Biomedical subjects
Publications and source records attributed to G R Hafez.
An 18-year-old female presented with a mass involving the liver which was resected. Microscopically, it was diagnosed as monophasic synovial sarcoma. Cytogenetic study (FISH) revealed translocation t(X; 18), confirming the diagnosis.
BACKGROUND: Transplantation of donor-derived malignancies during organ transplantation fortunately is very rare. Discontinuation of immunosuppressive medications under these circumstances has previously resulted in complete tumor rejection. Ectopic adrenocorticotropic hormone (ACTH) production may result in Cushing syndrome and is not an uncommon paraneoplastic feature of small cell carcinoma of the lung. Theoretically, in the organ transplantation setting, the resulting high cortisol levels could suppress a tumor-rejection immune response. However, to the authors' knowledge, no such clinical scenario has been described in the literature published to date. METHODS: A 25-year-old living related kidney transplant recipient presented with Cushing syndrome 32 months after transplantation. The donor had been diagnosed with small cell carcinoma of the lung 22 months earlier. On further evaluation, the kidney recipient was diagnosed with donor-derived small cell lung carcinoma of the transplanted kidney. She was found to have extensive disease involving the liver and retroperitoneum. Despite discontinuation of immunosuppressive medications, the disease progressed and cortisol levels remained elevated during 6 weeks of observation. RESULTS: The patient received six cycles of cisplatin and etoposide, which resulted in resolution of her hypercortisolemia and a complete remission of her donor-derived small cell carcinoma. At last follow-up, she was 12 months from completing her therapy and continued in complete remission. CONCLUSIONS: Donor-derived small cell carcinoma and ectopic ACTH production can occur in a patient after kidney transplantation.
Salivary gland myoepithelioma (ME) is a neoplasm derived from myoepithelial cells that lacks the ductal and broad mesenchymal differentiation seen in the vast majority of mixed tumors. This report describes the cytologic findings of a cystic ME presenting in the midline of the dorsal tongue, a site where no salivary glands are generally present. The tumor was well circumscribed and composed of sheets of monotonous epithelioid cells without ductal cells. The cells were positive for S-100 protein and ultrastructurally had features of myoepithelial cells. The fine needle aspiration (FNA) biopsy findings, differential diagnosis, histology, immunohistochemistry, and electron microscopic features of this interesting and uncommon neoplasm are presented. To the best of our knowledge, there have been no cytologic reports of ME of the tongue.
ThinPrep purportedly increases the sensitivity of cervicovaginal cytology for detecting abnormal squamous and glandular cells. The value of additional slides from residual Preservcyt material to characterize difficult lesions is unknown. Fifty-eight cases were studied to determine the utility of additional slides for diagnosis and to assess cellular uniformity. In 32 (55%), repeat slides helped make a definitive diagnosis, including 18 atypical squamous cells of uncertain significance (ASCUS) reclassified as low-grade squamous intraepithelial lesion (LGSIL) (13), high-grade squamous intraepithelial lesion (HGSIL) (4), or endometrial adenocarcinoma (1); 5 LGSIL reclassified as HGSIL; 3 atypical glandular cells of uncertain significance (AGUS) reclassified as LGSIL (1) or HGSIL (2); 2 LGSIL?HGSIL classified as LGSIL; and 4 cases confirmed as LGSIL (2) or HGSIL (2). Results were compared to follow-up clinical information, including subsequent cervicovaginal samples and biopsies. The number of abnormal cells was similar between slides in most cases. We conclude that, while ThinPreps prepared from the same vial have similar numbers of abnormal cells, additional slides can be helpful for diagnosis in select cases.
We used a histopathological-fluorescence in situ hybridization (histo-FISH) parallel examination technique to identify the micro-foci of prostate cancer with chromosome 8p deletion at the interface area adjacent to the tumor. The archival paraffin embedded prostate tissue sections from 27 prostate cancer patients were evaluated. Seventy-eight percent of the patients showed chromosome 8p deletion in the tumor sections. Eight of the 27 patients (30%) had been found positive for tumor micro-foci with chromosome 8p deletion at the tumor interface area. There is a strong trend for patients with late stage tumors to have positive findings for tumor micro-foci at the interface area (p<0.002). Our data suggests that the formation of tumor micro-foci with chromosome 8p deletion and ploidy change at the interface area is a significant development in the advanced prostate cancer, and identification of these micro-foci may serve as a prognostic parameter in the clinical assessment of prostate cancer patients.
Metastases to inguinofemoral lymph nodes in patients with carcinoma of the vulva alter the prognosis and treatment of this disease. Our goal was to determine if immunohistochemical staining could reveal occult metastatic nodal disease not detected with routine hematoxylin and eosin staining. We retrospectively examined a total of 110 lymph nodes from 10 patients who had undergone lymph node dissection and found to have all negative nodes. Paraffin embedded lymph nodes were immunostained with a monoclonal antibody directed against multiple low- and high-molecular weight cytokeratins. Micrometastases were not detected in any lymph nodes examined with immunohistochemistry. All positive and negative controls yielded satisfactory results. It is concluded that immunohistochemistry with cytokeratin antibodies does not provide greater sensitivity than routine hematoxylin and eosin staining for the detection of nodal metastases in vulvar carcinoma.
A 43-year-old woman had unilateral exophthalmos caused by primary orbital Ewing sarcoma. Specialized immunohistochemical stains, primarily MIC-2 (CD99), aided in the diagnosis of Ewing sarcoma. Twenty-two months after radiotherapy and multiagent chemotherapy, the patient remained tumor free. To our knowledge, this is the first reported case of orbital Ewing sarcoma to present in an adult beyond the fourth decade of life.
The eleventh case of primary infiltrating ductal carcinoma of the vulva is reported with a review of the literature. The infiltrating tumor is associated with an intraductal component as well as noninvolved mammary-like glandular tissue (ectopic breast tissue) and metastases to inguinal lymph nodes. Estrogen receptor and progesterone receptor immunohistochemical staining is negative utilizing the HSCORE method. The treatment regimen is patterned after approach to node-positive breast carcinoma.
This study examines whether changes in beta 2-microglobulin (B2M) serum levels are useful in the early detection of post-transplant lymphoproliferative disease (PTLD). Serum B2M is monitored daily post-transplant at our center as a marker of change in lymphocyte activation. We identified 16 cases (16/1359; 1.2%) of PTLD from among 1359 kidney and kidney-pancreas transplants. Those with CNS lymphoma (two patients) and titer change only (one) were not included in this review. Thirteen patients had serum titer and clinical evidence of EBV activity; 12 of these patients had histological evidence of PTLD (lymph node 6, kidney 3, and generalized disease 3). Three patients died with disseminated PTLD infection. Nine are alive but only two have the original transplant kidney. All patients received quadruple immunosuppression for induction, and 11 were subsequently treated with OKT3 or ALG for rejection. The mean number of days of induction ALG therapy was 14.8 d (20 mg/kg/d). The mean number of days of OKT3 therapy for rejection was 14.4 d (5 mg/d). During rejection the highest mean creatinine level was 6.8 mg/dL, and the highest mean B2M level was 16.4. With PTLD, the highest mean creatinine level was 7.0 mg/dL and the highest mean B2M level was 32.3 mg/L. The difference in creatinine levels was not significant, but the difference in B2M levels was significant (p < 0.01). We conclude that B2M levels are useful markers in differentiating rejection from PTLD.
BACKGROUND: Conventional pathologic classifications of human renal cell carcinoma (RCC) give little insight into oncogenesis and little assistance in predicting the clinical behavior of this disease. Identification of specific genetic alterations involved in the development of RCC using fluorescence in situ hybridization (FISH) however, may help provide foundations for classification, prognosis, and clinical management of the patients. METHODS: Archival, paraffin embedded tissue sections from 30 human non-papillary RCCs were examined with a dual color FISH technique for loss of chromosomes 3p and 14q. Telomeric DNA probes from 3p or 14q and an internal ploidy control probe, centromeric probe of chromosome 2, were applied directly to the tumor sections. The correlations between loss of 3p or 14q, and tumor ploidy, with tumor grade, pathologic stage, and patient outcome were assessed. RESULTS: Ninety percent of the patients (27) lost chromosome 3p, and 36.7% of the patients (11) had chromosome 14q deletions. The loss of 3p in the samples tested was unrelated to patient age, gender, outcome, tumor stage, or histologic grade. However, the deletion of 14q was significantly correlated with higher stage (P = 0.01), histologic grade (P = 0.01), and patient outcome (P < 10(-4)). CONCLUSION: The close correlation of 14q loss with higher stage, higher histologic grade, and poorer outcome for patients with nonpapillary RCC indicates that it may be a promising prognostic marker.
The diagnosis of primary retroperitoneal masses is approached best by CT scan-guided transretroperitoneal core biopsy or by open biopsy. Excisional or wedge biopsy is the preferred method for undiagnosed lymphadenopathy. Resection without biopsy is indicated for large or enlarging nonfunctional primary adrenal masses.
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The efficacy of RS-61443 and cyclosporine utilized either alone or in combination was assessed in both a segmental heterotopic and total orthotopic canine intestinal transplant model. Twenty-eight dogs underwent segmental (150-cm) heterotopic intestinal transplants and five dogs total orthotopic transplants. Five heterotopic groups were compared: group 1, no immunosuppression; group 2, cyclosporine and prednisone; group 3, RS-61443, cyclosporine and prednisone; group 4, RS-61443 and prednisone; and group 5, RS-61443 and subtherapeutic cyclosporine. Group 3 animals achieved a median survival of 136 days, while the median survivals of groups 1, 2, 4, and 5 were < or = 10 days (P < .001). Twenty deaths in groups 1 through 5 were secondary to allograft rejection, two were due to infection, and two were unexplained. Four animals in group 3 were sacrificed, one at 83 days due to diarrhea and weight loss and three at the termination of the study. The median survival of five dogs undergoing total orthotopic transplantation (group 6) was 27.0 days and was significantly longer than groups 1, 4, and 5 (P < .01). No dog in this group had intestinal rejection--however, four were sacrificed due to weight loss and one died of malnutrition. The combination of RS-61443 and cyclosporine significantly prolonged intestinal allograft survival in both the heterotopic and orthotopic transplant models. Clinically, this combination may be promising for both combined liver-intestinal and isolated intestinal transplantation.
Chondrosarcoma of the larynx is an unusual tumor, with only approximately 200 cases having been reported. This tumor is relatively nonaggressive and tends to remain localized in the larynx. Two cases with aggressive clinical behavior manifested by regional or distant metastasis are presented. In the first case, cervical node metastasis appeared 6 months after total laryngectomy. A dedifferentiated chondrosarcoma was identified by pathologic examination. In the other case, clavicular metastasis developed 7 years after initial local excision. Despite additional treatments, the patient later developed cervical node, lung, and vertebral metastasis. Transformation from low-grade to dedifferentiated chondrosarcoma was verified by pathologic examination. We believe this case to be the first reported laryngeal chondrosarcoma with bone metastasis. A review of the literature regarding regional and/or distant metastasis of laryngeal chondrosarcoma, including the present observations, reveals a total of 20 cases. In all cases, tumor grade has been directly correlated with the development of metastasis.
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BACKGROUND: Alcoholism is the leading cause of end-stage liver failure in the United States, but the application of liver transplantation to the treatment of alcoholic liver disease remains controversial because of medical and ethical concerns. Information about the outcome of patients who undergo transplantation for alcoholic cirrhosis would help to resolve these concerns. METHODS: The results of 41 patients (Group 1) with alcoholic liver disease were compared with those of patients who underwent liver transplantation for other medical problems (group 2) at this center. Thirty of the 32 survivors from group 1 and 30 matched subjects from group 2 were interviewed to assess substance dependence, recidivism, and activity level. RESULTS: Compared with control subjects, patients with alcoholic liver disease had equivalent patient and graft survival rates and achieved an equal level of postoperative health. These results were achieved even though patients with alcoholic liver disease had significantly worse liver failure and more morbidity before surgery, and one third of the patients in this group were not abstinent before transplantation. CONCLUSIONS: We conclude that patients with alcoholic liver disease merit equal consideration for liver transplantation compared with other causes of liver failure. Treatment of the addictive disorder should be included before and after surgery.
Methods of accurately assessing the suitability of donor livers prior to transplantation are required if the incidence of primary nonfunction (PNF) is to be reduced. This study evaluated the ability of donor liver biopsies to predict the development of primary nonfunction after transplantation. From June 1987 until May 1990, 170 liver transplants were performed in 147 patients. A total of 124 donor liver biopsies were obtained and divided into three groups. Group 1 biopsies (n = 77) were obtained after revascularization of the liver, group 2 biopsies (n = 19) were obtained prior to donor hepatectomy but examined only after implantation, and group 3 biopsies (n = 28) were obtained as in group 2, but were examined prior to implantation. Three of 89 (3.4%) livers interpreted as having normal histology developed primary nonfunction, while one of 26 (3.8%) biopsies interpreted as having a minimal or moderate amount of fatty infiltration developed primary nonfunction. PNF occurred in 7 of 8 livers with severe fatty infiltration (3), hydropic degeneration (3), and centrilobular necrosis (1). A fourth liver with hydropic degeneration and poor function ultimately failed requiring retransplantation 8 weeks later. Analysis of liver function revealed progressive elevation in aspartate-aminotransferase, alanine-aminotransferase, lactate dehydrogenase, and serum ammonia (NH3) with increasing degrees of fatty infiltration. Donor age and weight was also found to be significantly higher in livers with fatty infiltration. This study suggests that donor liver biopsies demonstrating normal histology or minimal-to-moderate fatty infiltration function adequately, but that donor livers with severe fatty infiltration or hydropic degeneration function poorly and should not be transplanted.
This report describes the first known case of delayed hemorrhage of a persistent ectopic pregnancy following surgical and medical therapy. A 2.5-cm ampullary pregnancy without cardiac activity was removed by laparoscopic salpingostomy. The serum beta-hCG level before laparoscopy was 1542 mIU/mL, increasing to 3163 mIU/mL by the eighth postoperative day. Administration of methotrexate and citrovorum factor caused a 48% decline in the level of serum beta-hCG over 72 hours, but did not prevent delayed hemorrhage by the tubal gestation. This case emphasizes that close surveillance during the treatment of persistent ectopic pregnancy should continue until serum beta-hCG is undetectable.