Nephroblastoma-like tumors in patients with testicular germ cell tumors.

Nephroblastoma-like tumors (NLTs) developed in metastatic sites in nine men with testicular germ cell tumors (GCTs). These tumors had a characteristic "triphasic" admixture of primitive tubular structures, sometimes with a glomeruloid pattern, blastema and stroma. Skeletal muscle differentiation was apparent in two cases. Specific neuroendocrine markers (synaptophysin and chromogranin A) were negative. All patients were treated by surgical excision. Six patients were alive with no evidence of disease from 4 to 12 years after diagnosis of GCT and NLT. One patient was alive with disease 6 years after diagnosis of GCT and 3 years after diagnosis of NLT. One man who also had metastatic primitive neuroectodermal tumor (PNET) had short survival, and one patient died of postoperative infection. We conclude that patients with testicular GCTs in whom NLTs develop in metastatic sites often experience prolonged survival. Surgical excision appears to be adequate treatment for NLT arising in metastatic testicular GCT in most patients. It is important to distinguish NLTs from PNETs in metastatic GCTs because of the more aggressive course and the frequently fatal outcome of the latter.

Mucin-hypersecreting intraductal neoplasms of the pancreas: a precursor to cystic pancreatic malignancies.

BACKGROUND: Muncin-hypersecreting intraductal pancreatic neoplasms were first described in 1982 and have been observed in increasing numbers since. They are observed primarily by endoscopic retrograde cholangiopancreatography (ERCP) and are characterized by an intraductal papillary neoplasm that secretes thick mucin, causing pancreatic duct dilatation and obstructive pancreatitis. METHODS: Twenty patients are presented, 14 male and six female, with an average age of 59 +/- 11 years. All patients presented with abdominal pain, and most had nausea and vomiting, weight loss, and documented pancreatitis. Of the preoperative studies, ERCP was positive in all patients. Computed tomography scan, endoscopic ultrasonogram, and cytologic findings were less sensitive. Tumor markers were only positive in one patient. All 20 patients were treated surgically. Nine underwent Whipple procedure, one patient had a total pancreatectomy, and nine had distal pancreatic resections. The first patient in the series did not have a pancreatic resection, and his disease evolved into a lethal cystadenocarcinoma causing his death 99 months later. RESULTS: Histopathologic findings were interpreted as borderline malignant in 17 of the 20 patients, and three patients had evidence of invasive adenocarcinoma. Two of these three patients had nodal or distant metastases at the time of diagnosis, and all three died of adenocarcinoma. Seventeen of the patients are alive and well, although two of three with positive pancreatic margins have had recurrent symptoms and have been successfully reresected. CONCLUSIONS: The mucin-producing intraductal papillary tumor of the pancreas is a newly described variant of pancreatic cancer. It presents with symptoms of pancreatitis and has a progressive but more indolent course than the more lethal invasive ductal cancers. Patients with unexplained pancreatitis should undergo ERCP investigation, and aggressive surgical therapy should be carried out because the prognosis for this lesion, when appropriately treated, is more favorable than the usual pancreatic cancer.

Primitive neuroectodermal tumors arising in testicular germ cell neoplasms.

Twenty-nine young men (mean age 29 years) had primitive neuroectodermal tumors (PNETs) arising in germ cell tumors (GCTs). Nine patients had PNETs confined to the testis, eight patients had PNETs in the testis and at metastatic sites, and 12 patients had PNETs identified only at extratesticular sites. Immunohistochemistry was of use in the further classification of these PNETs as neuroblastoma, medulloepithelioma, peripheral neuroepithelioma, or ependymoblastoma. The histologic pattern of PNETs in the testis (neuroblastoma or medulloepithelioma) did not predict which tumors metastasized. PNETs localized to the testis did not affect prognosis. Eight patients with no PNETs outside the testis were free of disease 1 month to 10 years after diagnosis. PNETs in extratesticular sites were an adverse prognostic factor. Nineteen patients with extratesticular PNETs had adequate clinical follow-up. Thirteen are dead of disease from 4 months to 5 1/2 years (mean 26 months) after diagnosis, four are alive with disease 6 months to 2 years after diagnosis, and two have no evidence of disease with short follow-up (6 and 17 months). Mean survival was longer (34 months) for patients whose extratesticular PNET was neuroblastoma than for those with other types of PNETs (13 months). Chemotherapy directed against GCTs was not effective in patients who developed metastatic PNETs of GCT origin. We conclude that extratesticular PNETs in patients with testicular GCTs are usually fatal, but patients with neuroblastomatous metastases may have a more prolonged course.

Desmoplastic small round cell tumors of the paratesticular region. A report of six cases.

Desmoplastic small round cell tumor (DSRCT) typically occurs in the abdomen but may also present at other sites. We report six cases of paratesticular DSRCT. The patients, who ranged in age from 17 to 37 (mean, 28) years, presented with a scrotal mass (five cases) or testicular pain (one case). Grossly, the tumors were white to tan and firm. Typically, they involved the paratesticular soft tissue, serosal surfaces and the epididymis near the junction with the rete testis. Microscopically, the tumors consisted of nests of mitotically active "small blue cells" with scant cytoplasm embedded in a densely fibrotic stroma. Two tumors showed focal tubule formation; one of these also formed rosettes. The tumors exhibited the typical immunophenotype of DSRCT (positivity for keratin, vimentin, desmin, and neuron-specific enolase but nonreactivity with HBA-71 and anti-S-100). Four tumors metastasized to lymph nodes (retroperitoneal, cervical, and two unspecified); pulmonary metastases occurred in one of these cases and in one patient without lymph node metastases. One of the above patients treated with chemotherapy, died of disease at 16 months. The patients with pulmonary metastases (one of whom also had lymph node metastases) were treated with aggressive chemotherapy and are alive and apparently disease-free at 2.5 and 3 years, respectively. Three of the six patients, two of whom had known metastases, were lost to follow-up. The DSRCT of the paratestis has histologic and immunohistochemical features identical to its abdominal counterpart and must be differentiated from other "small blue cell" tumors of the paratesticular region.

Proliferating thymolipoma: ultrastructural, immunohistochemical, and flowcytometric study.

A superior-anterior mediastinal tumor was excised from a 50-year-old man. The 207-g mass was encapsulated and multilobulated. It contained adipose tissue and abnormal thymic tissue. In some areas the thymic tissue was characterized by cords and nests of epithelial cells lying within either the adipose tissue or a myxoid matrix. Other areas were characterized by cortical thymic tissue with increased numbers of epithelial cells. Foci of normal medullary tissue were present. The prominent epithelial cells were immunoreactive for cytokeratin and nonimmunoreactive for vimentin, S-100, chromogranin, and parathyroid hormone. Flow cytometry showed that the lymphocyte populations were consistent with a late cortical thymic phenotype. The tumor was diploid. By electron microscopy, the prominent epithelial cells had desmosomes and a few tonofilaments. The cytoplasm contained additional organelles including mitochondria, polyribosomes, and occasional lysosomes. Nuclei were oval and had relatively smooth contours, prominent nucleoli, and moderate quantities of heterochromatin. Basal lamina was present around many nests and cords of cells. This is the first such study of a tumor with this histology.

Urachal cystadenoma with abundant glycogen: ultrastructural study.

A cystadenoma arose in the urachus of a 32-year-old man. The mass was a multilocular cystic tumor filled with light yellow mucoid material. It was located in the anterior abdominal wall between the umbilicus and the dome of the urinary bladder. Overall, the mass was 14 cm x 8 cm x 5 cm, with the largest internal cyst being 6 cm in diameter. The lesion was characterized histologically by columnar cells with focal cellular and nuclear stratification. Ultrastructural examination revealed columnar cells with abundant glycogen, moderately pleomorphic microvilli without prominent filamentous cores, and apical mucin vacuoles. Nuclei had pleomorphic contours. An intact basal lamina was present. A similar urachal cystadenoma has not been described.

Hepatoblastomas: an ultrastructural and immunohistochemical study.

Seven hepatoblastomas were studied by electron microscopy, and four of these were studied by immunohistochemistry. Five tumors were purely epithelial, and two were mixed epithelial-mesenchymal. They showed a spectrum of cellular differentiation ranging from primitive epithelial cells to differentiated cells resembling adult hepatocytes. Glycogen, lipid, basal lamina, and canaliculi were present in all cases. Mitochondria with large, membrane-bound, amorphous inclusions were present in one tumor, and large, complex, basal cell processes were present in two tumors. Ultrastructural features most characteristic of hepatocytes were most common in fetal type hepatoblastomas. Immunoreactive chromogranin cells were present in two tumors, one of which also contained immunoreactive somatostatin cells. The somatostatin-positive tumor had cells with granules resembling those seen in somatostatin-containing cells of normal pancreas and somatostatin-containing neuroendocrine carcinomas. Other immunoreactive substances were present, including alpha 1-antitrypsin (four cases), vimentin (embryonal cells in four cases; fetal cells in three cases), low-molecular weight cytokeratin (embryonal cells in three cases; fetal cells in four cases), and high-molecular weight cytokeratin (embryonal cells in one case; fetal cells in two cases). Osteoidlike material was positive for epithelial membrane antigen, vimentin, and S-100 protein.

Improved intracellular morphology of Pneumocystis carinii from rat lung by postfixation with a mixture of potassium ferrocyanide and osmium tetroxide.

Pneumocystis carinii infected rat lungs were postfixed with a mixture of OsO4 and K4Fe(CN)6. A marked improvement in staining of cell membranes, endoplasmic reticulum, nuclear membranes and glycogen was observed. These improvements were seen in both the trophic and cystic forms of the organisms. The addition of K4Fe(CN)6 did not improve the staining of cell walls, microtubules or ribosomes. Trophozoites were seen attached to both type 1 and type 2 pneumocytes by filopodia and/or intercalation of the cell body of P. carinii with the host lung cells. It is expected that the improvement in ultrastructural detail will allow better understanding of the ultrastructure of P. carinii and provide insights into the modes of action of various antimicrobial compounds on this organism.

Fine-needle aspiration biopsy of small round blue cell tumors of childhood.

One hundred twenty-eight palpable and deep-seated fine-needle aspiration biopsies (FNAB) were done on pediatric patients at James Whitcomb Riley Hospital for Children and Indiana University Hospital between 1985 and 1988. During that 4-year period, 71 (56%) benign and 49 (38%) malignant diagnoses were made. Only eight (6%) of the FNAB were considered inadequate. Thirty-nine (80%) of the malignant aspirates were small round blue cell tumors of childhood (SRBCT). The SRBCT consisted of 21 (54%) lymphomas, 7 (18%) Ewing's sarcomas, 3 (8.5%) neuroblastomas, 3 (8.5%) rhabdomyosarcomas, 2 (5.0%) medulloblastomas, 2 (5.0%) Wilms' tumors, 1 (3.0%) retinoblastoma, and 1 (3%) granulocytic sarcoma. Fifteen (38%) of the SRBCT aspirates were obtained to render a primary diagnosis and 24 (62%) documented recurrence. Various combinations of electron microscopy, immunocytochemistry, and other special stains were used to confirm the diagnosis in 11 (28%) cases. These cases consisted of five lymphomas, two rhabdomyosarcomas, two Ewing's sarcomas, one neuroblastoma, and one granulocytic sarcoma. The technique of FNAB is a successful diagnostic tool for documenting primary and recurrent SRBCT in a pediatric population.

Endoscopic detection of a tiny cecal ulcer containing carcinoma in-situ.

A 3-mm cecal ulcer without any adjacent polypoid structure was detected in a 66-year-old asymptomatic man undergoing screening colonoscopy. Biopsies demonstrated carcinoma in-situ. The literature on tiny colonic carcinomas and carcinoma in-situ in the absence of any polyp is reviewed in this article.

The role of activation of neutrophils and microvascular pressure in acute pulmonary edema.

Activated polymorphonuclear neutrophils (PMN) can mediate vascular injury in the lung. This study compared activated aggregate PMN (emboli) to activated PMN that were previously adhered to the microvasculature (non-embolic) in the isolated perfused rat lung. Permeability and microvascular pressure (Pmv), components of PMN-induced edema, were examined by continuous measurement of wet weight, pulmonary arterial and left atrial pressures, and by intermittent determination of double occlusion pressure. PMN that were activated with phorbol myristate acetate and then perfused into the lung formed aggregates that lodged primarily in the precapillary bed, increasing arterial resistance. Although these PMN had minimal direct contact with the capillary endothelium, edema rapidly developed and Pmv was progressively elevated. If PMN were allowed to adhere in the capillary bed, a minimal and nonprogressive increase in Pmv and lung weight occurred. When these adherent PMN were then activated, there was a progressive rise in both Pmv and lung weight. The free radical scavenger catalase prevented this edema formation but not the rise in pressure. In control lungs with matched elevation of Pmv, edema did not develop. In another group of lungs with activation of pre-adherent PMN in which Pmv was maintained at control levels, edema formation was greatly delayed. These data show that: (1) the activated PMN free radical products alone caused permeability injury in the lung because neither contact of the PMN with the capillary endothelium nor embolization was necessary, and (2) increased Pmv does not cause edema but greatly increases the rate of edema formation when the endothelium is injured.

Ultrastructure of the epidermal-dermal junction and cutaneous basal lamina in Bowen's disease.

Ten tissue sections from 10 examples of Bowen's disease were excised from paraffin blocks, rehydrated, and incubated in 90% formic acid at 45 degrees C for 18 h. The epidermis was gently removed with the aid of a dissecting microscope, and the remaining dermis with attached basal lamina was processed for scanning electron microscopy. This surface showed a well-preserved basal lamina. The dermal papillae in the areas of Bowen's disease were elongated and had frequent secondary protrusions. The normal 0.5 mu interconnecting corrugations were often replaced by either broad, coarse corrugations or by large areas of smooth-to-undulating basal lamina. This study demonstrates marked alterations in spatial interactions between neoplastic epidermis and underlying dermis in Bowen's disease.

Role of microvascular pressure in reactive oxygen-induced lung edema.

O2 radicals are important in the pathogenesis of acute lung injury. The purpose of this investigation was to determine the role that microvascular pressure plays in edema induced by reactive O2 species generated by xanthine oxidase. In isolated rat lungs perfused with Krebs buffer plus 4% albumin, 5 mM glucose, and 2 mM xanthine at constant flow (13 ml/min), addition of xanthine oxidase (0.02 U/ml) caused a progressive increase in both pulmonary arterial and microvascular pressure (double occlusion method), which preceded the onset of edema. Both the pressure rise and edema formation were blocked by catalase, suggesting that vascular injury was related to H2O2 production. Lungs not exposed to free radicals that had microvascular pressure elevated to match that of the xanthine oxidase-perfused lungs showed only a small, reversible (nonedematous) weight gain. Lungs exposed to xanthine oxidase but perfused at constant microvascular pressure (5 Torr, similar to control lungs) showed a significant delay in protein-rich edema formation. These data indicate that reactive O2 metabolites induced lung injury, which is accompanied by increased microvascular pressure. Although the rise in microvascular pressure was shown not to be essential for edema formation, it does play a role in acceleration of the rate of transvascular fluid loss.

An enzyme immunoassay procedure for cancer antigen 125 evaluated.

The performance of a new enzyme immunoassay (EIA) procedure (Abbott Labs.) for cancer antigen 125 (CA 125) met or exceeded the manufacturer's claims for all analytical variables examined. Overall correlation with results obtained with a radioimmunoassay (RIA) were good. However, near the decision thresholds typically chosen to define a positive result for ovarian carcinoma, EIA results were 10 to 20 arbitrary units/mL less than the RIA results. At specific decision thresholds, therefore, the sensitivities and specificities of the EIA and RIA procedure differed. Adjusting the decision thresholds gave a similar optimum efficiency for each procedure: EIA, 82.9% (decision threshold, 35 units/mL); RIA, 83.4% (decision threshold, 54 units/mL). Receiver-operating characteristic curves showed that the two procedures' ability to distinguish patients with active ovarian carcinoma from those with disease in remission was the same.

Osteosarcoma of the uterine cervix associated with hyperplastic and atypical mesonephric rests.

The authors describe a unique case of osteosarcoma associated with atypical mesonephric rests occurring in the right lateral wall of the uterine cervix. The tumor was examined histologically, cytologically, immunohistochemically, and ultrastructurally and was compared with another osteosarcoma that filled an entire uterine cavity. Comparison with other neoplasms of the uterine cervix indicates that the lesion should be classified separately. Previously reported neoplasms associated with mesonephric rests within the cervix are also reviewed.

Glycoconjugate expression in human renal oncocytomas. A lectin histochemical study.

A panel of lectins chosen for its specificity for segments of the nephron was used in an avidin-biotin-peroxidase reaction to stain 13 human renal oncocytomas and a specimen of oncocytomatosis. The lectins were derived from Lotus tetragonolobus, Glycine max, Dolichos biflorus, and Arachis hypogaea. Two patterns predominated: one of staining with the lectins of D biflorus and G max, suggesting distal tubular or collecting-duct differentiation, and one of staining with the lectin of L tetragonolobus, suggesting proximal tubular differentiation.

Spindle cell sarcoma of the heart in childhood: light microscopic, ultrastructural, and immunohistochemical evidence for smooth muscle, endothelial, and fibroblastic differentiation.

We describe the clinical presentation and pathological features of a cardiac sarcoma that occurred within the right atrial cavity of a 14-year-old boy. The patient presented with a 2-month history of increasingly severe heart failure. Tumor tissue obtained by biopsy showed light microscopic features of leiomyosarcoma. Immunohistochemical reactions and ultrastructural studies provided evidence of tumor cell differentiation along three cell lines--smooth muscle, fibroblastic, and endothelial--suggestive of origin from a multipotent subendothelial reserve cell. Postmortem examination disclosed a large necrotic tumor filling the right atrial chamber. Implants were present on the pericardium, but there were no other metastatic lesions. The difficulty of making a diagnosis of these rare neoplasms when the tumor is small and potentially curable results in a grim prognosis.

Pancreatic cystadenoma in an infant: ultrastructural study.

A 10 x 6 x 4 cm multicystic cystadenoma arose in the pancreas of a 4-month-old male. Microscopically, the cysts were lined by short columnar or cuboidal cells that contained neither mucin nor glycogen. The lining cells had occasional nucleoli, contained electron dense vacuoles and apical aggregates of filaments, and were associated with a basal lamina. This is the youngest patient reported as having pancreatic cystadenoma, and the ultrastructure of the neoplasm was different from the 6 previously studied adult cases, suggesting that infantile and adult cystadenomas are different in nature.

Basal lamina fenestrations in the human colon: transmission and scanning electron microscope study.

Basal lamina at the interface between colonic epithelial cells and the lamina propria was exposed by incubating colonic specimens in 1% boric acid solutions. Examination of this epithelial-stromal interface by scanning electron microscopy (SEM) showed a smooth, slightly undulating basal lamina covering crypts and luminal surfaces. The basal lamina on the luminal surfaces had numerous round or ovoid fenestrations, most measuring 2.5-4.0 microns. These were continuous with channels in the collagen fiber network of the lamina propria. Except very near the surface, no fenestrations were found in the basal lamina lining the crypts. Transmission electron microscopy (TEM) of serial thin sections of colonic mucosa without the epithelial cells removed showed only a few actual basal lamina fenestrations. Rarely, epithelial cell processes extended into the lamina propria through the basal lamina. Most of the fenestrations seen by SEM appeared to correspond spatially by TEM to foci of close contact between the basal lamina and underlying fibroblastic cell processes. At these sites the basal lamina and fibroblastic cell process might be removed along with the overlying epithelial cells during processing with boric acid. These data support functional differences in epithelial-stromal interaction between cell populations lining the luminal surface and those making up the crypt lining and pericryptal fibroblast sheath. The TEM findings demonstrate that the human colonic basal lamina is not absolutely continuous and that the development of basal lamina fenestrations and epithelial cell processes extending into the lamina propria is not pathognomonic of neoplastic transformation and stromal invasion.