Leiomyosarcoma of the pulmonary veins.

Primary sarcomas of the great vessels are rare, but the most common site is the inferior vena cava. Herein are reported five new cases arising from the pulmonary veins with clinicopathologic correlation and comparison to previously reported cases. All new cases occurred in women ranging in age from 23 to 64 years at diagnosis (mean, 56 years). They had symptoms suggestive of left heart failure, including three patients with dyspnea, one with hemoptysis, and one with cough. Three cases showed tumor extension along the pulmonary veins into the left atrium. Tumors ranged in size from 2.8 to 7 cm in greatest dimension. Histologically, all were leiomyosarcomas. They were highly cellular tumors. Three cases had predominantly spindle cell morphology and two were predominantly epithelioid; one had foci of calcification. Most showed extensive necrosis. All tumors were reactive with antibodies to actin and desmin. Two cases were reactive with antibodies to MIC-2 (dotlike); two cases showed reactivity to keratin antibodies; and two showed reactivity for estrogen, progesterone receptor protein, or both. None were positive for antibodies to S-100 protein. All cases were treated with surgical excision. Follow-up ranged from 2 months to 21 years (mean, 4.8 years). Two patients were alive and well; two were alive with metastases; and one died of disease. Pulmonary vein sarcomas represent intermediate- to high-grade leiomyosarcoma. Although often lethal, complete surgical excision can lead to long-term survival. They occur predominantly in women and may express hormone receptors. Therefore, hormonal manipulation may offer promise as adjuvant therapy.

Fine needle aspiration cytology of the oxyphil variant of papillary carcinoma of the thyroid. A report of three cases.

BACKGROUND: A number of histologic variants of papillary carcinoma of the thyroid have been described, including an oxyphil cell subtype (OVPC). Few OVPC cases have been detailed cytologically. CASES: Smears prepared from aspiration biopsies, as well as the corresponding histologic sections and clinical histories, were reviewed for three cases. Two patients had asymptomatic thyroid tumors, and the third developed neck tumors after thyroid cancer surgery. All smears revealed scattered papillary groups and monolayered sheets. The large, neoplastic cells had abundant, granular cytoplasm and eccentrically placed nuclei. Nuclear grooves and intranuclear inclusions were variably present. Psammoma bodies and colloid were not identified. Histologically the tumors consisted predominantly of oxyphil cells arranged in papillary patterns and with nuclear features of usual papillary carcinoma (UPC). CONCLUSION: OVPC can be diagnosed in smears composed predominantly of large oxyphil cells but showing features associated with UPC and can be cytologically distinguished from follicular oxyphilic tumors and UPC.

The effect of a selective 5-lipoxygenase inhibitor, zileuton, on tissue damage in acute colonic inflammation in rats.

Though the mechanism of tissue damage induced by colonic inflammation in ulcerative colitis is unknown, it has been established that the inflammatory mediator and potent neutrophil (PMN) chemotaxin, leukotriene B4(LTB4), is present in elevated amounts in the inflamed mucosa. The unique role of 5-lipoxygenase in the production of leukotrienes has made it a target for inhibition. This study used a rat model of acute colonic inflammation induced by a single IP injection of Mitomycin-C to test the efficacy of a specific and potent 5-lipoxygenase inhibitor zileuton in the treatment of colonic inflammation. We hypothesized that after inducing colitis in rats with mitomycin-C, the administration of oral zileuton would inhibit leukotriene production, thus preventing PMN infiltration and subsequent tissue damage. Zileuton decreased colonic tissue damage as measured by Histological score. However, zileuton did not significantly decrease neutrophil infiltration measured by mucosal PMN or myeloperoxidase (MPO) levels. Although zileuton was successful in significantly decreasing the frequency of severe colitis in our model, the fact that the decrease in PMN count and MPO level was not statistically significant suggests that another mechanism may be involved in its anti-inflammatory effect.

Cytologic features of clear cell carcinoma of the urethra and urinary bladder.

Clear cell carcinoma (CCL) arising in the lower urinary tract is unusual and we report the cytohistologic findings of three cases retrieved from our files. All patients presented with bleeding, and the tumors were localized in either the urethra or bladder base. Filter and cytocentrifuge preparations of the urine were studied and all cases displayed numerous scattered aggregates or single tumor cells in an inflammatory background. The enlarged cells had abundant clear, wispy cytoplasm with discrete vacuolation. Hobnail and signet ring cells were apparent. The nuclei had granular to vesicular chromatin with prominent often multiple nucleoli. The tumors were histologically distinctive and typically had a tubulocystic configuration with varying proportions of papillary and diffuse patterns. One patient has died of metastatic cancer and two are presently free of tumor. The cytohistologic features of this cancer are characteristic and from our review we conclude that this lesion can be diagnosed by cytologic means.

Gastric mucosal injury after hepatic arterial infusion chemotherapy with floxuridine. A clinical and pathologic study.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) of liver metastases of colon cancer with an implantable pump is associated with liver and gastrointestinal complications. METHODS: The authors retrospectively studied the clinical features and gastric histopathology of nine patients who received HAIC and had gastritis develop and in whom biopsy specimens were available. RESULTS: Gastritis was heralded in these patients by epigastric pain and tenderness, nausea, vomiting, weakness, and anorexia. In seven patients, 18 gastric ulcers were endoscopically detected. Mucosal damage developed despite prophylactic antiulcer therapy and healed only upon cessation of HAIC. These observations suggest that the predominant drug given, floxuridine, was the responsible toxic agent. Seventeen biopsy specimens were reviewed, and all exhibited varied histologic evidence of inflammation, reactive glandular changes, and cell necrosis. These mucosal changes were present even in tissues obtained from patients without ulcers. In addition, floxuridine-induced glandular atypia was noted in eight biopsy samples from six patients. The crowded glands were distorted and lined by large cells that included bizarre forms with pleomorphic nuclei. CONCLUSIONS: Gastric injury in HAIC appeared analogous to the general features encountered in reactive gastritis resulting from chemical irritants. The glandular atypia is peculiar to HAIC, and although the changes were morphologically alarming, in this clinical situation care should be exercised not to interpret floxuridine-induced atypia as carcinoma.

Esophagitis and esophageal motor abnormalities in patients with chronic spinal cord injuries.

To investigate the frequency and severity of esophagitis and esophageal dysmotility in patients with chronic spinal cord injury (SCI), 46 males with chronic SCI completed a questionnaire regarding gastrointestinal symptomatology. Eleven of these patients subsequently underwent upper gastrointestinal (GI) endoscopy with esophageal biopsies and 10 of the 11 also had esophageal motility studies. A significantly higher percentage of SCI patients experienced heartburn (SCI 61%; controls (C) 40%), esophageal chest pain (SCI 33%; C 6.4%), and intermittent dysphagia (SCI 30%; C 8.5%). Forty-five percent of SCI patients had endoscopic evidence of mild esophagitis, and 91% of them had histologic evidence of esophagitis. SCI patients had low amplitude, slowly propagating abnormal (double-peaked) peristatic esophageal contractions. We conclude that SCI patients experience significantly more esophageal symptoms than controls. They have a higher incidence of esophagitis and esophageal motor abnormalities. The clinical relevance of these abnormalities remains to be evaluated.

Mitomycin C-induced colitis in rats: a new animal model of acute colonic inflammation implicating reactive oxygen species.

The mechanism of the tissue damage induced by colonic inflammation in ulcerative colitis is not established. We therefore developed and characterized a simple new rat model of acute colonic inflammation induced by a single systemic injection of mitomycin C. After an intraperitoneal injection of mitomycin-C, colon histologic examination revealed transient (3 to 14 days) diffuse, colonic inflammation and injury that, like human ulcerative colitis, was limited to the mucosal layer. The rest of the gastrointestinal tract was spared. Gut permeability, as measured by urinary excretion of orally administered lactulose and mannitol, was unchanged 3 days after injection, when inflammation was already present; permeability was increased at 7 days, when inflammation was maximal. Mitomycin C did not produce inflammation in experimentally bypassed segments of small bowel despite the presence of colonic-type bacteria, suggesting that lack of intraluminal bacteria was not responsible for the absence of inflammation in the small intestine. Chemiluminescence, a means of estimating levels of reactive oxygen species, was greater in the intact, inflamed colon of mitomycin C-treated rats than in bypassed segments. Moreover, inflamed mucosal scrapings produced more in vitro luminol-enhanced chemiluminescence. Furthermore, the reactive oxygen species scavengers allopurinol, catalase, and WR-2721 decreased inflammation severity. We therefore conclude: (1) the mitomycin C-treated rat is a novel, easy to prepare animal model of acute inflammation of colonic mucosa, with morphologic similarities to the acute phase of ulcerative colitis in human beings; (2) increased gut permeability in mitomycin C-treated rats is the result, not the cause, of the inflammation; and (3) reactive oxygen species play an important role in colonic inflammation and tissue injury in this model, and possibly in human ulcerative colitis.

Barrett's esophagus. The cytology of dysplasia in comparison to benign and malignant lesions.

Barrett's esophagus (BE) is the replacement of esophageal squamous epithelium by columnar-lined mucosa and carries an increased risk of carcinoma. Endoscopic surveillance has been suggested, but esophageal brush cytology (BC) has not been widely utilized. Cytologic descriptions of BE, especially dysplasias, are sparse. We studied matched cytologic and histologic materials from 26 patients with BE and 4 patients with concurrent BE and adenocarcinoma. In six patients without dysplasia on biopsy, BE was recognized on BC by the presence of goblet cells within clusters of uniform columnar cells with vesicular nuclei. Dysplasia in 18 BC samples revealed small clusters of haphazardly oriented, mildly pleomorphic cells. Their larger nuclei had thickened membranes, evenly dispersed chromatin and occasional multiple nucleoli. The cytologic differentiation of histologically graded low- and high-grade dysplasia was difficult. The carcinoma cases displayed numerous isolated cells exhibiting flagrant malignant features. We conclude that BE lesions are cytologically distinctive and suggest that BC may play a role in surveillance.

Retroperitoneal mesenchymal chondrosarcoma. Report of a case diagnosed by fine needle aspiration cytology.

An unusual case of retroperitoneal mesenchymal chondrosarcoma diagnosed by fine needle aspiration (FNA) biopsy is described. CT-guided FNA of a mass arising in retroperitoneal soft tissues yielded an amorphous, myxoid material containing two distinct and separate populations of tumor cells. One was an undifferentiated, monomorphic, small cell component with granular cytoplasm and round central nuclei. The second population was an overtly malignant chondroid component scattered within an abundant myxoid matrix showing foamy cytoplasm, marked nuclear pleomorphism and frequent multi-nucleation. These cytologic findings were distinctive and similar to the histologic findings. The differential diagnosis and the possible pitfalls in the FNA diagnosis of this relatively rare tumor are discussed.

Immunophenotype of small cell lung carcinoma. Expression of NKH-1 and transferrin receptor and absence of most myeloid antigens.

NKH-1 is a monoclonal antibody that reacts with human natural killer (NK) cells and neural tissue. Because other monoclonal antibodies reacting with NK cells have been found on small cell lung carcinoma (SCLC), frozen tissue sections of 22 lung tumors including nine SCLC, two bronchial carcinoids, and 11 non-SCLC were tested for the presence of NKH-1 antigen by a sensitive alkaline phosphatase/anti-alkaline phosphatase technique. The labeling reactions of NKH-1 in frozen tissue sections were compared with reactions of a panel of 21 other monoclonal antibodies against NK cells, leukocyte antigens, cytokeratins, or nonlineage specific antigens. The antibody NKH-1 reacted strongly and diffusely with all of the SCLC and bronchial carcinoids but with none of the non-SCLC. NKH-1 also strongly labeled peripheral nerves in tissues adjacent to tumor. Two antibodies to cytokeratins reacted with all of the tumors and outlined tumor cells well, distinguishing them from surrounding stromal cells and leukocytes. OKT9, an antibody against transferrin receptor labeled all SCLC and eight of 11 non-SCLC but did not react with bronchial carcinoid. The antibodies Leu-M1, OKT10, Leu-7, and My4 reacted with 67%, 33%, 22%, and 11%, respectively, of the SCLC tested. The remaining 14 antibodies, including several with leukocyte specificity, labeled neither SCLC nor bronchial carcinoid. Thus, SCLC has a distinct immunophenotype (NKH-1 positive, keratin positive, and transferrin receptor positive), which may be helpful distinguishing this tumor from other tumors of lung including non-SCLC. SCLC infrequently expresses other leukocyte-associated antigens.

Quantitation of estrogen receptor content and Ki-67 staining in breast carcinoma by the microTICAS image analysis system.

The microTICAS image analysis system, originally designed for karyometry using Papanicolaou-stained or Feulgen-stained smears and tissue sections, has been adapted to assess tissue sections stained by immunohistochemical techniques. This system was used to quantitate growth fractions and the estrogen receptor (ER) content of breast carcinomas stained by immunoperoxidase techniques. The results were similar to those obtained with nonautomated methods of quantitating immunohistochemically stained tissue sections and, in the case of ER content, were similar to the results obtained with cytosol estrogen binding methods. The findings show that the microTICAS system provides an objective alternative to visual counting of labeled cells in tissue sections stained for growth fraction or for ER content by immunohistochemical methods.

Alpha-lactalbumin in "common" epithelial tumors of the ovary. An immunohistochemical study.

Alpha-lactalbumin (AL) has been widely used as an immunohistochemical marker for mammary carcinoma. The authors have investigated the AL reactivity of 36 unselected ovarian epithelial neoplasms using the avidin-biotin-peroxidase immunoperoxidase technic. In eight serous cystadenocarcinomas, both the primary neoplasm and its metastases were examined. Of the 36 tumors, 7 (19.4%) showed positive staining for AL and 5 were of the serous type. The serous tumors showed moderate to strong staining reaction. Three serous cystadenocarcinomas were AL positive in both primary and metastatic sites, while the remaining five were negative in all sites. One mucinous cystadenoma and one clear cell carcinoma showed weak to moderately positive AL reactivity. There was no good correlation between AL positivity and the presence of malignancy or between AL positivity and tumor grade. In view of the relatively high AL reactivity in ovarian neoplasms, it is advisable to exercise caution in interpreting the presence of AL positivity as specific marker for mammary carcinoma.

Assessment of tumor cell kinetics by immunohistochemistry in carcinoma of breast.

Cell proliferation was assessed in 33 invasive breast carcinomas by an immunoperoxidase procedure using the monoclonal antibody, Ki-67, which reacts with a nuclear antigen in proliferating cells. The antibody labeled a variable proportion of tumor cells ranging from 3% to 60%. High numbers of Ki-67-positive cells were found in tumors with high mitotic rates, high nuclear grade, high histologic grade, and in premenopausal women. Tumors with low and intermediate Ki-67 labeling rates often had high estrogen receptor content, whereas tumors with high Ki-67 labeling rates were usually estrogen receptor negative. These correlations are similar to those previously reported for other measurements of cell cycle kinetics such as thymidine labeling index and suggest that immunohistochemical staining of invasive breast carcinoma for the Ki-67 epitope may provide cell cycle information not otherwise readily available to the clinician and may be useful in assessing prognosis in carcinoma of the breast.

Hepatitis in patients receiving intraarterial chemotherapy for metastatic colorectal carcinoma.

Fifty-one patients with metastatic colorectal carcinoma confined to the liver received intraarterial chemotherapy through the hepatic artery via a subcutaneous pump. The chemotherapy consisted of sequential 14-day infusions of floxuridine (FUDR) and dichloromethotrexate (DCMTX) or a 14-day infusion of FUDR and bolus mitomycin (MMC). Twenty-four patients (47%) developed hepatitis with an elevation of hepatic serum transaminase (serum glutamic oxaloacetic transaminase, SGOT, or serum glutamic-pyruvic transaminase, SGPT). The median time to develop hepatitis was 11 weeks after initiation of chemotherapy. The morphologic effects of chemotherapy were evaluated in eight patients with hepatitis. All the patients with hepatitis had normalization of the serum transaminases after temporary cessation of chemotherapy. There was a trend toward a greater chance of remission in patients who developed hepatitis. Sixty-seven percent of the patients with a therapeutic response had hepatitis, whereas only 33% of the patients without a response had hepatitis. However, this difference was not statistically significant. The occurrence of hepatitis was not related to FUDR dose, drug program (FUDR-DCMTX vs. FUDR-MMC), pump flow rate, hepatic arterial anatomy, sex, or age of the patients.

Liver pathology following hepatic arterial infusion chemotherapy. Hepatic toxicity with FUDR.

The authors reviewed the liver histopathology and the clinical features of eight patients with liver metastases from colorectal cancer who were treated by hepatic arterial infusion chemotherapy (HAIC) via an implantable pump (Infusaid). Before HAIC, these patients had no evidence of hepatitis, and results of liver biopsies performed on three patients showed only minor morphologic alterations. All the liver tumors responded to HAIC, but all patients developed hepatitis. Clinical findings included nausea, vomiting, abdominal pain and jaundice. Serum transaminases, alkaline phosphatase and bilirubin levels were increased. Clinical observations suggested that 5-fluoro-2'-deoxyuridine (FUDR), the predominant drug given, was the hepatotoxic agent. Toxic effects were hepatocyte necrosis, steatosis, cholestasis, central vein sclerosis, and alterations in the portal triad. In addition, central vein lesions like those in veno-occlusive disease, and micronodular cirrhosis resembling that induced by alcohol, were encountered. Although individual susceptibility to FUDR appeared to vary, portal triad fibrosis was present in all eight cases and, together with central vein sclerosis and cirrhosis, appeared to be related to the dose and duration of HAIC.