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Clinical screening of monoclonal antibodies 323/A3, cSF-25 and K928 for suitability of targetting tumours in the upper aerodigestive and respiratory tract.

Immunohistochemical characterization of three monoclonal antibodies (MAbs), designated 323/A3, SF-25 and K928, on a panel of 330 head and neck and lung tumours indicated their potential for targetting tumours in the upper aerodigestive and respiratory tract. Subsequently, MAbs were screened in a clinical phase I/II radioimmunoscintigraphic (RIS) trial for the detection of primary tumours and lymphnode metastases in patients with histologically proven squamous cell carcinoma of the head and neck (HNSCC). In 10 HNSCC patients MAbs 323/A3 F(ab')2 (n = 3), chimeric (mouse-human) SF-25 IgG (n = 1), and K928 IgG (n = 6) were evaluated for their suitability for tumour targetting. Monoclonal antibodies 323/A3 and K928 were shown to be capable of detection of HNSCC. However, there was uptake at non-tumour sites, for MAb 323/A3 in the thyroid gland, liver and skeleton, probably bone marrow, and for MAb K928 in liver, spleen and the skeleton, probably bone marrow. At a higher K928 dose, uptake in the liver was diminished but still substantial. cSF-25 was not capable of detecting HNSCC, due to the rapid and extensive uptake at non-tumour sites such as liver, spleen, brain and the skeleton, probably bone marrow. Radioactivity uptake at non-tumour sites could be mainly explained by the presence of good accessible antigenic sites and will definitely limit the application of these pan-carcinoma MAbs for therapeutic purposes.

Aged↗

Features of extramedullary and extraosseous multiple myeloma: a report of 19 patients from a single center.

Extramedullary (EM) localizations at diagnosis or during the course of multiple myeloma (MM) are rare. We conducted a large retrospective study to more accurately describe the clinical and laboratory features of this entity, and the outcome of these manifestations. The charts of 19 eligible patients out of 432 patients with MM were retrieved from the hematology department of the Institut Paoli-Calmettes Cancer Center. Median age was 61 (range: 39-79) with a female/male sex ratio of 8/11. Ten patients were found to have EM and extraosseous tumor at the time of MM diagnosis, and nine patients developed EM tumor during the course of the disease. Neither the stage of the disease, the LDH level, or the type of immunoglobulin (Ig) was found to be associated with the development of EM disease. Patients who developed EM tumor during the course of MM had a lower serum Ig and a higher monoclonal Bence-Jones proteinuria at the diagnosis of MM than patients who presented with EM tumor at diagnosis. Multiple sites were usually involved. Resistance to chemotherapy was frequent and response to thalidomide was poor. Eight out of the 19 patients responded to high-dose chemotherapy. The remaining 11 patients progressed while on therapy. With a median follow-up of 13 months (range: 2-65), six patients are alive, four patients are in partial remission and two patients in present progressive disease. In conclusion, EM tumors are a rare manifestation of MM, with a cumulative incidence of 4.6% of MM. Multiple sites are usually involved. The response to chemotherapy is very poor with a very low response rate to thalidomide. The prognosis is very poor, especially when the diagnosis of EM tumor is concurrent with the diagnosis of MM.

Adult↗

Malignant melanoma: impact of superficial US on management.

PURPOSE: To evaluate the impact of superficial ultrasonography (US) on clinical management of melanoma. MATERIALS AND METHODS: Superficial US in areas at high risk for local recurrence or nodal metastases was performed in 33 patients with cutaneous melanoma. Impact categories were assigned to each US study (n = 55): category 3, US added information that altered clinical management; category 2, US added information that did not change management; category 1, no added information and management unchanged; category 0, not helpful or was misleading. RESULTS: Twenty-two US studies (40%) were category 3: detection of nonpalpable metastases altered surgical therapy (n = 2), demonstration of pharmacodynamic response to chemotherapy (n = 5), and determination of benignancy or malignancy (n = 15). Nine (16%) were category 2: identification of nonpalpable metastases did not alter management. Twenty-two (40%) were category 1: supported clinical impression of no metastases (n = 18) or helped confirm cutaneous, subcutaneous, or nodal metastases (n = 4). Two (4%) were category 0: missed proved metastases. CONCLUSION: Superficial US affected management of melanoma by allowing detection and characterization of masses, guidance of biopsy, and assessment of pharmacodynamic response.

Female↗

PET-CT fusion imaging in differentiating physiologic from pathologic FDG uptake.

Interpretation of positron emission tomographic (PET) scans in the absence of correlative anatomic information can be challenging. PET-computed tomography (CT) fusion imaging is a novel multimodality technology that allows the correlation of findings from two concurrent imaging modalities in a comprehensive examination. CT demonstrates exquisite anatomic detail but does not provide functional information, whereas 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) PET reveals aspects of tumor function and allows metabolic measurements. Subtle findings at FDG PET that might otherwise be disregarded or interpreted as physiologic variants may lead to detection of a malignant process after being correlated with simultaneously acquired CT findings. Alternatively, equivocal CT findings, which could represent malignant tumor, reactive changes, or fibrosis, can be clarified with the help of the additional metabolic information provided by concurrent FDG PET. Accurate interpretation of FDG PET scans requires a thorough knowledge of the normal physiologic distribution of FDG and of normal variants that may reduce the accuracy of PET studies, thereby significantly affecting patient treatment. Although in rare instances PET-CT cannot help resolve the diagnostic dilemma, it is enjoying widespread acceptance in the medical imaging community, usually allowing differentiation of physiologic variants from juxtaposed or mimetic neoplastic lesions and more accurate tumor localization.

Adult↗

Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype.

Melanoma is the most lethal skin cancer. Most deaths from melanoma result from metastases. Semaphorins have been shown to inhibit neuronal and endothelial cell migration, but the effects of semaphorins on tumor metastasis have not been documented. We found that semaphorin 3F (SEMA3F) was markedly downregulated in highly metastatic human cell lines in vitro and in vivo, which suggested that it may be a metastasis inhibitor. Metastatic human melanoma cells were transfected with SEMA3F and implanted into mice; the resultant tumors did not metastasize. Rather, the primary tumors resembled benign nevi characterized by large areas of apoptosis, diminished vascularity, inhibition of hyperplasia in overlying epidermal cells, and encapsulated tumor borders delineated by thick layers of fibroblasts and collagen matrix. This phenotype is in stark contrast to highly invasive, vascular mock-transfected tumors. In vitro, tumor cells expressing SEMA3F had a diminished capacity to adhere and migrate on fibronectin. Consistent with semaphorin-mediated chemorepulsion of neurons, tumor cells expressing SEMA3F were chemorepulsive for vascular and lymphatic endothelial cells expressing neuropilin-2 (NRP2), a novel mechanism for a tumor angiogenesis inhibitor. The repulsive activity was abrogated by NRP2 RNA interference. Together these results indicate that SEMA3F is a potent metastasis inhibitor that targets both tumor and stromal cells and raise the possibility of SEMA3F having therapeutic potential.

Animals↗

Giant lymph node hyperplasia in angiohamartomatous soft tissues.

The first case of Castleman's benign lymphoma associated with angiohamartomatous alterations in peripheral fibroadipose tissue is reported, and a pathogenetic connection is hypothesized. The lesion was encountered in a 48-year-old man; it was situated in the left and inferior retroperitoneal area with extension to the inguinal region of the same side.

Adipose Tissue↗

Ultrasonography for evaluation of the carotid artery in head and neck cancer.

The dynamic relationship of lymph node metastases to surrounding vascular structures in the neck is important for preoperative patient assessment. When carotid artery involvement is suspected, this relationship often determines whether or not to operate. In the case of adhesive neck metastases along the internal jugular vein, it becomes possible to predict preoperatively if the integrity of this vein may be preserved. Ultrasonography has the ability to differentiate subtle from gross adherence, or simple compression from vascular invasion. This is done by manually palpating the tumor mass and asking the patient to perform various maneuvers while observing on a monitor the relationship of the tumor mass to the nearby artery. This article correlates the preoperative computed tomography/magnetic resonance imaging (CT/MRI) and ultrasound findings in 41 patients with large nodal metastases which were subsequently confirmed during surgery. In case of positive ultrasonographic invasion of the carotid artery, a transcranial Doppler ultrasonography (TCD) exam was performed to confirm adequate crossflow. Our experience with ultrasonography and TCD in patients with suspected involvement of the carotid artery shows reliable results and obviates in our hands the routine need for more complex, invasive, and expensive tests.

Carotid Arteries↗

[Phase III trial of 99mTc-rhenium colloid for lymphoscintigraphy].

A multicenter study was carried out on 191 patients (196 examinations) with lymphatic system disorders to evaluate the efficacy and safety of 99mTc-rhenium Colloid, a tracer for lymphoscintigraphy (TCK-17). Local pain and swelling occurred at the site of injection in 79.6% and 5.1% of patients, respectively, and 2 patients experienced mild fever. The accuracy was calculated on the basis of the results obtained by other diagnostic methods. Lymphoscintigraphy using TCK-17 was sensitive diagnostic procedures, but low specificity. The efficacy was classified into five grades: "Excellent", "Good", "Moderate", "Equivocal", and "Poor". 67.3% of all examination were evaluated as "Excellent" or "Good". This study revealed TCK-17 was a useful radiopharmaceutical for lymphoscintigraphy because of its safety and effectiveness.

Adult↗

[Specifics of regional metastases of adrenal malignant tumors].

Radicality of surgical treatment of the adrenal gland malignant tumor (AGMT) depends on its primary complete excision as well as all the regional metastases (RM). This trusts the necessity of studying of the regional metastatic spreading ways. There were investigated the regional metastatic spreading ways in 257 patients with AGMT, treated in 1968-2002 yrs in the clinic. In 33% of the patients with AGMT RM were revealed. Regional metastatic spreading was as usual lymphogenic one. RM were usually revealed in lymphatic nodes of renal hilus, paranephral and paraaortal fat tissue. That's why while doing the operative intervention for AGMT it is necessary to perform revision of the renal hilum lymphatic nodes, as well as paranephral and paraaortal fat tissue and muscles of the back.

Abdominal Neoplasms↗

Experimental model for metastasis of intraocular melanoma: preventive role of natural killer cells.

A murine melanoma cell line, B16-BL6, was inoculated in various body sites of the mouse, including the anterior chamber of the eye, and an analysis was carried out of the relationship between the anatomical site of tumor inoculation and the tumor growth or the pattern of tumor metastasis. It was found that not only the primary tumor growth but also the metastatic pattern was greatly affected by the site of the primary tumor. Fifteen days after the tumor transplantation, the mean weight of the primary tumors transplanted in the ear or in the abdominal flank became five to ten times larger than those transplanted in the eye or in the footpad. Furthermore, intraocular melanomas rapidly developed lung metastasis, whereas subcutaneous melanoma primarily developed lymph node metastasis. It was also found that natural killer cells had a preventive role in the early phase of hematogenous dissemination from the intraocular melanoma.

Animals↗

[Fine needle aspiration cytology of metastatic malignant melanoma. Improvement of results with ultrasound control].

A review of 315 fine-needle aspiration cytologies (FNAC) carried out from 1984 through 1992 in 157 patients with suspected metastatic melanoma was carried out: 176 results were confirmed by histological examination and 139 by clinical follow-up. In the first period, from 1984 through 1988, we observed 5 false-negative results out of 123 evaluable FNACs. All were caused by technical failure. In the second period, from 1988 through 1992, all fine-needle biopsies of impalpable masses were done with ultrasound guidance. Thus, we were able to avoid further false-negative results. No errors in interpretation were found. We obtained 219 true-positive and 91 true-negative results with 97.8% sensitivity, 100% specificity, 98.4% accuracy, 100% positive and 94.8% negative predictive value. In 3 cases with metastatic melanoma the cytological diagnosis only was 'malignant tumor', while in another 5 patients the cytodiagnosis of melanoma was not definitive. Immunocytology was helpful in these cases in identifying melanoma. FNAC allowed the correct diagnosis of a second malignancy in 4 cases (one papillary thyroid cancer, one Hodgkin's disease, two non-Hodgkin's lymphomas). No complications occurred. In our opinion, FNAC--for poorly defined lesions with ultrasound guidance--is a very rapid, safe and accurate method that allows reliable diagnosis of metastatic melanoma.

Adolescent↗

Prostatic adenocarcinoma metastases mimicking small cell carcinoma on fine-needle aspiration.

Prostate adenocarcinoma (PA) is known to metastasize widely to bone, lung, lymph nodes, and other sites. We have observed a rare, although distinctive, neuroendocrine (NE) cytomorphology of metastatic PA on fine-needle aspiration (FNA) that mimics small cell carcinoma (SCC). From a total of 117 cases, eight cases of metastatic PA diagnosed on FNA showed cytomorphologic features indistinguishable from SCC. All specimens were reviewed, along with immunoperoxidase (IPOX) studies using prostate specific (PSA, PSAP) and NE markers (synaptophysin, chromogranin, etc.). The patients ranged in age from 51-68 (mean age = 63). The PSA levels at the time of FNA ranged from <0.1 to 2,892 ng/ml (normal postprostatectomy <0.2 ng/ml). Sites of FNA included liver (two), soft tissue (five), and lymph node (one). FNA was performed from 11 mo to 6 yr after the initial diagnosis of the primary tumor. All primary PA were of high Gleason grade ranging from 7-9. None of the primary PA showed neuroendocrine morphology. Cytomorphologic characteristics observed on FNA included predominantly single cells with occasional sheets or loose cell aggregates. A predominant NE nuclear morphology was evident (i.e., hyperchromasia, fine dusty chromatin, inconspicuous nucleoli, nuclear molding, chromatinic crush artifact, karyorrhexis, mitoses, etc.), with none of the tumors displaying glandular formation. Taken together, these features gave these metastases a cytomorphology indistinguishable from SCC. IPOX studies revealed PSA-positivity (5/7), PSAP-positivity (4/7), and only focal NE markers positivity (3/6). Metastatic prostate carcinoma may rarely mimic a SCC (6.8% in this study). This often necessitates further patient workup to identify the primary source for the patient's metastasis, particularly if the patient has multiple lesions. An accurate diagnosis of these lesions as PA metastases is essential for effective, timely treatment and therapeutic design.

Adenocarcinoma↗

[Diagnostic value of tissue polypeptide antigen in serum of larynx cancer patients].

UNLABELLED: Tissue polypeptide antigen (TPA) is a serological tumour marker used in the diagnosis, management and follow-up of patients with head and neck cancer. The aim of this study was to evaluate the diagnostic and prognostic significance of pretreatment TPA serum levels in patients with larynx cancer. The predicting ability of this tumour marker with respect to histological type, pathological state and lymph node metastasis was also assessed. MATERIALS AND METHOD: Concentrations of the TPA in the serum from 35 patients were measured by immunoradiometric assay. RESULTS: The results showed the sensitivity value for the group of 35 patients was 29.4%, but in clinical stage IV was 70%. TPA levels correlate with T classification and lymph node metastasis. In T4 tumors it was significantly higher than in T2 (p=0.047). TPA levels were significantly higher in patients with nodal invasion and were generally lower in patients with spinocellular carcinoma (p=0.0048). CONCLUSION: Our date indicate that TPA is of limited usefulness in the primary diagnosis in patients with larynx cancer, but is useful in detecting lymph node metastasis.

Aged↗

Monoclonal antibodies against SU-DHL-1 cells stain the neoplastic cells in true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease.

Three murine monoclonal antibodies, named 2H9, 1E9 and 1A2, were produced after immunization of BALB/c mice with cells of the SU-DHL-1 cell line from a true histiocytic lymphoma. In frozen sections from various lymphomas, 2H9 and 1A2 selectively stained the cell membranes of neoplastic cells in true histiocytic lymphoma and Hodgkin's disease. Antibody 1E9 stained the nuclear membranes of the tumor cells in true histiocytic lymphoma and malignant histiocytosis. No staining was seen in 56 cases of B and T cell lymphoma. Several tissue culture cell lines, including T cell acute lymphoblastic leukemia and pre-B cell lines, were not stained. With 2H9, however, a positive reaction was noted for two Epstein-Barr virus (EBV)-positive African Burkitt's lymphoma cell lines (Daudi and P3HRI), one human T cell lymphoma/leukemia-virus-positive cell line (HUT 102), and one EBV-transformed normal B lymphoblastoid cell line (RPMI 8057). In normal lymphoid tissues, 2H9 and 1E9 reacted with the nuclear membranes of histiocytes and interdigitating reticulum cells, whereas 1A2 stained only rare cells of an unknown type. All three antibodies failed to react with B or T cells in frozen tissue sections of normal lymphoid tissues. The use of these three antibodies should facilitate the diagnosis of histiocyte and interdigitating reticulum (IR) cell-related neoplasms, namely, true histiocytic lymphoma, malignant histiocytosis, and Hodgkin's disease. True histiocytic lymphoma and Hodgkin's disease exhibit similar reactivities with these three and with two other monoclonal antibodies (HeFi-1 and Tac), suggesting that these two types of lymphoma are related. In contrast, malignant histiocytosis was negative for 2H9, 1A2, Tac, and HeFi-1. The difference in the phenotypic expression of true histiocytic lymphoma and malignant histiocytosis indicates that they are two different disease entities.

Animals↗

Congenital fibrosarcoma of the upper extremity.

Congenital or infantile fibrosarcoma is a rare soft-tissue neoplasm that should be considered in the differential diagnosis of a large extremity mass presenting at birth. These tumors are notoriously misdiagnosed at birth as either hemangiomas or lymphatic malformations. Definitive diagnosis is made by physical examination, special radiologic studies, and biopsy. Although histologically similar to fibrosarcomas occurring in adults, the congenital lesions differ in their clinical behavior; metastases are rare, local recurrence is common, and the prognosis is good with wide local excision combined with chemotherapy. Amputation should be reserved for chemoresistant patients in whom the involvement of neurovascular structures by the tumor make a limb-sparing aggressive excision impossible.

Adult↗