Pathology of large-caliber stereotactic biopsies in nonpalpable breast lesions.

We report the surgical pathology experience with large caliber stereotactic biopsies for non-palpable breast lesions in 217 patients. The aim is to compare the demographics to another somewhat similar center (#2), and to published results with the much smaller stereotactic needle biopsies, including our own historical controls. The large caliber tissue specimens yielded proportionally fewer nonspecific diagnoses, with remaining areas of difficulty. An evolving diagnostic strategy is outlined.

Pathology of the breast in children, adolescents, and young adults.

The pathologic spectrum of breast disease in children and adolescents is broad and includes entities more commonly seen in older patients. In general, the vast majority of breast masses in young patients are benign with fibroadenomas, gynecomastia, and macromastia accounting for the majority of surgical specimens. Malignant tumors are more likely to be secondary or metastatic than primary. Rhabdomyosarcoma and hematolymphoid tumors comprise a majority of malignant diagnoses in children. Primary carcinomas and sarcomas are rare, especially if sarcomas arising in the setting of cystosarcoma phyllodes are excluded.

Sequence-ready contig for the 1.4-cM ductal carcinoma in situ loss of heterozygosity region on chromosome 8p22-p23.

We report the construction of an approximately 1.7-Mb sequence-ready YAC/BAC clone contig of 8p22-p23. This chromosomal region has been associated with frequent loss of heterozygosity (LOH) in breast, ovarian, prostate, head and neck, and liver cancer. We first constructed a meiotic linkage map for 8p to resolve previously reported conflicting map orders from the literature. The target region containing a putative tumor suppressor gene was defined by allelotyping 65 cases of sporadic ductal carcinoma in situ with 18 polymorphic markers from 8p. The minimal region of loss encompassed the interval between D8S520 and D8S261, and one tumor had loss of D8S550 only. We chose to begin physical mapping of this minimal LOH region by concentrating on the distal end, which includes D8S550. A fine-structure radiation hybrid map for the region that extends from D8S520 (distal) to D8S1759 (proximal) was prepared, followed by construction of a single, integrated YAC/BAC contig for the interval. The approximately 1730-kb contig consists of 13 YACs and 27 BACs. Fifty-four sequence-tagged sites (STSs) developed from BAC insert end-sequences and 11 expressed sequence tags were localized within the contig by STS content mapping. In addition, four unique cDNA clones from the region were isolated and fully sequenced. This integrated YAC/BAC resource provides the starting point for transcription mapping, genomic sequencing, and positional cloning of this region.

Colonic chicken skin mucosa: an endoscopic and histological abnormality adjacent to colonic neoplasms.

OBJECTIVES: We recently described an endoscopic finding of pale yellow-speckled mucosa adjacent to colonic neoplasms. This resembled the appearance of chicken skin and was named chicken skin mucosa (CSM). CSM differs from previously reported gastrointestinal xanthelasmas in that this entity always occurs in association with colonic neoplasms. The prevalence, endoscopic characteristics, clinical significance, and possible etiology were investigated. METHODS: Eight hundred fifty-two consecutive colonoscopies were prospectively evaluated for the presence of CSM associated with either cancer or adenomas > or = 1 cm. Electron microscopy and histopathology using hemotoxylin and eosin, mucicarmine, and oil red O stains were performed. Twelve consecutive colon cancer resection specimens were prospectively examined to determine the presence of histologic CSM. RESULTS: CSM was adjacent to eight of 10 distal colorectal cancers, one of four proximal colon cancers, 16 of 42 distal adenomas, and three of 44 proximal adenomas. Four of seven resected distal cancers demonstrated histological evidence of CSM. Biopsies of the CSM revealed that lipid-filled macrophages in the lamina propria were responsible for this endoscopic appearance. Electron microscopy showed that the surface epithelial cells had small intestine-like microvilli. CSM was not seen with other colonic conditions and was not associated with the laxative preparation. In four instances, identification of the CSM alerted the endoscopist to the presence of polyps in locations difficult to visualize. CONCLUSIONS: CSM is an endoscopic entity that occurs as a result of fat accumulation in macrophages in the lamina propria of the mucosa adjacent to colonic neoplasms. Small intestine-like microvilli were present in CSM and the pathophysiological implications remain to be elucidated.

Treatment with 16,16'-dimethyl prostaglandin E2 before and after induction of colitis with trinitrobenzenesulfonic acid in rats decreases inflammation.

Colitis was induced in rats by intrarectal administration of trinitrobenzene sulfonic acid (80 mg/kg, in 30% ethanol). An acute inflammation with ulcers and neutrophil infiltration developed that evolved into a chronic inflammation and luminal narrowing with attendant smooth muscle hypertrophy. We assessed the effects of 16,16-dimethyl prostaglandin E2, administered either before or after trinitrobenzene sulfonic acid, on the development of inflammation. Inflammation was assessed by gross appearance using a grading scale (0-4) and by histology. The number of neutrophils present in inflamed colonic tissue was quantitated by the myeloperoxidase assay. The production of lipoxygenase products was monitored by incubation of colonic specimens with [14C]arachidonic acid and separation of the products by thin-layer chromatography and high-pressure liquid chromatography. Levels of leukotriene B4 were measured in tissue extracts by high-pressure liquid chromatography and ultraviolet absorbance. Eicosanoid production was also assayed by incubating colonic specimens and assaying the media for prostaglandin E2, leukotriene B4, and leukotriene C4 by radioimmunoassay. Trinitrobenzene sulfonic acid treatment resulted in a greatly increased amount of leukotriene B4 in the media. Treatment with 16,16-dimethyl prostaglandin E2 before administration of trinitrobenzene sulfonic acid resulted in a lower inflammation index, lower myeloperoxidase activity, and decreased production of leukotriene B4. Administration of 16,16-dimethyl prostaglandin E2 24 h after administration of trinitrobenzene sulfonic acid was also effective in reducing the inflammatory response. Treatment with 16,16-dimethyl prostaglandin E2 also prevented the development of long-term architectural changes 3 wk after administration of trinitrobenzene sulfonic acid. Rectal administration of dimethyl prostaglandin E2 also diminished the colitis induced by direct injection of trinitrobenzene sulfonic acid into the colonic wall.

Surgical therapy in two patients with pedunculated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) occurring as an appendage from the main hepatic parenchyma is a rare entity, of which two cases are herein described. Because proper surgical management of this tumor (pedunculated HCC) is unclear, the world's literature was reviewed to determine optimal therapy. Thirty-four cases were documented, including the two cases reported herein. Diagnosis was usually obscure, despite modern invasive and noninvasive methods, and laparotomy or autopsy were required for specific identification of tumor type. Sixteen resections were reported among 18 explorations. One patient had transarterial embolization. Fifteen received medical therapy only. Surgically treated patients usually died of metastatic disease, whereas most medically treated patients died of gastrointestinal or tumor hemorrhage. Pedunculated HCC may be more amenable to curative resection than ordinary HCC due to its unique localization and growth pattern.

Arachidonate lipoxygenase products and renal allograft rejection in dogs.

The production of 12-hydroxyeicosatetraenoic acid (12-HETE) and leukotriene B4 (LTB4) was studied in renal tissue obtained from renal allografts and normal kidneys of nonimmunosuppressed dogs that had undergone unilateral renal allotransplantation. We have shown that allografted renal cortex undergoing rejection synthesizes significantly greater quantities of 12-HETE than normal or autotransplanted control renal cortex. There was no significant increase in 12-HETE production by allografted medulla undergoing rejection. Production of LTB4 was significantly greater in the rejecting renal cortex compared to control renal cortex but was not different in the rejecting compared to normal renal medulla. Production of 12-HETE and LTB4 was significantly inhibited by the lipoxygenase-cyclooxygenase inhibitor BW755C, suggesting that production of these compounds was enzyme catalyzed. Histologic examination of renal tissue undergoing rejecting revealed varying degrees of tissue destruction and cellular infiltration. These histologic parameters correlated with the magnitude of 12-HETE production in the allografts. Our findings therefore indicate that arachidonate lipoxygenase products are generated in increased amounts by renal cortical tissue undergoing rejection and suggest that these products may be involved in the rejection process.

Benign extrinsic compression of the common bile duct: a case report.

Painless obstructive jaundice is usually the result of malignant compression of the distal common bile duct. Infrequently extrinsic benign lesions may also cause ductal obstruction and be mistaken for a malignant process. A case of compression of the distal common bile duct is described. Preoperative evaluation was most consistent with a cystadenocarcinoma of the head of the pancreas. At operation we found an enlarged and calcified periductal lymph node with associated fibrosis and compression and obstruction of the distal common duct. Massive dilatation of the distal common duct and the cystic duct remnant gave it the appearance of a cystic mass in the superior border of the head of the pancreas. Resection and choledochoduodenostomy were curative.

So-called glandular schwannoma: ependymal differentiation in a case.

A cervical root tumor in a patient with neurofibromatosis showed a biphasic pattern of spindle and epitheloid cells with prominent "gland" formation, characteristic of the so-called glandular schwannoma. Electron microscopy and histochemistry of the "glands" disclosed features consistent with an ependymal differentiation. It is noted that there is a curious preferential association of ependymal lesions and neurofibromatosis, the pathogenesis of which is not understood.

Presence of inflammatory cells associated with exaggerated arachidonic acid metabolism in renal injury.

Unilateral ureter obstruction induces an exaggerated prostaglandin release from isolated perfused rabbit kidneys in response to vasoactive peptides. Perfused hydronephrotic kidneys also exhibit the release of thromboxane A2 which is not detected with normal or contralateral kidneys. Reversal of the ureteral obstruction causes a decreased production of PGs and TxA2 in response to bradykinin. Morphological examination of the HNK demonstrates an enlarged interstitial space containing a fibroblast-like cell and the presence of mononuclear cells. Administration of endotoxin to the perfused HNK elicits the release of PGE2 and TxB2 consistent with the ability of endotoxin to stimulate arachidonic acid metabolism in cultured macrophage. Rabbit CLK and the cat HNK, which are deficient in macrophages, exhibit minimal PGE2 and no detectable TxA2 release after endotoxin stimulation. Cells cultured from the rabbit HNK cortex contain fibroblast-like cells and phagocytic cells which respond to BK with a profound PG production. Conditioned media from mononuclear cells have been shown by others to stimulate PGE2 production from fibroblasts. Other models of renal disease (renal venous constriction and glycerol-induced tubular necrosis) exhibit exaggerated PG and TxA2 release and facilitated cortical microsomal AA metabolism. These data suggest that proliferation of fibroblast-like cells and the presence of mononuclear cells may be involved in this exaggerated PG and TxA2 production underlying renal injury.

Metabolic and cellular alterations underlying the exaggerated renal prostaglandin and thromboxane synthesis in ureter obstruction in rabbits. Inflammatory response involving fibroblasts and mononuclear cells.

Unilateral ureter obstruction in rabbits produced profound changes in endogenous and exogenous renal arachidonic acid metabolism. Isolated perfused hydronephrotic kidneys (removed after 3 or 10 d of ureter obstruction) responded to bradykinin stimulation with a markedly enhanced release of prostaglandin E2 and thromboxane A2. Reversal (3 or 10 d) of the ureter obstruction resulted in a reduction in the vasoactive peptide-induced release of prostaglandin E2 and thromboxane A2 from the perfused hydronephrotic kidney. However, postobstruction reversal of prostaglandin production by the agonist-stimulated perfused kidney was not reflected in the cortical microsomal cyclooxygenase activity, which is greatly enhanced during ureter obstruction and does not decrease after removal of the obstruction. Histological analysis of the renal cortex in rabbits with ureteral obstruction revealed a proliferation of fibroblast-like cells and the presence of mononuclear cells; removal of the obstruction did not result in a disappearance of cortical fibroblasts but did result in a decrease of monocytes. The critical involvement of mononuclear cells in the exaggerated arachidonate metabolism that occurs during hydronephrosis was exhibited by the demonstration that: (a) only the perfused hydronephrotic rabbit kidney responded to administration of endotoxin with a sustained release of prostaglandin E2 and thromboxane A2; (b) the contralateral rabbit kidney, which is devoid of mononuclear cells, did not respond to endotoxin; and (c) the hydronephrotic cat kidney, which exhibits a fibroblast proliferation with a low number of mononuclear cells, did not respond to endotoxin. Thus, proliferation of fibroblast-like cells and the presence of mononuclear cells appear to be involved in the exaggerated prostaglandin and thromboxane production underlying hydronephrosis. The increase in microsomal cyclooxygenase activity is apparently most closely correlated with the increased fibroblastic activation and cellularity, whereas mononuclear cells (possibly via monokines) seem to be critical for the markedly enhanced prostaglandin and thromboxane release induced by endotoxin and bradykinin.

Clinical and histologic indications for extensive pancreatic resection in nesidioblastosis.

Nine children with nesidioblastosis underwent pancreatic resection at St. Louis Children's Hospital. Four of these underwent 99 percent of near-total resection. Only one child required permanent insulin therapy postoperatively. Pathologic examination of the resected pancreases revealed a diffuse disturbance of the pancreatic architecture. Prolonged hypoglycemia can have devastating neurologic sequelae. Based on clinical experience and the pathologic demonstration of a diffuse process in the affected pancreas, it is advocated that near-total (99 percent) pancreatectomy is the primary procedure of choice for this disease.

Acromegaly and Cushing's syndrome associated with a foregut carcinoid tumor.

We report an 18-yr-old youth with a metastatic foregut carcinoid tumor, Cushing's syndrome, and hypersomatotropic gigantism. Administration of cyproheptadine caused a dramatic fall in urinary cortisol excretion and plasma ACTH levels associated with clinical remission of the Cushing's syndrome. GH secretion was not affected by cyproheptadine administration. Ectopic ACTH secretion was confirmed by RIA of tumor extracts and immunohistochemical demonstration of ACTH-containing cells in hepatic metastases. There were two sources of GH production demonstrated in this patient. Ectopic secretion of GH by the carcinoid hepatic metastases was documented by both RIA and immunohistochemical techniques. A somatotrophic pituitary tumor was also present. The histological characteristics of this tumor suggest adenomatous hyperplasia rather than de novo neoplastic change as the likely mechanism of its pathogenesis. GH releasing factor-like activity was demonstrated in extracts of plasma and in extracts of the carcinoid tumor. We conclude that cyproheptadine exerted an effect on the ectopic ACTH-producing cells but not on the ectopic GH-producing cells or on adenohypophyseal GH secretion. Production of a GH releasing factor-like activity by the carcinoid tumor may have caused the pituitary somatotrophic tumor.