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Biomedical subjects

D M Parham

Publications and source records attributed to D M Parham.

At least 127 records · Page 7Linked to original sources

Simplified method of grading primary carcinomas of the breast.

AIMS: To produce a simplified prognostic index for breast cancer. METHODS: A retrospective study of 105 cases of primary infiltrating breast adenocarcinoma (not otherwise specified) was performed. Mitotic counts and semiquantitative assessment of tumour necrosis, fibrosis tubule formation, nuclear pleomorphism were made in histological sections of the primary tumour. Statistical analysis was performed to determine which of these parameters best predicts the observed survival. RESULTS: Mitotic count and necrosis correlated best with survival. This allowed the formation of a simple prognostic index based on these two parameters. CONCLUSIONS: This new prognostic index, with four tumour grades, seemed to be superior to Bloom's grading method, with greater separation of the prognostic groups. In particular, there is clear segregation of a group of patients with a distinctly poor prognosis.

Adenocarcinoma↗

Renal tumors in childhood.

A great variety of tumors and tumor-like lesions affect the kidneys in childhood. We have discussed the practical aspects of the examination of tumors because the pathologist's role is becoming more critical to the staging and management of these patients. The use of newer techniques shows promise in renal tumors, and flow cytometry with DNA ploidy analysis may prove useful in more precisely identifying high-risk patients. Invaluable data continue to be generated from the large cooperative groups, particularly the National Wilms' Tumor Study, which helps refine our understanding of the renal tumors and their proper management. Close collaboration between the oncologist, the radiologist, the surgeon, the pathologist, and the radiation oncologist is the mainstay in providing the best possible outcome for these patients.

Adolescent↗

Rhabdomyosarcoma. A new classification scheme related to prognosis.

We classified 159 cases of rhabdomyosarcoma (RMS) according to the conventional scheme adopted by the World Health Organization and a modified conventional scheme established at the National Cancer Institute (NCI), Bethesda, Md. The major modification in the NCI scheme was the inclusion of compact round-cell RMS with scant myogenesis in the group of alveolar RMS despite lack of an alveolar architecture. These tumors were previously considered to be embryonal RMS, but their cytologic features are quite different from those seen in embryonal RMS and are indistinguishable from those encountered in alveolar RMS. These tumors are referred to as "solid alveolar RMS." Survival curves were constructed with the method of Kaplan-Meier and compared with the unstratified and stratified methods of Mantel-Haenszel (with stratification factors being stage, site, and age) and with the Cox regression analysis. Both histologic schemes showed a statistically significant prognostic value in unstratified analyses, but the NCI scheme demonstrated prognostic value even in stratified analyses and in the Cox regression analysis in our series of cases. The data indicate that the NCI scheme can serve as a highly predictive, independent prognostic factor in RMS and that the alveolar category should be expanded to include the solid round-cell RMS, even in the absence of a classic alveolar architecture.

Adolescent↗

Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasms. Results of an Intergroup Rhabdomyosarcoma study project.

The authors assessed a panel of immunohistochemical stains against 109 pediatric solid tumors, primarily rhabdomyosarcomas, under the auspices of the Intergroup Rhabdomyosarcoma Study. Fresh tumor tissue received from participating organizations was divided into portions that were either frozen or fixed in formalin, alcohol, or B5. Immunostaining was performed by the avidin-biotin complex method using monoclonal antibodies to desmin, neurofilaments, vimentin, cytokeratin, and leukocyte common antigen on cryostat sections. Tissue was also embedded in paraffin and stained with antimuscle-specific actin (MSA) and polyclonal antibodies to desmin, creatine kinase M subunit (CKM), myoglobin, and neuron-specific enolase (NSE). Antidesmin staining of cryostat sections was the most sensitive indicator of rhabdomyosarcoma (58 of 62 specimens positive). Results with this reagent in alcohol-fixed and formalin-fixed tissue were similar (46 of 56 positive versus 43 of 56 positive, respectively) and comparable with results with anti-MSA in formalin-fixed tissue (43 of 55 positive). However, the proportion of cells stained by antidesmin was higher in alcohol-fixed tissue than in formalin-fixed tissue. Staining with antimyoglobin and anti-CKM was much less satisfactory, with positivity rates of 17 of 37 and 11 of 57, respectively, in formalin-fixed rhabdomyosarcomas. Immunostaining of muscle markers revealed evidence of myogenesis in six undifferentiated sarcomas and in two sarcomas with inadequate histologic study on hematoxylin-eosin-stained sections. However, positivity was also noticed in samples of fibromatosis, Wilms' tumor, ectomesenchyoma, peripheral primitive neuroectodermal tumor, renal rhabdoid tumor, myositis ossificans, malignant fibrous histiocytoma, and embryonal sarcoma of the liver. The authors conclude that combined use of antidesmin and anti-MSA enhances the diagnosis of childhood sarcomas, especially when employed with other techniques such as electron microscopic study.

Actins↗

Variant translocations of chromosome 13 in alveolar rhabdomyosarcoma.

In three cases of alveolar rhabdomyosarcoma with variant translocations, two tumors contained an identical translocation, t(1;13)(p36.1;q14); the third tumor contained a t(8;13)(p21;q14). All three patients were 2 years old, markedly younger than the median age for patients with t(2;13)-positive alveolar rhabdomyosarcoma. The alteration of genetic material on chromosome 13 may be of primary importance in the development of alveolar rhabdomyosarcoma.

Child, Preschool↗

Metastatic small cell tumor of bone with 'true' rosettes and glial fibrillary acidic protein positivity.

A 15-year-old black girl was admitted to St. Jude Children's Research Hospital with a lytic lesion involving the right fourth metacarpal bone with a solitary metastasis to the ipsilateral axillary lymph node. Histologic examination of both the primary lesion and metastasis revealed a primitive small round cell lesion. Abundant rosettes with central lumina were present in the metastasis. Immunohistochemical stains performed on sections of the metastasis were strongly positive for glial fibrillary acidic protein (GFAP) and negative for neuron-specific enolase (NSE), S-100 protein, and Leu-7. Electron microscopic examination of the metastasis revealed lumen formation with apical microvilli and juxtaluminal junctional complexes. This tumor exhibits features that are suggestive, but not definitive, of primitive ependymal differentiation and further expands the morphologic and immunophenotypic range of small round cell tumors of bone.

Adolescent↗

MyoD1 protein expression in alveolar soft part sarcoma as confirmatory evidence of its skeletal muscle nature.

A typical case of alveolar soft part sarcoma was found to express in a strong and widespread fashion the marker MyoD1 protein. This nuclear phosphoprotein is the product of a regulatory gene that controls the commitment of a cell to myogenic lineage; it therefore provides strong and perhaps definitive evidence in support of the skeletal muscle nature of this enigmatic neoplasm.

Cell Transformation, Neoplastic↗

The potential for renal salvage in nonmetastatic unilateral Wilms' tumor.

The potential for resection with renal salvage, and the ability of computed tomographic (CT) criteria to predict this potential, were evaluated retrospectively in 43 children with nonmetastatic unilateral Wilms' tumor (stage I, II, or III at diagnosis). CT criteria for renal salvage were (a) tumor involving only one pole and occupying less than one third of the kidney; (b) functioning kidney; (c) no invasion of collecting system or renal vein; and (d) clear margins between tumor, kidney, and surrounding structures. Preoperative CT scans met these criteria in only two of the 43 cases. Surgical and/or pathologic reports confirmed CT-based findings in all cases. Most of the tumors were large (median vertical and transverse diameters both = 10 cm), and only three patients were estimated to have more than 50% functioning renal tissue. A prospective trial would be necessary to evaluate the long-term benefits and possible complications of renal salvage procedures in patients with Wilms' tumor. Given the small proportion of patients likely to be eligible for such procedures, and the currently excellent cure rates in low-stage disease, such as trial would be difficult to implement.

Child↗

The cytological prediction of cervical intraepithelial neoplasia in colposcopically directed biopsies.

The tissue sections and preceding cervical smears of 1262 women who had colposcopic cervical biopsies were reviewed and the reports correlated. Close correlation between the cytological and histological findings, to within one histological grade of cervical intraepithelial neoplasia (CIN), was noted in 86% of cases. However, the biopsy was negative, or contained evidence of wart virus infection only, in 24% of cases where dyskaryotic cells had been observed in the cervical smear. Of particular concern was the fact that negative histological findings were recorded in 13% of cases where the smear contained cells showing a moderate dyskaryosis and in 1.26% of cases where the smear showed severe dyskaryosis. This suggests that colposcopically directed biopsies do not always reflect the underlying pathological changes in the cervix. Management of these cases is discussed. In 45 women with a normal cervical smear prior to biopsy, histology revealed seven cases of CIN 3 and one case of invasive squamous carcinoma. This indicates that referral for colposcopy is advisable whenever there is clinical suspicion of cancer, even if the cervical smear report is normal.

Biopsy↗

The changing phenotypic appearance of a malignant vulval neoplasm containing both carcinomatous and sarcomatous elements.

We describe the changing phenotypic appearance over a 7-year period of a malignant neoplasm of the vulva. This lesion was studied by light and electronmicroscopy and immunohistochemical techniques. The tumour contained both carcinomatous and sarcomatous elements including osteosarcomatous differentiation. To our knowledge osteosarcomatous differentiation has not been reported previously at this site. We submit that the best term for this type of neoplasm, based on tumour differentiation rather than reputed histogenesis, is carcinosarcoma. Tumours such as these occurring in the female genital tract should be distinguished from metastatic mixed Müllerian tumours.

Biomarkers↗

Fungal sinusitis in immunocompromised children with neoplasms.

This paper reviews the treatment and diagnosis of immunocompromised patients with fungal sinusitis at St Jude Children's Research Hospital. Sinusitis of all types was found to be more common in patients with hematopoietic neoplasms than in patients with solid tumors; 42% of patients with leukemia had abnormal sinus radiographs. Eight cases of pathologically proven fungal sinusitis were identified. All patients were undergoing chemotherapy for either acute myeloblastic leukemia or acute lymphoblastic leukemia and had neutrophil counts less than 100 cells/mm3. The most common findings were fever, facial pain, and abnormal sinus radiographs. Surveillance cultures of the upper aerodigestive system did not reliably predict sinus pathogens. An aggressive treatment approach consisting of early administration of amphotericin B (intravenously and via catheter irrigations of the sinuses) and surgical drainage is advocated. There was an 80% survival rate in patients in remission who were undergoing maintenance chemotherapy. All patients undergoing chemotherapy for relapse died.

Aspergillosis↗

Relationship of tumor-cell ploidy to histologic subtype and treatment outcome in children and adolescents with unresectable rhabdomyosarcoma.

Clinical and histopathologic features are often inadequate for accurate prediction of relapse or survival of individual patients with rhabdomyosarcoma (RMS). We therefore studied the cellular DNA content (ploidy) of RMS cells in relation to histology and response to therapy in 37 patients with unresectable tumors. Using flow cytometric techniques, we found that about one third of patients had diploid tumor stem lines, regardless of the histologic subtype. In the group with abnormal ploidy, a hyperdiploid classification (1.10 to 1.80 times the DNA content of normal diploid cells) was exclusively associated with embryonal histology (P = .001). By contrast, near-tetraploidy (1.80 to 2.60 times the DNA content of normal cells) was strongly associated with alveolar histology (P = .001). Thus, in these histologic subtypes of RMS, abnormal ploidy appears to arise through different mechanisms. Tumor-cell ploidy had a significant impact on survival that was especially apparent in patients with unresectable, nonmetastatic (group III) tumors. In this subgroup, hyperdiploidy conferred the best prognosis and diploidy the worst (P less than .0001). None of the eight patients with diploid tumors survived for more than 18 months. Tumor-cell ploidy was the best predictor of treatment outcome for patients with either embryonal (P less than .001; relative risk, 25.5) or alveolar (P = .073; relative risk 7.1) RMS and contributed significantly after adjustment for disease stage and anatomic site. Patients with unresectable diploid RMS have an unacceptably high risk of treatment failure, justifying new therapeutic approaches for this distinct subgroup.

Adolescent↗

Impact of intensified therapy on clinical outcome in infants and children with neuroblastoma: the St Jude Children's Research Hospital experience, 1962 to 1988.

To gauge the impact of intensified therapy on the survival of infants (younger than 1 year, n = 129) and children (greater than or equal to 1 year of age, n = 275) with neuroblastoma, we analyzed the results of eight successive clinical trials comparing various combinations of antineoplastic drugs, surgery, and radiotherapy. Changes in treatment did not affect the survival of children with involved noncontiguous lymph nodes or distant metastatic disease until the combination of cisplatin and teniposide (CDDP/VM26) was added to a basic regimen of cyclophosphamide and doxorubicin (CTX/DOX). The resulting 4-year survival was 28% +/- 5% (SE) compared with 7% +/- 2% for previous treatments (P less than .001 by the log-rank test). The 4-year survival of infants with metastatic disease was improved by administering CTX/DOX to all patients, reserving CDDP/VM26 for those whose disease was resistant to the former combination: 82% +/- 6% versus 45% +/- 8% in earlier studies; P less than .001. In the subset of infants whose tumors had disseminated to bone or bone marrow at diagnosis, this therapeutic approach increased the probability of long-term survival from 48% +/- 10% to 85% +/- 9% (P = .01). The small group of children over 1 year of age with localized unresectable tumors also fared significantly better with the switch to CTX/DOX chemotherapy (4-year survival, 93% +/- 7% v 42% +/- 13%; P = .02). Multivariate analysis indicated that young age, limited-disease stage, nonadrenal primary site, and intensified treatment were independent predictors of a more favorable outcome. We conclude that substantial advances in the treatment of neuroblastoma have occurred over the past 25 years at this institution. The current overall 4-year survival probability of 57% +/- 4% compares favorably with estimates for most other common solid tumors of childhood.

Age Factors↗

Immunohistochemical and ultrastructural spectrum of hepatic sarcomas of childhood: evidence for a common histogenesis.

Hepatic sarcomas of childhood, which appear heterogeneous by standard morphologic criteria, pose challenging diagnostic and nosologic problems to the pediatric surgical pathologist. To identify features of these tumors that might help to clarify their origin and histologic classification, we studied 13 undifferentiated (embryonal) sarcomas of the liver (UESL) and two intrinsic hepatic rhabdomyosarcomas (RMS) using immunohistochemical and electron microscopic techniques. Immunohistochemical staining was performed on 14 tumors with use of commercially available antibodies against a variety of markers, as well as peanut agglutinin lectin; electron microscopy was performed on five UESL and both RMS. Desmin was expressed by 6/12 UESL and 2/2 RMS, muscle-specific actin by 5/12 UESL and 2/2 RMS, neuron-specific enolase by 1/12 UESL and 1/2 RMS, alpha-1-antitrypsin by 8/12 UESL and 1/2 RMS, and alpha-1-antichymotrypsin by 10/12 UESL and 1/2 RMS. Cytokeratin expression was observed in only four UESL. The overlap of immunohistochemical staining patterns and ultrastructural features shown by these obstensibly different tumors suggests a common histogenesis, perhaps from a multipotential mesenchymal stem cell.

Actins↗

Sarcomas (other than Ewing's) of flat bones in children and adolescents. A clinicopathologic study.

The clinicopathologic features and response to therapy of 28 patients with non-Ewing's flat bone sarcoma treated at St. Jude Children's Research Hospital, Memphis, Tennessee, over a 25-year period were reviewed. Twenty-two patients had osteosarcoma, four malignant fibrous histiocytoma, one chondrosarcoma, and one fibrosarcoma. Ages at diagnosis ranged from 3 to 24 years (median, 15 years). Primary sites were craniofacial bones in ten patients, pelvis eight, scapula four, ribs two, metatarsal bones two, clavicle one, and vertebra one. All primary tumors were associated with soft tissue extension; none of the patients had metastatic disease at presentation. Six cases represented second malignancies that arose 5 to 16 years after irradiation for an unrelated tumor. Complete excision was possible in ten patients, eight of whom received postoperative chemotherapy. Five of these patients remain free of disease 1.8+ to 13+ years (median, 8.1 years) from diagnosis. Prolonged remissions after adjuvant chemotherapy were achieved in only two of 18 patients after incomplete surgical resection or biopsy. The median survival time in this group was 1 year (range, 0.2-7.7+ years). The remaining 16 patients had progressive local disease, but only two developed concurrent metastases. Thus, complete surgical resection appears to maximize disease-free survival in patients with non-Ewing's flat bone sarcoma. For the large percentage of patients in whom total resection is not possible, because of soft tissue extension and local invasion of bulky tumors, preoperative chemotherapy may increase the likelihood of complete excision and improve long-term survival.

Adolescent↗