Case 2. Desmoplastic small cell tumor with divergent differentiation.
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Abdominal Neoplasms↗
Biomedical subjects
W L Gerald
Publications and source records attributed to W L Gerald.
The immunologic approach to analysis of malignant lymphoma. Mantle zone lymphoma of the ileocecal region.
We studied an unusual type of lymphoma of the ileocecal region using an established protocol that combines morphologic, flow cytometric, and immunohistochemical analyses. This lymphoma grew as multiple submucosal nodules, some of which had coalesced into a mass in the terminal ileum. Histologically, the lesion resembled a lymphoma of follicular center-cell origin except for germinal centers that appeared reactive and greatly expanded follicular mantles. Flow cytometric studies showed that the lymphoma contained a monoclonal, kappa+ population of B-lymphocytes. Evaluation of sections of frozen tissue by an immunoperoxidase technique revealed that the germinal centers were polyclonal (nonneoplastic) and that the neoplastic cells were confined to the mantle zone. The additional information led to classification of the neoplasm as the mantle zone variant of intermediate lymphocytic lymphoma. This type of lymphoma may pursue a more aggressive course than a follicular lymphoma derived from the germinal center. We review our general approach to the analysis of hematolymphoid neoplasms and discuss how certain techniques may be useful adjuncts in the evaluation of these types of tumors.
Antibodies, Monoclonal↗
Sex dimorphism and hormonal regulation of rat tissue kallikrein mRNA.
The regulation of rat tissue kallikrein mRNA levels was investigated by RNA filter hybridization using a kallikrein cDNA probe and by in vitro translation of isolated RNA. The synthesis of a 37 kDa polypeptide has been hybrid-arrested by the tissue kallikrein cDNA in cell-free translation assays directed by submandibular mRNA and the quantitation of this protein was used as a measure of translational activity of kallikrein mRNA. In Northern blot analyses, relative kallikrein mRNA levels were found to be 60-fold higher in submandibular gland than in pancreas and 20-fold higher than in kidney. In addition, it was noted that kallikrein mRNA is differentially regulated in tissues from male and female animals. Rat submandibular gland kallikrein mRNA is 2-times more abundant in male animals as in females. This trend is reversed in kidney, where the kallikrein mRNA in females is twice that in male animals. Relative submandibular gland kallikrein mRNA levels were found to be responsive to hormonal manipulation as measured by both Northern blotting and cell-free translation assays. Castration of male animals resulted in a decrease of kallikrein mRNA which could be partially restored by treatment with thyroxine and almost completely restored by testosterone treatment. The submandibular gland kallikrein mRNA in normal female rats was increased up to 30% by administration of testosterone or thyroxine. Adrenalectomized female rats showed a decrease in submandibular kallikrein mRNA which was significantly increased by testosterone, thyroxine, aldosterone and cortisol, with the largest effect being a 2- to 2.4-fold increase in cortisol-treated rats. These results indicate that hormones regulate tissue kallikrein synthesis in the rat submandibular gland, at least in part, by altering kallikrein mRNA accumulation.
Adrenalectomy↗
Immunological identification of rat tissue kallikrein cDNA and characterization of the kallikrein gene family.
A tissue kallikrein cDNA was identified by direct immunological screening with affinity-purified anti-rat tissue kallikrein antibody from a rat submandibular cDNA library constructed with the expression vector pUC8. Sequence analysis of the kallikrein cDNA revealed an encoded protein 97% homologous to the partial amino acid sequence of rat submandibular kallikrein. This cDNA was used to hybrid-select kallikrein-specific RNA from submandibular gland. Translation of the hybrid-selected RNA in a cell-free assay system resulted in the production of a 37 kDa peptide representing the preproenzyme. In addition, hybrid-selection of RNA under less stringent conditions showed cross-hybridization with other submandibular gland mRNA species. In correlation with these results, analysis of rat genomic DNA showed extensive hybridization, suggesting a family of closely related kallikrein-like genes. Consequently, a Charon 4A rat genomic library was screened for kallikrein genes by hybridization with rat tissue kallikrein cDNA. Thirty-four clones were isolated and found to be highly homologous by hybridization and restriction enzymes analyses. Fourteen unique clones were identified by restriction enzyme site polymorphisms within DNA segments which hybridized to the kallikrein cDNA probe and it was estimated that at least 17 different kallikrein-like genes are present in the rat. Sequence and structural analysis of one of the genomic clones revealed a gene structure similar to that of other serine proteinases. Comparison of the partially sequenced exon regions of the gene with the sequence of rat tissue kallikrein cDNA reveals 89% identity when aligned for the greatest homology. However, the genomic sequence predicts termination codons in all three translational reading frames, implying that this gene is nonfunctional, i.e., a pseudogene. Comparison of the rat genomic sequence to a kallikrein-like gene from the mouse reveals extensive preservation of exons, less identity within introns and no significant homology between extragenic regions.
Animals↗
Squamous cell carcinoma in situ in condyloma acuminatum.
This is the 14th case report of squamous cell carcinoma in situ developing in perianal condyloma acuminata. A 72-year-old nonhomosexual man suffered this lesion 11 months after his condyloma was first fulgurated. The lesion was excised locally. He received no local or systemic chemotherapy. Random biopsies on several occasions since that time have not shown any evidence of local recurrence. Squamous-cell carcinoma in situ in perianal condyloma must be distinguished from Bowen's disease and extramammary Paget's disease of the perianal skin, both of which have associated skin rashes. Although Bowen's disease and extramammary Paget's disease frequently are associated with either local or distant malignancies, no such association has been found for squamous cell carcinoma in situ in condyloma unless the patient also has the acquired immunodeficiency syndrome (AIDS). Since this lesion is a premalignant lesion like Bowen's disease and extramammary Paget's disease, squamous cell carcinoma in situ in condyloma is treated by local excision. If the margins are free of tumor, the resection is curative. No local or systemic recurrence of this condition has been reported following adequate local resection. Patients with condyloma acuminata should undergo treatment to eliminate all of the warts. When the condylomata recur, or when the patient has AIDS, the lesions should be examined histologically for evidence of premalignant or malignant degeneration.
Aged↗
Expression of a DNA replication gene cluster in bacteriophage T4: genetic linkage and the control of gene product interactions.
The results of this study bear on the relationship between genetic linkage and control of interactions between the protein products of different cistrons. In T4 bacteriophage, genes 45 and 44 encode essential components of the phage DNA replication multiprotein complex. T4 gene 45 maps directly upstream of gene 44 relative to the overall direction of reading of this region of the phage chromosome, but it is not known whether these two genes are cotranscribed. It has been shown that a nonsense lesion of T4 gene 45 exerts a cis-dominant inhibitory effect on growth of a missense mutant of gene 44 but not on growth of phage carrying the wild-type gene 44 allele. In previous work, we confirmed these observations on polarity of the gene 45 mutation but detected no polar effects by this lesion on synthesis of either mutant or wild-type gene 44 protein. In the present study, we demonstrate that mRNA for gene 44 protein is separable by gel electrophoresis from gene 45-protein-encoding mRNA. That is, the two proteins are not synthesized from one polycistronic message, and the cis-dominant inhibitory effect of the gene 45 mutation on gene 44 function is probably expressed at a posttranslational stage. We propose that close genetic linkage, whether or not it provides shared transcriptional and translational regulatory signals for certain clusters of functionally related cistrons, may determine the intracellular compartmentalization for synthesis of proteins encoded by these clusters. In prokaryotes, such linkage-dependent compartmentation may minimize the diffusion distances between gene products that are synthesized at low levels and are destined to interact.
DNA Replication↗
Unusual postirradiation sarcoma of chest wall.
This paper reports a sarcoma of the chest wall following postoperative radiation therapy for breast carcinoma. A total of 9346 rads was delivered at a 2-cm tissue depth from two treatment courses separated by a five-year interval. The sarcoma appeared 16 years following the initial radiation course. The existence of two mesenchymal elements in the lesion led to the final diagnosis of malignant mesenchymoma. Criteria for evaluating a possible radiation-induced malignancy are discussed.
Breast Neoplasms↗
Desmoplastic small round cell tumors: prognostic indicators and results of surgical management.
BACKGROUND: Desmoplastic small round cell tumors (DSRCT or DSCT) are rare aggressive cancers of adolescence and early adulthood. There are few reported series to guide clinical therapy. This study correlates survival with treatment variables, including aggressive surgical debulking. METHODS: Thirty-two patients with documented DSRCT received treatment at our institution. Demographic, clinical, and treatment variables were correlated with progression-free survival using log-rank statistics. RESULTS: Thirty patients were male (96%), and two were female (4%), with a median age at diagnosis of 22 years. The primary site of disease in 97% of cases was the abdomen or pelvis. Twenty-nine patients (91%) had extensive disease involving peritoneal surfaces, lymph nodes, or discontinuous organs. All 32 patients received systemic chemotherapy. Fifteen (47%) underwent tumor debulking greater than 90% at diagnosis or during therapy. A complete or very good response to therapy occurred in 13 patients, and depended on surgical removal of bulk disease in all. Thirteen patients remained progression-free, but three of these patients died from treatment toxicity. Improved survival was correlated with a complete or very good partial response to multimodality therapy, surgical debulking of more than 90% either before or after chemotherapy, and use of the P6 protocol. CONCLUSIONS: DSRCT is an aggressive cancer that occurs predominantly in young males. Improved survival is correlated with intense chemotherapy and aggressive resection.
Abdominal Neoplasms↗