Flow cytometry, cellular DNA content, and prognosis in human malignancy.

The use of flow cytometry to analyze the cellular DNA content of human malignancies has become increasingly commonplace. The relationship between abnormalities in DNA content or proliferative characteristics and prognosis is becoming clear for a variety of malignancies in part through new techniques that permit analysis of archival material. High- and low-risk groups of patients with early breast and bladder carcinomas, non-small-cell lung cancer, and colorectal, ovarian, and cervical carcinoma can be distinguished on the basis of abnormal stemline DNA content. In several hematologic and common pediatric malignancies, the prognostic relevance of DNA content flow cytometry has been similarly established. Though the interpretation of tumor cell cycle analyses is less certain, this characteristic may also be prognostically important. However, generalizations cannot be made when applying flow cytometric DNA analysis to clinical decision making. The prognostic importance of an abnormal DNA histogram for an individual patient must be assessed on the basis of the relevant data base for that particular tumor type. The current extent of this data base for various malignancies is reviewed.

Evidence for neural origin and PAS-positive variants of the malignant small cell tumor of thoracopulmonary region ("Askin tumor").

The differential diagnoses of childhood and adolescent tumors composed of small round cells include a distinctive clinicopathological entity called malignant small cell tumor (MSCT) of the thoracopulmonary region in childhood. In the present study, 15 such tumors that fulfilled the criteria by Askin et al. were examined for features of possible neural differentiation by light and electron microscopy (EM). With hematoxylin-eosin stain (H&E) the tumors were made up of small undifferentiated cells; rosette formation was noticed in four cases. By immunohistochemistry all 15 tumors were positive for neuron/specific enolase (NSE), which is a specific marker for neural elements and their tumors including neuroblastomas. Ten of 15 MSCT had positive PAS staining. Ultrastructurally dense core (neurosecretory) granules and cell processes indicative of neuronal differentiation could be recognized in 10 of 14 tumors. The dense core granules were often atypical. Filamentous cytoskeleton, never observed in Ewing's sarcoma, was often present. Based on the current results, MSCT of the thoracopulmonary region can be considered a peripheral neuroectodermal tumor with the possible origin in intercostal nerves. MSCTs are generally misdiagnosed as Ewing's sarcoma due to their primitive appearance in H&E sections and their periodic acid-Schiff positivity. NSE immunostaining, preferably augmented by electron microscopy, is necessary for their correct diagnosis.

Histologic and immunohistochemical investigation of neuroblastomas and correlation with prognosis.

Forty-one confirmed cases of childhood neuroblastoma diagnosed over a 13-year period were reviewed and reclassified. Most of the tumors were stained using a peroxidase antiperoxidase method for neuron specific enolase (NSE), protein gene product (PGP) 9.5, and S100 protein, all of which have previously been reported to be positive in some neuroblastomas. The relation to prognosis of the histology and immunohistochemistry was studied. There was a significant trend toward improved survival with increasing degree of differentiation, and with decreasing mitosiskaryorrhexis index (MKI) in the stroma-poor group. There was no significant correlation between immunohistochemical staining and survival, although the presence and amount of staining for all three markers tended to increase with tumor differentiation. This study concludes that histologic classification in neuroblastoma is helpful in assessing prognosis but that the clinical features are generally more reliable as indicators of prognosis. The immunohistochemistry of markers used did not contribute towards assessment of prognosis.

Peripheral neuroepithelioma in childhood. Immunohistochemical demonstration of epithelial differentiation.

Peripheral neuroepithelioma arising from the chest wall of a 4-year-old girl is described. She died of local recurrence 15 months after surgery. Light- and electron-microscopic as well as immunohistochemical findings confirmed the neuroectodermal nature of the tumor. A distinctive histologic feature was the presence of clustered epitheliallike cells, which immunohistochemically stained positive for both keratin and carcinoembryonic antigen. The epithelial nature of these peculiar cells is presented.

Thoracic lymphangiomatosis.

We report the case of a 33-year-old man with thoracic lymphangiomatosis. The patient had experienced a 17-year history of recurrent chylothoraces and worsening cor pulmonale. The neoplasm was composed of histologically benign lymphatic channels lined by endothelial cells containing factor VIII-related antigen by immunohistochemical staining. The neoplasm filled the chest cavity, thereby compressing the lungs and involving the pleura, mediastinum, and thoracic vertebrae. We contrast this case with previous reports of lymphangiomatosis.

[Immunohistochemical findings in intrathoracic tumors. II. Demonstration of alpha 1-antitrypsin in tumor tissue]. / Immunhistochemische Befunde bei intrathorakalen Tumoren. II. Nachweis von alpha 1-Antitrypsin im tumorgewebe.

Immunohistological investigations for demonstration of alpha 1-antitrypsin were undertaken in different intrathoracic tumors. 60% of them showed deposits of alpha 1-antitrypsin in tumor tissue. Among different histological types, bronchial carcinomas showed the highest percentage of positive findings (= 75%). Negative findings were observed in carcinoid tumors and different neurogenic tumors.

Ganglioside composition of human neuroblastomas. Correlation with prognosis. A Pediatric Oncology Group Study.

The ganglioside composition of neuroblastoma samples from 53 patients was determined. Tumor sites included the adrenals (15), and the thoracic (20), abdominal (15), and pelvic (3) areas. Age of the patients at the time of surgery ranged from 1 day to over 10 years and the Stage of the tumors from A to D. Differences in ganglioside patterns were observed, with neuroblastomas from patients who were either disease positive or dead of disease tending to have more monosialogangliosides and fewer gangliotetraose gangliosides of the B series (formula; see text) than tumors from patients who were disease-free. More specifically, six of the seven patients lacking GT1b died of disease, suggesting that the absence of GT1b is indicative of a poor prognosis.

Gangliosides in neuroblastomas.

Neuroblastomas from children presenting with tumors at various ages and different primary sites (abdominal, adrenals, pelvic, and thoracic) were studied. Analysis of the ganglioside patterns of 53 tumors indicated that patients who were either disease positive 2 yr following surgery or dead of disease, had significantly (p less than 0.005) less GT1b plus GD1b than tumors from patients that were disease free 2 yr post surgery. The presence of GD2 in 45 of the tumors correlates well with the suggestion that it can be used as a marker in neuroblastoma diagnosis. Children with thoracic neuroblastomas have a significantly better prognosis than children with tumors in other anatomic sites. Analysis of the ganglioside composition of these tumors only, indicated that they had a significantly higher (p less than 0.005) concentration of GT1b and GD1b and a significantly lower concentration (p less than 0.025) of monosialogangliosides than those patients who were dead of disease or had persistent disease. These results suggest that low levels of GT1b and GD1b correlate with a poor prognosis. The thoracic neuroblastomas may be comprised of more "differentiated" neuroblastoma cells (ganglioside patterns more similar to the CNS), and this may contribute to the fact that about 85% of children with thoracic neuroblastoma recover. To understand why the ganglioside pattern may serve as a prognostic indicator for neuroblastoma, it is necessary to know whether gangliosides have specific roles in neuronal differentiation. Our approach to this question is to compare the effect(s) of added ganglioside or the corresponding oligosaccharide on neuroblastoma cells. Results obtained suggest that the oligosaccharide from GM1 is able to enhance neuritogenesis by S20Y murine neuroblastoma cells to the same extent that GM1 does.

Soft tissue gliomatosis--heterotopic glial tissue in the subcutis: a case report.

A subcutaneous nodule composed of heterotopic glial tissue is reported. The lesion was present in the subcutaneous tissue of the chest wall in a 2-year-old female. Histologically it was composed of loosely textured fibrillary neuroglial tissue in a densely hyalinized collagenous stroma. Immunohistochemical staining for glial fibrillary acidic protein was positive. The possible origin of this soft tissue glial heterotopia is discussed and the subject of heterotopic glial tissue is reviewed.

[An autopsied case of malignant paraganglioma of the posterior thoracic cavity].

An autopsied case of a malignant paraganglioma of the posterior thoracic cavity is reported. A 68-year-old man had complained of chest discomfort, and serial examinations revealed a functioning paraganglioma with bone metastasis. After death a pathological examination revealed that the tumors consisted of alveolarly arranged cells and well developed capillary vessels. Numerous neurosecretory granules were observed on viewing by electron microscopy. An immunohistochemical examination showed that most of the tumor cells were positive for NSE, while only a few cells were positive for the S-100 protein. These results indicate that a paraganglioma originating from the aortic sympathetic paraganglia had similar features of a carcinoid and a neuroblastoma.

Monoclonal antibody HML-1, a marker for intraepithelial T cells and lymphomas derived thereof, also recognizes hairy cell leukemia and some B-cell lymphomas.

Current views regard monoclonal antibody HML-1 as an exquisite marker for intraepithelial T cells and primary intestinal and cutaneous T-cell lymphomas. We show that HML-1 reacted with 11 of 12 cases of hairy cell leukemia, with 1 of 13 cases of primary gastrointestinal B-cell lymphoma, and with an unclassified large-cell B lymphoma of the thoracic wall. We conclude that HML-1 is not restricted to the T-cell lineage and that the HML-1 antigen is expressed in a small subset of both T- and B-cell neoplasms.