G. Richard Dickersin

SOLITARY FIBROUS TUMORS OF THE PLEURA: EIGHT NEW CASES AND REVIEW OF 360 CASES IN THE LITERATURE

Three‐hundred‐sixty cases of solitary fibrous tumor of the pleura from the literature are analyzed, and eight new cases are described. Of patients reported on prior to 1972, 72% had symptoms due to the tumor at the time of diagnosis, but only 54% of patients reported on since then were symptomatic. This probably reflects earlier diagnosis as a result of increased use of chest radiographs in asymptomatic populations. Cough, chest pain, dyspnea, and/or pulmonary osteoarthropathy are each found in at least one‐third of patients who have symptoms. Approximately 80% of solitary fibrous tumors of the pleura originate in the visceral and 20% in the parietal pleura. In the literature and in this experience these tumors are on the whole circumscribed. They range in size from 1–36 cm with a mean of 6 cm. Many are pedunculated on pleural‐based pedicles that contain hypertrophic arteries and veins. Histologic examination of the tumor usually discloses cellular areas alternating with hyalinized and/or necrotic areas. Spindle‐shaped cells typically have minimal nuclear pleomorphism and rare or absent mitoses. Numerous thin‐walled vessels constitute an additional feature of large tumors. Electron microscopical examination reveals features of both fibroblasts and mesothelial cells. Solitary fibrous tumors behave in a benign fashion in 88% of cases after surgical resection. In 12% of the cases the tumor is responsible for the patients death because of its extensive intrathoracic growth, by virtue of either late diagnosis or unresectable recurrence. No single histologic feature allows a definite prognosis. The best indicator of a good prognosis is the presence of a pedicle supporting the tumor. Also favorable is circumscription of the tumor without invasion of lung, mediastinum, or chest wall. Nuclear pleomorphism and a high mitotic rate are seen in larger tumors but do not necessarily indicate a poor prognosis if the tumor is circumscribed. Solitary fibrous tumors of the pleura are not associated with asbestos.

Ovarian sex cord tumor with annular tubules. Review of 74 cases including 27 with Peutz‐Jeghers syndrome and four with adenoma malignum of the cervix

The sex cord tumor with annular tubules (SCTAT) is a distinctive ovarian neoplasm the predominant component of which has morphologic features intermediate between those of the granulosa cell tumor and those of the Sertoli cell tumor; focal differentiation into either granulosa cell or Sertoli cell tumor may occur. Of the 74 cases that form the basis of this investigation 27 were associated with the Peutz‐Jeghers syndrome; these tumors were all benign and were typically multifocal, bilateral, very small or even microscopical in size and calcified. Twelve of the 27 patients had symptoms suggestive of hyperestrinism attributable to the SCTAT; menstrual irregularity had occurred in eleven cases and post‐menopausal bleeding in one. Four of the 27 patients had “adenoma malignum” of the cervix and two of them died of it. The 47 tumors from patients without evidence of the Peutz‐Jeghers syndrome were unilateral and usually large. Twenty‐five of them were accompanied by symptoms suggestive of hyperestrinism, such as menstrual irregularity, postmenopausal bleeding or sexual precocity; seven were malignant and four of these were fatal.

Crohn's disease: Transmission electron microscopic studies: II. Immunologic inflammatory response. Alterations of mast cells, basophils, eosinophils, and the microvasculature

Transmission electron microscopy was done using surgically resected specimens from 12 patients with Crohns disease and three control subjects. Nonulcerated involved areas of ileum as well as proximal, grossly uninvolved resection margins were chosen for study. Specimens for transmission electron microscopy were prepared for viewing by a variety of techniques. Six hundred five Epon embedded blocks were studied by light microscopy, and 112 of these were viewed in the transmission electron microscope. Study of the immunologic inflammatory response revealed a number of changes of interest. The number of mast cells was markedly increased, and they were found predominantly in edematous submucosa and between smooth muscle cells in the muscular coats of the involved gut. Evidence of focal and complete degranulation of mast cells was frequently seen. Basophilic leukocytes, some of which had degranulated, were also identified. Another frequently encountered cell, the eosinophil, showed changes in the granules, which might reflect the release of eosinophil granule materials. Eosinophils also contained an increased number of small dense granules of the arylsulfatase containing type. Eosinophils, basophils, and mast cells formed close associations. Evidence of acute and chronic damage to vascular endothelia was present. Small lymphocytes, plasma cells, macrophages, and epithelioid cells were present. Multinucleated giant cells were infrequently encountered. Lymphoblasts, however, were rarely seen.

Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases

Background. Desmoplastic neurotropic melanoma (DNM) is a rare variant of malignant melanoma, the natural history and histogenesis of which still are being defined.

Cytokeratin expression in epithelioid vascular neoplasms

Seven epithelioid and eight non-epithelioid vascular tumors were studied by the avidin-biotin-peroxidase method for the presence of endothelial- and epithelial-associated markers, using Ulex europaeus agglutinin-1 (UEA-1) lectin, and antibodies directed against factor VIII-related antigen, (FVIII-RA), vimentin, keratin, carcinoembryonic antigen, and epithelial membrane antigen. The cases included four epithelioid hemangiomas, two epithelioid hemangioendotheliomas (EHE), one epithelioid angiosarcoma (EAS), four common non-epithelioid capillary hemangiomas, and four non-epithelioid angiosarcomas. Staining for FVIII-RA, UEA-1, and vimentin were observed in all cases. The EAS showed staining for keratin in formalin-fixed, paraffin-embedded sections and in frozen sections. Staining for keratin was also observed in frozen sections of one EHE. Both keratin-positive vascular tumors were confirmed with electron microscopy. Carcinoembryonic antigen and epithelial membrane antigen stains were negative in all cases. Our results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin. This is important since these tumors may closely resemble carcinomas by routine light microscopy. This study further underscores the importance of using a broad panel of immunohistochemical markers in the diagnostic workup of soft-tissue neoplasms.

Small cell carcinoma of the ovary with hypercalcemia: A report of eleven cases

Eleven cases of a small cell ovarian cancer associated with hypercalcemia that was reversed by removal of the tumor are reported and compared with three similar cases in the literature. The 14 cases account for 50% of recorded cases of ovarian‐cancer‐related hypercalcemia. The 14 tumors occurred in women between the ages of 13 and 35, with an average of 22 years and, with two exceptions, behaved clinically in an aggressive fashion. Light and electron microscopic study confirmed the epithelial nature of the neoplasms but failed to disclose their specific subtype or origin.

Hepatoid yolk sac tumor of the ovary (Endodermal sinus tumor with hepatoid differentiation) : A light microscopic, ultrastructural and immunohistochemical study of seven cases

Seven cases of ovarian yolk sac tumor (endodermal sinus tumor) with patterns resembling those of hepatocellular carcinoma were encountered in patients 7–43 years of age. Two of the patients had gonadal dysgenesis with a 46XY karyotype. At operation three tumors were confined to the ovary and four were associated with intra‐abdominal metastases. Two of the Stage I tumors recurred within one year. The hepatoid pattern was a prominent feature of all the tumors and was exclusive in four of them. In one specimen it merged almost imperceptibly with a polyvesicular vitelline pattern. The hepatoid component of the tumors was characterized by discrete masses, nests and/or broad bands of large polyhedral cells with central nuclei and prominent nucleoli; gland‐like spaces, some of which contained mucin, were occasionally evident. Each tumor contained numerous PAS‐positive, diastase‐resistant intracytoplasmic and extracytoplasmic hyaline bodies. Alpha‐fetoprotein and alpha‐1‐antitrypsin were identified by immunoperoxidase and immunofluorescence techniques in four tumors and albumin in two. Immunoperoxidase stains for chorionic gonadotropin were negative in four cases. Ultrastructural analysis of two specimens disclosed features similar to those of hepatocellular carcinoma.

Crohn's disease: transmission electron microscopic studies. III. Target tissues. Proliferation of and injury to smooth muscle and the autonomic nervous system.

Transmission electron microscopy was done on surgical specimens from 12 patients with Crohns disease and three control subjects. Nonulcerated involved areas of ileum as well as proximal, grossly uninvolved resection margins were chosen for study. Specimens for transmission electron microscopy were prepared by a variety of techniques and 112 blocks were examined by electron microscopy. The study was concentrated on two target tissues of the gut: the autonomic nervous system and the smooth muscle. Proliferative and injurious changes were found in each. Proliferation, myofibroblastic transformation, hypercontraction, and necrosis characterized the smooth muscle changes seen in Crohns disease of the ileum. Autonomic nervous system changes included proliferation of axons containing dense core granules (catecholamines) and axonal necrosis. The possible pathogenetic significance of these changes is discussed here and in the accompanying article beginning on page 606 of this issue.

CENTRAL NERVOUS SYSTEM NEUROCYTOMA AND NEUROBLASTOMA IN ADULTS-REPORT OF EIGHT CASES

SummaryThe clinical features, pathologic findings and treatment courses of eight adults with central nervous system small-cell neuronal tumors were reviewed. Five patients had central neurocytomas, two patients central nervous system neuroblastomas, and one patient a neurocytoma-like spinal cord tumor. The neurocytomas were intraventricular, moderately cellular tumors with bland nuclei and perinuclear halos. Patients with neurocytoma were treated with surgery, radiation therapy, and/or chemotherapy, and have followed favorable clinical courses. The neuroblastomas were intraparenchymal, hypercellular tumors with necrosis and frequent mitoses. Patients with neuroblastomas were treated with surgery, radiation therapy and chemotherapy, with some clinical response, but overall poor survival. One of the two patients developed extracranial metastasis. The spinal cord tumor had histologic features of neurocytoma, and responded well to biopsy and radiation therapy. The cases are compared with the varieties of small-celled neuronal tumors described in the literature, and pathologic, histogenetic and treatment implications are discussed.

Fatty acid ethyl esters decrease human hepatoblastoma cell proliferation and protein synthesis.

BACKGROUND/AIMS Fatty acid ethyl esters (FAEEs) are nonoxidative products of ethanol metabolism. They have been implicated as mediators of ethanol-induced organ damage because FAEE and FAEE synthase have been found specifically in the organs damaged by ethanol abuse. This study showed toxicity specifically related to FAEE or their metabolites for intact human hepatoblastoma-derived cells (HepG2). METHODS The lipid core of human low-density lipoprotein (LDL) was extracted and the LDL particle reconstituted with either ethyl oleate or ethyl arachidonate. Cultured HepG2 cells were incubated with LDL containing FAEE. Cell proliferation was measured by [methyl-3H]thymidine incorporation. Protein synthesis was determined using L-[35S]methionine. RESULTS Incubation of cells with 600 mumol/L ethyl oleate or 800 mumol/L ethyl arachidonate decreased [methyl-3H]thymidine incorporation into HepG2 cells by 31% and 37%, respectively. LDL reconstituted with 400 mumol/L ethyl oleate decreased protein synthesis in intact HepG2 cells by 41%. Electron microscopy revealed significant changes in cell morphology, particularly involving the cell nucleus. FAEE delivered in reconstituted LDL were rapidly hydrolyzed and the fatty acids re-esterified into phospholipids, triglycerides, and cholesterol esters, with preference for triglycerides. CONCLUSIONS These findings provide evidence that FAEE are toxic for intact human hepatoblastoma cells and that they or their metabolites may be an important causative agent in ethanol-induced liver damage.