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Metastatic capability of Leishmania (Viannia) panamensis and Leishmania (Viannia) guyanensis in golden hamsters.

The pattern and kinetics of internal dissemination and frequency of cutaneous metastatic lesions resulting from experimental infection of golden hamsters with Leishmania (Viannia) panamensis and Leishmania (Viannia) guyanensis were examined. Nineteen strains were evaluated: 16 L. (V.) panamensis isolated from patients and 3 L. (V.) guyanensis, 2 isolated from human cases and 1 WHO reference strain originating from a sandfly vector. Lymphatic dissemination occurred within 3 mo and was observed for 16 of 16 (100%) of L. (V.) panamensis and 3 of 3 (100%) of L. (V.) guyanensis. Parasites were cultured infrequently from liver and spleen: 3 of 125 (2%) L. (V.) panamensis and 1 of 22 (5%) L. (V.) guyanensis. Decreased frequency of isolation from the inoculation site and draining lymph nodes over time was accompanied by increased frequency of isolation from distant lymph nodes. Dilution of triturated tissue samples resulted in an increased efficiency of parasite culture. Both primary lesions and secondary cutaneous metastatic lesions were more severe in hamsters infected with L. (V.) guyanensis than with L. (V.) panamensis. Cutaneous metastatic lesions were produced more frequently by L. (V.) guyanensis, 24 of 46 hamsters (52%), than by L. (V.) panamensis, 28 of 252 hamsters (11%). Individual Leishmania strains displayed distinctive propensities to produce cutaneous metastases, manifested as a reproducible phenotype. Metastatic pathogenicity was independent of the inoculum dose, supporting the dissociation of infectivity and pathogenicity.

Animals↗

Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP-NeuAc:LacCer alpha 2-3 sialyltransferase (GM3 synthase).

The glycosphingolipid patterns were analyzed on two clones derived from a human melanoma cell line and selected for their respectively high and low metastatic ability in immunosuppressed newborn rats. Conversely to the weakly metastatic cells which exhibited a pattern similar to that of the parental cell line, highly metastatic human melanoma cells appeared to be deficient in ganglioside biosynthesis. An accumulation of lactosylceramide was found in the latter cells, with low amounts of GM3 as the only ganglioside detected and a fourfold decreased activity of GM3 synthase (EC 2.4.99.9). After subcutaneous injection of metastatic cells in newborn rats, the cells proliferating in the tumor induced at the injection site re-expressed the four common gangliosides of melanoma: GM3, GM2, GD3 and GD2, whereas the cells growing in the lungs as metastatic nodules were deficient in ganglioside synthesis and showed an accumulation of lactosylceramide. Taken together, our results suggest that the human melanoma cells which are able to escape from the primary tumor and invade the lungs have an impaired ganglioside biosynthesis with a deficient GM3 synthase.

Animals↗

[Studies on DNA content in ploidy patterns of esophageal cancer].

The present study was undertaken to evaluate the nuclear DNA content of esophageal cancer cells consequent on the process of growth and progression of the cancer. In experimental animal studies, 47 esophageal cancers were induced in male Wistar rats by oral administration of N-amyl-N-methylnitrosamine (AMN) and were analysed in the study of ploidy patterns. The study was also carried out to determine the DNA content in the ploidy patterns in man. Primary tumors associated 421 metastatic lymph nodes in the 62 patients with thoracic esophageal cancer were subjected for the study of ploidy patterns. The nuclear DNA content was determined by means of flow cytometry. In the study of the experimentally-induced esophageal cancer in rats, aneuploidy was found in 18% at a depth of submucosa, 30% at proprial muscle, 59% at adventitia, and in 50% at a depth of neighboring structures, respectively. Clinically in man, the incidence of DNA diploidy and aneuploidy in the 62 primary cancers was 56% and 44%, respectively. In the 421 metastatic lymph nodes, diploid was found in 73% and aneuploid in 11%, while the combination of diploid and aneuploid was observed in 16%. Difference in the DNA index (DI) between the primary cancers and metastatic lymph nodes was found in 29 cases (46.8%), and the difference increased with progression of the cancer. Two hundred and ninety seven metastatic lymph nodes of 29 cases were subdivided into 4 groups based on the extent of the cancerous nests, and the DI value was found to be increased in proportion to the extension. With the results, the DI value of esophageal cancer appeared to be changed dependently by the variation of cell populations in the cancer or in the DNA content of the cancer cells.

Aneuploidy↗

Immunohistologic detection of the epidermal growth factor receptor in human esophageal squamous cell carcinoma.

Epidermal growth factor receptor (EGF-R) expression was studied immunohistologically in 38 patients with esophageal squamous cell carcinoma. The EGF-R was faintly expressed in basal and parabasal layers of normal esophageal epithelia and in cancer nests of 20 patients; it was strongly expressed in all areas of dysplastic epithelia and in cancer nests of 18 patients. The patients with strongly expressed EGF-R had lymph node metastases more frequently, and their prognosis was poorer than those with faintly expressed EGF-R. The EGF-R expression showed a mosaic pattern in 17 patients and a diffuse pattern in 21 patients. The patients with a mosaic pattern had lymph node metastases more frequently and a worse prognosis than those with a diffuse pattern. Expression of EGF-R in metastatic lymph nodes was similar to that in strongly expressing areas of primary cancers with a mosaic pattern. Thus EGF-R expression may be an important indicator for malignancies of esophageal squamous cell carcinomas because primary cancer cells with strongly expressed EGF-R metastasize to lymph nodes more frequently.

Adult↗

Computed tomography scanning and post-lymphangiogram radiography in the follow-up of patients with metastatic testicular cancer.

The use of computed tomography (CT) and lymphangiography in the follow-up of 50 patients with intra-abdominal metastatic testicular cancer was assessed. The pattern and time course of loss of lymphangiographic contrast medium from different node groups is described. Computed tomography was more effective than lymphangiography in assessing the presence of residual metastatic disease and showed residual disease in 21 patients when lymphangiography follow-up radiographs showed evidence of disease in only seven. In the detection of relapse, lymphangiography follow-up showed evidence of nodal enlargement in four of eight cases when CT showed evidence of relapse in all eight. Computed tomography is superior to lymphangiography in the follow-up of patients with metastatic testicular cancer both in monitoring response of known disease to treatment and in the detection of relapse.

Abdominal Neoplasms↗

A cell culture, chromosomal and quantitative DNA analysis of a metastatic epithelioid sarcoma. Deletion 1p, a possible primary chromosomal abnormality in epithelioid sarcoma.

The chromosomal banding pattern and the in vitro growth characteristics of a metastatic epithelioid sarcoma are described. The cultured tumor cells retained growth characteristics as well as ultrastructural and immunohistochemical properties similar to the cells of the primary tumor. Cytogenetic analysis revealed a modal range in the diploid-hypodiploid region, a finding which was corroborated by quantitative DNA determinations of both the primary tumor and a lymph node metastasis. Fourteen different marker chromosomes were identified. The most frequent clonal rearrangement was a 1p-marker resulting from a short arm terminal deletion, i.e., del (1) (p21-22). A similar 1p- marker has previously been observed in an established epithelioid sarcoma cell line. The finding of an apparently identical 1p-marker in two of two analyzed epithelioid sarcomas suggests that this rearrangement may be a primary cytogenetic abnormality in epithelioid sarcoma. An elevated ras p21 expression was demonstrated using immunohistochemical methods. The possible involvement of the N-ras gene and/or a tumor suppressor in the 1p deletion is considered.

Chromosome Aberrations↗

Microarray gene expression profiling of cell lines from primary and metastatic tongue squamous cell carcinoma: possible insights from emerging technology.

BACKGROUND: To identify common gene expression patterns among two uniquely matched pairs of primary and metastatic oral squamous cell carcinoma (OSCC) cell lines derived from the same two patient donors. METHODS: Two pairs of cell lines derived from the primary tumors and lymph node metastases of the same two patients were used to obtain microarray-based gene expression profiles. Reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to confirm observed changes for some of the candidate genes. RESULTS: Approximately 50% of the genes profiled were expressed in all four cell lines. Cluster analysis identified a group of 17 genes whose expression correlated inversely with metastatic progression. Only 10 common genes were differentially expressed in both pairs of primary and metastatic cells. A group of 28 highly expressed genes was common for both metastatic cell lines, among them some of the known metastasis-related genes such as laminin receptor, thymosin beta-4 and beta-10 and metallopanstimulin. CONCLUSIONS: Groups of presumed metastasis-related genes are highly heterogeneous and vary significantly between the two patients. Thus, it is unlikely that the metastatic phenotype of these OSCC cells is acquired by de-regulation of a single gene or a group of few genes. Most likely, multiple combinations of differentially expressed genes are involved in facilitating metastatic spread of these oral carcinoma cell lines.

Carcinoma, Squamous Cell↗

Fine-needle aspiration biopsy of large-cell undifferentiated carcinoma of the salivary glands: presentation of two cases, literature review, and differential cytodiagnosis of high-grade salivary gland malignancies.

Primary undifferentiated carcinoma of the salivary glands is a rare, high-grade neoplasm which accounts for a very small number (1-5.5%) of malignant salivary gland tumors. The large-cell variant (LCU) is less well-characterized than the small-cell form. We report on the fine-needle aspiration (FNA) biopsy findings of 2 cases of LCU, one arising in the parotid gland, and the other in a buccal mucosa accessory salivary gland. The 2 cases were similar in composition: isolated and loosely cohesive large cells with abundant cytoplasm, and variability pleomorphic nuclei with prominent nucleoli. One case also featured multinucleated tumor giant cells and macrophage polykaryons; the latter has not previously been described in FNA biopsies of LCU. There was no evidence of squamous, myoepithelial, or widespread mucinous differentiation by morphological, cytochemical, or immunohistochemical analyses (focal rare mucin production identified on special stains in one case). The differential diagnosis is lengthy and consists of other high-grade primary salivary gland malignancies as well as metastatic lesions, including melanoma. The pattern of immunohistochemical reactivity (positive keratin, negative S-100, and HMB-45 antigens), and lack of conspicuous mucin production of significant lymphoidinfiltrate, were useful in establishing the correct diagnosis.

Aged↗

Pain due to epidural tumor in cancer patients. Report of two cases and differential diagnosis.

The cases of two patients with inguinal pain as the only symptom of a T12 metastatic lesion is reported. The patterns of pain referrals from tumor lesions to the spine, epidural space, and spinal cord are reviewed. Focal back pain and pain reported in a distal distribution can both be associated with epidural or cord disease. The differential diagnosis of back pain in patients with cancer can be difficult but may be crucial in differentiating important neurological complications of systemic neoplasms.

Adenocarcinoma↗

Liver metastases induced by implantation of VX2 cancer into the gastrointestine.

An experimental model with a high frequency of spontaneous liver metastases was induced by implantation of VX2 cancer cells into the gastrointestinal walls of 36 rabbits, and the developmental process of primary cancer lesions and metastases was examined histologically. Gastric and colonic cancer lesions showed similar growth patterns in both primary and metastatic lesions: the average diameter of primary lesions enlarged from 0.7-0.8 cm on Day 7 to 2.4-2.8 cm on Day 28. The frequency and average diameter of liver metastases were 25% and microscopically certificated levels on Day 14, 25% and 3 mm on Day 21, and 50% and 8 mm on Day 28 in the gastric wall-implantation group. They were, respectively, 20% and microscopically recognized levels on Day 14, 40% and 2 mm on Day 21, and 80% and 9 mm on Day 28 in the colonic wall-implantation group. Thus, the frequency and diameter of the metastases increased in parallel with the primary cancer growth. Liver metastases occurred only in animals with vascular invasion in primary lesions, though none of the animals with the invasion always showed the metastases. These results suggest that vascular invasion of cancer cells in the primary lesions may be a premise of liver metastases, and that this experimental model may be utilized as a useful tool for studying many aspects of the pathogenesis and/or therapy of the spontaneous liver metastases in gastrointestinal cancer.

Animals↗

Simultaneous renal and transitional cell carcinomas in same kidney with subsequent lymph node metastasis: DNA flow cytometric study.

We report the DNA content in simultaneous renal and papillary transitional cell carcinomas in the same kidney with a subsequent metastasis of the transitional cell carcinoma to a left supraclavicular lymph node. The flow cytometric DNA analysis revealed aneuploid stemlines with identical DNA indices in both the transitional cell carcinoma and the metastatic lesion and a diploid pattern in the renal cell carcinoma. A discussion of these findings and the potential implication of DNA ploidy analysis in similar situations is presented.

Aged↗

Sarcomatoid tumours of the breast in Denmark from 1977 to 1987. A clinicopathological and immunohistochemical study of 100 cases.

One hundred sarcomatoid breast tumours, which had been diagnosed and registered in Denmark from January 1977 to January 1987, were subclassified using a combination of conventional morphological evaluation and immunohistochemistry, and the diagnosis was in each case related to clinical follow-up of 5-14 years or until death of the patient. Conventional histological examination resulted in 36 benign, 19 borderline and 18 malignant phyllodes tumours, 1 angiosarcoma and 26 non-specified sarcomatous tumours, 6 with small carcinoma-like foci. Immunohistochemical staining revealed that 23 of the non-phylloid sarcomatous tumours showed a tumour cell reaction for epithelial markers, predominantly cytokeratin and, therefore, the tumours were interpreted as metaplastic carcinomas. Clinical follow-up showed for phyllodes tumours and for the three cytokeratin-negative sarcomatous tumours local recurrence rates of 21 and 33%, respectively, whereas metastases only occurred from the angiosarcoma and from one borderline phyllodes tumour with five recurrences (5%). In contrast, metaplastic carcinomas gave rise to distant metastases in 50% of cases but no local recurrences. Axillary lymph nodes had been examined in 28 cases, 13 from metaplastic carcinomas. Only two of these showed metastatic spread, both with a pattern similar to the primary tumour. The differences in survival between patients with metaplastic carcinoma and patients with a borderline/malignant phyllodes tumour or a cytokeratin-negative sarcomatous tumour has in this study proven to be highly significant (P < 0.0001), and we find it of importance to use immunohistochemistry in the subclassification of sarcomatous breast tumours for appropriate surgery, reliable prognostic outlook and optimal postoperative therapy.

Actins↗

Intra-abdominal desmoplastic small-cell tumours with divergent differentiation. Report of two cases and review of the literature.

Two intraabdominal desmoplastic small cell tumours presenting in young adult males and involving the entire peritoneum, with no evident single primary site, have been studied. The histological pattern was suggestive of a metastatic small cell epithelial neoplasm, but immunohistochemical study revealed strong reactivity for cytokeratins, vimentin and desmin indicating synchronous epithelial and myogenous differentiation. In addition epithelial membrane antigen and neuron specific enolase were also positive. Electron microscopy showed fairly undifferentiated tumour cells with striking desmosome-like junctions, containing prominent paranuclear whorls of intermediate filaments, and a typical myofibroblastic stroma around neoplastic islands. Although the histogenesis of these recently described and rare tumours still remains uncertain, it seems that they constitute a reproducible entity which requires differential diagnosis from other small cell tumours of childhood and young adulthood.

Abdominal Neoplasms↗

Selected complications in the patient with cancer: spinal cord compression, malignant bowel obstruction, malignant ascites, and gastrointestinal bleeding.

The growth rate of a tumor, patterns of tumor growth and metastatic spread, and toxicity of therapy contribute to the type and severity of complications. Four common critical care complications resulting from compressive and invasive properties of tumors include spinal cord compression, malignant bowel obstruction, malignant ascites, and gastrointestinal bleeding. Knowledge of the clinical presentations of each of these complications provides a foundation for nursing assessment.

Ascites↗

Surgical treatment of malignant melanoma.

The surgical treatment of malignant melanoma is dependent on early diagnosis and a thorough understanding of the options available to patients who present with more deeply invasive lesions. There has been a shift in therapy of primary skin lesions to using narrower (1-2 cm) margins of excision. Decisions regarding treatment of the regional lymph nodes are predicated upon understanding the overall risk of metastatic spread and delineating the pattern spread of the malignant cells. The concept of intraoperative lymphatic mapping can greatly aid the clinician in deciding (1) which lymph node group is the primary drainage basin for any particular area of skin, and (2) which lymph node is the first node to receive lymphatic drainage from any given area (the so-called "sentinel lymph node."). Surgical resection of metastases can result in prolongation of survival in carefully selected patients.

Decision Making↗

p53 expression, growth, and spontaneous metastasis of the human GI 101 breast carcinoma in athymic nude mice.

The human GI 101 breast carcinoma cell lines produces spontaneous metastasis to the lungs when xenografted subcutaneously in female athymic nude mice. To establish the time-course of tumor growth and distant metastasis to the lungs and axillary lymph nodes, 5 mm3 of tumor tissue was implanted in the subaxial region of female athymic nude mice. Micrometastases in the lung were first detected 3 weeks after tumor implantation. The incidence of lung metastasis and the number of tumor emboli were correlated with the volume of the primary tumors. Ipsilateral axillary lymph node metastasis was observed within 17 weeks, indicating that metastasis to the lymph node is a later event. Unlike pulmonary micrometastases which were in the form of clusters of four to six tumor cells, metastasis to the lymph nodes were in nodules of poorly differentiated and larger tumor cells. Immunohistochemistry evaluation of p53 oncoprotein in the primary and metastatic tumor cells showed different patterns of subcellular accumulation. Cytoplasmic staining was mainly detected in the primary and secondary tumor cells disseminated to the lungs. In contrast, nuclear staining was only detected in tumor cells infiltrated to the axillary lymph nodes. There was no gain of loss of positivity of p53 accumulation (i.e., qualitative measurements) as the tumor grew in size. The data indicate that the GI 101 tumor cells could be used as a useful model for studying the malignant progression of hormone-independent breast cancer, antimetastatic drugs, and early events in tumor metastasis.

Animals↗

Anti-Müllerian hormone is a specific marker of sertoli- and granulosa-cell origin in gonadal tumors.

Sex cord stromal tumors are gonadal neoplasms containing Sertoli, granulosa, Leydig, or thecal cells, which originate from cells derived from either the sex cords (Sertoli and granulosa cell tumors) or the specific mesenchymal stroma (Leydig and thecal cell tumors) of the embryonic gonad. Only granulosa and Sertoli cells produce anti-Müllerian hormone (AMH). Our purpose was to investigate whether AMH can be used as a specific marker of human granulosa or Sertoli cell origin in gonadal tumors, to distinguish them from other primary or metastatic neoplasms, using immunohistochemistry. We studied 7 juvenile and 6 adult-type granulosa cell tumors of ovarian localization and 3 extraovarian metastases, 20 other ovarian tumors, 6 testicular Sertoli cell tumors, 2 gonadoblastomas, and 13 extragonadal tumors. Granulosa cell tumors, both juvenile- and adult-type of either ovarian or metastatic localization, showed an heterogeneous pattern of AMH immunoreactivity: Areas containing intensely or weakly AMH-positive cells were intermingled with AMH-negative areas. Although in most cases AMH-positive areas represented a minor proportion of tumor cells, we found a positive reaction in all the cases examined. In testes, although normal prepubertal Sertoli cells were intensely positive, testicular Sertoli cell tumors showed large areas of negative reaction, with few positive cells scattered throughout the tumor. AMH was also reactive in most of the cells of sex-cord origin in gonadoblastomas. No AMH immunoreaction was observed in other gonadal and extragonadal tumors. We conclude that AMH expression is conserved in only a small proportion of tumor cells of granulosa or Sertoli cell origin; however, a positive reaction in a few cells helps to distinguish between granulosa or Sertoli cell tumors or gonadoblastomas and other gonadal tumors of different origin.

Adrenal Cortex Neoplasms↗

Massive hemoptysis from an endobronchial metastasis of thyroid papillary carcinoma.

A 68-year-old female was admitted to our hospital with massive hemoptysis. She had undergone total thyroidectomy and postoperative radioisotope therapy for thyroid papillary carcinoma associated with multiple lung metastases one year before the present disorder. The right middle lobe was resected because of lethal airway bleeding from the lobe. Pathological examination showed an endobronchial metastasis 30 mm in size at the segmental bronchi. Other numerous small metastatic lesions exhibited two growth patterns: subepithelial endobronchial metastasis at the peripheral bronchi and visceral pleural metastasis. Endobronchial metastasis is an extreme type of lung metastasis of thyroid carcinoma, and can cause massive hemoptysis as the lesion increases in size.

Aged↗