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Biomedical subjects

K R Geisinger

Publications and source records attributed to K R Geisinger.

At least 91 records · Page 5Linked to original sources

The effects of estrogen, progesterone, and tamoxifen alone and in combination with cytotoxic agents against human ovarian carcinoma in vitro.

The effects of estradiol (E), medroxyprogesterone acetate (MPA), and tamoxifen (TAM) on the growth of a human ovarian carcinoma cell line, BG-1, were evaluated using a tumor clonogenic assay (HTCA). BG-1 contains significant quantities of estrogen and progesterone receptors. Growth inhibition by TAM and growth stimulation by MPA were demonstrated using continuous drug exposure. Estradiol resulted in a marginal increase in colony formation. With each of these three drugs, the greatest response occurred in the larger colonies (generally greater than or equal to 60 microns). Combinations of each of these three steroidal agents with three different cytotoxic drugs were studied in the HTCA. Synergistic activities were produced with TAM combined with either cisplatin or doxorubicin. Additive effects were seen with TAM and cyclophosphamide. Although predominantly additive or synergistic, the effects were variable with MPA and all three cytotoxic agents. Combinations of estradiol with cytotoxic agents were no more active than the cytotoxics alone. These findings indicate a biological rationale for hormonal manipulation as therapy in ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Angiosarcoma of the heart: pericardial fluid cytology.

The unique cytomorphologic aspects of a cardiac angiosarcoma in pericardial fluid are presented. Smears and cell block preparations revealed clusters of malignant pleomorphic oval to spindle-shaped cells concentrically layered about amorphous acellular cores. The cytologic findings were correlated with histologic, immunohistochemical, and electron microscopic findings in the necropsy material.

Heart Neoplasms↗

Fine-needle aspiration cytology of granulocytic sarcoma and myeloid metaplasia.

The fine-needle aspiration (FNA) cytology of two cases of granulocytic sarcoma involving the breast is reported along with the FNA cytology of one case of myeloid metaplasia (extramedullary hematopoiesis) involving an axillary lymph node. Two patients had known myeloproliferative disorders, while granulocytic sarcoma of the breast was the initial presentation of an unsuspected acute granulocytic leukemia in the other patient. Diff-Quik-stained preparations aided in the diagnosis of all three cases. Immunoperoxidase stains for factor VIII-related antigen helped confirm the megakaryocytic differentiation of the cells in the FNA cytology of myeloid metaplasia. Electron microscopic (EM) examination performed on the aspirated material also showed megakaryocytic differentiation of the bizarre cells. FNA cytology can make a specific diagnosis of granulocytic sarcoma and myeloid metaplasia. The workup of these unusual extramedullary myeloproliferative masses was aided when immunocytochemistry and EM were performed on the aspirated material.

Adult↗

Radiation-induced proctitis cystica profunda in the rat.

Therapeutic pelvic irradiation is notorious for the production of clinically significant sequela after a long latency. One of the rarest of these complications is proctitis cystica profunda (PCP). To study the histologic changes of chronic radiation proctitis, we evaluated 35 female Wistar rats that had received a single exposure of 22.5 Gy of radiation to the rectum and were then followed for one year. We identified PCP and its precursor lesions in 18 rats. The fully developed lesion consisted of a focal expansion of the submucosa by dilated cystic spaces lined by a single layer of benign epithelial cells. Usually, PCP evolved as glands herniated between small defects in the muscularis mucosae. Mitotic figures were not recognized in the cells lining the herniating glands. In two rats, the radiation had apparently caused large ulcers, which had subsequently reepithelialized, resulting in prominent submucosal glandular tissue. Although the number of goblet cells in the displaced epithelium was reduced, the cells had rather mature appearances ultrastructurally. Glands displaced into the submucosa were encased by an intact basal lamina but lacked in muscularis.

Animals↗

DNA content and proliferative index in cutaneous squamous cell carcinoma and keratoacanthoma.

The histologic separation of keratoacanthomas (KA) and well-differentiated squamous cell carcinoma (WDSCC) using established criteria may present a diagnostic dilemma in the individual case. The authors questioned whether the DNA index (DI) and/or the proliferative index (PI), as shown by flow cytometry (FCM) might assist in this differential diagnosis. Thirty-six well-differentiated squamous cell lesions of skin were independently classified as either WDSCC or KA by a panel of three pathologists. Six poorly differentiated squamous cell carcinomas (PDSCC) also were included in this study. Sections from paraffin blocks were prepared by standard techniques and analyzed by FCM. Mean DI values were: KA 0.96%, WDSCC 0.99%, and PDSCC 0.88%. The differences in the mean DIs were not statistically significant. Mean PI values were as follows: KA 16.7%, WDSCC 14.8%, and PDSCC 20.2%. Differences were not statistically significant. The authors conclude that the FCM measurements of DI and PI do not help in separating KA and WDSCC of skin.

Adult↗

Islet cell neoplasms. A fine-needle aspiration cytology study with immunocytochemical correlations.

Islet cell neoplasms (ICNs) are uncommon tumors that may present with bizarre endocrine manifestations. Only rarely have their fine-needle aspiration (FNA) cytomorphologic characteristics been reported. The authors have studied FNAs of ICNs in ten patients, including immunocytochemistry (ICC) directly on the aspirates. FNA yielded moderately to markedly cellular specimens with numerous individual cells and large aggregates. Although moderate pleomorphism was present in three cases, striking uniformity in nuclear size and contour and in delicate nuclear membranes was evident. Typically the round nuclei were eccentric, imparting a plasmacytoid appearance. Cytoplasmic granularity was noted in only a minority of tumor cells. Five of the ICNs were positive for chromogranin (CG). In comparison, seven ICNs were positive for CG in tissue sections. None of the cytologic material showed immunoreactivity with insulin, glucagon, somatostatin, or gastrin. Histologic material showed positivity for these hormones in 33% (three of nine), 22% (two of nine), 22% (two of nine), and 11% (one of nine), respectively. Although CG is the most useful immunocytochemical marker for ICNs, and thus is helpful in confirming a diagnosis of ICN in FNA material, it is negative in half of the cases and may be negative when the histologic material is positive.

Adenoma, Islet Cell↗

Primary malignant lymphoma arising in postmastectomy lymphedema. Another facet of the Stewart-Treves syndrome.

In rare cases, primary malignant lymphomas may arise in the soft tissues. Only one previous case has arisen in the context of chronic lymphedema. Because of the clinical appearance of such lesions, which resemble violaceous nodular or plaquelike tumors, they may be confused clinically with lymphedema-associated angiosarcomas occurring after radical mastectomy (Stewart-Treves syndrome). Furthermore, the histologic appearance of some lymphomas and angiosarcomas may also be similar. We studied two women with primary postmastectomy lymphedema-related malignant lymphoma in the soft tissues of the upper arm. These tumors arose 11 and 30 years, respectively, after radical removal of ductal mammary carcinomas. Histologically, one neoplasm mimicked metastatic carcinoma or epithelioid angiosarcoma; whereas the other was initially confused with a variety of pathologic entities, including vasculitis, epithelioid hemangioma, and malignant fibrous histiocytoma. The lymphoid nature of both lesions was confirmed by immunoreactivity for leukocyte common antigen in addition to the B-lymphocyte marker, L26. Conversely, vascular and epithelial determinants were absent. One patient's disease pursued an indolent course; she died of unknown causes but with no evidence of lymphoma at last follow-up. The second patient is currently in remission on chemotherapy. Awareness of the existence of lymphedema-related malignant lymphoma and familiarity with methods used for its distinction from epithelioid vascular sarcomas should prevent unnecessary surgery.

Aged↗

Fine needle aspiration biopsy cytology of hepatoblastoma.

Fine needle aspiration biopsy (FNAB) from four patients with histologically proven hepatoblastoma (HB) is reviewed. Patient ages ranged from 5 mo to 19 mo; two were male and two were female. Initial cytologic diagnoses were hepatoblastoma in two cases, malignant neoplasm consistent with liver cell tumor in one case, and probable Wilm's tumor in a fourth case. Cytologic features were similar in all cases and included highly cellular smears composed of a uniform population of small to intermediate sized round to oval cells. Extramedullary hematopoietic cells were obvious in smears of one patient. Neither bile nor extracellular stroma was seen. Immunohistochemical stains performed in two cases demonstrated positive staining for low-molecular-weight cytokeratins expressing polypeptides 8 and 18 of the Moll classification. Staining for vimentin, carcinoembryonic antigen, and epithelial membrane antigen was negative. alpha-Fetoprotein and alpha 1-antitrypsin stains were equivocal because of high background staining. Electron microscopy from three cases showed cells with features of immature hepatocytes. Three tumors were subsequently examined histologically by surgical biopsy, and one at autopsy. All were epithelial-type HB containing a mixture of "fetal" and "embryonal" hepatocytes. These results demonstrate the successful mimicry of FNAB cytology of hepatoblastoma to its histologic counterpart and its clinical utility in the diagnosis of intrahepatic masses of children.

Biopsy, Needle↗

The histologic development of acid-induced esophagitis in the cat.

Acute reflux esophagitis in man is characterized histologically by infiltrates of segmented leukocytes, epithelial proliferation, and ulcers. Our feline model, which includes each of these features, is produced by the infusion of 0.1 N HCl at a rate of 1 ml per min into the distal esophagus of adult cats for varying periods of time. Our histologic scoring system includes both the intensity and the distribution of four morphologic features, namely basal cell hyperplasia (BCH), intraepithelial segmented leukocytes (IEL), subepithelial leukocytes (SEL), and ulcers. Each of these four categories are scored from 0 to 4, with a potential score of 16. We evaluated the effects of duration of acid exposure by infusing cats with HCl for 5 min (N = 4), 15 min (N = 12), 20 min (N = 12), and 30 min (N = 6), followed by autopsy 24 h later. Mean scores (+/- SE) were as follows: 5 min, 3.0 (+/- 1.7); 15 min, 9.0 (+/- 1.0); 20 min, 11.17 (+/- 1.06); 30 min, 15.17 (+/- 0.54). Differences between 5 and 15 min, 15 and 30 min, and 20 and 30 min were significant (P less than 0.05). Basal cell hyperplasia appeared to be the most sensitive marker of acid injury; ulcers denoted severe injury associated with longer exposure periods. Although an occasional eosinophil was seen, the majority of the segmented leukocytes were neutrophils. We also studied healing histologically by examining cats at 1 d (N = 6), 2 d (N = 6), 3 d (N = 11), and 4 d (N = 6) after a 30 min exposure to HCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fine-needle aspiration cytology of malignant hemangiopericytomas with ultrastructural and flow cytometric analyses.

A hemangiopericytoma (HPC) is an uncommon soft-tissue neoplasm that may arise in many body sites. The cytologic features of fine-needle aspirates (FNAs) of HPCs have only rarely been described in the literature. We examined FNAs of malignant HPCs from the head and neck region (three) and the retroperitoneum (one) in four adults (aged 38 to 83 years). All four FNAs yielded cellular specimens that consisted of uninuclear tumor cells with high nuclear-cytoplasmic ratios. The cytomorphological spectrum included nuclei that were oval to elongate and had very finely granular, evenly distributed chromatin with one or two small but distinct nucleoli. Hemangiopericytomas yield aspirates that may be considered malignant and may suggest sarcoma. Histologically, all four neoplasms manifested high mitotic activity. The ultrastructural features of all four tumors were supportive of the diagnosis of HPC. Although a specific primary diagnosis of HPC on FNA of a soft-tissue mass is unlikely, cytologic analysis may allow diagnosis of recurrent or metastatic HPC. We were able to perform flow cytometric determinations of tumor DNA content on three of the resected neoplasms. In two, an aneuploid pattern was found, including the neoplasm with the most marked pleomorphism in the FNA. The third was diploid.

Adult↗

Characterization of a human ovarian carcinoma cell line with estrogen and progesterone receptors.

The potential significant therapeutic and prognostic roles for the sex steroid receptors in ovarian cancer are recognized. The authors present in detail the biochemical, morphologic, cytogenetic, and growth characteristics of an ovarian carcinoma cell line, BG-1, which has functional estrogen and progesterone receptors (23 and 300 fmol/mg protein, respectively) in clinically significant levels. In particular, BG-1 has a DNA index of 1.14, a stable karyotype with specific translocations, and produces and secretes CA 125 into the media.

Adenocarcinoma↗

Endoscopic biopsy is diagnostic in gastric antral vascular ectasia. The "watermelon stomach".

Gastric antral vascular ectasia was endoscopically diagnosed in seven patients. Pathologic characteristics of this entity were defined retrospectively, by studying endoscopic pinch biopsy slides from these seven patients and antrectomy specimens from five patients. A scoring system was developed, and the seven patients were compared prospectively with various control groups. Abnormalities of mucosal vessels (fibrin thrombi and/or ectasia) consistently distinguished patients from control antrectomies, normal biopsies, acute gastritis biopsies and atrophic gastritis biopsies (P = 0.02, all comparisons). Spindle cell proliferation into mucosa also was characteristic of gastric antral vascular ectasia, distinguishing this disease from normals, acute gastritis, and atrophic gastritis (P less than or equal to 0.039, each comparison). The presence of abnormal mucosal vessels (fibrin thrombi and/or ectasia) and spindle cell proliferation was similar in patient antrectomies compared to patient endoscopic biopsies. Therefore, we conclude that endoscopic biopsies can reliably diagnose gastric antral vascular ectasia, a vascular disorder characterized by abnormal mucosal vessels and spindle cell proliferation.

Aged↗

Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats.

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.

Animals↗

The clear-cell variant of uterine epithelioid leiomyoma. An immunohistologic and ultrastructural study.

A case of a rare uterine clear-cell epithelioid leiomyoma is presented, emphasizing immunohistologic and ultrastructural findings. The presence of actin, vimentin, desmin, muscle-specific antigen, and smooth-muscle-specific actin in tumor cells indicates a smooth-muscle origin, confirmed by electron microscopy. Numerous vacuolated mitochondria produced the cytoplasmic "clearing" on light microscopy.

Actins↗

Immunohistochemical study of uterine stromal sarcoma and rhabdomyosarcoma.

The cytoplasmic filament composition of two pure high-grade endometrial stromal sarcomas and five pure endometrial rhabdomyosarcomas was studied using the immunoperoxidase avidin-biotin method. Ultrastructural correlates were performed on the same tissues. While four of the seven tumors presented as high-grade undifferentiated neoplasms, they were readily categorized on the basis of immunocytochemical findings in which the five rhabdomyosarcomas were positive for muscle-specific actin (HHF 35) and the two stromal sarcomas were positive for vimentin only. Ultrastructure on the HHF 35-positive cases showed the presence of thick filaments and Z-band material, whereas the other tumors showed no cytoplasmic differentiation. Muscle-type actin differs stromal cells, and is useful when used in conjunction with a panel of antibodies in the categorization of undifferentiated endometrial sarcomas.

Biomarkers, Tumor↗