Successful treatment of pure endodermal sinus tumors in adult men.

Seven adult men with pure endodermal sinus tumors (EST) were treated with cyclical combination chemotherapy Cytoxan (cyclophosphamide; Bristol-Myers Company, Evansville, IL), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin/vinblastine and bleomycin (CISCAII/VBIV) and surgery at the University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1978 through 1985. Six tumors were of extragonadal origin (four anterior mediastinum, one pelvic, one prostate), and one was of gonadal origin with retroperitoneal metastasis. All patients presented with advanced local disease and a relative absence of distant metastasis. Alpha-fetoprotein (AFP) levels were elevated in six patients (median, 4,400 ng/mL; range, 2,580 to 31,200 ng/mL). Six patients achieved a complete remission (CR): one with chemotherapy alone, one with initial surgery followed by chemotherapy, and four with chemotherapy followed by consolidative surgery. The remaining patient died of progressive disease. Of the six patients who achieved a CR, five are alive with no evidence of disease (+17, +23, +34, +43, +59 months); one patient developed recurrent disease at 6 months after completion of therapy and is currently undergoing salvage chemotherapy. Of the four patients who underwent postchemotherapy surgery, three were operated on for a marker-negative stable mass; in these patients, no viable tumor was found at pathologic review. The remaining patient underwent surgery for a stable mass with a persistent elevation in AFP levels. He was found to have 95% necrosis with 5% viable tumor and remains disease free without further therapy. The observed changes in AFP levels correlated with regression and progression of tumor; a normal AFP was consistent with a CR, and elevation was consistent with residual tumor. These seven patients demonstrate that when adult men with EST are treated aggressively with combination chemotherapy and surgery, high cure rates can be achieved.

A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors.

To evaluate the relative efficacy of cisplatin, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (CISCA) versus methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC), a prospective randomized trial was performed in patients with advanced metastatic urothelial tumors. Patients were stratified by histologic disease type and degree of tumor dissemination. Equal distribution of the clinical characteristics was achieved. One hundred ten patients with metastatic disease of the urinary tract (86 bladder, 16 renal pelvis, seven ureter, one prostatic urethra) met eligibility criteria and were enrolled on study. These represented 82% of the total patients seen during the study period in the Section of Genitourinary Oncology who met the eligibility criteria. The combined complete and partial response rate was significantly higher for patients treated with MVAC than for those treated with CISCA (65% v 46%; P less than .05). The survival duration of MVAC-treated patients was significantly longer than that of CISCA-treated patients (mean, 62.6 weeks; median, 48.3; range, 5.0+ to 162.3+ v mean, 40.4 weeks; median, 36.1; range, 7+ to 147.1+). We conclude that MVAC chemotherapy is superior to CISCA chemotherapy, achieving a higher response rate and a longer survival for equivalent patients with metastatic urothelial tumors.

Primary chemotherapy for clinical stage II nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients.

Fifty patients with clinical stage II nonseminomatous germ cell tumor of the testis (NSGCTT) were treated with primary chemotherapy followed by a retroperitoneal lymph node dissection (RPLND) in selected patients. The study population included 34 patients with retroperitoneal masses and elevated levels of serum biomarkers (alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [BHCG] ), five with needle aspiration biopsy-proven retroperitoneal metastases but normal levels of biomarkers, and 11 in whom there were rising levels of serum biomarkers but no radiographic evidence of retroperitoneal metastases. Forty-eight patients (96%) achieved a complete response (CR), with a mean disease-free survival of 132 weeks (range, 55 to 273 weeks). Two patients developed recurrent disease. One died and one achieved a second CR with further therapy (48 + weeks). Postchemotherapy RPLND was required in 11 patients (22%). Patients with embryonal carcinoma had a lower frequency of RPLND (8%) than patients with teratomatous elements in their primary tumor [36%, P = .014]. To reduce the frequency of double therapy (surgery +/- chemotherapy), we propose individualized therapy. Patients presenting with clinical stage II embryonal carcinoma of the testis should receive primary chemotherapy. Patients with clinical stage II NSGCTT and teratomatous elements in their primary tumor continue to require an RPLND. Those patients with intermediate volume disease (greater than 2 cm less than or equal to 5 cm in maximum diameter) may be treated with an RPLND only. Patients with higher volume teratomatous elements (greater than 5 cm less than or equal to 10 cm in maximum diameter) are likely to require the combination of chemotherapy and surgery.

The prognostic importance of Gleason grade in prostatic adenocarcinoma: a long-term follow-up study of 648 patients treated with radiation therapy.

PURPOSE: It is common practice to histologically grade adenocarcinoma of the prostate using the Gleason system. Whereas the prognostic utility of this grading is well known, few studies have comprehensively evaluated it for patients undergoing definitive radiation therapy and generally accepted guidelines as to which Gleason grades should be "lumped" have not been established. This study reports the results of univariate and multivariate evaluation of the prognostic significance of Gleason grade in 648 patients followed for a median of 6.5 years after radiation therapy for T1 to T4, N0, or NX, MO prostate cancer. METHODS AND MATERIALS: The correlation between Gleason grade and local recurrence, metastatic relapse, any disease relapse, and patient survival was evaluated using univariate and multivariate methods. Analysis was also stratified according to whether the grading was assigned on a needle biopsy or on a transurethral resection specimen. RESULTS: The large number of Gleason grades required grouping of grades for meaningful analysis and we found that a four-tier system (grades 2 and 3, 155 patients; grades 4-6, 290 patients; grade 7, 92 patients; and grades 8-10, 111 patients) correlated best with outcome. In univariate analysis, this four-tier grouping correlated significantly with local recurrence, distant metastases, any relapse, and survival. The incidences of distant metastasis at 10 years were: grades 2 and 3, 13%; grades 4-6, 34%; grade 7, 52%; and, grades 8-10, 63%. The survival rates at 10 years were: grades 2 and 3, 64%; grades 4-6, 60%; grade 7, 46%; and grades 8-10, 24%. In multivariate analysis, Gleason grade was the single most important determinant of outcome for each endpoint. These results applied equally to needle biopsy and transurethral resection specimens. CONCLUSION: Tumor grade is the single most significant determinant of outcome following radiotherapy for clinically localized prostate cancer. The Gleason system is a valid method for grading tumors to be irradiated. A four-tier grouping into grades 2 and 3, grades 4-6, grade 7, and grades 8-10 appears to be adequate and simple.

Fifteen year radiotherapy experience with chondrosarcoma of bone.

A retrospective analysis of 20 patients with chondrosarcoma of bone treated for cure between 1961 and 1976 using supervoltage radiotherapy and/or neutrons is presented. Radiotherapy was used alone or in combination with other modalities. The 20 patients were divided into four groups: 1) 11 patients who received radiotherapy alone, 2) three patients who received postoperative radiotherapy following less than radical local excision, 3) three patients who received radiotherapy with chemotherapy but without surgery, and 4) three patients who received radiotherapy for tumor recurrent after surgery. Typical tumor doses ranged from 4000 to 7000 rad at 1000 rad/week using parallel-opposed fields. Failure of radiotherapy was indicated by progression of symptoms and increasing tumor size. At 53 months, the average follow-up, the survival rate is 65% (13/20), including one patient with distant metastases, and two patients who developed local recurrent disease after radiotherapy and were surgically salvaged. Seven patients died with uncontrolled local disease; six of them also had distant metastases. Five patients developed severe complications. All four patients treated with a combination of neutron and photon beam alone show no evidence of local failure, compared with only one of the seven patients treated with conventional radiotherapy alone.

Muscularis mucosa of urinary bladder. Importance for staging and treatment.

We report the results of a histologic evaluation of muscle (muscularis mucosa) in the lamina propria of the urinary bladder performed on 100 consecutive cystectomy specimens. Muscle fibers were found in the lamina propria lying parallel to the mucosa and forming a distinct muscularis mucosa in three cases; they were interrupted or discontinuous in 20 cases, and dispersed or scattered, forming thin bundles, in 71 cases. In six cases, there were no muscle fibers in the lamina propria. In addition, we noticed that the lamina propria contains large vessels that run along the length of the lamina propria in a continuous or interrupted fashion. When muscle fibers are present, they are associated with these vessels. Since prognosis and management of muscle invasive carcinomas (stage B) is different from that of lamina propria-invasive tumors (stage A), pathologists and urologists should be aware of the presence of a muscularis mucosa in the urinary bladder.

Metastatic prostatic carcinoma presenting as an oncocytic tumor.

We discuss a 63-year-old man who presented with a metastatic tumor in an inguinal lymph node. By light microscopy, the tumor cells were characterized by a finely granular eosinophilic cytoplasm. A diagnosis of metastatic oncocytic carcinoma was made based on the results of an ultrastructural examination, which showed the cytoplasm of the tumor cells to be filled with mitochondria. Results of immunocytochemical studies showed positive reactivity for prostatic acid phosphatase and prostate-specific antigen. A transurethral resection of the prostate showed an oncocytic adenocarcinoma of the prostate, apparently the first of its kind, which was demonstrated to be the site of origin of the inguinal lymph node metastasis.

Fibrous dysplasia and cemento-ossifying fibroma. A histologic spectrum.

Fibrous dysplasia (FD) and cemento-ossifying fibroma (COF) are benign fibro-osseous lesions that are generally considered to be separate entities, distinguished by histologic and radiographic features. In our experience, some lesions lack the classic clinical, radiographic, or pathologic features of FD or COF and rather have overlapping features of both entities. Consequently, these cases are frequently diagnosed nonspecifically as fibro-osseous lesions. We examined 56 gnathic and extragnathic fibro-osseous lesions of bone morphologically, clinically, and radiographically to determine whether they can be reliably distinguished and whether their distinction has any clinical or prognostic significance. The lesions exhibited a broad morphologic spectrum of patterns ranging from pure FD (24 cases) to pure COF (10 cases). Twenty-two lesions contained a mixture of both patterns; 11 lesions with a predominant FD pattern contained calcified spherules histologically indistinguishable from those characteristically seen in COF. The remaining 11 lesions contained areas of typical FD adjacent to areas of COF. The lesions examined also demonstrated considerable radiographic overlap, and FD could not be reliably distinguished from COF. The recurrence rate was low for all lesions regardless of the histologic pattern. Because of histologic and radiographic overlap and similar low recurrence rate of FD and COF, we consider them to be related lesions, and COF is probably an opposing end of a morphologic spectrum of FD.

Lesions described as nodular mesothelial hyperplasia are primarily composed of histiocytes.

It is known that, on occasion, histiocytic proliferations can be confused with reactive mesothelial cell hyperplasia or with a malignant process. We report four cases of histiocytic proliferation, two occurring in the pleura in a 23-year-old woman and a 78-year-old woman, respectively, one in a hernial sac of a 2-year-old boy, and one in the lamina propria of the bladder of a 74-year-old man with a noninvasive papillary transitional cell carcinoma. The morphologic features of the pleural lesion of the 23-year-old woman and of the hernial sac lesion of the 2-year-old boy, as well as the bladder lesion, were similar to those reported in cases of the so-called nodular mesothelial hyperplasia. The pleural lesion in the 78-year-old woman consisted of a proliferation of cells with a signet ring-like morphology that was originally interpreted as either an unusual form of mesothelial hyperplasia or a metastatic signet ring cell adenocarcinoma. Because of mitotic activity and some cellular atypia in the bladder lesion, the possibility of invasive transitional cell carcinoma into the lamina propria was considered before immunohistochemical studies were performed. Staining for keratin showed only a few positive cells in the hernial sac and pleural lesions, whereas most cells reacted for the histiocytic marker CD68. Immunohistochemical studies on the bladder lesion also demonstrated strong staining for CD68, but no reactivity for keratin was observed. Based on these results, it is concluded that all of the lesions are primarily reactive histiocytic proliferations and because they may occur in other locations aside from the serosal membranes, the designation "nodular histiocytic hyperplasia" appears to be more appropriate than that of nodular mesothelial hyperplasia. It is important that the reactive nature of these lesions be recognized because on occasion they may present high mitotic activity or may show signet ring-like morphology and thus they can be confused with a malignancy.

Signet-ring-cell carcinoma of the prostate. Electron-microscopic and immunohistochemical studies of eight cases.

Primary signet-ring-cell carcinoma of the prostate is extremely rare. We report eight patients with prostatic adenocarcinomas containing significant numbers of signet-ring cells, one of whom presented initially with supraclavicular lymph node metastasis. Patient ages ranged from 50 to 80 years (mean, 67.5). None of the patients had received any form of therapy before biopsy or surgery. All patients presented with advanced disease (five with stage C and three with stage D). All tumors were poorly differentiated adenocarcinomas, M.D. Anderson Hospital system grade IV, Gleason's combined score of 9 or 10. The signet-ring cells were negative for neutral and acid mucins but immunoreactive for prostatic-specific antigen and prostatic acid phosphatase. Ultrastructurally, the signet-ring-cell appearance resulted either from the presence of intracytoplasmic lumina or from vacuoles. Signet-ring cells were also present at the metastatic sites. We conclude that (a) signet-ring-cell carcinoma of the prostate is a variant of poorly differentiated adenocarcinoma of the prostate; and (b) when a metastatic signet-ring-cell carcinoma with negative intracytoplasmic mucin is identified, a prostatic origin should be considered, and prostatic-specific antigen and prostatic acid phosphatase immunostaining should be performed.

Seminal vesicle involvement by in situ and invasive transitional cell carcinoma of the bladder.

We report six cases of seminal vesicle involvement by transitional cell carcinoma of the bladder among 187 consecutive cystoprostatectomy specimens. Two of these six cases showed mucosal spread without stromal invasion (type A); the remaining four cases presented a direct extension (type B) from muscle-invasive carcinomas of the bladder. Type A involvement of the seminal vesicle was associated with a long history of superficial bladder cancer with similar mucosal spread to the prostatic ducts, acini, and ejaculatory ducts. One type A case showed extensive pagetoid spread of transitional cell carcinoma to the urethral meatus and collecting ducts of the kidney. Because the clinical significance of mucosal spread or direct invasion of seminal vesicles is not clear, pathologists and urologists need to be aware of these phenomena. More cases should be analyzed to determine further clinicopathologic implications.

Heterologous elements in the dedifferentiated component of dedifferentiated liposarcoma.

Five cases of dedifferentiated liposarcoma in which heterologous elements were present in the dedifferentiated component are presented. Two patients, men 54 and 66 years of age, had retroperitoneal atypical lipomatous tumors (well-differentiated liposarcomas) that recurred (after 2.5 and 12 years, respectively) as dedifferentiated liposarcomas with rhabdomyosarcomatous elements in the dedifferentiated components. The third patient, a 63-year-old woman, had a retroperitoneal dedifferentiated liposarcoma whose dedifferentiated component demonstrated focal osteoid formation. The fourth patient, a 36-year-old woman, had two seemingly separate retroperitoneal masses, one composed of atypical lipomatous tumor with foci of smooth muscle and the other of leiomyosarcoma; despite the apparent separation, it was thought more logical to consider this a dedifferentiated liposarcoma with leiomyosarcoma as the dedifferentiated component than two unrelated neoplasms. The fifth patient, a 45-year-old man, had a mediastinal dedifferentiated liposarcoma with angiosarcomatous areas in the dedifferentiated component. The relatively short follow-up thus far available on these cases has not demonstrated tumor behavior significantly different from that of dedifferentiated liposarcoma as a whole.

DNA ploidy in testicular germ cell neoplasms. Histogenetic and clinical implications.

Flow cytometry was used to determine the DNA ploidy pattern of 148 testicular germ cell neoplasms (seminomas and nonseminomas in pure and mixed histologic phenotypes) and in situ carcinoma (CIS) adjacent to these tumors. The great majority (96.0%) manifested aneuploid DNA contents with minimal intratumoral heterogeneity (2.5%). The mean DNA indices (DI) of CIS (1.7 +/- 0.18), pure seminoma (1.82 +/- 0.55), and the seminoma component of mixed germ cell neoplasms (1.76 +/- 0.13) were statistically similar. The mean DI of nonseminomas pure (1.46 +/- 0.29) or as a component of mixed tumors (1.43 +/- 0.32) was significantly lower (p greater than 0.001) than those of CIS and seminomas. Our data suggest that the similarity between the DNA indices of CIS and seminomas provide evidence that both lesions constitute a temporal evolutionary step in the progression of germ cell tumors and that nonseminomas may subsequently arise from either CIS or seminoma by further loss of chromosomal DNA. These characteristic findings support the nonstochastic theory for germ cell evolution and progression and may be useful in the clinicopathologic evaluation of testicular masses.

Clear cell cribriform hyperplasia of prostate. Report of 10 cases.

We report 10 patients with clear cell cribriform hyperplasia of the prostate. Their ages ranged from 62 to 87 years, with a mean of 72 years. The clinical diagnosis in all patients was benign nodular hyperplasia; all the patients are alive and have shown no evidence of recurrent disease. Follow-ups ranged from 1 month to 7 years (median: 12.5 months; mean: 24.6 months). Pathologically, this lesion has a cribriform arrangement of clear cells with a complex papillary growth simulating the cribriform pattern of prostatic carcinoma. In fact, in five of the 10 cases, the referring diagnosis was either carcinoma or possible carcinoma. Cytologically, however, there is no nuclear atypia, mitosis, or prominent nucleoli, and typically there is a double epithelial cell layer at the periphery of the involved acini. In summary, clear cell cribriform hyperplasia is a benign hyperplastic process with a complex papillary-cribriform structure and should not be confused with prostatic carcinoma. The key feature for the diagnosis is the preservation of nodular configuration with a bland cytology and double cell layer lining the involved acini.

The prostatic capsule: does it exist? Its importance in the staging and treatment of prostatic carcinoma.

Pathologic evaluation of tumor extent in a radical prostatectomy specimen for prostatic adenocarcinoma is extremely important in staging and planning further therapy. We studied whole-organ sections of 50 prostate glands, obtained at either radical prostatectomy for adenocarcinoma or cystoprostatectomy for bladder cancer, to evaluate the so-called capsule of the prostate, the prostatic apex, and the surgical margins. The outer surface of the prostatic portion of the specimen was totally inked with different colors for the anterior, posterior, left, and right areas. Cross sections were processed for histologic examination, and the apex (distal 1.5 cm) was amputated and radially sectioned (like a cervical cone). We found that the "capsule" is made up of a band of concentrically placed fibromuscular tissue that is an inseparable component of the prostatic stroma. The outer surface of this tissue gives rise to a few bundles of fibromuscular stroma that penetrate and disappear into the periprostatic connective tissue stroma. The apex is sparse in glandular elements, particularly in the anterior portion, and the outer fibromuscular layer is no longer present. Thus we conclude that the prostate does not have a true capsule, but only an outer fibromuscular band.

Adenomatous hyperplasia of the rete testis. A clinicopathologic study of nine cases.

Adenomatous hyperplasia of the rete testis is an uncommon lesion that has recently been described. Nine cases of adenomatous hyperplasia were identified in two institutions from 1980 to 1989. At diagnosis the nine patients ranged in age from 30 to 74 years (mean, 59 years; median, 66 years). Three patients presented with a grossly identifiable solid or cystic testicular hilar mass. In six cases adenomatous hyperplasia was an incidental microscopic finding--five from orchiectomy specimens and one from an autopsy specimen. Microscopically, the hyperplasia consisted of a tubulopapillary epithelial proliferation of rete testis. The lining cells were cuboidal to low columnar and lacked nuclear pleomorphism or mitotic figures. The involvement of the rete testis was predominantly diffuse. In seven cases the seminiferous tubules showed atrophic changes. Ultrastructural and immunohistochemical (keratin, epithelial-membrane antigen: positive; vimentin, muscle-specific actin, desmin, and S-100: negative) studies done on one case showed similar features to those of nonhyperplastic rete testis epithelium. No patient with adenomatous hyperplasia showed local recurrence or metastasis. Possible pathogeneses include hormonal imbalance or stimulatory influence that remains as yet unidentified.

Distinguishing Cowper's glands from neoplastic and pseudoneoplastic lesions of prostate: immunohistochemical and ultrastructural studies.

Mucin-producing Cowper's glands, which are situated in the urogenital diaphragm, can be sampled inadvertently by transurethral resection of the prostate and rarely by needle biopsy. Because they are small, closely packed glandular units, Cowper's glands can be misinterpreted as prostatic adenocarcinoma. A panel of immunoperoxidase and mucin stains performed on 10 Cowper's glands showed negative immunoreactivity for prostatic-specific antigen, prostatic alkaline phosphatase, S-100 protein, and carcinoembryonic antigen. Acini in nine of the 10 Cowper's glands were negative for high-molecular-weight cytokeratin K-903 (34beta E12). One case showed faint focal staining of cells around the periphery of acinar units. Smooth muscle actin consistently stained the periphery of acini in all cases. Ultrastructural examination of one Cowper's gland showed the presence of myoepithelial cells at the periphery of the acini. Contrary to previous reports, the acini were lined by a prominent secretory cell layer underlain by an attenuated myoepithelial cell layer. A negative stain for K-903. without additional immunohistochemical study on Cowper's glands taken during transurethral resection or needle biopsy, may substantiate an erroneous diagnosis of prostatic adenocarcinoma. This potential misdiagnosis of carcinoma can be averted if samples stain positive for mucin and smooth muscle actin and negative for prostate-specific antigen and prostatic alkaline phosphatase.

Histologic variations in the epididymis: findings in 167 orchiectomy specimens.

Nonpathologic morphologic variations in the epididymal histology in 167 orchiectomy specimens were analyzed to assess and document the nature, frequency, and possible relation to patient age and underlying testicular pathology. Variations in histology included intranuclear eosinophilic inclusions, lipofuscin pigment, cribriform hyperplasia, Paneth cell-like metaplasia, and nuclear atypia. Intranuclear eosinophilic inclusions were observed in 72.5% of patients, and they appeared to occur at an older age than cribriform hyperplasia and Paneth cell-like metaplasia. Lipofuscin pigment was found in 32.9% of patients; this change was observed predominantly in ductuli efferentes and was more commonly associated with obstructive changes. Cribriform hyperplasia was seen in 41.9% of patients, and it occurred in 1 normal testis and in 33 testes with diverse pathologic alterations. Paneth cell-like metaplasia characterized by bright eosinophilic intracytoplasmic hyaline-like granules and globules, was present in 8.3% of patients and was accompanied by changes of obstruction in almost all instances. The globules were strongly periodic acid-Schiff positive, both before and after diastase digestion, and were negative for chromogranin A, KP-1, and MAC387 immunostains. Nuclear atypia, similar to that seen in seminal vesicles, was focally present in 13.8% of patients and tended to occur at an older age. The authors conclude that variations in epididymal morphology are fairly common and, therefore, surgical pathologists should be aware of these changes. Although exuberant in some patients, in no cases did these variations cause serious diagnostic problems.

Micropapillary variant of transitional cell carcinoma of the urinary bladder. Histologic pattern resembling ovarian papillary serous carcinoma.

Eighteen cases of transitional cell carcinoma (TCC) of the urinary bladder containing a micropapillary component (MPC) (> 90%, three cases; 50-90%, nine cases; < 50%, six cases) are presented. The patients' mean age was 66.6 years (range, 47-81 years) with a male predominance (male-to-female ratio of 5:1). The MPC was part of the surface noninvasive TCC in 16 cases and part of the invasive portion of the TCC in all 18 cases. Eight patients had metastases, each with a predominant (> or = 50%) MPC in the metastases; local recurrence was documented in one case, and the tumor was locally invasive into pelvic structures in three cases. Histologically, the surface MPC comprised slender, delicate filiform processes or small papillary clusters of tumor cells, whereas the deep MPC was composed of infiltrating tight clusters of micropapillary aggregates that were often present within lacunae. Vascular-lymphatic invasion was consistently present in the micropapillary areas. The cytologic features of the MPC were those of grade 3 TCC. A concurrent TCC in situ was identified in 10 cases, noninvasive papillary TCC component in all cases, and glandular differentiation of the invasive TCC in five cases. The initial stage at presentation was usually high stage: one patient with stage A, nine with stage B, six with stage C, and two with stage D. Follow-up data (mean, 44.8 months; range, 6-96 months) indicated that four patients were alive with disease, seven patients were dead of disease, and there was no evidence of disease in seven patients. In five cases, DNA ploidy analyzed by static image analysis showed nondiploid indices within the micropapillary TCC component, and in three cases the DNA index of the MPC (noninvasive, invasive, or at metastatic site) exceeded the DNA index of the noninvasive papillary TCC. In conclusion, the presence of a MPC in TCC is associated with high-grade and high-stage TCC with a tendency to vascular invasion. Our data suggest that a surface MPC in bladder biopsy specimens is a poor prognostic histologic feature and, if the biopsy does not contain muscularis propria, deeper biopsies should be recommended to determine the presence of muscle invasion.

Paneth cell-like change of the prostate gland. A histological, immunohistochemical, and electron microscopic study.

Paneth cell-like change (PCLC) of the prostatic glandular epithelium was focally observed in one case of normal glandular epithelium, two cases of glandular and stromal hyperplasia, one case of prostatic intraepithelial neoplasia, and four cases of prostatic adenocarcinoma. The distinctive cells were characterized by bright, eosinophilic cytoplasmic granules on routine hematoxylin and eosin-stained material. The cytoplasmic granules in the benign prostatic epithelium were periodate-Schiff's procedure (PAS)-positive and diastase resistant and immunohistochemically negative for lysozyme, neuron-specific enolase, chromogranin, and serotonin. The eosinophilic granules in the prostatic intraepithelial neoplasia and adenocarcinoma cases were immunohistochemically positive for chromogranin, serotonin, and neuron-specific enolase, and negative for lysozyme. By electron microscopy the eosinophilic granules represented exocrine-like or lysosomal-like vesicles in the benign epithelium and neuro-endocrine granules in the malignant epithelium. The lesion represents a prostatic epithelial PCLC rather than a Paneth cell metaplasia. PCLC is the common histological manifestation of two different phenomena: (a) a PAS-positive and diastase-resistant eosinophilic cytoplasmic granular change in benign prostatic epithelium, and (b) endocrine differentiation with neuroendocrine granules in dysplastic and malignant prostatic epithelia. The importance of recognizing PCLC lies in its differentiation from other possible prostatic cytoplasmic inclusions.