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: implications for radioresistance

PURPOSE: To investigate the presence of hypoxia in human prostate carcinoma by using pimonidazole immunohistochemical labeling in radical prostatectomy specimens. METHODS AND MATERIALS: Forty-three patients (median age, 69 years; range, 49-83 years) with localized prostate adenocarcinoma received 0.5 gm/m2 i.v. pimonidazole 16-24 h before radical prostatectomy. Hypoxia was detected with a monoclonal antibody directed against pimonidazole and scored in formalin-fixed, paraffin-embedded sections. Median and maximal vessel counts were measured with CD34. RESULTS: Thirty-seven patients completed the study. Pimonidazole binding was present in prostate carcinomas in 34 of 37 patients (92%) and in benign prostatic hyperplasia in 35 of 37 patients (95%). A positive correlation of 3+ pimonidazole binding with Gleason score was demonstrated (Spearman's rank, p = 0.044). Vascularity scores did not correlate with hypoxic status or clinical prognostic parameters. CONCLUSION: Prostate carcinoma and benign prostatic hyperplasia have significant areas of hypoxia; greater hypoxia scores are seen with more aggressive prostate cancer. It is postulated that a hypoxic microenvironment within the prostate might be responsible for the promotion of secondary genetic alterations and angiogenic stimulation, leading to malignant progression, a more aggressive cell phenotype, and greater radioresistance. Modification of radiation regimens to specifically target hypoxia might improve local tumor control.     

Small cell carcinoma of the prostate. II. Immunohistochemical and electron microscopic studies of 18 cases

To evaluate the histogenesis of small cell carcinoma of the prostate, 18 cases of this tumor (9 pure small cell and 9 combined adeno- and small cell carcinoma) were studied using immunohistochemical methods. Seven of the small cell components also were assessed by electron microscopic examination. Using neuron-specific enolase (NSE), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA) on tissue sections, three distinctive immunostaining patterns of small cell carcinoma components were identified: staining positive for NSE and negative for PSA and PAP (10 cases), staining positive for PSA and PAP and negative for NSE (3 cases), and negative reaction for all three antigens (5 cases). Electron microscopic study demonstrated neurosecretory granules in two cases. Based on the immunostaining and electron microscopic findings, small cell carcinomas of the prostate appear to be a heterogeneous group of tumors. Some of them are neuroendocrine carcinomas whereas others are poorly differentiated adenocarcinomas or, possibly, reserve cell carcinomas. Differences in immunostaining patterns or presence and absence of adenocarcinoma component do not reflect any differences in the uniformly poor prognosis of small cell carcinomas, in which median survivals is 7.7 months. The authors believe that, because of such heterogeneity, small cell carcinomas of the prostate arise from multipotential prostatic epithelium and that an origin from specific neuroendocrine cells need not be implicated.     

Secondary colonic adenocarcinoma of the prostate histologically mimicking prostatic ductal adenocarcinoma

PURPOSE: To study the clinical presentation and pathological features of secondary colonic adenocarcinoma of the prostate. MATERIALS AND METHODS: Six cases of colonic adenocarcinoma extending into the prostate were retrieved from the surgical pathology and autopsy files of the period 1985-1999. Immunostaining for prostatic acid phosphatase (PAP), prostate specific antigen (PSA), cytokeratin 7 (CK7), cytokeratin 20 (CK20) and carcinoembryonic antigen (CEA) was carried out in all cases. Clinical charts were also reviewed. RESULTS: Secondary colonic carcinoma spread into the prostatic stroma and along the prostatic ducts. In all four surgical cases, patients with a known history of rectal carcinoma presented with symptoms of urinary obstruction after 12 to 36 months of being free of recurrent or metastatic disease. In three surgical cases the secondary carcinoma involved the prostatic urethra in a form mimicking endometrioid carcinoma, which led to an incorrect diagnosis of prostatic endometrioid carcinoma in one case. The tumor cells were immunoreactive to CK20 and CEA and not reactive to CK7, PAP and PSA. CONCLUSIONS: Colonic carcinoma involving the prostate may mimic prostatic duct carcinoma due to the ductal and urethral involvement. Using a panel of immunostaining and clinical history is helpful in the differential diagnosis.     

WISH-PC2: a unique xenograft model of human prostatic small cell carcinoma

Prostatic small cell carcinoma is an aggressive subtype of prostate cancer that usually appears as a progression of the original adenocarcinoma. We describe here the WISH-PC2, a novel neuroendocrine xenograft of small cell carcinoma of the prostate. This xenograft was established from a poorly differentiated prostate adenocarcinoma and is serially transplanted in immune-compromised mice where it grows within the prostate, liver, and bone, inducing osteolytic lesions with foci of osteoblastic activity. It secretes to the mouse Chromogranin A and expresses prostate plasma carcinoma tumor antigen-1, six-transmembrane epithelial antigen of the prostate, and members of the Erb-B receptor family. It does not express prostate-specific antigen, prostate stem cell antigen, prostate-specific membrane antigen, and androgen receptor, and it grows independently of androgen. Altogether, WISH-PC2 provides an unlimited source in which to study the involvement of neuroendocrine cells in the progression of prostatic adenocarcinoma and can serve as a novel model for the testing of new therapeutic strategies for prostatic small cell carcinoma.     

The induction of NB rat prostatic carcinomas

The NB rat prostate adenocarcinoma model is one in which microscopic carcinoma can be induced via the use of testosterone and estrogen silastic implants. There is an incidence of large, grossly-positive tumors; which approaches 10% to 15%. Seventy-three percent of the animals subjected to this induction method for periods of 9 to 18 months developed at least microscopic carcinoma. The earliest appearance microscopic foci of carcinoma was after three months of implantation, in which one of 30 animals so treated did show carcinoma. However, 88% of the animals treated for 18 months or longer showed microscopic carcinoma.     

Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia.

There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen for the expression of BMPs one to six in the prostatic tissue of patients with benign prostatic hyperplasia (BPH), non-metastatic prostatic adenocarcinoma and metastatic prostatic adenocarcinoma. BMPs were expressed in both benign and malignant prostate tissue and in the prostate tumour cell lines, PC3 and DU145. BMPs were also expressed in ocular melanoma tissue, a tissue which rarely metastasizes to bone. BMP-6 expression was detected in the prostate tissue of over 50% of patients with clinically defined metastatic prostate adenocarcinoma, but was not detected in non-metastatic or benign prostate samples or in ocular melanoma tissue. These findings suggest that the BMPs may play a role in the osteoinductive activity of prostate metastases and that the pattern of expression of BMPs may be important in the pathogenesis of osteoblastic metastases associated with prostate adenocarcinoma.     

Radiation-Induced Leiomyosarcoma of the Prostate after Brachytherapy for Prostatic Adenocarcinoma

Radiation therapy (RTx) has been employed as a curative therapy for prostatic adenocarcinoma. RTx-induced sarcomas (RISs) are rare, late adverse events, representing less than 0.2% of all irradiated patients. RISs are more aggressive tumors than prostatic adenocarcinomas. Herein, we present a case with RTx-induced prostatic leiomyosarcoma after permanent brachytherapy for prostatic adenocarcinoma. A 69-year-old male presented with dysuria and gross hematuria. Six years previously, he had been diagnosed with localized prostate cancer and was treated by permanent brachytherapy. Urethroscopy showed stenosis by a tumor at the prostate. Transurethral prostatectomy was performed for a diagnosis. Based on pathological findings, the diagnosis was leiomyosarcoma of the prostate. He was treated with three cycles of neoadjuvant chemotherapy (CTx) that consisted of doxorubicin and ifosfamide (AI), followed by a prostatocystectomy with intrapelvic lymphadenectomy. The tumor extended from the prostate and infiltrated the bladder wall and serosa with lymphatic and venous invasion. The surgical margin was negative, and no residual prostatic adenocarcinoma was observed. The proportion of necrotic tumor cells by neoadjuvant CTx was around 50%. Subsequently, adjuvant CTx was offered, but the patient chose a follow-up without CTx. Local recurrence and lung metastasis were detected by computed tomography 3 months after the surgery. He was treated again with AI. However, CTx was not effective and he died 6 months after the operation. In conclusion, an effective treatment strategy for prostatic sarcoma should be developed in the near future, although the clinical feature of prostatic sarcoma remains unclear due to its rare incidence.Key words: Radiation-induced sarcoma, Brachytherapy, Leiomyosarcoma, Prostatic sarcoma, p53     

Intraluminal crystalloids in prostatic adenocarcinoma. Immunohistochemical, electron microscopic, and x-ray microanalytic studies

Histochemical, immunohistochemical, electron microscopic, and x-ray microanalytic studies were performed on crystalloids within glandular lumina of adenocarcinomas of the prostate. In a review of light microscopic sections of 343 prostatic adenocarcinomas, unequivocal crystalloids were identified in 35 cases (10.2%). Immunohistochemical and ultrastructural studies revealed distinct differences between these crystalloids and the Bence Jones crystals of multiple myeloma: anti-kappa and anti-lamda immunostaining was negative, and the characteristic lattice-like architecture of Bence Jones crystals was not seen. Differences from corpora amylacea also were demonstrated. X-ray microanalysis did not elucidate the nature of the prostatic crystalloids, and their biochemical composition and mode of formation remain uncertain. Detection of the crystalloids in light microscopic sections nevertheless can aid in the diagnosis of prostatic adenocarcinoma, particularly when the tissue is distorted by crushing artifact, or if the tumor is so well-differentiated that it can be confused with atypical hyperplasia or inflammatory atypia. When intraluminal crystalloids are detected in prostatic glands that appear histologically benign or atypical, study of additional levels or a repeat biopsy should be undertaken.     

Continence after radical prostatectomy with bladder neck preservation.

PURPOSE: Bladder neck preservation during radical prostatectomy has been advocated for improving urinary continence. We evaluate bladder neck preservation looking at continence rates, surgical cancer control and bladder neck contracture. MATERIALS AND METHODS: A total of 40 patients underwent retropubic radical prostatectomy for clinically localized carcinoma of the prostate. The prostatic urethra was dissected in continuity with the bladder away from the lumen of the prostate, which allows for a true urethra-to-urethra anastomosis. RESULTS: Continence was noted immediately in 26 patients, within 2 weeks in 9 and within 6 weeks in 3. Only 2 patients required pads 3 months postoperatively. Microscopic positive surgical margins were noted in 2 of 40 patients. In 1 patient the urethral margins were not involved with carcinoma. In the other patient the urethra was not the sole positive margin and microscopic positive margins were noted elsewhere. Early results of cancer control were good. CONCLUSIONS: Early follow-up of this technique of radical retropubic prostatectomy suggest that preservation of the continence mechanism at the level of the bladder neck and prostatic urethra results in significantly improved postoperative urinary continence without adversely affecting cancer control.     

Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature

Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.     

Disseminated prostatic carcinoma simulating primary lung cancer. Indications for immunodiagnostic studies

Recognition of disseminated adenocarcinomas potentially responsive to current treatment programs is an important objective in the management of cancer patients. Metastatic adenocarcinoma of the prostate gland is a malignant entity which often can be palliated effectively by hormonally based therapeutic strategies. In cases of metastatic prostate cancer presenting with typical clinical features, the correct diagnosis can be readily achieved, but in patients with less obvious presentations the diagnosis of prostatic carcinoma may be overlooked. In the current report, a group of elderly men presenting with a clinical syndrome resembling either metastatic primary adenocarcinoma of the lung or primary adenocarcinoma of the lung coexisting with prostate cancer were found in fact to have metastatic prostatic carcinoma as their sole disease process. In each case, cytologic characterization of clinically involved tissue specimens by the prostate specific antigen and prostatic acid phosphatase immunohistochemical markers enabled clinical investigators to arrive at the correct diagnosis. Other clinical features, such as a positive bone scan and an enlarged prostate gland on physical exam and/or radiographic studies were noted to be present in these patients. All the patients in the current series responded to hormonal treatment regimens once the diagnosis of metastatic prostate cancer had been established. In elderly male patients presenting with what appears to be primary adenocarcinoma of the lung, the diagnosis of metastatic prostate cancer should be considered and when necessary evaluated by the use of appropriate clinical and immunohistochemical studies.     

Prostatic involvement in bladder cancer. Prostate mapping in 20 cystoprostatectomy specimens

Twenty prostate glands from patients with either high-grade papillary tumors (19 patients, 15 of whom also had peripheral carcinoma in situ) or multifocal carcinoma in situ (1 patient) of the bladder who underwent cystoprostatectomy were studied histologically by mapping. Prostatic duct involvement by urothelial carcinoma was noted in nine patients, two with extensive involvement and seven with focal involvement confined to periurethral ducts. Carcinoma in situ of the bladder was observed in each of the nine patients and intraepithelial permeation appeared to be the predominant manner of spread of cancer cells into the prostate. The prostatic involvement was clinically silent and it may be a potential source of failure of conservative modalities of treatment of high-grade bladder cancer. A routine diagnostic transurethral prostatic biopsy may be recommended in the workup of patients with carcinoma in situ and high-grade carcinomas of the bladder. An incidental observation was the presence of 14 occult prostatic adenocarcinomas.     

An unusual variant of prostatic adenocarcinoma with metastasis to testis.A case report

Ductal adenocarcinoma of the prostate is considered to be a rare variant of prostatic adenocarcinoma when compared to the more common acinar adenocarcinoma. We report here a case of ductal adenocarcinoma of the prostate in a 68-year old man who presented with complaints of abdominal pain, retention of urine and hematuria of one month duration. Clinical examination showed prostatomegaly. The serum Prostate Specific Antigen (PSA) value was raised to 79ng/mL. Histopathological and immunohistochemical evaluation of resected specimen of prostate revealed ductal adenocarcinoma of the prostate. The patient was lost to follow up and presented four years after the initial diagnosis with metastasis to the bone and testis. Though prostatic cancers have the ability for wide spread dissemination, metastasis to testis is rare. Immunohistochemical staining with PSA and Prostatic Acid Phosphatase (PAP) can help in establishing prostatic nature of the neoplasm. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors. Keywords: Prostate, ductal adenocarcinoma, metastasis, testis.     

Endometrioid adenocarcinoma of the prostate: A clinicopathologic and immunohistochemical study

On retrospective review of the tumor registry files between 1979 and 1992 at the North Iowa Medical Center, six cases of endometrioid adenocarcinoma of the prostate were identified among 1582 cases of prostatic carcinoma. Along with long-term clinicopathologic follow-up, immunohistochemical studies of the prostatic tumor tissues were performed. All six cases of endometrioid carcinoma, together with control cases of benign prostatic hypertrophy (BPH) and ordinary adenocarcinoma of the prostate had unequivocal diffuse positive staining for PSA and similar reactivity to ER-D5 and PS2. Thus, endometrioid carcinoma is most likely derived from the prostate or prostatic urethral duct rather than the utricle. However, due to its unusual initial clinical manifestations, biological behavior, and distinctive histomorphology, the term “endometrioid adenocarcinoma of the prostate” is worth preserving. © Wiley-Liss, Inc.     

A case of small cell carcinoma of the prostate

A case of a small cell carcinoma of the prostate that occurred in a 68-year-old man is reported. Needle biopsy of the prostate showed an adenocarcinoma. A second biopsy revealed both an adenocarcinoma and a small cell carcinoma. A subsequent third biopsy revealed only a small cell carcinoma, and the patient died of respiratory failure 26 months after the initial presentation. An autopsy revealed the tumor that had replaced the prostate extended into the bladder and rectum. Widespread metastatic foci, showing a histologic pattern of solely a small cell carcinoma, were present in various organs. The adenocarcinoma component was seen restricted to the prostatic region. Immunoperoxidase staining for prostate-specific antigen, prostate-specific acid phosphatase, gamma-seminoprotein, and leu-7 showed positivity only in the adenocarcinoma, whereas neuron-specific enolase was positive only in the small cell carcinoma.