Desmoplastic primitive neuroectodermal tumor with divergent differentiation. Broadening the spectrum of desmoplastic infantile neuroepithelial tumors.

We report an unusual large, multicystic, posterior fossa neuroepithelial neoplasm involving the cerebellum, brain-stem, and quadrigeminal cistern of a 9-month-old girl. The neoplasm consisted of variably sized, sharply demarcated nests of small cells with a high nuclear-cytoplasmic ratio and moderately basophilic nuclei, embedded in a desmoplastic, immature-appearing, mesenchymal stroma. The nests contained mitoses but none were seen in the stroma. Glial fibrillary acidic protein (GFAP), neurofilament protein, synaptophysin, and cytokeratin (AE-1) were expressed in the nests. Mesenchymal cells were negative for neural markers but positive for vimentin and desmin. The neoplasm was interpreted as a mixed mesenchymal and primitive neuroectodermal tumor (PNET) with histologic features reminiscent of a recently described intraabdominal desmoplastic small cell tumor. The tumor responded poorly to chemotherapy and a second operation was performed 1 year later. The second specimen bore no resemblance to the original and consisted of epithelial-like nests and clusters of neoplastic cells frequently interrupted by sinusoidal vessels. Tumor cells had medium-sized vesicular nuclei with small nucleoli, and a granular cytoplasm. Occasional less cellular islands of neuropil-like tissue contained larger cells having eccentric, vesicular nuclei with prominent nucleoli and abundant pink cytoplasm. Mitoses were not conspicuous. Many cells expressed synaptophysin, neurofilament protein, and GFAP. Neurofilament protein was strongly positive in the larger, neuron-like cells and synaptophysin stained the neuropil-like areas strongly but was less prominent in the neuronal perikarya. Unexpectedly, the neuropil-like areas expressed epithelial membrane antigen, whereas the neuronal cells were negative for chromogranin A. The peculiar histologic picture, combination of phenotypic markers, and remarkable biologic behavior of this unusual tumor defies classification according to existing nomenclature and exemplifies the broad range of phenotypes expressed by primitive neuro-epithelial neoplasms.     

Neurofibromatosis type 1: brain stem tumours

We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. Received: 21 November 1996 Accepted: 22 December 1996     

Sebaceous carcinoma of the head and neck. Case report and literature review.

Sebaceous carcinoma is uncommon, with fewer than 400 cases reported. Usually, lesions arise in the meibomian glands of the eyelid; however, extraocular lesions within the head and neck have been reported. Regardless of the location, sebaceous malignancies must be considered aggressive neoplasms with a potential for regional and distant metastasis. Diagnosis may be difficult, given the low incidence and inconsistencies in histopathologic classification. Recently, needle aspiration cytologic characteristics have been delineated, with this procedure becoming increasingly useful in establishing the diagnosis. Treatment requires wide surgical excision with removal of involved regional lymph nodes. Opinions are divided regarding the use of postoperative irradiation or chemotherapy. Records of all patients with sebaceous carcinoma of the head and neck treated at UCLA Medical Center, Los Angeles, over the last 35 years were reviewed. The clinical and pathologic features are discussed, and the literature is summarized.     

Mutations of the human thyrotropin-beta subunit glycosylation site reduce thyrotropin synthesis independent of changes in glycosylation status.

In recent studies, site-directed mutagenesis has been used to alter the tripeptide glycosylation recognition sequences of glycoprotein hormone subunits, thereby affecting their structure and function. However, it is not known whether these effects result from changes in glycosylation status, amino acid sequence, or both. We therefore studied the synthesis of wild-type and mutant recombinant human thyrotropins produced by transient transfection of a human cell line. Mutating the TSH-beta subunit glycosylation recognition sequence, Asn-Thr-Thr (codons 23-25), to either Gln-Thr-Thr or Asn-Thr-Tyr abolished subunit glycosylation, as demonstrated by the inability to incorporate 3H-carbohydrates. However, a third mutation (Asn-Thr-Ser) contained an intact glycosylation recognition sequence site, and was shown to retain glycosylation. The mutations that abolished TSH-beta subunit glycosylation resulted in greater than 90% decreases in TSH synthesis. However, the glycosylation recognition sequence mutant that retained beta subunit glycosylation exhibited a 70% decrease in TSH production. These decreases were not attributable to the intracellular accumulation of TSH or its free beta subunit. We also engineered two TSH-beta subunit mutations that did not alter the glycosylation recognition sequence. A glycine to arginine mutation adjacent to the glycosylation recognition sequence, in a region thought to be critical for heterodimer formation, abolished TSH production. In contrast, shortening the TSH-beta subunit carboxyterminus by six amino acids increased TSH synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Locoregional chemotherapy in the treatment of liver metastasis of breast carcinoma]

Locoregional chemotherapy enables specific treatment of organ metastases by using a dosage of medication that is maximally effective but only has minimal side effects on other organs. Since 1983, we have applied this procedure in patients whose liver represented the only target-organ of metastases. Between 1983 and 1990, locoregional chemotherapy was performed in 59 women suffering from liver metastases of breast cancer. The average age of our patients was 52 years. 4 patients were treated for solitary metastases that could not be resected, in 5 patients the infiltration of hepatic parenchyma with metastases accounted to 25%, in 32 patients hepatic infiltration ranged between 25% and 75% and in 18 patients it surpassed 75%. In 39% of our patients, a partial remission occurred. The mean period of survival after beginning of treatment was 149 days, whereas the longest survival time lasted 1009 days. We conclude that the locoregional chemotherapy, destined for treatment of liver-metastases of breast cancer, with a mean survival time of only five months could insufficiently satisfy our expectations. Therefore, a decision to administer such palliative therapy should be made on an individual basis. In our opinion, one indication represents solitary metastases that are not resectable, a further indication is pain due to expansion of the liver capsule because of diffuse metastases.     

Women's Satisfaction with Their Involvement in Health Care Decisions During a High‐Risk Pregnancy

ABSTRACT: Background: Increasingly, women seek involvement in decisions about their health care. The purpose of this study was to examine women's experience of, and satisfaction with, their involvement in health care decisions during a high‐risk pregnancy. Methods: Forty‐seven women with hypertension or threatened preterm delivery (including multiple births) were interviewed after the birth of their child. They received prenatal care at home from nurses in a community program or were hospitalized. The in‐depth interviews were audiotaped and transcribed; data were analyzed using constant comparative methods. Results: Women identified an increased feeling of responsibility for the health of their baby and themselves, but differed in choosing active or passive involvement in health care decisions. Women who wanted active involvement achieved it through one of three processes: struggling for, negotiating, or being encouraged. Women who wanted passive involvement and women facing health crises used the process of trusting in the expertise of nurses and physicians. Women were satisfied if the care from health care professionals was congruent with how they wanted to be involved in decision‐making. Conclusions: Although most women want to be actively involved in health decision‐making during a high‐risk pregnancy, some prefer a passive role. The setting of prenatal care, community‐based or in‐hospital, was less important than the ability of nurses and physicians to support the woman in her preferred role in decision‐making. (BIRTH 30:2 June 2003)     

Development and evaluation of a breast cancer prevention decision aid for higher-risk women

Objective To develop and evaluate the effectiveness of a breast cancer prevention decision aid for women aged 50 and older at higher risk of breast cancer. Design Pre‐test–post‐test study using decision aid alone and in combination with counselling. Setting Breast Cancer Risk Assessment Clinic. Participants Twenty‐seven women aged 50–69 with 1.66% or higher 5‐year risk of breast cancer. Intervention Self‐administered breast cancer prevention decision aid. Main outcome measures Acceptability; decisional conflict; knowledge; realistic expectations; choice predisposition; intention to improve life‐style practices; psychological distress; and satisfaction with preparation for consultation. Results The decision aid alone, or in combination with counselling, decreased some dimensions of decisional conflict, increased knowledge (P < 0.01), and created more realistic expectations (P < 0.01). The aid in combination with counselling, significantly reduced decisional conflict (P < 0.01) and psychological distress (P < 0.02), helped the uncertain become certain (P < 0.02), and increased intentions to adopt healthier life‐style practices (P < 0.03). Women rated the aid as acceptable, and both women and practitioners were satisfied with the effect it had on the counselling session. Conclusion The decision aid shows promise as a useful decision support tool. Further research should compare the effect of the decision aid in combination with counselling to counselling alone.