Pleomorphic xanthoastrocytoma: DNA flow cytometry and outcome analysis of 12 patients

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is an astrocytic tumor occurring primarily in childhood and adolescence with some malignant histologic features but a relatively slow clinical course. However, some tumors progress more rapidly and can undergo malignant degeneration. The authors attempted to determine whether various histologic features or tumor cell proliferative indices might help identify lesions at risk for early progression and distinguish PXAs from malignant gliomas. METHODS: In a retrospective study of 12 patients with PXA, the tumor's histologic features and DNA flow cytometric parameters were compared with their clinical course. DNA flow cytometry values for the S- and G2-phase of the PXAs also were compared with control group samples of malignant and low grade astrocytomas. RESULTS: Of the 12 tumors at initial diagnosis, 5 were considered typical PXAs whereas 7 had some atypical features (4 with paucity of reticulin fibers, 1 with focal necrosis, and 2 with both atypical reticulin and focal necrosis). During the follow-up period (range, 3.75-11 years; mean, 6.8 years), 2 patients had recurrences; 1 atypical reticulin PXA progressed to glioblastoma after 6.5 years and the 1 tumor with focal necrosis recurred at 6 months and again at 2 years with typical histologic features. DNA flow cytometry parameters of the typical PXA group were similar to values for malignant astrocytoma and significantly higher than values for control specimens of low grade astrocytomas. There were no distinctive DNA flow cytometric features that could distinguish this last tumor from others with a more benign clinical course. CONCLUSIONS: Measurements of the S-phase and G2-phase obtained from DNA flow cytometry and atypical histologic features cannot reliably identify PXA patients at risk for early progression and overall are significantly higher than values obtained for low grade gliomas. Therefore, frequent (i.e., two to three times per year) postoperative clinical and radiologic examinations are necessary to judge the appropriateness of adjuvant therapy in patients with PXA. The paradox of slow growth but DNA flow cytometry consistent with aggressive malignant lesions may represent a cell-cycle arrest mechanism in these lesions that could be verified in subsequent studies.     

Anaplastic pleomorphic xanthoastrocytoma

Well-documented cases of malignant degeneration in pleomorphic xanthoastrocytoma and of anaplastic pleomorphic xanthoastrocytoma are rare in the literature. We report 2 cases of pleomorphic xanthoastrocytoma, 1 of which demonstrated clear evidence of malignant degeneration in the absence of prior radiation therapy over an 18-year period. Both anaplastic tumors were characterized by foci of necrosis and increased mitotic activity (3 and 2 mitotic figures/10 high-power fields). Both tumors demonstrated focal positive staining for glial fibrillary acidic protein and showed marked reticulin deposition. An MIB-1 labeling index (marker of cell proliferation) in the initial low-grade-appearing tumor in case 1 was 0.1%. The recurrent tumor in case 1 had an MIB-1 labeling index of 4.9%, and the anaplastic tumor in case 2 had an MIB-1 labeling index of 5.4%. Significant cyclin D1 immunoreactivity was not observed in either anaplastic tumor. Two percent to 3% of tumor cells stained positive with p53 protein antibody in the recurrent anaplastic tumor in case 1. Although histology may not reliably predict aggressive behavior in pleomorphic xanthoastrocytomas, the presence of increased mitosis, necrosis, and increased cell proliferation labeling indices may be indicative of a higher grade tumor.     

Multiple pleomorphic xanthoastrocytoma tumors in a 12-year-old girl

This report presents a case of multiple bilateral hemispheric tumours (pleomorphic xanthoastrocytoma) in a practically asymptomatic 12-years-old girl. The tumours were removed radically in a staged procedure, with a favorable clinical outcome. Clinical history and neuropathologic findings are described. A review of pertinent literature is included.     

Increased mitotic activity as a negative prognostic indicator in pleomorphic xanthoastrocytoma. Case report

Pleomorphic xanthoastrocytoma is a recently characterized neoplasm with a favorable prognosis despite aggressive histological features. The authors report a case of pleomorphic xanthoastrocytoma that recurred 4 years after complete gross resection. The original tumor exhibited histological features characteristic of this neoplasm, but up to 4 mitoses/10 high-power fields were present focally. The recurrent tumor contained small foci of classical pleomorphic xanthoastrocytoma, but consisted predominantly of glioblastoma multiforme. Transitional zones contained nests of glial fibrillary acidic protein (GFAP)-immunopositive cells surrounded by delicate collagenous and reticulin-rich septa. Electron microscopy of the transitional zone showed continuous basal lamina investing cells containing bundles of intermediate filaments. These were GFAP-positive by immunogold electron microscopy, confirming the astrocytic nature of pleomorphic xanthoastrocytoma. This example illustrates the capacity of this tumor to evolve into glioblastoma. The indolent clinical behavior of most pleomorphic xanthoastrocytomas is evident from a literature review, which confirms the prolonged survival of many patients after onset of symptoms. Completeness of excision, subjectively assessed at surgery, did not influence the risk of recurrence or survival up to 10 years after initial resection. Postoperative radiotherapy did not improve survival, but may reduce the probability of recurrence; more studies are needed to corroborate this finding. The data compiled herein support the designation of pleomorphic xanthoastrocytoma as a distinct astrocytic neoplasm with a favorable prognosis. An increased mitotic rate has not previously been correlated with a worse outcome, and should not be used to exclude this diagnosis. However, anaplastic transformation of pleomorphic xanthoastrocytoma confers a much worse prognosis, and this case suggests that increased mitotic activity may be a negative prognostic indicator since it may herald subsequent anaplastic transformation.     

Pleomorphic adenoma of skin (chondroid syringoma) involving the eyelid

Lid tumours are fairly common. However, pleomorphic adenoma (chondroid syringoma) is quite rare. In a series of 207 eyelid tumours and tumour like lesions, pleomorphic adenoma was observed in a male aged 41 years; its incidence being 0.48%.     

Pleomorphic adenoma of the parotid gland. Results of surgical treatment

Twenty years experience of lateral parotidectomy as suspical treatment for pleomorphic adenoma are reviewed. All cases were managed at the ORL Clinic of the University of Zürich. 167 patients were followed for the frequency of possible recurrent tumors. Three patients (3/123) operated primarily developed a recurrences. Recurrences appeared after an average of 10 years, ranging from 1-30 years. The follow-up time varied from 1 to 21 years (average, 8 years). 39% (13 of 33) of the patients, who were re-operated for a recurrent tumor, developed another recurrence. The second recurrence appeared after an average of 10 years, ranging from 1-22 years. A persistent partial paresis of the facial nerve was found in 1% of the patients operated primarily and in 9% of the patients operated more than once. No paralysis was seen. We now choose "en-bloc" resections of pleomorphic adenomas without intra-operative opening of the tumor capsule as the treatment of choice. This treatment was possible in 83% of all cases, using a lateral parotidectomy. If tumor extends into the medial parotid lobe, total parotidectomy is required.     

Pleomorphic lobular carcinoma of the breast: clinicopathologic features of 12 cases

Pleomorphic lobular carcinoma (PLC) of the breast was recently identified as a histologic variant of infiltrating lobular carcinoma (ILC) with a poor prognosis. Twelve cases identified from a large series of breast carcinomas were studied retrospectively. Of 11 cases with adequate follow up, 9 were fatal. This was significantly worse than either infiltrating ductal carcinoma (IDC) or classical ILC (P < or = .002), even when stratified by axillary lymph node status. Among the fatal cases, the median survival time was 2.1 years, significantly shorter than that for classical lobular, but not ductal, carcinoma A distinctive pattern of in situ carcinoma, which has been described as PLC in situ, was identified in 7 of the 12 patients. This in situ component was composed of tumor cells with nuclear atypia, cytologically similar to the invasive tumor. Most PLCs lacked estrogen and progesterone receptors and stained with BRST-2, an antibody to gross cystic disease fluid protein-15, suggesting the presence of apocrine differentiation. In summary, PLC has many of the histologic features of ILC but has anaplastic nuclei, abundant cytoplasm, and apocrine differentiation. PLC is often aneuploid, usually lacks steroid receptors, and has a significantly poorer prognosis than does classical ILC.     

Pleomorphic adenoma of the breast; a potential for the misdiagnosis of malignancy on fine needle aspiration (FNA)

Despite the fact that estrogen replacement therapy has been demonstrated to be of great value to postmenopausal women, many patients are still reluctant to use it. This is primarily because of fears that sex hormone therapy increases the risk of developing uterine and breast cancer. Because retrospective epidemiological studies have failed to clarify the issue for breast cancer, ambitious prospective trials have been initiated to determine the role of hormones in the development of breast cancer and cardiovascular disease. The main studies have been the Women's Health Initiative, the Postmenopausal Estrogen/Progestin Intervention (PEPI) Trial, the Heart and Estrogen-Progestin Replacement Study (HERS), the Women's International Study of long Duration Oestrogen after Menopause (WISDOM) and the Million Women Study. Only the PEPI Trial has been completed. It showed a substantial benefit for women using hormone replacement therapy, but was insufficiently powerful to determine whether such therapy affected the incidence of breast cancer. Despite the immense costs involved and the considerable time that must elapse before results are published, it is imperative that these major prospective studies are completed, analysed and published. Only then can physicians advise their patients in an appropriate manner.