Upper limb reflex sympathetic dystrophy associated with occult malignancy

Reflex sympathetic dystrophy, characterized by pain, swelling, vasomotor instability, and trophic changes in an extremity, has been infrequently described in patients with occult malignancy. Two cases of reflex sympathetic dystrophy associated with local tumor involvement are reported. Both patients had a history of cancer in clinical remission. Despite aggressive physical therapy measures, the patients' symptoms persisted. Workup of the first patient found an apical paravertebral mass in the lung; biopsy revealed recurrent breast carcinoma. In the second case, workup found an axillary mass contiguous with the lower brachial plexus. Biopsy revealed lymphoma, a second primary malignancy. In both cases, medical treatment of the tumor was instituted, with consequent improvement of hand and shoulder function. Both patients required prolonged hospitalization and multiple procedures that might have been avoided if malignancy had been suspected. Spontaneous development of reflex sympathetic dystrophy in patients with a history of cancer should alert the physician to the possibility of occult malignancy.     

Intraoperative detection of occult colon cancer micrometastases using 125 I-radiolabled monoclonal antibody CC49

BACKGROUND: The detection of locally-disseminated disease is one of the principal goals of oncologic surgery. For this study, a hand-held, gamma-detecting probe was used intraoperatively to assess the extent of colorectal carcinoma in patients previously injected with radiolabeled antibody to the TAG-72 antigen (CC49); this technique is known as Radioimmunoguided Surgery (RIGS) (Neoprobe Corporation, Dublin, OH). RIGS-positive areas (i.e. those with increased signal over background) have previously been shown to contain carcinoma in a high proportion of cases. However, some RIGS-positive areas had no tumor detectable by clinical examination or routine histopathologic analysis. This study was undertaken to determine if the presence of occult metastases might account for this disparity. METHODS: A total of 57 regional lymph nodes (LN), resected from 16 patients with primary (9) or recurrent (7) colorectal carcinoma, were studied. The patients were injected with 125I labeled CC49 murine monoclonal antibody approximately 3 weeks prior to surgery. After routine histologic evaluation, the LN were analyzed for occult metastases; paraffin sections were cut at 5 levels (50 micron apart) and were examined by histology (hematoxylin and eosin stain [H & E]) and by immunohistochemistry (IHC) with a cocktail of monoclonal antibodies to cytokeratins. RESULTS: Fifty-seven LN were included in this study; 17 were H & E-positive (i.e., contained tumor by routine histologic examination [overt tumor]), while 40 LN were H & E-negative (i.e., no evidence of tumor after routine histologic examination). Thirty-nine LN were RIGS-positive, but only 14 of these were H & E-positive. Of the 25 RIGS-positive/H & E-negative LN, 10 (40%) demonstrated the presence of occult metastases after serial section/IHC analysis. Thus, a total of 27 LN contained metastatic carcinoma (17 overt, 10 occult); routine histologic analysis was able to identify tumor in only 17 of these 27 LN (63%), while the probe signaled the presence of tumor in 24 of these LN (89%). None of the RIGS-negative/H & E-negative LN were found to have occult metastases (0/15). Specific immunoreactivity with CC49 antibody was observed in 5 of 15 RIGS-positive/H & E-negative LN in which no tumor could be identified by any method (histopathology or IHC. CC49 immunoreactivity was not observed in 15 RIGS-negative/H & E-negative LN. CONCLUSIONS: The finding of a RIGS-positive LN had a significant association with the presence of tumor cells (P < 0.05). In this study, the RIGS procedure was more sensitive than clinical or histopathologic examination in detecting the regional spread of a tumor. Furthermore, in LN that showed no evidence of tumor by routine histopathologic examination, a positive RIGS reading was significantly associated with the presence of occult LN metastases (P < 0.01). This study is the first to demonstrate the detection of histologically occult tumor by a remote imaging device. RIGS assessment is a highly sensitive method for detecting occult tumor deposits, and may guide therapeutic intervention in patients with colorectal carcinoma.     

Angiosarcoma of the liver in children

The clinico-pathological features of four cases of pediatric hepatic angiosarcomas are described. One case was initially diagnosed in infancy and underwent resection of a left-sided benign hemangioendothelioma of the liver. Further resection of a lesion in the right liver was followed by malignant transformation. Primary hepatic resection of the tumor was not possible in three other cases, and all received courses of chemotherapy without significant tumor shrinkage. One child underwent liver transplantation but died 4 months later of immunosuppression complications. The remaining three children died of disseminated malignancy. Histological verification of malignancy was difficult in three cases in which there was discrepancy between the rapid growth of the liver tumor and the microscopic features of benign hemangioendothelioma.     

Occult cancer in patients with venous thromboembolism: which patients, which cancers

We have previously demonstrated that patients with idiopathic venous thromboembolism (VTE) have a higher frequency of underlying cancer. Now we present a retrospective analysis of our 5-year experience with a series of 674 consecutive otherwise healthy patients, and a more restricted battery of diagnostic tests. Occult cancer was found in 15 patients during admission. The diagnostic tools which led to suspect occult cancer were: abdominal CT-scan (4 patients); high carcinoembryonic levels (2 patients); and high prostate-specific antigen levels (9 patients). Eight further patients were diagnosed of cancer after discharge. Cancer was more commonly found in patients with idiopathic VTE: 13/105 patients (12%) versus 10/569 patients (2%); p <0.01; O.R.: 7.9 (95% CI: 3.14-20.09). During the same period of time we diagnosed VTE in 147 patients with previously known cancer. When overall considered, VTE was the first sign of malignancy in most patients with prostatic and pancreatic carcinoma. On the contrary, most patients with breast, lung, uterine and brain cancers developed VTE as a terminal event of the disease. At variance with VTE patients and previously known cancer, most patients with occult malignancy were at an early stage. Further studies are needed to confirm whether patients with idiopathic VTE could benefit from screening for occult cancer. Meanwhile, our findings may serve as guidelines for physicians in this field.     

Nephrotic syndrome, renal failure, and renal malignancy: an unusual tumor-associated glomerulonephritis

The association between malignancy and glomerular disease has been appreciated for over three decades. Although the relationship between membranous glomerulonephritis or minimal-change nephrotic syndrome and carcinoma or lymphoma, respectively, are the most widely known, several other glomerular lesions have been described in patients with malignancy. In this article, a patient who presented with nephrotic syndrome, volume overload, and renal failure, who was subsequently found to have a renal mass, is described. Resection of the mass, which proved to be a renal cell carcinoma, led to resolution of proteinuria and improvement of renal function. Pathology on the noninvolved portion of the kidney revealed a membranoproliferative glomerular lesion, a lesion usually associated with lymphomas and not previously described with renal carcinoma. Although a role of tumor antigens and anti-tumor antibodies in producing glomerular immune deposits has been speculated upon, the evidence for this assertion was spotty. However, reports of remission of proteinuria after tumor treatment or removal support a role of tumor products in pathogenesis. Although the association between proteinuria and malignancy is rare, it should be kept in mind, particularly in older patients with membranous glomerulonephritis where the possibility of malignancy needs to be further evaluated.     

Meningoradiculitis revealing an occult medulloblastoma-PNET in an adult

Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumor (PNET) is occasionally described in children. We report the case of an 64 year old-man who presented a meningo-radiculopathy with progressive injury of the cauda equina and then the ocular motor nerves, revealing an occult medulloblastoma-PNET.     

New therapies in the treatment of malignant pleural mesothelioma

It can be safely stated that currently there exists no standard therapy for malignant mesothelioma. The "standard" methods of chemotherapy, radiation therapy, and surgery have all been used with little improvement in overall survival. Trimodality therapy that involves a combination of all three standard treatment modalities has been shown to improve survival in selected patients. New and innovative treatment strategies clearly are needed for a disease which, because of the disappointment with standard therapy, is most commonly approached with only palliative intent. The location of this malignancy and its tendency to remain localized make it an ideal target for intracavitary approaches using photodynamic therapy, targeted cytokines, and gene therapy. Strategies using modulation of the immune system in an attempt to elicit a specific response to the tumor have been combined with chemotherapy to optimize response. Lessons learned from treating this localized malignancy with novel therapies may have much broader implications for other tumors in which systemic disease predominates.     

How to take a weapons history: interviewing children at risk for violence at school

BACKGROUND: Malignant melanoma is the most common metastatic tumor of the gastrointestinal tract and can present with abdominal pain, small bowel obstruction, or occult gastrointestinal bleeding. Diagnosing abdominal pain due to metastatic melanoma is best accomplished by intraluminal studies and computed tomography. Surgical resection of the tumor burden limited to the gastrointestinal tract has been shown to extend periods of palliation in this poor long-term survival group. OBJECTIVES: We will review a case of abdominal pain in a melanoma patient and review the literature.     

Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.     

Diagnosis of occult thyroid carcinoma by thyroid ultrasonography with fine needle aspiration cytology

OBJECTIVE: To assess the role of ultrasonography and fine needle aspiration cytology (FNAC) in preoperative diagnosis of patients with occult thyroid carcinoma (OTC). STUDY DESIGN: Data on 768 thyroid carcinoma patients receiving primary treatment at Chang Gung Medical Center were retrospectively reviewed. Of these patients, 97 had OTC. To detect small thyroid nodules early and define the characteristics of clinically palpable nodules, thyroid ultrasonography with FNAC were performed on 67 histopathologically proven OTC patients. Analysis for diagnostic value was done for ultrasonography and FNAC. RESULTS: In the 67 patients receiving ultrasonography with FNAC, 23 were preoperatively diagnosed as having papillary thyroid carcinoma and 1 as having follicular carcinoma. The tumor size of these 24 preoperative FNAC-proven OTC was 0.81 +/- 0.23 cm (mean +/- SD). In the remaining patients, 10 presented pictures suspicious for malignancy, with a mean tumor size 0.63 +/- 0.24 cm, and 33 (49.3%) were diagnosed as having benign thyroid lesions in preoperative FNAC. The tumor size in these 33 lesions was 0.58 +/- 0.24 cm. Fifty-seven of the 67 OTC patients received frozen sections. Thirty-eight papillary thyroid carcinomas and four follicular carcinomas were correctly diagnosed on frozen sections. CONCLUSION: Although the rate is not high, high-resolution ultrasonography and FNAC is the best approach to preoperative diagnosis for OTC patients today.     

Trans-species gene transfer for analysis of glucocorticoid-inducible transcriptional activation of transiently expressed human CYP3A4 and rabbit CYP3A6 in primary cultures of adult rat and rabbit hepatocytes

BACKGROUND: The sensitive detection of circulating tumor cells and micrometastases may have important therapeutic and prognostic implications. METHODS: The molecular detection of occult tumor cells can be accomplished by amplifying tumor specific abnormalities present in the DNA or mRNA of malignant cells with the polymerase chain reaction (PCR). This approach has been used mainly for hemato-lymphoid malignancies. The other main PCR strategy for the detection of minimal residual disease (MRD) involves amplification of tissue-specific mRNA. This method was applied for the detection of occult disease in solid tumors. RESULTS: PCR was shown to be superior to conventional techniques in detecting circulating tumor cells and micrometastases allowing the identification of 1 tumor cell diluted with 10(6)-10(7) normal cells. The central question of whether PCR positivity reliably predicts relapse remains unanswered for many tumor types. Serial analysis of a large number of samples is needed and currently undertaken in many institutions. CONCLUSIONS: PCR is a highly sensitive method for the detection of circulating tumor cells and micrometastases in solid and hematopoietic malignancies. If PCR positivity is found to be a reliable tool, this will likely have a major impact on the treatment of many cancers. Patients could be selected for systemic therapy at an earlier stage when the metastatic tumor burden is low. PCR may improve the preoperative staging of patients with epithelial malignancies and therefore help avoid unnecessary radical procedures. Furthermore, this test may be useful in monitoring the effectiveness of adjuvant therapy, the intensity and duration of which is tailored to the individual patient. The impact of this PCR based approach on clinical oncology is likely to be profound.     

Association of extrarenal Wilms'' tumor with a horseshoe kidney

Nephroblastoma (Wilms' tumor) is the most common renal malignancy in childhood. Extrarenal Wilms' tumor is uncommon, and the diagnosis is almost always postsurgical. The authors report two cases, located in the sigmoid mesocolon, one of these having an associated horseshoe kidney. Both were treated with excision followed by chemotherapy. They are now 36 months and 7 months postchemotherapy, respectively, and are symptom and recurrence free. Both had favorable histological findings. Association with a horseshoe kidney raises an important issue regarding the histogenesis of these tumors. The authors believe that there is a nexus between the fusion of metanephric blastema during the sixth to seventh week of intrauterine life and the "ectopic" metanephric blastema cells that may give rise to extrarenal Wilms' tumor. Association with a horseshoe kidney with an extrarenal Wilms' tumor has been reported on five previous occasions. The authors closely examine the link between the two.     

Selection-dependent trends of autogeny and blood feeding in an autogenous strain of Culex tarsalis (Diptera:Culicidae)

The purpose of this report is to examine the outcomes for patients with an underlying diagnosis of malignancy who have had Greenfield vena caval filters placed for protection from pulmonary embolism, and to identify areas requiring further study. This was a retrospective review of data obtained from the Greenfield filter registry and the University of Michigan Tumor Registry for 166 patients treated at the University of Michigan Medical Center between January 1988 and June 1994. The 84 men and 82 women (mean age 57.8 years) had a mean survival time of 10 (range 1-68) months. This differs significantly from patients in the filter registry who do not have malignancy (P<0.0001). Some 51% experienced recurrence of their malignancy at a mean of 20 months; this timing corresponds to development of new or recurrent thrombembolism and filter placement. Distant metastases were present in 72% of patients at the time of filter placement. In conclusion, as anticipated, filter patients with malignancy have a significantly shorter survival time than those with other concurrent diseases. A temporal association between the progression of the malignancy and the occurrence of thromboembolism is observed in this population and requires further study. Future studies regarding the use of vena caval filters in these patients and the role of diagnostic screening for deep venous thrombosis and occult recurrence of malignancy should focus on efficacy, safety, cost and patient quality of life rather than on survival.     

Expression of p53 and vascular endothelial growth factor associated with tumor angiogenesis and prognosis in gastric cancer

We performed six immediate free flap reconstructions after tumor ablation in 5 children under the age of 15 years presenting with head and neck malignancy. One patient underwent free flap transfer on two separate occasions because of tumor recurrence. There were no flap losses nor were there any complications related to microvascular surgery. Although a pediatric head and neck malignant tumor is rare, surgical resection is the primary therapeutic role for those that are amenable to complete excision. Pediatric microsurgery provides a safe and reliable procedure for reconstruction of head and neck defects after extirpation of the tumor.     

Myeloma stem cells in autografting in multiple myeloma

Autologous transplantation has been used increasingly over the last 10 years for the treatment of multiple myeloma. As is the case in other cancers treated by high-dose therapy and stem cell rescue, the contribution of occult tumor cells in the graft to relapse posttransplant remains to be resolved. In this report, we review the biology and differentiation of plasma cells in the context of their significance as an origin of relapse in multiple myeloma.     

Refining hollow obturator base using light-activated resin

Inclusion body myositis (IBM) is a separate class of the inflammatory myopathies with recently proposed clinical and pathological diagnostic criteria. An association between inflammatory myopathies and malignancy has been questioned in the literature. Recent reviews of the inflammatory myopathies suggest that only dermatomyositis is associated with malignancy. The largest study to date of patients with IBM found that 15% had a malignancy (6 of 40). We report the first documented case of IBM and concurrent transitional cell carcinoma of the bladder. We suggest that a causal relationship between IBM and malignancy may exist because of significantly improved functional strength gained after tumor removal.     

Accuracy of frozen section in the evaluation of salivary tumors

The records of 333 patients who underwent surgery were reviewed to document the accuracy of frozen section in the evaluation of salivary gland tumors. Frozen sections were obtained in 310 patients. The final pathologic diagnoses included 210 benign tumors and 45 malignancies. The sensitivity for the detection of malignancy was 69%, and the specificity was 96%. The specific accuracy to correctly identify the type of malignancy present was only 51%. In four patients, a false-positive diagnosis of malignancy was made. Frozen section was much more accurate in the evaluation of benign salivary tumors. Forty-three of 45 Warthin's tumors were correctly identified by frozen section. Two tumors thought to be Warthin's tumors on frozen section proved to be low-grade mucoepidermoid carcinomas. One tumor reported to be a benign mixed tumor was actually a malignant mixed tumor. In this series of patients, frozen section proved to be no more accurate in the evaluation of salivary tumors than what has been reported in the literature for fine-needle aspiration biopsy.     

The postpubertal change in the playful defense of male rats depends upon neonatal exposure to gonadal hormones

Only 19 cases of metastases at the cannula insertion site after laparoscopy for gynecological malignancy have been reported in the literature. One case has been diagnosed with cervical squamous cell carcinoma, whereas the others have been diagnosed with ovarian cancer and borderline ovarian tumor. We present a novel case of laparoscopy-site abdominal wall metastasis from endometrial cancer after laparoscopic-assisted vaginal hysterectomy (LAVH). The 56-year-old female patient exhibited metastases of an abdominal wall trocar site and a perineal site after undergoing LAVH and laparoscopic-assisted (LA) bilateral pelvic lymph node sampling as well as LA para-aortic lymph node sampling for treating endometrial carcinoma, surgical staging IIIC, G3. The interval between the surgical extirpation of endometrial carcinoma and diagnosis of the tumor recurrence was 6 months, suggesting that overmanipulation of the diseased organ during laparoscopic surgery may have resulted in tumor spillage, intraperitoneal dissemination, and wound contamination. Although this procedure has been proven beneficial to patients with benign disease or early-stage gynecologic malignancies, laparoscopic-assisted vaginal hysterectomy may not be efficacious to eradicate advanced gynecological malignancy.     

Epidermal growth factor family and renal cell carcinoma: expression and prognostic impact

OBJECTIVE: Expression and prognostic impact of some exponents of the epidermal growth factor (EGF) family in renal cell carcinoma (RCC) were examined. MATERIALS AND METHODS: EGF, transforming growth factor-alpha (TGF-alpha), EGF receptor (EGF-R), and c-erb B-2 were determined immunohistochemically in formalin-fixed paraffin-embedded tumor samples of 30 patients with locally confined RCCs. The prognostic significance of these growth factors and their receptors as well as of tumor stage and malignancy grade was examined with respect to survival and tumor recurrence by following up the fate of the patients after nephrectomy (mean follow-up time 5.2 years). RESULTS: The members of the EGF family and their receptors studied were expressed to a variable degree in all RCCs investigated. However, using log-rank tests in Kaplan-Meier plots only tumor stage (p < 0.0007) and malignancy grade (p < 0.007) but none of the growth factors or receptors studied (p > 0.05, respectively) exhibited prognostic significance with respect to both survival and disease-free period. On the contrary, there was a significant correlation between EGF and TGF-alpha (p < 0.001), EGF and EGF-R (p = 0.028), EGF-R and c-erb B-2 (p = 0.0009), and-inversely related-between TGF-alpha and tumor stage (p = 0.047) and between EGF-R and malignancy grade (p = 0.03). The coexpression of the factors studied also showed no prognostic relevance. CONCLUSION: The expression of these members of the EGF family seems not to bear evaluable prognostic information for clinical use in the case of RCC.     

Pediatric tuberculosis in rural South Africa--value of directly observed therapy

The case is reported of a 27-year-old patient who developed multiple recurrences of a carcinoma arising from richly stromal pleomorphic adenoma of the parotid gland over 13 years. Originally the tumor was classified as a benign pleomorphic adenoma because there were no cytological characteristics of malignancy. Later on the diagnosis had to be modified to that of a carcinoma arising from a pleomorphic adenoma because of the infiltrating growth pattern of the tumor. A multicentric local recurrence and metastases on the left side of the neck supported the correct diagnosis. This case demonstrates that, beside the classic cytological criteria of malignancy invasion and penetration of the capsule can be decisive for the diagnosis of malign transformed pleomorphic adenoma. Treatment and prognosis of salivary gland tumors assume a clear determination of their diguity. The unusual course in this case of a pleomorphic adenoma originally diagnosed as benign demonstrates the importance of regular follow-up.