Squamous cell carcinoma in rudd Scardinius erythrophthalmus: histopathology, ultrastructure, and transmission

The histopathology and ultrastructure of a skin neoplasm in rudd Scardinius erythrophthalmus (L.) are described and the neoplasm is diagnosed as squamous cell carcinoma. In the early stage, tumour cells appear singly or in clusters close to the epidermis; then tumour cells are seen in the dermis as epithelial pearls/nests, cords or sheets with central keratin; and with further development of the neoplasm, tumour cells appear as large sheets and masses, enclosing extensive keratinous formations and foci of necrotic cells, infiltrating deeper into the dermis and penetrating the muscle layers. Increasing vascularity and inflammation are associated with all stages of progression. In some cases metastases are observed in the viscera. Electron microscopic examination shows that the neoplastic cells are joined by desmosomes; the cytoplasm contains abundant mitochondria and rough endoplasmic reticulum. The neoplasm was successfully transmitted experimentally to healthy rudd when tumour cells were inoculated subcutaneously. Eight of 19 surviving test fish developed tumour growth at the site of tumour cell injection and/or in a corresponding site on the opposite of the body. One of these 8 fish, which developed a neoplasm, also showed a microscopic internal tumour in the viscera. One of the 19 test fish showed a microscopic tumour in the spleen, even though no skin tumour was visible in this fish. No tumours were found in control fish. In contrast, intraperitoneal injection of tumour cells into healthy rudd did not result in transmission of the neoplasm.     

银鲫精母细胞型精原细胞瘤的病理学观察

自银鲫(Carassius gibelio)中发现了一例自发性精母细胞型精原细胞瘤, 详细描述了该肿瘤的组织病理和超微结构。在组织学上, 该肿瘤具有薄膜包被、扩张性生长, 具有高度细胞性和弥漫性结缔组织, 伴有淋巴细胞浸润。透射电镜显示, 该肿瘤显著的特征是含有未分化的精母细胞, 且支撑细胞稀少。对比正常银鲫的精巢组织结构, 排除了其他肿瘤类型, 最终将该肿瘤鉴定为精母细胞型精原细胞瘤。系在低等脊椎动物中首次发现具有淋巴细胞浸润的精母细胞型精原细胞瘤, 丰富了鱼类性腺肿瘤的基础资料, 也为构建人类精母细胞型精原细胞瘤动物模型提供了依据。     

Development of a testicular tumour during cisclomiphene therapy

Enlargement of an atrophic testis occurred in an oligospermic patient during long-term therapy with a low dosage of cisclomiphene. Orchidectomy revealed an adult teratoma combined with an atypical seminoma. The development of a germinal-cell neoplasm during pituitary-gonadal stimulation therapy raises the question of a possible cause-effect relationship. Available evidence does not support this possibility. However, it is less clear whether hormonal influences may promote the growth of a germ-cell tumour focus. Therefore, prolonged treatment with such agents demands close supervision, particularly in patients with a predisposition to gonadal carcinogenesis.     

Fine structure of the fat body and nephrocytes in the life-stages ofDermacentor variabilis

The fine structure of the fat body and associated nephrocytes of the American dog tick,Dermacentor variabilis (Say), was described in unfed larvae, unfed nymphs, and in unfed and fed adults of both sexes. The fat body consisted of one type of cell, the trophocyte. Morphological changes that occured in the trophocytes of both sexes were dependent on feeding. The ultrastructure of feeding male trophocytes was distinct from trophocytes of feeding females. In the feeding female, the trophocyte developed an ultrastructure characteristic of cells that produce secretory proteins. A type of scalariform cell junction was found associated with rough endoplasmic reticulum of the trophocytes. Nephrocytes were closely associated with trophocytes but were not part of the fat body. Nephrocyte ultrastructure was unaltered throughout the life-stages we examined, except at the end of oviposition. Organelles in the nephrocytes were not randomly distributed, but were found in distinct regions of the cytoplasm. Slit diaphragms at the surface of the nephrocytes were extracellular specializations that had a periodic ultrastructure.     

T cell-lymphoma in the eyelid of a 9-year-old English Setter

Background

Eyelid tumours are frequently found in dogs, most of these being benign. In case of an ulcerating eyelid tumour, malignancy must be considered. We report a unique case of a low-grade peripheral T-cell lymphoma in the eyelid of a 9-year-old English Setter.

Case presentation

A 9-year-old Setter presented with a 6-month history of an eyelid ulcer. A malignant eyelid neoplasm was suspected, and the lesion was surgically excised. No other treatment was applied, and 19 months after excision the dog was still well. Histopathology revealed a diffuse lymphocytic infiltrate in the eyelid skin. Ulceration of the epithelium was seen, and the underlying tumour was composed of round and poorly demarcated pleomorphic tumour cells. The cytoplasm was pale and the nuclei heterogeneous. Numerous mitoses were present. The tumour cells stained strongly for CD3. The final diagnosis was a peripheral T-cell lymphoma not otherwise specified (NOS).

Conclusions

This is the first described case of a solitary T-cell lymphoma NOS in the haired eyelid skin in a dog. Lymphoma should be considered in case of a persistent eyelid ulcer and a biopsy should be performed. T-cell lymphoma is generally an aggressive disease; however, indolent cases are well known, and as this case shows, complete excision of a solitary T-cell lymphoma can be curable. Canine cutaneous epitheliotropic T-cell lymphoma is an important differential diagnosis, which must be recognized as the prognosis is very poor and systemic treatment is mandatory. The sub-classification of canine lymphoma is not complete, and further studies are needed to identify lymphoma subgroups and provide treatment guidelines.

     

Value of gallium scanning in seminoma of the testis.

Whole-body scanning using gallium-67-citrate gave consistently accurate tumour localisation in patients with seminoma of the testis. Thirteen out of 15 scans performed in patients with disseminated seminoma in relapse gave good imaging in all disease areas. Scans in patients with teratoma of the testis were less consistently positive; of nine scans performed in patients with disseminated teratoma seven were entirely negative and two scans lightly imaged large disease masses in two patients. In eight patients with combined (seminoma and teratoma) tumours the scan seemed to reflect the dominant tumour type at the time of scanning. In one of these patients the scans changed from positive to negative, being positive when seminoma was the dominant tumour and negative when a teratoma developed. Gallium-67-citrate scanning is useful in managing seminoma of the testis, both for determining the extent of disease present at initial presentation and for routine follow-up. It may be useful in the differential diagnosis of combined tumours when tumour masses are greater than 2 cm in diameter.     

An oestrogen-producing seminoma responsible for gynaecomastia.

In feminising testicular tumours, oestrogens can be either secreted by the tumour itself or produced by normal Leydig cells in response to paracrine and/or endocrine stimulation by hCG. Typical hormonal Leydig cell tumour patterns include: plasma oestradiol levels > 300 pmol/l on day 3 following an hCG injection, reduced plasma testosterone, and normal plasma hCG and gonadotrophin levels. Except for elevated plasma oestradiol levels, opposite results are observed in seminomas. We report a case of oestrogen-secreting seminoma mimicking a Leydig cell tumour. A 24-year-old Caucasian patient had complained of gynaecomastia for 6 months before admission. Hormonal pattern was typical of Leydig cell tumour. A 1.4 cm tumour was found in the left testis and confirmed on sonography. Considering the likely diagnosis of Leydig cell tumour, the patient was treated by tumourectomy. Surprisingly, pathological examination revealed a pure seminoma. Perifusion experiments showed that the tumour was able to secrete significant amounts of oestradiol. In addition, hCG induced a two-fold increase in oestradiol production from perifused tumour explants. Immunohistochemistry revealed that the tumour was composed of nests of seminoma cells intermingled with lymphoid infiltrates. Tumour cells also expressed aromatase, the hCG/LH receptor and the Leydig cell marker relaxin-like factor, but were betahCG-negative. These results demonstrate that a pure seminoma of the testis is able to synthesise and secrete oestrogens. They also illustrate that the body of proof favouring the diagnosis of feminising Leydig cell tumour of the testis is not rigorously specific.     

Dual tumours in the GI tract: synchronous and metachronous stromal (GIST) and epithelial/neuroendocrine neoplasms

Gastrointestinal stromal tumours (GIST) constitute the most frequent group of mesenchymal tumours in the gastrointestinal tract (GI). During the last several decades major advances have been taken in the diagnostics, treatment, and understanding of its pathogenesis. However, much less is known about the either metachronous or synchronous concurrence of GIST and other tumours of different histogenesis. In the present study clinicopathological data of 43 patients with histologically proved gastrointestinal stromal tumour were studied mainly in regard of the occurrence of a secondary neoplasm. Among the 43, 7 cases were found with secondary tumour mainly of epithelial origin. In three cases (cases 3, 5, and 7) GIST concurred with colorectal adenocarcinoma, in one case (case 1) GIST occurred in a patient with a 3-years-history of chronic lymphocytic leukaemia (CLL), in other two (cases 2 and 4) the stromal tumour was combined with in situ adenocarcinoma of the stomach and carcinoid of the pancreas, respectively. In case 6, GIST concurred with a duodenal Brunner gland adenoma. In five cases the stromal tumour and the other neoplasm occurred synchronously, and in four of them, being the stromal tumour clinically silent, GISTs were intraoperative findings. This confirms the importance of surgical intraabdominal control before closure. In one hand the repeated concurrence of GIST and colorectal adenocarcinoma in our series, and on the other hand, that of GIST and adenocarcinoma of the stomach in the literature, may indicate an at least partly common factor, which may be involved in the pathogenesis of these neoplasms.     

Effect of tamoxifen citrate on reproductive parameters of male dogs

Tamoxifen is a synthetic, nonsteroidal Type I antiestrogenic compound that competitively blocks estrogen receptors with a mixed antagonist-agonist effect. The manifestation of these different actions depends on each species, organ, tissue and cell type considered. Very little is known about the effect of antiestrogens in dogs. The objectives of this study were to determine the effects of tamoxifen citrate on some testis, prostate, hormone, and semen parameters in seven Beagle dogs with uncomplicated spontaneous benign prostatic hyperplasia. Two dogs were normospermic, four were oligozoospermic, and one was azoospermic. The dogs were allocated to a control pre-treatment period, followed by a treatment period, and five post-treatment periods (the duration of each period was 4 weeks). During the treatment period, 2.5mg tamoxifen citrate was given p.o. daily for 28 days to all the dogs. Maximum scrotal width, testicular consistency, libido semen parameters, prostatic volume, serum testosterone concentrations, and side effects were assessed. Tamoxifen negatively affected testis size and libido (P<0.01), and decreased prostatic volume (P<0.01) and testosterone concentrations during treatment. Semen quality deteriorated to nadir values (P<0.01) approximately one spermatic cycle after treatment and returned to pre-treatment values on the second cycle after treatment in all the dogs, except one young oligoazoospermic dog, in which the sperm count was higher ( P<0.01 ) at that time. No side effects were observed and fertility was conserved at the end of the study. Tamoxifen acted more like an agonist than antagonist on the gonadal axis and, therefore, upon both the prostate and testis. Therefore, tamoxifen may have therapeutic applications in dogs.     

Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours

Metastatic cancer in adults usually has a fatal outcome. In contrast, advanced testicular germ cell tumours are cured in over 80% of patients using cisplatin-based combination chemotherapy [1]. An understanding of why these cells are sensitive to chemotherapeutic drugs is likely to have implications for the treatment of other types of cancer. Earlier measurements indicate that testis tumour cells are hypersensitive to cisplatin and have a low capacity to remove cisplatin-induced DNA damage from the genome [2] [3]. We have investigated the nucleotide excision repair (NER) capacity of extracts from the well-defined 833K and GCT27 human testis tumour cell lines. Both had a reduced ability to carry out the incision steps of NER in comparison with extracts from known repair-proficient cells. Immunoblotting revealed that the testis tumour cells had normal amounts of most NER proteins, but low levels of the xeroderma pigmentosum group A protein (XPA) and the ERCC1-XPF endonuclease complex. Addition of XPA specifically conferred full NER capacity on the testis tumour extracts. These results show that a low XPA level in the testis tumour cell lines is sufficient to explain their poor ability to remove cisplatin adducts from DNA and might be a major reason for the high cisplatin sensitivity of testis tumours. Targeted inhibition of XPA could sensitise other types of cells and tumours to cisplatin and broaden the usefulness of this chemotherapeutic agent.     

Phenotypic variations and dynamic topography of transformed cells in an experimental model of diethylstilbestrol-induced renal tumour in male Syrian hamster

This work explores the phenotypic changes affecting transformed cells in an experimental model of diethylstilbestrol (DES)-induced renal tumours in male Syrian hamster. This estrogen-induced neoplasm presents an important cytological pleomorphism and its origin remains largely controversial. In order to characterize phenotypic variations during tumour progression, the occurrence of seven lineage markers was analysed by a morphometric approach in kidney sections of DES-exposed hamsters (6–;11 months). S100 protein, neuron-specific enolase (NSE) and vimentin are expressed by a large percentage of malignant cells during tumour development. Glial fibrillary acidic protein (GFAP), protein gene product 9.5 (PGP 9.5) and desmin are mostly evidenced in advanced neoplasm whereas Leu 7 always presents a focal expression. As evidenced by double-label immunofluorescence, the coexpression of three important neuroectodermal lineage markers (S100, NSE and PGP 9.5) in earliest tumour buds points to a peripheral nerve sheath origin for this neoplasm thus confirming previously published data. For each marker, the fluctuations of expression levels during tumour progression as well as the spatial heterogeneity of distribution suggest variable phenotypic differentiation of transformed cell populations. This observation is largely corroborated by double-label immunofluorescence showing coexpression modification of several markers during tumour progression. This points to a complex dynamic and spatial self-organization of different phenotypes within neoplasms. Altogether, these results support the concept that DES-induced kidney tumours are not made of unstructured cell populations but represent adaptive complex dynamic biosystems.     

Localization of inhibin in testes of human, bonnet monkey, dog and rat by immunoperoxidase technique

Immunocytochemical study on the localization of inhibin in the testes of human, bonnet monkey, dog and rat was carried out using indirect immunoperoxidase technique, in order to investigate the cell types involved in inhibin production/storage. A positive reaction was observed in the testes of human, monkey and dog while it was negative in rat testis using specific antiserum to human testicular inhibin generated against homogeneous preparation of human testicular inhibin in our laboratory. Inhibin was found to be localized in Sertoli cells, spermatogonia and primary spermatocytes of human, monkey and dog testes. A weak positive reaction was observed in spermatids of human testis only. Interestingly, Leydig cells of human, monkey and dog testes showed positive reaction indicating presence of inhibin in these cells also.     

Differential expression of estrogen receptors alpha and beta in the reproductive tracts of adult male dogs and cats

Expression of estrogen receptors (ERs) in the reproductive tracts of adult male dogs and cats has not been reported. In the present study, ERalpha and ERbeta were localized by immunohistochemistry using ER-specific antibodies. ERalpha was found in interstitial cells and peritubular myoid cells in the dog testis, but only in interstitial cells of the cat. In rete testis of the dog, epithelial cells were positive for ERalpha staining, but in the cat, rete testis epithelium was only weakly positive. In efferent ductules of the dog, both ciliated and nonciliated cells stained intensely positive. In the cat, ciliated epithelial cells were less stained than nonciliated epithelial cells. Epithelial cells in dog epididymis and vas deferens were negative for ERalpha. In the cat, except for the initial region of caput epididymis, ERalpha staining was positive in the epithelial cells of epididymis and vas deferens. Multiple cell types of dog and cat testes stained positive for ERbeta. In rete testis and efferent ductules, epithelial cells were weakly positive for ERbeta. Most epithelial cells of the epididymis and vas deferens exhibited a strong positive staining in both species. In addition, double staining was used to demonstrate colocalization of both ERalpha and ERbeta in efferent ductules of both species. The specificity of antibodies was demonstrated by Western blot analysis. This study reveals a differential localization of ERalpha and ERbeta in male dog and cat reproductive tracts, demonstrating more intensive expression of ERbeta than ERalpha. However, as in other species, the efferent ductules remained the region of highest concentration of ERalpha.     

Characteristics of cryptic/ectopic and contralateral scrotal testes in dogs between 1 and 2 years of age

Testicular malposition represents a common developmental genital defect in dogs and can affect one or both testes. In both humans and dogs, unilateral cryptorchism is more frequently detected and thought to be the expression of a genetic abnormality affecting both the undescended and scrotal testis. In the dog, there is evidence of degenerative processes affecting the maldescended testis. However, the histologic and functional changes that occur in the scrotal testis of unilateral cryptorchid or ectopic individuals remain a source of debate. Because the bilateral surgical removal of the testes leads to some undesirable side effects, the aim of this study was to evaluate the necessity for performing bilateral orchiectomy in young unilateral cryptorchid dogs. A morphologic study of both cryptic/ectopic and scrotal testes in young dogs affected by unilateral testicular maldescent was therefore conducted. The study was conducted on 10 dogs aged 1 to 2 yr and affected by unilateral testicular maldescent. We found that, in young dogs, even if no neoplastic lesions were observed, morphologic abnormalities are detectable between 1 and 2 yr of age in the maldescended testes with severity dependent on testicular position. In contrast, in the scrotal testes, the histologic and immunohistochemical exam failed to find signs of incorrect development or morphologic abnormalities. The results seem to suggest that, though the early removal of the undescended testis is recommended, continuous monitoring of the scrotal testis for the life of the dog is preferable to removing it considering the undesirable side effects related to castration.     

Canine cryptorchism and subsequent testicular neoplasia: case-control study with epidemiologic update

A retrospective study of 2,912 cryptorchid dogs identified 14 breeds with significantly high risk. Among six distinct closely interrelated breed groups (e.g., toy, miniature, and standard poodles), the risk in the smaller breed was always greater than that in the larger relative, suggesting that genetically influenced maldescent could be, in part, related to physical size or the rate of growth of the involved structures. Testicular tumors were diagnosed in 5.7% of the cryptorchid dogs; half had only Sertoli cell tumors, one-third had only seminomas. The relative risk for Sertoli cell tumor or seminoma was not directly related to a familial risk for cryptorchism. Using the health experience of a control population composed of male dogs with anal sac disease (N = 4,184), there is an estimated relative risk of 9.2 in cryptorchid dogs to develop a testis tumor (95% confidence interval, 5.9-14.3) and 4.2 in dogs with inguinal hernia (95% confidence interval, 1.8-9.5). Considering that the anatomical development of the genital tract, testis descent, and tunic relationships in dog are very similar to that in man, and that the associations of cryptorchism and inguinal hernia with testis neoplasms are also similar, the dog should be an excellent model system to further investigate the causes of human cryptorchism.     

The fate of fetal Leydig cells during the development of the fetal and postnatal rat testis

The ultrastructure and developmental fate of the fetal generation of Leydig cells of the rat testis was studied from the 17th day of fetal life up to 100 days after birth. The number of fetal Leydig cells per testis was determined by light microscopic morphometric analysis of semithin plastic sections. In fetal testes (days 17-22 postconception), Leydig cells exhibited a characteristic ultrastructure, containing smooth endoplasmic reticulum, many lipid inclusions and glycogen. Testes of 17-day-old fetuses contained about 25 x 10(3) fetal Leydig cells, rapidly increasing to 90 x 10(3) per testis in 21-day-old fetuses. After birth, fetal Leydig cells per testis remained relatively constant up to 2 weeks (80-90 x 10(3) per testis) and were identified by light and electron microscopy which showed their numerous lipid inclusions, their tendency for clustering and their association with interstitial tissue fibroblasts which partly encapsulated the fetal Leydig cells. From 21-100 days after birth, fetal Leydig cell numbers were quite variable with a mean of 45-60 x 10(3) per testis. These results are the first to show that the fetal generation of Leydig cells persist in the adult testis and do not undergo early postnatal degeneration or dedifferentiation into other interstitial cells. The simultaneous occurrence of the fetal Leydig cells and the adult population of Leydig cells indicates that these cells are distinct cell generations which are developmentally unrelated.     

Modulation of MLC-2v gene expression by AP-1: Complex regulatory role of Jun in cardiac myocytes

Walker 256 tumour-bearing rats were fed pelleted chow containing low-gamma-linolenic acid (GLA) (2.98%) or high-GLA (5.55%) during the twelve-day period after subcutaneous implantation of the tumour. The presence of n-6, polyunsaturated GLA in the diet caused a concentration-dependent decrease in tumour growth, reaching an almost 50% reduction in final tumour weight in the high-GLA group. The eicosatrienoic acid content of the whole tumour homogenate and of the Percoll-purified mitochondrial fraction was increased by the GLA-rich diets. Changes in the fatty acid composition of the cytoplasmic acyl CoA pool were also found, with increases in GLA content in both the low- and high-GLA groups. Additionally, increases in eicosatrienoic acid and arachidonic acid were found in the high-GLA group. Both the cytoplasmic acyl CoA content and the mitochondrial acyl CoA synthetase activity were increased by GLA in the diet and lipid peroxidation was also increased as determined by an increase in TBARS content. Changes in mitochondrial fatty acid composition were accompanied by a decrease in the mitochondrial membrane potential in the high-GLA group. Tumours from the control and GLA groups were examined by transmission electron microscopy. This revealed an increase in mitochondrial area and volume in the high-GLA group, in comparison with the control group, as well as a change in general cell ultrastructure, with many cells found in an apoptotic state or in a necrotic state, possibly secondary to apoptosis. The data presented show that the addition of GLA to the diet of Walker 256 tumour-bearing rats can greatly decrease the rate of development of the tumour burden. This may be, in part, due to the accumulation of poorly metabolised acyl CoA's within the tumour cell cytoplasm which, when coupled with altered mitochondrial composition, membrane potential and ultrastructure, may be a signal for cell death.