Primary rhabdomyosarcoma of the female breast: report of a case and review of the literature.

We report the case of a primary breast rhabdomyosarcoma in a 51-year-old white woman. The tumor occupied the upper outer quadrant of the right breast. There was no association with the underlying pectoral muscle, and the patient was free of any other benign or malignant neoplastic processes outside the breast. Microscopically, the breast tumor was composed of primitive myoblasts and numerous rhabdomyoblasts at various stages of development, many of which exhibited cytoplasmic cross striations on routine hematoxylin-eosin staining.

Intracystic papillary carcinoma of the female breast with secretory activity: the significance of aspiration cytology as diagnostic procedure.

We report the case of an intracystic papillary carcinoma of the breast in an elderly woman. Gross and microscopic observations support the contention that intracystic fluid is partly a result of secretory activity by the neoplastic epithelial cells and that, intracystic hemorrhage, which may contribute to it, is a secondary event complicating the primary process. Cytology of the aspirated fluid was negative for malignant cells. It is concluded that in the case of large cystic breast lesions, aspiration cytology may not be helpful in establishing the malignant nature of the lesion and that a negative cytology should be interpreted with caution, always taking under consideration the clinical picture of the disease. A concomitant adenocarcinoma was also present in the opposite breast, the second case reported in the literature.

Incidence and distribution of opportunistic lung infections in AIDS patients related to intravenous drug use: a study of bronchoalveolar lavage cytology by the Diff-Quik stain.

The present study was undertaken in order to determine the incidence and distribution of opportunistic lung infections in patients with acquired immunodeficiency syndrome related to intravenous drug use. One hundred ninety seven patients of both sexes were investigated. Based on bronchoalveolar lavage cytology, a total of 156 (79%) patients were found to harbor opportunistic lung infections by the Diff-Quik staining procedure. Seventy-nine percent of the males and 80% of the females were positive. Pneumocystis carinii was the most common of the opportunistic infections accounting for 83% of the positive cases. Cryptococcus, Candida sp., and Aspergillus sp. were also identified in a small number of patients. Cytomegalovirus was not detected in any of the cases under study. There were no sex-related differences in the distribution of the various infectious agents, males and females being equally affected.

Uterine leiomyoblastoma (epithelioid leiomyoma) neoplasm of low-grade malignancy. A histopathologic study.

Uterine leiomyoblastomas are neoplasms of smooth muscle origin, which despite their benign histopathologic characteristics, have been shown to invade locally, metastasize, and recur, resulting in the patient's death. In an effort to define possible cellular changes that could explain the disparity between histopathologic features and biologic behavior, we have studied a series of three uterine leiomyoblastomas that, in routine sections, exhibited benign morphological characteristics. A detailed histopathologic study revealed, in all three cases, randomly distributed clusters of neoplastic cells with overt malignant features, such as cellular and nuclear atypia, abnormal mitoses, local infiltrating tendencies, and vascular invasion. These findings suggest that uterine leiomyoblastomas should be viewed as neoplasms of low-grade malignancy of a distinct clinicopathologic entity.

Morphologic, biologic and biochemical characteristics of three human pancreatic ductal adenocarcinomas established as xenotransplants in the nude mouse.

Three new human pancreatic adenocarcinomas of ductal origin, covering the spectrum of well differentiated to poorly differentiated neoplasms, have been established as xenotransplants in the nude mouse. Histopathological and ultrastructural features confirmed the neoplasms' ductal origin and were consistently reproduced through serial transplant generations. Carcinoembryonic antigen was only elaborated by the well differentiated neoplasms and production of lactate dehydrogenase isoenzymes was characteristic of each tumor. The morphological and biological features of these tumors make them a valuable addition to the very small number of available pancreatic tumor lines in studies aiming at clarifying many aspects of the biology of this type of neoplasia.

Schedule dependency of the combination methotrexate-vinblastine against human urothelial cancer grown in nude mice.

The combination of methotrexate (MTX) and vinblastine (VLB) was evaluated using different doses and treatment schedules in human transitional cell carcinoma line SW-1738, TCC-K1 and TR-49 grown in the nude mouse. Maximally tolerated weekly doses of MTX, 30 mg/kg, and VLB, 3 mg/kg, were given intraperitoneally for four consecutive weeks singly, concurrently, and separated by 24, 48 and 72 hour intervals. MTX-VLB drug sequence was not a factor in determining tumor regression or response rates when the second agent was administered 24 or 48 hours after the first agent. However, when VLB was administered 72 hours after MTX, a significant statistical difference (0.005 greater than p greater than 0.001) was observed for all tumor lines studied compared to either controls, simultaneous administration of both agents and/or VLB administered 24 or 48 hours after MTX. Additionally, dose reduction of either agent by 30% proved ineffective. Thus, tumor response to MTX-VLB combination was dependent both on schedule and dose. Application of this schedule dependency may be beneficial in management of urothelial tract tumors.

Experimental studies on the response of nude mouse-grown human urothelial cancer to high dose of 1-beta-D-arabinofuranosylcytosine.

The effect of 1-beta-D-arabinofuranosylcytosine (ara-C) on human bladder transitional cell carcinomas (TCC) was evaluated using nude mouse-grown established tumor lines SW-780, SW-1738, TCC-K1, and PR49. In the nude mouse tumors grew subcutaneously and evaluation of response to treatment was based on tumor volume analysis. Ara-C was administered intraperitoneally at a dosage of 250 mg/kg on days 1 to 4. All four tumor lines showed an initial phase of considerable regression during the treatment week. This was followed by a variable period of tumor growth arrest after which a gradual tumor regrowth was observed. The results of the present study suggested that ara-C may alter the growth rate of TCC, its effect becoming apparent during the time of its administration and for a short period thereafter. These observations indicate that more studies are warranted at both the experimental and clinical levels to further evaluate dosage and treatment schedule. The results of such additional studies may determine the importance of ara-C in the management of patients with bladder cancer.

Morphological, biological, biochemical, and karyotypic characteristics of human pancreatic ductal adenocarcinoma Capan-2 in tissue culture and the nude mouse.

Human pancreatic ductal adenocarcinoma Capan-2, derived from a 56-yr-old male Caucasian, has been studied in both tissue culture and the nude mouse. In tissue culture, tumor cells showed epithelial-like features, whereas in the nude mouse, the tumor grew as a well-differentiated adenocarcinoma, resembling histopathologically the original neoplasm. Ultrastructurally, the neoplastic cells showed characteristics of ductal epithelium. The allozyme phenotypic profile of Tumor Capan-2 was determined in eight genetically determined loci, and chromosome studies showed a hypotetraploid pattern with a number of morphological and numerical changes. Carcinoembryonic antigen was produced in trace amounts, and lactate dehydrogenase was represented only by Isoenzyme 5, regardless of environmental conditions. The characteristics of Capan-2 tumor make it a valuable addition to the small number of available pancreatic tumor lines in studies aiming at clarifying certain aspects of the biology of this type of malignancy.

Time dependence of the radiation-modifying effect of cis-diamminedichloroplatinum II (cisplatin, DDP) on human urothelial cancer grown in nude mice.

Previous reports have indicated that human urothelial cancer is more sensitive to combination radiation-cisplatin than to either treatment given alone and that the treatment schedule may be an important factor in determining the magnitude of tumor response. In the present study we have investigated the effect of timing and the sequence of combination "radiation-cisplatin" on human urothelial cancer grown in nude mice. Tumors were exposed to 1000 rad x-irradiation and received cisplatin treatment in the amount of 5 mg/kg once on each specified day before or after radiation. Best tumor responses, characterized by significant tumor growth delay and tumor regression, were observed when cisplatin was given on Day 3 and 6 postradiation. The present work has indicated that timing and sequence of treatments in the combination "radiation-cisplatin" are important factors in determining tumor response and may be of assistance in formulating the most effective clinical trials of urothelial cancer patients.

Enhanced therapeutic effect of cis-diamminedichloroplatinum(II) against nude mouse grown human pancreatic adenocarcinoma when combined with 1-beta-D-arabinofuranosylcytosine and caffeine.

We demonstrated previously that the effect of cis-diamminedichloroplatinum(II) (cisplatin) against pancreatic cancer was substantially enhanced by the addition to the chemotherapeutic regimen of 1-beta-D-arabinofuranosylcytosine and caffeine. To obtain information on the factors influencing tumor response to this combination treatment, we investigated two adenocarcinomas of the exocrine pancreas grown in the nude mouse, tumors Capan-1 and SW-1990. Tumor response to cisplatin, characterized by tumor regression and tumor growth arrest, was observed when it was given in the upper limits of tolerance (5 mg/kg). Caffeine and 1-beta-D-arabinofuranosylcytosine singly and in combination had no effect on tumor growth; neither did they influence the effect of cisplatin when combined singly with the latter. However, the triple combination of cisplatin, 1-beta-D-arabinofuranosylcytosine, and caffeine resulted in complete tumor regression. The enhancing effect of the triple combination depended on tumor sensitivity to cisplatin and the amount of cisplatin administered and required rather large amounts of caffeine. The present report indicates that certain combination regimens may enhance the therapeutic effect of cisplatin against pancreatic carcinoma.

Response of nude mouse-grown adenocarcinomas of the human exocrine pancreas to cis-diamminedichloroplatinum(II), diammine[1,1-cyclobutanedicarboxylato(2-)-O,O'-platinum], and mitoguazone dihydrochloride.

The effect of cisplatin, carboplatin, and mitoguazone dihydrochloride on pancreatic cancer was evaluated using pancreatic ductal adenocarcinomas Capan-1, Capan-2, and PR54 grown in the nude mouse. In single agent treatments, cisplatin, given in the amount of 5 mg/kg once/week for 4 consecutive weeks, was most effective, resulting in tumor regression, growth arrest, and a growth delay period of 6 and 4 months for tumors Capan-1 and PR54, respectively. Treatment with carboplatin was less effective, with a tumor response related to treatment schedule. For the same amount of total dose of carboplatin administered, best results were obtained when treatment was given 3 times weekly instead of in single weekly injections. Mitoguazone dihydrochloride exhibited no antitumor effect. The results of the present work may be of significance in the management of pancreatic cancer patients.

Response of nude mouse-grown human urothelial cancer to cis-diamminedichloroplatinum(II), diammine[1,1-cyclobutanedicarboxylato(2-)-O,O'-platinum], and mitoguazone dihydrochloride.

A comparative study of the effect of cis-diamminedichloroplatinum(II) (cisplatin), diammine[1,1-cyclobutanedicarboxylato(2-)-O,O'-platinum] (carboplatin), and mitoguazone dihydrochloride on urothelial cancer was conducted using transitional cell carcinomas of the urinary bladder grown in the nude mouse. Tumors SW-780 and TCC-K1 represented transitional cell carcinoma, Grade II, whereas Tumor PR49 represented a fast-growing Grade III neoplasm. Of the agents studied, cisplatin was most effective, resulting in tumor response related to the dose administered. Response to carboplatin was clearly related to treatment schedule. For the same amount of total dose administered, better results were obtained when treatment was given three times weekly instead of once every week. Furthermore, cisplatin was more effective against the less differentiated PR49 tumor in contrast to carboplatin, which showed more activity against the better differentiated SW-780 and TCC-K1 tumors. None of the tumors tested responded to mitoguazone dihydrochloride. The results of the present study may assist in formulating better treatment modalities against urothelial cancer, taking into account factors such as tumor grade, growth rate, treatment schedule, and the patient's tolerance which may ultimately influence tumor response.

Response to ionizing radiation of human bladder transitional cell carcinomas grown in the nude mouse.

The sensitivity to ionizing radiation of three human bladder transitional cell carcinomas grown in the nude mouse was investigated at four different radiation levels, 500, 1,000, 2,000 and 4,000 rad. Each tumor line exhibited a response pattern which reflected to a certain degree tumor differentiation and growth rate in the nude mouse. Exposure to 1,000 rad was the minimum amount of radiation required to produce a distinct, although transient, tumor response in all three tumor lines characterized by a growth delay of 3-4 weeks, whereas maximum tumor response was observed at the 4,000 rad radiation level. These studies would permit a better understanding of the behavior of human bladder cancer to ionizing radiation and may further facilitate efforts at identifying effective radiosensitizing agents that may result in maximizing tumor response.

Morphological, biological, and biochemical characteristics of human bladder transitional cell carcinomas grown in tissue culture and in nude mice.

The morphological, biological, biochemical, and karyotypic characteristics of four human bladder transitional cell carcinoma lines, SW-780, SW-800, SW-1738, and SW-1710, were investigated. In tissue culture, each cell line presented a distinct phenotypic expression. All but line SW-1710 grew when transplanted in the nude mouse. Light and electron microscopic studies showed morphological characteristics similar to the tumors of origin, being independent of the passages in tissue culture medium, tumor cell extracts, and the plasma of nude mouse-grown tumors, showing isoenzyme quantitative distribution typical for each cell line. In addition, each cell line exhibited a unique genetically determined enzyme phenotypic profile which, along with the karyotypic analysis, makes their identification feasible. These characteristics make the described tumor lines a valuable tool in studying various aspects of the biology of human bladder transitional cell carcinoma.

Establishment and characterization of human pancreatic adenocarcinoma cell line SW-1990 in tissue culture and the nude mouse.

A new tumor line derived from a human pancreatic ductal adenocarcinoma of a 56-year-old Caucasian male was established in tissue culture and the nude mouse. In tissue culture, the neoplastic cells grew as large, epithelial-like, mucin-producing cells. Injection s.c. of 1 X 10(6) cultured neoplastic cells into nude mice resulted in tumor formation histologically closely resembling the original neoplasm. Ultrastructurally, the neoplastic cells showed characteristics of ductal epithelium. The allozyme phenotypic profile of the line was established in 14 genetically determined loci, and chromosome studies showed a near-tetraploid pattern. Production of macromolecules such as lactate dehydrogenase and carcinoembryonic antigen were present in measurable amounts in culture media, tumor cell extracts, nude mouse-grown tumors, and the serum of tumor-bearing mice in amounts relative to tumor size. Pancreatic enzymes were not detected. These characteristics make tumor line SW-1990 a valuable tool in studying various aspects of the biology of human pancreatic cancer.

Experimental studies on the radiation-modifying effect of cis-diamminedichloroplatinum II (DDP) in human bladder transitional cell carcinomas grown in nude mice.

The effect of cis-diamminedichloroplatinum II (DDP) and ionizing radiation on human bladder transitional cell carcinoma (TCC) was evaluated in nude mouse-grown human tumors following administration of single-agent and combination treatment. Combination of DDP and radiation resulted in accelerated tumor regression and substantially delayed tumor regrowth. The potentiating effect of DDP on ionizing radiation was related to timing and sequence of treatments and was independent of tumor sensitivity to DDP. Best results, as judged by tumor growth curve characteristics, histopathologic changes, and absence of tumor metastases, were obtained when DDP was administered at an early stage following radiation treatment.

Histopathologic evaluation of response to treatment of human tumors grown in the nude mouse.

The histopathologic changes following chemotherapy treatment of a number of human tumors grown in nude mice were evaluated. On the basis of the histopathologic profile, three response levels were recognized--a mild response, a moderate response and a severe response. Severe response was characterized by arrest of cell division and profound nuclear-cytoplasmic degenerative changes. Regrowth of effectively treated tumors originated in clusters of cells most probably representing resistant tumor cell clones. Histopathologic changes represent a sensitive indicator of the response of nude mouse grown human tumors to anticancer agents. Availability and correct interpretation of the post-treatment histopathologic picture is of importance in selecting the proper combination treatment which would maximize tumor response.

Human pancreatic adenocarcinoma line Capan-1 in tissue culture and the nude mouse: morphologic, biologic, and biochemical characteristics.

Human pancreatic ductal adenocarcinoma line Capan-1 was studied in tissue culture and the nude mouse. In tissue culture, the neoplastic cells grew as large epithelial-like mucin-producing cells. Subcutaneous and intraperitoneal transplantation of neoplastic cells into nude mice resulted in tumor formation characterized by marked invasiveness and distant metastases. Histologically, the tumor appeared as a well-differentiated mucin-producing adenocarcinoma morphologically resembling the tumor of origin. Chromosomal analysis showed a human karyotype with a chromosome number between 51-61. Lactate dehydrogenase and beta 2-microglobulin used as tumor markers were present in both tissue culture and the serum of tumor-bearing mice. The neoplasm, which was characterized by an increased level of cAMP, had lost completely the ability to respond to secretin stimulation. The tumor grown in the nude mouse was resistant to treatment with 5-fluorouracil, behavior identical to that of the original tumor. Diphtheria toxin resulted in complete tumor destruction. Because Capan-1 tumor grown in the nude mouse shows morphologic, biologic, and biochemical characteristics similar to the tumor of origin, it may be an invaluable tool in furthering understanding of the biology of human pancreatic cancer.

Histopathologic changes in the peripheral lymphoid organs of athymic nude mice transplanted with human tumor.

Lymph nodes of tumor-bearing nude mice were evaluated histologically and were found to differ significantly from those of nontumor-bearing control animals. Microscopically, the observed changes wee classified into three patterns, namely histiocytosis, plasmacytosis and formation of germinal centers. The majority of tumor-bearing (63%) showed marked histiocytosis which was either diffuse or nodular involving primarily lymph nodes draining the site of the tumor. Plasmacytosis, affecting lymph nodes at various anatomical sites, was evident in 43% of mice, and in 37% of animals formation of germinal centers was observed. Germinal center formation was always associated with plasmacytosis and markedly increased IgG, IgM and IgA serum levels. There was no repopulation of the thymus-dependent areas by lymphocytes and graft-versus-host reaction was absent.

Biological behavior of human malignant tumors grown in the nude mouse.

The biological behavior of a number of nude mouse-grown human epithelial tumors of different histogenetic background was studied. They included three transitional cell carcinomas and a mucin-producing carcinoma of the urinary bladder, two pancreatic adenocarcinomas, a colon adenocarcinoma, a breast ductal carcinoma, and an epidermoid carcinoma. Microinvasion was a constant finding in all tumors examined. All but one of the tumors studied showed macroinvasion and metastases. Tumors transplanted s.c. in the anterior aspect of the lateral thoracic wall metastasized primarily to the regional and mediastinal lymph nodes. In certain cases, systemic metastases were observed affecting the submaxillary, contralateral axillary, and inguinal lymph nodes. Lung metastases occurred through the lymphatic and hematogenous routes. It is concluded that the nude mouse-grown human tumors investigated in the present study show overt malignant behavior recapitulating the biological characteristics of the tumor of origin.