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T M Ulbright

Publications and source records attributed to T M Ulbright.

At least 91 records · Page 5Linked to original sources

Choriocarcinoma-like lesions in patients with testicular germ cell tumors. Two histologic variants.

Nine men with testicular germ cell tumors developed one of two types of histologically similar cystic lesions that had features of choriocarcinoma. In five cases, these choriocarcinoma-like lesions (CCLL) were felt to represent an unusual proliferation of teratomatous epithelium (teratomatous CCLL); whereas in four cases, the CCLL was felt to represent a nonbiphasic and cystic form of choriocarcinoma similar to the atypical choriocarcinoma described by Mazur et al. except for its cystic nature. Both types usually occurred as focal findings associated with teratomas. Eight of nine patients had received chemotherapy prior to excision of the CCLL. Teratomatous CCLLs often had a lacelike arrangement of atypical epithelium around cysts that contained homogeneous secretion. Mucicarmine stains were positive in four of five cases of teratomatous CCLLs. Cystic atypical choriocarcinoma consisted of stratified mononucleated cells lining cysts containing a coagulum of eosinophilic material. Stains for human chorionic gonadotropin (HCG) were positive in three of four cases of cystic atypical choriocarcinoma, although serum HCG elevations were either negative or just slightly elevated preoperatively. Five patients with a CCLL who were clinically free of disease following surgical excision and who received no additional chemotherapy remained well on follow-up (average, 1.9 years). We encourage the separate recognition of these lesions so that future studies may determine their clinical significance more precisely.

Adult↗

The significance of atypia within teratomatous metastases after chemotherapy for malignant germ cell tumors.

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.

Adolescent↗

Primary carcinoma of the fallopian tube: evidence for activity of cisplatin combination therapy.

The records of 23 patients with confirmed carcinoma of the fallopian tube, treated between 1966 and 1983, were reviewed. Patients ranged in age from 41 to 88 years. A pelvic mass was the most common preoperative finding (61%), followed by abnormal bleeding (43%), and pain (39%). Fifteen patients had stage I or II disease, 8 had Stage III or IV disease. In patients with metastatic disease, involvement of the peritoneal surfaces, bowel, and omentum were noted most often. Lymph nodes were the most common site(s) of recurrent disease. Twelve evaluable patients with measurable disease were treated with cisplatin and cyclophosphamide (PC) +/- doxorubicin (PAC). There were 9 complete and 2 partial responses, a 92% response rate. Incorporation of cisplatin therapy appears to have resulted in improved short-term survival.

Adenocarcinoma↗

Poorly differentiated (small cell) carcinoma of the ovary in young women: evidence supporting a germ cell origin.

The clinical and pathologic features, including immunohistochemistry and electron microscopy, of six cases of poorly differentiated carcinoma of the ovary (small cell carcinoma) are presented. These tumors occurred in six young patients ranging in age from 10 to 24 years. Two patients had hypercalcemia. All tumors were unilateral, and four patients had advanced stage disease at presentation. Histologic features included sheets, nests, and cords of cells in a fibrous stroma, focal microcysts, and a dimorphic population of small and large cells. Eosinophilic, hyaline globules occurred in five cases, intercellular basement membrane-like substance in two cases, and glycogen in all cases. Five of six cases stained strongly for cytokeratin and vimentin; intracytoplasmic laminin was identified in three cases; and three cases were believed to show faint positivity for alpha-1-antitrypsin. Stains for alpha-fetoprotein were negative. Ultrastructural examination of two cases showed granular material in dilated rough endoplasmic reticulum, intermediate filaments, intracytoplasmic dense globules, maculae adherens, and extracellular basement membrane-like material. All of the cases proved rapidly fatal despite various therapies, as did a histologically similar testicular tumor that was admixed with seminoma and teratoma. We interpret these findings to indicate that this ovarian cancer is most likely of germ cell origin, and it may be related to yolk sac tumor, although it is clearly distinct from the classical yolk sac tumor.

Adolescent↗

The differential diagnosis of yolk sac tumor and seminoma. Usefulness of cytokeratin, alpha-fetoprotein, and alpha-1-antitrypsin immunoperoxidase reactions.

Yolk sac tumor and seminoma may have a similar appearance in focal areas. Small biopsies may therefore be difficult to interpret. The authors studied 20 yolk sac tumors and 21 seminomas to investigate the utility of immunohistochemical markers in this differential diagnosis. All yolk sac tumors stained positively for cytokeratin (CK) but so did 43% of seminomas. The CK positivity of yolk sac tumors was generally more diffuse and intense, however, there was an overlap in the spectrum of intensity of CK positivity in yolk sac tumor and seminoma. Alpha-fetoprotein (AFP) was a less sensitive (55%) marker for yolk sac tumor than CK, but AFP was quite specific in this differential diagnosis because no seminoma stained for AFP. Alpha-1-antitrypsin was not a very useful marker because of poor sensitivity and specificity. The interpretation of light microscopic patterns remains of paramount importance in the differentiation of solid yolk sac tumor from seminoma.

Diagnosis, Differential↗

Distribution of phosphodiesterase I in normal human tissues.

Phosphodiesterase I (PDE I) is an exonuclease capable of hydrolyzing a variety of phosphate ester and pyrophosphate bonds. Cell fractionation and histochemical studies in animal tissues have localized PDE I in the plasma membrane of various epithelia. This suggests a role for the enzyme in active transport. Distribution of PDE I in human tissues has not previously been studied. We have produced a polyclonal antiserum to bovine intestinal PDE I and have demonstrated crossreactivity with the human intestinal enzyme. This polyclonal antiserum was used in PAP immunocytochemistry to localize immunoreactive PDE I in a variety of human tissues. Localization was prominent in the gastrointestinal tract, including the cytoplasm of gastric mucosa parietal cells, cytoplasm of surface epithelium and isolated crypt cells in small intestine, and the colonic epithelial cytoplasm and brush border. Parotid gland acinar cells and scattered ductal cells showed positive cytoplasmic staining. Acinar and scattered pancreatic islet cells contained immunoreactive PDE I, as did Kupffer cells of the liver sinusoids. Immunoreactive PDE I was found in all vascular endothelia. The epithelium of the urinary tract showed extensive immunoreactivity. This included the distal convoluted and collecting tubules of the kidney, and ureteral and bladder urothelium. In previous histochemical studies of animal tissues, no evidence of PDE I activity was noted in male or female reproductive tract. In this study, immunoreactive PDE I was localized to human Sertoli cells and to basal epithelium of the epididymis and prostate acini. Fallopian tube epithelium of female reproductive tract also demonstrated immunoreactive PDI I, as did several cell types in term placenta. Our immunocytochemical results with human tissues differ significantly from previous histochemical studies in animal tissues, principally in the genitourinary system. This may be due in part to the different detection systems employed as well as the higher sensitivity of the immunoperoxidase technique. This underscores the importance of adjunct techniques in tissue surveys. The widespread epithelial distribution of immunoreactive PDE I detected by this polyclonal antibody implies an integral role in cell function, probably in active transport.

Histocytochemistry↗

Recent developments in the pathology of germ cell tumors.

This article describes some of the recent developments in the pathology of germ cell tumors of the testis. Many germ cell tumors show different types of differentiation. Two different explanations for this phenomenon include the differentiation of other germ cell elements from totipotential embryonal carcinoma cells or the direct differentiation of neoplasms from a malignant intratubular germ cell. Although the concept that there is a subset of seminomas having a poorer prognosis still exists, the histologic identification of such "anaplastic seminoma" remains an unachieved goal, and we, therefore, do not recommend the use of the term anaplastic seminoma at present. A recent analysis of spermatocytic seminomas has failed to demonstrate that they are capable of meiotic division. They are composed of cells differentiating in the direction of spermatocytes, but they have not achieved that stage. The prognosis, in general, remains excellent, although recently sarcomas have been reported in association with spermatocytic seminomas with metastasis of the sarcomatous elements. The presence of human chorionic gonadotropin-producing syncytiotrophoblastic giant cells in otherwise pure seminomas does not appear to adversely affect the prognosis. Yolk sac tumors have a varied histology that many pathologists do not recognize. The presence of intercellular basement membrane (parietal differentiation) is useful in the recognition of yolk sac tumor. Sometimes solid foci of yolk sac tumor may be mistaken for seminoma, and alpha-fetoprotein and cytokeratin stains may be useful in this situation, although the presence of basement membrane, hyaline globules, and focal microcysts by light microscopy may obviate the need to use them. Hepatic and enteric (or endometrioid) differentiation may occur in yolk sac tumors and cause diagnostic confusion. The development most "non-germ" cell malignancies in patients with germ cell tumors appears to occur by transformation of aneuploid teratomatous elements at the primary or metastatic site. The identification of such malignancies depends on the recognition of invasion by the elements rather than on high-grade cytologic atypia. Unusual patterns of choriocarcinoma and yolk sac tumor may be encountered following chemotherapy, and there is circumstantial evidence that some sarcomas and carcinomas occurring in patients with testis cancer may develop directly from yolk sac tumor.

Drug Therapy↗

Evaluation of the reproducibility of the World Health Organization classification of common ovarian cancers. With emphasis on methodology.

Seven pathologists independently classified 50 slides of ovarian tumors using category I of the World Health Organization classification (WHO I), each case being seen twice under different random code numbers. Intraobserver reproducibility and interobserver reproducibility, based on consistent interpretations, were both suboptimal. However, scrutiny suggested that no pathologist was a source of excessive variability, nor was suboptimal interobserver reproducibility simply due to intraobserver variability. Neither could excessive variability be attributed to skewing of results by a subgroup of unclassifiable cases. However, clearcut sources of variability were identified among the categories of WHO I, namely, mixed epithelial, unclassified epithelial, and undifferentiated carcinoma. There was also considerable variability in distinguishing serous and endometrioid neoplasms, and in identifying tumors of low malignant potential. These findings should not be misconstrued as implying that pathologists in routine practice cannot diagnose common ovarian cancers reproducibly for patient care purposes. Availability of clinical and macroscopic data, extensive sampling, histochemistry, and consultation combine, in an uncontrolled and highly individualistic fashion, to render routine service work very different from this highly controlled formal exercise. Furthermore, at the current state of the therapeutic art, many of the taxonomic problems identified in this study may have little clinical significance. Nonetheless, this study has strengthened the evidence that there may be important problems in classifying common ovarian cancers reproducibly using WHO I, and that WHO I may require greater clarity to enhance reproducibility. Current emphasis on quality assurance dictates reconsideration of the literature on reproducibility of histopathologic taxonomy, which has tended to inculpate pathologists as sources of variability. Virtually all of this literature is subject to some degree of skepticism due to deficiencies in methodology. Consideration of the question of how to measure reproducibility in anatomic pathology leads us to suggest that the community of pathologists should address the need to decrease ambiguity in classification systems as an important step toward optimizing reproducibility.

Female↗

The differentiation of carcinomas of teratomatous origin from embryonal carcinoma. A light and electron microscopic study.

Carcinomas derived from teratomatous epithelium occur rarely in the metastases of patients with testicular cancer. These carcinomas of teratomatous origin (CTO) are easily confused with residual embryonal carcinoma (EC). For that reason, we compared the light and electron microscopic appearances of 6 CTOs with those of 12 ECs. As seen by light microscopy, the CTOs formed glands and more frequently had well-defined cytoplasmic borders, eosinophilic cytoplasm, and nonoverlapping, regular nuclei with small or absent nucleoli and little chromatin clumping and clearing, compared with the ECs. Mucin was present in the cells or glandular lumina of three CTOs but was absent in all the ECs. The demonstration of cytoplasmic glycogen was of no differential aid. The most useful differentiating ultrastructural features were long tight junctions and telolysosomes, which occurred in all of the EC but which were absent in the six cases of CTO. Desmosomes with inserting tonofilaments were present in three cases of CTO but were much less developed in EC. Two cases of CTO had microvilli with anchoring rootlets; such anchoring rootlets were not observed among EC. The distinction of CTO from residual EC is important, because CTO will likely need to be treated in a different manner.

Cell Transformation, Neoplastic↗

Pancreatic amylase expression in human pancreatic development.

Enzymatic and immunologic methods were used to study amylase expression in amniotic fluid and human pancreatic tissue from fetuses of various gestational ages. A starch-coated slide assay was used to quantitate amylase activity in amniotic fluids, and samples with activity were studied by electrophoresis to determine the presence of salivary amylase (Amy1) and pancreatic amylase (Amy2) isozymes. Immunohistochemical studies were performed with both a rabbit anti-human Amy1 antibody and a murine anti-human Amy2 antibody (Amy2/SP2/1). Amy2/SP2/1 was used to discriminate between Amy1 and Amy2. Both Amy1 and Amy2 activities were present in amniotic fluid from 14 weeks' gestation, and immunologic activity was present in pancreatic tissue sections from 15.9 weeks' gestation.

Amniotic Fluid↗

Microimmunoassay permits determination of concentrations in immunohistochemistry controls.

A competition enzyme-linked immunosorbant assay (CELIA) can be used to determine the amount of antigen needed to immunoabsorb an antiserum. This is demonstrated using both polyclonal and monoclonal antibodies against human amylase. This method is of especial value when the tissue is particularly difficult to obtain, and especially valuable when CELIA has already been completed.

Amylases↗

Yolk sac differentiation in germ cell tumors. A morphologic study of 50 cases with emphasis on hepatic, enteric, and parietal yolk sac features.

We assessed 50 germ cell tumors with areas of yolk sac tumor (YST) for a variety of features including histologic patterns; hyaline droplets; syncytiotrophoblastic elements; hepatic, enteric, and parietal yolk sac differentiation; and granulomatous reaction. Of prime interest was the fact that many YSTs formed hepatic-like foci (22%), enteric-like glands (34%), and parietal yolk sac structures (92%). Hepatoid areas were characterized by nests and cords of polygonal, acidophilic cells with prominent nucleoli and intense cytoplasmic staining for alpha-fetoprotein. Enteric differentiation occurred as well-defined glands with a sharp, striated border and relatively bland nuclear features. Ultrastructurally these glands had apical microvilli with associated glycocalyx and long anchoring rootlets. The apical cytoplasm and luminal contents stained for carcinoembryonic antigen. Parietal yolk sac differentiation was characterized by the intercellular accumulation of basement membrane substance as generally thick and longitudinally arranged bands of eosinophilic material. Such material, by electron microscopy, was both intra- and extracellular, and had irregular outlines and inhomogeneous electron density. It contrasted with the strictly intracellular, round, homogeneous, hyaline globules that, we believe, represent visceral yolk sac differentiation. This intercellular material stained positively for laminin, a basement membrane component. Assessment of 22 embryonal carcinomas and 24 germinomas failed to show hepatic, enteric, and parietal yolk sac features, with one possible exception. We believe these features, especially parietal yolk sac differentiation, are helpful in differentiating YSTs from embryonal carcinomas and germinomas.

Carcinoembryonic Antigen↗

Second-look laparotomy after chemotherapy in the management of ovarian malignancy.

Eighty-eight patients with ovarian malignancy underwent second-look laparotomy as part of their plan of management at Indiana University Hospital. Thirty-five patients (39.8%) were found to have no gross or microscopic evidence of persistent neoplasm, and an additional 16 (18.2%) had only microscopic tumor. Patients with initial Stage III or IV disease were less likely to have negative findings at laparotomy than were patients with Stage I or II disease. A complete initial cytoreductive operation (residual disease = 0 cm) correlated positively with negative findings at laparotomy. Endometrioid histologic findings were associated with a favorable condition at the second look, but tumor grade was associated with superior survival only for patients with grade 0 disease. Eight of 30 patients (26.7%) with invasive carcinoma and negative findings at second-look laparotomy have had tumor recurrence (2 to 63 months), and five of eight have died. Intraperitoneal chromic phosphorus salvage therapy for patients with microscopic disease was promising, with eight of 15 treated patients (53.3%) alive after therapy, with no evidence of disease from 16 to 56 months after the second look. Second-look laparotomy has been the major determinant of continued or alternative therapy for patients with ovarian malignancy. Second-look laparotomy has been incorporated into the standard management plan without a formal clinical trial. The need for a second look may be reduced by identifying patients who do not benefit from the procedure. Patients with persistent disease confirmed by noninvasive means can continue therapy without laparotomy. There is also a subgroup of patients with a favorable prognosis whose therapy could be safely discontinued without laparotomy.

Adenocarcinoma↗

Angiosarcoma associated with germ cell tumors.

In two patients with malignant germ cell tumors angiosarcoma developed through two apparently different mechanisms. In one case the angiosarcoma probably developed as a complication of therapeutic radiation, since radiation changes were demonstrated in tissue adjacent to the neoplasm and since the angiosarcoma was not associated with elements of germ cell tumor. The absence of associated germ cell elements does not support the development of the angiosarcoma from a teratoma. In the second case, however, it is likely that the angiosarcoma developed as a result of malignant change within teratomatous foci, since angiosarcomatous elements were intermingled with teratomatous elements and the patient's primary germ cell tumor contained malignant and atypical teratomatous elements as well as prominent vascular proliferation. Malignant change within teratomatous components of germ cell tumors is a phenomenon of increasing importance in this era of effective chemotherapy for germ cell tumors. The development of angiosarcoma as a potential complication of testicular carcinoma has not been reported previously.

Adolescent↗

Metastatic and independent cancers of the endometrium and ovary: a clinicopathologic study of 34 cases.

Twenty-one of 34 simultaneous cancers involving the endometrium and ovary were classified as endometrial primary tumors with ovarian metastases. The criteria for this classification were either a multinodular ovarian pattern (major criterion) or two or more of the following minor criteria: small (less than 5 cm) ovary(ies), bilateral ovarian involvement, deep myometrial invasion, vascular invasion, and tubal lumen involvement. Twelve cancers were classified as independent neoplasms, primarily by the absence of the above criteria. Although they were classified as independent, the histologic features of the endometrial and ovarian tumors were the same in 11 of these 12 cases. Only one case represented an ovarian primary tumor with an endometrial metastasis. Both the group believed to have endometrial primaries with ovarian metastases and that with independent primaries showed high incidences of associated endometrial hyperplasia, supporting the belief that the endometrium is a primary site in both groups. The cancers classified as metastatic, with no known spread outside the endometrium-myometrium and ovary, were found to involve other sites significantly (P less than 0.01) more frequently than those classified as independent. Grade 3 endometrioid carcinoma, adenosquamous carcinoma, and malignant mixed müllerian tumors occurred only in the metastatic group, whereas the independent group had a variety of endometrioid and nonendometrioid tumors.

Carcinoma↗

Common epithelial tumors of the ovary: proliferating and of low malignant potential.

Ovarian tumors of low malignant potential (LMP) must be distinguished from benign, "proliferating" ovarian tumors and from frank ovarian carcinoma. Serous and mucinous tumors of LMP demonstrate epithelial stratification, the formation of epithelial tufts, cytologic atypia, and mitotic activity, but they do not demonstrate stromal invasion by epithelial cells, which is a feature of frank carcinoma. Mucinous carcinoma may also be recognized by epithelial stratification exceeding three cell layers and the formation of true cribriform glandular patterns. Although controversial, we do not at present recognize a LMP tumor of endometrioid type but prefer to classify those endometrioid neoplasms with a prominent fibrous stroma and glandular complexity similar to adenomatous endometrial hyperplasia as proliferating endometrioid adenofibromatous and cystadenofibromatous tumors. There is only mild cytologic atypia in such tumors. Because of the moderate to marked cytologic atypia that occurs in some clear cell neoplasms with a prominent fibrous stroma, we believe those tumors do merit a designation of LMP tumors. In both the proliferating endometrioid and LMP clear cell adenofibromatous and cystadenofibromatous tumors, carcinoma must be excluded by an absence of stromal invasion, which is frequently recognized by a confluent glandular pattern. The histologic features of proliferating Brenner tumors are similar to those of low grade, papillary, noninvasive, urothelial carcinoma, whereas we propose that Brenner tumors of LMP show high grade cytologic atypia but remain noninvasive in the ovary.

Adenocarcinoma↗

The development of non-germ cell malignancies within germ cell tumors. A clinicopathologic study of 11 cases.

Eleven male patients had germ cell tumors of the testis (7), mediastinum (3), or retroperitoneum (1) in which non-germ cell malignancies developed. Such malignant non-germ cell elements were present in the primary excisions of five patients and were subsequently found in additional resected tissue in 10 of 11 patients. In the patients who had multiple pathology specimens examined, a progression from atypia to predominant non-germ cell malignancy was often found. The authors believe these malignant elements arose within teratomatous foci, since eight of nine cases had teratoma in the primary tumor, and teratoma was found in subsequently resected tissue in one additional case. Cisplatin therapy frequently "unmasked" the non-germ cell malignant elements by destroying the more chemosensitive germ cell cancers. The prognosis was worst for five patients who developed progressive embryonal rhabdomyosarcoma: two of these patients died of local spread of tumor, whereas a third died of metastatic sarcoma. Only one patient, who had total surgical excision of rhabdomyosarcoma, survived. Other forms of sarcoma that developed within germ cell tumors did not appear to adversely affect the prognosis beyond that of teratoma. It is currently recommended, when feasible, that patients with teratoma and sarcoma undergo total surgical excision. Further treatment with cisplatin regimens, after eradication of the germ cell component, has not been helpful. The role of other forms of chemotherapy remains speculative.

Adolescent↗

Secondary ovarian neoplasia. A clinicopathologic study of 35 cases.

The authors reviewed the clinical and pathologic features of 35 cases of secondary ovarian neoplasms in which the clinical presentation was that of a primary ovarian tumor. The most common secondary neoplasms to mimic an ovarian tumor were colonic adenocarcinoma, breast carcinoma, lymphoma, carcinoid, and gastric adenocarcinoma. It was found that a classification based on gross appearance was useful in evaluating these neoplasms. Solid neoplasms with either a diffuse or nodular gross appearance had distinct histologies so that accurate diagnosis was possible. Cystic neoplasms, especially colon adenocarcinomas, were deceptive and frequently misclassified as primary ovarian adenocarcinoma. Since all of the metastatic colonic carcinomas had mucus-containing cells, the main differential diagnosis was between metastatic colonic carcinoma and primary mucinous carcinoma of the ovary. The absence of a mucus-cell predominant pattern and the lack of transition from benign-appearing epithelium to malignant epithelium are two useful criteria in making this important distinction. Other features may also prove helpful.

Adolescent↗