The efficacy of early adjuvant radiation therapy for pT3N0 prostate cancer: a matched-pair analysis.

PURPOSE: This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group. METHODS AND MATERIALS: At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA (<10 ng/ml vs. >10 ng/ml), Gleason score (<7 vs. > or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml). RESULTS: After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone. CONCLUSIONS: These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.

Durable efficacy of early postoperative radiation therapy for high-risk pT3N0 prostate cancer: the importance of radiation dose.

OBJECTIVES: To determine the durable efficacy of early postoperative radiation therapy (RT) in patients with pT3N0 prostate cancer who were at an increased risk of biochemical failure. We also evaluated the long-term benefit derived from using higher RT doses. METHODS: Seventy-nine patients with pathologic Stage T3N0 prostate cancer and high-risk postoperative features underwent RT within 6 months after surgery. No patient received prior hormonal therapy. Fifty-nine patients had positive surgical margin, 29 had pathologic seminal vesicle invasion, and 27 had persistently elevated postoperative prostate-specific antigen (PSA) levels. Freedom from biochemical relapse (bNED) was defined as an undetectable (less than 0.2 ng/mL) PSA level. Median follow-up time was 39 months, and the median radiation dose was 64.8 Gy. All patients were followed for at least 2 years to be considered biochemically controlled. RESULTS: Patients receiving adjuvant RT for an undetectable pre-RT PSA level had a 3-year bNED rate of 90%, compared with 44% for those receiving salvage RT for a detectable level (P < 0.0001). In the group of adjuvant patients, RT doses more than 61.2 Gy resulted in a 3-year bNED rate of 90% compared with 64% for those receiving a lower dose (P=0.015). The salvage patients irradiated with a dose of 64.8 Gy or greater had a 3-year bNED rate of 52% compared with 18% for those irradiated with lower doses (P=0.048). Severe late RT-related complications were infrequent and did not correlate with dose. CONCLUSIONS: In patients with high-risk pT3N0 prostate cancer, an RT dose response may exist. Although some studies suggest limited durable efficacy for early postoperative RT, our data suggest that RT doses of 64.8 Gy or more appear superior to prevent future biochemical failures. A prospective randomized study evaluating a postoperative RT dose response is warranted.

Molecular pathological analysis of testicular diffuse large cell lymphomas.

The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyzed. These lymphomas occurred in men with a median age of 69 years (range, 37 to 87 years). Nine of the 14 patients with follow-up died of lymphoma (median survival, 12 months). All cases were diffuse large B-cell lymphomas that were positive for CD20 and commonly showed plasmacytoid differentiation (10 of 20 cases). Three cases were Burkitt's-like large cell lymphomas. Infiltration by lymphoma in the seminiferous tubules was seen in most cases. All lymphomas were negative for human herpesvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reaction (PCR), suggesting that these viruses are not involved in the pathogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cases. Nucleotide sequences of the V-D- and J segments of the immunoglobulin heavy chain gene (IgH) rearrangements obtained in 12 cases after PCR amplification were analyzed and compared with known germlines. The frequency of VH-family use in testicular DLBCL was similar to that reported for normal peripheral blood lymphocytes and follicular lymphomas. This contrasts with the previously published findings of preferential use of the VH3- or VH4-family by nodal DLBCL. Comparison with the published germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutation, as indicated by intraclonal variation in IgH sequence, was observed in all sequenced cases, suggesting direct antigen stimulation, which represents another difference between primary testicular and nodal DLBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respects. Their histological and molecular features show some similarities to those seen in marginal zone (MALT) lymphomas.

Effect of higher radiation dose on biochemical control after radical prostatectomy for PT3N0 prostate cancer.

PURPOSE: The appropriate radiation dose has not been determined for postoperative radiation therapy (RT) of prostate cancer. Postoperative PSA level is a useful marker of local residual disease, and may allow evaluation of RT dose-response after radical prostatectomy. METHODS AND MATERIALS: Between 1989 and 1996, 86 consecutive patients with pT3N0 prostate cancer who did not receive prior hormonal therapy or chemotherapy were irradiated postoperatively. All patients received 55.8 to 70.2 Gy (median = 64.8 Gy) to the prostatic/seminal vesicle bed. Patients were judged to be free of biochemical failure (bNED) if their PSA remained undetectable or decreased to undetectable level (< 0.2 ng/ml). The median follow-up time was 32 months from time of irradiation. RESULTS: Univariate and multivariate analyses of variables showed that the preRT PSA level was the most significant predictor of improved bNED survival (p < 0.001). Actuarial analyses of radiation dose grouped with preRT PSA levels found higher radiation dose to be significant (p < 0.05). For the 52 patients with an undetectable preRT PSA level, the 3-year bNED rate was 91% for patients irradiated to 61.5 Gy or more and 57% for those irradiated to lower doses (p = 0.01). For the 21 patients with preRT PSA level > 0.2 and < or = 2.0 ng/ml, the 3-year bNED rate was 79% for patients irradiated to 64.8 Gy or more and 33% for those irradiated to a lower dose (p = 0.02). No other preRT PSA interval or radiation dose level was associated with a dose-response function. CONCLUSION: In patients with pT3N0 prostate cancer after radical prostatectomy, a radiation dose-response function may be present and depends on the preRT PSA value. Patients with high postoperative PSA levels (> 2.0 ng/ml) may be less likely to benefit from higher doses of RT, and should be considered a group for which systemic therapy should be tested.

Pathologic seminal vesicle invasion after radical prostatectomy for patients with prostate carcinoma: effect of early adjuvant radiation therapy on biochemical control.

BACKGROUND: The authors evaluated the effect of postoperative radiation therapy on freedom from biochemical failure (bNED) in men with prostate carcinoma who had pathologic seminal vesicle invasion after radical prostatectomy and negative pelvic lymph node dissection (pT3cN0). METHODS: Between 1989 and 1995, 375 men underwent radical prostatectomy at Thomas Jefferson University Hospital. Fifty-three men (13%) had pT3cN0 prostate carcinoma and were the subject of this analysis. Men in whom prostate specific antigen (PSA) could not be detected were deemed free of biochemical failure. RESULTS: Of the 53 men with pT3cN0 prostate carcinoma, 18 had an elevated PSA immediately after surgery and received salvage radiation therapy (RT). The 3-year bNED rate for this group was only 38%. At 3 months, PSA could not be detected in the other 35 men. Fifteen of those 35 men underwent early adjuvant RT, and the other 20 were observed for biochemical failure. The 3-year bNED rate for the 15 patients treated with immediate adjuvant RT was 86%, compared with 48% for the 20 men who were observed (P = 0.01). CONCLUSIONS: These data suggest that early adjuvant RT for men with pT3cN0 prostate carcinoma and no detectable PSA postoperatively reduces the likelihood of future biochemical failure. Men with pT3cN0 prostate carcinoma and a persistently elevated postoperative PSA level are less likely to benefit from RT and should be considered for systemic therapy.

Color Doppler imaging in predicting the biologic behavior of prostate cancer: correlation with disease-free survival.

OBJECTIVES: We investigated the association of transrectal color Doppler imaging (CDI) signal detection in localized prostate cancer with biologic behavior as assessed by tumor Gleason grade, seminal vesicle invasion, capsular and margin status, and actuarial biochemical freedom from relapse. METHODS: From 1991 to 1996, transrectal ultrasound with CDI and biopsy was performed in 2718 men using a 7.0-MHz probe optimized to detect color-coded blood flow within the gland and along the capsular margin. Color flow was graded on a scale from 0 to 2+, with 0 and 1+ representing no detectable flow and normal flow, and 2+ indicating increased flow. Color flow maps were constructed in 47 men with clinically localized prostate cancer treated by radical prostatectomy (RP) and compared to their whole mount RP specimen step sections. RESULTS: Color flow detected within the index tumor was graded as 2+ in 22 of 47 patients and 0 or 1+ in the remaining 25. Tumors graded 2+ correlated with higher Gleason grade, higher incidence of seminal vesicle invasion, and higher relapse rate, with only 11 of 22 patients disease free based on undetectable prostate-specific antigen (PSA) levels. In contrast, 24 of 25 patients with tumors graded 0 or 1+ are free of biochemical relapse with a median follow-up of 30.9 months. Patients with increased flow were 10.2 times more likely to relapse even after correction for other prognostic variables. In addition, tumors with 2+ capsular flow correlated with a higher incidence of non-organ-confined disease. CONCLUSIONS: Color-coded Doppler flow within the tumor and overlying capsule appears to correlate with both tumor grade and stage, respectively. Detection and grading of color-coded flow within biopsy-proven cancers may identify patients with a high likelihood of biochemical relapse.

Cytologic features of pulmonary malakoplakia related to Rhodococcus equi in an immunocompromised host.

Cytologic features are described in bronchial brushings of a large cavitary lung mass from an immunosuppressed patient who had undergone liver transplantation. Scattered histiocytes with abundant eosinophilic, vacuolated cytoplasm were noted in a background of bronchial cells. Within approximately one fourth of the histiocytes, targetoid intracytoplasmic inclusions were present, consistent with Michaelis-Gutmann bodies. They were diffusely positive by histo-chemical staining with von Kossa, Gomori methenamine silver, and periodic acid-Schiff stains, and focally positive with Prussian blue stain. Cultures of the abscess yielded Rhodococcus equi. The characteristic microscopic features of pulmonary malakoplakia can be discerned in bronchial brushings, and should be sought, particularly in immunocompromised patients.

Leiomyosarcoma of the renal vein.

The preoperative diagnosis for primary leiomyosarcoma of the renal vein, an extremely rare tumor, is difficult. The tumor predominantly occurs in women and on the left side. Its natural history is toward distant metastases and a poor 5-year survival rate. Nephrectomy and en-bloc surgical resection remain the mainstay of therapy. We present three such cases and review the world literature.

Induction androgen deprivation plus prostatectomy for stage T3 disease: failure to achieve prostate-specific antigen-based freedom from disease status in a phase II trial.

OBJECTIVES: There is interest in treating prostate cancer with induction androgen deprivation prior to radical prostatectomy. Data on long-term prostate-specific antigen (PSA)-based survival analyses among patients treated with neoadjuvant hormonal therapy (NHT) and prostatectomy are limited. In 1991 we instituted a pilot study for T3 disease based on endorectal coil magnetic resonance imaging (eMRI), mandatory negative laparoscopic nodal dissection prior to hormonal manipulation, and prostatectomy followed by pathologic and PSA-based outcome determinations. METHODS: Of 26 patients, 21 had negative laparoscopic lymphadenectomy followed by 4 months of NHT (leuprolide +/- flutamide) prior to radical prostatectomy. eMRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3-month intervals. Prostatectomy specimens were evaluated by 3-mm whole-mount step sections. RESULTS: Prior to prostatectomy, biochemical response was documented in all patients and downsizing was observed by eMRI in 57%. Pathologic downstaging to a lower stage (T2c or lower) was achieved in 48%. However, the actuarial 3-year freedom from biochemical relapse rate was only 24%. CONCLUSIONS: Using laparoscopy to exclude node-positive patients and 4 months of NHT appears to result in pathologic and initial biochemical evidence of regression. These factors have not translated into improved freedom from biochemical relapse among patients with Stage T3 disease treated with NHT and prostatectomy. Recent data strongly suggest a beneficial effect in patients with clinical T2 disease treated with NHT and radical prostatectomy. The NGT and radical prostatectomy approach appeared to offer no clear advantage when compared with PSA-based benchmarks achieved with conformal irradiation or NHT followed by external beam treatment among patients with clinical T3 disease.

Metanephric adenoma: histology, immunophenotype, cytogenetics, ultrastructure.

Metanephric adenoma is a rare renal neoplasm that is histologically and clinically unique. We found this neoplasm in a 54-year-old woman. This large, well-circumscribed, solid, tan tumor showed histologic similarity to developing metanephric tubular epithelium. It is composed of uniformly small epithelial cells forming tubules. Immunohistochemical evaluation showed that the tumor cells express proximal tubule marker URO-2 and wt1 gene protein product, commonly expressed in Wilms' tumors. Ultrastructurally, the epithelial cells were characterized by the presence of cilia on the luminal side and were resting on an abundant basement membrane. Cytogenetic analysis showed normal female karyotype. The unique features of metanephric adenoma should be clinically and pathologically recognized because of its invariably benign course.

Prostate carcinoma: assessment of diagnostic criteria for capsular penetration on endorectal coil MR images.

PURPOSE: To assess the accuracy of using several criteria to evaluate endorectal coil magnetic resonance (MR) images for penetration of the prostatic capsule. MATERIALS AND METHODS: Thirty patients with prostate carcinoma underwent MR imaging and prostatectomy. Specified sites of potential capsular penetration on MR images were blindly evaluated by three readers for six diagnostic criteria. These evaluations were compared with pathologic findings of capsular penetration and were analyzed by means of receiver operating characteristic (ROC) analysis. RESULTS: The area under the ROC curve (Az) for the readers' overall impression of capsular penetration varied from .72 to .77. Highest mean Az's were for the criteria of capsular thickening (.74) and nodular extracapsular tumor (.72), although the latter finding had poor sensitivity (15%). Interobserver variation was low for all findings. CONCLUSION: Sensitivity and specificity were generally low for the diagnostic criteria. The usefulness of endorectal coil MR imaging in staging prostate cancer may be limited by the lack of diagnostic signs that uniformly identify extracapsular penetration.

Deoxyribonucleic acid flow cytometry of testicular Leydig cell tumors.

We analyzed by flow cytometry the deoxyribonucleic acid content of 13 paraffin embedded, formalin-fixed Leydig cell tumors of the testis. Of the tumors 10 were clinically benign (9 diploid and 1 aneuploid) and 3 were malignant (aneuploid). The benign aneuploid tumor showed moderate cellular atypia and a low mitotic count (less than 2 per 10 high power fields). Our study suggests that the majority of Leydig cell tumors are diploid and the less common malignant tumors are typically aneuploid, and that deoxyribonucleic acid flow cytometric findings can be useful as a prognostic indicator in these tumors.

Angiomyolipoma of the nasal cavity: case report and review of the literature.

An unusual localization of intranasal angiomyolipoma is described in an adult male patient with no signs of tuberous sclerosis. The lesion was composed of mature fat cells, vascular spaces with lack of elastic tissue, and presence of bundles of mature smooth muscle cells. Antibodies to intermediate filaments revealed presence of vimentin and absence of desmin in both smooth muscle bundles and in vessel walls. A review of the literature has shown that this is only the third reported case of the angiomyolipoma of the nasal cavity, and some important differences between this entity and renal angiomyolipoma are described.

Renal cell carcinoma in the presence of adult polycystic kidney disease.

A case of autosomal dominant polycystic kidney disease associated with widely metastatic renal cell carcinoma is reported. The patient had presented with pneumothorax, weight loss, leukocytosis, lytic bone lesions, and hypercalcemia. Despite intensive diagnostic search for a neoplasm, no firm evidence of malignancy was found. However, at the autopsy, widely metastatic, papillary renal cell carcinoma was found originating in the left kidney. Many metastases showed central necrosis mimicking small cysts.

Renal capsular hemangioma.

We present a rare example of hemangioma of the renal capsule. This benign mesenchymal tumor can present diagnostic difficulties, since it can radiographically and macroscopically simulate more common tumors of the kidney, including renal cell carcinoma. If the diagnosis is made or suspected preoperatively or during surgery a more conservative surgical approach should be considered.

Benign adrenocortical masses: diagnosis with chemical shift MR imaging.

Benign adrenocortical masses often contain lipid; metastases and pheochromocytomas do not. Standard and lipid-sensitive (chemical shift) magnetic resonance (MR) images of the adrenal glands in 31 patients with 45 adrenal masses were reviewed to determine if simple visual analysis of these images would increase diagnostic specificity. Lipid was considered present if signal intensity of the adrenal mass relative to other tissues decreased on chemical shift images relative to comparable standard images. Both myelolipomas and 26 of 27 benign cortical masses displayed a loss of signal intensity on at least one chemical shift image; all 12 metastases, the three hemorrhages, and a cyst did not. Opposed-phase images were slightly more sensitive than fat-suppressed images in depicting lipid within benign cortical masses. All masses had higher signal intensity than that of the liver on standard T2-weighted MR images. Chemical shift MR imaging can demonstrate lipid within benign adrenocortical masses and thus increase specificity, potentially obviating biopsy and aggressive follow-up.

Hoarseness; a unique clinical presentation for renal cell carcinoma.

The first reported case of an isolated metastasis to the larynx from a regionally localized renal cell carcinoma presenting clinically as hoarseness is discussed. Aggressive management and outcome are presented.

Heterotopic mucinous cystadenoma of the pancreas.

A 46-year-old female who had been experiencing severe diarrhea and marked weight loss underwent exploratory laparotomy because of a mass near the tail of the pancreas noted on CT scan. Pathologic examination revealed a mucinous cystadenoma of the pancreas occurring in heterotopic pancreatic tissue. This is the second reported case of mucinous cystadenoma occurring in heterotopic pancreatic tissue.

Malignant mesothelioma of the tunica vaginalis testis.

Malignant mesothelioma of the tunica vaginalis is an extremely rare tumor. Appropriate treatment consists of inquinal orchiectomy with close followup. Treatment of locally recurrent malignant mesothelioma of the tunica vaginalis has not been standardized. We recommend radical resection for the initial presentation of locally recurrent disease rather than saving surgical resection as salvage therapy after other treatment modalities have failed. We report case 37 of malignant mesothelioma of the tunica vaginalis and review the literature.

Cutaneous malakoplakia simulating relapsing malignant lymphoma.

This report describes the case of a 42-year-old man with malignant lymphoma, diffuse large non-cleaved cell type, who developed cutaneous malakoplakia in the left groin. The patient had widespread lymph node involvement, including a left inguinal mass which was clinically thought to represent recurrent lymphoma. The inguinal mass failed to regress after chemotherapy and irradiation, although lymphoma in other sites responded to chemotherapy. A skin biopsy of the area showed an ulcer and an abscess involving the dermis and subcutaneous tissue. Microscopically, a diffuse infiltrate of foamy histiocytes was seen with numerous intracellular and extracellular, round and laminated bodies. Some of these bodies had a "targetoid" appearance, stained strongly with von-Kossa's calcium stain and showed the typical appearance of Michaelis-Gutmann bodies by electron microscopy. Cultured monocytes from the peripheral blood of the patient showed ultrastructural features similar to their tissue counterparts, suggesting a systemic involvement of the monocyte macrophage lineage. This case represents an unusual presentation of malakoplakia of the skin associated with relapsing malignant lymphoma in a patient on immunosuppressive drugs.