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Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor.To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell).Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases.All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin.In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 protein accumulation (P = .0477). Prolonged chemotherapy, however, was associated with little or no change in survival among patients whose tumor expressed those markers. The present study adds support to the hypothesis linking c-erbB-2 and p53 expression to drug resistance.

The presence of estrogen receptors (ER) in human prostatic tissue is a longstanding, controversial issue. In a few experimental animal models androgen deprivation was shown to be associated with a spontaneous increased ER expression in prostatic tissue. We intended to study whether these observations also apply to human prostatic tissue.Estrogen receptor expression by stromal and glandular cells was studied by immunohistochemistry in prostatectomy specimens of 21 patient with prostate cancer, treated for 3 months with a luteinizing hormone-releasing hormone (LHRH) agonist and flutamide. In addition 2 patients treated with estrogens were also examined. For comparison, ER expression was also studied in a series of 18 prostatectomy specimens of untreated patients.The specimens of patients treated with androgen blockade showed atrophic changes of the gland as well as basal cell hyperplasia, features characteristic for this therapy. Although stromal cells of prostatectomy specimens from untreated patients were largely ER negative, those of patients exposed to androgen ablation therapy or estrogen therapy had an intense nuclear ER expression in a great number of stromal cells around prostatic glands. Sporadic epithelial cells lining the glands displayed some nuclear ER expression. Prostatic glands from treated patients with basal cell hyperplasia lacked ER expression. In all treated and untreated cases the carcinoma cells were ER negative.Androgen deprivation leads to an upregulation of stromal ER expression in human prostate. Estrogen-induced morphological epithelial changes could be explained by a paracrine interaction between stromal and epithelial cells.

About 13% of patients treated for a pharyngeal cancer suffer from a second primary cancer. Excessive consumptions of tobacco and/or alcohol are recognized as risk factors of second primary cancers in these patients. Epidemiologic studies suggest that antioxidant vitamins could have a protective effect on the occurrence of second primary cancers; however, this hypothesis should be confirmed by randomized clinical trials. A better knowledge of the risk factors of second primary cancers in patients with a pharyngeal cancer could help reducing the occurrence of second primary cancers and improving the follow-up of these patients.

Second primary cancers often occur in head and neck cancer patients successfully treated by radiation therapy. Experimental and epidemiological data suggest that these second primaries might be prevented by antioxidant vitamins, in particular beta-carotene and alpha-tocopherol. A randomized double-blind clinical trial is being conducted in Canada to determine whether vitamin supplementation with beta-carotene (30 mg/d) and alpha-tocopherol (400 IU/d) reduces the incidence of second primaries in head and neck cancer patients treated by radiation therapy.

Sarcomatoid carcinoma of the prostate is a rare tumor that can be difficult to distinguish from a true sarcoma. The authors report 12 patients in whom the typical light microscopic appearance of prostatic adenocarcinoma was accompanied by the appearance of spindled or pleomorphic sarcomatoid areas within the same specimen or in subsequent accessions. Immunostaining or electron microscopic study demonstrated epithelial differentiation within the sarcomatoid area(s) in 6 of the 11 patients in whom special studies were performed. All nine patients for whom follow-up data were available died of disease within 3 to 48 months (median time until death, 12.0 months) after the appearance of the sarcomatoid carcinoma, and the clinical course in each instance was characterized by aggressive local recurrence. Our experience confirms that sarcomatoid carcinoma of the prostate is an aggressive variant of prostatic adenocarcinoma.

Malignant fibrous histiocytoma is a very aggressive sarcoma. After the tumor has disseminated, chemotherapy is of little influence on the course of the disease because of the resistance to most chemotherapy regimens. We evaluated by immunohistochemistry the prognostic influence of the expression of a member of the stress polypeptides family, the heat-shock protein of 27 KDa (HSP-27). HSP-27 was found to be associated with an aggressive behavior in breast carcinoma and was related to chemoresistance in cell cultures. Forty-three malignant fibrous histiocytomas with no evidence of metastases at the time of diagnosis and resected between 1974 and 1985 were retrieved from the files of the Pathology Department of L'Hôtel-Dieu de Québec hospital. The immunostaining was performed on Bouin-fixed, paraffin-embedded tissue. Regardless of the percentage of positive cells, HSP-27 was expressed in the cytoplasm of 25 (58.1%) cases. HSP-27 expression was associated with a more favorable prognosis, and a significant correlation was observed with overall survival (P less than 0.025) and metastasis-free survival (P less than 0.05). HSP-27 expression was found to be the strongest prognostic factor, and multivariate analysis revealed that it was independent of tumor size, necrosis, and histological subtype. However, in the 13 patients with recurrent disease who underwent chemotherapy, the antigenic expression did not help to predict the treatment response. HSP-27 expression is one of the rare prognostic markers in this tumor type.

This is a retrospective study of 37 patients with endometrial carcinoma and presence of tumor on endocervical curettage (clinical Stage II). We intended to correlate the presence or absence of endocervical stromal invasion with the clinical behavior and other prognostic factors. Based on the endocervical curettage, three categories (CAT) were defined: CAT I: tumor fragments only (seven cases); CAT II: endocervical tissue and free-floating tumor fragments (13 cases); and CAT III: endocervical tissue and tumor with evidence of stromal invasion (17 cases). Five tumors were partly of clear cell and/or papillary serous types and three of them belonged to CAT I. Six of seven tumors with a nuclear Grade 3 were in CAT III (p less than 0.05). Nine patients had local recurrence, metastases, or died of their disease (median follow-up: 56 mo) and seven of them were in the CAT III (p less than 0.05). We conclude that despite the presence of tumor on the endocervical curettage, the lack of endocervical tissue invasion is associated with a lower nuclear grade and a less aggressive behavior. These tumors should be regarded and treated as Stage I disease. Special attention must be paid to staging of clear cell and papillary serous adenocarcinomas because of the tendency for these tumors to contaminate the endocervical curettage.

In order better to define the extent of protein synthesis capacity of the human prostate, we have studied the translation of selected serum proteins using isolated poly(A)+ RNA preparations and the rabbit reticulocyte lysate system. The translation of alpha 1-acid glycoprotein could be conclusively demonstrated but there was no apparent translation of albumin and plasmatic transferrin. Labeled alpha 1-acid glycoprotein was identified by specific immunoprecipitation with a commercial anti alpha 1-acid glycoprotein antiserum and correct processing by canine pancreatic microsomal membranes. Furthermore, we have shown by the immunoperoxidase technique that alpha 1-acid glycoprotein was indeed localized mainly in prostatic epithelial cells in 2 out of 2 patients with benign prostatic hypertrophy and in 3 out of 11 patients with prostatic adenocarcinoma. The significance of the synthesis and secretion of alpha 1-acid glycoprotein by prostatic cell themselves is presently unknown. However, we think that it could represent an interesting subject to explore further in relation with prostatic inflammation.

Eight Sertoli-Leydig cell tumors (SLCT) of the ovary were studied by immunostaining for alpha-fetoprotein (AFP). Immunostaining was positive only in cells resembling Leydig cells in three cases and in both Sertoli and Leydig cells in one instance. In one SLCT with positive immunostaining, serum AFP was available and was elevated. Serum level was not measured in the seven other cases. Despite the small number of cases, this study suggests that AFP expression in ovarian SLCT is not unusual. The serum AFP level may, however, depend on the size of the tumor, the proportion of Leydig cells present, and their ability to produce and to release AFP into the bloodstream.

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.

A 39-year-old woman presented with arterial hypertension. Examination of the patient revealed elevated plasma renin activity, hyperaldosteronemia, hypokalemia, and a pelvic mass. Subsequently, an 11-cm right ovarian tumor mass with histologic features of an unusual stromal cell tumor was resected. Immunohistochemical studies demonstrated renin production by tumor cells. Organelles resembling mature renin granules were identified by electron microscopy. Although blood pressure normalized after the initial surgery, the hypertension resumed with later recurrence of the tumor. We believe the tumor originated from renin-secreting ovarian stromal cells, possibly granulosa cells.

Light microscopic, immunocytochemical and ultrastructural studies were performed on chondrosarcomas which contained a second, noncartilagenous mesenchymal component. Attention was focused on the nonchondroid portion of each tumor in an attempt to elucidate the histogenesis of this mixed variant of chondrosarcoma. The immunoreactivity of 20 tumors was studied using antisera for S-100 protein, alpha-1-antitrypsin, alpha-1-antichymotrypsin, smooth muscle myosin, desmin, and myoglobin. Cells of the nonchondroid portion stained for alpha-1-antichymotrypsin in 12 of 20 cases, and these were predominantly tumors that had been classified as fibrosarcoma or malignant fibrous histiocytoma by conventional light microscopic study. Staining for S-100 protein was consistently negative, whereas the chondrosarcoma component stained in 14 cases. Six tumors stained for desmin, and four of the six were positive for myoglobin and two for smooth muscle myosin; in four, a rhabdomyosarcomatous component was identified in the hematoxylin and eosin-stained sections. Electron microscopic study was performed on ten tumors and there was a good correlation between the immunohistochemical and ultrastructural findings. Three of the ten were pure rhabdomyosarcomas while the others displayed a range of ultrastructural appearances that can be seen in fibrosarcomas and malignant fibrous histiocytomas. The findings from this study support the view that the tumors are formed by the synchronous differentiation of two separate clones of cells.

During a 37-year period, 26 patients were seen who had chondrosarcoma with additional mesenchymal components ("dedifferentiated low-grade chondrosarcoma"). Sixteen were men and 10 were women aged 30 to 85 years (median, 61 years). The tumors' chondroid areas were of borderline or low-grade malignancy. The additional mesenchymal component was histologically classified as malignant fibrous histiocytoma (16), rhabdomyosarcoma (4), low-grade fibrosarcoma (3), osteosarcoma (2), and undifferentiated sarcoma (1). Preferred locations were pelvis (10) and femur (8). Symptoms had been present for 1 year or less in most cases. Pain was the most common symptom. In 15 of 26, major amputation was the primary treatment. Twelve patients received chemotherapy, usually after developing metastatic disease, but only one achieved a partial response. Median disease-free interval after diagnosis was 4 months, median survival was 6 months, and 19 patients died within 1 year. Of 4 who survived longer than 18 months, 3 presented with a low-grade fibrosarcoma. Survival and development of metastasis appeared unrelated to cell type, initial treatment, or chemotherapy, except when the tumor's initial nonchondroid component was low-grade fibrosarcoma.

Analysis of cellular DNA and RNA contents of 249 bladder irrigation specimens from 129 patients with a history of transitional cell carcinoma (TCC) of the bladder was performed using acridine-orange flow cytometry (FCM). Washings from patients with prior intravesical chemotherapy or radiation therapy were compared to those from patients with no history of treatment other than tumor resection to evaluate the reliability of FCM for the detection of tumor and the influence of prior local therapy on that reliability. Five FCM patterns were defined on the basis of DNA and RNA indexes in relationship to peripheral blood lymphocytes. FCM results were compared to cytologic findings in 237 cases, cystoscopic findings in 230 cases, and histologic data in 99 cases. Presence of a single diploid stem line was associated with absence of bladder tumor in 71% of cases from patients treated with surgery alone or with radiation therapy, but there was residual tumor in 53% of patients exposed to prior local chemotherapy. An elevated RNA content in a diploid cell population did not provide additional diagnostic information. Presence of an aneuploid stem line was associated with tumor in 85% of cases, regardless of prior therapy. Aneuploidy predicted the appearance of tumor in four of six patients with a negative cystoscopy. Tetraploidy (greater than 10% of total cell population) was associated with tumor in 79% of patients treated with surgery alone, whereas no tumor was found in more than 50% of patients who had undergone prior chemotherapy or radiation therapy. This study stresses the importance of prior treatment history in evaluating the results of DNA-FCM for bladder cancer. It demonstrates the unreliability of FCM diploid and tetraploid cell populations in patients previously treated by local chemotherapy or radiation. However, it also supports prior observations that DNA-aneuploidy and DNA-tetraploidy are useful for detecting and predicting bladder cancer in patients submitted to surgery alone.

Three cases of primary small cell carcinoma of the kidney with light microscopic, immunohistochemical, and electron microscopic findings are reported. Two patients died of disseminated disease 8 months and 1 year, respectively, after the diagnosis and the third was free of tumor after 18 months. Immunohistochemical studies revealed keratin immunostaining of tumor cells in two cases and staining for neuron-specific enolase in the third. The third case also showed a few dense neurosecretory granules at the ultrastructural level. Although no strong conclusions regarding histogenesis can be drawn, this study indicates that small cell carcinoma of the kidney exists and does not necessarily exhibit a neuroendocrine differentiation. Small cell carcinoma of the kidney must be considered in the differential diagnosis of malignant renal tumor, especially in cases in which a large necrotic tumor is present. Based on the few cases presented in this study and on the one previously reported case, small cell carcinoma of the kidney appears to be an aggressive tumor.

This report is a review of the spectrum of prostatic spindle cell lesions that are usually benign, but have morphologic features suggestive of high-grade malignancy. The problem is complicated further by the extreme rarity and heterogeneity of such lesions. Sixteen cases of atypical prostatic spindle cell proliferations are reported, and the differential diagnosis with malignancy is reviewed.

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.

Sixty-one patients with malignant mixed müllerian tumor (MMMT) of the uterus were seen at L'Hôtel-Dieu de Québec between 1950 and 1986, and the histopathologic material was available for review in 58 cases. Of the morphologic parameters studied, the histologic grade of both epithelial and mesenchymal components correlated with the initial stage. Patients with stages I and II disease had a significantly better survival rate than those with stages III and IV (P less than 0.006). Twenty-five patients with a minimum follow-up of two years were initially stage I or II. All six patients of this subgroup with an epithelial component of serous carcinoma type were dead of their disease at 2 yr. Although not statistically significant, tumor necrosis, the mode of tumor invasive (pushing and infiltrative), and the ratio of epithelial to mesenchymal components tended to influence the outcome. The mitotic rate, the type of mesenchymal components, and vascular and myometrial invasion were of no prognostic significance. We conclude that the outcome of patients with uterine MMMT is mainly influenced by the initial stage and the type of epithelial component. The influence of tumor necrosis, the ratio of epithelial to mesenchymal component, and the mode of tumor invasion deserve further studies.

A review of acridine-orange DNA and RNA flow cytometry (FCM) histograms of 249 bladder irrigation specimens from 129 patients with a previous history of transitional cell carcinoma (TCC) reveals that aneuploidy and tetraploidy (greater than 10% of total cell population) are reliable markers to detect the presence of bladder tumor in patients treated by surgical resection of tumor only. Tetraploidy is unreliable when the patient received intravesical chemotherapy or radiation therapy but aneuploidy remains accurate. A comparison of the reliability of FCM compared with cytology indicates an overall lower sensitivity and specificity for FCM (respectively, 52% and 73%) as opposed to cytology (respectively, 62% and 92%). Sensitivity is improved and raised to 77% if FCM and cytology are used in conjunction and reaches 82% in patients treated by surgery only and 88% in those who received radiation therapy. The lowest sensitivity and specificity obtained with FCM are in patients treated by intravesical chemotherapy (respectively, 44% and 58%) and the highest are in those treated by surgery without additional therapy (56% and 83%). This study demonstrates that FCM criteria for diagnosis of TCC of urinary bladder on bladder irrigation specimens depends on patient's treatment history. It also indicates that sensitivity and specificity of cytology to detect bladder tumor are superior to those obtained with FCM but both methods may be considerably improved if they are used in conjunction.