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PubMed1998

Malignant neoplasm in kidney transplantation.

BACKGROUND: The kidney recipient is at a higher risk for cancer than is the general population, although the incidence of neoplasms in general is considered lower in Japan than in Western countries. The cause of this increased risk associated with either transplantation or geography has not yet been established. METHOD: The incidences and sites of malignant neoplasms were analyzed in 285 kidney recipients, who had been followed up for 3007 patient-years. The relationship between immunosuppressive states, the numbers of CD4-positive T lymphocytes, and the presence of malignant neoplasms was studied retrospectively. RESULTS: Eighteen malignant neoplasms were found in 17 of the 285 patients (6%). The malignancies developed in these patients an average of++ 1 26.5 months after transplantation. The incidence was only 3.9% at 10 years, increasing to 13.9% at 20 years. No difference in the time-course incidence was found between azathioprine-based and cyclosporin-based immunosuppressive regimens. The malignancies developed in the digestive organs in more than half of the patients, and were mainly in the liver, colon and rectum, and stomach, with a relatively low incidence of skin cancer and lymphoma. There was only one case of Epstein-Barr virus genome found in 5 specimens that were tested. Concerning the immunosuppressive state, CD4-positive T lymphocyte counts were not related directly with malignancies in our series. CONCLUSION: The cumulative incidence of malignancy increased markedly in the second posttransplant decade. The site of cancers in kidney recipients mirrors that of general Japanese malignancies. Our results revealed neither the cause nor predictor for malignancies in kidney transplant patients.

Adolescent↗

PubMed2001

Intraductal papillary-mucinous tumors of the pancreas: differential diagnosis between benign and malignant tumors by endoscopic ultrasonography.

OBJECTIVES: Recently, intraductal papillary-mucinous tumor (IPMT) of the pancreas has increasingly been recognized. However, differential diagnosis between benign and malignant IPMT is often difficult using conventional imaging modalities. The purpose of this study was to retrospectively investigate the value of endoscopic ultrasonography (EUS) for differentiating malignant from benign IPMT. METHODS: A total of 51 patients with IPMT were preoperatively examined by EUS. The endosonograhic findings were compared with histopathological findings of the resected specimens. RESULTS: In main duct type IPMT, the diameter of the main pancreatic duct (MPD) was > or =10 mm in seven of the eight malignant tumors, compared with two of the seven benign tumors (p < 0.05). In branch duct type IPMT, three of the four large tumors (>40 mm) with irregular thick septa were malignant lesions. In both main duct type IPMT and branch duct IPMT, eight patients had large mural nodules (>10 mm); seven of the eight tumors were malignant and one of the eight tumors was benign. When the tumor was diagnosed as malignant according to above three findings, EUS was able to differentiate between malignant and benign IPMT with an accuracy of 86%. CONCLUSIONS: Main duct type tumors with > or =10 mm dilated MPD, branch duct type tumors (>40 mm) with irregular septa, and large mural nodules (>10 mm) strongly suggest malignancy on EUS. EUS would be a useful modality for differentiating between benign and malignant IPMT.

Adenocarcinoma, Mucinous↗

PubMed1998

Application of the polymerase chain reaction for the diagnosis of malignant lymphoma of the nasal and oral cavities.

Difficulties are often encountered in the diagnosis of malignant lymphoma of the oral and nasal cavities by histology and immunohistochemistry because these malignancies may be complicated by inflammation and necrosis. In the present study, immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements were examined by the polymerase chain reaction (PCR) in formalin-fixed and paraffin-embedded specimens obtained from 18 patients; the advantages of this method were evaluated. Twelve of these patients were diagnosed as having malignant lymphoma and six had tumors highly suggestive of malignant lymphoma. Fourteen (78%) of the 18 cases were diagnosed as malignant lymphoma histologically and immunohistochemically. Sixteen (89%) of the 18 cases were shown to be monoclonal by PCR. The four cases that could not be histologically or immunohistochemically diagnosed as malignant lymphoma showed monoclonal gene rearrangement by PCR. As a result, six patients suspected of having a malignant lymphoma were diagnosed as having one. The diagnosis of malignant lymphoma by PCR alone still has various problems. However, when the results of PCR are evaluated together with histopathological and immunohistochemical results, PCR makes a useful contribution to the diagnosis of malignant lymphomas of the nasal and oral cavities.

DNA, Neoplasm↗

PubMed1979

A retrospective histological study of 669 cases of primary cutaneous malignant melanoma in clinical stage I. The consequences of a reclassification of the original group of lentigo maligna melanomas.

A selected series of primary malignant melanoma of the skin, clinical stage I, was originally classified according to Clark's system. The consistency of this classification was tested by two Brisbane pathologists who indicated that we had misinterpreted some cases of superficial spreading malignant melanoma as lentigo maligna melanoma. We have therefore reclassified the original group of 86 lentigo maligna melanomas. This resulted in a total series of 37 (5.5%) lentigo maligna melanomas, 301 (45%) superficial spreading malignant melanomas, 194 (29%) nodular malignant melanomas (unchanged) and 137 (20.5%) unclassifiable malignant melanomas. The diagnosis of lentigo maligna melanoma was not made unless the epidermis was atrophic and dermal solar elastosis was present. The new group of lentigo maligna melanomas is dominated by cases on the head among patients over 50 years of age (especially women). This is in better agreement with other studies than our previous findings. The relationship with tumour cell type, pigmentation, mitotic count, atypia, transsectional profile, level of invasion, ulceration, vascular invasion, lymphocyte infiltration and prognosis shown by the new groups of lentigo maligna melanoma and superficial spreading malignant melanoma indicates that the cases by which the diagnosis has been changed are relatively benign. Our previous conclusions are still valid. The lentigo maligna melanoma is still the most benign type and nodular malignant melanoma still the most malignant type of melanoma. The superficial spreading malignant melanoma still represents an intermediate tumour type, although it has deviated in the benign direction.

Adult↗

PubMedDate not supplied

Comparison between malignant and nonmalignant splenic masses in dogs using contrast-enhanced computed tomography.

The ability of computed tomography (CT) to distinguish malignant from nonmalignant splenic masses was evaluated in 21 dogs with 24 masses. CT scans of the abdomen were performed pre- and postintravenous contrast medium administration before splenectomy or euthanasia. Splenic masses were evaluated objectively based on Hounsfield units (HU) and volume. Subjective criteria included location within the spleen (head, body, or tail), margination, homogeneity, and attenuation compared to the remaining splenic parenchyma. Characteristics of malignant and nonmalignant masses were compared. The nonmalignant masses were divided into splenic hematomas and nodular hyperplasia for further analysis. Fourteen (58.3%) of the masses were nonmalignant; 10 (41.7%) were malignant. Malignant splenic masses had significantly lower attenuation values, measured in HU, than nonmalignant splenic masses, on both pre- and postcontrast images (P<0.05). On postcontrast images, there was a significant difference in attenuation characteristics among all three subsets of splenic masses (malignant, hematoma, hyperplasia), with nodular hyperplasia having the highest HU values (90.3), hematomas having intermediate HU values (62.5), and malignant splenic masses having the lowest HU values (40.1). A receiver operator characteristic curve of postcontrast medium HU values revealed 55 as the best threshold value to distinguish malignant from nonmalignant masses, with those less than the threshold value being malignant. Abdominal CT is a useful diagnostic imaging modality for evaluation of focal canine splenic masses, with a significant difference in imaging characteristics between malignant and nonmalignant masses.

Animals↗

PubMed2001

De novo malignancy after paediatric renal replacement therapy.

AIMS: To determine frequency, type, determinants, and outcome of malignancies in children with end stage renal failure. METHODS: All Dutch patients, aged less than 15 years, who started chronic renal replacement therapy between 1972 and 1992 and who were at least 18 years old on 1 January 1997, were retrospectively studied. RESULTS: Mean follow up from first renal replacement therapy was 15.5 years. Twenty two malignancies were found in 21 of 249 patients. Skin cancer accounted for 59% and non-Hodgkin lymphoma for 23% of malignancies. At 25 years after first renal replacement therapy, the probability of developing a malignancy was 17% (95% CI: 9 to 24%). Compared to the general population the incidence rate for overall cancer was tenfold higher. For non-melanoma skin cancer and non-Hodgkin lymphoma, standardised risks were 222 and 46 respectively. The use of more than 20 mg/kg cyclophosphamide showed an association with increased risk of malignancy. Six patients died as a result of their malignancy, accounting for 9.5% of overall mortality. Whereas four out of five patients with non-Hodgkin lymphoma died, the most frequent malignancy, skin cancer, did not contribute to mortality. CONCLUSION: The long term risk of certain malignancies is significantly increased in children who have undergone renal replacement therapy. As an important contributor to overall mortality, awareness of this risk of malignancy in these patients is necessary, especially after treatment with cyclophosphamide.

Adolescent↗

PubMed2006

Adrenal lesions: characterization with fused PET/CT image in patients with proved or suspected malignancy--initial experience.

PURPOSE: To retrospectively evaluate the accuracy of the fused positron emission tomographic (PET)/computed tomographic (CT) image for characterization of adrenal lesions in patients who have proved malignancy or are suspected of having malignancy. MATERIALS AND METHODS: Institutional review board approval was received for this retrospective HIPAA-compliant study, and informed consent was waived. Forty-one adrenal lesions in 38 patients (21 men, 17 women; mean age, 66 years; range, 37-86 years) were evaluated with PET/CT. Of the 41 lesions, nine were assumed to be malignant with documentation of enlargement (n = 8) or reduction in size in response to treatment (n = 1), and 32 were assumed to be benign with documentation of stability for 6 months (n = 31) or with confirmation with biopsy results (n = 1). The PET examination findings were positive when adrenal lesion maximum standardized uptake values (SUVs) exceeded hepatic maximum SUVs. CT contrast medium washout analysis was used to further characterize two lesions with PET findings positive for malignancy. The t test was used to assess significant (P < .05) differences between fluorine 18 fluorodeoxyglucose (FDG) uptake of benign lesions and that of malignant lesions. RESULTS: At PET/CT, findings for all malignant lesions were positive (mean adrenal lesion-liver activity ratio, 4.04; range, 1.53-17.08). Of the 32 benign lesions, most (30 of 32) had activity less than that of the liver (mean ratio, 0.66; range, 0.22-0.94). PET/CT demonstrated sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 93.8%, 81.8%, 100%, and 95.1%, respectively. Incorporating contrast material-enhanced CT with delayed imaging increased specificity to 100% because two lesions with PET findings positive for malignancy were characterized as benign. There was a significant difference between maximum SUV (P < .05) and the ratio of adrenal lesion-liver FDG activity (P < .001) in benign versus malignant adrenal lesions. CONCLUSION: PET/CT provides a powerful combination of functional and attenuation information for adrenal lesion characterization. All malignant lesions were detected at PET/CT, with no false-negative results.

Adrenal Gland Neoplasms↗

PubMed2005

Cutaneous vasculitis in the course of hematologic malignancies.

BACKGROUND: In patients with hematologic malignancies, cutaneous vasculitis is an important manifestation which may be secondary either to the malignancy itself or to many frequent events in these patients such as infections or drug intake. OBJECTIVE: To assess the underlying events responsible for cutaneous vasculitis in patients with hematologic malignancies. METHODS: Twenty-three patients with hematologic malignancies who had a skin biopsy in a single institution between January 1990 and June 1995 disclosing vasculitis were included in this study. Clinical, biological and immunological data, infectious enquiry and drug exposure were reviewed. RESULTS: The 23 patients represented 22% of 95 patients with hematologic malignancies in whom 105 skin biopsies were done. A lymphoproliferative disorder was found in 12/23 (52%) and a myeloproliferative disease in 11/23 (48%). The cutaneous vasculitis developed concomitantly with the malignancy in 39%, before in 26% and after the diagnosis of malignancy in 35%. The hematologic condition seemed to be the sole cause for vasculitis in 61% of the patients while the vasculitis could be attributed to another mechanism than the hematologic malignancy itself in 39%. These consisted in infections, medication and mixed cryoglobulinemia in 13% each. CONCLUSION: Cutaneous vasculitis constitutes a symptom developing in association with hematologic malignancy and may follow, accompany and also precede the condition. However, search for other triggering factors such as infection, drugs and cryoglobulinemia is required since they are the culprits of the vasculitis in 39% of cases.

Adult↗

PubMed1982

CAMP differences between clones of high and low malignant fibrosarcoma cells.

The levels of 3',5'-cyclic adenosine monophosphate (cAMP) were measured in a high malignant and a low malignant clone of murine fibrosarcoma cells isolated from a common parent in a normal mouse fibroblasts at various stages of growth. There was an inverse correlation between the degree of malignant potential and the cAMP levels. The normal fibroblasts had the highest cAMP at all time periods measured. The high malignant cells had the lowest levels and the low malignant cells were intermediary. The degree of susceptibility of each population to the growth inhibiting effects of dibutyryl cAMP, a cAMP analogue, was also measured. There was a direct correlation between degree of malignant potential and susceptibility to growth inhibition. These findings strongly support our belief that the low malignant cells represent a state of malignancy that is intermediary between the high malignant cells and the normal fibroblasts. cAMP differences may contribute to this.

Animals↗

PubMed2000

Malignant pheochromocytoma. Chromaffin granule transmitters and response to treatment.

Chromaffin granule transmitters such as chromogranin A and catecholamines have been used in the diagnosis of pheochromocytoma, but the diagnostic and prognostic value of chromogranin A have not been explored in malignant pheochromocytoma. We evaluated these transmitters in patients with pheochromocytoma (n=27), both benign (n=13) and malignant (n=14). Patients with benign pheochromocytoma were studied before and after surgical excision (n=6), whereas patients with malignant pheochromocytoma were evaluated before and after combination chemotherapy with regular cycles of cyclophosphamide/dacarbazine/vincristine (nonrandomized trial in n=9). During treatment, patient responses to chemotherapy were divided according to anatomic and clinical criteria: responders (n=5) versus nonresponders (n=4). Plasma chromogranin A rose progressively (P<0.0001) from control subjects (48.0+/-3.0 ng/mL) to benign pheochromocytoma (188+/-40.5 ng/mL) to malignant pheochromocytoma (2932+/-960 ng/mL). Parallel changes were seen for plasma norepinephrine (P<0.0001), though plasma epinephrine was actually lower in malignant than benign pheochromocytoma (P=0.0182). In bivariate analyses, chromogranin A, norepinephrine, and epinephrine discriminated between pheochromocytoma and control subjects (all P<0.0001), whereas in a multivariate analyses, norepinephrine was the best discriminator (P:=0.011). Chromogranin A was significantly different in benign versus malignant pheochromocytoma on both bivariate (P=0.0003) and multivariate (P:=0.011) analyses. After excision of benign pheochromocytoma, chromogranin A (P=0.028), norepinephrine (P=0.047), and epinephrine (P=0.037) all fell to values near normal. During chemotherapy of malignant pheochromocytoma (n=9), plasma chromogranin A (P=0.047) and norepinephrine (P=0.02) fell but not epinephrine. In 5 responders to chemotherapy, there were significant declines in chromogranin A (P=0.03) and norepinephrine (P=0.03) but not epinephrine; in 4 nonresponders, none of the transmitters changed. Plasma chromogranin A varied longitudinally with tumor response and relapse. We conclude that plasma chromogranin A is an effective tool in the diagnosis of pheochromocytoma, and markedly elevated chromogranin A may point to malignant pheochromocytoma. During chemotherapy of malignant pheochromocytoma, chromogranin A can be used to gauge tumor response and relapse.

Adolescent↗

PubMed1985

Immunological reactivity of serum ferritin in patients with malignancy.

Serum ferritin has been suggested as a tumor marker in the diagnosis of certain malignancies and for following the activity or dissemination of the malignant process. Since neoplastic tissues generally contain more acidic isoferritins than their normal tissue counterparts, it has also been suggested that the specific assay of such isoferritins in serum may be of particular value in the diagnosis of malignancy. In this work, we have evaluated ferritin concentration in the serum of normal subjects and patients with acute nonlymphocytic leukemia, Hodgkin's disease, breast cancer and lung cancer by simultaneously using three different immunoassays: an immunoradiometric assay based on polyclonal antibodies against human liver (basic, L-subunit rich) ferritin, a radioimmunoassay based on polyclonad antibodies against HeLa cell (acidic, H-subunit rich) ferritin, and an immunoradiometric assay based on the monoclonal antibody 2A4 raised against human heart (acidic, H-subunit rich) ferritin. Most of the patients studied had increased values for liver-type ferritin in the absence of increased iron stores. Binding of serum ferritin to concanavalin A did not prove to be useful in distinguishing a tumor-specific basic isoferritin. The HeLa ferritin assay was found to be less specific than the heart ferritin assay in the detection of acidic isoferritins, and did not provide any advantage over the liver assay in detecting the increased levels of serum ferritin associated with malignant disease. Heart-type ferritin was found in one-fifth of normal sera and 64% of sera from patients with malignancy. Values were very low compared with those for basic ferritin, ranging from less than 0.1 to 17% of total serum ferritin (geometric mean value 1.3%) in patients with malignancy. These findings indicate that at present there is little application for serum ferritin immunoassays based on antibodies to HeLa cell or heart ferritin in the diagnosis or monitoring of malignant disease. This seems to be due to the presence in human serum of biding factors which are responsible for the rapid clearance of acidic isoferritins from the circulation. The serum concentration of basic ferritin, however, can be useful in the diagnosis and management of some malignancies, and it is possible that studies on cell isoferritins can be important in biologic monitoring of neoplastic disorders. It should also be noted that the increased levels of serum ferritin found in patients with malignancy can exert adverse effects on the host immune response and perhaps an inhibitory effect on hematopoiesis.

Antibodies, Monoclonal↗

PubMed2006

Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues.

BACKGROUND: In prostate cancer, normal citrate-producing glandular secretory epithelial cells undergo a metabolic transformation to malignant citrate-oxidizing cells. m-Aconitase is the critical step involved in this altered citrate metabolism that is essential to prostate malignancy. The limiting m-aconitase activity in prostate epithelial cells could be the result of a decreased level of m-aconitase enzyme and/or the inhibition of existing m-aconitase. Earlier studies identified zinc as an inhibitor of m-aconitase activity in prostate cells; and that the depletion of zinc in malignant cells is an important factor in this metabolic transformation. However, a possibility remains that an altered expression and level of m-aconitase enzyme might also be involved in this metabolic transformation. To address this issue, the in situ level of m-aconitase enzyme was determined by immunohistochemical analysis of prostate cancer tissue sections and malignant prostate cell lines. RESULTS: The immunocytochemical procedure successfully identified the presence of m-aconitase localized in the mitochondrial compartment in PC-3, LNCaP, and DU-145 malignant prostate cell lines. The examination of prostate tissue sections from prostate cancer subjects demonstrated that m-aconitase enzyme is present in the glandular epithelium of normal glands, hyperplastic glands, adenocrcinomatous glands, and prostatic intraepithelial neoplastic foci. Quantitative analysis of the relative level of m-aconitase in the glandular epithelium of citrate-producing adenomatous glands versus the citrate-oxidizing adenocarcinomatous glands revealed no significant difference in m-aconitase enzyme levels. This is in contrast to the down-regulation of ZIP1 zinc transporter in the malignant glands versus hyperplastic glands that exists in the same tissue samples. CONCLUSION: The results demonstrate the existence of m-aconitase enzyme in the citrate-producing glandular epithelial cells; so that deficient m-aconitase enzyme is not associated with the limiting m-aconitase activity that prevents citrate oxidation in these cells. The level of m-aconitase is maintained in the malignant cells; so that an altered enzyme level is not associated with the increased m-aconitase activity. Consequently, the elevated zinc level that inhibits m-aconitase enzyme is responsible for the impaired citrate oxidation in normal and hyperplastic prostate glandular epithelial cells. Moreover, the down-regulation of ZIP1 zinc transporter and corresponding depletion of zinc results in the increase in the activity of the existing m-aconitase activity in the malignant prostate cells. The studies now define the mechanism for the metabolic transformation that characterizes the essential transition of normal citrate-producing epithelial cells to malignant citrate-oxidizing cells.

Aconitate Hydratase↗

PubMed2003

Risk of malignancy in an unselected cohort of Icelandic patients with systemic lupus erythematosus.

In the present literature there is still controversy as to whether patients with systemic lupus erythematosus (SLE) are at increased risk of developing malignant diseases. In recent years a number of epidemiological studies have been conducted and some have suggested an association between SLE and malignant diseases while other studies have not. The objective of this study was to investigate this relationship in an unselected cohort of Icelandic patients with SLE. All patients diagnosed with SLE registered in the Icelandic SLE database were compared to the Icelandic cancer registry. For completeness, hospital charts and outpatient notes were also reviewed. The study period was from 1957 to the end of 2001. The O/E (observed/expected ratio), CI and P-value were calculated for total number of malignancies as well as individual malignancy types. Of 238 patients diagnosed with SLE (213 women and 25 men) 39 malignancies were diagnosed in 36 patients; 32 women and four men. Of the 36 patients, 27 were diagnosed subsequently with SLE and malignant disease. The mean age at diagnosis of SLE was 43.2 years (range 10-81) and at time of diagnosis of malignancy 62.7 years (range 43-86). The O/R for the whole study population was 1.38 (CI 0.89-1.87, P = 0.063), 1.45 for the women (CI 0.91-1.99, P = 0.051) and 1.03 for the men (CI 0.22-2.66, P = 0.560). The O/R for the most frequent malignancies diagnosed subsequently to SLE was 6.43 for squamous cell skin cancer (CI 1.31-18.5, P = 0.012), 5.48 for lymphoma (CI 0.64-19.6, P = 0.052), 2.46 for uterine cancer (CI 0.29-8.78, P = 0.196), 2.0 for ovarian cancer (CI 0.23-7.14, P = 0.264), 1.72 for lung cancer (CI 0.36-4.95, P = 0.254) and 1.6 for breast cancer (CI 0.65-3.23, P = 0.154). The total number of patient-years at risk was 2774 years. The results from this study on an unselected cohort of Icelandic SLE patients do not suggest an overall association between SLE and malignancy. Squamous cell skin cancer was the only individual cancer type that was statistically increased in the population and the numbers for lymphoma were borderline statistically significant.

Adolescent↗

PubMed1996

Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas.

BACKGROUND: An excess risk of second malignancies has been reported in survivors of Ewing's sarcoma. We examined a multiinstitutional data base to reevaluate the risk among survivors of Ewing's sarcoma and to identify possible causal factors. METHODS: Information was derived from a data base that included 266 survivors of Ewing's sarcoma. Cumulative incidence rates of second malignancies were calculated. Contributions of clinical features, type and dose of chemotherapy, and cumulative radiation dose to the risk of second malignancies were evaluated. RESULTS: After a median follow-up duration of 9.5 years (range, 3.0 to 30), 16 patients have developed second malignancies, which included 10 sarcomas (five osteosarcomas, three fibrosarcomas, and two malignant fibrous histiocytomas) and six other malignancies (acute myeloblastic leukemia, acute lymphoblastic leukemia, meningioma, bronchioalveolar carcinoma, basal cell carcinoma, and carcinoma-in-situ of the cervix). The median latency to the diagnosis of the second malignancy was 7.6 years (range, 3.5 to 25.7). The estimated cumulative incidence rates at 20 years for any second malignancy and for secondary sarcoma were 9.2% (SD = 2.7%) and 6.5% (SD = 2.4%), respectively. The cumulative incidence rate of secondary sarcoma was radiation dose-dependent (P = .002). No secondary sarcomas developed among patients who had received less than 48 Gy, while the absolute risk of secondary sarcoma was 130 cases per 10,000 person-years of observation among patients who had received > or = 60 Gy. CONCLUSION: The overall risk of second malignancies after Ewing's sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose-dependency of secondary sarcomas justifies modification in therapy to reduce radiation doses.

Adolescent↗

PubMed2000

Second malignancies after treatment of early-stage breast cancer: lumpectomy and radiation therapy versus mastectomy.

PURPOSE: To determine the risk of second malignancies after lumpectomy and radiation therapy (LRT), and to compare it with that in a similar cohort of early-stage breast cancer patients undergoing mastectomy without radiation (MAST). PATIENTS AND METHODS: Between January 1970 and December 1990, 1,029 breast cancer patients at our institution underwent LRT. A cohort of 1,387 breast cancer patients who underwent surgical treatment by mastectomy (MAST), and who did not receive postoperative radiation during the same time period, served as a comparison group. Second malignancies were categorized as contralateral breast versus nonbreast. In the cohort of patients undergoing LRT, a detailed analysis was carried out with respect to age, disease stage, smoking history, radiation therapy technique, dose, the use of chemotherapy or hormone therapy, and other clinical and/or pathologic characteristics. RESULTS: As of March 1999, the median follow-up was 14.6 years for the LRT group and 16 years for the MAST group. The 15-year risk of any second malignancy was nearly identical for both cohorts (17.5% v 19%, respectively). The second breast malignancy rate at 15 years was 10% for both the MAST and LRT groups. The 15-year risk of a second nonbreast malignancy was 11% for the LRT and 10% for the MAST group. In the subset of patients 45 years of age or younger at the time of treatment, the second breast and nonbreast malignancy rates at 15 years were 10% and 5% for patients undergoing LRT versus 7% and 4% for patients undergoing mastectomy (P, not statistically significant). In the detailed analysis of LRT patients, second lung malignancies were associated with a history of tobacco use. There were fewer contralateral breast tumors in patients undergoing adjuvant hormone therapy, although this did not reach statistical significance. The adjuvant use of chemotherapy did not significantly affect the risk of second malignancies. CONCLUSION: There seems to be no increased risk of second malignancies in patients undergoing LRT using modern techniques, compared with MAST. Continued monitoring of these patient cohorts will be required in order to document that these findings are maintained with even longer follow-up periods. With nearly 15 years median follow-up periods, however, these data should be reassuring to women who are considering LRT as a treatment option.

Adult↗

PubMed2005

Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma.

PURPOSE: Although the risk of myelodysplastic syndrome (MDS) has been well-described following autologous bone marrow transplantation (ABMT), the risk of solid tumors has been poorly characterized. We report the incidence and outcome of solid tumors at 10-year follow-up in a large cohort of uniformly treated patients who underwent ABMT for non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between 1982 and 1997, 605 patients underwent ABMT for B-cell NHL, with uniform conditioning with cyclophosphamide and total-body irradiation followed by reinfusion of autologous bone marrow purged with anti-B-cell monoclonal antibodies. Current information on relapse of disease and second malignancies was obtained via an institutional review board-approved questionnaire sent to the referring oncologists. RESULTS: Forty-two solid tumors, six non-MDS hematologic malignancies, 39 nonmelanoma skin cancers, and 68 cases of MDS/acute myelogenous leukemia (AML) were observed at a median follow-up of 9.5 years. A cumulative incidence model using death as a competing risk found that the 10-year incidence of second malignancy is 21%, with 10.0% non-MDS malignancies. The projected incidence of all malignancies at 15 years is 29%. The principal risk factor for second malignancy is increased age at ABMT (P = .0002). In the entire cohort, 9.6% of patients have died of second malignancy. CONCLUSION: Lengthy follow-up demonstrates a significant incidence of second malignancies after ABMT for NHL. Although the incidence of MDS/AML starts to plateau, the incidence of solid tumors continues to rise. Second malignancies are responsible for a significant fraction of overall mortality following ABMT.

Adult↗

PubMed2006

Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration.

CONTEXT: Thyroid nodules and goiter are common, and fine-needle aspiration biopsy (FNAB) is the first investigation of choice in distinguishing benign from malignant disease. OBJECTIVE: The objective of the study was to assess whether simple clinical and biochemical parameters can predict the likelihood of thyroid malignancy in subjects undergoing FNAB. DESIGN: The design was a prospective cohort. SETTING: The study was conducted at a single secondary/tertiary care clinic. PARTICIPANTS: One thousand five hundred consecutive patients without overt thyroid dysfunction (1304 females and 196 males, mean age 47.8 yr) presenting with palpable thyroid enlargement between 1984 and 2002 were evaluated by FNAB of the thyroid. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURES: Goiter type was assessed clinically and classified as diffuse in 183, multinodular in 456, or solitary nodule in 861 cases. Serum TSH concentration at presentation was measured in a sensitive assay in patients presenting after 1988 (n = 1183). The final cytological or histological diagnosis was determined after surgery (n = 553) or a minimum 2-yr clinical follow-up period (mean 9.5 yr, range 2-18 yr). RESULTS: The overall sensitivity and specificity of FNAB in predicting malignancy were 88 and 84%, respectively. The risk of diagnosis of malignancy rose in parallel with the serum TSH at presentation, with significant increases evident in patients with serum TSH greater than 0.9 mU/liter, compared with those with lower TSH. Binary logistic regression analysis revealed significantly increased adjusted odds ratios (AORs) for the diagnosis of malignancy in subjects with serum TSH 1.0-1.7 mU/liter, compared with TSH less than 0.4 mU/liter [AOR 2.72, 95% confidence interval (CI) 1.02-7.27, P = 0.046], with further increases evident in those with TSH 1.8-5.5 mU/liter (AOR 3.88, 95% CI 1.48-10.19, P = 0.006, compared with TSH < 0.4 mU/liter) and greater than 5.5 mU/liter (AOR 11.18, 95% CI 3.23-8.63, P < 0.001, compared with TSH < 0.4 mU/liter). Males (AOR 1.8, 95% CI 1.04-3.1, P = 0.04), younger patients (AOR 1.1, 95% CI 1.01-1.15, P = 0.025), and those with clinically solitary nodules (AOR 2.53, 95% CI 1.5-4.28, P = 0.001) were also at increased risk. Based on these findings, a formula to predict the risk of the diagnosis of thyroid malignancy in individual patients, taking into account their gender, age, goiter type determined clinically, and serum TSH, was calculated. CONCLUSIONS: The risk of malignancy in a thyroid nodule increases with serum TSH concentrations within the normal range. In addition to patient's gender, age, and goiter type, the serum TSH concentration at presentation is an independent predictor of the presence of thyroid malignancy. We propose that these simple clinical and biochemical factors can serve as an adjunct to FNAB in predicting risk of malignancy.

Adolescent↗

PubMed1997

Spinal epidural metastasis as the initial manifestation of malignancy: clinical features and diagnostic approach.

The objective of our study was to delineate clinical features and specific diagnostic and therapeutic implications of spinal epidural metastasis (SEM) occurring as the initial manifestation of malignancy (IMM)-a less common event than SEM in the setting of previously established malignancy (PEM). We performed a retrospective review of the clinical histories of 337 patients seen at Mayo Clinic with a radiographically verified diagnosis of SEM between January 1, 1985, and December 31, 1993. Twenty percent of all cases of SEM occurred as SEM-IMM. Carcinoma of the lung, cancer of unknown primary site, multiple myeloma, and non-Hodgkin's lymphoma were disproportionately represented in SEM-IMM, together accounting for 78% of SEM-IMM patients and only 26% of SEM-PEM patients. Inversely, breast and prostate carcinoma contributed only 12% of SEM-IMM patients but 51% of SEM-PEM patients. Only 27% of patients with SEM-IMM had nonspecific symptoms suggesting malignancy, and in only 24% did the history or physical examination suggest the primary site of malignancy. Percutaneous needle biopsy of the vertebral lesion was diagnostic of malignancy in 18 of 19 patients (95%), and no complications ensued. Fifteen patients underwent diagnostic laminectomy with biopsy, and one had a fatal complication. Survival after the diagnosis of SEM did not differ between patients with SEM-IMM and those with SEM-PEM; the median survival was 6.6 months. SEM not uncommonly occurs as the presentation of malignancy, and often it produces the only symptoms or signs of malignancy. The great majority of neoplasms presenting with SEM are carcinomas of the lung, unknown primary lesions, and hematologic malignancies. Computed tomography-guided needle biopsy is a safe, efficacious means of diagnosing malignancy, allowing for rational diagnostic workup and staging. In most patients it obviates a diagnostic spinal surgical procedure.

Adolescent↗