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T M Ulbright

Publications and source records attributed to T M Ulbright.

At least 37 records · Page 2Linked to original sources
PubMed1999

Microcystic Leydig cell tumors mimicking yolk sac tumor: a report of four cases.

We report four cases of Leydig cell tumor of the testis with a microcystic pattern that mimicked yolk sac tumor. The patients ranged in age from 27 to 35 years and, except for one tumor that was discovered incidentally, presented with testicular masses. All tumors were intratesticular, and three were well circumscribed by a rim of fibrous tissue, whereas one showed minor, focal extension into the adjacent testis. The tumors typically had a vaguely lobular architecture subdivided by fibrous bands. Three of the cases had a complex microcystic appearance caused by individually vacuolated cells and coalescent cystic spaces; this pattern accounted for the majority of two tumors. Another case had focal collections of Leydig cells with prominent cytoplasmic vacuoles but lacked the coalescent spaces. The microcyst contents ranged from optically clear to eosinophilic or lightly basophilic, with the latter having the staining qualities of acid mucopolysaccharide. Three tumors had uniform, bland nuclei and low mitotic rates (<1 mitotic figure per 10 high power fields), but one had marked, random nuclear pleomorphism and an average mitotic rate of five mitotic figures per 10 high power fields. By immunohistochemistry, all were diffusely positive for vimentin; two of three were positive for inhibin, and one showed focal positivity for cytokeratin (CAM 5.2). All were negative for alpha-fetoprotein and placentalike alkaline phosphatase and, apart from having microcystic and solid areas, lacked other features typical of yolk sac tumor. Clinical follow-up ranged from 2 months to 2 years with no patient having recurrence or metastasis. The distinction of Leydig cell tumor from yolk sac tumor has important clinical implications because patients with the former usually receive only clinical follow-up, but the latter often requires chemotherapy.

Adult↗
PubMed1998

Nephroblastoma-like tumors in patients with testicular germ cell tumors.

Nephroblastoma-like tumors (NLTs) developed in metastatic sites in nine men with testicular germ cell tumors (GCTs). These tumors had a characteristic "triphasic" admixture of primitive tubular structures, sometimes with a glomeruloid pattern, blastema and stroma. Skeletal muscle differentiation was apparent in two cases. Specific neuroendocrine markers (synaptophysin and chromogranin A) were negative. All patients were treated by surgical excision. Six patients were alive with no evidence of disease from 4 to 12 years after diagnosis of GCT and NLT. One patient was alive with disease 6 years after diagnosis of GCT and 3 years after diagnosis of NLT. One man who also had metastatic primitive neuroectodermal tumor (PNET) had short survival, and one patient died of postoperative infection. We conclude that patients with testicular GCTs in whom NLTs develop in metastatic sites often experience prolonged survival. Surgical excision appears to be adequate treatment for NLT arising in metastatic testicular GCT in most patients. It is important to distinguish NLTs from PNETs in metastatic GCTs because of the more aggressive course and the frequently fatal outcome of the latter.

Abdominal Neoplasms↗
PubMed1998

Identification of clinical stage A nonseminomatous testis cancer patients at extremely low risk for metastatic disease: a combined approach using quantitive immunohistochemical, histopathologic, and radiologic assessment.

PURPOSE: To evaluate previously determined predictors of metastasis in low-stage testis cancer in a consecutive group of clinical stage A patients. PATIENTS AND METHODS: Ninety-one consecutive clinical stage A nonseminomatous germ cell tumor (NSGCT) patients who underwent primary nerve-sparing retroperitoneal lymph node dissection (NSRPLND) had orchiectomy specimens and computed tomographic (CT) scans evaluated blindly in a quantitative fashion. These scores were then correlated with pathologic stage using previously determined paradigms. RESULTS: Using volume of embryonal carcinoma in the orchiectomy specimen, lymph node diameters in the primary landing zones and MIB-1 staining of the orchiectomy specimen, 41 patients were classified as low risk for metastasis. Forty of these 41 had pathologic stage A disease at RPLND. CONCLUSION: These parameters can identify a low-risk group of patients for metastasis who can be rationally offered surveillance.

Carcinoma, Embryonal↗
PubMed1998

Interphase chromosome painting of paraffin-embedded tissue in the differential diagnosis of possible germ cell tumors.

Germ cell tumors (GCTs) are the most frequent cancer in men aged 15 to 34 years. These tumors are highly responsive to therapy with platinum-containing regimens, and 80% of cases so treated can be considered cured. Cytogenetically, 80% of GCTs have an i(12p) regardless of tumor site or histopathology, and those that are i(12p) negative have other manifestations of 12p amplification. GCTs occasionally arise extragonadally, and such cases can be especially difficult to distinguish from poorly differentiated somatic carcinomas, a situation that poses a diagnostic and treatment dilemma We developed a technique for two-color fluorescence in situ hybridization chromosome painting on nuclei released from paraffin-embedded sections. In four tumors for which GCT was a differential diagnosis, we examined the 12p and 12q chromosome arm distributions by this technique. By use of 12p and 12q painting probes developed by microdissection, 12p and 12q were distinguished and their relative distributions evaluated. In each of the four cases, 12p regions seemed to be rearranged and over-represented relative to 12q regions. In three of the cases, an apparent i(12p) could be identified. These results support a diagnosis of GCT or GCT origin in these four cases. In tumors for which specific cytogenetic abnormalities are known, chromosome painting by fluorescence in situ hybridization using paraffin-embedded tissue is a useful technique to aid in the diagnosis of tumors that are difficult to differentiate. The patients can then be placed on treatment regimens appropriate for their specific tumor type.

Adult↗
PubMed1997

Bicolor fluorescence in situ hybridization on nuclei from formalin-fixed, paraffin-embedded testicular germ cell tumors: comparison with standard metaphase analysis.

Rearrangements of chromosome 12, especially i(12p), are common in testicular germ cell tumors (TGCT). We have developed 12p and 12q chromosome arm-specific painting probes for fluorescence in situ hybridization (FISH) through the use of chromosome microdissection. We developed a method to hybridize these probes to interphase nuclei released from formalin-fixed, paraffin-embedded tumors (PET). In this study, we compared simultaneous bicolor PET FISH painting with metaphase chromosome analysis of fresh tissue from the same tumor. Bicolor PET FISH produced patterns of 12p and 12q hybridization consistent with expectations based on metaphase chromosome analysis; adjoined 12p and 12q regions appeared to detect "normal" chromosome 12s, whereas relatively large isolated regions of 12p were suggestive of i(12p), and small 12p regions probably represent cryptic rearrangements of 12p. Fourteen tumors with successful cytogenetic analyses and available archival material from the same tumor source were selected for study. In a blinded analysis, PET FISH painting assessment was in very close agreement with karyotypic findings in seven subjects, in close agreement in five, and showed less agreement in two. Differences may be due in part to clonal selection during culture for metaphase studies, or regional selection within the tumor. Although PET FISH painting should not replace standard chromosome analysis, this study shows that it can reliably predict chromosome 12 constitution in TGCT, can serve as a useful adjunct to standard cytogenetics when such analysis is unsuccessful, and can provide limited karyotyping of archival materials.

Cell Nucleus↗
PubMed1997

Desmoplastic small round cell tumors of the paratesticular region. A report of six cases.

Desmoplastic small round cell tumor (DSRCT) typically occurs in the abdomen but may also present at other sites. We report six cases of paratesticular DSRCT. The patients, who ranged in age from 17 to 37 (mean, 28) years, presented with a scrotal mass (five cases) or testicular pain (one case). Grossly, the tumors were white to tan and firm. Typically, they involved the paratesticular soft tissue, serosal surfaces and the epididymis near the junction with the rete testis. Microscopically, the tumors consisted of nests of mitotically active "small blue cells" with scant cytoplasm embedded in a densely fibrotic stroma. Two tumors showed focal tubule formation; one of these also formed rosettes. The tumors exhibited the typical immunophenotype of DSRCT (positivity for keratin, vimentin, desmin, and neuron-specific enolase but nonreactivity with HBA-71 and anti-S-100). Four tumors metastasized to lymph nodes (retroperitoneal, cervical, and two unspecified); pulmonary metastases occurred in one of these cases and in one patient without lymph node metastases. One of the above patients treated with chemotherapy, died of disease at 16 months. The patients with pulmonary metastases (one of whom also had lymph node metastases) were treated with aggressive chemotherapy and are alive and apparently disease-free at 2.5 and 3 years, respectively. Three of the six patients, two of whom had known metastases, were lost to follow-up. The DSRCT of the paratestis has histologic and immunohistochemical features identical to its abdominal counterpart and must be differentiated from other "small blue cell" tumors of the paratesticular region.

Adolescent↗
PubMed1997

Trophoblastic tumors of the testis other than classic choriocarcinoma: "monophasic" choriocarcinoma and placental site trophoblastic tumor: a report of two cases.

We report two unusual forms of testicular trophoblastic tumor. One was a mixed germ cell tumor in a 19-year-old man that had a predominant component of nodules of cytotrophoblast cells with only rare syncytiotrophoblast cells. These nodules of "monophasic" choriocarcinoma were diffusely positive for human chorionic gonadotropin (hCG), which stained the syncytiotrophoblast cells more intensely; stains for human placental lactogen (HPL) highlighted only the latter cells. The second tumor occurred in a 16-month-old boy. It consisted of a pure proliferation of intermediate trophoblast cells and was identical to the placental site trophoblastic tumor of the uterus. The tumor cells showed diffuse immunoreactivity for HPL and patchy staining for hCG. Despite the occurrence of vascular wall invasion, the patient was alive and well at 8 years follow-up with no treatment other than orchiectomy. These cases show that trophoblastic tumors other than classic choriocarcinoma occur rarely in the testis. The differential diagnosis of the "monophasic" choriocarcinoma included seminoma and the solid variant of yolk sac tumor, but the tumor had larger, more irregular nuclei than those of seminoma and was not associated with distinctive yolk sac tumor patterns. The placental site trophoblastic tumor may be confused with Leydig cell tumor or choriocarcinoma, but awareness of its occurrence in the testis and the immunohistochemical findings should permit its recognition.

Adult↗
PubMed1997

Primitive neuroectodermal tumors arising in testicular germ cell neoplasms.

Twenty-nine young men (mean age 29 years) had primitive neuroectodermal tumors (PNETs) arising in germ cell tumors (GCTs). Nine patients had PNETs confined to the testis, eight patients had PNETs in the testis and at metastatic sites, and 12 patients had PNETs identified only at extratesticular sites. Immunohistochemistry was of use in the further classification of these PNETs as neuroblastoma, medulloepithelioma, peripheral neuroepithelioma, or ependymoblastoma. The histologic pattern of PNETs in the testis (neuroblastoma or medulloepithelioma) did not predict which tumors metastasized. PNETs localized to the testis did not affect prognosis. Eight patients with no PNETs outside the testis were free of disease 1 month to 10 years after diagnosis. PNETs in extratesticular sites were an adverse prognostic factor. Nineteen patients with extratesticular PNETs had adequate clinical follow-up. Thirteen are dead of disease from 4 months to 5 1/2 years (mean 26 months) after diagnosis, four are alive with disease 6 months to 2 years after diagnosis, and two have no evidence of disease with short follow-up (6 and 17 months). Mean survival was longer (34 months) for patients whose extratesticular PNET was neuroblastoma than for those with other types of PNETs (13 months). Chemotherapy directed against GCTs was not effective in patients who developed metastatic PNETs of GCT origin. We conclude that extratesticular PNETs in patients with testicular GCTs are usually fatal, but patients with neuroblastomatous metastases may have a more prolonged course.

Adolescent↗
PubMed1997

Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature.

We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. "Low" percentages (< or =35%) of tumor cells staining for proliferating cell nuclear antigen (PCNA) also may correlate with benign behavior, but some benign tumors have high PCNA values. Ki-67 values (MIB-1 antibody) did not correlate with biologic behavior, nor did immunostains for p53 protein.

Adolescent↗
PubMed1996

Adenocarcinoma of the cervix presenting as ovarian cancer: diagnostic considerations.

Patients with adenocarcinoma of the cervix usually present with either abnormal vaginal bleeding or abnormal papanicolaou smears. Rarely, they may present with an abdominopelvic mass. We report two patients with occult cervical adenocarcinoma who presented with an abdominopelvic mass and vaginal bleeding which simulated a primary ovarian cancer.

Adenocarcinoma↗
PubMed1996

Tumor proliferative activity is predictive of pathological stage in clinical stage A nonseminomatous testicular germ cell tumors.

PURPOSE: Traditional histopathological features have failed to predict accurately the pathological stage of clinical stage A nonseminomatous germ cell tumors of the testis. Based on pilot studies in nonconsecutive patients at our university, we evaluated nontraditional risk factors (cell cycle analysis by flow cytometry, deoxyribonucleic acid analysis by single cell cytophotometry [image analysis] and assessment of proliferative activity by immunohistochemistry) combined with histopathological features in consecutive patients with clinical stage A nonseminomatous testis cancer. MATERIALS AND METHODS: Orchiectomy specimens from 105 consecutive patients with clinical stage A nonseminomatous germ cell tumors who underwent retroperitoneal lymph node dissection (76 with pathological stage A disease and 29 with proved metastasis) were recut, histopathologically reviewed, immunohistochemically stained with proliferation markers (for example Ki-67/MIB-1), and examined by flow cytometry and image analysis. RESULTS: After multiple logistic regression analysis, the G2M+S cell cycle fraction of the aneuploid tumor stemline was the most predictive parameter of pathological stage (p = 0.0004). Using a cutoff of 41%, patients with metastasis were predicted with a sensitivity of 71%. Of 61 patients with a G2M+S value of less than 41%, 53 had pathological stage A cancer (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in patients at low risk for metastasis and MIB-1 immunohistochemical staining identified 23% of patients with pathological stage A tumor who were at extremely low risk for metastatic disease. CONCLUSIONS: Assessment of tumor cell proliferation cannot classify accurately high risk patients at a clinically applicable level. However, identification of patients at low risk for metastasis by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma may be possible at the 90% level. MIB-1 staining is able to classify patients at extremely low risk for metastasis. These parameters deserve further study, since identification of patients at extremely low risk for metastasis could potentially decrease overall morbidity in the management of clinical stage A nonseminomatous testis cancer.

Cell Division↗
PubMed1995

Adult primary pure teratoma of the testis. The Indiana experience.

BACKGROUND: Pure testicular teratoma in adults is a relatively rare malignant tumor with the ability to invade and metastasize. Pure teratoma generally is believed to be less aggressive and less likely to progress, to present in lower stages, and to have better survival rates then other forms of germ cell tumor. Consequently, clinical stage A patients with pure testicular teratoma commonly have been considered to be managed best by surveillance. METHODS: A computerized database search identified 41 patients presenting to Indian University with pure teratoma in the orchiectomy specimen. These patients were further subdivided into four groups based on clinical stage, as follows: Group I, 18 patients with clinical Stage A disease; Group II, 4 patients with clinical Stages A-B1 disease based on questionable computed tomography findings; Group III, 3 patients with clinical Stage B1 disease; Group IV, 16 patients with advanced stage (B3-C) disease. The experience with these patients was reviewed. RESULTS: The overall risk of lymph node metastasis in retroperitoneal lymph node dissection (RPLND) and the risk of relapse after RPLND for patients with low stage pure testicular teratoma (groups I-III) were 40 and 16%, respectively. In patients with clinical Stage A teratoma, the risk of retroperitoneal metastasis in RPLND was 16.7% and the relapse rate was 11.1%. In addition, nearly 37% of referred patients with pure teratoma presented with advanced disease. CONCLUSIONS: These data provide additional confirmation of the metastatic potential of pure testicular teratoma. The proper management of the adult clinical stage A patient with primary pure teratoma of the testis should not necessarily differ from the management of any other histologic type of nonseminomatous testicular tumor. Accordingly, histologic diagnosis of pure teratoma should not mandate surveillance. Instead, patients must be given adequate information regarding management options, as are all other patients presenting with clinical Stage A nonseminoma.

Adolescent↗
PubMed1995

Immunohistochemical assessment of tumor proliferation and volume of embryonal carcinoma identify patients with clinical stage A nonseminomatous testicular germ cell tumor at low risk for occult metastasis.

BACKGROUND: Thirty percent of patients with clinical Stage A nonseminomatous testicular germ cell tumor (NSGCT) are incorrectly clinically staged. In a previous retrospective study at Indiana University, the combination of tumor proliferation rates by flow cytometry and histopathologic evaluation defined risk groups for occult metastatic disease in these patients with clinical Stage A NSGCT: A new immunohistochemical proliferation marker (MIB-1) was therefore used to assess growth fraction in combination with histopathology in an effort to predict pathologic stage in patients with clinical Stage A NSGCT: METHODS: Primary orchiectomy specimens from 90 consecutive patients with clinical Stage A NSGCT (January 1992-November 1993) who underwent retroperitoneal lymph node dissection at Indiana University were histopathologically evaluated. Formalin fixed, paraffin embedded tissue sections were immunohistochemically stained using a monoclonal antibody against the nuclear proliferation-associated antigen Ki-67 (MIB-1). Satisfactory staining was obtained by using an antigen retrieval method based on microwave oven heating of paraffin sections. RESULTS: MIB-1 immunohistochemical staining showed significant differences in mean values between 65 patients (66.1%) with pathologic Stage A NSGCT and 25 (80.4%) patients with pathologic Stage B NSGCT (P = 0.0032). The negative predictive value for patients with pathologic Stage A disease was 87% using a cut-off of 80% or less MIB-1 positively stained cells. A combined approach, using the absolute volume of embryonal carcinoma per patient (< 2 ml) and MIB-1 immunostaining (< or = 80%) was able to define a group of 30% of all patients who were at extremely low risk for occult metastatic disease. CONCLUSIONS: MIB-1 immunostaining in combination with histopathology aided in defining a low risk group patients with clinical Stage A NSGCT but failed to identify patients at high risk for metastasis. The risk factors need to be tested in a prospective clinical trial to determine if they are potentially useful in assigning therapy to individual patients.

Antigens, Neoplasm↗
PubMed1995

Identification of multiple chromosome 12 abnormalities in human testicular germ cell tumors by two-color fluorescence in situ hybridization (FISH).

The distribution of segments of the short and long arms of chromosome 12 was distinguished by two-color fluorescence in situ hybridization (FISH) in 27 cytogenetically abnormal testicular germ cell tumors (TGCTs). A 12p-specific probe was developed by chromosomal microdissection and sequence-independent polymerase chain reaction (PCR) amplification and was combined with a commercially available whole-chromosome 12 painting probe. The TGCTs included both i(12p)-positive and i(12p)-negative primary tumors and lymph node metastases from patients in clinical stage I or stage II who were not previously treated with chemotherapy. Rearrangements of the short arm of chromosome 12 and overrepresentation of 12p DNA sequences were found in all cases. In addition, cryptic rearrangements of 12p were found in 39% (7/18) of the i(12p)-positive tumors and in 78% (7/9) of the i(12p)-negative tumors. Only 7% (2/27) of all tumors had cryptic rearrangements of 12q.

Chromosome Aberrations↗
PubMed1995

Prognostic factors in patients with pathological stage I non-seminomatous testicular germ cell tumors and tumor recurrence during follow-up.

Clinical staging in patients with stage I non-seminomatous germ cell tumors (NSGCTs) of the testis fails in 30% to correctly assess pathological stage since microscopic and small-volume retroperitoneal disease is not detectable on computed tomography of the abdomen. Patients staged by retroperitoneal lymph node dissection as pathological stage I incur a distant (chest or serological) tumor relapse rate of 7-15% during follow-up. Recently, we reported on new risk factors as predictors of pathological stage by flow cytometric DNA analysis in clinical stage I patients. These same methods were applied to a group of 14 pathological stage I patients who subsequently had either chest or serological recurrence. The findings in this group of patients were compared with those in a group of 47 pathological stage I patients who did not experience recurrence. In pathological stage I NSGCT patients with distant (chest or serological) tumor relapse, we found by histological evaluation and DNA analysis of the original orchiectomy specimen proliferative tumor activity to be significantly predictive of relapse. Much as proliferative activity of the primary tumor is predictive of retroperitoneal metastasis, it may be a predictor of recurrence in pathological stage I patients.

DNA, Neoplasm↗
PubMed1995

Prognostic significance of immunohistochemical proliferation markers (Ki-67/MIB-1 and proliferation-associated nuclear antigen), p53 protein accumulation, and neovascularization in clinical stage A nonseminomatous testicular germ cell tumors.

Histopathologic features alone fail to reliably stratify patients with clinical Stage A nonseminomatous germ cell tumors of the testis into groups with high and low risk for occult metastatic disease. Previous flow cytometric studies at Indiana University demonstrated a significant correlation between high proliferative activity and metastatic disease. The current study evaluated the prognostic significance of immunohistochemical markers related to tumor proliferation and aggressiveness in a consecutive series of clinical Stage A nonseminomatous germ cell tumors patients who underwent retroperitoneal lymph node dissection. Archival material of the orchiectomy specimens of 62 patients (45 pathologic Stage A, 17 with metastatic disease) was reviewed and immunohistochemically stained for Ki-67 antigen (MIB-1), proliferation-associated nuclear antigen (PC10), p53 protein (Pab1801), and Factor-VIII-related antigen (neovascularization). Staining with MIB-1 was significantly higher in the metastatic group (mean 80.2%, standard deviation [SD] 15.5) than in pathologic Stage A cases (66.3%, SD 27.9; P = 0.0032) and was predictive of metastatic status with a sensitivity of 82% and specificity of 69%. In this study, no patient with a MIB-1 value less than 52% had metastases. Proliferation-associated nuclear antigen and p53 staining correlated with MIB-1 values (R = 0.63 and 0.55, respectively) but did not correlate with metastatic status. Tumor angiogenesis was also not predictive of metastatic status. Assessment of proliferation rates using MIB-1 antibody in clinical Stage A nonseminomatous germ-cell-tumor patients may prove helpful in predicting metastatic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗