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1.
Am J Clin Pathol ; 113(4): 572-5, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10761460

ABSTRACT

Extramammary Paget disease (EPD) is an uncommon cutaneous malignant neoplasm that arises in areas rich in apocrine glands (perineum, vulva, and axilla). Apocrine gland origin or apocrine differentiation of cells of EPD has been suggested. Estrongen, progesterone, and androgen hormone receptors have been reported to exhibit a characteristic pattern of expression in mammary apocrine type carcinomas; however, their expression in EPD has not been elucidated fully. By using immunohistochemical methods, we studied the expression of steroid receptors in EPD on formalin-fixed paraffin-embedded tissue samples from 28 patients with EPD without associated visceral malignant neoplasms or adnexal carcinoma. Androgen receptor (AR) was identified in 15 of 28 cases. The proportion of AR-positive cells varied from 1% to more than 75%; 8 cases expressed AR in more than 10% of cells. Strong AR expression also was seen in the invasive carcinoma arising from 1 case of EPD. All cases lacked immunohistochemically detectable estrogen and progesterone receptors. The immunophenotype characteristic of apocrine carcinomas (AR-positive, estrogen receptor-negative, progesterone receptor-negative) was seen in a substantial proportion of EPD cases. Results suggest that AR expression is a factor in pathogenesis of EPD. This may be important for the therapy of recurrent or invasive disease.


Subject(s)
Paget Disease, Extramammary/metabolism , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Skin Neoplasms/metabolism , Adult , Aged , Apocrine Glands/cytology , Apocrine Glands/metabolism , Cell Count , Female , Humans , Immunoenzyme Techniques , Keratins/metabolism , Male , Middle Aged , Paget Disease, Extramammary/pathology , Skin Neoplasms/pathology
2.
Mod Pathol ; 13(4): 466-70, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10786816

ABSTRACT

The majority of ovarian sex cord tumors with annular tubules (SCTAT) are benign neoplasms that arise sporadically. In patients who have Peutz-Jeghers syndrome (PJS), ovarian SCTAT is often an incidental finding. Malignant behavior in SCTAT has heretofore been reported only in sporadic cases. We report a case of bilateral, malignant SCTAT developing in a 47-year-old woman who had PJS, originally diagnosed as adenocarcinoma on cervicovaginal cytology. Cervicovaginal and peritoneal fluid cytologic preparations were characterized by pseudopapillary clusters and three-dimensional tubes of tumor cells with scanty cytoplasm and high nuclear: cytoplasmic ratio. Examination of surgical resection specimens revealed bilateral, solid ovarian tumors composed of simple and complex annular tubules with hyaline cores, typical of SCTAT. Tumor emboli were present within salpingeal lymphovascular spaces and in both right and left pelvic lymph nodes. Flow cytometry of tumor cells demonstrated a diploid phenotype. This case represents the first documented example of bilateral, malignant SCTAT arising in a patient who had PJS, presenting with an atypical cervicovaginal smear.


Subject(s)
Ovarian Neoplasms/pathology , Peutz-Jeghers Syndrome/complications , Sex Cord-Gonadal Stromal Tumors/pathology , Female , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/complications , Sex Cord-Gonadal Stromal Tumors/complications , Vaginal Smears
3.
Gynecol Oncol ; 77(1): 55-65, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10739691

ABSTRACT

PURPOSE: The aim of this study was to compare survival and recurrence in clinical and surgical stage I-II papillary serous (PS), clear cell (CC), and endometrioid (EM) cancers of the endometrium and examine the prognostic utility of myometrial invasion. METHODS: Clinical, surgicopathologic, and survival data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. Prognostic variables examined included age, stage, grade, myometrial invasion, lymph-vascular space invasion (LVSI), and histology. PS and CC histologic subtypes were compared as both common category and discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Statistical analyses were performed using chi(2), Fisher's exact, and Wilcoxon rank sum tests, Cox regression analysis, and Kaplan-Meier survival analysis. RESULTS: PS tumors accounted for 9%, CC for 3%, and EM for 88% of cases. Recurrences were more frequent among PS (38%) and CC (22%) compared with EM (9%) (P < 0.001 and 0.08, respectively), and PS recurred more frequently than EM3 alone (20%) (P = 0.06). Among PS, CC, and EM3 patients with recurrences there were no statistical differences in the proportion that received preoperative or postoperative radiotherapy or chemotherapy. Prognostic factors for shorter survival included age >=60, surgical stage III+IV, presence of LVSI, histology (PS, CC, or EM3), and >=50% myometrial invasion. The estimated 5-year survival of PS+CC patients with <2 mm myometrial invasion is 0.56 compared to 0.93 for EM patients (P < 0. 001). PS + CC tumors confined to the endometrium had a 5-year survival of 0.60 compared to 0.98 and 1.00 for EM and EM3, respectively. The 5-year survival for surgically staged IA patients (0.57) was not different from stages IB and IC combined (0.53) (P = 0.72). The 5-year survival for surgical stage I + II PS + CC patients (0.56) was comparable to that for clinical stage I + II PS + CC patients (0.46) and remained significantly smaller than that for EM patients (0.86) (P < 0.001). CONCLUSION: Recurrences are more frequent among PS and CC tumors compared with EM and among PS compared with EM3. When controlled for surgical stage I-II tumors, 5-year survival for PS + CC patients remains comparable to that of clinical stage I-II patients and below that of EM. Prognostic factors for survival in PS and CC patients include age, stage, and LVSI. PS, CC, and EM3 subtypes together are predictors of poor survival. Thorough extended surgical staging is indicated in PS and CC tumors, and prospective trials of aggressive adjuvant therapies for surgical stage I-II tumors are needed to improve outcome in PS and CC patients.


Subject(s)
Adenocarcinoma, Clear Cell/pathology , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Papillary/pathology , Endometrial Neoplasms/pathology , Adenocarcinoma, Clear Cell/mortality , Adenocarcinoma, Clear Cell/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/mortality , Carcinoma, Endometrioid/surgery , Cystadenocarcinoma, Papillary/mortality , Cystadenocarcinoma, Papillary/surgery , Endometrial Neoplasms/mortality , Endometrial Neoplasms/surgery , Female , Humans , Hysterectomy , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Survival Analysis
4.
Transplantation ; 68(9): 1279-88, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10573064

ABSTRACT

BACKGROUND: Interstitial nephritis caused by BK polyomavirus is a recognized complication of renal transplantation. A study of renal transplant recipients at Duke University Medical Center was undertaken to evaluate diagnostic modalities and assess clinical outcomes in transplant polyomavirus infections. METHODS: Polyomavirus nephritis was identified in 6 of 240 patients who received renal transplants between January 1996 and June 1998 and an additional patient who underwent transplantation in 1995. The clinical records of these seven patients were reviewed, as were all renal biopsy and nephrectomy specimens. Electron microscopy (EM) was performed on negatively stained urine samples from 6 patients with polyomavirus infection and 23 patients with other diagnoses. RESULTS: Patients with polyomavirus infection shared several clinical features, including ureteral obstruction (5/7 patients), lymphocele (3/7), bacterial urinary tract infection (3/7), hematuria (3/7), cytomegalovirus infection (3/7), and immunosuppression with mycophenolate mofetil (6/7). All patients experienced elevations in serum creatinine, which stabilized or decreased in four patients with altered or decreased immunosuppression. The diagnosis of polyomavirus infection was established by renal biopsy and EM of urine in five patients, by biopsy alone in one, and by EM alone in one. Sequential examinations of urine by EM were used to monitor the course of infection in six patients. CONCLUSIONS: Interstitial nephritis due to BK polyomavirus occurred in 2.5% of patients receiving renal transplants at our center since 1996. Polyomavirus infection can cause transplant dysfunction and graft loss, but progression of the infection can frequently be abrogated with alterations in immunosuppressive therapy. Both renal biopsy and EM of urine samples are useful in the diagnosis and monitoring of polyomavirus infections.


Subject(s)
BK Virus/isolation & purification , Kidney Transplantation/adverse effects , Nephritis, Interstitial/diagnosis , Polyomavirus Infections/diagnosis , Tumor Virus Infections/diagnosis , Adult , Aged , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Microscopy, Electron , Middle Aged , Nephritis, Interstitial/pathology , Nephritis, Interstitial/therapy , Polyomavirus Infections/pathology , Polyomavirus Infections/therapy , Tumor Virus Infections/pathology , Tumor Virus Infections/therapy
5.
Gynecol Oncol ; 74(3): 385-94, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10479498

ABSTRACT

PURPOSE: The aim of this study was to identify similarities and differences in epidemiologic and surgicopathologic staging results for papillary serous (PS) and clear cell (CC) endometrial cancers compared with endometrioid (EM) carcinoma of the endometrium. METHODS: Clinical and surgicopathologic data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. PS and CC histologic subtypes were compared both as a common category and as discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Fisher's exact test was used to compare proportions with unordered categories (2x2 tables), while the chi(2) test for trend was used to compare proportions in 3x2 tables with ordered categories. Differences in medians were compared with the Wilcoxon rank-sum test. RESULTS: PS tumors accounted for 8%, CC for 2%, and EM for 90% of cases. Overall, 14% of tumors were changed to a different postoperative histology including 64% of PS, 50% of CC, and 8% of EM. Postoperative histology changes were 4% for EM1 and 21% for EM3. PS, CC, and EM3 had more surgical sampling performed than for other EM. Rates for lymph node dissections were similar for EM3 (81%), PS (72%), and CC (67%) tumors, although metastases were more frequent for PS and CC compared with EM3. When PS tumors were confined to the endometrium, paraaortic metastases occurred in 13%. LVSI increased with EM grade and was highest for PS and CC. Upstaging to surgical stage III-IV occurred in 47% of PS, 39% of CC, and 12% of EM. The majority of PS and CC tumors were confined to the inner one-third of the myometrium, compared with EM tumors, where grade correlated with depth of myometrial invasion. Extrauterine metastases occurred in 55% of PS and 45% of CC tumors confined to the inner one-half, compared with 17% of EM3. CONCLUSION: Frequent changes from preoperative to postoperative histology and grade may contribute to misassignment of preoperative and intraoperative risk as determined by depth of myometrial invasion for PS and CC patients. The higher frequency of extrauterine metastases in PS and CC tumors compared with EM3, despite similar surgical sampling rates, supports a more virulent behavior. The poor correlation between depth of myometrial invasion and risk for extrauterine metastases helps to explain poorer survival in PS and CC patients, in addition to more frequent upstaging. These results support routine extended surgical staging for women with preoperative or intraoperative diagnosis of PS and CC tumors. Intraoperative assessment of tumor grade and histology may be indicated and warrants further investigation.


Subject(s)
Adenocarcinoma, Clear Cell/epidemiology , Adenocarcinoma, Clear Cell/pathology , Carcinoma, Endometrioid/epidemiology , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Papillary/epidemiology , Cystadenocarcinoma, Papillary/pathology , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/pathology , Adenocarcinoma, Clear Cell/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/surgery , Cystadenocarcinoma, Papillary/surgery , Endometrial Neoplasms/surgery , Female , Humans , Middle Aged , Neoplasm Staging
6.
Am J Surg Pathol ; 23(7): 772-80, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10403299

ABSTRACT

Four children who developed oncocytoid renal cell carcinoma (RCC) after neuroblastoma are reported. One patient had multiple, bilateral RCCs. The mean age at time of diagnosis of RCC was 8.8 years (range, 5-13 years). The mean interval between neuroblastoma and RCC was 7.15 years (range, 3.1-11.5 years). The histologic findings of these RCCs did not fit within the spectrum of known renal epithelial neoplasms. Most of the neoplastic cells in all cases had eosinophilic, oncocytoid cytoplasm and were arranged in solid and papillary growth patterns. A subset of cells with reticular cytoplasm was also present. Immunohistochemical studies demonstrated keratins 8 and 18 in all neoplasms and keratin 20 in two cases. DNA ploidy analysis revealed that two of three neoplasms assessed were aneuploid. Cytogenetic studies revealed 45, XX, add or dup (7)(q32q36) in one neoplasm, and 83-89, XXXX, -1 ,-3, del (3)(q11.1q2?1), der(4)t(4;?22) (q32;q11.2), -14, -22 in a second tumor. Microsatellite polymerase chain reaction analysis detected no abnormalities in one neoplasm and allelic imbalance of chromosomes 2p31-32.2, 8p22, 9p22-24, 13q22, 20q13, and 22q11 in a second tumor. In case 4, two different RCCs excised 6 months apart were analyzed. The initial neoplasm showed allelic imbalance of chromosomes 2q31-32.2, 5q22, 5q31, 10p13-14, 13q22, 14q31, and 20q13. The subsequent neoplasm showed allelic imbalance of chromosomes 3p21.3, 14q31, and 20q13. The common presence of 14q31 and 20q13 abnormalities suggests that these two neoplasms were genetically related. In aggregate, these findings are distinctive, are not found in known types of RCC, and support the morphologic impression that oncocytoid RCC after neuroblastoma is a distinct clinicopathologic entity.


Subject(s)
Adenoma, Oxyphilic/pathology , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Neoplasms, Second Primary/pathology , Adenoma, Oxyphilic/epidemiology , Adenoma, Oxyphilic/genetics , Adenoma, Oxyphilic/metabolism , Adolescent , Aneuploidy , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/epidemiology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Karyotyping , Kidney Neoplasms/epidemiology , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Microsatellite Repeats/genetics , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/genetics , Neoplasms, Second Primary/metabolism , Neuroblastoma/therapy , Polymerase Chain Reaction , Polyploidy
7.
Clin Cancer Res ; 5(3): 587-91, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10100710

ABSTRACT

The molecular biology underlying the metastatic process in ovarian carcinoma remains poorly understood. For other neoplasms, the induction of angiogenesis by malignant cells has been shown to play a pivotal role in the process of tumor proliferation and metastasis. The purpose of this study was to characterize the degree of angiogenesis in epithelial ovarian malignancies and to determine whether the degree of neovascularization has prognostic significance for survival. Tissue sections obtained from 88 ovarian cancer patients were examined immunohistochemically for angiogenesis after staining with anti-human endothelial cell antibodies to von Willebrand factor and CD31. Light microscopy was performed, and individual microvessel counts were quantified at high power (x400). A chart review was completed, collating data regarding age, stage, grade, status of disease, and survival. Statistical exploratory methods were used to find potentially useful prognostic cutpoints for marker values of angiogenesis. Of the total 88 patients, tissue microvessel counts from 85 were evaluated via antibodies to von Willebrand factor and 87 for CD31. Overall, median survival was 2.7 years in women with cancers containing high microvessel counts versus 7.9 years in those with low microvessel counts (P = 0.03). A low microvessel count was associated with better 5-year survival in both early stage (I and II) and advanced stage (III and IV) disease. Our data suggest that the degree of neovascularization may have prognostic significance in epithelial ovarian carcinoma, especially for women with early-stage disease. In this group of women, the degree of angiogenesis may allow the selection of women at high risk for recurrence who may benefit from aggressive adjuvant therapy.


Subject(s)
Neovascularization, Pathologic , Ovarian Neoplasms/blood supply , Adult , Aged , Carcinoma/secondary , Female , Humans , Middle Aged , Neoplasm Metastasis , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Prognosis , Survival Analysis
8.
Int J Gynecol Cancer ; 9(2): 131-136, 1999 Mar.
Article in English | MEDLINE | ID: mdl-11240754

ABSTRACT

Carcinosarcoma is an aggressive neoplasm of the female genital tract, which comprises 1-2% of malignancies of the uterine corpus. Because of the broad range of differentiation exhibited by these tumors, the precise nature of the relationship between epithelial and stromal components in this unique tumor remain unclear. Previous studies have demonstrated that mutation and consequent overexpression of the tumor suppressor gene p53 occurs frequently in carcinosarcoma and is conserved from primary to metastastic sites. We examined p53 accumulation in formalin-fixed, paraffin-embedded archival sections in 19 cases previously shown to have mutations in the p53 gene and performed semi-quantitative analysis of the intensity of staining and relative density of positive cells and stromal and glandular elements. There was a high level of concordance of immunohistochemical staining for the p53 oncoprotein between glandular and stromal elements. These results further suggest a clonal origin for the diverse elements of carcinosarcoma.

9.
Clin Nephrol ; 49(2): 96-101, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9524779

ABSTRACT

BACKGROUND: The epidemiology, criteria for diagnosis and treatment of bacterial endocarditis has changed substantially in the past 2 decades, yet little attention has been given to the changing etiologies of renal insufficiency and the predictors of renal failure or the relationship between renal failure and mortality in patients with bacterial endocarditis. OBJECTIVE: To study the risk factors for the development of acute renal failure and death among patients with definite bacterial endocarditis. SETTING: Tertiary referral university medical center. METHODS: Retrospective chart review of 204 consecutive episodes of definite bacterial endocarditis as defined by the Duke criteria. Logistic regression was used to identify clinical and biochemical predictors of death and the development of acute renal failure. RESULTS: Two hundred and four episodes of endocarditis identified in 185 patients were evaluated. The overall mortality for the group was 20%. The presence of prosthetic valve endocarditis and thrombocytopenia was associated with increased risk of death in hospital. One third of the patients developed acute renal failure (defined as a serum Cr of 2 mg/dl or above). The presence of acute renal failure increased the odds (OR) of dying by 5 (p = 0.0001). Clinical and biochemical variables at presentation that were significantly associated by univariate analysis with the risk of developing acute renal failure were: increased age, a history of hypertension, thrombocytopenia, the presence of Staphylococcus aureus, and prosthetic valve infection. Age (OR 2.9, p = 0.002) and the degree of thrombocytopenia (OR 0.2, p = 0.0001) were independently associated with an increased risk of developing acute renal failure. Patients who developed acute renal failure as a result of septic syndrome or following cardiac surgery had a higher mortality when compared to other causes of acute renal failure. CONCLUSION: Acute renal failure associated with bacterial endocarditis remains a frequent clinical problem that is often associated with a fatal outcome. Patients with increased age, and the degree of thrombocytopenia were independent risk factors for developing acute renal failure.


Subject(s)
Acute Kidney Injury/etiology , Endocarditis, Bacterial/complications , Acute Kidney Injury/mortality , Acute Kidney Injury/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Kidney/pathology , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
10.
Am J Surg Pathol ; 21(9): 1037-46, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9298880

ABSTRACT

Acute graft-versus-host disease (GvHD) of the upper gastrointestinal (GI) tract is common after allogeneic bone marrow transplantation (BMT). However, diagnosis cannot be made on clinical presentation and endoscopic findings alone, because these are nonspecific, and histologic confirmation is often desirable. The diagnosis of gastric GvHD is often based on subtle findings with considerable potential for variability in interpretation. Evaluation of the reproducibility of diagnosis and recognition of histologic features of gastric GvHD was based on blinded review of 56 gastric biopsies (24 from patients with allogeneic BMT or unrelated umbilical cord blood transplantation and 32 control biopsies from patients who did not undergo BMT, of whom eight had active GI cytomegalovirus [CMV] infection). Histologic criteria for GvHD were apoptosis and gland destruction, sparse inflammatory infiltrate, and granular eosinophilic debris in dilated glands. Seventeen patients (22 biopsies) were judged to have clinical GvHD on the basis of skin or liver involvement and GI symptoms without other known cause. Eighteen of these 22 gastric biopsies were classified as GvHD by at least two of the three pathologists on initial review. Blinded histologic diagnosis of GvHD had a positive predictive value of 69%, a sensitivity of 82%, and specificity of 76%. False-positive results occurred in CMV gastritis, human immunodeficiency virus (HIV) infection, primary immunodeficiency, and after renal transplantation. Of individual features, granular debris in glands was a specific (94% specificity), but insensitive (41% sensitivity) marker for GvHD. Distinction between GvHD and CMV infection can be difficult, and GvHD can be confused with changes seen in HIV infection and other immunodeficiency states.


Subject(s)
Graft vs Host Disease/diagnosis , Graft vs Host Disease/pathology , Stomach Diseases/diagnosis , Stomach Diseases/pathology , Adolescent , Adult , Apoptosis , Biopsy , Bone Marrow Transplantation/adverse effects , Cell Transplantation , Child , Child, Preschool , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/pathology , Diagnosis, Differential , Epithelium/pathology , False Positive Reactions , Female , Fetal Blood/cytology , HIV Infections/diagnosis , HIV Infections/pathology , Humans , Infant , Male , Observer Variation , Reproducibility of Results , Sensitivity and Specificity , Single-Blind Method , Stomach/pathology , Transplantation, Homologous/adverse effects
11.
Diagn Cytopathol ; 16(2): 151-5, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9067109

ABSTRACT

We present a case of a high-grade endometrial stromal sarcoma metastatic to the abdomen with an unusual extracellular hyaline matrix material seen on fine needle aspiration biopsy. The patient was initially diagnosed with a stage IIIA high-grade endometrial stromal sarcoma and had received four cycles of chemotherapy over the past year. She subsequently developed an abdominal mass that consisted of discohesive small cells with scanty cytoplasm on fine needle aspiration. On the Diff-Quik-stained smears, metachromatic, extracellular hyaline material was identified. This appeared on the Papanicolaou-stained smear as cyanophilic material and did not react with reticulin stain. This case emphasizes the importance to the cytopathologist of including endometrial stromal sarcoma in the differential diagnosis of hyaline matrix material.


Subject(s)
Abdominal Neoplasms/pathology , Endometrial Neoplasms/pathology , Extracellular Matrix/pathology , Sarcoma, Endometrial Stromal/pathology , Abdominal Neoplasms/secondary , Ascitic Fluid/cytology , Biopsy, Needle , Endometrial Neoplasms/drug therapy , Female , Humans , Middle Aged , Sarcoma, Endometrial Stromal/secondary
13.
Oncogene ; 15(25): 3059-65, 1997 Dec 18.
Article in English | MEDLINE | ID: mdl-9444954

ABSTRACT

Progression of prostate cancer from an androgen sensitive to androgen insensitive tumor has previously been shown to be accompanied by a change in alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) in a rat model of prostate cancer. This change results in loss of the FGF-R2(IIIb) isoform and predominant expression of the FGF-R2(IIIc) isoform. We sought to determine whether this change in FGF-R2 splicing is also associated with androgen insensitivity in human prostate tumors. We analysed three well characterized human prostate cancer cell lines and three metastatic prostate tumors which have been maintained as xenografts in nude mice. One of the cell lines, LNCaP, and two of the xenografts, DUKAP-1 and DUKAP-2, have been characterized as androgen sensitive, whereas two of the cell lines, DU-145 and PC-3, and one of the xenografts, DU9479, display androgen independent growth. Using an RT-PCR based assay, we demonstrated that progressive loss of the FGF-R2(111b) isoform correlated with androgen insensitivity in these human prostate cancer models. These findings lend support to the hypothesis that that loss of FGF-R2(IIIb) may be one step in a series of events which lead to progression of human prostate cancer.


Subject(s)
Alternative Splicing , Fibroblast Growth Factors , Neoplasms, Hormone-Dependent/genetics , Prostatic Neoplasms/genetics , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Fibroblast Growth Factor/genetics , Receptors, Fibroblast Growth Factor/metabolism , Androgens/physiology , Animals , Disease Progression , Fibroblast Growth Factor 10 , Fibroblast Growth Factor 7 , Growth Substances/metabolism , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasms, Hormone-Dependent/metabolism , Prostatic Neoplasms/metabolism , Receptor, Fibroblast Growth Factor, Type 2 , Transplantation, Heterologous
14.
J Urol ; 156(4): 1272-4, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8808852

ABSTRACT

PURPOSE: Intestinal metaplasia of the urothelium occurs in chronically irritated retained urinary segments and can progress to enteric adenocarcinoma. We present a unique clinical experience with a closed segment ureter from a dysplastic kidney draining ectopically into the seminal vesicle with malignant degeneration to enteric adenocarcinoma. The implications of this experience for management of this anomaly are discussed. MATERIALS AND METHODS: Clinical and pathological data were assimilated with the urological and pathological literature. RESULTS: Pathological examination revealed replacement of the urothelium of the renal pelvis and ureter with intestinal type metaplasia and multifocal transformation to mucinous (tubular villose) poorly differentiated adenocarcinoma. Preoperative computerized tomography failed to identify the extensive malignancy. CONCLUSIONS: Our experience demonstrates that this anomaly is another scenario in which closed spaced nonfunctional urothelium can undergo malignant degeneration. Since monitoring such units for tumor progression does not seem to be possible presently, conservative treatment appears hazardous. This new recognition of the risk of malignant metaplastic degeneration is an additional rationale to consider complete extirpation of these lesions as the most appropriate treatment in young men.


Subject(s)
Abnormalities, Multiple , Adenocarcinoma/complications , Adenocarcinoma/surgery , Kidney/abnormalities , Seminal Vesicles/abnormalities , Ureter/abnormalities , Ureteral Neoplasms/complications , Ureteral Neoplasms/surgery , Aged , Humans , Male , Urothelium
15.
Int J Gynecol Pathol ; 15(4): 338-44, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8886881

ABSTRACT

This study evaluates the morphologic features of squamous epithelial repair of the uterine cervix, a condition describing a state of regeneration, and compares them with the features of its two histologic mimics, squamous metaplasia and mild dysplasia. The materials examined were from 20 patients with a histologic diagnosis of repair, 42 with cervical biopsy specimens of acceptable quality obtained within 3 weeks of a cervical smear showing repair, and 20 each with squamous metaplasia or mild dysplasia. Specimens with repair disclosed distinctive morphologic characteristics. On low-power magnification, the stroma was chronically inflamed (100%), often floridly (55%). The nuclei were uniform with absent or minimal pleomorphism (90%). The chromatin was bland and evenly distributed (70%). Nucleoli of a bull's eye or macronucleolar appearance (45%) were easily found. Mildly dysplastic epithelium, unlike reparative epithelium, was infrequently associated with an intensely inflamed stroma (20%); its nuclei were pleomorphic (100%) and commonly displayed coarse chromatin (75%) and mitoses (60%). Metaplastic epithelium ws also infrequently associated with an intensely inflamed stroma (10%). Nuclear pleomorphism (10%) and mitotic figures were infrequent (10%), never atypical (0%), and always basally located. Most nuclei had nucleoli, but the majority were small (80%). This study indicates that most cases of repair, mild dysplasia, and metaplasia can be readily distinguished, although due to overlapping features, some cases are difficult to classify as shown by interobserver variability.


Subject(s)
Cervix Uteri/pathology , Cervix Uteri/physiology , Regeneration , Cell Nucleus/pathology , Epithelium/pathology , Epithelium/physiology , Female , Humans , Metaplasia , Observer Variation , Stromal Cells/pathology
16.
Am J Clin Pathol ; 106(3): 319-24, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8816588

ABSTRACT

An effective, prospective, computer-guided method of correlation is reported. The mechanism for identification of cases, comparison of diagnoses, and reconciliation of discrepancies are explained. The results are similar to prior, retrospective, correlation studies. The benefits specific to this unique prospective approach include optimal capture of cases for correlation, minimization of errors before diagnoses are released to clinicians and patients, and internal standardization of diagnostic criteria. Three thousand four hundred and four consecutive paired cervicovaginal cytologies and biopsies were accessioned at the Pathology Department of Duke University Medical Center over a 43-month period. Of these, 481 paired cases (14%) had discordant diagnoses, defined as differing more than one degree of dysplasia or as dysplasia or carcinoma identified by only one modality. Additional evaluation reconciled the diagnostic differences in 35 cases. Eighteen initial diagnostic differences arose from cytologic screening errors, 16 from interpretive errors by staff pathologists, and one from superficial initial histologic sections. The remaining 446 discordances were attributed to sampling differences. The cytologic smear contained the diagnostic lesion in 40% of the cases and the biopsy the remainder, emphasizing the utility of pairing these sampling techniques in patients at risk for dysplasia.


Subject(s)
Cervix Uteri/pathology , Uterine Cervical Dysplasia/pathology , Biopsy , Diagnostic Errors , Female , Humans , Prospective Studies , Statistics as Topic , Uterine Cervical Dysplasia/diagnosis , Vaginal Smears
17.
Diagn Cytopathol ; 14(4): 321-4, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8725132

ABSTRACT

Low-grade adenosquamous carcinoma is an unusual variant of mammary carcinoma. This malignancy generally presents as a palpable mass without mammographic microcalcifications, and fine-needle aspiration may be the initial technique selected for diagnosis. To our knowledge, the cytologic findings associated with this neoplasm have not been reported. We report a case of low-grade adenosquamous carcinoma of the breast in a 57-yr-old woman, initially studied by fine-needle aspiration cytology and confirmed by excisional biopsy. The aspiration biopsy smears were characterized by low cellularity and small disoriented clusters containing uniform cells of small to medium size. Bipolar cells were not seen in the background. The diagnostic features and differential diagnosis of this unusual neoplasm are reviewed.


Subject(s)
Biopsy, Needle , Breast Neoplasms/pathology , Carcinoma, Adenosquamous/pathology , Diagnosis, Differential , Female , Humans , Middle Aged
18.
Med Pediatr Oncol ; 25(1): 52-9, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7753003

ABSTRACT

Renal cell carcinoma is unusual in children. We report a case of anaplastic renal cell carcinoma arising in a 7-year-old girl following treatment for Stage III neuroblastoma. The renal cell carcinoma has unusual histologic and ultrastructural features, which are discussed. The case is further unusual in that few children with advanced stage neuroblastoma survive long enough to develop second malignant neoplasms.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Neoplasms, Second Primary/pathology , Neuroblastoma/therapy , Anaplasia , Carcinoma, Renal Cell/ultrastructure , Child , Combined Modality Therapy , Female , Humans , Immunohistochemistry , Infant , Kidney Neoplasms/ultrastructure
19.
Arch Pathol Lab Med ; 119(1): 99-103, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7802567

ABSTRACT

Although simultaneous endometrial and ovarian tumors are observed occasionally, rarely are the two neoplasms histologically disparate. We report a case of simultaneous endometrial malignant mixed mesodermal tumor and ovarian serous adenocarcinoma with a single right external iliac lymph node metastasis. Using immunohistochemical profiles, we demonstrated that the two tumors are separate primary neoplasms and identified the origin of the metastatic deposit as the mixed malignant mesodermal tumor.


Subject(s)
Cystadenocarcinoma, Serous/pathology , Endometrial Neoplasms/pathology , Mixed Tumor, Mesodermal/pathology , Neoplasms, Multiple Primary/pathology , Ovarian Neoplasms/pathology , Female , Humans , Middle Aged
20.
Br J Haematol ; 88(4): 685-92, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7819094

ABSTRACT

To validate scientifically our prior empiric observations that patients develop significant haemopoietic dysplasia following solid organ transplantation, we developed a quantitative lineage-specific scoring system to evaluate dysplastic features of bone marrow aspirates and core biopsies. We used this scoring system to compare retrospectively randomly selected bone marrow aspirates and core biopsies from 19 patients undergoing orthotopic liver transplantation (OLT), 21 with a known history of human immunodeficiency virus (HIV) infection, and 18 with primary or chemotherapy-related myelodysplastic syndromes (MDS). Our results show that the OLT patient group developed significant but milder haemopoietic dysplastic changes than the HIV or MDS groups, and that the MDS group developed more severe dysplasia of the myeloid lineage than the other groups. The possible roles for drugs and infectious agents in the pathophysiology of dysplastic changes are discussed.


Subject(s)
Bone Marrow Diseases/etiology , HIV Infections/complications , Hematopoiesis , Liver Transplantation/adverse effects , Myelodysplastic Syndromes/pathology , Biopsy , Bone Marrow/pathology , Bone Marrow Diseases/pathology , Bone Marrow Diseases/physiopathology , Erythroblasts , HIV Infections/pathology , Humans , Megakaryocytes/pathology , Random Allocation , Retrospective Studies
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