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Biomedical subjects

D M Parham

Publications and source records attributed to D M Parham.

At least 73 records · Page 4Linked to original sources
PubMed1995

Malignant melanocytic lesions of unknown primary site in children and adolescents.

BACKGROUND: Metastatic melanoma with an unidentified primary site represents 4% of all newly diagnosed cases of malignant melanoma in adults. Little is known of the incidence and clinicopathologic features of this clinical entity in the pediatric population. METHODS: We reviewed all previously diagnosed cases of malignant melanoma in children and adolescents (< 21 years) who were treated at our institution and identified three patients who presented with metastatic melanocytic lesions with an unidentified primary site. RESULTS: This clinical presentation accounted for 9% of all malignant melanocytic lesions treated at our center over a 20-year period. The clinicopathologic features were similar to those seen in adults. Two patients died of progressive disease within two years of presentation; the third is alive and disease-free 18 years post-diagnosis. CONCLUSIONS: Although uncommon in the pediatric population, malignant melanoma should be considered in the differential diagnosis of poorly differentiated disseminated malignancy that involves lymph nodes or viscera with no identifiable primary tumor.

Adolescent↗
PubMed1995

Unusual cutaneous toxicity following treatment with dactinomycin: a report of two cases.

Dactinomycin-induced cutaneous toxicity is rare in pediatric patients not receiving radiation therapy. We describe dactinomycin-related lesions in the axilla, groin, and central line exit site of two children treated for rhabdomyosarcoma, neither of whom had received radiation treatment. One patient was initially treated with systemic antifungal therapy, and developed recurrent lesions on reexposure to the drug. The other was noted to have mild, diffuse hyperpigmentation. Skin biopsies revealed interface dermatitis with syringometaplasia in both cases. Both children recovered uneventfully within 4 weeks. Recognition of unusual rashes with a characteristic distribution in patients receiving dactinomycin should aid in diagnosis, and help avoid unnecessary therapeutic procedures.

Child↗
PubMed1995

Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon in young patients. To contribute to the understanding of these tumors, we reviewed the records of all patients treated for PNSTs at one institution over a 30-year period. METHODS: We reviewed the records of eight patients treated for benign PNSTs and 28 patients treated for 29 MPNSTs. We focused on the latter group, statistically testing several clinical factors for their significance in affecting survival. RESULTS: Five-year survival in patients with MPNSTs was 39%. The most significant prognostic factor was gross tumor resectability (p = 0.0004). Five-year survival for patients with resectable tumors was 65%, whereas no patient with unresectable disease survived > 25 months. Tumor grade, site, and patient race were also significant factors by univariate analysis but were not significant when adjusted for resectability. CONCLUSION: Gross tumor resection is crucial in treating malignant PNSTs. Supplemental radiation therapy is recommended for positive microscopic margins. More effective treatment is still being sought for unresectable disease.

Adolescent↗
PubMed1995

Use of monoclonal antibody 1H1, anticortactin, to distinguish normal and neoplastic smooth muscle cells: comparison with anti-alpha-smooth muscle actin and antimuscle-specific actin.

In preliminary experiments, we found that 1H1, a monoclonal antibody directed against the v-src substrate cortactin, reacts with smooth muscle, myoepithelium, myofibroblasts, and macrophages in formaldehyde-fixed human tissues. To evaluate the use of this antibody as a diagnostic reagent, we tested the immunohistochemical distribution of cortactin in 61 mesenchymal neoplasms, 11 neuroectodermal neoplasms, and eight embryonal epithelial neoplasms. The results were compared with those obtained using antibodies against alpha-smooth muscle actin and muscle-specific actin on a similar set of tissues. With the exception of positive staining in rhabdomyosarcoma, in this series only tumors with smooth muscle differentiation appeared to contain cortactin (16 of 19 leiomyosarcomas, one infantile fibrosarcoma, one malignant fibrous histiocytoma). Immunoelectron microscopy localized cortactin to the actin-associated dense bodies of the microfilament network. We conclude that cortactin may be a useful adjunct to alpha-smooth muscle actin and muscle-specific actin as a marker for the study and diagnosis of smooth muscle neoplasms and related lesions.

Actins↗
PubMed1995

Immunohistochemistry of MyoD1 in adult pleomorphic soft tissue sarcomas.

Adult pleomorphic rhabdomyosarcomas are difficult to distinguish from other pleomorphic soft tissue sarcomas. Immunostaining with the monoclonal antibody MyoD1 5.8A has recently shown promise as a sensitive and specific marker of rhabdomyosarcomas of childhood. To determine the usefulness of MyoD1 in distinguishing adult pleomorphic rhabdomyosarcoma from other pleomorphic sarcomas, we studied 21 cases of pleomorphic sarcoma, including six cases diagnosed as rhabdomyosarcoma. Immunostaining was accomplished using monoclonal antibodies against MyoD1, desmin, alpha-smooth-muscle actin, and muscle-specific actin on cryostat sections of frozen tumor. All cases of pleomorphic rhabdomyosarcoma stained positively with both desmin and MyoD1. Five cases diagnosed as nonrhabdomyosarcomatous pleomorphic sarcomas stained positively with desmin, but only one showed weak MyoD1 positivity. Three of these five cases were also positive with alpha-smooth-muscle actin. The results of this study suggest that the sensitivity and specificity of the MyoD1 antibody in the differential diagnosis of adult pleomorphic soft tissue sarcomas approaches that seen in pediatric rhabdomysarcomas.

Adult↗
PubMed1995

An inaccuracy.

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Brain Neoplasms↗
PubMed1995

Anti-CD45.

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Biomarkers, Tumor↗
PubMed1995

Ewing's sarcoma as a second malignant neoplasm in a child previously treated for Wilms' tumor.

PURPOSE: Second malignant neoplasms (SMNs) are a rare occurrence after the successful treatment of childhood cancer. For survivors of Wilms' tumor, the 10-year cumulative risk of developing an SMN has been estimated to be 1%. Bone sarcomas arising within the radiation field are a common occurrence, yet Ewing's sarcoma has been rarely reported as an SMN. PATIENTS AND METHODS: A 10-year-old girl presented with dyspnea 5 years after the diagnosis of stage III favorable histology Wilms' tumor and was found to have a right intrathoracic mass arising from the eighth and ninth ribs. The mass was located at the edge of the previous radiation field. RESULTS: Tumor cytogenetics and immunocytochemistry were helpful in establishing the diagnosis of Ewing's sarcoma. Treatment included combination chemotherapy, with hematopoietic growth factor support, and excluded anthracyclines and radiotherapy. More than 1 year after the diagnosis of Ewing's sarcoma, the patient has completed therapy with no evidence of disease. CONCLUSIONS: This is the first report to our knowledge of Ewing's sarcoma arising in the irradiation field of a patient treated previously for Wilms' tumor.

Child↗
PubMed1995

Second malignant neoplasms in children with retinoblastoma: the St. Jude Children's Research Hospital experience.

A retrospective review of 172 children with primary diagnosis of retinoblastoma (RB) was completed at St. Jude Children's Research Hospital to evaluate the incidence of second malignant neoplasm (SMN) development. Sixty-five patients presented with bilateral RB and 107 with unilateral RB. During follow-up, which ranged from 6 to 340 months (median = 170 months), 6 children (3.5%) developed SMN. All patients who developed SMN presented with bilateral disease (n = 5) or asynchronous bilateral disease (n = 1); two patients had a family history of RB. All had received irradiation. Four patients developed osteogenic sarcoma within this irradiated volume, one developed a basal cell carcinoma in the temporal region (within the irradiation field), and one was diagnosed with a lower extremity Ewing's sarcoma. Time to development of SMN ranged from 125 to 194 months post-irradiation. Initial irradiation total dose ranged between 32 and 45.76 Gy. Three patients were treated with anterior field irradiation and three received lens-sparing techniques (anterior/lateral n = 2, lateral n = 1). At last follow-up, 4/6 patients had died of SMN. The crude incidence is 3.5% with an estimation of risk using the density method of 24% at 20 years for SMN development. The specifics of the treatment associated with these second malignancies and the possible reasons for the reported incidence of SMN will be discussed.

Child↗
PubMed1995

Expression of the proto-oncogene rhombotin-2 is identical to the acute phase response protein metallothionein, suggesting multiple functions.

Rhombotin-2 (RBTN-2) is a LIM domain protein that, with the exception of thymocytes, is widely expressed during fetal development. Although RBTN-2 is crucial for normal erythropoiesis, the ectopic expression of RBTN-2 in T lymphocytes results in T-cell proliferation and leukemogenesis. Thus, while a proliferative function for RBTN-2 has been established in T-cells, neither its role in erythropoiesis nor its function(s) in other tissues are known. We have examined the expression and location of RBTN-2 in normal and malignant cells. Similar to fetal development, RBTN-2 RNA was detected in all normal adult tissues tested with the exception of colon and thymocytes. RBTN-2 RNA was not detected in all primary tumors and tumor cell lines, indicating RBTN-2 expression is not ubiquitous in proliferating cells. Using polyclonal antisera, RBTN-2 was detected predominantly in the nucleus of human hematopoietic cells. Significantly, human leukemic T cells with disruption of the RBTN-2 locus and thymocytes from transgenic mice with enforced expression of RBTN-2 showed similar nuclear location of RBTN-2 protein, consistent with the notion that RBTN-2 acts as a transcriptional regulator in T-cell proliferation. Surprisingly, in normal tissues, RBTN-2 showed a strikingly similar distribution to that of metallothionein-1, having both nuclear and cytoplasmic localization that suggested that RBTN-2 may be involved in the acute phase response. Indeed, similar to metallothionein-1, RBTN-2 mRNA was induced in thymocytes of mice exposed to zinc and in human thymocytes treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Since the LIM domain permits binding of multiple protein partners, the specific function of RBTN-2 may depend upon subcellular sequestration through interaction with different cofactors. Thus, in addition to its roles in erythropoiesis and T-cell leukemia, RBTN-2 may also be involved in the acute phase response.

Acute-Phase Proteins↗
PubMed1995

Multiplex RT-PCR assay for the differential diagnosis of alveolar rhabdomyosarcoma and Ewing's sarcoma.

Cytogenetic analysis has defined specific translocations associated with two of the most common small round cell tumors of childhood, t(11;22) in Ewing's sarcoma and t(2;13) in alveolar rhabdomyosarcoma. We and others have previously demonstrated the diagnostic utility of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for the detection of the t(11;22) encoded EWS/FLI-1 chimeric message in Ewing's sarcoma. More recently, we have cloned the t(2;13)(q35;q14) translocation and have shown that it results in the fusion of the PAX3 gene on chromosome 2 to FKHR, a novel member of the fork-head family of transcription factors on chromosome 13. To define the morphological spectrum of childhood sarcomas that express the t(2;13) encoded PAX3/FKHR chimeric message, we have performed RT-PCR analysis on samples from 44 primary pediatric sarcomas and 8 sarcoma cell lines. PAX3/FKHR chimeric messages were detected in 24 of 27 alveolar, 2 of 12 embryonal, and 0 of 1 pleomorphic rhabdomyosarcoma and in 1 of 2 ectomesenchymomas. In contrast, none of 8 Ewing's sarcomas or 2 undifferentiated sarcomas expressed this message. Chimeric transcripts were detected in all cases with cytogenetic evidence of the (2;13) translocation, and in each case the chimeric PAX3/FKHR message had the identical junction sequence, suggesting that genomic chromosome breaks were clustered in a single intron in both genes. By combining the PAX3/FKHR RT-PCR assay with primers for detection of the Ewing's sarcoma t(11;22) encoded EWS/FLI-1 chimeric transcript, we have developed a multiplex RT-PCR reaction that allows the rapid and accurate identification of either translocation in a biopsy sample.

Base Sequence↗
PubMed1995

Nonrhabdomyosarcomatous soft tissue sarcomas of childhood: formulation of a simplified system for grading.

Because of the rarity of pediatric nonrhabdomyosarcomatous soft tissue sarcomas, it is difficult to test standardized treatment protocols for individual tumor entities. Grading has been used successfully to predict outcome of adult sarcomas, but pediatric soft tissue tumors display a notable difference in clinical behavior when compared to older patients. To test systematically a standardized treatment strategy for pediatric nonrhabdomyosarcomastous soft tissue sarcomas devised by the Pediatric Oncology Group, the authors devised a grading schema using concepts of adult grading systems and integrating the unique clinical and morphologic features of pediatric sarcomas. Three grading tiers were devised: Grade I, which includes certain pediatric tumors with little propensity for malignancy; Grade II, which is composed of tumors excluded from Grades I or III by virtue of histologic diagnosis and having <5 mitoses/10 high-power fields or <15% geographic necrosis; and Grade III, which comprises certain tumors known to be clinically aggressive by virtue of histologic diagnosis and non-Grade I tumors with >4 mitoses/10 high-power fields or > 15% necrosis. An initial retrospective analysis on a series of lesions treated at a single institution indicated a strong predictive value for grading. Subsequent prospective studies by the Pediatric Oncology Group continue to verify the prognostic value of pediatric nonrhabdomyosarcomatous soft tissue sarcoma grading, and studies on individual pediatric nonrhabdomyosarcomatous soft tissue sarcomas, such as synovial sarcoma, also indicate the relatively poor outcome of higher grade lesions. Grade can be used to predict outcome of pediatric nonrhabdomyosarcomatous soft tissue sarcomas and to devise treatment strategies for experimental protocols.

Adolescent↗
PubMed1994

Giant actin inclusions in hematopoietic cells associated with transfusion-dependent anemia and grey skin discoloration.

We evaluated a 13-month-old boy with cytoplasmic inclusions in hematopoietic cells, transfusion-dependent anemia, splenomegaly, and striking grey skin discoloration. Bright blue inclusions, 1 to 5 microns in diameter, were observed, primarily in the cytoplasm, of 30% to 40% of myeloid cells and in occasional monocytes, megakaryocytes, and lymphocytes on Wright Giemsa-stained bone marrow and blood smears. They occasionally involved the nucleus. The inclusions lacked lysosomes, polysaccharides, or lipids. Ultrastructurally, they lacked limiting membranes and consisted of tightly packed microfilaments averaging 7 nm in diameter, consistent with the size of actin monofilaments. On light microscopy, the inclusions stained with a monoclonal antibody to muscle-specific actin. Inclusion-positive cells contained increased F-actin content and were defective in chemotactic factor-activated actin polymerization; inclusion-negative cells polymerized actin normally. Neutrophil and platelet numbers and functional studies were mildly abnormal. Anemia and skin discoloration resolved spontaneously after 18 months, but the giant inclusions have persisted to the present. We conclude that this child has a previously unreported constellation of clinical and laboratory findings comprising severe anemia, intermittent neutropenia and thrombocytopenia, abnormal neutrophil migration and platelet aggregation, giant inclusions of actin in hematopoietic cells, and grey skin discoloration.

Actins↗
PubMed1994

Paratesticular rhabdomyosarcoma: delayed effects of multimodality therapy and implications for current management.

BACKGROUND: The combined modalities of surgery, chemotherapy, and radiation therapy have greatly improved the survival rate in childhood paratesticular rhabdomyosarcoma, but the incidence of complications and late side effects is a cause for concern. METHODS: We reviewed the records of 18 patients treated for paratesticular rhabdomyosarcoma at St. Jude Children's Research Hospital between 1962 and 1989. Patients with Group I disease were treated with orchiectomy, retroperitoneal lymph node dissection, and multi-agent chemotherapy; more advanced cases also received radiation therapy with concurrent chemotherapy. RESULTS: Sequelae included esophageal and common bile duct stricture, inguinal nerve entrapment syndrome, and small bowel obstruction. Short stature was found in all children whose spines were irradiated via para-aortic fields (34-37 Gy) prior to puberty. Two of 18 patients died from treatment complications and one from progressive disease. CONCLUSIONS: Multimodality treatment offers an excellent prognosis in paratesticular rhabdomyosarcoma, but is associated with significant morbidity and mortality rates. A discussion of therapy components and their application to disease stages suggests possible approaches to optimizing treatment for this therapy-sensitive malignancy.

Adolescent↗
PubMed1994

Long-term survival associated with metastatic small cell carcinoma of the esophagus treated by chemotherapy, autologous bone marrow transplantation, and adjuvant radiation therapy.

A 44-year-old woman had small cell carcinoma of the esophagus complicated by liver and lymph node metastases. She was treated with aggressive combination chemotherapy, followed by autologous bone marrow transplantation and adjuvant radiation therapy. (The authors believe this to be the first use of autologous bone marrow transplantation for treatment of this condition.) This regimen resulted in apparent complete regression of the disease as documented by computed tomography and endoscopic study. Three years later, she again experienced general malaise and was found to have extensive recurrent disease in the lung, bone, and liver. Her condition deteriorated rapidly, and she died within 1 month. A review of the literature reveals that this patient survived longer than any others who have had this rare but aggressive tumor. The authors suggest that this form of therapy should be considered for future patients.

Adult↗