Glomus tumor of the temporal bone

A case story describing the typical symptoms and course of a glomus tumour of the temporal bone is presented. The most frequent symptoms are pulsatile tinnitus, unilateral hearing loss, aural fullness and paresis of the vagal nerve or other lower cranial nerves. The tumour is frequently visible by otoscopy. Despite being histologically benign, the tumour is infiltrative and may affect the surrounding cranial nerves or spread into the cranial cavity. The early signs and findings are vague. Since the sequelae are fewer when the tumour is treated while it is small, an increased awareness will be of benefit to the patients.     

Imaging of follicular dendritic cell tumours of the liver

Follicular dendritic cell tumour of the liver is a recently recognized entity. To date, only two cases have been described, both in the pathology literature. Histologically, it resembles an inflammatory pseudotumour and immunohistochemical and ultrastructural studies are required for its diagnosis. The ultrasound, computed tomography and angiographic features of two cases of follicular dendritic cell tumour of the liver are described in detail. One of the patients had multiple recurrences of this tumour. The imaging features are very similar to those of hepatocellular carcinoma. As follicular dendritic cell tumour is considered to be of low-grade malignant potential, in contrast to the dismal prognosis for hepatocellular carcinoma, it is important to be able to accurately distinguish between the two types of tumour prior to initiating definitive therapy.     

The tumour stroma of oral squamous cell carcinomas show increased vascularity compared with adjacent host tissue

For tumours to grow they must acquire an adequate blood supply, and the use of drugs to inhibit tumour vascularization is one promising approach to anti-cancer therapy. Clear information is therefore required on the vascular architecture of human tumours and animal tumour models used for testing anti-angiogenic therapies. Many previous studies on animal tumour models have shown that carcinomas are least vascular in their centres and that host tissues become more vascular with proximity to the tumour. However, we have previously found that many human colorectal carcinomas do not show this pattern. The present study on human oral squamous cell carcinomas (SCCs) again reveals significant differences. Paraffin sections from 24 SCCs were immunostained using the QBEnd-10 monoclonal antibody to demonstrate blood vessels, and these were quantified by interactive morphometry using a Kontron Videoplan system. In most carcinomas, viable tumour tissue was no less vascular in the tumour centre than in the tumour periphery. Although tumours are known to release angiogenic factors, viable tumour tissue was less vascular than adjacent host tissues. However, the tumour stroma, by itself, was more vascular than adjacent host tissues. Host tissue adjacent to tumour showed no obvious increase in vascular density with increasing proximity to the tumour edge, which suggests that tumour-released angiogenic factors are only effective over a short distance.     

Diagnosis and prognosis of salivary gland tumors. An interpretation of new revised WHO classification

An exact morphological classification of salivary gland tumours is necessary for international comparison of clinical tumour studies. The basis is formed by the TNM system for determining tumour stage ("staging") and the WHO classification as the underlying principle of identifying the pathohistological tumour state and cellular tumour differentiation ("grading"). The second, revised edition of the WHO classification of salivary gland tumours differs from the first in that the exact definition of a considerably greater number of tumour entities is given and in the consideration of additional factors concerning prognosis and therapy. In the present interpretation of salivary gland tumours, not only are solitary tumour entities defined, but new findings are also considered concerning immunohistochemical tumour markers, proliferation markers (Ki-67 resp. MIB 1, AgNORs, PC-NA), oncogenes and cell receptors as well as cytogenetic alterations as prognostic factors. In particular the new tumour entities of adenomas (myoepithelial adenoma, basal cell adenoma, canalicular adenoma) and carcinomas (acinic cell carcinoma, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma, salivary duct carcinoma, myoepithelial carcinoma) are characterized. In addition, the tumour-like lesions and differential diagnostic aspects are mentioned and a general review about new prognostic factors is presented.     

Laboratory detection of Dientamoeba fragilis

The authors report a case of a 25 years old woman in whom a coin lesion was fortuitously discovered. Initial investigations were negative and an exploratory thoracotomy was performed which enabled a benign clear cell tumour of the lung to be found (sugar tumour). This rare benign tumour whose cellular origin remains indeterminate is in general discovered in a fortuitous manner after a chest x-ray has been performed showing a round peripheral opacity. The diagnosis is confirmed following the excision of the tumour, complementary examinations are not helpful.     

Carcinosarcoma of the adult kidney

Carcinosarcoma of the adult kidney is a very rare tumour and there are only a few well documented cases in the literature. In this report such a tumour is described from a 50-year-old white male, which progressed very rapidly with widespread metastases. Histologically, the tumour consisted of renal cell carcinoma and fibrosarcomatous components. The interesting features in this case were that both the carcinomatous and sarcomatous elements of the tumour exhibited metastases separately to various organs.     

Combined effects of angiostatin and ionizing radiation in antitumour therapy

Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumour progression. Angiostatin, a proteolytic fragment of plasminogen that was first isolated from the serum and urine of tumour-bearing mice, inhibits angiogenesis and thereby growth of primary and metastatic tumours. Radiotherapy is important in the treatment of many human cancers, but is often unsuccessful because of tumour cell radiation resistance. Here we combine radiation with angiostatin to target tumour vasculature that is genetically stable and therefore less likely to develop resistance. The results show an antitumour interaction between ionizing radiation and angiostatin for four distinct tumour types, at doses of radiation that are used in radiotherapy. The combination produced no increase in toxicity towards normal tissue. In vitro studies show that radiation and angiostatin have combined cytotoxic effects on endothelial cells, but not tumour cells. In vivo studies show that these agents, in combination, target the tumour vasculature. Our results provide support for combining ionizing radiation with angiostatin to improve tumour eradication without increasing deleterious effects.     

Purification and partial characterization of an acid proteinase from Dirofilaria immitis

Tumour necrosis factor-alpha (TNF-alpha) is a pluripotent cytokine with its receptors distributed throughout many different cell types. Because of the diverse effects of the cytokine, it is difficult to clearly define its role in infection and immunity, and appreciate its clinical therapeutic value. We have identified peptides derived from the primary amino acid sequence of human TNF-alpha that have neutrophil-stimulating activity, as measured by enhanced chemiluminescence and superoxide production, and peptides which are both directly cytotoxic for tumour cells (WEHI-164) in vitro and also prevent TNF binding to tumour cells. However, only one of these neutrophil-stimulating peptides was toxic for tumour cells in vitro. Our results indicate that the region of amino acids 54-94 of human TNF-alpha has previously undescribed human neutrophil-stimulatory activity, while peptides encompassing the regions 43-68 and 132-150, which are in close proximity, as indicated in the recently determined three-dimensional structure of human TNF-alpha, have in vitro anti-tumour activity. These peptides also slowed tumour growth or induced tumour regression in WEHI-164 tumour-bearing mice. The peptide 73-94, which activated neutrophils but which was not cytotoxic for tumour cells in vitro, also caused in vivo tumour regression, presumably by activating neutrophils with the consequent release of free radicals at the tumour site. Peptide 63-83, which was able to activate neutrophils in vitro, did not possess tumour regression activity in vivo. The TNF peptides described in this report did not elicit procoagulant activity in cultured bovine aortic endothelial cells and as such are devoid of at least one of the potentially lethal side-effects of elevated TNF levels in vivo.     

Montgomery Lecture, 1975. Changing concepts of the prognosis and management of small malignant melanomas of the choroid

Recent studies have shown conclusively that patients with small choroidal melanomas tend to have a favourable prognosis and that this, in turn, is closely related to tumour cell type, mitotic activity, degree of trans-scleral extension, and other characteristics of the tumour. It has not yet been established whether enucleation of the tumour-containing eye increases or decreases the patient's chance for survival. The frequency with which we observe late metastatic deaths among patients who had seemingly been 'cured' by enucleation indicate that host factors are most important in determining whether or not a patient will succumb to his tumour. It is possible that nonsurgical methods of treatment may be as effective or even more effective than enucleation (a) by diminishing the changes of intravasation of tumour cells, and (b) by promoting a more favourable host response to the tumour. While the total experience in management by methods other than enucleation is small, the results reported to date with photocoagulation, radiation, and no therapy are encouraging. Only after a much larger experience with prolonged periods of evaluation (more than 10 years after recognition of the tumour) will we be able to compare the results with those obtained by enucleation.     

Evaluation of assay designs for assays using microtitre plates: results of a study of in vitro bioassays and immunoassays for tumour necrosis factor (TNF)

Biological assays for tumour necrosis factor (TNF) are primarily based on its cytotoxic effect in tumour cell lines, and many of these bioassays are carried out using microtitre plates. Many immunoassays for TNF also routinely use microtitre plates. Data from an international collaborative study, carried out by twenty participants in nine countries, each of whom evaluated seven different ampouled preparations of human tumour necrosis factor alpha (hTNF-alpha), one ampouled preparation of human tumour necrosis beta (hTNF-beta) and one ampouled preparation of mouse tumour necrosis factor alpha (mTNF-alpha) provided a unique opportunity for a broadly based evaluation and comparison of assay designs and results. The results of this evaluation can be applied to a wide range of in vitro assays based on cell cytotoxicity or proliferation. The results of this evaluation indicated that although it is difficult to achieve control of all factors which contribute to the variability of assay responses, assays may be designed to provide measures of the variation due to some factors and to improve reliability of estimates of relative potency.     

The reduction of tumour control with increasing overall time: mathematical considerations

The rate of loss of tumour control (dP/dt) with extension of treatment time is analysed to assess the relative contributions of radiobiological parameters (radiosensitivity, clonogen doubling time, clonogen numbers and fractionation schedule) on such loss. Linear quadratic modelling and Poisson statistics are used to study individual tumour responses. A heterogeneous tumour population is constructed by the use of random sampling techniques to allow for variations in intrinsic radiosensitivity and clonogen doubling times. Average tumour control probability is calculated for this population for two different fractionation schedules (60 Gy in 30 fractions and 50 Gy in 15 fractions), each given over 15-60 days. The magnitude of dP/dt will depend upon the tumour cure probability (P): the loss of control will be most significant for tumours which have a cure of 37% when the Poisson survival model is used. The analysis suggests that compensation for short unscheduled treatment gaps (e.g. by increasing the total dose or rescheduling with use of weekend treatment sessions) may only be required for difficult tumours (i.e. radioresistant and/or with short clonogen doubling times). Where pre-treatment clonogen numbers are relatively low as in small volume tumours or after surgical debulking, the model predicts that correction for short treatment gaps is probably not required if the average effective clonogen doubling times are longer than 5 days. Different dose-time-fractionation schedules, even though producing similar overall cure rates in clinical practice, may actually be achieving cures in different subpopulations within a population of tumours, since the value of dP/dt in each individual tumour will depend upon the set of radiobiological parameters given above. For a hypothetical randomly selected heterogeneous tumour population the predicted rates of loss of tumour control produced by an extension in treatment time are 0.9 and 1.1% per day, respectively, for the above fractionation schedules. These values are close to those reported in the clinical literature for the first 2 weeks of treatment prolongation (1-2% per day for squamous cell carcinomas). The Poisson method, when combined with random sampling techniques, consequently provides realistic data. Modelling of this clinical problem provides an insight into how tumour sub-populations, each characterized by its own set of radiobiological parameters, can influence the overall rate of loss of tumour control in a heterogeneous population. Random sampling techniques should be considered as necessary precursors for the assessment of the choices of dose-fractionation in future clinical trials particularly when more precise data regarding the radiobiological parameters and their statistical variations become available.     

Role of the vascular component in growth of solid tumors: a historical review

Angiogenesis is a fundamental biological process by which new capillary blood vessels are formed. It is essential in many physiological conditions, such as embryonic development, ovulation and wound repair, and pathological ones, such as arthritis, diabetic retinopathy, and tumours. Solid tumours have angiogenesis capacity, and tumour growth and metastasis are angiogenesis-dependent. Neoplastic cell populations can grow to form a clinically evident tumour only if the host produces a vascular network sufficient to sustain tumour growth. Furthermore, the new blood vessels provide a gateway for tumour cells to enter the circulation and metastasize to distant sites. Tumour angiogenesis is essentially mediated by angiogenic molecules elaborated by tumour cells. We review here the most important literature on this topic and emphasize the crucial and paradigmatic role of this biological process and its relevance in a possible anti-angiogenic therapeutic approach to the treatment of solid tumours.     

Kinetics of cell proliferation and cell loss in the peripheral and central parts of Walker tumours growing in rats and nude mice

In previous experiments it was shown that, in the submucosal part of Walker tumours transplanted to the gastric wall of rats, a lower rate of cell proliferation was seen in the peripheral zone, defined as the outer 100-120 mu of the tumours, than in the main tumour mass. The purpose of the present experiments was to investigate whether such differences are independent of the location of the Walker tumour, or were caused by local factors specific for the gastric mucosa, and whether specific cellular immunity cell proliferation at the periphery of a transplanted tumour. Cells from Walker 256 tumour were injected into the subcutaneous space in rats and in mutant nude mice, which lack T lymphocytes. In one series, the rats and mice were injected with 3H-TDR at different time intervals before sacrifice. In a second series vinblastine sulfate was injected 3 hours before sacrifice. Although all the animals were given the same tumour dose, the tumours in mice increased in size more slowly than those in rats. In the first-mentioned series, the mitotic counts, the labelled cells and the percentage labelled mitoses (PLM) in the main tumour mass and at the tumour perphery were counted. In the second series the mitotic rate in the same two regions was determined. A significantly lower rate of cell proliferation was demonstrated at the periphery compared to the main tumour mass in both rats and mice. Differences between the PLM curves in the two regions were also found. Possible explanations of these findings are discussed. It is concluded that the described growth pattern is probably a general characteristic of the Walker tumour, and that the low rate of proliferation at the periphery is not caused by specific immunological mechanisms mediated through T lymphocytes. If the growth rates were calculated on the assumtion that the actual tumour growth followed a Gompertz function, then the rate of cell loss in the tumour in mice was higher than that in the tumour in rats.     

Endothelial-cell proliferation in experimental tumours

The proliferation characteristics of vascular endothelium have been studied in 131 individual experimental tumours, representing 18 transplanted tumour lines. The labelling index (LI) is high in most tumours, with a mean value of 0.9%, regardless of the growth rate of the tumours, or whether different tumour types are considered or individual tumours from within one line are studied in detail. A similar high LI value has been found by others for a human tumour. These high LI values may even underestimate the proliferation in new capillary buds. The high proliferative index of tumour endothelium is in marked contrast with the previously reported low 3HTdR uptake into normal tissue blood vessels. It seems likely that it is the type of new vessels formed that will influence tumour growth rates more than the simple rate of endothelial-cell proliferation. The large difference between the proliferation characteristics of tumour endothelium and normal tissue endothelium, recently identified as a possible approach for tumour therapy, has now been confirmed for a range of animal tumours and a human tumour.     

Sclerosing stromal tumour of the ovary

Two cases of sclerosing stromal tumour of the ovary in young Melanesian females are described and the differential diagnosis is discussed. Sclerosing stromal tumour of the ovary is a rare benign tumour of ovarian stromal origin which is associated with endocrine activity in a few cases. One of the patients presented with signs of precocious puberty and the tumour in this patient was considered as a functioning lesion.     

Treatment of hemoglobin Bart''s hydrops with bone marrow transplantation

OBJECTIVE: It is currently proposed to perform tumour enucleation in mono-orchid patients presenting with a small germ cell tumour, in order to preserve physiological endocrine function. However, this conservative surgery must be accompanied by treatment of any carcinoma in situ lesions present in the remaining testicular parenchyma. MATERIAL AND METHODS: The presence of carcinoma in situ was investigated in 35 patients with germ cell tumour of the testis on samples obtained from the presumably healthy pulp of the orchidectomy specimen, adjacent to and away from the tumour. Samples away from the tumour were performed according to principle of surgical testicular biopsy. Histological examination also concerned the tissue situated in contact with the tumour. RESULTS: 25 patients (74.22%) presented intratubular germ cell dysplasia in the testicular parenchyma presumed to be healthy. These lesions were always concomitantly observed on samples performed adjacent to and away from the tumour. It was observed more frequently in seminomas, but was also observed in other histological forms. CONCLUSION: Because of the diffuse nature of carcinoma in situ in germ cell tumours of the testis, pulp samples adjacent to the tumour are sufficient to ensure the diagnosis during conservative surgery. Carcinoma in situ is currently treated by local radiotherapy.     

Myolipoma of the round ligament: report of a case with a review of the English literature

Tumours consisting of a mixture of mature adipose and smooth muscle tissues, including those designated lipoleiomyomas, fibrolipoleiomyomas and myolipomas, are exceedingly rare, but most often occur in the uterine corpus. We describe here a case of such a tumour arising in the right round ligament of a 44-year-old woman. The tumour, which measured approximately 20x15x10 cm, was well encapsulated and did not involve the intrapelvic organs. Intricate mixtures of adult adipose tissue and bland smooth muscle exhibited no cellular atypia or nuclear mitotic figures, and there was little vascular proliferation. We diagnosed the lesion as a myolipoma of soft tissue with dual differentiation, and have found only 13 cases of this tumour including our own in the English literature. The present tumour is the first reported in the round ligament. Although this tumour is rare, its recognition is important for the avoidance of erroneous diagnoses.     

Consideration on a case of carcinoma ex pleomorphic adenoma of the parotid gland

The authors report a case of carcinoma in an ex pleomorphic adenoma of the parotid gland that was recently referred to their attention. This form of carcinoma is not very frequent and in the literature it is reported in a percentage of cases ranging from 1.5 to 12%. The pathogenesis of this neoplasia is controversial and at the present state of the art there are authors who support the hypothesis of a malignant transformation of a previous pleomorphic adenoma, and those who sustain the onset of the tumour ex novo. At present, there is a tendency to differentiate the carcinoma ex pleomorphic adenoma from the malignant mixed tumour: the histological analysis of the former in fact shows a benign stromal component typical of pleomorphic adenoma associated with a malignant epithelial component, whereas in the malignant mixed tumour both the mesenchymal and epithelial components are malignant. The authors use this case report as a starting point to review their 20-year experience, of pleomorphic adenoma in order to evaluate the behaviour of this tumour, above all in relation to the phenomenon of recidivation and cancerization. They report recidivation in 3.5% of cases and no malignant degeneration. The surgical approach used varied depending on the site and size of the neoformation, as well as on whether the tumour was primary or recurrent.     

Properties and function in metabolism of schistosomal hexokinase

We have studied the role of cytokines in the spontaneous regression of AK-5 histiocytoma in syngeneic rats. Animals in which the tumour regresses show high levels of cytokines in the serum compared with animals which succumb to the tumour, and levels of IL-2, IL-4, IL-12, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are significantly higher in tumour tissue of the former. Thus there is an association between rejection of the tumour and the levels of cytokines present in the tumour mass. Our results also suggest a predominant Th1-type of response in those rats that display early tumour rejection.     

Ultrasound image of the hypothenar hammer syndrome

A case of clear cell odontogenic tumour, which occurred centrally in the mandible of a 56-year-old Japanese woman, is reported with its histochemical, immunohistochemical and ultrastructural findings. Histologically, the tumour nests were composed of large glycogen-rich clear cells and small non-clear polygonal cells and were separated by thin mature fibrous connective tissue septae. Immunohistochemically, both types of tumour cells showed positive expression of various cytokeratins, in particular cytokeratin 19, and of epithelial membrane antigen. Eosinophilic hyaline deposits and possible dentin-like structures were occasionally formed in contact with the epithelial nests and are regarded as indicative of the epithelial-mesenchymal inductive capacity of this tumour. The aggressive nature of the present tumour was assumed through its invasive growth pattern and occasional mitotic figures. Although it was diagnosed as clear cell odontogenic tumour according to the present WHO classification, the patient must be followed carefully because of its probable malignant nature.